New Evidences: Acidity Theory of Atherosclerosis

Both restriction and high salt intake may result in cardiovascular disease

2012-01-16T07:02:00.000-08:00

For centuries, salt has been regarded as essential to human health. Recently there has been an intense discussion on the benefits and potential harm of reducing salt (sodium chloride) intake in the general population. A long-term advocate of salt reduction is Dr. Graham MacGregor from Queen Mary University of London, UK. In the opposite side there is a growing number of Doctors who disagree about a generalized sodium restriction. One of these is Dr. Michael Alderman from the Albert Einstein College of Medicine, New York, USA, that says the available data provides no support for any universal recommendation of a particular level of dietary sodium (1, 2).
Anyway, it is important to emphasize that a general reduction in dietary salt intake can only be achieved by reducing the sodium chloride content of processed foods, as these account for 75% to 80% of the sodium chloride consumed daily (3). Even the existent table salt is industrially processed with the essential and trace minerals removed almost completely.
Recently an European study questioned the need to reduce the salt intake in the general population and refuted the computer-generated estimates of the lives and healthcare costs that would be saved by lowering sodium consumption. The authors have stressed that previous studies on which recommendations to lower sodium intake are based are all short term, controlled intervention trials, in which there are reductions in blood pressure in hypertensive patients and a small decrease in blood pressure in normotensive volunteers with sodium reduction, and these studies have been extrapolated to the population as a whole. The authors also note that the assumption that lower salt intake would in the long run lower blood pressure, has not confirmed in longitudinal population-based studies. The most controversial finding from this prospective population study involving 3681 participants, without cardiovascular disease, was that the lower sodium intake - as measured by 24-hour sodium excretion - was associated with higher cardiovascular mortality. In their study the authors say that the underlying mechanisms explaining the inverse association between cardiovascular mortality and 24-hour urinary sodium excretion might be that a salt intake low enough to decrease blood pressure also increases sympathetic nerve activity, decreases insulin sensitivity, activates the renin-angiotensin system and stimulates aldosterone secretion (4).
This European study is not the first to find that a low-sodium diet is detrimental for health. The NHANES study published in 2006, constituting a sample with 7154 participants, found that the low sodium diet was associated with the stimulation of the sympathetic nervous system, with an increase in mortality outcomes in cardiovascular disease and by all causes (5). In other short term trials was also observed activation of the renin-angiotensin-aldosterone system and in the sympathetic nervous system, a decrease in insulin sensitivity and increases in LDL cholesterol concentrations, triglycerides and uric acid (6).
Graham MacGregor, invited for commenting the study by Heartwire (7) have demonstrated irritation regarding the remarks on the possible underlying mechanisms cited in the European study (4), saying “We have shown in our meta-analysis that reducing salt by the amounts we are recommending does not increase sympathetic tone, there is a trivial increase in renin, and no evidence of any adverse effects, no physiologic meaning whatsoever” Dr. MacGregor also have reacted in 2003 (8), in a correspondence to Circulation on the findings by Grassi and colleagues that found effects of modest salt reduction on sympathetic activity (9).
On the other side, because plasma norepinephrine levels during high salt intake remain unaltered in salt-sensitive hypertensive patients but are reduced in normal subjects and non-salt-sensitive hypertensive patients, abnormal relationships between salt intake and sympathetic activity have been suggested (10). It is interesting to note about the discovery that a high sodium diet may depress arterial baroreceptor reflex in normotensive people, with sympathetic activation (11).
A recent review article by researchers at Boston University School of Medicine (BUSM) debunks the widely-believed concept that hypertension, or high blood pressure, is the result of excess salt causing an increased blood volume, exerting extra pressure on the arteries. Published online in the Journal of Hypertension (13), the study demonstrates that excess salt stimulates the sympathetic nervous system to produce adrenalin, causing artery constriction and hypertension. This study cites that several investigators throughout the 1960s and 1970s had reported elevated plasma catecholamine levels in up to 40% of patients with essential hypertension (14-17), as well as an association of increase in catecholamines with high sodium intake in experimental animals and humans (18-21).
Taking in view that both restriction and high intake of dietary sodium may be deleterious to human health, I do not share the opinion that indiscriminate restriction in dietary sodium intake at population level and as a universal recommendation is the a good solution to help in the prevention of cardiovascular disease. In my idea salt balance should be thought according individual requirements.
Moreover because we believe that sympathetic predominance is the primary factor in the cascade of events leading to cardiovascular disease, according our acidity theory of atherosclerosis (12).
Note:
A new study (22) has shown that people consuming too much salt and too little potassium in their diet have had a significantly raised risk of death from cardiovascular disease compared with those who had the lowest ratio of sodium to potassium. The study, with an average of 14.8 years of follow-up, collecting data on 12,267 people, isn't the first study to find an association between high blood pressure and high levels of salt consumption and low levels of potassium intake.
However, Dr. Elena Kuklina, co-author of this study, told to Heartwire (23) that this was the first large, nationwide study looking at sodium and potassium at the same time. She also told that "The major implications of their findings are that a diet balance in both nutrients is important. People should try to reduce sodium in particular by consuming less processed food, but also they should increase potassium intake".
Dr. Kublina have also stressed join Heartwire that people must understand the massive impact that processing has on foods. She cites, for example, that 100 g of unprocessed pork contains 61 of sodium and 340 mg of potassium, but turning this into ham alters that ratio significantly, to yield a whopping 921 mg of sodium and, to boot, reduces the potassium content to 240 mg.
Talking about the results of this study, Dr. David Brownstein, a colleague from THINCs, has made an interesting observation inside of our internal forum, on the high intake of salt depending of his kind if refined or unrefined salt. Dr. David told that "Refined salt lacks potassium. Refined salt use leads to sodium/potassium imbalances. This can be rectified by using unrefined salt which contains both sodium (lower amounts as compared to refined salt) and potassium. This article should have been titled "The problems with Refined Salt: Potassium Deficiency."
I agree with Dr. David Brownstein, on his opinion. Mainly taking the importance of alterations in sodium/potassium activity expressed in the acidity theory of atherosclerosis paper (12).
Carlos Monteiro
1. He FJ and MacGregor GA, . How far should salt intake be reduced? Hypertension 2003; 42:1093-1099. Full free text at http://hyper.ahajournals.org/cgi/reprint/42/6/1093
2. Michael H. Alderman, Evidence Relating Dietary Sodium to Cardiovascular Disease. Journal of the American College of Nutrition, Vol. 25, No. 3, 256S–261S (2006). Full free text at http://www.jacn.org/content/25/suppl_3/256S.full
3. Klaus D et al. Salt restriction for the prevention of cardiovascular disease. Dtsch Arztebl Int 2010; 107(26):457-62. Full free text at http://www.aerzteblatt.de/int/article.asp?id=77388
4. Stolarz-Skrypek K, et al. Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA 2011; 305:1777-1785
5. Cohen HW, et al. Sodium Intake and Mortality in the NHANES II Follow-up Study. The American Journal of Medicine (2006) 119, 275.e7-275.e149.
6. Jurgens G, Graudal NA. Effects of low sodium data versus high sodium diet on blood pressure, renin aldosterone, catecholamines cholesterols, and triglyceride. Cochrane Database Syst Rev. 2004; Issue 1. Art. No.: CD004022
7. New Salt paper causes controversy. Heartwire, May 3, 2011
8. He FJ and MacGregor GA. Salt intake and sympathetic activity. Circulation 2003 Apr 29; 107 ((16): 108 author reply. Full free text at http://circ.ahajournals.org/ggi/reprint/107/16/e108
9. Guido Grassi, et al. Short- and Long-Term Neuroadrenergic Effects of Moderate Dietary Sodium restriction in Essential Hypertension. Circulation. 2002;106: 1957-1961. Full free text at http://circ.ahajournals.org/cgi/reprint/106/15/1957
10. Campese VM, et al. Abnormal relationship between sodium intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension. Kidney Int., 1982; 21: 371-378
11. MA Creager, et al. Sodium depresses arterial baroreceptor reflex function in normotensive humans. Hypertension 1991;17;989-996
12. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
13. Volume-expanded' hypertension: the effect of fluid overload and the role of the sympathetic nervous system in salt-dependent hypertension, Journal of Hypertension, V30; N1: January 2012 doi: 10.1097/HJH.0b013e32834f6de1
14. de Champlain J, Farley L, Cousineau D, van Ameringen MR. Circulating catecholamine levels in human and experimental hypertension. CircRes 1976; 38:109–114.
15. Louis WJ, Doyle AE, Anavekar S. Plasma norepinephrine levels in essential hypertension. N Engl J Med 1973; 288:599–601.
16. Sever PS, Osikowska B, Birch M, Tunbridge RD. Plasma noradrenaline in essential hypertension. Lancet 1977; 1:1078–1081.
17. Lake CR, Kopin IJ, Ziegler MG, Coleman MD. Plasma catecholaminesand neurogenic hypertension. N Engl J Med 1977; 297:53–54.
18. de Champlain J, Krakoff L, Axelrod J. Interrelationships of sodium intake, hypertension, and norepinephrine storage in the rat. Circ Res 1969; 24 (Suppl):75–92.
19. Reid JL, Zivin JA, Kopin IJ. Central and peripheral adrenergic mechanisms in the development of deoxycorticosterone-saline hypertension in rats. Circ Res 1975; 37:569–579.
20. Murray RH, Luft FC, Bloch R, Weyman AE. Blood pressure responses to extremes of sodium intake in normal man. Proc Soc Exp Biol Med 1978; 159:432–436.
21. Nicholls MG, Kiowski W, Zweifler AJ, Julius s, Schork MA, Greenhouse J. Plasma norepinephrine variations with dietary sodium intake. Hypertension 1980; 2:29–32.
22. Yang Q, Liu T, Kuklina EV et al. Sodium and potassium intake and mortality among US adults. Prospective data from the Third National Health and Examination Survey. Arch Intern Med 2011, 171 (13):1183-91
23. Sodium/potassium ratio important for health. Heartwire, July 11, 2011

Why atherosclerosis is milder or non-existent in individuals with Down syndrome?

2011-12-16T08:07:00.000-08:00

Different necropsy studies have shown that the occurrence of atherosclerosis is milder or non-existent in subjects with Down syndrome (1, 2, 3, 4). Indeed, a study have suggested that women with Down syndrome (DS) may be less likely to express the insulin resistance syndrome*, and men and women with Down syndrome may possess fewer atherosclerotic risk factors than the comparison groups (5)
Confirming the results that DS individuals possess low levels of atherosclerosis a recent study have examined the relation between cardiovascular disease risk factors and intima-media thickness (IMT), a measure for atherosclerosis, in 52 adults with DS. The adults with DS possessed lower IMT, systolic blood pressure and diastolic blood pressure, than controls. The study’s conclusion was that the adults with DS may be protected against atherosclerosis despite elevated body fat and elevated cardiovascular risk factors (6).
It is interesting to note about the results from some studies demonstrating that at lower degrees of IMT, the thickening appears to reflect an equilibrium state in which the effects of pressure and flow on the arteries are in balance, given a characteristic relation between shear stress and local transmural pressure (7, 8).
A reasonable explanation for the reduced incidence of atherosclerosis is the altered autonomic regulation in individuals with DS, with effects of smaller changes in baroreflex sensitivity and in sympatho-excitation response (9, 10, 11). The reduced sympathetic response to stress in DS is supported by the low circulating catecholamines levels in response to incremental cycle ergometer exercise in individuals with DS (12).
In the acidity theory of atherosclerosis the sympathetic predominance is the primary step and shear stress is the last step in the cascade of events leading to the atherogenic process (13, 14)
Carlos Monteiro
*Note:
Insulin resistance may contribute to enhanced SNS activity (15) and SNS activity may similarly increase insulin resistance (16)

1. Ylä-Herttuala S, Luoma J, Nikkari T, Kivimäki T. Down's syndrome and atherosclerosis. Atherosclerosis. 1989 Apr;76(2-3):269-72.
2. Murdoch JC, Rodger JC, Rao SS, Fletcher CD, Dunnigan MG. Down's syndrome: an atheroma-free model? Br Med J. 1977 Jul 23;2(6081):226-8.
3. Moss TJ, Austin GE. Pre-atherosclerotic lesions in Down syndrome. J Ment Defic Res. 1980 Jun;24(2):137-41.
4. Chaney RH. Neurogenic atherosclerosis in mentally retarded persons. J Ment Defic Res. 1987 Sep;31 ( Pt 3):235-40
5. Draheim CC, McCubbin JA, Williams DP. Differences in cardiovascular disease risk between nondiabetic adults with mental retardation with and without Down syndrome. Am J Ment Retard. 2002 May;107(3):201-11
6. Draheim CC, Geijer JR, Dengel DR. Comparison of intima-media thickness of the carotid artery and cardiovascular disease risk factors in adults with versus without the Down syndrome. Am J Cardiol. 2010 Nov 15;106(10):1512-6
7. Gnasso A, et al. Association Between Intima-Media Thickness and Wall Shear Stress in Common Carotid Arteries in Healthy Male Subjects. Circulation. 1996;94:3257-3262
8. Bots M. L, et al. Increased Common Carotid Intima-Media Thickness. Adaptive Response or a Reflection of Atherosclerosis? Findings From the Rotterdam Study. Stroke. 1997;282442 .
9. Agiovlasitis S, Collier SR, et al. Autonomic response to upright tilt in people with and without Down syndrome. Res Dev Disabil. 2010 May-Jun;31(3):857-63.
10. Iellamo F, Galante A, et al. Altered autonomic cardiac regulation in individuals with Down syndrome. Am J Physiol Heart Circ Physiol. 2005 Dec;289(6):H2387-91.
11. Bo Fernhall and Mari Otterstetter. Attenuated responses to sympathoexcitation in individuals with Down syndrome. J Appl Physiol 94: 2158–2165, 2003.
12. Eberhard Y, Etarradossi J and Terminarias A. Biochemical changes and catecholamine response in Down’s syndrome adolescents in relation to incremental maximal exercise. J Ment Defic Res 35: 140-146, 1991
13. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
14. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at http://aciditytheory.blogspot.com/2010/02/sympathetic-predominance-primary-factor.html
15. Pikkujamsa SM, Huikuri HV, Airaksinen KE, Rantala AO, Kauma H, Lilja M, Savolainen MJ, Kesaniemi YA. Heart rate variability and baroreflex sensitivity in hypertensive subjects with and without metabolic features of insulin resistance syndrome. Am J Hypertens 1998;11:523–31
16. Moan A, Nordby G, Rostrup M, Eide I, Kjeldsen SE. Insulin sensitivity, sympathetic activity, and cardiovascular reactivity in young men. Am J Hypertens 1995;8:268–75

Sympathetic predominance: The link between diabetes and cardiovascular disease?

2011-10-20T13:42:00.000-07:00

It has long been recognized that cardiac autonomic neuropathy increases morbidity and mortality in diabetes and may have greater predictive power than traditional risk factors for cardiovascular events. Significant morbidity and mortality can now be attributable to autonomic imbalance between the sympathetic and parasympathetic nervous system regulation of cardiovascular function (1)
It is also interesting to notice that plasma lactate was strongly associated with type 2 diabetes in older adults as demonstrated in a recent paper (2). According to the authors plasma lactate deserves greater attention in studies of oxidative capacity and diabetes risk.
Both lines of studies come in favour of our point of view (3, 4,5) where the sympathetic predominance represents the primary factor in the cascade of events leading to a higher lactic acid production that provokes an increased perfusion pressure and effects on contractility of coronary arteries resulting in changes in hemodynamic shear stress and atherosclerosis as consequence.
Carlos Monteiro
1. Vinik AI, Zieglert D. Autonomic imbalance: prophet of doom or scope for hope? Diabet. Med. 28, 643-651 (2011) Full free text at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123705/
2. Stephen O Crawford et al, Association of blood lactate with type 2 diabetes: the Atherosclerosis Risk in Communities Carotid MRI Study. International Journal of Epidemiology 2010;1–9. Free full text at http://ije.oxfordjournals.org/content/early/2010/08/25/ije.dyq126.full.pdf+html
3. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at http://aciditytheory.blogspot.com/2010/02/sympathetic-predominance-primary-factor.html
4. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
5. Association of lipid abnormalities with lactate and coronary artery disease progression. Carlos Monteiro, October 3, 2010 at http://aciditytheory.blogspot.com/2010/10/lactate-coronary-artery-disease-insulin.html

Some news.....

2011-09-28T05:43:00.000-07:00

David M Diamond* made in public the following declaration in the THINCS Forum on June 22, 2011: “Carlos, your thesis on stress, acidic environment and CHD is brilliant. Particularly impressive is how you relate reduced pH to increased oxidation of LDL, which increases its atherogenicity”
* Ph.D, Professor, Depts of Psychology and Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD. Director, University of South Florida, Neuroscience Collaborative)

Sympathetic Predominance: The link between erectile dysfunction, atherosclerosis and cardiovascular disease?

2011-09-23T07:54:00.000-07:00

Erectile dysfunction affects 40% of men above 40 year old, in some degree, and two thirds of men over 70 have significant symptoms of ED.
The association between erectile dysfunction and coronary artery disease (CAD) was suggested years ago, by observational studies. More recently it was found that erectile dysfunction is an early marker of CAD, as the canary in the coal mine*.
Indeed some studies have demonstrated that coronary atherosclerosis is more severe in patients with vascular ED, with the authors considering that ED may be an additional, early warning sign of coronary atherosclerosis (1).
A recent meta-analysis of prospective cohort studies, involving 36,744 participants, have suggested that ED significantly increases the risk of cardiovascular disease, coronary heart disease, stroke, and all cause mortality, and the increase is probably independent of conventional risk factors (2)
Erection is initiated through the parasympathetic nervous system, activation of which overrides the sympathetic tone that maintains the penis in a nonerectile (flaccid) state. This state is maintained mainly through the release of norepinephrine from penile adrenergic nerves. Norepinephrine contracts the vasculature and cavernosal smooth muscle. Arousal/erection is associated with a decrease of norepinephrine release in the penis, with a release of nitric oxide, and with a reduction in penile smooth muscle tone. Thus, nitric oxide is a mediator of the parasympathetic vasodilation in erectile function (3). So, when the parasympathetic system is continuously disabled there is a reduced production of NO.
Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. ED is associated with smoking, excessive alcohol intake, abdominal obesity, diabetes, hypertension and decreased antioxidant defenses, all of which reduce NO production (4,). Recent studies have discussed about the benefits of lifestyle interventions like healthier eating habits, getting exercise and avoiding smoke for improving erectile dysfunction (5) and also targeting CAD risk factors reduction (4, 6).
It is interesting to note that ED and atherosclerosis have many risk factors in common like ageing, physical inactivity, improper diet, psychological stress, cigarette smoking, high blood pressure and diabetes. In relation to this point there are diverse studies showing that: a) increased sympathetic activity and mental stress may affect erectile function with studies suggesting that an elevated central sympathetic tone may be one of the causes of psychogenic impotence (7, 8, 9); b) a study suggested that drugs acting within the central nervous system that reduce the sympathetic antierectile flow and enhance the parasympathetic proerectile flow to the penis may restore penile erection in cases of erectile dysfunction of both psychogenic and organic origin (10); c) other study have demonstrated that patients complaining of daytime sexual dysfunction and found by sleep-related erection monitoring to suffer from organic erectile dysfunction, have altered cardiac autonomic balance during both stages of sleep (11); d) A study has shown that men with idiopathic ED have evidence of endothelial dysfunction in forearm resistance vessels, increased pulse pressure and impaired heart rate variability. According the authors this support the concept that erectile dysfunction is a predictor of cardiovascular dysfunction and a precursor of clinical cardiovascular disease (13). e) and, finally, a very recent study have shown that patients with ED exhibited different heart rate variability compared with normal controls. This suggested to the authors that the patients with ED may have some kind of imbalance in the autonomic nervous system (ANS) and it may be possible that general imbalance of the ANS is one of the causes of ED (12).
Taking in view the above studies and our postulation that sympathetic predominance is the primary factor in the cascade of events leading to the atherogenic spiraling (14, 15), we have to assume that it really is the link between ED and cardiovascular disease.
14. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
15. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at http://aciditytheory.blogspot.com/2010/02/sympathetic-predominance-primary-factor.html
Carlos Monteiro

*As long as the canary still singing, it is all ok. However, a dead canary is a warning of a larger problem.

References:
1. Chiurlia E et al. Subclinical coronary artery atherosclerosis in patients with erectile dysfunction. J Am Coll Cardiol, 2005; 46:1503-6
2. Dong JY et al. Erectile dysfunction and risk of cardiovascular disease. Meta-analysis of prospective cohort studies. J Am Coll Cardiol, 2011; 58:1378-1385
3. Andersson K, Stief C. Penile erection and cardiac risk: pathophysiologic and pharmacologic mechanisms. Am J Cardiol. 2000 Jul 20;86(2A):23F-26F
4. Meldrum DR et al. The link between erectile and cardiovascular health: the canary in the coal mine. Am J Cardiol. 2011 Aug 15; 108(4): 599-606
5. Horasanli K et al. Do lifestyle changes work for improving erectile dysfunction? Asian J Androl, 2008; 10(1):28-35
6. Gupta PB et al. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: A systematic review and meta-analysis. Arch Intern Med, 2011. Published online September 12.
7. Junemann KP et al. Neurophysiological aspects of penile erection: the role of the sympathetic nervous system. Br J Urol, 1989 Jul;64(1):84-92
8. Pagani M. Hypertension, stress and erectile dysfunction: potential insights from the analysis of heart rate variability. Curr Med Res Opin, 2000; 16 Suppl1:s3-8
9. Diederichs W et al. The sympathetic role as an antagonist of erection. Urol Res. 1991;19(2):123-6
10. Allard J, Giuliano F. Central nervous system agents in the treatment of erectile dysfunction: how do they work? Curr Urol Rep 2001 Dec;2(6):488-94
11. Lavie P et al. Cardiac autonomic function during sleep in psychogenic and organic erectile dysfunction. J Sleep Res. 1999 Jun;8(2):135-42
12. Lee JY et al. Heart rate variability in men with erectile dysfunction. Int Neurourol J 2011;15:87-91. Full free text at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138849/pdf/inj-15-87.pdf
13. Stuckey BG, Walsh JP ET al. Erectile dysfunction predicts generalised cardiovascular disease. Evidence from a case control study. Atherosclerosis 2007, 194(2):458-6414.

The positive impact of humor and negative of stress over the vascular function

2011-09-05T12:26:00.000-07:00

Chronic stress is correlated with increases in stress hormones cortisol and cathecolamines. There is strong scientific evidence linking negative emotional states like depression, anxiety, or anger with increased risk for cardiovascular disease. However, much less is known about the association between positive emotional states, the so called eustress, like laughter and happiness. The nicest of all laughter types is associated with humor and it is specified as mirthful laughter.
In this respect there are some studies made by Berk and colleagues, from the Loma Linda University, demonstrating that in comparison with chronic stress mirthful laughter reduced the levels of Cortisol by 39%; adrenaline by 70% and dopac by 38%. The conclusion in one of their papers was that humor appears to attenuate catecholamines and MI recurrence and thus could be an effective adjunct in post-MI care (1, 2, 3).
On the other hand Michael Miller, from the University of Maryland, presented a study at the European Society of Cardiology in the 2011 Congress (4) highlighting the link between endothelial function and laughter. His study showed that when people laughed their major blood vessels dilated allowing for easier blood flow, that indicates a reduced risk of cardiac events.
Dr. Miller’s idea to study positive emotions such as laughter came after studies that had shown that mental stress caused blood vessels to constrict. His first study about sense of humor and coronary artery disease was published in 2001 (5). In other paper, published in 2009 (6), he told about the tests made to confirm the hypothesis that mirthful laughter also favorably affect endothelial dependent flow-mediated vasodilation (FMD). In this way volunteers were randomized for two different phases in a randomized-crossover design. One phase included watching a movie or segment of popular comedies (ex: Saturday Night Live) whereas a second phase was to view a movie known to promote mental stress (ex: The opening segment of “Saving Private Ryan”). The assessment of endothelial dependent vasoreactivity was performed using high resolution ultrasound of the brachial artery, also referred as brachial artery reactivity test (BART). A total of 160 BART measurements were performed and demonstrated a divergent effect after watching a movie provoking mental stress as compared to mirthful laughter. Specifically, a 35% reduction in FMD compared to baseline followed mental stress whereas a 22% increase in FMD occurred in response to laughter (7). In 2008, Dr. Miller and colleagues, in an oral presentation entitled “Positive emotions and the endothelium: Does joyful music improve vascular health?”, made at the American Association Scientific Sessions, on 11/11/2008, conclude that the cardiovascular benefits of music are similar to those found in their previous study of mirthful laughter (8)
Dr. Sugawara and colleagues in 2010 have confirmed the findings from Dr. Miller saying that their results suggest mirthful laughter elicited by comic movies induces beneficial impact on vascular function (9).
Again, in the presentation made by Dr. Miller at the ESC, 2011, volunteers watched segments of a funny movie, such as the farce “There's Something About Mary” on one day and on another day watched the opening segment of the stressful movie “Saving Private Ryan”. When study volunteers watched the stressful movie, their blood lining developed a potentially unhealthy response called vasoconstriction, reducing blood flow. Overall, in this time, more than 300 measurements were made with a 30-50% difference in blood vessel diameter between the laughter and mental stress phases (4).
We think the above studies give additional evidence to our acidity theory of atherosclerosis (10), that has the following sequence of events:
I. Sympathetic dominance by continuous stress plus
II. Deficiency in production of endogenous digitalis-like compounds (DLCs) with alterations of Na(+), K(+)-ATPase activity results in:
III. Lowered pH (acidity) that increases perfusion pressure and provokes effects on contractility of coronary arteries leading to changes in hemodynamic shear stress and atherosclerosis as consequence.
Sympathetic activation, metabolic acidosis and vascular reactivity The studies by Berk and Miller confirm previous studies suggesting that the sympathetic activation with elevation of circulating catecholamine (adrenaline, etc..), cause coronary vasoconstriction and consequent reduction in blood flow.
On the other hand it is interesting to notice that increased lactate (or decreased blood pH) may evoke vascular smooth muscle relaxation and increase of blood flow (11).
These opposite forces working in sequence - with the sympathetic overdrive leading to metabolic acidosis -, in our view, may be reconciled to partially explain the occurrence of the resulting abnormal stretching/relaxing of coronary arteries, in different directions, simultaneously, producing atherosclerosis (10).Carlos Monteiro

1. Berk LS, Tan SA and Berk B. Cortisol and cathecolamine stress hormone drecrease is associated with the behavior of perceptual anticipation of mirthful laughter. The FASEB Journal. 2008; 22;946.11
2. Tans SA, Berk LS et al. Humor as an adjunct therapy in cardiac rehabilitation, attenuates cathecolamines and myocardial infarction recurrence. Adv Mind Body Med 2007; 22(3-4): 8-12
3. Berk LS et al. The neuroendocrine and stress hormone changes during mirthful laughter. Am J Med Sci 1989;6:390-396
4. Miller M. Laughter and vascular function, ESC 2011.
5. Clark A, Seidler A, Miller M. Inverse association between sense of humor and coronary heart disease. Int J Cardiol. 2001 Aug; 80(1):87-8
6. Miller M, Fry WF. The effect of mirthful laughter on the human cardiovascular system. Med. Hypothesis 2009; 73(5):636 . Full free text at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814549/pdf/nihms-154943.pdf
7. Miller M, Mangano C, Park Y, et al. Impact of cinematic viewing on endothelial function. Heart 2006; 92:261-262
8. Miller M, Beach V, Mangano C, Vogel RA. Positive emotions and the endothelium: Does joyful music improve vascular health? American Association Scientific Sessions, on 11/11/2008
9. Sugawara et al. Effect of mirthful laughter on vascular function. Am J Cardiol 106:856-9 (2010).
10. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
11. Celotto AC, Capellini VK et al. Effects of acid-base imbalance on vascular reactivity. Brazilian Journal of Medical and Biological Research (2008) 41:439-445 Full free text at http://www.scielo.br/pdf/bjmbr/v41n6/7099.pdf

Is it LDL cholesterol unquestionably and unequivocally a causal risk factor for myocardial infarction?

2011-08-15T05:44:00.000-07:00

It is my pleasure to share the following point of view of Dr. David Diamond, researcher, scientist and professor from the University of South Florida – and our colleague from THINCs – about low density lipoprotein and its relationship with the incidence of myocardial infarction:

“If only it were that simple, then reducing LDL by any means would reduce and even eliminate MI from occurring, and enable people to live longer. However, serum cholesterol levels had been reduced with treatments long before statins were developed, first with corn oil, and then GI surgery and cholestyramine and then there were the statins, including Baycol and Torcetrapib, which reduced LDL and even raised HDL. Baycol and Torcetrapib were very effective as LDL reducing agents, but they were also very effective at killing people, which is why they are no longer on the market. So lowering LDL levels, alone, is not sufficient to reduce the incidence of MI and to enable someone to survive the treatment.

The question should be, why are elevated levels of LDL associated with MI? The answer is that LDL is not "bad cholesterol" which is destined to harm blood vessel walls and "clog arteries" as drug company ads incorrectly state. Part of the problem is that LDL gets glycated by glucose, which distorts the lipoprotein sufficiently that it can't bind to the LDL receptor. The glycated LDL molecule then accumulates in the blood and becomes oxidized. It is the oxidized LDL that contributes to the deterioration of the blood vessel wall, not the native (normal) LDL. How do you stop sugar from glycating LDL? Keep blood sugar low through exercise and a low carb diet - 2 rather simple strategies which have never been compared head-to-head to statins in a clinical trial for reducing CHD, perhaps because the outcome would be unappealing to the drug companies that sponsor this research.

The other way of looking at LDL and MI is that when LDL becomes oxidized and glycated it becomes ineffective at doing what it's supposed to do, which is to kill bacteria (yes, LDL is a part of the immune system) and to build new cells. In response to the increasing concentration of oxidized (ineffective) LDL, the liver makes more LDL, thereby raising the concentration of total serum LDL. This is actually why total LDL levels can correlate with MI incidence, but it's actually the synergy between high sugar diets and oxidized LDL (and high blood pressure) which causes to damage to artery walls.

So, it's not that LDL is inherently atherogenic. The LDL molecule is an essential part of optimal health, serving to work with white blood cells to kill pathogens and to rebuild damaged tissue. It is the oxidization of LDL, which is precipitated by stress, smoking, lack of exercise and a high sugar diet, that is atherogenic. The literature on this work is vast, but I cite at the end of this little article some papers showing that ox-LDL levels are a much better indicator of CHD than native LDL (1, 2, 3).

I have reviewed only a small part of the thousands of medical papers and dozens of books I've read on this subject. Based on my reading, and the findings of experts in the field, there is good reason to be skeptical about the claims that statins have enhanced cardiac health in the absence of substantial side effects. In my recent talk** I reviewed well-documented evidence published in highly respected medical journals of more extensive adverse side effects of statins than is typically reported in the drug company sponsored research papers. For a relatively small reduction of cardiac events in the treated population, the cost of statins financially and in terms of insufficient improvement in overall health and survival is unjustified.”
* David Diamond, Ph.D, is Professor from the Depts of Psychology and Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD. Director, USF Neuroscience Collaborative, 4202 E. Fowler Ave (PCD 4118G), Tampa, FL 33620. His homepage is http://psychology.usf.edu/faculty/diamond/
** The web article that summarizes his talk and includes the on-line video is at http://www.cas.usf.edu/news/s/176/
References:
1. Margareta Kristenson, Bo Ziedén, et al. Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50. BMJ 1997;314:629–33
2. Christa Meisinger, Jens Baumert, et al. Plasma Oxidized Low-Density Lipoprotein, a Strong Predictor for Acute Coronary Heart Disease Events in Apparently Healthy, Middle-Aged Men From the General Population. Circulation 2005;112;651-657
3. Huiling Huang, Weiyi Mai, Dan Liu, et al. The oxidation ratio of LDL: A predictor for coronary artery disease. Disease Markers 24 (2008) 341–349

Note:
In the acidity theory of atherosclerosis we support a link between LDL oxidation and acidic pH presenting different studies showing this relationship (1).
1. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at
http://www.infarctcombat.org/AcidityTheory.pdf

Hemodynamic shear stress, calcification and atherosclerosis

2011-07-20T07:34:00.000-07:00

Atherosclerosis calcification occurs at sites of atherosclerotic plaques, where there is a combination of cellular necrosis, inflammation and cholesterol deposition.
Ectopic vascular calcification was viewed until recently as a passive consequence of aging. Although it is recognized that ectopic vascular calcification is a consequence of a dysregulated process, the specific molecular etiology remains unclear. There are conflicting ideas regarding the mechanisms underlying cardiovascular calcification, and the pathological and prognostic importance of vascular calcification still a matter of debate (1).
Osteoporosis, that is associated with calcium deficiency, has been also associated with atherosclerosis in many studies, with findings that bone mineral density declined while atherosclerotic plaque increased. We have discussed about this subject during the last year advocating acidosis as the link between these two diseases (2).
Coronary artery calcification measured by computed tomography (CT scans) is considered a radiographic confirmation of atherosclerosis, predicting cardiovascular events, and has been evaluated as a surrogate measure in randomized trials. However, in a study published in 2009 the annual rate of CAC increase was measured in 10 trials having observed a rate of 17% which was seen as moderately higher for patients with chronic kidney disease and those receiving dialysis. The study observed no consistent or reproducible treatment effect of any therapy on this outcome. These data have suggested to the authors that CAC may not be a suitable surrogate target for treatment trials in patients with cardiovascular or renal disease when measured after 12 months or reported on an annualized basis (3)
Nevertheless a very recently study from MESA (Multi Ethnic Study of Atherosclerosis) has shown that even healthy patients with low-density lipoprotein cholesterol (LDL-C) are associated with adverse coronary heart disease events if their CT scans demonstrate calcium buildup in their coronary arteries. Of 5,627 participants who were not receiving any baseline lipid-lowering therapies 3,714 (66%) had LDL-C 130mg/dl. Among the persons with low LDC-C, older age, male sex, hypertension, diabetes and low HDL-C were associated with adverse events (4).
It is interesting to notice that increased calcium content in diets supplemented with cholesterol has been show to decrease atherosclerosis in rabbits. Also, some epidemiological studies suggested that high levels of calcium in drinking water may decrease atherosclerosis (5).
Hemodynamic shear stress and calcification
A recent study developed in Switzerland, aimed to investigate regional plaque morphology and using intravascular ultrasound and virtual histology in coronary artery bifurcations, found that segments on the contralateral wall of the bifurcation which have previously identified as regions with low shear stress not only exhibited a higher plaque burden but also a higher degree of calcification (6). An analogous relationship was suggested by previous studies indicating that mechanical forces play a role in aortic valve calcification. Since calcium deposits occur almost exclusively on the aortic surfaces of AV leaflets it has been hypothesized that adverse pattern of fluid shear stress on the aortic surface of AV leaflets promotes calcification (7,8,9)
In the acidity theory of atherosclerosis the hemodynamic shear stress is an important step in the process leading to atherogenesis (10).
Carlos Monteiro
1. Johnson RC, Leopold JA and Loscalzo J. Vascular calcification: Pathological mechanisms and clinical implications. Circulation Research 2006; 99: 1044 -1059. Full free text at http://circres.ahajournals.org/content/99/10/1044.full
2. Acidity: The link between atherosclerosis and osteoporosis, January 5, 2010 at http://aciditytheory.blogspot.com/2010/01/acidity-link-between-atherosclerosis.html
3. McCullow PA and Chinnayan KM. Annual progression of coronary calcification in trials of preventive therapies: A systematic review. Arch Intern Med 2009, 169 (22):2064-70. Full free text at http://archinte.ama-assn.org/cgi/reprint/169/22/2064
4. Blankstein R, Budoff MJ, Shaw LJ et al. Predictors of coronary heart disease events among asymptomatic persons with low low-density lipoprotein cholesterol. J Am Coll Cardiol, 2011;58:364-374
5. HSU HH and Culley NC. Effects of dietary calcium on atherosclerosis, aortic calcification, and icterus in rabbits fed a supplemental cholesterol diet. Lipids in Health and Disease 2006, 5.16. Full free text http://www.lipidworld.com/content/5/1/16
6. Toggweiler S, Urbanek N, Schoenenberger AW, Erne P. Atherosclerosis, 2010 Oct;212(2):524-7
7. Hoehn D, Sun L and Sucosky P. Role of pathologic shear stress alterations in aortic valve endothelial activation. Cardiovascular Engineering and Technology 2010, V1;N2: 165-178. Full free text at http://www.springerlink.com/content/f777qk521lr48237/
8. Ge L, Sotiropoulos F. Direction and magnitude of blood flow shear stresses on the leaflets of aortic valves: is there a link with valve calcification? J Biomech Eng 2010 Jan;132(1): 014505
9. Yap CH, Saikrishnan N, Tamilselvan G and Yoganathan AP. Experimental measurement of dynamic fluid shear stress on the aortic surface of the aortic valve of the aortic valve leaflet. Biomech Model Mechanobiol, 2011 Mar 18
10. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

The final evidence: Milk and dairy products prevent heart attacks!

2011-06-06T07:39:00.000-07:00

Dr. J. E. Crewe, in 1929, along with the Mayo Foundation, reported uniformly excellent results using whole milk in the treatment of tuberculosis, diseases of the nervous system, cardiovascular and renal conditions, hypertension, and in patients who are underweight, run-down, etc. Striking results were seen in diseases of the heart and kidneys and high blood pressure. The milk used was, in all cases, the only kind of milk available in those days—raw milk from pasture-fed cows, rich in butterfat. Dr. Crewe asserted that the only problem of using raw milk to treat these diseases, was that it was too simple. So, the therapeutic use of milk didn’t attracted the interest from his colleagues in their patients (1).
In 1991, the New Scientist magazine reported that Dr. Peter Elwood, director of the Epidemiology Unit of Landough Hospital in Penarth, South Glamorgan, in his study of lifestyle involving 5,000 men between the ages of 45 and 59, with a duration of 10 years, found that men who drank the most full-fat milk and ate butter (rather than margarine) had a lower risk of suffering from heart attacks! (New Scientist 1991; 129(1759):17). According to Dr. David Williams article published the same year, discussing the findings of Peter Elwood, among those who drank at least a pint of milk per day, only 1% suffered heart attacks (2, 3).
Dr. Peter Elwood, in a paper published in 2004, reported the data about the Caerphilly Study dietary data, including consumption of milk, were they have collected by a semiquantative food frequency questionnaire, during a period of 1979-1983. The group was followed by 20-24 years in a population sample of 2,512 men aged 45-49, with incident ischemic heart disease and stroke events identified. The study reached the conclusion that their data provide no convincing evidence that milk consumption is associated with an increased risk of vascular disease (4). At the same time and in the same issue of the European Journal of Clinical Nutrition he had published another study saying that no group studies have provided convincing evidence to date on the milk to be harmful (5).
In 2007, Peter Elwood and his group published another study concluding that the consumption of milk and other dairy products is associated with a markedly reduced prevalence of metabolic syndrome, and these items, therefore, would fit well within a healthy eating pattern (6).
More recently, in 2009, a survey conducted by the Universities of Reading, Cardiff and Bristol found by reviewing the evidence from 324 published studies that milk intake may reduce the chances of dying from diseases such as coronary heart disease and stroke, in 15-20% (7).
Contrary to what is usually advocated by conventional medicine, that saturated fats can lead to myocardial infarction, a very recent study found that nutrients in milk and its derivatives (cheese, butter) actually neutralize the effects of cholesterol that the researchers (still) consider harmful. Their findings, taken from 3630 middle-aged men and women from Costa Rica, have shown that the intake of dairy products in those that had myocardial infarction was not different from those who had not. Assessing about the amount of dairy food that was ingested by the participants in the Epidemiologic study between 1994 and 2004, there was no link between consumption and risk of myocardial infarction, even among those who consumed as much as 593 grams per day. This research (8), confirm the results of several other studies showing the benefits of milk and dairy products in cardiovascular disease.
Interestingly to note is that endogenous digitalis like compounds (DLCs), similar to the cardiotonics used to treat heart failure, were found in tissues and fluids of animals and humans with increased concentration in amniotic fluid, umbilical cord, serum and urine of pregnant women and neonates, the saliva of pregnant women, and in the milk collected from women during breastfeeding at different days after birth. According to an article published in 1992 DLCs could be secreted or concentrated in human milk providing to children with a exogenous contribution of DLCs to replace the endogenous production which tends to decrease after the first few weeks of life out of the womb. The authors have place in the article that additional studies were needed before the physiological actions in children be assigned to DLCs in human milk (9).
Certainly there are other mechanisms that could explain the benefits of the whole milk in the prevention of diseases. However, we believe that the increased concentration of DLCs in milk fits perfectly with our postulation that an insufficient production of endogenous DLCs, to attend the demand in some medical conditions such as coronary artery disease, can be resolved through the use of cardiac glycosides in low doses as a supplement. This is confirmed by clinical studies using cardiac glycosides in prevention of acute coronary syndromes (10).
Some other benefits of milk fat in atherosclerosis:
Milk fat, included among animal ones, does not impend over sclerosis, on the contrary, it prevent diseases of cardiovascular system, because it contains various bioactive constituents (11), that:
a) limit synthesis of liver cholesterol and triglycerides (short chain saturated fatty acids, Omega-3 polyunsaturated fatty acids, oleic acid);
b) intensify estrification and metabolism of cholesterol (phospholipids, oleic acid, Omega-6 and Omega-3 polyunsaturated fatty acids in optimal proportions);
c) prevent cholesterol oxidation (conjugated linoleic acid--CLA, alpha-tokoferol, coenzyme Q10, vitamins A and D3, phospholipids),
d) reduce level of LDL-cholesterol in blood plasma (linolenic acids Omega-3, linoleic acid W-6, also oleic acid).
e) Unique components of milk fat i.e. short chain saturated fatty, conjugated linoleic acid, vaccenic acid (natural trans isomer), and other milk components possess additionally anticancerogenic activity.
Moreover, the fatty acid series n-3 (or omega-3), through its ability to reduce blood lactic acid production (12), and butyric acid (GABA), which has an inhibitory effect on the sympathetic nervous system (13) may possibly reduce the progression of coronary atherosclerosis, according to the concepts of the theory of acidity in atherosclerosis (10).
As Peter Elwood and colleagues said recently, “An evaluation based upon a single risk factor for a disease can, however, be misleading. At the same time as affecting lipid markers of heart disease, the consumption of milk and dairy produce is associated with an increase in the level of high-density lipoprotein cholesterol and with a reduction in blood pressure and furthermore, milk and dairy food items are likely to have effects upon many other biological mechanisms and disease processes” (14)
Carlos Monteiro
Referências:
1) Real Milk Cures Many Diseases, Dr. J. R. Crewe, Certified Milk Magazine, January 1929, em http://www.realmilk.com/milkcure.html
2) Milk Decreases Heart Attacks? Dr. David Williams, Alternatives Newsletter, 1991 em http://www.realmilk.com/heart_disease.html
3) Fuss over fat leads to rethink on publicity, issue 1759 of News Scientist magazine, 09 March 1991, page 17. Texto integral em http://www.newscientist.com/article/mg12917592.800-fuss-over-fat-leads-to-rethink-on-publicity-.html
4) Milk drinking, ischaemic heart disease and ischaemic stroke I. Evidence from the Caerphilly cohort. Elwood PC, Pickering JE, Hughes J, Fehily AM, Ness AR, Eur J Clin Nutr. 2004 May;58(5):711-7.
5) Milk drinking, ischaemic heart disease and ischaemic stroke II. Evidence from cohort studies. Elwood PC, Pickering JE, Hughes J, Fehily AM, Ness AR. Eur J Clin Nutr. 2004 May;58(5):718-24.
6) Milk and dairy consumption, diabetes and the metabolic syndrome: the Caerphilly prospective study, Elwood PC, Pickering JE, Hughes J, Fehily AM, J Epidemiol Community Health. 2007 Aug;61(8):695-8. Texto integral gratuito em http://jech.bmj.com/cgi/reprint/61/8/695.pdf
7) The survival advantage of milk and dairy consumption: an overview of evidence from cohort studies of vascular diseases, diabetes and cancer. Elwood et al . Journal of the American College of Nutrition. 2009 V27, N6, &23S-734S em http://www.jacn.org/cgi/content/abstract/27/6/723S
8) Aslibekyan S, Campos H, Baylin A. Biomarkers of Dairy intake and the risk of heart disease. Nutr Metab Cardiovasc Dis. May 4, 2011
9) Endogenous Digitalis-Like Factors in Human Milk, Aldo Clerico, Anna Pad, Maria Grazia Del Chicca, Pascal Biver,’ and Ottavio Giampietro, Clin Chem 38/4, 504-506 (1992). Texto integral gratuito em http://www.clinchem.org/cgi/reprint/38/4/504.pdf
10) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
11) Atherogenic properties of milk fat: facts or myths?, Cichosz G. Przegl Lek 2007; 64 Suppl 4:32-4
12) Ogilve GK, Fettman MJ et al. Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: A double-blind, randomized placebo-controlled study, Cancer; 2000, 88: 1016-28.
13) Hayakawa K et al. Effect of a gamma-aminobutyric acid enriched dairy product on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats. Br. J. Nutr 2004; 92:411-417
14. Peter Elwood et al. The consumption of milk and dairy foods and the incidence of vascular disease and diabetes: An overview of the evidence. Lipids. 2010 Oct;45(10):925-39. Full free paper at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950929/?tool=pubmed

Lactic acid elevation: the link between rheumatoid arthritis and atherosclerosis?

2011-05-04T15:10:00.000-07:00

Rheumatoid arthritis (RA) is considered a systemic autoimmune disease. However, what triggers the onset of rheumatoid arthritis still unknown.
Patients with RA have a high prevalence of preclinical atherosclerosis independent of traditional risk factors, suggesting that chronic inflammation, and, possibly, disease severity are atherogenic in this population (1).
Regarding this matter an editorial published at Circulation Journal in 1999 have discussed about the many similarities shared by RA and atherosclerosis (2).
Recent investigations found that the atherosclerotic process begins very early in the course of rheumatoid arthritis with the study revealing a significant increase in intima-media thickness, an indicator of atherosclerosis, in just 18 months (3).
Other investigators found a rapid increase in myocardial infarction risk following diagnosis of RA amongst patients diagnosed between 1995 and 2006 (4)
Studying about the matter we have looked for studies investigating cardiovascular autonomic dysfunction in rheumatic diseases. Although there are few studies in this direction, we have noticed that the sympathetic nervous system activity may be elevated in RA compared with health patients (5, 6). According our view the sympathetic predominance is the primary factor in the cascade of events leading to increased lactic acid and acidic environment generating atherogenesis (7, 8).
Also, we have discovered a study from the eighties showing high values of lactate in seropositive RA and crystal-induced arthritis, with the author suggesting that synovial lactate measurement could be a reliable indicator for differentiating inflammatory arthritides (9). In parallel, the amount of lactate released by the myocardium has been shown to be related to the severity of coronary artery disease (10, 11).
Going deeper on our research I got very surprised with the following information from a paper published in 1924 (12), entitled “The alleged role of lactic acid in arthritis and rheumatoid conditions”, that says:
“In 1858 Richardson published the results of extensive experiments on dogs in which the injection of large quantities of lactic acid, intraperitoneally, was followed by severe joint involvement. The condition of the joints was similar to that seen in acute arthritis, and Richardson suggested that the arthritic syndrome was due to an accumulation of lactic acid in the body. This theory found further support in 1877, when Foster reported that the administration of lactic acid by mouth to two diabetic patients resulted in painful and swollen joints. The pain and swelling persisted as long as the lactic acid administration was continued and disappeared promptly after the acid was discontinued. These early experiments were apparently never repeated or extended but they have exerted some influence in the formation of hypotheses regarding the disease”.
This paper from 1924 strengthen our thoughts placed in the article “Old experiments with rabbits and dogs provide powerful evidence for the Acidity Theory of Atherosclerosis” where was shown that acid-fed rabbits and dogs may develop atherosclerotic lesions (13).
Carlos Monteiro
1. Roman M. J, et al. Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med. 2006; 144: 249-256. Full free text at http://www.annals.org/content/144/4/249.full.pdf+html
2. Vincenzo Pasceri and Edward Yeh. Editorial, “A tale of two diseases - Atherosclerosis and Rheumatoid Arthritis“, Circulation, 1999; 100:2124-2126. Full free text at http://circ.ahajournals.org/cgi/content/full/circulationaha;100/21/2124
3. Sodergren et al. Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness. Arthritis Research & Therapy 2010, 12:R158. Full free text at http://arthritis-research.com/content/12/4/R158
4. Holmqvist M. E. et al. Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006”, J Intern Med 2010; 268:578-585.
5. Aydemir , V. Yazisiz et al. Cardiac autonomic profile in rheumatoid arthritis and systemic lupus erythematosus. Lupus (2010) 19, 255—261.
6. Dekkers JC et al. Elevated sympathetic nervous system activity in patients with recently diagnosed rheumatoid arthritis with active disease. Clin Exp Rheumatol. 2004 Jan-Feb;22(1):63-70.
7. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
8. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at http://aciditytheory.blogspot.com/2010/02/sympathetic-predominance-primary-factor.html
9. Gobelet C and Gerster J. C. Synovial fluid lactate levels in septic and non-septic arthritides. Annals of the Rheumatic diseases, 1984, 43, 742-745.
10. G. Jackson, Lynne Atkinson, M. Clark, B. Crook, P. Armstrong, and S. Oram, Diagnosis of coronary artery disease by estimation of coronary sinus lactate. British Heart Journal, 1978, 40, 979-983 Full free text at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC483520/
11 Gertz EW, Wisneski JA, Neese R, Bristow JD, Searle GL, Hanlon JT: Myocardial lactate metabolism: evidence of lactate release during net chemical extraction in man. Circulation 1981, 63: 1273-1279. Full free text at http://circ.ahajournals.org/cgi/reprint/63/6/1273
12. F . A Cajori et al. The alleged role of lactic acid in arthritis and rheumatoid conditions. Arch Intern Med. 1924;34(4):566-572.
13. Old experiments with rabbits and dogs provide powerful evidence for the Acidity Theory of Atherosclerosis, Carlos Monteiro, July 13, 2010 at http://aciditytheory.blogspot.com/2010/07/old-experiments-with-rabbitsand-dogs.html

The potential positive effect of improvement in baroreflex function on prevention and treatment of atherosclerosis

2011-03-09T06:27:00.000-08:00

The baroreflex or baroreceptor reflex is one of the body’s homeostatic mechanisms for regulating blood pressure by controlling heart rate, strength of heart contractions, and diameter of blood vessels. The most important arterial baroreceptors are located in the carotid sinus and in the aortic arch. These baroreceptors respond to stretching of the arterial wall so that if arterial pressure suddenly rises, the walls of these vessels passively expand, which stimulates the activation of these receptors. If arterial blood pressure suddenly falls, decreased stretch of the arterial walls lead to a decrease in receptor activation. The loss of the stabilizing influence of vagal control raise the susceptibility to sympathetic influences. On the other hand the result of the baroreceptor improvement is the inhibition of the sympathetic nervous system and activation of the parasympathetic nervous system.
It is interesting to notice the impairment or decrease of baroreflex sensitivity in front of some key factors for atherosclerosis, cardiovascular disease and stroke, like in ageing, ingestion of sugars, in special high-fructose diets and smoking.
Related to atherosclerosis there are some studies showing that in bilateral carotid atherosclerosis (1) and in greater intima-media thickness (2) the baroreflex sensitivity is reduced or impaired.
In this direction a study published in 2005 have indicated that arterial baroreflex dysfunction promotes the development of atherosclerosis in rats, and that inflammation may be involved in this process (3). The same authors have demonstrated in a very recent publication that low dose ketanserin, an anti-hypertensive, prevented the development of atherosclerosis in spontaneous hypertensive rats and rabbits at least in part via enhancement of arterial baroreflex function (4). Other anti-hypertensive drugs like Beta blockers may also enhance baroreflex sensitivity (5) with positive effects on atherosclerosis (6). Digitalis glycosides, another class of drugs, also augments cardiopulmonary baroreflex control of sympathetic activity (7), that probably is responsible for potential benefic effects of digitalis on atherosclerosis (6,8,9).
Aside of the above mentioned drugs there are some recent studies suggesting that polyunsaturated fatty acids - PUFA (19), cacao (10), vitamins like vitamin C (11,12), vitamin E (13) and folic acid (14,15), apart of aerobic exercise (16,17) and slow breathing (18), improve baroreflex sensitivity with possible positive effects on the treatment or prevention of atherosclerosis according to the acidity theory of atherosclerosis point of view (6) where sympathetic predominance is the primary factor in the cascade of events leading to the atherogenic spiraling.
Carlos Monteiro

1. Nasr N et al. Baroreflex sensitivity is impaired in bilateral carotid atherosclerosis. Stroke, 2005;36:1891-1895
2. Gianoros PJ et al. Greater intima-media thickness in the carotid bulb is associated with reduced baroreflex sensitivity. Am J Hypertens. 2002; 15(6): 486-491
3. Cai GJ et al. Arterial baroreflex dysfunction promotes atherosclerosis in rats. Atherosclerosis, 2005 Nov; 183(1):41-7
4. Yu YS et al. Effects of low-dose ketanserin on atherosclerosis in rats and rabbits. Can J Pysiol Pharmacol 2010 Nov;88(11):1054-60
5. Truijen J et al. Baroreflex sensitivity is higher during acute psychological stress in healthy subjects under B-adrenergic blockade. Clin Sci (Lond), Feb 2011; 120(4):161-167
6. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
7. Schobel HP et al. 1991.Contrasting effects of digitalis and dobutamine on baroreflex sympathetic control in normal humans, Circulation V84, 1118-1129. Full free paper at http://circ.ahajournals.org/cgi/reprint/84/3/1118
8. Jagielska J. et al. Digitoxin elicits anti-inflammatory and vasoprotective properties in endothelial cells: Therapeutic implications for the treatment of atherosclerosis?, doi:10.1016/j.atherosclerosis.2009.03.019
9. Kolkhof P et al. Cardiac glycosides potently inhibit C-reactive protein synthesis in human hepatocytes. Biochem Biophys Res Commun. 2010 Mar 26;394(1):233-9. Epub 2010 Mar 3.
10. Akita M et al., Effects of cacao liquor polyphenols on cardiovascular and autonomic nervous functions in hypercholesterolaemic rabbits. Basic Clin Pharmacol Toxicol. 2008 Dec;103(6):581-7.
11. Kevin D. Monahan et al, Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men. Am J Physiol Heart Circ Physiol 286: H2113–H2117, 2004.
12. Gianfranco Piccirillo et al., Influence of Vitamin C on Baroreflex Sensitivity in
Chronic Heart Failure. Hypertension. 2003; 41:1240-1245.
13. Peter Studinger et al., Effect of vitamin E on carotid artery elasticity and baroreflex gain in young, health adults. Autonomic Neuroscience, V 113, I1, Pages 63-70; 2004
14. Béchir M et al., Folic Acid Improves Baroreceptor Sensitivity in Hypertension. J Cardiovasc Pharmacol;45:44–48), 2005
15. Xiu-juan MA et al, Clonidine, moxonidine, folic acid, and mecobalamin improve baroreflex function in stroke-prone, spontaneously hypertensive rats. Acta Pharmacol Sin 2007 Oct; 28 (10): 1550–1558
16. Deley G et al., Arterial baroreflex control of cardiac vagal outflow in older individuals can be enhanced by aerobic exercise training. Hypertension, 2009;53:826-832
17. Effects of long-term exercise training on cardiac baroreflex sensitivity in patients with coronary artery disease: a randomized controlled trial. Clin Rehabil. 2011 Mar;25(3):217-27
18. Carlos Monteiro, Slow breathing increases baroreflex sensitivity and reduces sympathetic activity with benefic effects to cardiovascular disease, August 9, 2010 at http://www.aciditytheory.blogspot.com/
19. Radaelli A, Cazzaniga M, Viola A, et al. Enhanced baroreceptor control of the cardiovascular system by polyunsaturated fatty acids in heart failure patients J Am Coll Cardiol 2006;48:1600-1606. Free full text at http://content.onlinejacc.org/cgi/reprint/48/8/1600.pdf

Infection through bacteremia leads to sympathetic overactivity and then to the atherosclerotic process

2010-11-03T12:20:00.000-07:00

Research long suggested infection to be a cause or to promote atherosclerosis. This idea is supported by many reports and epidemiological studies (1).
However, main trials using antibiotics have failed to prove their protective effects in secondary prevention of coronary artery disease (2).
Periodontal disease, one of the most common chronic bacterial infection, may represent a favorable scenario to verify the connection of infection and atherosclerosis/cardiovascular disease.
The first researchers to indicate a relationship between oral infections and atherosclerosis were Mattila and colleagues. In their study published in 1989 they have identified periodontal disease as an independent predictor of elevated risk of myocardial infarction (3).
Several studies are suggesting an oral source for atherosclerotic plaque - associated bacteria with demonstration about the presence of viable periodontal pathogens in atherosclerotic plaques (4, 5, 6, 7). In this regard an interesting hypothesis was proposed in 2004 that periodontal infection may lead to brief episodes of bacteremia with inoculation of atherosclerotic plaque by periodontal pathogens such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitants and Tannerela forsythensis (8).
Related to the subject a recent review says that clinical procedures by dentists on the teeth and periodontal, along with the daily brush made by patients, produce a transient bacteremia, which may cause a secondary infection in a distant tissue or organ, including arteries. For the authors of this review it is evident that both endodontic surgical procedures and non-surgical instrumentation of root channels during endodontia can produce a transient bacteremia. Also, they have stressed that a tooth extraction causes bacteremia in 100% of times (9).
Coincidently to the present matter a study published last month revealed data from Medicaid patients showing that the risk of adverse vascular events sharply increases in the month following invasive dental treatment and then gradually returns to normal over six months (10).
However, an important information is generally left aside by investigators studying the connection between oral infection and atherosclerosis/cardiovascular disease. These investigators don’t take in consideration that the sympathetic nervous system is intensely activated during bacteremia. This was demonstrated by studies showing that the sympathetic tone rapidly increases after the experimental injection or infusion of bacteria and similarly during bacteremia in humans (11, 12, 13, 14).
Moreover, in a systematic review published in 2007 about 57 per cent of studies reviewed showed a positive relationship between stress/psychological factors and periodontal disease (15). These results are reinforced by a very recent study indicating that the sympathetic nervous system is involved in the development of periodontitis and that blockade of beta-receptors in periodontal tissue by a sympatholitic (propranolol) inhibited osteoclast differentiation and prevented alveolar bone loss induced by Porphyromonas gingivalis (16)
In the acidity theory of atherosclerosis point of view the sympathetic predominance is the primary factor in the cascade of events leading to the atherogenic spiraling.
Therefore, we think infection through bacteremia can be added to the long list of risk factors for atherosclerosis/cardiovascular disease, as mentioned in the acidity theory paper and in other previous articles published in this blog (17).
Carlos Monteiro
1. Epstein SE, Zhou YF, Zhu J. Infection and atherosclerosis. Emerging mechanistic
paradigms. Circulation 1999;100:20–8.
2. Anderson JL. Infection, antibiotics and atherothrombosis: end of the road or new beginnings?, N Eng J Med 2005;352:1706-1709
3. Mattila K, Nieminen MS, Valtonen VV, et al. Association between dental health and acute myocardial infarction. Br Med J 1989;298:779–82.
4. Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of
periodontal pathogens in atheromatous plaques. J Periodontol 71:1554–1560, 2000
5. Stelzel M, et al. Detection of Porphyromonas gingivalis DNA in aortic tissue by PCR. J Periodontol 73:868–870, 2002
6. Kozarov EV, Dorn BR, Shelburne CE, Dunn WA, Jr, Progulske-Fox A. Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Arterioscler Thromb Vasc Biol 25:e17–e18, 2005
7. Gaetti-Jardim E, Jr, Marcelino SL, Feitosa AC, Romito GA, Avila-Campos MJ. Quantitative detection of periodontopathic bacteria in atherosclerotic plaques from coronary arteries. J Med Microbiol 58:1568–1575, 2009
8. Giacona MB, Papapanou PN, Lamster IB, Rong IL, D’Agati VD, Schmidt AM, and Lalla E. Porphyromonas gingivalis induces its uptake by human monocytes/macrophages and promotes foam cell formation in vitro. FEMS Microbiol Letter. 241, 95-101, 2004
9. Cotti E, Dessi C, Piras A, Mercuro G. Can a chronic dental infection be considered a cause of cardiovascular disease? A review of the literature. International Journal of Cardiology, 2010, doi 10.1016/j.ijcard.2010.08.011
10. Minassian C, D’Aiuto F, Hingoriani AD, Smeeth L. Invasive dental treatment and risk for vascular events. A self-controlled case series. Ann Intern Med 2010; 153:499-506
11. Palsson J, Ricksten SE, Delle M, Lundin S. Changes in renal sympathetic nerve activity during experimental septic and endotoxin shock in conscious rats. Circ Shock 1988; 24:13341.
12. Jones SB, Kovarik MF, Romano FD. Cardiac and splenic norepinephrine turnover during septic peritonitis. Am J Physiol 1986; 250:R8927.
13. Leinhardt DJ, Arnold J, Shipley KA, Mughal MM, Little RA, Irving MH. Plasma NE concentrations do not accurately reflect sympathetic nervous system activity in human sepsis. Am J Physiol 1993; 265:E2848.
14. Straub RH, Pongratz G, Weidler C, Linde HJ, Kirschning CJ, Glück T, Schölmerich J, Falk W. Ablation of the sympathetic nervous system decreases gram-negative and increases gram-positive bacterial dissemination: key roles for tumor necrosis factor/phagocytes and interleukin-4/lymphocytes. Infect Dis. 2005 Aug 15;192(4):560-72.
15. Daiane C. Peruzzo, Bruno B. Benatti, Glaucia M.B. Ambrosano, Getúlio R. Nogueira-Filho, Enilson A. Sallum, Márcio Z. Casati, and Francisco H. Nociti Jr. A Systematic Review of Stress and Psychological Factors as Possible Risk Factors for Periodontal Disease. Journal of Periodontology, August 2007, Vol. 78, No. 8, Pages 1491-1504
16. Okada Y, Hamada N, Kim Y, Takahashi Y, Sasaguri K, Ozono S, Sato S. Blockade of sympathetic b-receptors inhibits Porphyromonas gingivalis-induced alveolar bone loss in an experimental rat periodontitis model. Arch Oral Biol. 2010 Jul;55(7):502-8.
17. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

Association of lipid abnormalities with lactate and coronary artery disease progression

2010-10-03T19:07:00.000-07:00

Lactate as a screening test for coronary artery disease
The association of increased lipid levels with abnormal lactate metabolism may provide a useful screening test for the detection of coronary artery disease (1). In fact it was demonstrated that plasma lipid abnormalities and myocardial lactate production at the time of the initial study were significantly associated with subsequent arteriographic progression (2).
In our opinion the raise in plasma lipids presented in these studies might be a response to injury of the arterial endothelium due to an increased release of lactate. The response to injury concept is supported by the acidity theory of atherosclerosis (4)
Lactate and severity of coronary artery disease
The amount of lactate released by the myocardium has been shown to be related to the severity of coronary artery disease (1,2,3). One of these studies (3) have shown heterogeneity of myocardial lactate metabolism at rest in patients with coronary-myocardial disease. Lactate was released or produced by the myocardium when there was no clinical evidence of ischemia and the chemical arterial-coronary sinus lactate difference showing net global lactate extraction (3).
Carlos Monteiro
1. G. Jackson, Lynne Atkinson, M. Clark, B. Crook, P. Armstrong, and S. Oram, Diagnosis of coronary artery disease by estimation of coronary sinus lactate. British Heart Journal, 1978, 40, 979-983 Full free text at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC483520/
2. Bemis CE, Gorlin R, et al. Progression of coronary artery disease: A clinical arteriographic study. Circulation, Vol XLVII, March 1973. Full free text at http://circ.ahajournals.org/content/47/3/455.full.pdf
3. Gertz EW, Wisneski JA, Neese R, Bristow JD, Searle GL, Hanlon JT: Myocardial lactate metabolism: evidence of lactate release during net chemical extraction in man. Circulation 1981, 63: 1273-1279. Full free text at http://circ.ahajournals.org/cgi/reprint/63/6/1273
4. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

Does serum lactic acid and lactate dehydrogenase (LDH) levels increase with age?

2010-09-05T01:55:00.000-07:00

Loiseleur and Morel were the first to report in 1931 about an increase of serum lactic acid with age (1).
However, in a study by Gottfried, Pelz and Clifford published in 1961 it was observed no difference in serum lactic acid levels between a group of 49 men and women over 70 years of age and a control group under 50 years of age (2).
Also, Davis and colleagues in a study published in 1966 have reported that serum lactic acid does not increase with age. In two groups of ambulatory patients with average age of 67 years, totaling 544 subjects who were free of overt acute diseases, the regression analysis for both serum lactic acid and LDH not revealed any significant change (3).
Contrasting with the reports from Gottfried (2) and Davis (3), a study by Nagamine and Shima published in 1989 indicated from the serum chemical analysis, obtained from 1822 male and 1870 women outpatients, the values for LHD were higher in female over 50 years of age than in their counterpart. When male and female were combined the normal reference ranges for LDH tended to be elevated. The values for total cholesterol and triglyceride reached a peak at a certain age (4).
Taking in view the conflicting results in the above mentioned papers, we think that new investigations are warranted in order to definitively clarify if serum lactic acid and LDH are increased with ageing, if there is correlation with cholesterol levels, and about the potential of causal relations, as preached by the acidity theory of atherosclerosis (5).
Recalling O. J. Pollak, 1952:
“Certainly all tissues change with age. There is anatomic and chemical aging. The acidity of tissues increases with age; this favors the precipitation of cholesterol”
Carlos Monteiro
1. Loiséleur J and R Morel. Influence de l’age et de L’état fonctionnel du foie sur la lacticémie. C. R. Soc. Biol, Paris, 106:35-37, 1931
2. Gottfried S. P., K. S. Pelz and R. C. Clifford. Carbohydrate metabolism in healthy old men over 70 years of age. Amer J. med. Sci, 242: 475-480, 1961
3. Davis R. L., Lawton A. H. et al. Serum lactate and lactic dehydrogenase levels of aging males. J. Gerontology 1966, Oct 21(4):571-4
4. Nagamine Y, Shima K. Changes in normal reference ranges for serum chemical analyses with ageing. Nippon Ronen Igakkai Zasshi. 1989 Jan;26(1):31-6.
5. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

Migraine, cardiovascular disease and higher lactic acid concentration in plasma

2010-08-25T09:25:00.000-07:00

People with migraine, particularly those with aura (temporary visual or sensory disturbances before or during a migraine headache) , are at increased risk of death from coronary heart disease and stroke, according to research published this week on the the British Medical Journal. The study assessed the impact of mid-life migraine episodes in 18,725 men and women born between 1907 and 1935 who took part in the Reykjavik Study (set up in 1967 by the Icelandic Heart Association to study heart disease in Iceland). In total the research team explored over 470,000 person-years of data with a follow-up of 26 years. Their conclusion was that migraine with aura is an independent risk factor for cardiovascular and all cause mortality in men and women(1).
Interesting is that migraine suffers have higher lactic acid concentration in plasma (2), a decisive risk factor for cardiovascular disease, according to the acidity theory of atherosclerosis (3).
Carlos Monteiro
1.Larus S Gudmundsson, Ann I Scher, Thor Aspelund, Jon H Eliasson, Magnus Johannsson,Gudmundur Thorgeirsson, Lenore Launer and Vilmundur Gudnason. Migraine with aura and risk of cardiovascular and all cause mortality in men and women: prospective cohort study. Published 24 August 2010, doi:10.1136/bmj.c3966, BMJ 2010;341:c3966. Full free text at http://www.bmj.com/cgi/content/full/341/aug24_1/c3966
2.Okada H, Araga S, Takeshima T, Nakashima K. Plasma lactic acid and pyruvic acid levels in migraine and tension-type headache. Headache. 1998 Jan;38(1):39-42.
3.Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

Slow breathing increases baroreflex sensitivity and reduces sympathetic activity with beneficial effects on cardiovascular disease

2010-08-09T11:34:00.000-07:00

Control breathing have been used as an effective strategy to calm down during stressful situations in daily life during centuries. The usual advice to “take a deep breath” under emotion circumstances such as stress, anxiety and anger is a clear indication of this, yet we do not normally stop to consider the connection between our breathing and emotional states. There is a study realized in Japan where two hundred and forty-one male and female undergraduates completed the questionnaire concerning stressful events in the real life and relaxation strategies they used to overcome these stressful events. The result clearly showed that the most numerous relaxation strategy was deep breathing. About 60% of subjects reported that they control breathing to calm down in their stressful situation. Many subjects have answered this question telling that abdominal breathing technique (diaphragmatic) was an effective strategy to calm down (1).
Relaxation through slower breaths ( fewer than 10 cycles per minute) , used in relaxation techniques like yoga and meditation, have been thought for a long time to have positive effects in the reduction of blood pressure.
Basic studies which support these empirical and clinical observations and looking to clarify the relationship between relaxation and respiratory functions, were started in the 1970s. A paper published in 1996 in Psychosomatic Medicine have referenced many of these basic studies in discussing about the therapeutic usages of the slowed respiration maneuver in attenuating the cardiac autonomic responses in patients with anxiety disorder (2).
However, despite the many clinical observations suggesting this direction, the medical science in general, particularly in cardiology, have overlooked about the influence of breathing and its relationship with the autonomic nervous system and the heart in weighing cardiac risk factors.
Fortunately, recent studies are shedding more light and evidences to the subject giving new grounds for the scientific establishment regarding the link breathing/emotional states. Their findings show that sympathetic activation and parasympathetic withdrawal is implicated in the pathogenesis of hypertension, obstructive sleep apnea, and congestive heart failure and that respiration contributes importantly to the decrease of sympathetic hyperactivity and the improvement of baroreflex sensitivity (3 - 13).
It is interesting to notice what Dr. William Davis, cardiologist and author of “The Heart Scan Blog”, said recently in an invited response to the article by Jimmy Moore “A Reader Asks ‘Does Acidic Blood Lead To Arterial Inflammation?’ Let’s Ask The Low-Carb Experts (14): “One final thought: Interestingly, the easiest and fastest way to increase the alkaline state of the blood is to breathe deeply. Deep breathing results in lower carbon dioxide in the blood, resulting in net alkalinization. Wouldn’t it be neat if we could study and quantify this response over time and its effects on atherosclerotic disease?”
Also interesting is that while some studies have documented greater total muscle sympathetic nerve activity (MSNA) during hypercapnia compared with hypoxia, other studies observed a higher MSNA response to hypoxia compared with hypercapnia in participants with slow and fast spontaneous breathing rates. Whereas the authors were unable to distinguish between chemo reflex, respiratory or cardiovascular induced activation their data suggest that hypercapnia and hypoxia cause distinct patterns of activation within regions normally associated with sympathetic control (15, 16).
Taking in view that continuous positive airway pressure treatment may reverse early signs of atherosclerosis (17) we think the slow breathing practice may also contribute for the prevention or regression of atherosclerosis, by reducing the sympathetic hyperactivity, be it stimulated by hypercapnia, hypoxia or other factors, according to the acidity theory concept (18, 19).
Moreover, hypertension is an important risk factor for the development of atherosclerosis, with these processes sharing some common mechanisms. The endothelium is usually placed as a probable central focus for the effects in both diseases, with evidences leading to the postulation that hypertension predispose and accelerate atherosclerosis (20).
Carlos Monteiro
Remarks:
Transcendental Meditation not only lowers colesterol (21) and blood pressure (22, 23) but also reduce atherosclerosis (18). Most interesting is that a meta-analysis of 31 studies found that TM produces a lowering of plasma lactate (24, 25). Lower plasma lactate indicates profound relaxation, since high concentrations of lactate have been associated with stress situations (for example high anxiety), and high blood pressure (20). More data about lactate, stress, hypertension and reduction of atherosclerosis on patients submitted to Ioga or TM at the acidity theory of atherosclerosis article (18).
1. Yutaka Haruki, I Homma, Akio Umezawa, Y Hasaoka. Facilitation and Emotion of Breathing During Changes in Emotion, Chapter by Akio Umezawa, Book Respiration and Emotion, Springer, 2001
2. Sakakibara M and Hayano J. Effect of Slowed Respiration on Cardiac Parasympathetic Response to Threat. Psychosomatic Medicine 58:32-37 (1996). Full free text at http://www.psychosomaticmedicine.org/cgi/reprint/58/1/32.pdf
3. Clark ME, Hirschman R., Effects of paced respiration on anxiety reduction in a clinical population, Biofeedback Self Regul. 1990 Sep;15(3):273-84.
4. Meles E, Giannattasio C, et al. Nonpharmacologic treatment of hypertension by respiratory exercise in the home setting, Am J Hypertens. 2004 Apr;17(4):370-4
5. Grossman E, Grossman A, et al. Breathing-control lowers blood pressure, Hum Hypertens. 2001 Apr;15(4):263-9.
6. Viskoper R, Shapira I et al. Nonpharmacologic treatment of resistant hypertensives by device-guided slow breathing exercises. Am J Hypertens. 2003 Jun;16(6):484-7.
7. Schein MH, Gavish B, et al. Treating hypertension with a device that slows and regularises breathing: a randomised, double-blind controlled study, J Hum Hypertens. 2001 Apr;15(4):271-8.
8. Elliot WJ, Izzo JL Jr, et al. Graded blood pressure reduction in hypertensive outpatients associated with use of a device to assist with slow breathing. J Clin Hypertens (Greenwich). 2004 Oct;6(10):553-9; quiz 560-1.
9. Oneda B, Ortega KC et al. Sympathetic nerve activity is decreased during device-guided slow breathing, Hypertension Research 33, 708-712 (July 2010) | doi:10.1038/hr.2010.74
10. Anderson DE, McNeely JD, Windham BG. Regular slow-breathing exercise effects on blood pressure and breathing patterns at rest, J Hum Hypertens. 2010 Mar 4. [Epub ahead of print]
11. Joseph CN, Porta C, et al. Slow Breathing Improves Arterial Baroreflex Sensitivity and Decreases Blood Pressure in Essential Hypertension, Hypertension 2005;46;714-718; originally published online Aug 29, 2005
12. Narkiewicz K et al. Sympathetic Neural Outflow and Chemoreflex Sensitivity Are Related to Spontaneous Breathing Rate in Normal Men. Hypertension 2006;47;51-55; originally published online Dec 12, 2005
13. Bernardi L, Porta C, Slow Breathing Increases Arterial Baroreflex Sensitivity in Patients With Chronic Heart Failure, Circulation 2002;105;143-145
14. Jimmy Moore “A Reader Asks ‘Does Acidic Blood Lead To Arterial Inflammation?’ Let’s Ask The Low-Carb Experts!”, published at http://livinlavidalowcarb.com/blog/?p=7270, in February 10, 2010:
15. Bernardi L, Gabutti A et al. Slow breathing reduces chemoreflex response to hypoxia and hypercapnia, and increases baroreflex sensitivity, Journal of Hypertension, V 19;I 12 - pp 2221-2229, 2001
16. Steinback C. et al. Hypercapnic vs. hypoxic control of cardiovascular, cardiovagal and sympathetic function, Am J Physiol Regul Integr Comp Physiol 296: R402-R410, 2009
17. Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi-Filho G. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 2007; 176: 706–712.
18. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
19. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at http://aciditytheory.blogspot.com/2010/02/sympathetic-predominance-primary-factor.html
20. Hypertension, atherosclerosis, stress and lactic acid, Carlos Monteiro,
Friday, November 27, 2009 at http://aciditytheory.blogspot.com/2009/11/hypertension-atherosclerosis-stress-and.html
21. Cooper M, Aygen M. Transcendental Meditation in the management of hypercholesterolemia, Journal of Human Stress 1979; 5:24-27
22. Schneider RH, Staggers F, Alexander C, et al. A randomized controlled trial of stress reduction for hypertension in older African Americans. Hypertension 1995; 26: 820-827
23. Alexander C, Schneider RH, Staggers F. A trial of stress reduction for hypertension in older African Americans (part II); sex and risk factor subgroup analysis, Hypertension 1996; 28:228-237
24. Michael C. Dillbeck, David W Orme-Johnson. Physiological differences between meditation and rest. American Psychologist, Vol 42(9), Sep 1987, 879-881
25. The Effects of the Transcendental Meditation Technique on Common Risk Factors and Overall Health. Adapted from Chalmers, R. Scientific Research on Maharishi's Vedic Approach to Health: Part I Transcendental Meditation Introduction and Overview of Research, January 1998, at http://www.tm.cme.edu/article.pdf

Obstructive sleep apnea: Intermittent hypoxia leads to sympathetic overactivity and then to atherosclerotic process

2010-07-26T07:56:00.000-07:00

Obstructive sleep apnea (OSA) syndrome is caused by upper airway collapse during inspiration, causing intermittent hypoxemia, hypercapnia, acidosis, sympathetic nervous system activation, and arousal from sleep.
Mounting evidence shows that OSA is a risk factor for cardiovascular disease which is supported by epidemiological association studies. Longitudinal cohort studies also provide evidence that patients with untreated severe sleep apnea have an increased rate of cardiovascular events. The prevalence of coronary artery disease (CAD) is 3 to 5 times higher in patients with OSA compared with control populations (1, 2, 3, 4, 5, 6, 7).
Atherosclerosis is recognized as the precursor stage of coronary-myocardial disease.
A very recent paper published in Circulation Journal (8), by far the largest study to date, has showed that moderate to severe obstructive sleep apnea increases the risk of coronary heart disease or death by 68% in men under the age of 70, but does not increase the risk for men over 70 or for women. A total of 1927 men and 2495 women 40 years of age and free of coronary heart disease and heart failure at the time of baseline polysomnography were followed up for a median of 8.7 years in this prospective longitudinal epidemiological study.
Increased carotid intima-media thickness (IMT) and plaque occurrence was reported in OSA patients without any other significant co-morbidity compared to matched controls (9, 10, 11, 12).
The prevalence of hypertension is very high and the incidence of hypertension increases as the number of apneic and hypopneic events per hour rises. The association of OSA and hypertension has additive effects on the development of atherosclerosis. Daytime hypertension develops secondary to the persistently elevated sympathetic state (13). In a recent study of 94 middle-aged patients, the intima-media thickness of carotid artery was positively related to systolic blood pressure and apnea-hypopnea index (14).
Pathophysiological mechanisms linking OSA to atherosclerosis
OSA patients experience intermittent hypoxaemia and CO2 retention that modify the autonomic and haemodynamic responses to sleep (15). Indeed, chronic intermittent hypoxia may lead to sympathetic overactivity (16, 17). A study has shown that with mild apneic events (duration < 20 seconds), pretreatment with 100% oxygen effectively eliminated most of the increase in sympathetic nerve activity (25).
It is interesting to notice that continuous positive airway pressure treatment may reverse early signs of atherosclerosis (18).
There is increasing evidence that intermittent hypoxia is independently associated with dyslipidemia (19). In addition to clinical data, animal experiments also support a role of intermittent hypoxia in the pathogenesis of dyslipidaemia in sleep-disordered breathing (20, 21, 22).
The studies above mentioned confirm old experiments performed on rabbits where oxygen deficiency was attained by placing the animals daily into a chamber with decreased oxygen content (down to 12%) for 3–6 hours, for 4 months. It was shown that prolonged hypoxia brings about a high hypercholesterolemia and greatly intensifies the development of aortic and coronary atherosclerosis (26).
The demonstration that chronic intermittent hypoxia may lead to sympathetic overactivity and dyslipidemia adds more evidence to the acidity theory concept (23), with intermittent hypoxemia joining to other key factors for atherosclerosis, as discussed recently in this blog (24).
Carlos Monteiro
1. Levy P, Pepin JL, McNicholas WT. Should all sleep apnoea patients be treated? Yes. Sleep Med Rev 2002; 6:17–26.
2. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea–hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005; 365: 1046–1053.
3. Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, et al. Ambulatory blood pressure after therapeutic and sub therapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet 2002; 359: 204–210.
4. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365:1046-1053.
5. Unruh ML, Enright PL, Polak JF, et al. The relationship of sleep apnea to carotid wall thickness among a large cohort of older adults. Sleep. 2005;20:A112.
6. Peker Y, Hedner J, Kraiczi H, Loth S. Respiratory disturbance index: an independent predictor of mortality in coronary artery disease. Am J Respir Crit Care Med. 2000;162:81-86.
7 Mooe T, Franklin KA, Holmstrom K, Rabben T, Wiklund U. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med. 2001;164:1910-1913.
8. Daniel J. Gottlieb et al. Prospective Study of Obstructive Sleep Apnea and Incident Coronary Heart Disease and Heart Failure. The Sleep Heart Health Study. Circulation, Published online before print July 12, 2010
9. Drager LF, Bortolotto LA, Lorenzi MC, Figueiredo AC, Krieger EM, Lorenzi-Filho G. Early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 2005; 172: 613–618.
10. Baguet JP, Hammer L, Levy P, et al. The severity of oxygen desaturation is predictive of carotid wall thickening and plaque occurrence. Chest 2005; 128: 3407–3412.
11. Minoguchi K, Yokoe T, Tazaki T, et al. Increased carotid intima–media thickness and serum inflammatory markers in obstructive sleep apnea. Am J Respir Crit Care Med 2005; 172: 625–630.
12. Baguet JP, Hammer L, Levy P, Pierre H, Launois S, Mallion JMv, et al. The severity of oxygen desaturation is predictive of carotid wall thickening and plaque occurrence. Chest 2005; 128: 3407-12.
13. Narkiewicz K, Somers VK. Sympathetic nerve activity in obstructive sleep apnoea. Acta Physiol Scand. 2003;177:385-390
14. Drager LF, Bortolotto LA, Krieger EM, Lorenzi-Filho G. Additive effects of obstructive sleep apnea and hypertension on early markers of carotid atherosclerosis. Hypertension 2009; 53 : 64-9.
15. Somers VK, Dyken ME, Mark AL, Abboud FM. Sympathetic nerve activity during sleep in normal subjects. N Engl J Med 1993; 328 : 303-7.
16. Johnson, T. S., J. B. Young, and L. Landsberg. Sympathoadrenal responses to acute and chronic hypoxia in the rat. J. Clin. Invest. 71: 1263-1272, 1983.
17. Greenberg HE, Sica A, Batson D, Scharf SM. Chronic intermittent hypoxia increases sympathetic responsiveness to hypoxia and hypercapnia. J Appl Physiol 1999; 86: 298–305. Full free text at http://jap.physiology.org/cgi/content/full/86/1/298
18. Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi-Filho G. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 2007; 176: 706–712.
19. Drager, Luciano F; Jun, Jonathan; Polotsky, Vsevolod Y. Obstructive sleep apnea and dyslipidemia: implications for atherosclerosis. Curr Opin Endocrinol Diabetes Obes. 2010 Apr;17(2):161-5.
20. Li J, Grigoryev DN, Y e SQ, Thorne L, Schwartz AR, Smith PL, et al. Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol 2005; 99 :
1643-8.
21. Li J, Thorne LN, Punjabi NM, Sun CK, Schwartz AR, Smith PL, et al. Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 2005; 97 : 698-706.
22. Li J, Savransky V, Nanayakkara A, Smith PL. O’Donnell CP, Polotsky VT. Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia. J Appl Physiol 2007; 102 : 557-63.
23. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
24. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at http://aciditytheory.blogspot.com/2010/02/sympathetic-predominance-primary-factor.html
25. Leuenberger U, Jacob E, Sweer L, Waravdekar N, Zwillich C, Sinoway L. Surges of muscle sympathetic activity during obstructive apnea are linked to hypoxemia. J Appl Physiol 1995;79:581– 8.
26. N. N. Kipshidze.The effect of oxygen deficiency on the development experimental atherosclerosis of the coronary arteries Bulletin of Experimental Biology and Medicine, Volume 47, Number 4, 447-453, 1958, DOI: 10.1007/BF00779624

Old experiments with rabbits and dogs provide powerful evidence for the Acidity Theory of Atherosclerosis (1)

2010-07-13T20:47:00.000-07:00

Follows a summary about 2 studies from the beginning of the last century showing that acid-fed rabbits and dogs may develop atherosclerotic lesions:
1) Experiments from Oswald Loeb, a well-known professor in pharmacology and scientist from the University of Gottingen - Germany, have demonstrated in study published in 1913, that lactic acid-fed rabbits and dogs have resulted in atherosclerotic lesions in these animals (2). The book “Arteriosclerosis and hypertension, with chapters on blood pressure" (3), by Louis M Warfield, M. D. (Johns Hopkins), showed the following commentary about the experiments from Oswald Loeb:
“Oswald Loeb produced changes in the arteries of rabbits by feeding them sodium lactate (lactic acid). His controls fed on other acids became cachectic, but showed no arterial changes. He further found that in 100 gm. of human blood there was normally from 15 to 30 mg. of lactic acid. After heavy work, he found as much as 150 gm. He considers that after adrenalin or nicotin injections, the function of the liver is so disturbed that lactic acid is not bound. The arteriosclerosis is actually due to the presence of free lactic acid in the circulation. He succeeded, also, in producing lesions of the intima in a dog fed for a long time on protein poor diet, plus lactic acid and sodium lactate.”
2) I. Adler, M.D., from the Laboratories of the New York Board of Health, told in his paper entitled “Studies on Experimental Atherosclerosis” (4), published in 1913, that a casual remark by Dr. P. A. Levene have suggested the simple procedure of adding dilute hydrochloric acid to the dog's food and thus producing a chronic hyperacidity. This led Adler to include acid-fed dogs in his experiments. He told in his paper that though only two dogs have thus far been fed with hydrochloric acid, presenting sclerotic affections, the possibility can not be denied, especially in view of the numerous negative results with other methods, that these positive results are not mere coincidences, but are probably due to the hydrochloric acid. Referring at the end of his paper about the acid-fed dogs presenting atherosclerotic lesions he stated “that the work is being continued, and definite conclusions would at this stage be premature; but perhaps it may be permitted, even now, to venture the statement that in all probability the theory which bases atherosclerosis on a purely mechanical etiology will not prove tenable. Whether mechanical factors come into play at all, and if so, to what extent, remains to be seen. It seems almost certain, at least in our present state of knowledge, influences, subject possibly to more or less nerve control, are dominant factors in the etiology of atherosclerosis. Perhaps it may be discovered also that cholesterin and its various modifications and combinations, while undoubtedly an element of importance in atherosclerosis of the rabbit and human beings, may not be the sole predominant etiological factor.“. He finished telling that “If it should turn out that so simple a procedure as adding a certain proportion of hydrochloric acid to the food of dogs is sufficient to produce lesions of the blood vessels closely analogous, if not wholly identical with human atherosclerosis, a revision of our present theories will become necessary“.
Carlos Monteiro
1. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
2. Loeb, O., Ueber experimentelle Arterienveraender ungen mit besonderer Beruecksichtigung der Wirkung der Milchsaeure auf Grund eigener Versuche, Deutsch. med. Wchnschr., 1913, xxxix, I819
3. Louis M Warfield, M. D., Third Edition, C. V. Mosby Company, 1920, with full free text at http://www.archive.org/stream/arteriosclerosis00warfuoft/arteriosclerosis00warfuoft_djvu.txt.
4. I. Adler, ‘Studies in Experimental atherosclerosis - A preliminary report’, The Journal of Experimental Medicine, 1913. Free full text at http://jem.rupress.org/content/20/2/93.full.pdf

Cigarette smoking in the development and progression of atherosclerosis: Is sympathetic overactivity the key factor to explain this association?

2010-05-05T11:32:00.000-07:00

Sympathetic overactivity seems, in our point of view (1), to be the key factor in cigarette smoking as responsible for the development and progression of atherosclerosis.
Cigarette smoking increases efferent sympathetic nerve traffic acutely, as well norepinephrine and epinephrine release. The adverse effects of cigarette smoking are related to the mixture of chemicals, including nicotine that has been largely accused for many of the adverse effects of smoking on the cardiovascular system, including autonomic imbalance, endothelial dysfunction and coronary blood flow dysregulation. The acute sympathoexcitatory effects of smoking on the cardiovascular system are partially mediated by catecholamine release, muscle sympathetic nerve excitation and peripheral chemoreceptor sensitivity increase, consecutive to nicotinic receptor stimulation in the autonomic nervous system (2).
Both active smoking and exposure to enviromental tobacco smoke are associated with the progression of atherosclerosis as indexed by intimal-medial thickness of the carotid artery assessed by ultrasound (8)
It is interesting to notice about the results from a study published in 2006 revealing that sublingual administration of a 4-mg tablet of Nicotine Replacement Therapy exerts acute deleterious cardiovascular effects and sympathetic activation (3).
Also interesting is the high sugar content (up to 20% - including high fructose corn syrup) of the popular brands of cigarettes (4,5). Sugars and other high-carbohydrate diets, particularly in the form of high-glycemic index carbohydrate, may also contribute for keeping the sympathetic nervous system overactive as discussed recently in this blog (6,7).
Carlos Monteiro
1. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
2. Adamopoulus D, van de Borne P and Argacha JF, New insights into the sympathetic, endothelial and coronary effects of nicotine. Clin Exp Pharmacol Physiol 2008; 35(4): 458-63
3. Najem B et al. Acute cardiovascular and sympathetic effects of nicotine replacement therapy. Hypertension 2006; 47:1162-67 Full free text at http://hyper.ahajournals.org/cgi/content/full/47/6/1162
4. Elson LA, Betts TE, Passey RD, The sugar content and the pH of the smoke of cigarette, cigar, and pipe tobbacos in relation to lung cancer. International Journal of Cancer, V 9, I 3; 666-675, 1972
5. Stavanja et al. Safety assessment of high fructose corn syrup (HFCS) as an ingredient added to cigarette tobacco. Exp Toxicol Pathol, 57(4): 267-81, 2006
6. Koop W. Chronically increased activity of the sympathetic nervous system: our diet-related “evolutionary” inheritance. The Journal of Nutrition, Health & Aging Volume 13, Number 1, 2009
7. Carlos Monteiro, Fermentable carbohydrates: A link between periodontal disease and cardiovascular disease? Thursday, April 15, 2010 at http://aciditytheory.blogspot.com/2010/04/fermentable-carbohydrates-link-between.html
8. Howard G et al, Cigarette smoking and progression of atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) Study. JAMA, 1998 Jan 14;279(2):119-24. Full free text at http://jama.ama-assn.org/cgi/reprint/279/2/119.pdf

Fermentable carbohydrates: A link between periodontal disease and cardiovascular disease?

2010-04-15T06:04:00.000-07:00

The first paper to indicate a link between dental disease and heart disease was wrote by Cleave and Campbell in 1966. In their article these researchers have postulated that excessive fermentable carbohydrates could led to both dental and systemic diseases (1). Yudkin, sharing the same opinion from Cleave, wrote in 1972: “My research on coronary heart disease has convinced me beyond doubt that sugar plays a considerable part in this terrifying epidemic” (2). While both Cleave and Yudkin had distinct hypotheses regarding which dietary carbohydrates caused chronic non-communicable diseases (CNCDs), they were unified regarding the significance of high-glycemic dietary carbohydrates and dental CNCDs. According to Cleave-Yudkin’s hypothesis—both dental and systemic CNCDs were due to an excess intake of fermentable carbohydrates, dental CNCDs were the early marker for systemic CNCDs, and dental CNCDs should be primarily prevented by restriction of fermentable carbohydrates.
Hujoel, in an excellent review paper published in 2009 (3) told that:
“In favor of Cleave-Yudkin’s hypothesis is the ability to predict and explain dental-systemic disease associations that were unknown when the hypothesis was formulated. It is now known, for instance, that markers of abnormal glucose metabolism, such as high levels of advanced glycation end-products or post-load plasma glucose concentration, have been related to diverse systemic outcomes such cardiovascular disease (Jandeleit-Dahm and Cooper, 2008). Similarly, the more a diet drops dental plaque pH, the more it spikes blood glucose levels, providing an elegant biological plausibility model for Cleave-Yudkin’s hypothesis that dental caries is an alarm bell for systemic CNCDs (Lingström et al., 1993)”.
Confirming the Cleave-Yudkin’s hypothesis an Italian study published last week has shown that high dietary glycemic load and carbohydrate intake from high-GI foods increase the overall risk of cardiovascular disease in women, but not in men. In practice the study shows that women who eat more white bread, white rice, pizza, and other carbohydrate-rich foods, that cause blood sugar to spike, are more than twice as likely to develop heart disease than women who eat less of those foods. This study involving 47 749 volunteers (15 171 men and 32 578 women), who completed a dietary questionnaire, had a median duration of 7.9 years of follow-up with 463 CHD cases (158 women and 305 men) identified. The authors said in their paper that a possible reason for the failure to find an association between a high glycemic diet and CHD among men could be that adverse changes in plasma HDL cholesterol and triglyceride levels, as a result of a high glycemic diet, are stronger risk factors for CVD in women than men (4).
It is interesting to notice that high-carbohydrate diets, particularly in the form of high-glycemic index carbohydrate, may keep the sympathetic nervous system overactive (5). Also that high carbohydrate diet may increase significantly the activity of serum lactate dehydrogenase (6).
All the points cited above supply evidences for our acidity theory of atherosclerosis (6).
Treatment of periodontal disease in prevention of atherosclerosis
Some recent studies have shown that treatment of periodontal disease results in benefits for the prevention of atherosclerosis. Tonetti and colleagues have shown that intensive periodontal treatment, 6 months after therapy, the benefits in oral health were associated with improvement in endothelial function (7). Piconi et al have confirmed that treatment of periodontal disease results in improvements of endothelial dysfunction, aside a reduction of the carotid intima-media thickness. The authors of this paper have concluded that these results offer further support to the hypothesis that periodontal disease predisposes to atherosclerosis, shedding some light on the mechanisms possibly associated with this hypothesis, and reinforce the idea that atherosclerosis is an immune-mediated disease (8).
An alternative hypothesis
Taking in view that some risk factors like smoking habits, stress, genetics, increasing age and high-carbohydrates diets contribute to both periodontitis and cardiovascular disease we have an alternative hypothesis through the following mechanisms:
- A street with double directions for driving -
1) From one side the transport from the mouth directly to the blood circulation, through the sublingual route, of sugars related to high-carbohydrate diets leading to an overactive sympathetic nervous system and then to the atherosclerotic process. This idea is based in the regular use of the sublingual route with diffusion directly in the venous circulation for fast effects of remedies including cardiovascular drugs.
2) On the other side the saliva concentrations representing a mix of local chronic inflammatory response plus the acidity of other body conditions derived mostly from chronic stress aside from other factors expressed by markers of blood acidity, lactate dehydrogenase activity, sympathetic nervous system activity and hypothalamic-pituitary-adrenal activity. In our view this second road may also contribute to dental disease.
Carlos Monteiro
1. Cleave TL, Campbell GD (1966). Diabetes, coronary thrombosis, and the saccharine disease Bristol,: Wright
2. Yudkin J (1972b). Sweet and dangerous; the new facts about the sugar you eat as a cause of heart disease, diabetes, and other killers. New York: P.H. Wyden, Inc.
3. Hujoel P, Dietary Carbohydrates and Dental-Systemic Diseases, J Dent Res 2009; 88; 490. Abstract at http://jdr.sagepub.com/cgi/content/abstract/88/6/490
4. Sabina Sieri,Vittorio Krogh, et al . Dietary Glycemic Load and Index and Risk of Coronary Heart Disease in a Large Italian Cohort, EPICOR Study. Arch Intern Med. 2010;170(7):640-647
5. Koop W. Chronically increased activity of the sympathetic nervous system: our diet-related “evolutionary” inheritance. The Journal of Nutrition, Health & Aging Volume 13, Number 1, 2009
6. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
7. Tonetti MS et al. Treatment of Periodontitis and Endothelial Function, NEJM - Volume 356:911-920, March 1, 2007
8. Piconi S et al.Treatment of periodontal disease results in improvements in endothelial dysfunction and reduction of the carotid intima-media thickness. FASEB J. 23, 1196–1204 (2009)

The link between air pollution and atherosclerosis: What is the right biological explanation?

2010-02-28T16:59:00.000-08:00

Studies around the world have consistently shown that both short and long term exposures to Particulate Matter (PM) air pollution are associated with a host of cardiovascular diseases, including myocardial ischemia and infarctions, heart failure, arrhythmias, strokes and increased cardiovascular mortality.
Very recently it was published a study in humans confirming the association of the exposure to ambient air pollution and atherosclerosis through the progression of carotid artery intima-media thickness (1).
In an interesting recent paper by Robert Brook (2) he states that there are three putative ‘general’ pathways to explain the biological mechanisms whereby PM exposure may be capable of mediating cardiovascular events: 1) autonomic mechanisms: parasympathetic nervous system withdraw and/or sympathetic nervous system activation; 2) the release of circulating pro-oxidative and/or pro-inflammatory mediators from the lungs (e. g. cytokines and activated immune cells) into the systemic circulation following PM inhalation that, in turn, indirectly mediate CV responses; and; 3) nano-scale particles and/or soluble PM constituents translocating into the systemic circulation after inhalation that then directly interact with the CV system. According to Robert Brook, chronic actions of PM and the enhancement of atherosclerosis, are most likely to be induced by the generation of a chronic pro-inflammatory state (pathway 2).
Taking in view the results of studies in humans showing that particulate air pollutants continuous exposition decreases the heart rate variability (3,4) and may lead to an impaired autonomic control with potential acceleration in the progression of atherosclerosis (5,6,7), with the due respect, I feel obliged to differ from Brook’s opinion regarding the biological mechanism related to chronic PM exposure and atherosclerosis.
In our view the sympathetic over activity may start the whole process of atherosclerosis which ends in the inflammatory state as hypothesized in the acidity theory of atherosclerosis (8) and discussed in our last article in this blog (9)
Carlos Monteiro
1. Nino Kunzli, Michael Jerrett, Raquel Garcia-Esteban, Xavier Basagana, Bernardo Beckermann, Frank Gilliland, Merce Medina, John Peters, Howard N. Hodis, Wendy J. Mack. "Ambient Air Pollution and the Progression of Atherosclerosis in Adults." PloS ONE 5(2): e9096. doi:10.1371/journal.pone.0009096, February 8, 2010. Full free text at http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.00090962. Brook RD, Cardiovascular effects of air pollution. Clinical Science (2008) 115, (175–187) Full free text at http://www.clinsci.org/cs/115/0175/1150175.pdf
3. Duanping Liao, Yinkang Duan, Eric A. Whitsel, Zhi-jie Zheng, Gerardo Heiss, Vernon M. Chinchilli, and Hung-Mo Lin. Association of Higher Levels of Ambient Criteria Pollutants with Impaired Cardiac Autonomic Control: A Population-based Study, Am J Epidemiol 2004;159:768–777
4. C. Arden Pope III, Matthew L. Hansen, Russell W. Long, Karen R. Nielsen, Norman L. Eatough, William E. Wilson, and Delbert J. Eatough. Ambient Particulate Air Pollution, Heart Rate Variability, and Blood Markers of Inflammation in a Panel of Elderly Subjects. Environmental Health Perspectives, V 112; N 3: March 2004
5. Heikki V. Huikuri; Vesa Jokinen; Mikko Syvänne; Markku S. Nieminen; K. E. Juhani et al, Heart Rate Variability and Progression of Coronary Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1979-1985.
6. Anders Gottsäter , Åsa Rydén Ahlgren, Soumia Taimour and Göran Sundkvist, Decreased heart rate variability may predict the progression of carotid atherosclerosis in type 2 diabetes Clinical Autonomic Research Volume 16, Number 3 / June, 2006
7. J. C. Longenecker, M. Zubaid, K.V. Johny, A.I. Attia, J. Ali, W. Rashed, C.G. Suresh, M. Omar. Association of low heart rate variability with atherosclerotic cardiovascular disease in hemodialysis patients. Med Princ Pract 2009;18:85-92
8. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
9. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at http://aciditytheory.blogspot.com/2010/02/sympathetic-predominance-primary-factor.html

Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling.

2010-02-22T11:01:00.000-08:00

Sympathetic overactivity has been found to be associated with blood pressure and lipid abnormalities (1,2,3). In this respect a recent study has demonstrated that sympathetic overactivity may favour the development of sustained hypertension and hypercholesterolemia early in life, and lead to increased susceptibility of vascular complications. (4).
In fact accumulating data collected in animals and humans suggest that metabolic syndrome is associated with markers of adrenergic overdrive. Several markers of adrenergic drive, such as plasma norepinephrine, norepinephrine spillover from adrenergic nerve terminals, heart rate and others, have all show an increase in the different conditions clustering in metabolic syndrome like obesity, hypertension and insulin resistance state (5,6). Evidence also has shown that the sympathetic activation participates in the development of hypertension-related target organ damage, such as left ventricular diastolic dysfunction (7).
It is well established that the sympathetic nervous system (SNS) activity is also influenced by food ingestion, and that diet composition plays an important role. What is interesting to note is that, among dietary types, carbohydrates (starch and sugars) ingestion significantly increases SNS activity, especially in high-glycemic load, with deleterious effects to human health (8). On the other side protein or fat ingestion have no significant sympathoexcitatory effect (9,10,11).
The evidences above mentioned strengthen our views regarding to the acidity theory of atherosclerosis where continuous stress is placed as the most important risk factor (12). However, this do not undermine the value of other key factors as expressed in our monography:
“The acidity theory of atherosclerosis does not underestimate the importance of other key factors for atherosclerosis like ageing, improper diet, environmental pollution, lifestyle, physical inactivity, tobacco smoking and genetic predisposition. However, most of these risk factors might result in altered autonomic nervous system, sympathetic bias, increased lactic acid and acidic environment thus propitiating atherogenesis. Our proposal may extend to any respiratory or metabolic disturbances resulting in acidosis.“
Carlos Monteiro
1. Masuo K, Mikami H, Ogihara T, Tuck ML. Sympathetic nerve hyperactivity precedes hyperinsulinemia and blood pressure elevation in a young, nonobese Japanese population. Am J Hypertens 1997; 10:77–83.
2. Nakao M, Nomura K, Karita K, Nishikitani M, Yano E. Relationship between brachial-ankle pulse wave velocity and heart rate variability in young Japanese men. Hypertens Res 2004; 27:925–931.
3. Arner P, Wahrenberg H, Lonnqvist F, Angelin B. Adipocyte betaadrenoceptor sensitivity influences plasma lipid levels. Arterioscler Thromb Vasc Biol 1993; 13:967–972.
4. Palatini P, Longo D, Zaetta V, Perkovic D, Garbelotto R and Pessina AC. Evolution of blood pressure and cholesterol in stage 1 hypertension: role of autonomic nervous system activity. Journal of Hypertension 2006, 24:1375-1381
5. Mancia G, Bousquet P et al. The sympathetic nervous system and the metabolic syndrome. Journal of Hypertension 2007, 25 (5):909-920
6.Grassi G, Quarti-Trevano F et al. Cariovascular risk and adrenergic overdrive in metabolic syndrome. Nutr Metab Cardiovasc Dis 2007, 17(6): 473-81
7. Grassi G, Seravalle G et al. Sympathetic and baroreflex cardiovascular control in hypertension-related left ventricular dysfunction. Hypertension 2009;53:205-209. Full free paper at http://hyper.ahajournals.org/cgi/content/full/53/2/205
8. Koop W. Chronically increased activity of the sympathetic nervous system: our diet-related “evolutionary” inheritance. The Journal of Nutrition, Health & Aging Volume 13, Number 1, 2009
9. Welle S, Ulavivat U, Campell G. Thermic effect of feeding in men: Increased plasma
norepinephrine levels following glucose but not protein or fat consumption. Metabolism 1981; 30: 953-958
10. Welle SL, Lilavivathana U,Campell RG. Increased plasma nor epinephrine concentrations and metabolic rates following glucose ingestion in man. Metabolism 1980; 29: 806-09
11. Tentolouris N, Tsigos D, Perea E et al. Differential effect of high-fat and high carbohydrate isoenergetic meals on cardiac autonomic nervous system activity in
lean and obese women. Metabolism 2003; 52: 1426-32
12. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

What causes the elevation of cholesterol levels in blood?

2010-02-05T09:45:00.000-08:00

Follows some suggestions from medical literature about factors, beyond the famous but wronged and simplistic idea that foods based on saturated fats cause the development of atherosclerosis (1, 22, 23), suggesting that stress, high carbohydrate diets and smoke may raise total cholesterol and low density lipoproteins levels:
1. Stress
a) Anxiety and cholesterol elevation (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
b) Hostility and cholesterol elevation (12, 13, 14)
c) Extreme physical exertion and cholesterol elevation (15)
2) High carbohydrate diets and cholesterol elevation (16, 17, 18).
3) Smoke and cholesterol elevation (19, 20).
It is interesting to notice that specially in stress conditions and in high carbohydrate diets there is a significant elevation in blood lactic acid, with paralleling elevation of cholesterol levels in blood which represents in our view, a healing response of the body to the vascular endothelial lesion (21).
As Dr. Malcolm Kendrick, a colleague from the International Network of Cholesterol Skeptics (THINCS), use to say: "Do cigarettes contain fat? No, not at all. So, how can smoking a cigarette, containing no fat or cholesterol, end up depositing fat and cholesterol in the artery walls. What is the mechanism for that?"
By the way, in a recent paper the authors have assessed all dietary interventions using Dietary Cholesterol (DC) or eggs and presented their own conclusions. They point out that short-term effects where there is a rise in plasma cholesterol with DC should be interpreted with caution because they differ from long-term effects where there is no relationship between DC and plasma cholesterol (22).
Carlos Monteiro
Note:
A recent meta-analysis of prospective epidemiologic studies during 5–23 years of follow-up of 347,747 subjects showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD. Consideration of age, sex, and study quality did not changed the results (23)
1. Uffe Ravnskov, Cholesterol Myths at http://www.ravnskov.nu/cholesterol.htm
2) Changes in plasma lipids with psychosocial stress are related to hypertension status and the norepinephrine stress response. Wirtz PH, Ehlert U, Bärtschi C, Redwine LS, von Känel R. Metabolism. 2009 Jan;58(1):30-7.
3. Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress, Elizabeth A. Bachen, Matthew F Muldoon et al, Psychosomatic Medicine 64:587-594 (2002)
4. Serum lipids, neuroendocrine and cardiovascular responses to stress in healthy Type A men, Fredrikson M, Blumenthal JA, Biol Psychol. 1992 Oct;34(1):45-58
5. Factors associated with the development of panic attack and panic disorder: survey in the Japanese population Kaiya H et al. Psychiatry Clin Neurosci. 2005 Apr;59(2):177-82a
6. Changes in mental well-being, blood pressure and total cholesterol levels during workplace reorganization: the impact of uncertainty, Taylor & Francis V15, N1 January 1, 2001: 14-18
7. Examination stress: changes in serum cholesterol, triglycerides and total lipids. Agarwal V, Gupta B, Singhal U, Bajpai SK. Indian J Physiol Pharmacol. 1997 Oct;41(4):404-8.
8. Wives of patients with acute myocardial infarction are at an increased risk of developing coronary artery disease, Papamichael Ch et al, J Cardiovasc Risk. 2002 Feb;9(1):49-52
9. Lipid reactivity to stress: I. Comparison of chronic and acute stress responses in middle-aged pilots, Stoney CM et al, Health Psychol. 1999 May;18(3):241-250
10. Associations between acute lipid stress responses and fasting lipid levels 3 years later, Andrew Steptoe and Lena Brydon, Health Psychology 2005, Vol. 24, No. 6, 601-607
11. Effect of preoperative stress on serum cholesterol level in humans. Sane AS, Kukreti SC, Experientia. 1978 Feb 15; 34(2): 213-4
12. Prevalence of hostility in young coronary artery disease patients and effects of cardiac rehabilitation and exercise training, Lavie CJ, Milani RV, Mayo Clin Proc. 2005 Mar;80(3):335-42
13.Richards JC, Hof A, Alvarenga M. Serum lipids and their relationships with hostility and angry affect and behaviors in men.Health Psychol. 2000 Jul;19(4):393-8.
14. Hostility-related differences in the associations between stress-induced physiological reactivity and lipid concentrations in young healthy women.Suarez EC, Harralson TL. Int J Behav Med. 1999;6(2):190-203.
15. Changes in lipoprotein profiles during intense military training. B. L. Smoak, J. P. Norton, E. W. Ferguson and P. A. Deuster. Journal of the American College of Nutrition, Vol 9, Issue 6 567-572
16. Metabolic effects of dietary fructose in healthy subjects.Swanson JE, Laine DC, Thomas W, Bantle JP. Am J Clin Nutrition 1992;55:851-6
17. Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch. Reiser S. Powell AS, Scholfield DI. Panda P. Ellwood KC. Canary II. Am J Clin Nutr 1989:49:832-9.
18. Hallfrisch J, Reiser 5, Prather ES. Blood lipid distribution of hyperinsulinemic men consuming three levels of fructose. Am J Clin Nutr 1983:37:740-8.
19. The Relationship Between Smoking, Cholesterol, and HDL-C Levels in Adult Women
Bert H. Jacobson; Steven G. Aldana; Troy B. Adams; Michael Quirk; Haworth, Women & Health, Volume 23, Issue 4 July 1996 , pages 27 - 38
20. Smoking and smoking cessation -- the relationship between cardiovascular disease and lipoprotein metabolism: a review. Chelland Campbell S, Moffatt RJ, Stamford BA. Atherosclerosis. 2008 Dec;201(2):225-35
21. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at
http://www.infarctcombat.org/AcidityTheory.pdf
22. Fernandez ML and Calle M. Revisiting Dietary Cholesterol Recommendations: Does the Evidence Support a Limit of 300 mg/d?, August 4, 2010
23. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease, Patty W Siri-Tarino, Qi Sun, Frank B Hu, and Ronald M Krauss. Am J Clin Nutr doi: 10.3945/ajcn.2009.27725. First published ahead of print January 13, 2010

Psoriasis linked to atherosclerosis: An unsolved mystery?

2010-01-11T03:37:00.000-08:00

During the last years several studies have reported that patients with psoriasis are more likely to have traditional cardiovascular risk factors, such as hyperlipidemia, hypertension, diabetes, obesity, tobacco use, and a history of previous myocardial infarction (1, 2).
Very recently a new study has suggested that psoriac patients have more propensity for coronary artery, cerebrovascular and peripheral vascular diseases resulting in increased mortality. This study compared rates of heart disease, stroke-related vascular disease and peripheral artery disease (PAD), and death among 3.236 people with psoriasis (mostly men between 50-60 years) and 2.500 people without this condition. Overall people with psoriasis were nearly twice as likely to have been diagnosed with heart disease, stroke related vascular disease or PAD. What’s more, 19.6% of people with psoriasis died during the study, compared with 9.9% of participants who did not have psoriasis (3).
In reality many recent studies are showing the prevalence of subclinical atherosclerosis in patients with psoriasis compared with health patients, through a marked increase in the carotid artery intima-media thickness, measured by ultrasonography (4,5,6 ,7,8).
Also, a study has shown that subclinical atherosclerosis in psoriac patients is significantly associated with increased sugar and triglyceride levels (6)
Other studies have shown that metabolic systems may be disturbed in association with psoriasis, with many compounds formed in excess from glucose, like lactic acid (9). It is interesting to notice that Boyd and Menter found that 13 (62%) of 21 patients with erythroderma, the most severe form of psoriasis, had elevated serum lactic deydrogenase (10). Another study have indicated a shift of enzymatic activity of lactate deydrogenase in erythrocyte in psoriasis towards LDH2 and LDH1, and thus to enhanced energy production by oxidation in psoriatic patients as compared with normal controls (11).
According to some researchers the mechanism by which premature atherosclerosis develops in psoriasis remains an unsolved mystery, becoming a focus of current research to further elucidate the pathophysiology underlying and connecting these two diseases (12).
Taking in view the above findings I think the acidity theory may offer a valid and potential pathophysiological mechanism to explain the link psoriasis/atherosclerosis (13)

1) Matthew Meier and Pranav B. Sheth, Clinical Spectrum and Severity of Psoriasis. Curr Probl Dermatol. Basel, Karger, 2009, vol 38, pp 1–20. Full free paper at http://www.online.karger.com/ProdukteDB/Katalogteile/isbn3_8055/_91/_51/CUPDE38_02.pdf
2) Mehta NN, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database. Eur Heart J. 2009 Dec 27.
3) Prodanovich S, Kirsner RS, Kravetz JD, Ma F, Martinez L, Federman DG.. Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch Dermatol. 2009 Jun;145(6):700-3.
4) El-Mongy S, Fathy H, Abdelaziz A, Omran E, George S, Neseem N, El-Nour N. Subclinical atherosclerosis in patients with chronic psoriasis: a potential association. J Eur Acad Dermatol Venereol. 2009 Nov 2
5) Balci DD, Balci A, Karazincir S, Ucar E, Iyigun U, Yalcin F, Seyfeli E, Inandi T, Egilmez E. Increased carotid artery intima-media thickness and impaired endothelial function in psoriasis. J Eur Acad Dermatol Venereol. 2009 Jan;23(1):1-6.
6) Tam LS, Shang Q, Li EK, Tomlinson B, Chu TT, Li M, Leung YY, Kwok LW, Wong KC, Li TK, Yu T, Zhu TY, Kun EW, Yip GW, Yu CM. Subclinical carotid atherosclerosis in patients with psoriatic arthritis. Arthritis Rheum. 2008 Sep 15;59(9):1322-31.
7) Eder L, Zisman D, Barzilai M, Laor A, Rahat M, Rozenbaum M, Bitterman H, Feld J, Rimar D, Rosner I. Subclinical atherosclerosis in psoriatic arthritis: a case-control study. J Rheumatol. 2008 May;35(5):877-82.
8) Gonzalez-Juanatey C, Llorca J, Amigo-Diaz E, Dierssen T, Martin J, Gonzalez-Gay MA. High prevalence of subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. Arthritis Rheum. 2007 Aug 15;57(6):1074-80.
9) Meynadier J, Guilhou JJ, The biochemistry of psoriasis. Ann Dermatol Syphiligr (Paris). 1976;103(5-6):525-45.
10) A. Boyd, A. Menter, Erythrodermic psoriasis: Precipitating factors, course, and prognosis in 50 patients.Journal of the American Academy of Dermatology, 1989, Volume 21, Issue 5, Pages 985-991
11) Malina L, Volek V, Bielicky T. The activity of lactate dehydrogenase in the erythrocytes in psoriasis. Z Haut Geschlechtskr. 1969 Oct 1;44(19):877-9.
12) Shelling ML, Federman DG, Prodanovich S, Kirsner RS. Psoriasis and vascular disease: an unsolved mystery. Am J Med. 2008 May;121(5):360-5.
13) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

Acidity: The link between Atherosclerosis and Osteoporosis.

2010-01-05T02:24:00.000-08:00

Although the prevalence of both atherosclerosis and osteoporosis increase with age, various and accumulating evidence indicate, since the initial studies (1, 2), a more direct relationship between these 2 conditions. Confirming this association, many recent studies have shown an increased carotid intima-media thickness (IMT), a marker for atherosclerosis, among women as they develop osteoporosis (3, 4).
A very recent study have reported that hip fracture is between two and five times more common in people with cardiovascular disease than in those with no history of the disease. The researchers from this study have found that bisphosphonates not only decrease the progression of osteoporosis, but also prevent the development of atherosclerosis and reduce total mortality rate (5).
Regarding this point it is interesting to note that bisphosphonates can reduce the elevated production of lactic acid in the body (6) what allow the acidity theory concept (7) to be a strong explanation for the link atherosclerosis/osteoporosis, taking in view the proposition from A. Wachman and D.S. Bernstein made in 1968 (8), and endorsed by others (9), that the body draws minerals from the bones to neutralize acid or alkaline challenges.
BTW, an editorial published at New England Journal of Medicine (Bone, Acid, and Osteoporosis, New England Journal of Medicine, V 330:1821-1822 , June 23, 1994) brings the following quote and comments:
"Life is a struggle, not against sin, not against the Money Power, not against malicious animal magnetism, but against hydrogen ions"1 Mencken H L. Exeunt omnes. Smart Set. 1919; 60: 138–145). These words, written by H.L. Mencken about the meaning of life and death, may also apply to the struggle of the healthy skeleton against the deleterious effects of retained acid.
Carlos Monteiro

1) Dent CE, Engelbrecht HE, Godfrey RC. Osteoporosis of lumbar vertebrae and calcification of abdominal aorta in women living in Durban. Br Med J. 1968;4:76-79.
2. Fujita T, Okamoto Y, Sakagami Y, Ota K, Ohata M. Bone changes and aortic calcification in aging inhabitants of mountain versus seacoast communities in the Kii Peninsula. J Am Geriatr Soc. 1984;32:124-128
3) J. Tamaki , M. Iki, Y. Hirano, Y. Sato, E. Kajita, S. Kagamimori, Y. Kagawa and H. Yoneshima. Low bone mass is associated with carotid atherosclerosis in postmenopausal women: The Japanese Population-based Osteoporosis (JPOS) Cohort Study , Osteoporosis International, V 20, N 1 / January, 2009
4) Hiroyuki Sumino, Shuichi Ichikawa, Shu Kasama, Takashi Takahashi, Hironosuke Sakamoto, Hisao Kumakura, Yoshiaki Takayama, Tsugiyasu Kanda, Masami Murakami and Masahiko Kurabayashi, Relationship between Carotid Atherosclerosis and Lumbar Spine Bone Mineral Density in Postmenopausal Women, Hypertension Research (2008) 31, 1191–1197;
5) Ulf Sennerby, Håkan Melhus, Rolf Gedeborg, Liisa Byberg, Hans Garmo, Anders Ahlbom, Nancy L. Pedersen, Karl Michaëlsson. Cardiovascular Diseases and Risk of Hip Fracture, JAMA. 2009;302(15):1666-1673.
6 Norman H. Bell and Ralph H. Johnson. Bisphosphonates in the treatment of osteoporosis, Endocrine, Volume 6, Number 2 / April, 1997.
7) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
8) Wachman A, Bernstein DS. Diet and osteoporosis. Lancet. 1968;1:958–9.
9) Frances A. Tylavsky, Lisa A. Spence Laura Harkness. The Importance of Calcium, Potassium, and Acid-Base Homeostasis in Bone Health and Osteoporosis Prevention. J. Nutr. 138: 164S–165S, 2008 full free paper at http://jn.nutrition.org/cgi/reprint/138/1/164S

Lactate as cause of secondary damage in acute ischemic stroke

2009-12-28T04:45:00.000-08:00

Atherosclerosis of the carotid arteries is a leading cause of ischemic stroke. Increased carotid artery intima-media thickness (IMT) is a marker of atherosclerosis and also a predictor for ischemic stroke that represents more than 80% of strokes, with the remainder due to hemorrhage.
Recent study involving 187 patients with acute ischemic stroke or transient ischemic attack (1) have indicated that lactate in cerebrospinal fluid, but not in blood, is a reliable marker for the metabolic crisis in acute ischemic stroke and a possible cause of secondary neuronal damage in cortical infarction resulting in unfavourable evolution in the sub acute phase of stroke and poor long-term outcome.
However, some researchers believe that whole blood lactate, as measured in this study, unlike serum lactate, is an unreliable measure of systemic lactate (2).
It is interesting to note that a study from 2004 found ischemic stroke acidosis-mediated activation of acid-sensing ion channels may play a role to ischemic damage of brain tissue (3).
Most interesting is that cardiac glycosides, besides its anti-atherosclerotic effects as discussed recently in this blog (4, 5), also can provide cerebral neuroprotection in front of ischemic stroke and in prevention of its occurrence (6).

1) Evaluation of lactate as a marker of metabolic stress and cause of secondary damage in acute ischemic stroke or TIA, Brouns R, Sheorajpanday R, Wauters A, Surgeloose DD, Mariën P, DE Deyn PP. Clinica Chimica Acta 397 (2008) 27–31
2) The Lactic Acid Response to Alkalosis in Panic Disorder: An Integrative Review Richard J. Maddock, M.D.J Neuropsychiatry Clin Neurosci 13:1, Winter 2001. Full free paper at http://neuro.psychiatryonline.org/cgi/content/full/13/1/22
3) Huang Y, McNamara JO. 2004. "Ischemic Stroke: “Acidotoxicity” Is a Perpetrator", Cell, Volume 118, Issue 6 , 17 September, Pages 665-666
4) The anti-atherosclerotic effects of cardiac glycosides, Carlos Monteiro at http://aciditytheory.blogspot.com/2009/11/anti-atherosclerotic-effects-of-cardiac_27.html
5) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
6) Cardiac Glycosides in Prevention of Stroke, Carlos Monteiro, ICP, July 10, 2006, Full text at http://www.infarctcombat.org/media/071006.html

Stress, lactic acid, hypertension, atherosclerosis and hair loss

2009-12-15T09:30:00.000-08:00

The last weekend I have read an article in New York Times Journal, entitled “The Claim: High Blood Pressure Will Increase People’s Risk of Losing Their Hair.” (http://www.nytimes.com/2009/12/08/health/research/08real.html), which caught my attention.
NYT have discussed the results and linked to some of the studies suggesting that hair loss may indicate an increased risk of high blood pressure and heart disease.
Curious about this information I have searched at Pubmed were I found a recent paper linking hair loss also to atherosclerosis, with the conclusion by the authors that severe vertex pattern of androgenetic alopecia should be considered to have an increased risk of subclinical atherosclerosis (1).
Going deeper I have found a postulation made in 1997 by Marino Salin, from Italy, telling if there is excess adrenergic tone in the metabolic system, then there is also vasoconstriction, ischemia and hypoxia and if there is hypoxia, glycolysis leads to lactic acid that causes caustic damage to the inner sheath and this sheath seems to be raised above the hair cuticle (2).
This postulation coincides with our thoughts about the acidity theory of atherosclerosis (3).
References
1) Dogramaci AC et al,Is androgenetic alopecia a risk for atherosclerosis? J Eur Acad Dermatol Venereol. 2009 Jun;23(6):673-7.
2) Marino Salin e Andrea Marliani, EDIZIONI ELETTRONICHE “TricoItalia” (Firenze) marzo 1997, BOLLETTINO della Società Italiana di Tricologia, La Teoria e la Clinica delle “INCIDENZE” nelle Alopecie. Full paper in Italian language at http://www.calvizieinfo.com/bollettino.pdf
3)Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

Hypertension, atherosclerosis, stress and lactic acid

2009-11-27T09:57:00.000-08:00

Hypertension is considered as an important risk factor for the development of atherosclerosis, with these processes sharing some common mechanisms. The endothelium is placed usually as a probable central focus for the effects in both diseases, with evidences leading to the postulation that hypertension predispose and accelerate atherosclerosis. Coronary myocardial-disease is the main death cause in hypertensive patients.
Stress is one of the suggested factors for the hypertension origin and its reduction may help to reduce an elevated blood pressure. Coincidently stress can also contribute for the development and subsequent complications of atherosclerosis what is evidenced in many studies (1).
The key mechanism according the acidity theory of atherosclerosis (1) as the triggering factor for hypertension and atherosclerosis, is the elevation of the lactic acid production in blood. It is interesting to note that lactic acid in blood plasma can have a significant elevation during stress situations , serving as an indicator of stress levels (2, 3). Also, high carbohydrate diet may increase significantly the activity of serum lactate dehydrogenase (4,5). On the other side the concentration of lactic acid in both venous and arterial blood may be significantly elevated in hypertension as showed a study published 45 years ago (6), which results were confirmed recently by the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study, that measured plasma lactate in 2066 older adults. This study came to the conclusion that high plasma lactate was independently associated with the odds of hypertension (7).
1) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
2) Sharda S, Gupta SN and Khuteta KP. 1975. Effect on mental stress on intermediate carbohydrate-and lipid-metabolism. Indian J Physiol Pharmacol. Apr-Jun;19(2):86-9.
3) Hall JB, Brown DA. 1979. Plasma glucose and lactic acid alterations in response to a stressful exam. Biol Psychol. May;8(3):179-88.
4) Marshall MW and Iacono JM (1976). Changes in lactate dehydrogenase, LDH isoenzymes, lactate, and pyruvate as a result of feeding low fat diets to healthy men and women. Metabolism. 1976 Feb;25(2):169-78.
5)Yoshimura T, Miyoshi T, et al. (1986). Effect of high carbohydrate diet on serum lactate dehydrogenase isozyme pattern in Japanese young men. Acta Biol Hung. 1986;37(3-4):243-8.
6) F. E. Demartini, P. J. Cannon, W. B. Stason, and J. H. Laragh. 1965. Lactic Acid Metabolism in Hypertensive Patients. Science 11 June, Vol. 148. no. 3676, pp. 1482 – 1484 em http://www.sciencemag.org/cgi/content/abstract/148/3676/1482
7) Abstract 5003: Association of Blood Lactate with Hypertension: The Atherosclerosis Risk in Communities Carotid MRI Study. J Hunter Young; Stephen O Crawford; Frederick L Brancati; Ron C Hoogeveen; Muhammad Amer; Christie M Ballantyne; Maria I Schmidt; Brad C Astor; Josef Coresh, Circulation. 2008;118:S_1129.), http://circ.ahajournals.org/cgi/content/meeting_abstract/118/18_MeetingAbstracts/S_1129-a

The anti-atherosclerotic effects of cardiac glycosides

2009-11-27T09:56:00.001-08:00

A recent study has showed that cardiac glycosides have anti-atherosclerotic effects (1). This was foreseen in the acidity theory of atherosclerosis, because these cardiotonics have properties of reduction of lactic acid concentration in blood and a specific sympathoinhibitory response by blocking the overproduction of catecholamine. (2). Also compatible with the acidity theory concept is the conclusion from the authors of the present study telling that low concentrations of digitoxin would help to avoid side effects and might represent a specific therapeutically option for the treatment of inflammatory cardiovascular disease, such as atherosclerosis.
1) Digitoxin elicits anti-inflammatory and vasoprotective properties in endothelial cells: Therapeutic implications for the treatment of atherosclerosis?, Joanna Jagielska, Gustavo Salguero, Bernhard Schieffer, Udo Bavendiek, doi:10.1016/j.atherosclerosis.2009.03.019
2) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

The potential anti-atherosclerotic effects of proton pump inhibitors

2009-11-27T09:54:00.000-08:00

A recent study has shown that calcium phosphate crystals of approximately 1 micron or less in diameter caused rapid rises in intracellular calcium concentration, an effect that was inhibited by the lysosomal proton pump inhibitor, bafilomycin A1 which also blocked vascular smooth muscle cell death. This suggested to the authors that calcium phosphate crystals are rapidly degraded in lysosomes and subsequent acidification leads to the release of calcium into the cell (1)
A study looking to demonstrate that when subintimal macrophages come into contact with LDL aggregates, an extracellular, acidic, hydrolytic compartment (a lysosomal synapse) is formed., with bafilomycin A1 blocking the free cholesterol production in this compartment (2)
Another study has discussed about the potential anti-atherosclerotic effects of proton pump inhibitors (3).
The above studies give great support to the acidity theory of atherosclerosis concept (4)
1) Calcium Phosphate Crystals Induce Cell Death in Human Vascular Smooth Muscle Cells: A Potential Mechanism in Atherosclerotic Plaque Destabilization, Alexandra E. Ewence et al, Circ. Res. 2008;103;e28-e34; at http://circres.ahajournals.org/cgi/content/full/103/5/e28
2) Macrophages Create an Acidic Extracellular Hydrolytic Compartment to Digest Aggregated Lipoproteins, Haka, A.S., I. Grosheva, E. Chiang, A.R. Buxbaum, B.A. Baird, L.M. Pierini and F.R. Maxfield. Mol. Biol. Cell, in press 2009, at http://www.molbiolcell.org/cgi/reprint/E09-07-0559v1
3) The potential anti-xanthoma and anti-atherosclerotic effects of proton pump inhibitors, M. R. Namazi, MD and M. Sharifian, MD. Journal of Clinical Pharmacy and Therapeutics (2008) 33, 579–580
4) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

LDL oxidation occurs within lysosomes in cells

2009-11-27T09:52:00.000-08:00

Recent evidence showed that LDL oxidation occurs not within the interstitial fluid of atherosclerotic lesions but within lysosomes in macrophages in atherosclerotic lesions. Most important, the study found that this oxidative modification was inhibited by the drug chloroquine, which increases the pH of lysosomes, as oxidation can be promoted by acidic pH (1, 2)
1) Low Density Lipoprotein Undergoes Oxidation Within Lysosomes in Cells, Yichuan Wen and David S. Leake, Circ. Res. 2007;100;1337-1343; em http://circres.ahajournals.org/cgi/content/full/100/9/1337
2) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf