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
Monday, July 26, 2010
Tuesday, July 13, 2010
Old experiments with rabbits and dogs provide powerful evidence for the Acidity Theory of Atherosclerosis (1)
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
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
Wednesday, May 5, 2010
Cigarette smoking in the development and progression of atherosclerosis: Is sympathetic overactivity the key factor to explain this association?
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
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
Thursday, April 15, 2010
Fermentable carbohydrates: A link between periodontal disease and cardiovascular disease?
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)
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)
Sunday, February 28, 2010
The link between air pollution and atherosclerosis: What is the right biological explanation?
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
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
Monday, February 22, 2010
Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling.
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
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
Friday, February 5, 2010
What causes the elevation of cholesterol levels in blood?
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
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
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