“Cholesterol & Thrombosis Are Not the Cause of Stroke!!!”

I’m delighted to inform you about our new hypothesis for the cause and therapeutic of stroke. It is backed by a large and strong number of scientific evidences.

The article is titled: ‘Intense Stress Leading to Raised Production and Accumulation of Lactate in Brain Ischemia – The Ultimate Cause of Acute Stroke: Mechanism, Risk Factors and Therapeutics.’

It is published in Positive Health Online, Edition 247, July 2018 at http://www.positivehealth.com/article/heart/intense-stress-leading-to-accumulation-of-lactate-in-brain-ischemia.

“In severe ischemia (and tissue hypoxia) oxygen delivery to brain cells is insufficient for normal energy production, and acid-base homeostasis is threatened by the accumulation of acid equivalents (metabolic acidosis)”. Stig Rehncrona, MD, PhD – Lund University, Sweden, 1985 [1]

Abstract

The present paper introduces a new hypothesis postulating that acute stress, chronic stress overload and other risk factors with intense sympathetic nervous system activity may induce a raised lactate production and accumulation in brain ischemia. This represents, in our view, the ultimate cause for the triggering of acute stroke, resulting in the cerebral infarction.

It explains how stress (sympathetic dominance) may lead to a raised lactate production.

The fundamental therapeutic for prevention and management of acute stroke, according to this proposed concept, are old drugs called cardiac glycosides (CGs).

Studies using cardiac glycosides have demonstrated neuroprotective effects in experimental brain ischemia, on the protection against vasospasm in subarachnoid hemorrhage, sympatho-inhibitory effects and a potent inhibition of glycolysis (glucose consumption and lactate).

The use of CGs has also show a very low total mortality (including for stroke) in cardiac patients taking low doses of these drugs.

Cardiac glycosides like digoxin and lanatoside C are drugs approved by the U.S. Federal Drugs Administration (FDA), and by other similar organizations around the world, with some of these having also approval for the use of digitoxin and other CGs . Therefore, these drugs can be prescribed for prevention and in the management of acute stroke, with no major obstacles, by a well informed physician.

The paper also discusses on the limitations and failures in the concept of thrombus as the cornerstone of acute ischemic stroke (AIS)

___________________________________________________

You can see links to a collection of recent published medical articles and presentations by ourselves at (https://www.facebook.com/infarctcombat.org/)

Carlos Monteiro

New Book (2016) 

“Fat and Cholesterol Don’t Cause Heart Attacks 

And Statins Are Not The Solution” 

Edited by Prof. Dr. Paul Rosch this book is a tribute to Dr. Uffe Ravsnkov, an extraordinary and tireless researcher, founder of “The International Network of Cholesterol Skeptics (THINCS)”. Among other bookstores you can find this book at https://www.amazon.com/Cholesterol-Cause-Attacks-Statins…/…/

Uffe Ravsnkov’s monograph, “The Cholesterol Myths”, can be read free of charge, at https://www.smashwords.com/books/view/486704 

The present book contains 17 chapters written by a select group of medical researchers and scientists. 

I’m honored to participate in this tribute to Uffe Ravsnkov.

My chapter is entitled “Stress as Cause of Atherosclerosis – The Acidity Theory”.

During the last year I have presented an article about the acidity theory of atherosclerosis, developed in 2006, addressing its history, pathophysiology, therapeutics, risk factors and external markers. There I also have wrote about individuals with lower degree or absence of atherosclerosis, and on the reversion or lower progression of atherosclerosis through the use of sympatholytic drugs and by stress reduction approaches (http://goo.gl/AejGAV). 

In this book (Chapter 10) I extend the discussion about the etiology of the Acidity Theory of Atherosclerosis, aside to present new risk factors and other diseases associated to atherosclerosis, under its point of view. Also, I brought up for discussion the inverse association between cancer and atherosclerosis, confirmed by recent studies*. Follows the abstract:

Abstract
The link between stress and atherosclerosis is well-known with many studies and postulations in this regard. However, there is a general unawareness that stress can induce hyperlactatemia and lactic acidosis, because this relationship has been little discussed in medical science. The influence of adrenaline on lactic acid production was first noticed by Carl Ferdinand Cory in 1925. The heart is an organ of high metabolic activity – that cannot rest as other body muscles, being susceptible to drops in pH during ischemia and hypoxia. The chronic elevated catecholamine release, triggered by sympathetic dominance, may accelerate the myocardial glycolysis leading to significant increase in lactate production. Risk factors for atherosclerosis like hypertension, diabetes, cigarette smoking, stress conditions and high carbohydrate diets are linked to autonomic dysfunction. These risk factors present as well an increased concentration of lactate in plasma. Blood lactate is also associated with carotid atherosclerosis. Plasma lipid abnormalities and myocardial lactate production were significantly associated with subsequent arteriographic progression. The amount of lactate released by the myocardium has been shown to be related to the severity of coronary artery disease. Reduced pH increases the oxidation of low-density lipoprotein that is considered to have a significant role in atherogenesis. According to the acidity theory of atherosclerosis the acidosis evoked by sympathetic dominance or continuous stress leads to changes in shear stress, the final stage in the development of atherosclerotic lesions. The importance of mechanical forces such as those derived from changes in hemodynamic shear stress, as a decisive factor for atherosclerosis, was advocated by Meyer Texon since1957.

* You can also see the studies confirming about the inverse association between cancer and atherosclerosis at our article Cancer, Atherosclerosis and Sympathetic Dominance, Positive Health Online, issue 223, 2015 

"Acidity Theory of Atherosclerosis: History, Pathophysiology, Therapeutics and Risk Factors

My recent article "Acidity Theory of Atherosclerosis: History, Pathophysiology, Therapeutics and Risk Factors -- a Mini Review" was published at http://www.positivehealth.com/article/heart/acidity-theory-of-atherosclerosis-history-pathophysiology-therapeutics-and-risk-factors-a-mini-revie
Carlos Monteiro

High carbohydrate diets significantly activate SNS, while proteins and fats don't

Many studies are suggesting that high-carbohydrate diets, particularly in the form of high-glycemic index load, may activate the sympathetic nervous system with deleterious effects to human health (1). On the other side protein or fat ingestion have no significant sympathoexcitatory effect (2,3,4).

Also, the sympathetic activation have been linked in several studies to obesity, hypertension, insulin resistance, diabetes, and even atherosclerosis (5, 6, 7)

If the above studies are right, continuing to give support to high carbohydrate diets is both a wrong choice as well a bad advice.

Carlos Monteiro

References:
1) 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
2) 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
3) Welle SL, Lilavivathana U,Campell RG. Increased plasma nor epinephrine concentrations and metabolic rates following glucose ingestion in man. Metabolism 1980; 29: 806-09
4) 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
5)Troisi RJ, Weiss ST, Parker DR, Sparrow D, Young JB and Landsberg L. Relation of obesity and diet to sympathetic nervous system activity.  Hypertension. 1991;17:669-677 at http://hyper.ahajournals.org/content/17/5/669.full.pdf
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) Book "Acidity Theory of Atherosclerosis: New Evidences", 2012, Amazon.com http://tinyurl.com/7KK4a78

Why alcoholics have a lower risk for coronary heart disease

The Spanish EPIC cohort study (European Prospective Investigation into Cancer), published in 2010, including 15630 men and 25808 women, has concluded that alcohol intake (moderate, high and very high consumption) in men aged 29–69 years was associated with a more than 30% lower CHD incidence (1).

Reading an old article by Leary (2) from 1935, I see that his interest in arteriosclerosis arose out of information that a class persons suffering from alcoholism appeared to show a lesser degree of atherosclerosis than their ages would justify. So, I have searched for recent papers that could confirm this relationship and found a study from 1997 comparing a cohort of alcoholics who underwent a medico-legal autopsy during a five-year period with non-alcoholic controls who did not differ from the alcoholics in selection criteria. This study has show in the examinations, that alcoholic men and old women had a significantly lower degree of atherosclerosis in the coronary arteries (3)

A paper published in 2002 may have the answer to why alcoholics have a significantly lower degree of atherosclerosis in the coronary arteries and risk for coronary heart disease (4). Regarding this paper, a release from EurekAlert (5), with an interview by William Lovallo, one of the authors, told that:

“Before testing alcoholics for their responses to a public-speaking task, researchers first needed to establish if their sympathetic nervous system was able to respond at all. "This would tell us if their blunting was specific to psychological stressors like public speaking," said Lovallo, "or due to a generalized autonomic deficit."

He and his colleagues examined 20 alcohol-dependent subjects, abstinent for 21 to 28 days, and 10 age-matched nonalcoholics. All subjects were males between the ages of 22 and 55 years. The researchers used impedance cardiography and dinamap blood pressure monitoring to assess the participants' heart rate, stroke volume, cardiac output, total peripheral resistance, mean arterial pressure, systolic blood pressure, and diastolic blood pressure during orthostasis and public speaking. Self-reported mood was also assessed during these two tasks.

Cardiovascular responses to orthostasis were similar for the two groups. However, the alcoholics had blunted heart-rate responses to public speaking even though they reported similar anxiety responses to the nonalcoholics. This suggests a disconnection between perception of threat and resulting physiological responses among the alcoholics.

"The similar cardiovascular responses to orthostasis among the alcohol-dependent patients indicate that their autonomic nervous systems were working normally," said Lovallo. "Yet when we asked them to prepare and memorize a short speech and then deliver the speech to a video camera, the patients reacted with little or no change in heart rate, and of course, they failed to have a cortisol response. The patients reacted as if the social challenge of public speaking had no special meaning for them. So, the sympathetic nervous system in the patients looked normal, but their response to a psychological stressor was almost absent. When faced with a socially meaningful stressor, neither part of their fight-flight mechanism was working."

These results support the concept of the acidity theory where sympathetic predominance is the primary factor leading to atherosclerosis (6)

Carlos Monteiro

1. L Arriola, P Martinez-Cambor, N Larranaga, M Basterretxea. Alcohol intake and the risk of coronary heart disease in the Spanish EPIC cohort study. Heart 2010;96:124-130 doi:10.1136/hrt.2009.173419
2. Leary T. Atherosclerosis, the important form of arteriosclerosis, a metabolic disease. Vol 104, N7. JAMA, 1935
3. Thomsen JL. Atherosclerosis in alcoholics. Forensic Sci Int. 1995 Oct 30;75(2-3):121-31 and in Ugeskr Laeger. 1997 Feb 3;159(6):757-.60
4. Tera L. Panknin, Stacey L. Dickensheets, Sara J. Nixon, William R. Lovallo. Attenuated Heart Rate Responses to Public Speaking in Individuals With Alcohol Dependence. Alcohol Clin. Exp. Res. 2002 Jun; 26 (6): 841
5. Alcoholics have 'blunted' responses to psychological stressors such as public speaking. Public release date: 17-Jun-2002 at
http://www.eurekalert.org/pub_releases/2002-06/ace-ah061002.php
6. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

A review from the book "Acidity Theory of Atherosclerosis: New Evidences", 2012 (Paperback)

Think that fat causes heart disease? Think again!

By Zoe V. Harcombe* Review at Amazon

This must be the academic equivalent of the "Collection of short stories" format so popular in the fiction world. It's a collection of articles, all different, but related by a common theme - heart disease.

I really enjoyed the format - it gives a taste of each topic without going into massive detail on each. The comprehensive references point the way if you want to know more about any particular factor in coronary artery disease. I never knew that the condition of having Down syndrome seems to have some protective properties when it comes to heart disease. What about the role of bacteria, or lactic acid? Is erectile dysfunction trying to tell us something? More familiar topics, such as smoking and stress, are covered but in a really new and often surprising way. I lost count of the number of times I learned something new or saw a well known topic covered in an innovative way.

I like the way the author thinks and challenges everything and makes connections between seemingly unrelated things. I also liked the inputs from colleagues - for example David Diamond's contribution to the article "Is LDL unquestionably and unequivocally a causal risk factor for heart attack?" The role of glucose (not fat) in the working of the body was fascinating and should be far more widely known.

You cannot fail to learn something if you read this book. If you are interested in our number one killer of humans - men especially - this is well worth your time.

*Zoe Harcombe, Author of The Obesity Epidemic: What caused it? How can we stop it? at http://www.theobesityepidemic.org/
Website: http://www.zoeharcombe.com/
Blog: http://www.zoeharcombe.com/blog/

A review from the book "Acidity Theory of Atherosclerosis: New Evidences", 2012 (Kindle Edition)

A Must Read for Anyone Taking Statin Drugs

By Dr. Stephanie Seneff, Senior Research Scientist, MIT*. Review at Amazon.com

This is a fabulous book, highly recommended for anyone who has the slightest doubt about the lipid theory for cardiovascular disease. The book is jam packed with fascinating observations at every page turn. The writing is not dumbed down for the masses (not an "easy" read), but on the other hand the author does not get caught up in biological jargon that might cause the non-expert to get lost.

The basic premise of the book is that cardiovascular disease is caused by the build-up of acid in the blood, which, in turn, is caused by excitation of the sympathetic nervous system (fight-or-flight response). Each chapter is short and compelling, building on the theory with support from a different slant. While details are left out, a long list of references at the end of every chapter allows the interested read to delve further if they so desire.

The book effortlessly explains many observed associations with heart disease. For example, cigarette smoke is a risk factor because nicotine excites the sympathetic nervous system. Meditation reduces risk because deep breathing promotes the expulsion of carbon dioxide, an acid promoter. A newly learned fact that I relished is that the adrenal glands produce a natural cardiac glycoside similar to digoxin, which is used therapeutically to treat heart failure. Cholesterol is the substrate, and statin drugs interfere with its synthesis, which may help explain the observed association between statin therapy and heart failure.

By the time you arrive at the final chapter, you have seen clearly how all the risk factors for cardiovascular disease can be explained by the acid theory, and this is where he lays it out "plain and simple" and ties it all together. After having read this book, you will never again believe that lowering LDL levels has any merit in the treatment of cardiovascular disease.

*Homepage of Dr. Stephanie Seneff at MIT:
http://people.csail.mit.edu/seneff

*Dr. Seneff essay on sulfur and heart disease and other chronic diseases:
http://people.csail.mit.edu/seneff/sulfur_obesity_alzheimers_muscle_wasting.html

*Dr. Stephanie Seneff interviewed by Dr. Mercola:
http://articles.mercola.com/sites/articles/archive/2011/09/17/stephanie-seneff-on-sulfur.aspx

A review from the book "Acidity Theory of Atherosclerosis: New Evidences", 2012 (Paperback)

By Livin' La Vida Low-Carb Man "Jimmy Moore"*. Review at Amazon.com

Rethinking What Really Contributes To Heart Disease

For the past few decades we have been led to believe that the reason why people develop heart disease is because they are consuming too much saturated fat and cholesterol in their diet that it has led to "clogged arteries" that give us a heart attack and puts us one foot in the grave. The weeping and gnashing of teeth that takes place over this has people scared half to death to consume any fat or cholesterol anymore. But what if that theory of atherosclerosis was just plain wrong? This is what author Carlos Monteiro explores in his book ACIDITY THEORY IN ATHEROSCLEROSIS: NEW EVIDENCES (VOLUME 1).

Monteiro does a brilliant job at examining other aspects of vascular health that people may not even realize exists. Try some of these on for size and see if you knew they had any relation to the health of your heart:

- People with Down's syndrome tend to have very little heart disease
- Diabetics are more likely to develop heart disease
- If you a man with ED, then you are very likely at risk for heart disease
- Wanna make your heart healthier? Marry a comedian
- LDL cholesterol plays a lot less role in a cardiovascular event than people realize
- Salt intake is pretty much irrelevant in whether you develop heart disease or not
- If you have rheumatoid arthritis, then you are at greater risk for atherosclerosis
- The health of your teeth can play a factor in developing heart disease

For some, the information contained in this book will rock your world and make you rethink most of what you thought was true about the development of arterial plaque. Monteiro's alternative theory that this is really all about acidity in the body and that this leads to a chain reaction of events the increases LDL oxidation which makes atherosclerosis become a reality is absolutely plausible if not probable. And lest you think this book is just full of a bunch of opinions by a wayward voice, think again. Monteiro does an outstanding job of providing literally hundreds of excellent scientific references for you to do further research on each of his points.

This book should be required reading for every first-year medical school student so they can have a much broader focus on some of the true causes of atherosclerotic development that can lead to myocardial infarction. And here's the headline-making secret that you don't hear many people talking about--it's not necessarily about what your LDL or total cholesterol is! That's why statin medications are pretty much useless in preventing heart attacks from happening and why you need to read the ACIDITY THEORY OF ATHEROSCLEROSIS for an alternative viewpoint that just might be spot on. It's time we start rethinking what REALLY contributes to heart disease.

* Jimmy Moore Blog & Podcast

http://www.livinlavidalowcarb.com/blog
http://www.thelivinlowcarbshow.com/shownotes
livinlowcarbman@charter.net
Author of "21 Life Lessons From Livin' La Vida Low-Carb: How The Healthy Low-Carb Lifestyle Changed Everything I Thought I Knew" (BookSurge 2009) Order Jimmy's book at Amazon.com 

Both restriction and high salt intake may result in cardiovascular disease

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?

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?

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.....

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?

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

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?

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

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