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Recommendation for your heart

Recommendation:  healthy lifestyle (weight control, strenuous exercise*, low-fat diet).  Avoid tobacco smoke and other sources of reactive oxygen such as exhaust from vehicles.  Don’t allow chronic infections to go untreated.  Avoid all NSAIDs but for aspirin.  Take a 325 mg aspirin per day (this higher dose because of its cancer risk reduction). 

Putting it all together:  There are two major factors in coronary disease, the inflammatory response and that of the amount of the building materials for atherosclerosis—the cholesterol family of compounds.  Misleadingly it is the latter that has all the press and all the treatment.

 Plaque buildup is accelerated with high levels of LDL, but LDL level is not the driving engine, rather it is the inflammatory response within the artery wall (IR).  In other words, LDL is statistically relevant, but not that relevant, while the inflammatory response (IR) is very relevant. The poorly correlated LDL is easy to track:  current LDL level gives a good indication as to LDL levels over the past decade, and it is frequently measured.  On the other hand, current IR is poorly correlated to past levels, and is rarely tested for.  IR testing is both more expensive and rare (his-CRP, SSS proteins levels are two measures of IR).  Moreover, these markers of inflammation are not sufficiently specific:  inflammation in other tissues besides the artery wall will produce elevated CRP and SSS protein level.  Moreover, current high levels of markers doesn’t indicate if the current inflammation is of the sort that is correlated with coronary disease or provide information concerning various past inflammations.  Risk factors measured by inflammation markers, health problems, and cholesterol profile, are mere risk factors; viz., they are not test which affirm a disease. 

 Plaque build up occurs through oxidative damage to LDL, which occurs within the artery walls.   White blood cells play a crucial role through 5-LO, 12-LO, and 15-LO pathways which are involved in the oxidation of LDL (see  This process occurs within the artery wall.  Thus the very process of forming plaque is isolated and affecting the blood test.  (see for a very informative illustration of this process).  High levels of LDL means there is more of it for oxidative process to use in the build of plaque, and a a strongly positive test for the markers of inflammation could be a result of one of the types of infects which indirectly play a role in the white-cell mediated process within the artery wall.  For example gingivitis (gum disease) is correlated with atherosclerosis. There is an industry of lowering LDL because big PhARMA makes billions, and thus we test for cholesterol so that they can sell cholesterol lowering drugs. 

            Many results confirm that IR (inflammation response) is the main culprit: 1) the reduction in LDL level which is dramatic with the use of statins produces only a modest reduction in MI.  2) the use of VIOXX over 2 years resulted in a 200% increase in mortality among the elderly (exposed in the VIGOR study) because it increased the IR.  3) IR has a large body of research articles and its mechanism has been described in detail (see for example  4)  the role of tobacco—a pack a day over 20 years results in over a doubling the rate of deaths from MI.(see  The main cause is the circulation of reactive oxygen from carbon monoxide, which causes the oxidative damage to LDL.  5) Certain infections such as gingivitis are correlated with increased risk.  Point 2) needs further elucidation:  VIOXX and all COX-2 inhibitors--but for aspirin--shut off the mechanism which terminates the inflammatory response in the artery walls:  the inflammation response runs unchecked even when the cause has been removed.  Naproxin also given in the VIGOR increased mortality by 50%.  The elderly who all ready have significant atherosclerosis, COX-2 inhibitors such as VIOXX and Naproxin acceleration it and thus caused in the VIGOR study such a dramatic increase in MIs and deaths.  Points 1) & 2) are particularly dispositive:  modest reduction in MI with dramatic reduction in LDL, while allowing plaque formation to run unchecked produced a dramatic increase in MI.  Lower by drugs LDL is grossly over rated.      


It is not atherosclerosis that causes most of the MI, but rather unstable plaque.  Three imaging study have shown that “Most artery flow disrupting events occur at locations with less than 50% lumen narrowing (~20% stenosis is average).”  However, when the unstable plaque leaks it will reach clog a narrow opening down stream.  With atherosclerosis, this will often be a major coronary or ceberal artery  (see second illustration at; without atheroclerosis it will plug a smaller vessel.  Because of this nearly everyone over the age of 40 has unstable plaque, and thus is at risk of a MI or stroke. 


“Atherosclerosis is a common condition in both the developed and developing world and is now recognised to be an inflammatory condition leading to the development of ischaemic heart disease, cerebrovascular disease and peripheral vascular disease”-- British Journal of Anaesthesia 2006 97(6):758-769; doi:10.1093/bja/ael303, G.M. Howard. 


One would hope that a treatment reducing the inflammatory response would be developed.  However, such intervention would negatively affect both resistance to illnesses and infections and increase their severity.  Given the complexity of the immune response, it is not likely that such an approach would in the near future be developed.  Thus like cancer prophylactic measures are the best course.  The best of all interventions are the lifestyle changes:  strenuous exercise,* weight loss, and avoiding tobacco smoke.  To this add avoiding all NSAIDs but for aspirin.


*Strenuous exercise, which gets up the heart rate to about 80% of maximum, stimulates the development of new coronary vessels, and also widens them.  This reduces the risk of a clot blocking a major coronary vessel.   

Hemscott Report at

AstraZeneca's CORONA trial shows Crestor adds no extra benefit for patients

LONDON (Thomson Financial) - AstraZeneca PLC's long-awaited 'CORONA' trial examining the possible benefits of the company's Crestor heart product has failed to show any additional benefit for patients when used in addition to the leading heart treatment, the company said.

Patients taking Crestor had an average 8 pct improved prognosis, but this was not statistically significant, Astra said.

The widely predicted result means that AstraZeneca has to find other ways of extending Crestor's patent life.

Crestor sales in the year-to-date were 2 bln usd, the company said. jh1/slj



The Wall Street Journal at 

November 5, 2007, 8:01 am

Crestor Comes Up Short in Heart Failure

Posted by Ron Winslow


In the statin wars, there’s little question that AstraZeneca’s cholesterol-lowering drug Crestor is the most powerful when it comes to lowering LDL, the bad cholesterol, and giving a boost to good HDL.

But the company lacks–and craves–for Crestor what arch-rival Pfizer has for Lipitor, the world’s biggest selling drug, and what Merck and Bristol-Myers long had for their now off-patent statins: hard data that the effect on patients’ cholesterol reduces deaths, heart attacks and other consequences of heart disease.  {Evidence strongly suggest that it is the effect upon thrombus that lowers the death rate.  The same may be obtained with aspirin—jk}

Today, researchers are reporting results of the AstraZeneca’s 5,011-patient Corona trial testing Crestor in heart failure patients, and the company still hasn’t found what it was looking for. During nearly three years of follow-up, patients taking Crestor had an 8% reduction in the combined outcomes death from cardiovascular causes and non-fatal heart attacks and strokes compared to placebo. That difference wasn’t large enough to be statistically significant.

Heart failure seems an unlikely spot to test a statin–evidence that cholesterol levels play a role in the disease is sparse. But AstraZeneca’s challenge was that the benefits of statins were already well-established in coronary artery disease by such landmark trials as Merck’s 4S study and Bristol-Myers Care study. What was left to try?

“It was hardly ethical to do a placebo-controlled trial” in already established areas of statin benefit, Michael Cressman, executive director, strategic development for Crestor at AstraZeneca, told the Health Blog at the American Heart Association’s science meeting in Orlando where the Corona data were unveiled this morning. And a head-to-head study against Lipitor, for instance, would have required tens of thousands of patients, with no assurance that Crestor would prove substantially better at reducing deaths and heart attacks.

The Corona data have a few positives for Crestor. The drug reduced heart-related hospitalization, and the study didn’t find any evidence that statins might harm patients with heart failure–a previously unanswered and controversial question. But in the Corona study deaths from heart failure, which typically result from irregular heart beats caused by abnormalities in the heart’s electrical system dominated over deaths from artery blockages, plumbing problems that statins help prevent.

“Coming into the statin world as late as we did made it very difficult,” Cressman says. “The low-hanging fruit had already been picked.”

Those who have a financial interest in the outcome manipulate the results, Major study finds that all 37 journal articles positive effects over stated; the average was 32%. Statins cause erectile dysfunction, cognitive imparement, and cancer.  

Lipitor (2011) lifetime sales $131 billion, tops all drugs.  Plavix at $60 billion is second.



52% short term


LA Times, Health section, July 21, 2008  --  excerpts

Vytorin, the combination drug (simvastatin (better known by its commercial name Zocor) and ezetimibe--known as Zetia) prescribed to lower cholesterol, sustained another blow today, when the author of a major clinical trial announced that the medication had failed to drive down hospitalization and death due to heart failure in patients with narrowing of the aortic valve. In the process, researchers in Norway detected a significant blip in cancers in the 1,800 subjects they followed

Today's findings suggested something more ominous: the incidence of cancer -- and of dying of cancer -- was significantly higher in the patients taking Vytorin. Altogether, 67 patients on placebo developed cancer during the trial. Among subjects on Vytorin, 102 developed cancers of various kinds.*  This is the second adverse press—the first being in March 08, when the ENHANCE trial found that Vytorin fared no better than a placebo at reducing plaque buildup on the walls of patients' arteries.* *

Comments by jk

Simvastatin (Zocor) is off patent.  Thus in a scramble for profits a combination drug (on patent) was introduced.  Direct to consumer market cost $155 in 07—mainly TV ads. 

*  The pressing issue is that since the development  of Statins, the very first animal studies in the 60s it has been known that Statins increase the incidents of cancer.  However, nearly all studies done thereafter have not included cancer. 

*  Several studies have failed to find a reduction in the build of plaque, even thought the statins including Zocor, reduce LDL and cholesterol.  Few studies include the principle reason for taking a statin, namely a reduction in the death rate.  Claims for such reduction probably entail a failure to control the contravening variable, aspirin usage.  Given a pile of evidence, including the very mechanism of plaque formation, which involves inflammation process, I must conclude that the use of statins is highly suspect.  Given the harm done including cognitive impairment, weakness, and cancer, if my skepticism is born out, the harm done by statins as a course of treatment will far surpass that of VIOXX which killed over 200,000 people world wide by accelerating atherosclerosis.