Statins, Heart Disease and Inflammation

There are a few lines of evidence. One is that people with immune diseases like rheumatoid arthritis and lupus have a raised risk of heart attacks. It’s also known that white blood cells and immunological hormones assist cholesterol damage in arteries.

And it is also known that statins - cholesterol-lowering medications - reduce the risk of heart attacks more than you’d expect from their cholesterol reduction, and they have immune effects.

Summarizing the findings from the three recent papers, they suggest that while cholesterol lowering is still vital, reducing inflammation - the immune reaction in arteries - is important too.

In one study of people on statins, the lower the inflammation, the lower the heart attack risk. In another study of people on a statin, the lower the bad form of cholesterol and inflammation, the slower artery blockage progressed. And a third study of markers of inflammation showed an association with the risk of heart disease.

Some lifestyle changes may help lower inflammation, like exercise and diet if you don’t like fancy medications, but that’s yet to be proven conclusively.

Dr. Norman Swan

For Reference

Title: New England Journal of MedicineAuthor: Nissen S et al, Statin therapy, LDL cholesterol, C-reactive protein and coronary heart disease. URL: http://content.nejm.org/ 2005, vol 352, pp 29-38.
Title: New England Journal of MedicineAuthor: Ridker PM et al, C-reactive protein levels and outcomes after statin therapy. URL: http://content.nejm.org/ 2005, vol 352, pp 20-28..
Title: New England Journal of MedicineAuthor: Ehrenstein MR et al, Statins for atherosclerosis - a good as it gets? URL: http://content.nejm.org/ 2005, vol 352, pp 73-75.
Title: New England Journal of MedicineAuthor: Pai J et al, Inflammatory markers and the risk of coronary heart disease in men and women. URL: http://content.nejm.org/ 2004, vol 351, 2599-2610.
ABC Flameez

Looking Beyond Cholesterol

Inflammation and Heart Disease

Looking Beyond Cholesterol

Cardiovascular disease (CVD) continues to be the leading cause of death for Americans. We’ve learned that smoking, elevated serum cholesterol levels, hypertension, and diabetes place people at greatly increased risk of heart disease and sudden cardiac death. But for many of the 250,000 people who succumb each year from sudden cardiac death, cholesterol - now the main focus of prevention efforts - is simply not a factor. Cholesterol screening fails to identify about 50% of those who have heart attacks in the US, because their total cholesterol is either normal or only slightly elevated (1). And that fact has aled researchers on a decade-long search to find new factors that can help predict who is at risk for heart disease and stroke.

C-Reactive Protein: Emerging Risk Factor

The most important new risk factor to emerge is C-reactive protein (CRP), a protein produced in the liver and released into the blood stream when inflammation is present (2). High levels of this protein may explain why some people with low cholesterol develop heart disease, or why strict adherence to a cholesterol-lowering diet sometimes fails to prevent serious heart problem. In fact, an estimated 25-30 million people fall into the low cholesterol/high CRP category. In the ongoing Physicians’ Health Study of 22,000 men, only CRP was predictive of those who suffered sudden cardiac deaths over 17 years of follow-up (3). For some women, too, CRP appears to be a better predictor of stroke, heart attack and other signs of CVD than low-density lipoprotein or LDL, the “bad” cholesterol (4).

Inflammation and CVD

There’s been a major shift in thinking about atherosclerosis - the gradual process where hardened cholesterol substances called plaque, cause clogged and narrowed arteries. Once thought to be simply a disease where too much cholesterol is stored in artery walls, it’s now widely accepted that inflammation is central to every aspect of the atherosclerotic process, from its initiation, to its progression, to the rupture of plaque. We now know that local inflammation helps trigger heart attack or stroke by making plaque less stable and therefore more likely to rupture and generate artery-blocking clots. People with elevated CRP either have plaques that are more inflamed, or they have a more easily triggered inflammatory response that makes their plaques more prone to rupture.

The CRP Test

CRP is measured by a simple inexpensive blood test. The best results are obtained through two separate tests that are done at least two weeks apart, with their results averaged. Experts from the Center for Disease Control and Prevention (CDC) and the American Heart Association (AHA) concluded in 2002 that people considered to be at “intermediate” risk of a heart attack, stroke, or other CVD event, should be tested for CRP. Those with CRP with levels of one milligram per liter (1 mg/L) or more should be treated aggressively to bring their levels down. Intermediate risk is defined as people with a 10-20% chance of developing CHD within 10 years, based on age, total cholesterol level, smoking status, systolic blood pressure (the upper number), and level of protective HDL.

The CDC and AHA don’t recommend CRP testing for those at low risk of CHD, or for those at high risk either. High risk people are those who are already having symptoms or signs of trouble and should already be getting aggressive treatment. The rationale for not testing low risk people (younger aged, non-smokers with low total cholesterol and high HDL), is that a high CRP reading (over 3) wouldn’t change their official recommended course of treatment - dietary and lifestyle changes.

Most clinicians look at blood cholesterol as an indication of how much plaque is likely to be in the arteries, while CRP signals how likely that plaque is to rupture and release dangerous plaque-containing clots into the blood stream. It’s important to remember that one test doesn’t replace the other, and both cholesterol and CRP screening have value.

Part II:Anti-Inflammatory Action Plan

Science Based Health

References

Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis 124:S1-9, 1996.

Hackam DG and Anand SS. Emerging risk factors for artherosclerotic vascular disease: A critical review of the evidence. JAMA 290:932-40, 2003.

Albert CM et al. Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 105(22):2595-9, 2002.

Ridker PM et al. Comparison of C-reactive protein and low density lipoprotein cholesterol levels in the prediction of first CVD events. N Eng J Med 347:1557-65, 2002.

Sesso HD et al. C-reactive protein and the risk of developing hypertension. JAMA 290:3000-2, 200

The Statin Scam

The television ad featuring artificial heart inventor Dr. Robert Jarvik, who by the way can’t row a skull, and never practiced medicine, claims that Lipitor will lower heart attack risk by 36%. Now, who wouldn’t want to do that?

However, the fine print required says, “in a large clinical study 3% of people taking placebo had a heart attack and 2% of those taking Lipitor had a heart attack.” Let’s do the math.

For every 100 people in the trial that lasted for 3 1/2 years, three people on placebo, and two people on Lipitor had heart attacks-that is one less heart attack for every 100 people. In other words, 100 people had to take the drug for 3 1/2 years to prevent one heart attack. What this really means is 99 out of 100 people taking the drug had no benefit.

This is explained in a little known statistic called Number Needed to Treat (NNT). In the case of Lipitor, 100 patients would have to be treated for 3 1/2 years to possibly eliminate one heart attack. Let’s compare that to today’s antibiotic treatment to eradicate ulcer causing H. pylori stomach bacteria.

The NNT is 1.1, which means, give the antibody to 11 people and 10 will be cured. Several recent scientific papers peg the NNT for statins at 250. Dr. Jerome R. Hoffman, Professor of Clinical Medicine at UCLA asks:

“What if you put 250 people in a room and told them that they each would have to pay over $1000 per year for a medicine they must take every day, that may give them diarrhea and muscle pain, and that 249 would get no benefit, how many would take that?”

Marketing over Medicine!

Drug companies have a responsibility to their shareholders to make a profit, and we need them to develop new medicines. However, when they grossly overstate the benefits and spend huge amounts of money influencing physicians it turns bad and leads to potential corruption.

The National Cholesterol Education Program, (NCEP) 2004 guidelines that lowered the targets for cholesterol treatment and recommended many more Americans take statins was issued by a panel on which 8 of 9 experts at financial ties to the drug industry.

“The guideline and process went awry” says Dr. Henry C. Barry of the Michigan State University College of Medicine. Dr. Barry and 34 other experts sent a petition of protest to the National Institutes of Health, saying the evidence was weak and the panel biased because of its ties to the drug industry.

I and all other physicians whose speak out take great risks-medicine and government agencies do not like criticism. At a recent meeting, a prominent statin boosting physician who advises the NCEP says that Dr. Rodney A. Hayward, Professor of Internal Medicine at the University of Michigan Medical School “should be held accountable in a court of law for doing things to kill people” because Dr. Hayward had the audacity to suggest that “current evidence supports ignoring LDL cholesterol altogether.”

We would expect this kind of vitriol from zealots and extremists not from government agencies or scientists. If we spent a fraction of the money that we do on cholesterol testing, cholesterol lowering drugs, and doctor visits on educating people about proper diet, exercise and weight loss we would be far healthier.

–Dr. Dwight Lundell