Aspirin, Lipoprotein A, CRP, Anti-oxidants, Heart disease

There have been a number of articles published recently in Lancet, Journal of the AMA, and newspapers about primary prevention of heart disease. By primary prevention, we mean the reduction of risk of a heart attack in patients who have not had a heart attack. Since the greatest risk for having a heart attack is having had one, the number of patients in a study of primary prevention has to be larger and last for a longer time than a study of secondary prevention, where aspirin, beta-blockers, statins, etc., have been shown to be of help.

I should also mention that the over-riding problem in prevention of any disease is not lack of communication between doctors and patients,or lack of information on the part of patients, but the unwillingness of patients to change their behavior (and no, I am not blaming the victim). Most patients know that they should exercise, lose weight, and stop smoking to reduce their primary heart attack risk, but how many do, even if, as in NYC, the amount of calories per dish is published in the menu of every chain restaurant?

1) C-reactive protein, or CRP. Numerous studies have shown a correlation between elevated CRP and heart attacks. This correlation is about as strong as that between elevated homocysteine and heart attacks. However, just as pulling down on the metal elevator arrow in the lobby of a skyscraper does not bring the elevator down, lowering the homocysteine has not been shown to lower heart attack risk. Whether the CRP as a marker for inflammation means that inflammation is a primary risk factor remains to be seen. A recent published genetic analysis (similar to the Lp(A) analysis) seem to show that lowering CRP does NOT lower the risk for heart disease.

2) Aspirin. First we have to decide if we mean 81mg/day, 325 mg/day, or 325 mg twice a day. Since aspirin blocks platelet clumping for 7 days, it is not clear why the studies involved daily aspirin, rather than once or twice a week. In addition, none of the studies to date controlled for aspirin resistance, where aspirin at the suggested dose does not prevent platelet clumping. It has been a "consensus" that absent any other risk factors (smoking, diabetes,etc.) that aspirin prevention should start at age 45 for men and 55 for women. However, a recent article Lancet cast severe doubt on this recommendation, so your guess is as good as mine.

3) Lp(A), or lipoprotein A. A recent article used genetic analysis to suggest that elevated Lp(A) is an independent risk factor for heart attacks. However, no one has shown that lowering Lp(A), prevents heart attacks, nor do we have a good drug to lower Lp(A). The same could be said in reverse about low HDL, the "good" cholesterol.

4) Anti-oxidants. The prophylactic use of anti-oxidants should be approached with caution. Prospective studies have shown that extra daily Vitamin E increases the primary risk for heart attacks, and prophylactic beta carotene increases the risk for lung cancer in cigarette smokers. A recent study at Memorial Sloan-Kettering showed in vitro that vitamin C inhibited the killing effect of chemicals on cancer cells. Selenium and vitamin E have been shown to have no protective effect against prostate cancer.

The conceptual problem is, of course, that correlation does not imply causation. Just recall how coffee drinking was "shown" to be a risk factor for heart attacks until it was realized that more coffee drinkers than non-drinkers smoke cigarettes. We always have to beware of confounding factors, as well as a common cause that elevates both the risk of disease and the marker. Does anyone really understand why female Pima Indians of the American Southwest have such a high incidence of cholecystitis, or the female Parsees of India (Zoroastrians transplanted from the Mideast) have such a high incidence of breast cancer?