Homocysteine: A Risk Factor Worth Ignoring

Last month’s New England Journal of Medicine has a great lesson about how we should think about risk factors.

It’s been long known that homocysteine is a risk factor for heart disease. That means that, when looking at large numbers of people, those with high levels of homocysteine have more heart attacks on average than those with low levels. Too frequently, we confuse a risk factor with a cause, and we jump to the conclusion that homocysteine causes heart attack. A risk factor, however, is not necessarily a cause. It may simply be a marker of risk.

It has also been long known that supplements of vitamin B12, vitamin B6 and folic acid decrease homocysteine levels in patients with elevated levels. This persuaded many doctors (me included) to recommend these vitamins to our patients with elevated homocysteine in the hopes that doing so would help prevent heart attacks. A study in April’s New England Journal of Medicine demonstrates that our hopes were not founded.

The study randomly assigned patients who recently had a heart attack to take the vitamin supplements or placebo. The patients who were on vitamin supplements had significant lowering of their homocysteine but no difference in their risk of a future heart attack. The implications are clear: homocysteine is a marker of cardiac risk, but altering it does not alter the risk itself.

I’m asking my patients taking the supplements for heart-attack prevention to discontinue them. We should instead be focusing our attention on risk factors for heart disease that have been proven to prevent heart attacks when well controlled: blood pressure, cholesterol, diabetes, and smoking.

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