Coronary Heart Disease Risk Factors - Part II
Homocysteine

Homocysteine is a chemical (amino acid) that is found naturally in the blood. Homocysteine helps LDL Cholesterol ("bad cholesterol") build fatty plaques in the coronary arteries. Initial studies show that a higher than average level signals an increased risk for CHD.

According to Reference 1, the role of homocysteine was first observed in the 1960s and 1970s. Patients with certain metabolic disorders that resulted in extremely high levels of homocysteine in the blood and urine, subsequently developed arterial or venous thrombosis by 30 years of age. The risk was significantly reduced by high-dose B vitamins which partially lower homocysteine levels back towards the normal range. Subsequently, it was postulated that mild to moderate elevations of homocysteine in the general population similarly predispose to atherosclerosis. Consequently, one might expect B vitamin therapy to lower homocysteine and with it - CHD risk.

Reference 2 provides a meta-analysis of several studies involving homocysteine. There were a total of 5073 CHD events and 1113 stroke events in a total of 30 studies that were included. Corrections were made to isolate the effect of homocysteine from other cardiovascular risk factors. They found that a 25% lower homocysteine level (3 micro-mol/Liter) corresponded to an 11% (0.83 - 0.95 Margin of Error) lower CHD risk, and a 19% (0.69 - 0.95 Margin of Error) lower stroke risk. They conclude that elevated homocysteine is at most a modest independent predictor of CHD and stroke in healthy people. Whether lowering homocysteine has any impact on CHD remains to be seen.

In reference 3, results of comparing high doses of folic acid, vitamin B6 and vitamin B12 to low doses over a period of 2 years were obtained in a trial involving 3680 adults, with a mean age of 66, who had a stroke. They found that lowering of homocysteine did not have a measurable effect on the risk of subsequent CHD or stoke events. They find that an initial homocysteine value that is lower by 3 micro-mol/Liter is associated with a 26% lower risk of CHD events, and a 10% lower risk of stroke - in the low vitamin dose group only!

Update (4/15/2006): two new studies, both published in NEJM online, March 2006, also conclude that vitamin therapy to lower homocysteine is not effective. Given the thousands of patients involved in these studies, the results should be considered conclusive

Reference 4 deals with vitamin therapy after "Percutaneous Coronary Intervention". Percutaneous means "through the skin". The study deals with treatment after inserting a stent - a device implanted in a blood vessel to keep it open. It is often necessary to replace a stent after a certain period. An initial 6-month study (reference 5) indicated that vitamin therapy decreased the rate at which the restenting was required. In reference 4, the study was extended to a full year. They found that the rate at which there was a need to reopen the artery was reduced from 16% to 9.9%. The risk reduction associated with this was 0.62 (0.40 - 0.97 Margin of Error). However, they did not find a statistically significant reduction in the total number of CHD events.

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