Heart Attacks, A Test Collapses

MRFIT Trial: Does high cholesterol cause heart disease?

Here’s another trial for thought:
They come up with great names for research trials. MRFIT actually means Multiple Risk Factor Intervention Trial. Done in the early 1970’s to prove that the risk factors associated with heart disease were cigarette smoking, high cholesterol, and high blood pressure.

Out of 362,000 middle aged men, 12,000 had cholesterol higher than 290 mg/ml. At that time, it was believed they were a heart attack waiting to happen. The investigators thought that this men were so ready to “have the big one” that interventions would show a dramatic benefit. These men were followed for seven years at a cost of $115 million. They were split into two groups: one group that would carry on the same way they had been living, eating, drinking, smoking or whatever and the other group that was counselled to eat a low-fat, low-cholesterol diet, drinking skim milk, eating no more than two eggs a week, using margarine instead of butter, avoiding red meat and all pastries and baked goods.

     Wall Street Journal, in 1982, announced the long awaited results: “Heart Attacks: A Test Collapses. The latter group, who had been counseled to “eat healthier”, had more deaths.
      Twenty-one percent of the men in that group had quit smoking. They also had more lung cancer than the “carry on” group. The question brewing was, “Does lowering cholesterol put men at risk for developing cancer. By 1980, study after study showed a link between lowering cholesterol and cancer. We know that saturated fats are heart-healthy. Removing meats, butter and eggs increases our risk for heart disease.

MRFIT Mortality

The Multiple Risk Factor Intervention trial was a very large controlled diet trial conducted in the 1980s. It involved an initial phase in which investigators screened over 350,000 men age 35-57 for cardiovascular risk factors including total blood cholesterol. 12,866 participants with major cardiovascular risk factors were selected for the diet intervention trial, while the rest were followed for six years.
During the six years of the observational arm of MRFIT, investigators kept track of deaths in the patients they had screened. They compared the occurrence of deaths from multiple causes to the blood cholesterol values they had measured at the beginning of the study. Here’s a graph of the results.

Coronary heart disease does indeed rise with increasing total cholesterol in American men of this age group. But total mortality is nearly as high at low cholesterol levels as at high cholesterol levels. What accounts for the increase in mortality at low cholesterol levels, if not coronary heart disease? Stroke is part of the explanation. It was twice as prevalent in the lowest-cholesterol group as it was in other participants. But that hardly explains the large increase in mortality.

Possible explanations from other studies include higher cancer rates and higher rates of accidents and suicide. But the study didn’t provide those statistics.

The MRFIT study cannot be replicated, because it was conducted at a time when fewer people were taking cholesterol-lowering drugs. In 2009, a 50-year old whose doctor discovers he has high cholesterol will likely be prescribed a statin, after which he will probably no longer have high cholesterol. This will confound studies examining the association between blood cholesterol and disease outcomes.