What do we gain by modifying risk factors for coronary disease?

There is no doubt about the association between coronary heart disease (CHD) and smoking, high serum cholesterol and high blood pressure, but association does not mean causation. To prove causation we must mount intervention trials and show that changing a risk marker changes total mortality: a) Trials of dietary reduction of serum lipids: The US Veterans dietary study and the North Karelia project showed no significant reduction in total mortality, nor did the Multiple Risk Factor Intervention Trial (MRFIT) or the WHO "paired-factories" Collaborative Group Study, where other risk factors were also being corrected. In the latter study there was a barely significant reduction in non-fatal CHD but fatal CHD, like total mortality was unchanged. b) Trials of lipid-lowering drugs: The first large-scale study, using clofibrate, showed an increase in total mortality; the screening of 500,000 men and the comparison of cholestyramine with placebo for the top 5% of lipid levels resulted in 68 deaths on the active resin and 71 on placebo. Less expensive measures (alcohol testing; safer roads) could surely do more good to half a million men? These 3 lives "saved" were "lost" in the Helsinki gemfibrozil study where there were 45 deaths in the active group and 42 in the placebo group. c) Effect of blood-pressure reduction. The assumption that reducing a risk marker will reduce CHD was challenged by the massive MRC Mild-to-Moderate Hypertension trial which showed no significant effect of treatment on CHD, CHD death or total mortality, even though stroke mortality was modestly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)