TL;DR: A bunch of businessmen in Helsinki were selected for a long-term study on cardiological issues (cardiovascular disease, coronary heart disease). Some were identified to be in a high CVD risk group. Then, that group was split into intervention group and control group.<p>> The multifactorial intervention consisted of both intensive lifestyle modification (diet, exercise, smoking, alcohol) and contemporary drug treatment (using mostly diuretics and beta-blockers for hypertension, clofibrate and probucol for hyperlipidaemia). Control groups were in usual care.<p>In the end, higher original CVD risk <i>was</i> found to correspond to higher mortality, and a few of previously somewhat-noncontroversial facts were confirmed (alcohol consumption, smoking, BMI contributing to poorer health).<p>What’s interesting, though, is that after checking mortality and causes of death in the national registry later those in the intervention group were found to do <i>worse</i> than high-risk non-intervention (control) group.<p>The “refused” group (which consisted of both low-risk and high-risk men who declined to participate in the intervention) also had higher mortality.<p>I’m sure there’s a bunch of confounding variables (I’d particularly look at using all the meds as part of the intervention), but it’s interesting.<p>> A national register-based follow-up for mortality and causes of death through 1989 (i.e. 10 years post-trial) in the intervention and control groups unexpectedly showed that all-cause and especially cardiac mortality was increased in the intervention group as compared with high-risk controls. The controversial results were published in JAMA in 19854 and post-trial results 1991. The results raised wide international discussion in both medical journals and the lay press.<p>> Thus far, explanations of this adverse result have not surfaced; for example, cholesterol lowering, or the lower HDL cholesterol induced by probucol treatment in the intervention group, did not explain the adverse result. Psychological stress associated with the guidance for lifestyle changes in the intervention group has been hypothesized to be an explanatory factor. Long-term follow-up and new analyses of baseline factors in a hypothesis-generating manner are ongoing.<p>My intuition is that approaching individual metrics like low cholesterol, etc. as “causing” better health is not necessarily effective, if they’re more of indicators of some other underlying cause.