High proinsulin concentration precedes acute myocardial infarction in a nondiabetic population

Hyperinsulinemia has been shown tio have strong and consistent associations with a cluster of cardiovascular risk factors. Yet the associations betwee n hyperinsulinemia and coronary heart disease (CHD) have been weak, at best , and often inconsistent. Most previous studies have analyzed the insulin l evel using a radioimmunoassay method, which does not separate proinsulin fr om intact (true) insulin, New methods separating the two have demonstrated that proinsulin may be at least as strongly or even more strongly associate d than intact insulin with a CHD-promoting risk factor profile. In this inc ident case-control study of a nondiabetic population, 67 cases of first acu te myocardial infarction (AMI) were compared with 127 individually age- and sex-matched controls. Blood sampling was collected prior to disease outcom e. Proinsulin and intact insulin levels were measured using highly sensitiv e two-site sandwich enzyme-linked immunosorbent assays (ELISAs), The highes t quartile of proinsulin, in contrast to intact insulin, showed a greater t han threefold increase in AMI compared with the lowest quartile, with an od ds ratio (OR) and 95% confidence interval (CI) of 3.5 and 1.2 to 9.9, respe ctively. The increased risk of AMI persisted after controlling for total ch olesterol, smoking status, diastolic blood pressure, and antihypertensive m edication, and disappeared after additional control was used for the body m ass index. High levels of proinsulin, even in a nondiabetic population, see m to be a strong and independent risk factor for AMI, The mechanism underly ing the relationship may be direct via effects on fibrinolysis or, probably more plausibly, indirect, where proinsulin is a marker of an underlying me tabolic disturbance. Copyright(C) 1999 by W.B. Saunders Company.