Hyperinsulinemic microalbuminuria. A new risk indicator for coronary heart disease.

BACKGROUND

Both hyperinsulinemia and microalbuminuria have been shown to increase coronary heart disease (CHD) risk, but the interaction among hyperinsulinemia, microalbuminuria, and the risk for CHD has not been investigated in previous studies.

METHODS AND RESULTS

The risk of CHD in relation to hyperinsulinemia and microalbuminuria was examined in a cohort of 1069 elderly nondiabetic subjects from Kuopio, east Finland, during 3.5 years of follow-up. The overall incidence of CHD death was 2.8%, and 6.9% of study subjects died of CHD or had a nonfatal myocardial infarction (later referred to as all CHD events). In the highest fasting-insulin quintile (fasting insulin > or = 114.0 pmol/L), there was a slightly but insignificantly higher incidence rate of both CHD mortality and all CHD events compared with lower quintiles. The incidence rates of CHD mortality and all CHD events were significantly higher in the highest urinary albumin/creatinine ratio (ACR) quintile (ACR > or = 3.22 mg/mmol) compared with lower quintiles (P < .05 and P < .01, respectively). Hyperinsulinemic microalbuminuria (simultaneous presence of fasting insulin > or = 114.0 pmol/L and ACR > or = 3.22 mg/mmol) markedly increased the risk of CHD mortality (12.5%, P < .001) and all CHD events (18.8%, P < .001) compared with normoinsulinemic subjects without microalbuminuria (2.2% and 5.8%, respectively). In univariate logistic regression analyses, hyperinsulinemic microalbuminuria was a strong predictor of both CHD death (odds ratio [OR], 5.93; P < .001) and all CHD events (OR, 3.39; P = .002). Multivariate logistic regression analyses were also performed, including sex, current smoking, waist-hip ratio, systolic blood pressure, and HDL cholesterol, with insulin, ACR, or both as independent variables. Even after adjustment for these variables, hyperinsulinemic microalbuminuria remained a strong predictor of CHD death (OR, 7.91; P < .001) and all CHD events (OR, 2.95; P = .014). The group with hyperinsulinemic microalbuminuria was characterized by the most adversely affected risk factor pattern (high triglycerides > or = 2.3 mmol/L, low HDL cholesterol < or = 0.9 mmol/L in men and < or = 1.20 mmol/L in women, and hypertension).

CONCLUSIONS

Simultaneous occurrence of hyperinsulinemia and microalbuminuria identifies a group of subjects with a highly increased risk for CHD in elderly nondiabetic subjects.