Hyperinsulinemia and the Risk of Cardiovascular Death and Acute Coronary and Cerebrovascular Events in Men

This Finnish cohort study followed 1,521 middle-aged men to determine whether fasting insulin levels predicted cardiovascular death and acute coronary events — and whether any association survived adjustment for the metabolic factors that typically accompany insulin resistance.

Hyperinsulinemia was modestly associated with cardiovascular mortality in unadjusted analysis. After adjustment for its metabolic companions — obesity, hypertension, dyslipidemia, and the broader insulin resistance cluster — the independent association attenuated substantially. The signal did not disappear, but the residual independent contribution was modest.

The finding illustrates a recurring challenge in metabolic epidemiology: insulin resistance travels with hypertension, abdominal obesity, dyslipidemia, and low-grade inflammation, making it difficult to isolate insulin’s independent atherogenic contribution. Whether hyperinsulinemia causes cardiovascular events directly or is primarily a marker of the metabolic syndrome’s broader pathology remains unresolved.

We rate the evidence moderate. A carefully conducted Finnish cohort study with honest reporting of mediation; the finding supports metabolic syndrome as an integrated risk entity and cautions against treating fasting insulin as an independent therapeutic target isolated from its metabolic context.