Background The epidemiologic data on heart failure are scarce. This study aimed at identifying predictors of left ventricular systolic dysfunction in a cohort of middle-aged men with a 20-year follow-up. Methods A population-based cohort of 431 50-year-old men was examined with blood pressure and anthropometric measurements together with lipid, glucose, and insulin determinations. A reinvestigation 20 years later also included echocardiography, ambulatory blood pressure monitoring, hyperinsulinemic euglycemic clamp, and oral glucose tolerance test. Sixteen subjects were found to have left ventricular systolic dysfunction at age 70 years, defined as an ejection fraction ≤0.40. A control group of 48 subjects matched on myocardial infarction, hypertension, diabetes, and use of cardiovascular medication, but with an ejection fraction >0.40, was used in a nested case-control analysis. Results At age 50 years, heart rate (P <.01), plasma proinsulin (P <.05), and the proportion of dihomogammalinolenic acid in serum cholesterol esters (P <.05) were increased and serum phosphate decreased (P <.01) in the subjects identified with left ventricular systolic dysfunction at age 70 years compared with controls. No major metabolic abnormalities were associated with left ventricular systolic dysfunction at age 70 years compared with controls. Conclusion Factors associated with insulin resistance precede left ventricular systolic dysfunction independently of ischemic heart disease and hypertension after 20 years of follow-up. (Am Heart J 2001;142:720-4.)