BackgroundAn inconsistent relationship has been reported between insulin and hypertension incidence. Free fatty acids are related to insulin-resistance and may have a direct effect on hypertension. We examined the effect of free fatty acids on hypertension incidence, taking into account other abnormalities of the insulin-resistance syndrome.MethodsIn all, 2968 non-hypertensive and non-diabetic Caucasian men were followed for 3 years. Hypertension incidence was defined as systolic blood pressure (SBP) ≥160 mmHg or diastolic blood pressure (DBP) ≥95 mmHg or drug treatment for hypertension.ResultsFree fatty acid elevation was a highly significant risk factor for hypertension when controlled for age, family history of hypertension, alcohol consumption, body mass index, iliac circumlerence and weight change. Further controlling for SBP, heart rate and fasting insulin and glucose did not decrease its predictive power (hazard rate ratio [RR]=1.58, 95% confidence interval [CI]: 1.30–1.91 comparing the 90th to the 10th percentiles at fasting; RR=1.54, 95% CI: 1.33–1.79 at 2 h). In a forward stepwise model controlled for age, family history of hypertension, alcohol consumption and SBP, the selected variables explaining the occurrence of hypertension were, in order, weight change, 2-h free fatty adds, iliac circumference and fasting free fatty acids, whereas body mass index, heart rate, insulin, glucose and other lipids did not enter into the model.ConclusionsFree fatty acids elevation, when controlled for all known risk factors and other abnormalities of the insulin-resistance syndrome, is a risk factor for hypertension. These results highlight the possible benefits of treatment using free fatty acid oxidation inhibitors.