ObjectiveTo determine whether combinations of metabolic risk factors (obesity, diabetes and hypercholesterolemia) influence the magnitude of left ventricular (LV) mass and prevalence of LV hypertrophy.DesignCross-sectional, relational.MethodsA total of 1627 hypertensive (85.9% treated, 1036 women, 1041 African Americans) and 342 normotensive (180 women, 183 African Americans) participants in theHypertensionGeneticEpidemiologyNetwork (HyperGEN) Study, without prevalent cardiovascular disease, were studied. Echocardiographic LV mass, normalized by height2.7or fat-free mass or body surface area (BSA) and the ratio of stroke volume to pulse pressure as a percentage of predicted (as a crude estimate of arterial compliance) were analyzed in relation to obesity [by body mass index (BMI)], central fat distribution (by waist circumference), diabetes (by ADA criteria) and hypercholesterolemia.ResultsObesity, hypercholesterolemia, and diabetes were more frequent among hypertensives than normotensives (allP<0.001). After controlling for age, sex, race and type and combination of antihypertensive medication, LV mass/height2.7, but not LV mass/fat-free mass and LV mass/BSA, increased with the number of metabolic risk factors, both in normotensive and hypertensive participants, also after further adjustment for blood pressure (allP<0.001). Stroke volume/pulse pressure also decreased in hypertensive, but much less in normotensive subjects, with increasing number of metabolic risk factors, independently of relevant confounders (P<0.0001). Prevalence of LV hypertrophy was predicted by older age, hypertension, central fat distribution, black race and independently increased with the number of associated metabolic risk factors (P<0.0001).ConclusionsThe progressive addition of metabolic risk factors including central obesity, diabetes and hypercholesterolemia is associated with higher LV mass normalized by height2.7, independently of hypertension and other important biological covariates. Obesity played a major role in this association. This finding indicates that LV mass is a potentially useful bioassay of strategies of global cardiovascular prevention.