Small, dense low-density lipoproteins (LDL) are predictors of cardio- and cerebro-vascular events in subjects with the metabolic syndrome

Small, dense low-density lipoproteins (LDL) are a feature of the metabolic syndrome (MS) but their predictive role still remains to be established. We performed a 2-year follow-up study in 124 subjects with MS (63 +/- 6 years), as defined by the American Heart Association/National Heart, Lung and Blood Institute guidelines, to assess clinical and biochemical predictors of cerebro- and cardio-vascular events. Beyond traditional cardiovascular risk factors, we measured LDL size and subclasses by gradient gel electrophoresis. Clinical events were registered in the 25% of subjects. At univariate analysis subjects with events had increased prevalence of elevated fasting glucose (P = 0.0117), smoking (P = 0.0015), family history of coronary artery disease (P = 0.0033) and higher levels of total- and LDL-cholesterol (P = 0.0027 and P = 0.0023, respectively); LDL size was lower (P < 0.0001), due to reduced larger subclasses and increased small, dense LDL (all P < 0.0001). At multivariate analysis the following were independent predictors of events (univariate odd ratios were calculated): low HDL-cholesterol (OR 15.4, P = 0.0238), elevated fasting glucose (OR 12.1, P = 0.0102), elevated small, dense LDL (OR 11.7, P = 0.0004), elevated blood pressure (OR 9.2, P = 0.0392), smoking (OR 4.8, P = 0.0054). This is the first study that assessed the predictive role of small, dense LDL beyond traditional cardiovascular risk factors in subjects with MS.