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Discuss the contribution of low-density lipoprotein subclass abnormalities to cardiovascular risk among individuals with low high-density lipoprotein cholesterol levels.Low high-density lipoprotein cholesterol levels are commonly encountered among patients with early onset cardiovascular disease. Most often, a low high-density lipoprotein cholesterol level is not an isolated abnormality, but it is usually associated with a number of other lipoprotein abnormalities. Data from the Framingham Offspring Study demonstrate that among subjects with high-density lipoprotein cholesterol, 1.0 mmol/L (39 mg/dL), low-density lipoprotein particle numbers were considerably higher than indicated by the level of low-density lipoprotein cholesterol because these subjects had excess numbers of small cholesterol-depleted low-density lipoprotein particles. Elevated numbers of low-density lipoprotein particles identify individuals at highest risk for atherosclerotic vascular disease and cardiovascular events.As high levels of low-density lipoprotein particles are a robust predictor of cardiovascular events, strategies targeted at raising low levels of high-density lipoprotein cholesterol must account for low-density lipoprotein particle interactions.