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Background  The prognosis for hyper-high-density lipoprotein (HDL) cholesterolemic patients has not been fully elucidated. We conducted a post hoc analysis of MEGA study data to investigate prospectively the incidence of cardiovascular events and cancer in hyper-HDL cholesterolemic patients.    Methods  A total of 7832 patients with mild hypercholesterolemia were randomly allocated to either the National Cholesterol Education Program step 1 diet alone ( n  = 3966) or the diet plus pravastatin ( n  = 3866) and followed for 5 years. The incidences of coronary heart disease (CHD), CHD plus cerebral infarction (CI), cardiovascular disease (CVD), and cancer were calculated using the Cox proportional hazards model according to the level of HDL cholesterol (HDL-C).    Results  CHD incidence was lower in patients with HDL-C >60–90 mg/dL (-52%,  p  = 0.0018) and HDL-C > 90 mg/dL (-46%,  p  = 0.4007) than in patients with HDL-C ≤ 60 mg/dL. The incidences of CHD, CHD plus CI, and CVD were significantly lower in patients with HDL-C >60–90 mg/dL than in those with HDL-C ≤ 60 mg/dL in both diet-alone and diet-plus-pravastatin groups. Cancer incidence was not increased in patients with HDL-C >60–90 mg/dL.    Conclusion  Patients not receiving statin therapy should aim for a target HDL-C of between 60 and 90 mg/dL to achieve a significant reduction in CHD without the occurrence of adverse events.    Trial registration  Clinical trials.gov  NCT00211705 .

Cardiovascular and cancer events in hyper-high-density lipoprotein cholesterolemic patients: a post hoc analysis of the MEGA study