Introduction: The purpose of this study was to assess the prevalence of emerging cardiac risk factors in individuals with a family history of premature coronary heart disease (CHD) and who were predicted to be low-risk for cardiovascular (CV) disease based on their Framingham risk score. Methods: We prospectively evaluated 89 younger men and women with a family history of premature CHD and who had a low Framingham risk score. Patients with CHD or CHD equivalents were excluded. All patients were screened for emerging clinical and lipid risk factors. Results: Coronary calcium was present in 38% of patients and C-reactive protein >3 mg/dl was present in 24% of patients. Low levels of high-density lipoprotein (HDL 2 ) cholesterol were the most prevalent emerging lipid risk factor and was present in 72% of the study group. More individuals had low levels of HDL 2 than total HDL (34% versus 71%; p-value = 0.001). Triglyceride-(TG)-rich remnant lipoproteins were present in 49% of patients. Conclusions: The Framingham risk score poorly predicts CV risk in younger healthy persons with a family history of premature CHD. The prevalence of subclinical CHD and emerging clinical and lipid risk factors is high in these patients. The most prevalent lipid risk factor was low levels of HDL 2 . Individuals with a family history of premature CHD may benefit from screening for emerging risk factors to better assess their CV risk.Key words: coronary calcium, Framingham risk score, premature coronary heart disease Introduction Individuals whose parents or siblings develop coronary heart disease (CHD) at a young age are at increased risk of developing CHD themselves. A family history of premature CHD is recognized as a major risk factor for CHD in the National Cholesterol Education Program (NCEP) adult treatment panel (ATP) III guidelines, 1 and recent emphasis has been placed on screening individuals with a family history of premature CHD for established cardiovascular (CV) risk factors in order to reduce their risk of developing CHD. However, previous studies have shown that individuals with a family history of premature CHD often have normal lipid levels and few identifiable major risk factors for CHD, despite having a high prevalence of subclinical coronary artery disease (CAD). 2 -4 We hypothesized that the CV risk in the offspring of individuals with premature CHD would be underestimated by the Framingham risk score, and that their increased CV risk might be explained by factors beyond traditional CV risk factors. The NCEP ATP III guidelines have identified several emerging clinical and lipid risk factors that may contribute to CHD risk, 1 and previous studies have shown a high prevalence of these emerging risk factors in patients
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