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High "population attributable fraction" for coronary heart disease mortality among relatives in monogenic familial hypercholesterolemia

Austin, MA; Zimmern, RL; Humphries, SE; (2002) High "population attributable fraction" for coronary heart disease mortality among relatives in monogenic familial hypercholesterolemia. GENET MED , 4 (4) 275 - 278. 10.1097/01.GIM.0000020749.39075.2A.

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Abstract

Purpose: To estimate "population attributable fraction" (PAF) for coronary heart disease (CHD) mortality in a population of first-degree relatives of patients with monogenic familial hypercholesterolemia (FH) compared with the PAF for hypercholesterolemia in the general population. Methods: PAF was calculated as {f(R - 1)/[1 + f(R - 1)]}, where f is the frequency of the risk factor (hypercholesterolemia) and R is the relative risk for the association of hypercholesterolemia and CHD death. For FH relatives, f was assumed to be 50%, based on a fully penetrant, dominant mode of inheritance, and R values were obtained from the prospective Simon Broome Register data. PAFs for hypercholesterolemia and CHD death in the general population were based on the Framingham risk equations for the 95th percentile of cholesterol and CHD mortality. Results: Over all ages, 44% and 57% of 5-year CHD mortality could potentially be prevented among male and female first-degree relatives in FH families, respectively, by cholesterol reduction. In contrast, values for 5-year CHD death for hypercholesterolemia in the general population were uniformly lower at all ages, with overall 5% and 10% of fatal CHD prevented among men and women, respectively. Conclusion: These results strongly support the view that family based testing strategies of relatives of probands with monogenic hypercholesterolemia, followed by effective lipid lowering drug treatment, is a highly effective way of reducing CHD deaths among these relatives.

Type:Article
Title:High "population attributable fraction" for coronary heart disease mortality among relatives in monogenic familial hypercholesterolemia
DOI:10.1097/01.GIM.0000020749.39075.2A
Keywords:coronary heart disease, hypercholesterolemia, population attributable fraction, mortality, CARDIOVASCULAR RISK-FACTORS, PREVENTION, MUTATIONS, CHOLESTEROL, SIMVASTATIN, PRAVASTATIN, MANAGEMENT, PROGRAM, TRIAL, GENE
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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