How To Identify Familial Premature Myocardial Infarction: Comparing Approaches To Identify Familial Hypercholesterolemia.

How best to identify families with premature myocardial infarction is unclear. We compared approaches to identify familial premature myocardial infarction in the general population using different familial hypercholesterolemia (FH) criteria and low-density lipoprotein (LDL) cholesterol cut-points. Clinical and mutation criteria for FH and LDL cholesterol cut-points were applied for identification of familial premature myocardial infarction in 106,732 individuals from the Copenhagen General Population Study. FH criteria identified 898 (13%) cases with familial premature myocardial infarction, leaving 5856 (87%) cases undetected. The ORs for familial premature myocardial infarction, compared with the respective remainder groups, were 4.7 (95% CI, 3.7 to 6.0) for clinical FH by Dutch Lipid Clinic Network criteria, 4.4 (4.0 to 4.7) for Simon Broome criteria, 2.1 (95% CI, 1.7 to 3.6) for Make Early Diagnosis to Prevent Early Death criteria, 2.1 (95% CI, 1.4 to 3.3) for FH mutation, and 1.4 (95% CI, 1.3 to1.6) for LDL cholesterol ≥5 mmol/L (193 mg/dL). For these risk groups, the sensitivity (true positive rate) for identification of familial premature myocardial infarction were 1.3%, 13%, 1.6%, 0.9%, and 7.1%, respectively. Compared with universal screening of a similar fraction of the population, the relative increase in sensitivity for these risk groups was 3.8-fold [fraction of population examined: 0.3%, 3.3-fold (4%), 2.0-fold (0.8%), 2.0-fold (0.4%), and 1.4-fold (5.3%), respectively]. Criteria for FH identify a small fraction of individuals with familial premature myocardial infarction in the general population. Actively identifying families with premature myocardial infarction would be of potential preventive importance, and this study provides data that could be used to choose the best method for such family identification.

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