Clinically suspected familial hypercholesterolemia in acute myocardial infarction: prevalence, prognosis, and angiographic coronary disease extent in a Korean multicenter cohort

Abstract Background Familial hypercholesterolemia (FH) is a well-established risk factor for coronary artery disease (CAD). However, its significance among patients with acute myocardial infarction (AMI) remains incompletely characterized, particularly in East Asia. Methods We analyzed data from a multicenter, retrospective AMI registry in Korea. Clinically suspected FH was defined as possible, probable, or definite FH using available components of the Dutch Lipid Clinic Network criteria. This registry-derived phenotype was not equivalent to confirmed FH. The primary outcome was coronary events, defined as a composite of cardiovascular death, recurrent myocardial infarction, or unplanned revascularization, and was compared between patients with clinically suspected FH and those with unlikely FH. Among patients with clinically suspected FH, we additionally examined associations between admission low-density lipoprotein cholesterol (LDL-C), CAD extent, and subsequent coronary events. Results Among 8,868 eligible patients, 694 (7.8%) were classified as having clinically suspected FH. After multivariable adjustment, the clinically suspected FH phenotype was associated with a higher risk of coronary events (hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.13–1.56; p < 0.001). Within the clinically suspected FH group, higher admission LDL-C levels were associated with more extensive CAD (adjusted odds ratio, 1.32; 95% CI, 1.07–1.62; p = 0.009). Patients with three-vessel disease had a higher risk of coronary events than those with single-vessel disease (adjusted HR, 1.95; 95% CI, 1.13–3.36), with a significant indirect association between LDL-C and coronary events through CAD extent. Conclusions A registry-derived clinically suspected FH phenotype is associated with increased risk of recurrent coronary events after AMI. Within this group, admission LDL-C was associated with CAD extent, and CAD extent was associated with subsequent coronary outcomes. These findings do not establish an FH-specific mechanism. Trial registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02806102.