LDLR variants and higher LDL-C levels are associated with premature coronary disease requiring revascularization in patients with familial hypercholesterolemia-a TCVGH-TPMI cohort analysis

The specific impacts of LDLR and APOB variants on premature coronary artery disease (CAD) that requires revascularization are less explored in Han Chinese with familial hypercholesterolemia (FH). We investigated these genetic drivers within the Taichung Veterans General Hospital-Taiwan Precision Medicine Initiative (TCVGH-TPMI) cohort. This study aimed to investigate the associated factors related to premature CAD that required percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery in a genetically diagnosed FH cohort. 749 subjects from the TCVGH-TPMI cohort with familial hypercholesterolemia (FH)-related variants were entered for analysis. Premature CAD was defined as revascularization (PCI/CABG) at age < 45 (men) or < 55 (women). Demographic and laboratory data were compared between premature and usual-onset revascularized CAD groups. Among the 749 subjects with FH, 84 received revascularization for significant CAD. Seventeen (20.2%) had premature and 67 with usual age onset of significant CAD post revascularization. Premature CAD subjects more frequently presented as acute coronary syndrome (64.7% vs. 25.4%, p = 0.004) and had significantly higher level of maximum untreated LDL-C (210.5 ± 42.6 vs. 173.8 ± 45.2 mg/dL, p = 0.003) and higher eGFR than subjects of usual-age onset. Binary logistic regression identified that higher untreated LDL-C (OR 1.026; 95% CI 1.008–1.045, p = 0.006) and LDLR variant (vs. APOB ) (OR 6.9; 95% CI 1.107–43.330, p = 0.039) were significantly associated with premature onset of CAD revascularization. While diabetes and lower eGFR were associated with usual-onset CAD, this is likely to reflect age-related progression rather than a protective effect. In FH with CAD after revascularization, patients with premature onset presented more frequently as acute coronary syndrome, carried LDLR variants and with higher level of maximum untreated LDL-C than those with usual-age onset.