👤 Daniela Vasile

Premature coronary artery disease (CAD) poses diagnostic challenges, particularly in patients with minimal traditional risk factors. High lipoprotein(a) [Lp(a)] is an independent, genetically determined risk factor for atherosclerotic cardiovascular disease, and it contributes to early and progressive CAD. We report the case of a 35-year-old African American woman with recurrent chest pain who was diagnosed with severe multivessel CAD despite minimal traditional cardiovascular risk factors. Further evaluation revealed markedly high Lp(a) levels. She underwent successful percutaneous coronary intervention and achieved optimal low-density lipoprotein cholesterol (LDL-C) control with high-intensity statin therapy and a PCSK9 inhibitor. Despite aggressive lipid-lowering therapy, she developed recurrent angina within 6 months, and repeat coronary angiography demonstrated disease progression. This case highlights the role of high Lp(a) in driving premature and progressive CAD independent of LDL-C levels. Early identification of high Lp(a) may improve risk stratification and inform management strategies. High Lp(a) may contribute to premature and progressive CAD even with optimal LDL-C control, supporting consideration of Lp(a) testing in young patients with unexplained or familial CAD. Show less

We sought to determine the frequency and phenotype of mutations in myosin binding protein C (MYBPC3) in a large outpatient cohort of patients with hypertrophic cardiomyopathy (HCM) seen at our tertiary referral center. Mutations in MYBPC3 are one of the most frequent genetic causes of HCM and have been associated with variable onset of disease and prognosis. However, the frequency of mutations and associated clinical presentation have not been established in a large, unrelated cohort of patients. Using deoxyribonucleic acid from 389 unrelated patients with HCM, each protein coding exon of MYBPC3 was analyzed for mutations by polymerase chain reaction, denaturing high-performance liquid chromatography, and direct deoxyribonucleic acid sequencing. Clinical data were extracted from patient records blinded to patient genotype. Of 389 patients with HCM, 71 (18%) had mutations in MYBPC3. In all, 46 mutations were identified, 33 of which were novel (72%). Patients with MYBPC3 mutations did not differ significantly from patients with thick filament-HCM, thin filament-HCM, or genotype-negative HCM with respect to age at diagnosis, degree of hypertrophy, incidence of myectomy, or family history of HCM or sudden death. Patients with multiple mutations (n = 10, 2.6%) had the most severe disease presentation. This study defines the frequency and associated phenotype for MYBPC3 and/or multiple mutations in HCM in the largest cohort to date. In this cohort, unrelated patients with MYBPC3-HCM virtually mimicked the phenotype of those with mutations in the beta-myosin heavy chain. Patients with multiple mutations had the most severe phenotype. Show less