Cardiovascular disease risk in patients with elevated LDL-C levels: FH vs. non-FH

Abstract

IntroductionCoronary artery disease (CAD) remains the primary cause of death worldwide, and familial hypercholesterolemia (FH) is a common disease that leads to CAD. This study aimed to explore the difference in CAD risk between FH and non-FH patients with high low-density lipoprotein cholesterol (LDL-C) levels.MethodsIndividuals (≥18 years) who underwent coronary angiography (CAG) from June 2016 to September 2020 were consecutively enrolled. Participants with LDL-C levels ≥4.0 mmol/L were ultimately included in this study. For all participants, next-generation sequencing was performed with expanded gene panels including 11 genes (LDLR, APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, LIPA, LPA, APOBR, LRPAP1, and STAP1).ResultsA total of 223 individuals were included in this study. According to the CAG findings, 199 CAD patients and 24 non-CAD patients were included. The proportions of FH genes, regardless of whether 3 major genes or all 11 genes were sequenced, were not significantly different between the CAD and non-CAD groups (P > 0.05). In addition, all CAD patients were divided into a triple vessel disease (TVD) group and a non-TVD group. The TVD group had a greater proportion of patients with mutations in 3 FH major genes (P < 0.05). In addition, TC, LDL-C and modified LDL-C (MLDL-C) levels were higher and the estimated glomerular filtration rate (eGFR) was lower in the TVD group than in the non-TVD group (all P < 0.05). However, multivariate logistic regression analyses revealed that only the eGFR was an independent risk factor for TVD (OR 0.99; 95% CI: 0.98–1.00, P < 0.05). To eliminate the impact of the eGFR, subgroup analysis was conducted, and the results indicated that among CAD patients in the high-eGFR group, having FH mutations in 3 major genes was an independent risk factor for TVD (OR 3.00; 95% CI: 1.16–7.79, P < 0.05). In total, 104 FH-related mutations were detected in this study.ConclusionsFH mutation did not increase the rate of CAD in individuals with an MLDL-C level ≥4.0 mmol/L. However, among CAD patients (MLDL-C level ≥4.0 mmol/L) with almost normal renal function (≥87.4 ml/min/1.73 m2), the probability of enduring TVD in those with FH mutations in 3 major genes was 3.00 times greater than that in those without FH mutations.