Cardiology Department, Hospital Clínico San Carlos, IDISSC, Facultad de Medicina, Universidad Complutense, C/Profesor Martín Lagos s/n, 28040 Madrid, Spain.
Fundación Hipercolesterolemia Familiar, Madrid, Spain.
Eur Heart J. 2021 Jun 7;42(22):2201-2211. doi: 10.1093/eurheartj/ehaa1066.
Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH.
SAFEHEART is a long-term prospective cohort study of a population with FH and non-affected relatives (NAR). We analysed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3712 with FH; 1310 NAR). Fifty patients with FH (1.48%) and 3 NAR (0.27%) required AVR [odds ratio 5.71; 95% confidence interval (CI): 1.78-18.4; P = 0.003] after a mean follow-up of 7.48 (3.75) years. The incidence of AVR was significantly higher in patients with FH (log-rank 5.93; P = 0.015). Cox regression analysis demonstrated an association between FH and AVR (hazard ratio: 3.89; 95% CI: 1.20-12.63; P = 0.024), with older age, previous ASCVD, hypertension, increased LDL-CLp(a)-years, and elevated Lp(a) being independently predictive of an event.
The need for AVR due to AVS is significantly increased in FH patients, particularly in those who are older and have previous ASCVD, hypertension, increased LDL-CLp(a)-years and elevated Lp(a). Reduction in LDL-C and Lp(a) together with control of hypertension could retard the progression of AVS in FH, but this needs testing in clinical trials.ClinicalTrials.gov number NCT02693548.
家族性高胆固醇血症（FH）和脂蛋白（a）[Lp（a）]升高是与早发性动脉粥样硬化性心血管疾病（ASCVD）相关的遗传性疾病。主动脉瓣狭窄（AVS）是最常见的瓣膜性心脏病，低密度脂蛋白胆固醇（LDL-C）和 Lp（a）可能参与其病理生物学过程。我们研究了在分子定义的 FH 患者中，需要主动脉瓣置换（AVR）的严重 AVS 的频率和预测因素。
SAFEHEART 是一项 FH 患者及其无相关亲属（NAR）的长期前瞻性队列研究。我们分析了该队列中因 AVS 而需要 AVR 的频率和预测因素。共纳入 5022 名受试者（3712 名 FH；1310 名 NAR）。50 名 FH 患者（1.48%）和 3 名 NAR（0.27%）需要 AVR[比值比 5.71；95%置信区间（CI）：1.78-18.4；P=0.003]，平均随访 7.48（3.75）年后。FH 患者的 AVR 发生率明显更高（对数秩检验 5.93；P=0.015）。Cox 回归分析表明 FH 与 AVR 之间存在关联（风险比：3.89；95%CI：1.20-12.63；P=0.024），年龄较大、既往 ASCVD、高血压、LDL-CLp（a）-年增加和 Lp（a）升高是事件的独立预测因素。
在 FH 患者中，由于 AVS 而需要 AVR 的情况明显增加，特别是年龄较大且有既往 ASCVD、高血压、LDL-CLp（a）-年增加和 Lp（a）升高的患者。降低 LDL-C 和 Lp（a），同时控制高血压，可能会减缓 FH 中 AVS 的进展，但这需要临床试验来验证。临床试验编号 NCT02693548。
