Gallo Antonio, Pérez de Isla Leopoldo, Charrière Sybil, Vimont Alexandre, Alonso Rodrigo, Muñiz-Grijalvo Ovidio, Díaz-Díaz José L, Zambón Daniel, Moulin Philippe, Bruckert Eric, Mata Pedro, Béliard Sophie
Department of Endocrinology and Prevention of Cardiovascular Disease, Institute of Cardio Metabolism and Nutrition, La Pitié-Salpêtrière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France; Laboratoire d'imagerie Biomédicale, Institut National de la Santé de la Recherche Médicale (INSERM) 1146, Centre National de la Recherche Scientifique 7371, Sorbonne University, Paris, France.
Cardiology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Fundación Hipercolesterolemia Familiar, Madrid, Spain.
JACC Cardiovasc Imaging. 2021 Dec;14(12):2414-2424. doi: 10.1016/j.jcmg.2021.06.011. Epub 2021 Jul 14.
This study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH).
Common cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD).
REFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death.
We included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%.
CAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.
本研究旨在调查冠状动脉钙化（CAC）评分对SAFEHEART（西班牙家族性高胆固醇血症队列研究）风险方程（SAFEHEART-RE）在杂合子家族性高胆固醇血症（HeFH）心血管风险预测中的额外贡献。
常用的心血管风险方程对HeFH并不精确。由于HeFH的表型变异性高，CAC评分有助于更好地对动脉粥样硬化性心血管疾病（ASCVD）风险进行分层。
REFERCHOL（法国家族性高胆固醇血症登记处）和SAFEHEART是两个正在进行的关于HeFH的全国性登记处。我们分析了接受CAC定量的HeFH一级预防患者的数据。我们使用概率加权Cox比例风险模型来估计风险比（HRs）。受试者工作特征曲线下面积（AUC）和净重新分类改善（NRI）用于比较将CAC评分添加到SAFEHEART-RE中对ASCVD预测的增量贡献。ASCVD定义为冠心病、中风或短暂性脑缺血发作、外周动脉疾病、复苏的心脏骤停死亡和心血管死亡。
我们纳入了来自两个登记处的1624名患者（平均年龄：48.5±12.8岁；男性：45.7%）。在中位随访2.7年（四分位间距：0.4 - 5.0年）后，81名受试者发生了ASCVD。与CAC评分为0相比，CAC评分>100与发生ASCVD的HR为32.05（95%CI：10.08 - 101.94）相关。受试者工作曲线分析显示，单独的CAC评分在ASCVD预测中表现良好（AUC：0.860[95%CI：0.853 - 0.869]）。将log（CAC + 1）添加到SAFEHEART-RE中导致对ASCVD的预测显著改善（SAFEHEART-RE + log（CAC + 1）的AUC：0.884[95%CI：0.871 - 0.894]，而SAFEHEART-RE的AUC：0.793[95%CI：0.779 - 0.818]；P < 0.001）。仅考虑硬性心血管终点时，这些结果也得到了证实。添加CAC评分与估计的总体净重新分类改善45.4%相关。
在接受他汀类药物治疗的HeFH患者中，CAC评分证明了其在改善心血管风险分层和ASCVD预测方面的作用。
