Cardiovascular Metabolic Center, State Key Laboratory of Cardiovascular Diseases, Fu Wai Hospital, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 BeiLiShi Road, XiCheng District, Beijing, China.
J Transl Med. 2021 Dec 7;19(1):498. doi: 10.1186/s12967-021-03166-w.
Although the presence of physical signs [tendon xanthomas and/or corneal arcus (TX/CA)], are associated with the risk of coronary artery disease in patients with heterozygous familial hypercholesterolemia (HeFH), their relationship with genotypes and clinical characteristics has not been fully determined. This study aimed to examine the association of TX/CA with genetic mutation, lipid- and inflammation-related markers, the severity of coronary stenosis or calcification, and cardiovascular events (CVEs) in patients with HeFH.
LDLR, APOB, and PCSK9 genes were screened in 523 HeFH patients, and patients with TX/CA (n = 50) were 1:4 propensity score-matched to patients without TX/CA (n = 200) to adjust for age and sex. Laboratory markers (proprotein convertase subtilisin/kexin type 9 [PCSK9], lipoprotein(a) and high-sensitivity C-reactive protein [hsCRP]), computed tomography angiography, coronary angiography, and follow-up for CVEs were performed.
Patients with physical signs had significantly higher low-density lipoprotein cholesterol levels; higher PCSK9 or hsCRP concentrations; more LDLR positive mutations; and higher prevalence of high tertiles of Gensini, SYNTAX and Jeopardy scores as well as coronary artery calcium scores than did those without. Over an average follow-up of 3.7 years, the incidence of CVEs was significantly higher in patients with TX/CA (log-rank p < 0.001). Patients with physical signs and mutation positivity had threefold higher risks of CVEs (adjusted hazard ratio 3.34, 95% confidence interval 1.04-10.72, p = 0.024).
Physical signs were associated with genotypes and phenotypes, and worse outcomes in patients with HeFH, suggesting that these signs may help in risk stratification in these patients.
虽然存在物理体征（腱黄瘤和/或角膜弓（TX/CA））与杂合子家族性高胆固醇血症（HeFH）患者患冠状动脉疾病的风险相关，但它们与基因突变、血脂和炎症相关标志物、冠状动脉狭窄或钙化的严重程度以及心血管事件（CVE）之间的关系尚未完全确定。本研究旨在检查 TX/CA 与 HeFH 患者的遗传突变、血脂和炎症相关标志物、冠状动脉狭窄或钙化的严重程度以及心血管事件（CVE）之间的关系。
在 523 名 HeFH 患者中筛选 LDLR、APOB 和 PCSK9 基因，将 TX/CA（n=50）患者与无 TX/CA（n=200）患者按年龄和性别进行 1:4 倾向评分匹配。进行实验室标志物（前蛋白转化酶枯草溶菌素/克氏蛋白酶 9 [PCSK9]、脂蛋白（a）和高敏 C 反应蛋白 [hsCRP]）、计算机断层血管造影、冠状动脉造影和心血管事件的随访。
有物理体征的患者的低密度脂蛋白胆固醇水平显著升高；PCSK9 或 hsCRP 浓度更高；LDLR 阳性突变更多；高 Gensini、SYNTAX 和 Jeopardy 评分以及冠状动脉钙化评分的第三分位数的患病率更高。在平均 3.7 年的随访中，TX/CA 患者的 CVE 发生率明显更高（对数秩 p<0.001）。有物理体征和突变阳性的患者发生 CVE 的风险增加了三倍（调整后的危险比 3.34，95%置信区间 1.04-10.72，p=0.024）。
物理体征与 HeFH 患者的基因型和表型以及较差的预后相关，这表明这些体征可能有助于这些患者的风险分层。
