Rubba Paolo, Gentile Marco, Marotta Gennaro, Iannuzzi Arcangelo, Sodano Marta, De Simone Biagio, Jossa Fabrizio, Iannuzzo Gabriella, Giacobbe Carola, Di Taranto Maria D, Fortunato Giuliana
1 Dipartimento di Medicina Clinica e Chirurgia, Università 'Federico II' di Napoli, Italy.
2 UO Medicina Interna, AORN 'A Cardarelli' di Napoli, Italy.
Eur J Prev Cardiol. 2017 Jul;24(10):1051-1059. doi: 10.1177/2047487317702040. Epub 2017 Mar 29.
Background Familial hypercholesterolemia is a common autosomal dominant disease, caused by mutations leading to elevated low-density lipoprotein (LDL) cholesterol and, if untreated, to premature cardiovascular disease. Methods Patients (young adults with a family history of hypercholesterolaemia or premature cardiovascular disease) with LDL cholesterol concentration ≥4.9 mmol/l, after excluding Familial Combined Hyperlipidaemia, were evaluated for causative mutations, Dutch Lipid Clinic Network score calculation and non-invasive ultrasound examination of carotid arteries. Results Of the 263 patients, 210 were heterozygotes for LDL receptor ( LDLR) mutations, four had APOB gene mutations, one PCSK9 gene mutation, while 48 had no evidence of mutations. Among 194 unrelated index cases 149 had mutations (77%). Among patients with LDLR mutations ( n = 145), there were five compound heterozygotes, 75 patients with null mutations and 65 with missense mutations. As many as 178 patients underwent a follow-up and treatment (statin ± ezetimibe), achieving a mean reduction of 49% in LDL cholesterol, with 21% of patients reaching the LDL goal of 2.6 mmol/l. In a multivariate analysis, carotid plaques, at ultrasound examination, were associated with the presence of genetic mutation ( p = 0.001), LDL cholesterol ( p < 0.001), Dutch Lipid Clinic Network score ( p < 0.001), independently of age, gender, smoking habits and systolic blood pressure. The presence of carotid plaque ( p = 0.017), LDL cholesterol ( p < 0.003), Dutch Lipid Clinic Network score ( p < 0.001) were independently associated with premature cardiovascular disease. Conclusions We identified patients with causative mutations in 82% of the cases under study. In addition to LDL cholesterol and Dutch Lipid Clinic Network score, carotid plaques in ultrasound evaluation provide direct evidence of premature vascular disease and are associated with high risk for cardiovascular events.
家族性高胆固醇血症是一种常见的常染色体显性疾病，由导致低密度脂蛋白（LDL）胆固醇升高的突变引起，若不治疗，会导致早发性心血管疾病。方法：对低密度脂蛋白胆固醇浓度≥4.9 mmol/l的患者（有高胆固醇血症家族史或早发性心血管疾病家族史的年轻人），在排除家族性混合型高脂血症后，评估其致病突变、计算荷兰脂质诊所网络评分并进行颈动脉的无创超声检查。结果：在263例患者中，210例为低密度脂蛋白受体（LDLR）突变的杂合子，4例有载脂蛋白B（APOB）基因突变，1例有前蛋白转化酶枯草溶菌素9（PCSK9）基因突变，而48例无突变证据。在194例无亲缘关系的索引病例中，149例有突变（77%）。在LDLR突变患者（n = 145）中，有5例复合杂合子，75例为无效突变患者，65例为错义突变患者。多达178例患者接受了随访和治疗（他汀类药物±依折麦布），低密度脂蛋白胆固醇平均降低49%，21%的患者达到了2.6 mmol/l的低密度脂蛋白目标。在多变量分析中，超声检查发现的颈动脉斑块与基因突变的存在（p = 0.001）、低密度脂蛋白胆固醇（p < 0.001）、荷兰脂质诊所网络评分（p < 0.001）相关，与年龄、性别、吸烟习惯和收缩压无关。颈动脉斑块的存在（p = 0.017）、低密度脂蛋白胆固醇（p < 0.003）、荷兰脂质诊所网络评分（p < 0.001）与早发性心血管疾病独立相关。结论：我们在所研究的病例中82%识别出了有致病突变的患者。除了低密度脂蛋白胆固醇和荷兰脂质诊所网络评分外，超声评估中的颈动脉斑块为早发性血管疾病提供了直接证据，并与心血管事件的高风险相关。
