Arnesen Kjell-Erik, Phung Ann Vinh, Randsborg Karoline, Mork Irene, Thorvall Marlene, Langslet Gisle, Svilaas Arne, Wium Cecilie, Ose Leiv, Retterstøl Kjetil
Lipid Clinic, Oslo University Hospital, Oslo, Norway.
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Front Pharmacol. 2021 Mar 2;11:560958. doi: 10.3389/fphar.2020.560958. eCollection 2020.
Real world evidence on long term treatment of patients with familial hypercholesterolemia (FH) is important. We studied the effects of intensive lipid lowering medication (LLM) and optimized lifestyle in the study TTTFH-Treat To Target FH. Adults with a first known total cholesterol of mean (95% CI) 9.8 mmol/L (9.5, 10.1) were included consecutively in their routine consultation during 2006. Of the patients 86.4% had a pathogenic FH-mutation and the remaining were clinically diagnosed. We included 357 patients and 279 met for follow-up after median 10.0 (min 8.1, max 12.8) years. Mean (95% CI) low density lipoprotein (LDL-C) was reduced from 3.9 (3.8, 4.1) to 3.0 (2.9, 3.2). More men than women used high intensity statin treatment, 85.2 and 60.8%, respectively. Women ( = 129) had higher LDL-C; 3.3 mmol/L (3.0, 3.5), than men; ( = 144) 2.8 mmol/L (2.6, 3.0), = 0.004. Add-on PCSK9 inhibitors ( = 25) reduced mean LDL-C to 2.0 (1.4, 2.6) mmol/L. At enrollment 57 patients (20.4%) had established atherosclerotic cardiovascular disease (ASCVD), and 46 (80.4%) of them experienced a new event during the study period. Similarly, 222 (79.6%) patients had no detectable ASCVD at enrollment, and 29 of them (13.1%) experienced a first-time event during the study period. A mean LDL-C of 3.0 mmol/L was achievable in FH, treated intensively at a specialized clinic with few users of PCSK9 inhibitors. LDL-C was higher (0.5 mmol/L) in women than in men. In patients with ASCVD at enrollment, most (80.7%) experienced a new ASCVD event in the study period. The FH patients in primary prevention had more moderate CV risk, 13% in ten years.
关于家族性高胆固醇血症（FH）患者长期治疗的真实世界证据很重要。我们在TTTFH-靶向治疗FH研究中研究了强化降脂药物（LLM）和优化生活方式的效果。2006年，首次已知总胆固醇平均为（95%CI）9.8 mmol/L（9.5，10.1）的成年人在其常规会诊中被连续纳入研究。86.4%的患者有致病性FH突变，其余为临床诊断。我们纳入了357名患者，279名患者在中位10.0（最小值8.1，最大值12.8）年后接受随访。低密度脂蛋白（LDL-C）平均（95%CI）从3.9（3.8，4.1）降至3.0（2.9，3.2）。使用高强度他汀类药物治疗的男性多于女性，分别为85.2%和60.8%。女性（n = 129）的LDL-C更高，为3.3 mmol/L（3.0，3.5），高于男性（n = 144）的2.8 mmol/L（2.6，3.0），P = 0.004。添加前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂（n = 25）可将平均LDL-C降至2.0（1.4，2.6）mmol/L。入组时，57名患者（20.4%）已患有动脉粥样硬化性心血管疾病（ASCVD），其中46名（80.4%）在研究期间发生了新的事件。同样，222名（79.6%）患者入组时未检测到ASCVD，其中29名（13.1%）在研究期间发生了首次事件。在专科诊所接受强化治疗且很少使用PCSK9抑制剂的FH患者中，平均LDL-C可达到3.0 mmol/L。女性的LDL-C比男性高（0.5 mmol/L）。入组时患有ASCVD的患者中，大多数（80.7%）在研究期间发生了新的ASCVD事件。一级预防中的FH患者心血管风险更为中等，十年内为13%。
