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Abstract：
BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal semi-dominant disease, characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-c) from conception and accelerated atherosclerotic cardiovascular disease, often resulting in early death. The aim of this study was to evaluate the prevalence of clinically defined FH in Chinese Han patients with acute coronary syndrome (ACS) and compare the long-term prognosis of ACS patients with and without FH receiving lipid-lowering therapy containing statins after a coronary event.
METHODS: All ACS patients were screened at the Second Affiliated Hospital of Xi\'an Jiaotong University between Jan 2019 and Sep 2020, and 531 participants were enrolled. All were examined for FH under the Dutch Lipid Clinical Network (DLCN) criteria, and those patients were divided into definite/probable FH, possible FH and unlikely FH. The severity of coronary artery disease was evaluated by the Gensini scoring system. Plasma levels of total cholesterol (TC), triacylglycerol (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), very low-density lipoproteins-cholesterol (VLDL-c), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)) were determined centrally at baseline and the last follow-up visit in the fasting state. The non-high-density lipoprotein cholesterol (non-HDL-c) concentration, the TC/HDL-c and apoB/apoA1 ratios were calculated. After FH patients received lipid-lowering treatment containing statin, the target LDL-c levels recommended by the guidelines (LDL-c < 1.8 mmol/L or < 1.4 mmol/L and a reduction > 50% from baseline) were evaluated, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the 12-month follow-up was recorded.
RESULTS: The prevalence of clinically definite or probable FH was 4.3%, and the prevalence of possible FH was 10.6%. Compared with the unlikely FH patients with ACS, the FH patients had higher levels of TC, LDL-c, apoB, Lp(a), non-HDL-c, TC/HDL-c and apoB/apoA1 ratio, more severe coronary artery diseases and greater prevalence of left main and triple or multiple vessel lesions. After lipid-lowering therapy containing statins, a minority of FH patients reached the target LDL-c levels defined by the guidelines (χ2 = 33.527, P < 0.001). During the 12-month follow-up, a total of 72 patients experienced MACCE. The survival curve in patients in the FH group was significantly lower than that in the unlikely FH group (HR = 1.530, log-rank test: P < 0.05). Furthermore, the survival curve in patients with high LDL-c (≥ 1.8 mmol/L) was significantly lower than that in patients with low LDL-c (< 1.8 mmol/L) at the 12-month follow-up visit (HR = 1.394, log-rank test: P < 0.05). No significant difference was observed between patients with LDL-c levels ≥ 1.4 mmol/L and with < 1.4 mmol/L at the 12-month follow-up visit by using Kaplan-Meier survival analysis (HR = 1.282, log-rank test: P > 0.05).
CONCLUSIONS: FH was an independent risk factor for MACCE in adult patients after a coronary event during long-term follow-up. However, there was inadequate high-intensity statins prescriptions for high-risk patients in this current study. It is important for FH patients to optimize lipid-lowering treatment strategies to reach the target LDL-c level to improve the long-term prognosis of clinical outcomes.
METHODS: All ACS patients were screened at the Second Affiliated Hospital of Xi\'an Jiaotong University between Jan 2019 and Sep 2020, and 531 participants were enrolled. All were examined for FH under the Dutch Lipid Clinical Network (DLCN) criteria, and those patients were divided into definite/probable FH, possible FH and unlikely FH. The severity of coronary artery disease was evaluated by the Gensini scoring system. Plasma levels of total cholesterol (TC), triacylglycerol (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), very low-density lipoproteins-cholesterol (VLDL-c), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)) were determined centrally at baseline and the last follow-up visit in the fasting state. The non-high-density lipoprotein cholesterol (non-HDL-c) concentration, the TC/HDL-c and apoB/apoA1 ratios were calculated. After FH patients received lipid-lowering treatment containing statin, the target LDL-c levels recommended by the guidelines (LDL-c < 1.8 mmol/L or < 1.4 mmol/L and a reduction > 50% from baseline) were evaluated, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the 12-month follow-up was recorded.
RESULTS: The prevalence of clinically definite or probable FH was 4.3%, and the prevalence of possible FH was 10.6%. Compared with the unlikely FH patients with ACS, the FH patients had higher levels of TC, LDL-c, apoB, Lp(a), non-HDL-c, TC/HDL-c and apoB/apoA1 ratio, more severe coronary artery diseases and greater prevalence of left main and triple or multiple vessel lesions. After lipid-lowering therapy containing statins, a minority of FH patients reached the target LDL-c levels defined by the guidelines (χ2 = 33.527, P < 0.001). During the 12-month follow-up, a total of 72 patients experienced MACCE. The survival curve in patients in the FH group was significantly lower than that in the unlikely FH group (HR = 1.530, log-rank test: P < 0.05). Furthermore, the survival curve in patients with high LDL-c (≥ 1.8 mmol/L) was significantly lower than that in patients with low LDL-c (< 1.8 mmol/L) at the 12-month follow-up visit (HR = 1.394, log-rank test: P < 0.05). No significant difference was observed between patients with LDL-c levels ≥ 1.4 mmol/L and with < 1.4 mmol/L at the 12-month follow-up visit by using Kaplan-Meier survival analysis (HR = 1.282, log-rank test: P > 0.05).
CONCLUSIONS: FH was an independent risk factor for MACCE in adult patients after a coronary event during long-term follow-up. However, there was inadequate high-intensity statins prescriptions for high-risk patients in this current study. It is important for FH patients to optimize lipid-lowering treatment strategies to reach the target LDL-c level to improve the long-term prognosis of clinical outcomes.
摘要：
背景：家族性高胆固醇血症（FH）是一种常染色体半显性疾病，以受孕引起的低密度脂蛋白胆固醇（LDL-c）水平显着升高和动脉粥样硬化性心血管疾病加速为特征，往往导致过早死亡。这项研究的目的是评估临床定义的FH在中国汉族急性冠脉综合征（ACS）患者中的患病率，并比较有和没有FH的ACS患者在冠状动脉事件后接受包含他汀类药物的降脂治疗的长期预后。
方法：所有ACS患者于2019年1月至2020年9月在西安交通大学第二附属医院进行筛查，纳入531名参与者。根据荷兰脂质临床网络（DLCN）标准检查所有FH，这些患者被分为确定/可能的FH，可能的FH和不太可能的FH。通过Gensini评分系统评估冠状动脉疾病的严重程度。血浆总胆固醇（TC）水平，三酰甘油（TG），HDL-胆固醇(HDL-c)LDL-胆固醇(LDL-c),极低密度脂蛋白胆固醇（VLDL-c），载脂蛋白A1（apoA1），在基线和最后一次空腹随访时，对载脂蛋白B（apoB）和脂蛋白（a）（Lp（a））进行了集中测定。非高密度脂蛋白胆固醇（non-HDL-c）浓度，计算TC/HDL-c和apoB/apoA1比值。FH患者接受含有他汀类药物的降脂治疗后，评估了指南推荐的目标LDL-c水平（LDL-c<1.8mmol/L或<1.4mmol/L，与基线相比降低>50％），并记录12个月随访期间主要不良心脑血管事件(MACCE)的发生情况.
结果：临床确定或可能的FH的患病率为4.3％，可能FH的患病率为10.6%。与不太可能发生FH的ACS患者相比，FH患者的TC水平较高，LDL-c,apoB,Lp(a),非HDL-c,TC/HDL-c和apoB/apoA1比值，冠状动脉疾病更为严重，左主干和三支或多支血管病变的患病率更高。在含有他汀类药物的降脂治疗后，少数FH患者达到了指南定义的目标LDL-c水平(χ2=33.527,P<0.001)。在12个月的随访中，共有72例患者经历了MACCE。FH组患者的生存曲线明显低于不太可能FH组（HR=1.530，log-rank检验：P<0.05）。此外，在12个月随访时，高LDL-c（≥1.8mmol/L）患者的生存曲线明显低于低LDL-c（<1.8mmol/L）患者（HR=1.394，对数秩检验：P<0.05）。通过Kaplan-Meier生存分析，LDL-c水平≥1.4mmol/L和<1.4mmol/L的患者在12个月的随访中没有发现显着差异（HR=1.282，对数秩检验：P>0.05）。
结论：FH是长期随访中发生冠状动脉事件后成年患者MACCE的独立危险因素。然而,在本研究中,针对高危患者的高强度他汀类药物处方不足.FH患者优化降脂治疗策略以达到目标LDL-c水平对改善临床预后具有重要意义。
方法：所有ACS患者于2019年1月至2020年9月在西安交通大学第二附属医院进行筛查，纳入531名参与者。根据荷兰脂质临床网络（DLCN）标准检查所有FH，这些患者被分为确定/可能的FH，可能的FH和不太可能的FH。通过Gensini评分系统评估冠状动脉疾病的严重程度。血浆总胆固醇（TC）水平，三酰甘油（TG），HDL-胆固醇(HDL-c)LDL-胆固醇(LDL-c),极低密度脂蛋白胆固醇（VLDL-c），载脂蛋白A1（apoA1），在基线和最后一次空腹随访时，对载脂蛋白B（apoB）和脂蛋白（a）（Lp（a））进行了集中测定。非高密度脂蛋白胆固醇（non-HDL-c）浓度，计算TC/HDL-c和apoB/apoA1比值。FH患者接受含有他汀类药物的降脂治疗后，评估了指南推荐的目标LDL-c水平（LDL-c<1.8mmol/L或<1.4mmol/L，与基线相比降低>50％），并记录12个月随访期间主要不良心脑血管事件(MACCE)的发生情况.
结果：临床确定或可能的FH的患病率为4.3％，可能FH的患病率为10.6%。与不太可能发生FH的ACS患者相比，FH患者的TC水平较高，LDL-c,apoB,Lp(a),非HDL-c,TC/HDL-c和apoB/apoA1比值，冠状动脉疾病更为严重，左主干和三支或多支血管病变的患病率更高。在含有他汀类药物的降脂治疗后，少数FH患者达到了指南定义的目标LDL-c水平(χ2=33.527,P<0.001)。在12个月的随访中，共有72例患者经历了MACCE。FH组患者的生存曲线明显低于不太可能FH组（HR=1.530，log-rank检验：P<0.05）。此外，在12个月随访时，高LDL-c（≥1.8mmol/L）患者的生存曲线明显低于低LDL-c（<1.8mmol/L）患者（HR=1.394，对数秩检验：P<0.05）。通过Kaplan-Meier生存分析，LDL-c水平≥1.4mmol/L和<1.4mmol/L的患者在12个月的随访中没有发现显着差异（HR=1.282，对数秩检验：P>0.05）。
结论：FH是长期随访中发生冠状动脉事件后成年患者MACCE的独立危险因素。然而,在本研究中,针对高危患者的高强度他汀类药物处方不足.FH患者优化降脂治疗策略以达到目标LDL-c水平对改善临床预后具有重要意义。
