脂蛋白(a)升高与家族性高胆固醇血症对动脉粥样硬化性心血管疾病患者的等效影响。
Equivalent Impact of Elevated Lipoprotein(a) and Familial Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease.
作者信息
Hedegaard Berit Storgaard, Bork Christian Sørensen, Kaltoft Morten, Klausen Ib Christian, Schmidt Erik Berg, Kamstrup Pia Rørbæk, Langsted Anne, Nordestgaard Børge Grønne
机构信息
Department of Cardiology, Viborg Regional Hospital, Regional Hospital Central Jutland, Viborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
出版信息
J Am Coll Cardiol. 2022 Nov 22;80(21):1998-2010. doi: 10.1016/j.jacc.2022.09.021.
BACKGROUND
Genetically elevated plasma lipoprotein(a) and familial hypercholesterolemia each result in premature atherosclerotic cardiovascular disease (ASCVD); however, a direct comparison in the same population is needed of these 2 genetic traits on the risk of ASCVD.
OBJECTIVES
We determined the level of plasma lipoprotein(a) that is equivalent to low-density lipoprotein (LDL) cholesterol in clinically and genetically diagnosed familial hypercholesterolemia on risk of myocardial infarction and ASCVD.
METHODS
We examined the CGPS (Copenhagen General Population Study) with determination of lipoprotein(a) and familial hypercholesterolemia in 69,644 individuals followed for 42 years, during which time, 4,166 developed myocardial infarction and 11,464, ASCVD.
RESULTS
For risk of myocardial infarction, the plasma lipoprotein(a) level equivalent to LDL cholesterol in clinical familial hypercholesterolemia was 67 mg/dL (142 nmol/L) for MEDPED (Make Early Diagnosis to Prevent Early Death), 110 mg/dL (236 nmol/L) for Simon Broome, 256 mg/dL (554 nmol/L) for possible DLCN (Dutch Lipid Clinic Network), and 402 mg/dL (873 nmol/L) for probable+definite DLCN, whereas it was 180 mg/dL (389 nmol/L) for genetic familial hypercholesterolemia. Corresponding values for ASCVD were 130 mg/dL (280 nmol/L), 150 mg/dL (323 nmol/L), 227 mg/dL (491 nmol/L), 391 mg/dL (849 nmol/L), and 175 mg/dL (378 nmol/L), respectively. Individuals with both elevated lipoprotein(a) and either familial hypercholesterolemia or a family history of premature myocardial infarction had a higher risk of myocardial infarction and ASCVD compared with individuals with only 1 of these genetic traits, with the highest HRs being for lipoprotein(a) upper 20% vs lower 50% of 14.0 (95% CI: 9.15-21.3) for myocardial infarction and 5.05 (95% CI: 3.41-7.48) for ASCVD.
CONCLUSIONS
Lipoprotein(a) levels equivalent to LDL cholesterol in clinical and genetic familial hypercholesterolemia were 67 to 402 mg/dL and 180 mg/dL, respectively, for myocardial infarction and 130 to 391 mg/dL and 175 mg/dL, respectively, for ASCVD.
背景
血浆脂蛋白(a)基因水平升高和家族性高胆固醇血症均会导致早发性动脉粥样硬化性心血管疾病（ASCVD）；然而，需要在同一人群中对这两种遗传特征导致ASCVD的风险进行直接比较。
目的
我们确定了在临床和基因诊断的家族性高胆固醇血症中，与低密度脂蛋白（LDL）胆固醇等效的血浆脂蛋白(a)水平对心肌梗死和ASCVD风险的影响。
方法
我们对哥本哈根普通人群研究（CGPS）进行了研究，测定了69644名个体的脂蛋白(a)和家族性高胆固醇血症，并对其进行了42年的随访，在此期间，4166人发生心肌梗死，11464人发生ASCVD。
结果
对于心肌梗死风险，在临床家族性高胆固醇血症中，与LDL胆固醇等效的血浆脂蛋白(a)水平，对于MEDPED（早期诊断预防早死）为67mg/dL（142nmol/L），对于西蒙·布鲁姆标准为110mg/dL（236nmol/L），对于可能的荷兰脂质诊所网络（DLCN）标准为256mg/dL（554nmol/L），对于很可能+确诊的DLCN标准为402mg/dL（873nmol/L），而对于基因家族性高胆固醇血症为180mg/dL（389nmol/L）。ASCVD的相应值分别为130mg/dL（280nmol/L）、150mg/dL（323nmol/L）、227mg/dL（491nmol/L）、391mg/dL（849nmol/L）和175mg/dL（378nmol/L）。与仅具有这些遗传特征之一的个体相比；同时具有脂蛋白(a)升高以及家族性高胆固醇血症或早发性心肌梗死家族史的个体发生心肌梗死和ASCVD的风险更高，其中脂蛋白(a)处于最高20%与最低50%相比，心肌梗死的最高风险比（HR）为14.0（95%CI：9.15-21.3），ASCVD为5.05（95%CI：3.41-7.48）。
结论
在临床和基因家族性高胆固醇血症中，与LDL胆固醇等效的脂蛋白(a)水平，对于心肌梗死分别为67至402mg/dL和180mg/dL，对于ASCVD分别为130至391mg/dL和175mg/dL。
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