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载脂蛋白 B/载脂蛋白 A-I 比值与脂蛋白(a)与主动脉瓣狭窄发生率的关系:来自 EPIC-诺福克前瞻性人群研究的见解。

apoB/apoA-I Ratio and Lp(a) Associations With Aortic Valve Stenosis Incidence: Insights From the EPIC-Norfolk Prospective Population Study.

机构信息

Department of Vascular Medicine Amsterdam Cardiovascular Sciences Amsterdam UMC University of Amsterdam Amsterdam The Netherlands.

Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval Québec Canada.

出版信息

J Am Heart Assoc. 2019 Aug 20;8(16):e013020. doi: 10.1161/JAHA.119.013020. Epub 2019 Aug 13.


DOI:10.1161/JAHA.119.013020
PMID:31407609
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6759902/
Abstract

Background Apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio and lipoprotein(a) (Lp[a]) are associated with aortic valve stenosis (AVS) disease progression. Clinical characteristics such as age, sex, and presence of concomitant coronary artery disease may strongly modify these associations; however, these effects have not been well defined in longitudinal studies. We set out to assess these associations between apoB/apoA-I ratio, Lp(a), and AVS incidence in a large population study. Methods and Results We analyzed data from 17 745 participants (mean age, 59.2±9.1 years; men, 44.9%) in the EPIC-Norfolk (European Prospective Investigation Into Cancer in Norfolk Prospective Population Study) population study in whom apoB/apoA-I and Lp(a) levels were measured. Participants were identified as having incident AVS if they were hospitalized or died with AVS as an underlying cause. After a median follow-up of 19.8 years (17.9-21.0 years) there were 403 (2.2%) incident cases of AVS. The hazard ratio for AVS risk was 1.30 (95% CI, 1.19-1.41; P<0.001) per SD increase in apoB/apoA-I. Adjusting for age, sex, and coronary artery disease, there was no significant association between apoB/apoA-I and AVS incidence (hazard ratio, 1.06; 95% CI, 0.97-1.17 [P=0.215]). Elevated Lp(a) (>50 mg/dL) remained an independent risk factor for AVS after adjustment for age, sex, low-density lipoprotein cholesterol, and concomitant coronary artery disease (hazard ratio, 1.70; 95% CI, 1.33-2.19 [P<0.001]). Conclusions In this population study, apoB/apoA-I ratio was associated with risk of AVS incidence, especially in younger and female participants and those without concomitant coronary artery disease. Lp(a) was an independent risk factor for AVS incidence. Interventional trials are needed to investigate whether modulating apoB/apoA-I or lowering Lp(a) can prevent or slow down AVS.

摘要

背景 载脂蛋白 B/载脂蛋白 A-I(apoB/apoA-I)比值和脂蛋白(a)(Lp[a])与主动脉瓣狭窄(AVS)疾病进展相关。年龄、性别和并存的冠状动脉疾病等临床特征可能会强烈改变这些关联;然而,这些影响在纵向研究中尚未得到很好的定义。我们着手评估apoB/apoA-I 比值、Lp(a)与大人群研究中 AVS 发生率之间的这些关联。

方法和结果 我们分析了欧洲前瞻性癌症-诺福克(European Prospective Investigation Into Cancer in Norfolk Prospective Population Study)人群研究中 17745 名参与者(平均年龄 59.2±9.1 岁;男性 44.9%)的数据,这些参与者的 apoB/apoA-I 和 Lp(a) 水平被测量。如果参与者因 AVS 作为潜在病因住院或死亡,则确定为发生 AVS。中位随访 19.8 年(17.9-21.0 年)后,有 403(2.2%)例发生 AVS。apoB/apoA-I 每增加 1 个标准差,AVS 风险的风险比为 1.30(95%CI,1.19-1.41;P<0.001)。在调整年龄、性别和冠状动脉疾病后,apoB/apoA-I 与 AVS 发生率之间无显著关联(风险比,1.06;95%CI,0.97-1.17[P=0.215])。在调整年龄、性别、低密度脂蛋白胆固醇和并存的冠状动脉疾病后,升高的 Lp(a)(>50mg/dL)仍然是 AVS 的独立危险因素(风险比,1.70;95%CI,1.33-2.19[P<0.001])。

结论 在这项人群研究中,apoB/apoA-I 比值与 AVS 发生率相关,尤其是在年轻、女性参与者以及无并存冠状动脉疾病的参与者中。Lp(a)是 AVS 发生率的独立危险因素。需要进行干预试验以研究调节 apoB/apoA-I 或降低 Lp(a)是否可以预防或减缓 AVS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72c6/6759902/2e5cbfe6f78c/JAH3-8-e013020-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72c6/6759902/2e5cbfe6f78c/JAH3-8-e013020-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72c6/6759902/2e5cbfe6f78c/JAH3-8-e013020-g001.jpg

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本文引用的文献

[1]
Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis.

J Am Coll Cardiol. 2019-5-7

[2]
Kidney Dysfunction and the Risk of Developing Aortic Stenosis.

J Am Coll Cardiol. 2019-1-29

[3]
Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk.

Circulation. 2019-3-19

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PCSK9 Involvement in Aortic Valve Calcification.

J Am Coll Cardiol. 2018-12-18

[5]
ApoB/ApoA-I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study.

J Am Heart Assoc. 2018-2-10

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JACC Cardiovasc Imaging. 2019-1

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Symptom Onset in Aortic Stenosis: Relation to Sex Differences in Left Ventricular Remodeling.

JACC Cardiovasc Imaging. 2017-12-13

[8]
Lipoprotein(a) and the Apolipoprotein B/A1 Ratio Independently Associate With Surgery for Aortic Stenosis Only in Patients With Concomitant Coronary Artery Disease.

J Am Heart Assoc. 2017-12-15

[9]
Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials.

Lancet. 2016-9-21

[10]
PCSK9 R46L Loss-of-Function Mutation Reduces Lipoprotein(a), LDL Cholesterol, and Risk of Aortic Valve Stenosis.

J Clin Endocrinol Metab. 2016-9

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