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低LDL-C水平和低SBP的联合暴露对心血管疾病终生风险的影响
作者:小柯机器人 发布时间:2019/9/4 17:04:27

英国剑桥大学Brian A. Ference与合作团队评估了较低的低密度脂蛋白胆固醇(LDL-C)和低收缩压(SBP)联合暴露对心血管疾病终生风险的影响。相关论文9月2日在线发表于《美国医学会杂志》。

2006年到2010年共有438952名参与者在英国生物银行注册,并在2018年进行了随访,平均年龄为65.2岁,54.1%为女性,24980名受试者经历了第一次严重冠状动脉事件。根据LDL-C和SBP基因评分将参与者分为终身暴露低LDL-C、低SBP,或两者均低组。主要冠状动脉事件包括冠状动脉死亡、心肌梗死或冠状动脉血运重建。

与对照组相比,LDL-C基因评分高于中位数的受试者LDL-C水平降低了14.7 mg/dL,主要冠状动脉事件的优势比为0.73。SBP基因评分高于中位数的受试者SBP降低了2.9 mm Hg,主要冠状动脉事件的优势比为0.82。两种基因评分均高于中位数的受试者LDL-C降低了13.9 mg/dL,收缩压降低3.1 mm Hg,主要冠状动脉事件的优势比值为0.61。

遗传风险评分越高,LDL-C水平和SBP越低,主要冠状动脉事件剂量依赖性的风险越低。在荟萃回归分析中,LDL-C降低38.67 mg/dL,SBP降低10 mm Hg,主要冠状动脉事件的优势比为0.22,心血管死亡的优势比为0.32。

综上,低LDL-C水平和低SBP的终身遗传暴露与较低的心血管风险相关。

附:英文原文

Title: Association of Genetic Variants Related to Combined Exposure to Lower Low-Density Lipoproteins and Lower Systolic Blood Pressure With Lifetime Risk of Cardiovascular Disease

Author: Brian A. Ference, MD, MPhil, MSc1,2; Deepak L. Bhatt, MD, MPH3; Alberico L. Catapano, PhD4; Chris J. Packard, DSc5; Ian Graham, MD6; Stephen Kaptoge, PhD2; Thatcher B. Ference1; Qi Guo, PhD1,2; Ulrich Laufs, MD, PhD7; Christian T. Ruff, MD, MPH8; Arjen Cupido1,9; G. Kees Hovingh, MD, PhD9; John Danesh, DPhil2; Michael V. Holmes, MBBS, PhD10; George Davey Smith, MD, DSc11; Kausik K. Ray, MD, MPhil12; Stephen J. Nicholls, MBBS, PhD13; Marc S. Sabatine, MD, MPH8

Issue&Volume: 2 September 2019

Abstract:

Importance  The relationship between exposure to lower low-density lipoprotein cholesterol (LDL-C) and lower systolic blood pressure (SBP) with the risk of cardiovascular disease has not been reliably quantified.

Objective  To assess the association of lifetime exposure to the combination of both lower LDL-C and lower SBP with the lifetime risk of cardiovascular disease.

Design, Setting, and Participants  Among 438?952 participants enrolled in the UK Biobank between 2006 and 2010 and followed up through 2018, genetic LDL-C and SBP scores were used as instruments to divide participants into groups with lifetime exposure to lower LDL-C, lower SBP, or both. Differences in plasma LDL-C, SBP, and cardiovascular event rates between the groups were compared to estimate associations with lifetime risk of cardiovascular disease.

Exposures  Differences in plasma LDL-C and SBP compared with participants with both genetic scores below the median. Genetic risk scores higher than the median were associated with lower LDL-C and lower SBP.

Main Outcomes and Measures  Odds ratio (OR) for major coronary events, defined as coronary death, nonfatal myocardial infarction, or coronary revascularization.

Results  The mean age of the 438 952 participants was 65.2 years (range, 40.4-80.0 years), 54.1% were women, and 24?980 experienced a first major coronary event. Compared with the reference group, participants with LDL-C genetic scores higher than the median had 14.7-mg/dL lower LDL-C levels and an OR of 0.73 for major coronary events (95% CI, 0.70-0.75; P < .001). Participants with SBP genetic scores higher than the median had 2.9-mm Hg lower SBP and an OR of 0.82 for major coronary events (95% CI, 0.79-0.85, P < .001). Participants in the group with both genetic scores higher than the median had 13.9-mg/dL lower LDL-C, 3.1-mm Hg lower SBP, and an OR of 0.61 for major coronary events (95% CI, 0.59-0.64; P < .001). In a 4 × 4 factorial analysis, exposure to increasing genetic risk scores and lower LDL-C levels and SBP was associated with dose-dependent lower risks of major coronary events. In a meta-regression analysis, combined exposure to 38.67-mg/dL lower LDL-C and 10-mm Hg lower SBP was associated with an OR of 0.22 for major coronary events (95% CI, 0.17-0.26; P < .001), and 0.32 for cardiovascular death (95% CI, 0.25-0.40; P < .001).

Conclusions and Relevance  Lifelong genetic exposure to lower levels of low-density lipoprotein cholesterol and lower systolic blood pressure was associated with lower cardiovascular risk. However, these findings cannot be assumed to represent the magnitude of benefit achievable from treatment of these risk factors.

期刊信息

JAMA-Journal of The American Medical Association:《美国医学会杂志》,创刊于1883年。隶属于美国医学协会,最新IF:51.273
官方网址:https://jamanetwork.com/
投稿链接:http://manuscripts.jama.com/cgi-bin/main.plex