Interplay Between Chronic Kidney Disease, Hypertension, and Stroke

孟德尔随机化 医学 肾功能 冲程(发动机) 优势比 内科学 肾脏疾病 肌酐 血压 心脏病学 脑出血 遗传变异 基因型 基因 工程类 生物化学 化学 蛛网膜下腔出血 机械工程
作者
Dearbhla Kelly,Marios K. Georgakis,Nora Franceschini,Deborah Blacker,Anand Viswanathan,Christopher D. Anderson
出处
期刊:Neurology [Lippincott Williams & Wilkins]
卷期号:101 (20) 被引量:3
标识
DOI:10.1212/wnl.0000000000207852
摘要

Background and Objectives

Chronic kidney disease (CKD) increases the risk of stroke, but the extent through which this association is mediated by hypertension is unknown. We leveraged large-scale genetic data to explore causal relationships between CKD, hypertension, and cerebrovascular disease phenotypes.

Methods

We used data from genome-wide association studies of European ancestry to identify genetic proxies for kidney function (CKD diagnosis, estimated glomerular filtration rate [eGFR], and urinary albumin-to-creatinine ratio [UACR]), systolic blood pressure (SBP), and cerebrovascular disease (ischemic stroke and its subtypes and intracerebral hemorrhage). We then conducted univariable, multivariable, and mediation Mendelian randomization (MR) analyses to investigate the effect of kidney function on stroke risk and the proportion of this effect mediated through hypertension.

Results

Univariable MR revealed associations between genetically determined lower eGFR and risk of all stroke (odds ratio [OR] per 1-log decrement in eGFR, 1.77; 95% CI 1.31–2.40; p < 0.001), ischemic stroke (OR 1.81; 95% CI 1.31–2.51; p < 0.001), and most strongly with large artery stroke (LAS) (OR 3.00; 95% CI 1.33–6.75; p = 0.008). These associations remained significant in the multivariable MR analysis, controlling for SBP (OR 1.98; 95% CI 1.39–2.82; p < 0.001 for all stroke; OR 2.16; 95% CI 1.48–3.17; p < 0.001 for ischemic stroke; OR 4.35; 95% CI 1.84–10.27; p = 0.001 for LAS), with only a small proportion of the total effects mediated by SBP (6.5% [0.7%–16.8%], 6.6% [0.8%–18.3%], and 7.2% [0.5%–24.8%], respectively). Total, direct and indirect effect estimates were similar across a number of sensitivity analyses (weighted median, MR-Egger regression).

Discussion

Our results demonstrate an independent causal effect of impaired kidney function, as assessed by decreased eGFR, on stroke risk, particularly LAS, even when controlled for SBP. Targeted prevention of kidney disease could lower atherosclerotic stroke risk independent of hypertension.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
CLY完成签到,获得积分10
1秒前
1秒前
LDG发布了新的文献求助10
1秒前
chang_top应助AZE采纳,获得20
2秒前
量子星尘发布了新的文献求助10
2秒前
lalala发布了新的文献求助10
2秒前
2秒前
含蓄绿兰发布了新的文献求助10
2秒前
SYLH应助gjw采纳,获得10
3秒前
ED发布了新的文献求助200
3秒前
4秒前
情怀应助怕孤单的问雁采纳,获得10
4秒前
4秒前
5秒前
5秒前
鲜于飞薇发布了新的文献求助10
6秒前
FashionBoy应助刘佳敏采纳,获得10
7秒前
SYLH应助gjw采纳,获得10
8秒前
风轻萤发布了新的文献求助10
8秒前
LXL0125完成签到,获得积分10
8秒前
传奇3应助自觉紫安采纳,获得10
9秒前
9秒前
尤幻雪发布了新的文献求助30
9秒前
朴实的悲完成签到,获得积分20
9秒前
笑点低的小天鹅完成签到,获得积分10
9秒前
老实鞯完成签到 ,获得积分20
10秒前
10秒前
略略略发布了新的文献求助10
10秒前
赘婿应助momo采纳,获得10
10秒前
青衣北风发布了新的文献求助10
11秒前
wdlc发布了新的文献求助20
11秒前
hhj发布了新的文献求助10
11秒前
11秒前
12秒前
弗洛洛发布了新的文献求助20
12秒前
深情安青应助饱满的靖易采纳,获得30
13秒前
英姑应助molamola采纳,获得10
13秒前
bkagyin应助万万没想到采纳,获得10
13秒前
xiaotudou95发布了新的文献求助10
14秒前
zlzl完成签到,获得积分10
15秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 360
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3971091
求助须知:如何正确求助?哪些是违规求助? 3515797
关于积分的说明 11179488
捐赠科研通 3250872
什么是DOI,文献DOI怎么找? 1795536
邀请新用户注册赠送积分活动 875891
科研通“疑难数据库(出版商)”最低求助积分说明 805207