Causal Links Between Renal Function and Cardiac Structure, Function, and Disease Risk.

IF 3 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Global Heart Pub Date : 2024-11-06 eCollection Date: 2024-01-01 DOI:10.5334/gh.1366

Xiaoqin Zhou, Weiqiang Ruan, Lijun Zhao, Ke Lin, Jing Li, Huizhen Liu, Ting Wang, Guiying Zhang

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Abstract

Background: Chronic kidney disease (CKD) increases the risk of adverse cardiovascular outcomes. However, the causal relationships between renal function and cardiovascular diseases (CVD) remain incompletely understood. This study aimed to determine the causal relationships between genetic susceptibility to impaired renal function and the risk of CVD endpoints, as well as cardiac structure and function detectable by cardiac magnetic resonance imaging (CMR).

Methods: Bidirectional Mendelian randomization (MR) analyses were conducted using summary-level data from genome-wide association studies. The exposures were blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and CKD. The outcomes included atrial fibrillation, coronary artery disease (CAD), myocardial infarction, heart failure, stroke, and various CMR parameters. Sensitivity analyses, multivariable MR adjusting for cardiometabolic traits, and replication in the FinnGen cohort were performed.

Results: Elevated BUN levels (OR 1.505; 95% CI 1.077 to 2.103; P = 0.017) were causally associated with increased CAD risk, but this relationship was attenuated after adjusting for cardiometabolic traits. Increased UACR was causally linked to higher risks of CAD (OR 1.260; 95% CI 1.042 to 1.523; P = 0.017), myocardial infarction (OR 1.424; 95% CI 1.137 to 1.783; P = 0.002), and stroke (OR 1.182; 95% CI 1.012 to 1.379; P = 0.035), with the association for stroke remaining significant after multivariable adjustment. Reduced eGFR was causally related to decreases in ascending aorta diameter, proximal pulmonary artery diameter, right atrial size, left ventricular stroke volume, and right ventricular volumes, even after accounting for potential confounders. CKD was causally associated with a reduced pulmonary artery-to-aorta ratio and proximal pulmonary artery diameter.

Conclusions: This comprehensive MR study establishes causal roles of genetic susceptibility to impaired renal function influencing cardiovascular outcomes and cardiac structure.

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肾功能与心脏结构、功能和疾病风险之间的因果关系。

背景：慢性肾脏病（CKD）会增加心血管不良后果的风险。然而，人们对肾功能与心血管疾病（CVD）之间的因果关系仍不甚了解。本研究旨在确定肾功能受损遗传易感性与心血管疾病终点风险之间的因果关系，以及心脏磁共振成像（CMR）可检测到的心脏结构和功能：利用全基因组关联研究的汇总数据进行了双向孟德尔随机化（MR）分析。暴露因子为血尿素氮（BUN）、估计肾小球滤过率（eGFR）、尿白蛋白-肌酐比值（UACR）和慢性肾脏病。结果包括心房颤动、冠状动脉疾病（CAD）、心肌梗死、心力衰竭、中风和各种 CMR 参数。研究人员进行了敏感性分析、调整心脏代谢特征的多变量 MR 分析，并在 FinnGen 队列中进行了复制：BUN水平升高（OR 1.505; 95% CI 1.077 to 2.103; P = 0.017）与CAD风险增加有因果关系，但在调整了心脏代谢特征后，这种关系有所减弱。UACR 增加与较高的 CAD 风险（OR 1.260；95% CI 1.042 至 1.523；P = 0.017）、心肌梗死（OR 1.424；95% CI 1.137 至 1.783；P = 0.002）和中风（OR 1.182；95% CI 1.012 至 1.379；P = 0.035）有因果关系，经多变量调整后，与中风的关系仍然显著。即使考虑了潜在的混杂因素，eGFR 的降低与升主动脉直径、肺动脉近端直径、右心房大小、左心室每搏容积和右心室容积的减少也有因果关系。慢性肾功能衰竭与肺动脉与主动脉比值和肺动脉近端直径减小存在因果关系：这项全面的磁共振研究确定了肾功能受损的遗传易感性对心血管结局和心脏结构的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Global Heart Medicine-Cardiology and Cardiovascular Medicine

CiteScore

5.70

自引率

5.40%

发文量

审稿时长

5 weeks

期刊介绍： Global Heart offers a forum for dialogue and education on research, developments, trends, solutions and public health programs related to the prevention and control of cardiovascular diseases (CVDs) worldwide, with a special focus on low- and middle-income countries (LMICs). Manuscripts should address not only the extent or epidemiology of the problem, but also describe interventions to effectively control and prevent CVDs and the underlying factors. The emphasis should be on approaches applicable in settings with limited resources. Economic evaluations of successful interventions are particularly welcome. We will also consider negative findings if important. While reports of hospital or clinic-based treatments are not excluded, particularly if they have broad implications for cost-effective disease control or prevention, we give priority to papers addressing community-based activities. We encourage submissions on cardiovascular surveillance and health policies, professional education, ethical issues and technological innovations related to prevention. Global Heart is particularly interested in publishing data from updated national or regional demographic health surveys, World Health Organization or Global Burden of Disease data, large clinical disease databases or registries. Systematic reviews or meta-analyses on globally relevant topics are welcome. We will also consider clinical research that has special relevance to LMICs, e.g. using validated instruments to assess health-related quality-of-life in patients from LMICs, innovative diagnostic-therapeutic applications, real-world effectiveness clinical trials, research methods (innovative methodologic papers, with emphasis on low-cost research methods or novel application of methods in low resource settings), and papers pertaining to cardiovascular health promotion and policy (quantitative evaluation of health programs.