Supplemental Digital Content is available in the text. Urinary biomarkers are associated with cardiovascular disease, but the nature of these associations is not well understood. We performed multivariable-adjusted regression models to assess associations of random spot measurements of the urine sodium-potassium ratio (UNa/UK) and urine albumin adjusted for creatinine with cardiovascular risk factors, cardiovascular disease, and type 2 diabetes mellitus (T2D) in 478 311 participants of the UK Biobank. Further, we assessed the causal relationships of these kidney biomarkers, used as proxies for kidney function, with cardiovascular outcomes using the 2-sample Mendelian randomization approach. In observational analyses, UNa/UK showed significant inverse associations with atrial fibrillation, coronary artery disease, ischemic stroke, lipid-lowering medication, and T2D. In contrast, urine albumin adjusted for creatinine showed significant positive associations with atrial fibrillation, coronary artery disease, heart failure, hemorrhagic stroke, lipid-lowering medication, and T2D. We found a positive association between UNa/UK and albumin with blood pressure (BP), as well as with adiposity-related measures. After correcting for potential horizontal pleiotropy, we found evidence of causal associations of UNa/UK and albumin with BP (β systolic BP ≥2.63; β diastolic BP ≥0.85 SD increase in BP per SD change in UNa/UK and urine albumin adjusted for creatinine; P≤0.04), and of albumin with T2D (odds ratio=1.33 per SD change in albumin, P=0.02). Our comprehensive study of urinary biomarkers performed using state-of-the-art analyses of causality mirror and extend findings from randomized interventional trials which have established UNa/UK as a risk factor for hypertension. In addition, we detect a causal feedback loop between albumin and hypertension, and our finding of a bidirectional causal association between albumin and T2D reflects the well-known nephropathy in T2D.

中文翻译：

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英国生物库中的尿白蛋白、钠、钾和心血管结果

文本中提供了补充数字内容。尿液生物标志物与心血管疾病有关，但这些关联的性质尚不清楚。我们进行了多变量调整回归模型，以评估尿钠钾比 (UNa/UK) 的随机现场测量值和肌酐调整后的尿白蛋白与心血管危险因素、心血管疾病和 2 型糖尿病 (T2D) 的相关性，共 478英国生物银行的 311 名参与者。此外，我们使用 2 样本孟德尔随机化方法评估了这些用作肾功能代理的肾脏生物标志物与心血管结局的因果关系。在观察性分析中，UNa/UK 与心房颤动、冠状动脉疾病、缺血性中风、降脂药物和T2D。相比之下，根据肌酐调整的尿白蛋白与心房颤动、冠状动脉疾病、心力衰竭、出血性中风、降脂药物和 T2D 显着正相关。我们发现 UNa/UK 和白蛋白与血压 (BP) 以及肥胖相关措施之间存在正相关。在校正潜在的水平多效性后，我们发现了 UNa/UK 和白蛋白与 BP 之间存在因果关系的证据（β 收缩压 ≥2.63；β 舒张压 BP ≥0.85 SD，UNa/UK 的每 SD 变化和尿白蛋白调整为肌酐; P≤0.04)，以及白蛋白与 T2D (比值比 = 1.33 每 SD 变化的白蛋白，P = 0.02)。我们使用最先进的因果关系分析对尿液生物标志物进行了全面研究，并扩展了随机干预试验的结果，这些试验已将 UNa/UK 确定为高血压的危险因素。此外，我们检测到白蛋白和高血压之间的因果反馈回路，我们发现白蛋白和 T2D 之间存在双向因果关系，这反映了众所周知的 T2D 肾病。