BACKGROUND Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events including stroke. Hypertension has been proposed as the principal confounder of this relationship but its role has not been systematically examined. AIM We aimed to determine if proteinuria remains an independent predictor of stroke after more complete adjustment for blood pressure. SUMMARY OF REVIEW We performed a systematic review, searching MEDLINE and EMBASE (to February 2018) for cohort studies or randomized controlled trials that reported stroke incidence in adults according to baseline proteinuria ± glomerular filtration rate. Study and participant characteristics and relative risks were extracted. Estimates were combined using a random effects model. Heterogeneity was assessed by χ 2 statistics and I2, and by subgroup strata and meta-regression, with a particular focus on the impact of more complete adjustment for blood pressure on the association. The quality of cohort studies and post hoc analyses was assessed using the Newcastle-Ottawa Scale. We identified 38 studies comprising 1,735,390 participants with 26,405 stroke events. Overall, the presence of any level of proteinuria was associated with greater stroke risk (18 studies; pooled crude relative risk 2.00, 95%CI 1.63-2.46; p < 0.001) even after adjustment for established cardiovascular risk factors (33 studies; pooled adjusted relative risk 1.72, 1.51-1.95; p < 0.001), albeit with considerable heterogeneity between studies (p < 0.001; I2 = 77.3%). Moreover, the association did not substantially attenuate with more thorough adjustment for hypertension: single baseline blood pressure measure (10 studies; pooled adjusted relative risk = 1.92, 1.39-2.66; p < 0.001); history or treated hypertension (four studies; pooled adjusted relative risk = 1.76, 1.13-2.75, p = 0.013); multiple blood pressure measurements over months to years (four studies; relative risk = 1.68, 1.33-2.14; p < 0.001). CONCLUSIONS Even after extensive adjustment for hypertension, proteinuria is strongly and independently associated with incident stroke risk, possibly indicating a shared renal and cerebral susceptibility to vascular injury that is not fully explained by traditional vascular risk factors.

中文翻译：

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蛋白尿作为卒中的独立预测因子：系统评价和荟萃分析。

背景技术蛋白尿已成为包括中风在内的不良心血管事件的重要血管危险因素。高血压被认为是这种关系的主要混杂因素，但尚未系统地检查其作用。目的我们旨在确定在更完全地调整血压后，蛋白尿是否仍是卒中的独立预测因子。综述我们进行了系统的综述，从MEDLINE和EMBASE（至2018年2月）中搜索队列研究或随机对照试验，以根据基线蛋白尿±肾小球滤过率报告成人卒中发生率。提取研究和参与者特征以及相对风险。使用随机效应模型对估计值进行合并。通过χ2统计量和I2评估异质性，以及亚组分层和荟萃回归，尤其着重于更完整地调整血压对协会的影响。使用Newcastle-Ottawa量表评估队列研究和事后分析的质量。我们确定了38项研究，包括1,735,390名参与者，发生了26,405起中风事件。总体而言，即使在对已确定的心血管危险因素进行调整（33次研究；合并校正后）后，任何水平的蛋白尿都与较高的中风风险相关（18个研究；合并的相对粗风险为2.00，95％CI 1.63-2.46； p <0.001）。相对风险1.72，1.51-1.95； p <0.001），尽管研究之间存在相当大的异质性（p <0.001； I2 = 77.3％）。此外，对于高血压的更彻底的调整，这种关联并没有明显减弱：单项基线血压测量（10项研究；汇总调整后相对危险度= 1.92，1.39-2.66； p <0.001）；既往病史或已治疗的高血压（四项研究；合并调整后相对危险度= 1.76，1.13-2.75，p = 0.013）；在数月至数年内进行多次血压测量（四项研究；相对风险= 1.68，1.33-2.14； p <0.001）。结论即使对高血压进行了广泛的调整，蛋白尿仍与卒中的发生风险密切相关，可能表明肾脏和大脑对血管损伤有共同的易感性，而传统血管危险因素并未对此做出充分解释。在数月至数年内进行多次血压测量（四项研究；相对风险= 1.68，1.33-2.14； p <0.001）。结论即使对高血压进行了广泛的调整，蛋白尿仍与卒中的发生风险密切相关，可能表明肾脏和大脑对血管损伤有共同的易感性，而传统血管危险因素并未对此做出充分解释。在数月至数年内进行多次血压测量（四项研究；相对风险= 1.68，1.33-2.14； p <0.001）。结论即使对高血压进行了广泛的调整，蛋白尿仍与卒中的发生风险密切相关，可能表明肾脏和大脑对血管损伤有共同的易感性，而传统血管危险因素并未对此做出充分解释。