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Proteinuria Is an Independent Risk Factor for First Incident Stroke in Adults Under Treatment for Hypertension in China.

ABSTRACT: Conflicting evidence exists regarding whether reduced estimated glomerular filtration rate (eGFR) and proteinuria are independent risk factors for stroke and its subtypes in hypertensive patients. This study investigated the association of these renal measures with first incident stroke in adults under treatment for hypertension in China.The study included 19 599 adults aged 45 to 75 years who participated in the China Stroke Primary Prevention Trial. Baseline eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Proteinuria was assessed by qualitative dipstick urinalysis and in a subset by the quantitative albumin-creatinine ratio method. Cox regression analysis was used to examine the effects of eGFR and proteinuria on the risk of first incident stroke. During a median of 4.5 years of follow-up, a total of 585 first strokes (472 ischemic strokes) were identified. Compared to participants without proteinuria, participants with proteinuria (trace or more by dipstick) had a 35% increased risk of first stroke: the adjusted hazard ratio (HR) (95% CI) was 1.35 (1.09-1.66, P=0.005). The results were robust in subgroup analyses. In a subset with data on proteinuria measured by quantitative albumin-creatinine ratio, a similar association was found. In both independent and combined analyses with proteinuria, eGFR was not significantly associated with stroke.In adults under treatment for hypertension in China, baseline proteinuria measured by dipstick or quantitative albumin-creatinine ratio, but not reduced eGFR, was found to be an independent risk factor for first incident stroke and ischemic stroke.

SUBMITTER: Zhang C

PROVIDER: S-EPMC4845256 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Proteinuria Is an Independent Risk Factor for First Incident Stroke in Adults Under Treatment for Hypertension in China.

Zhang Chunyan C Wang Xiaobin X He Mingli M Qin Xianhui X Tang Genfu G Xu Xin X Wang Yu Y Huo Yong Y Cai Yefeng Y Fu Jia J Zhao Gang G Dong Qiang Q Xu Xiping X Wang Binyan B Hou Fan Fan FF

Journal of the American Heart Association 20151218 12

<h4>Background</h4>Conflicting evidence exists regarding whether reduced estimated glomerular filtration rate (eGFR) and proteinuria are independent risk factors for stroke and its subtypes in hypertensive patients. This study investigated the association of these renal measures with first incident stroke in adults under treatment for hypertension in China.<h4>Methods and results</h4>The study included 19 599 adults aged 45 to 75 years who participated in the China Stroke Primary Prevention Tria ...[more]

PMID: 26683219

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Project description:BACKGROUND AND OBJECTIVES:The natural history of kidney disease among blacks who carry the APOL1 high-risk variants varies, with only a subgroup progressing to ESRD. We aimed to determine whether the APOL1 risk variants are associated with incident proteinuria in the context of hypertension-attributed CKD, and whether subsequent kidney function decline after the onset of proteinuria differs by APOL1 risk status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using Cox models, we studied the association between APOL1 risk status and incident proteinuria (defined as a doubling of urine protein-to-creatinine ratio to a level ?0.22 g/g creatinine) among African-American Study of Kidney Disease and Hypertension (AASK) trial participants with APOL1 genotyping and without proteinuria at baseline. RESULTS:Of the 480 participants in our study, 82 (17%) had the high-risk genotypes (2 alleles), and 254 (53%) developed proteinuria over a median follow-up of 6.8 years. At baseline, mean eGFR was lower in the APOL1 high-risk group compared with the low-risk group (0 or 1 allele; 49.6 versus 53.2 ml/min per 1.73 m2, respectively; P=0.02), but median proteinuria was similar (0.04 g/g creatinine for both groups; P=0.43). Individuals with the high-risk genotypes were 1.72-fold more likely to develop incident proteinuria compared with those with the low-risk genotypes (95% confidence interval, 1.27 to 2.32), independent of age, sex, ancestry, baseline eGFR, baseline systolic BP, and randomized treatment groups. Although eGFR declined faster after the onset of proteinuria, this rate did not differ significantly by APOL1 risk status. CONCLUSIONS:Among blacks with established moderate CKD, the APOL1 high-risk variants are associated with greater risk of incident proteinuria. After proteinuria onset, kidney function declines more rapidly but does not differ by APOL1 risk status. This suggests that factors that lead to proteinuria, beyond APOL1, may additionally drive CKD progression.

Project description: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 ? 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.

Dataset Information

Proteinuria Is an Independent Risk Factor for First Incident Stroke in Adults Under Treatment for Hypertension in China.

Publications

Proteinuria Is an Independent Risk Factor for First Incident Stroke in Adults Under Treatment for Hypertension in China.

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