Comparison of Associations of Reduced Estimated Glomerular Filtration Rate With Stroke Outcomes Between Hypertension and No Hypertension
Background and Purpose—We compared the association of low estimated glomerular filtration rate (eGFR) with stroke outcomes among patients with hypertension and without hypertension.
Methods—We used the China stroke registry to identify patients on discharge with the diagnosis of stroke in 2012 and 2013. Low eGFR was defined as <60 mL/min/1.73 m2. Multivariable analysis was used to evaluate the association of low eGFR with 1-year all-cause mortality, recurrent stroke, poor functional outcome defined as 3 to 6 in modified Rankin Scale (mRS), and ordinal mRS, where the interaction of eGFR category and hypertension status was investigated.
Results—Of 5082 patients without hypertension, 221 patients (4.4%) had low eGFR, as compared with 1378 patients (8.6%) previously diagnosed with hypertension. In patients without hypertension, the adjusted odds ratios with 95% confidence interval of low eGFR was 1.88 (1.23–2.88) for all-cause mortality, 1.36 (0.66–2.83) for recurrent stroke, 2.14 (1.45–3.16) for poor functional outcome, and 2.07 (1.58–2.70) for ordinal mRS. In patients with hypertension, low eGFR was associated with all stroke outcomes: 1.80 (1.50–2.16) for all-cause mortality, 1.52 (1.20–1.91) for recurrent stroke, 1.30 (1.11–1.52) for poor functional outcome, and 1.31 (1.18–1.46) for ordinal mRS. The significant interaction between eGFR categories and hypertension was only found for poor functional outcome (P=0.046) and ordinal mRS (P=0.002).
Conclusions—Effect of low eGFR on all-cause mortality and recurrent stroke in patients without hypertension was not significantly different from that in patients with hypertension, but low-eGFR patients without hypertension had a higher risk of stroke-related disability than those with hypertension.
Stroke has become the second cause of death (88 per 100 000 population) and the third cause of disability-adjusted life years (15 per 1000 population) worldwide in 2010.1,2 Low estimated glomerular filtration rate (eGFR), 1 of 2 key renal measures for chronic kidney disease, is related to the risk of cardiovascular events in many studies.3–5
Hypertension has been estimated to be responsible for at least 50% of deaths because of stroke6 and is both a cause and consequence of chronic kidney disease.7 However, there is little data evaluating the association of low eGFR with adverse outcomes in stroke patients with the presence or absence of hypertension. Thus, the goal of the current study was to use the China national stroke registry phase II to compare the association between low eGFR and stroke outcomes in hypertensive versus nonhypertensive patients.
The study population included patients who survived a stroke at discharge in China national stroke registry phase II. From June 2012 to January 2013, 21 075 patients were included in the final analysis after excluding patients because of missing eGFR value and loss to 1-year follow-up. (Figure 1; Table I in the online-only Data Supplement). Written informed consents were obtained from patients or their legally authorized representatives. The study was approved by the central institutional review board at Beijing Tiantan hospital.
eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation with adjusted coefficient of 1.1 for the Asian population.8,9 eGFR values were stratified into 3 categories: <60, 60 to 89, and ≥90 mL/min/1.73 m2, which were based on the classification for chronic kidney disease assessment and management10 but modified for the following reason: participants with moderate or severe renal insufficiency and kidney failure were pooled together into the category of eGFR <60 mL/min per 1.73 m2 because of the small sample size. Low eGFR was defined as <60 mL/min/1.73 m2.
Follow-up was performed by telephone interview at 12 months after disease onset. Outcome data collected contained all-cause mortality, recurrent stroke, and poor functional outcome. Composite end points included all-cause mortality and recurrent stroke. Poor functional outcome was defined by modified Rankin Scale of 3 to 6 (mRS, score range from 0 [no symptoms] to 6 [death]). And mRS was also analyzed as an ordinal outcome with 6 categories in this study.
Differences of continuous variables between eGFR categories were tested with t test or Kruskal–Wallis test depending on if the data are normally distributed or not, respectively. The χ2 test (or Fisher exact test with frequencies <5) was used for categorical variables. The association between eGFR strata and clinical outcomes was evaluated using a logistic or proportional odds regression model with eGFR of ≥90 mL/min/1.73 m2 as the reference group adjusting for covariates among all patients stratified by hypertension status. We also tested the statistical significance of the interaction between eGFR category and hypertension in the adjusted model using all subjects.
Further information about study participants, data collection, and statistical analysis are available in the online-only Data Supplement.
Of 5082 patients without hypertension, 221 patients (4.4%) had low eGFR and of 15 993 patients with hypertension, 1378 patients (8.6%) experienced low eGFR. The Table demonstrates baseline characteristics of nonhypertensive and hypertensive patients with stroke according to eGFR categories. Figure I and Table II in the online-only Data Supplement demonstrate 1-year incidences of stroke outcomes among nonhypertensive and hypertensive patients according to eGFR categories. Odds ratios with 95% confidence interval of eGFR levels for stroke outcomes according to hypertensive status were reported in Figure 2. The significant interaction between eGFR categories and hypertension was only found for poor functional outcome (P=0.046) and ordinal mRS (P=0.002). We observe that among eGRF <60 mL/min/1.73 m2, there were slightly higher percent of subjects with mRS scores in the range of 3 to 6 in nonhypertension group than in hypertension group (Table II in the online-only Data Supplement).
In this national cohort study of stroke, low eGFR was associated with all-cause mortality, the composite end point of all-cause mortality and recurrent stroke, poor functional outcome, and ordinal mRS in both patients without and with hypertension, whereas the association of low eGFR with recurrent stroke only existed in those with hypertension. The magnitude of associations of low eGFR with all-cause mortality and composite end points in patients without hypertension were similar to those with hypertension, but associations for poor functional outcome and ordinal mRS in nonhypertensive patients were stronger than those in hypertensive patients. We did not observe the interaction of eGFR and hypertension for all stroke outcomes except for poor functional outcome and ordinal mRS. Our results were consistent with results of previous studies.11,12 Importantly, our data provide additional information on stroke disability in a national-level registry.
There were several limitations to this study that should be addressed. First, our cohort only comprised Chinese adult patients with stroke, and the results might not be generalizable to other races or ethnicities. Second, patients with lack of baseline serum creatinine and missing follow-up information were excluded, and our results may have been subject to selection bias, such as differences in the presence of coronary heart disease. Third, we were not able to control for the potentially nephroprotective effects of postdischarge antihypertensive medication use because of lack of information on patient adherence during the follow-up period.
Effect of low eGFR on all-cause mortality and recurrent stroke in patients without hypertension was not significantly different from that in those with hypertension, but low-eGFR patients without hypertension had a higher risk of stroke-related disability than those with hypertension.
We thank all participating hospitals, their physicians and nurses, and the CNSR II Steering Committee members.
Sources of Funding
Funding for this study was provided by NINDS D43 TW008308 training for the prevention and treatment of stroke and the Ministry of Science and Technology of the People’s Republic of China (2008ZX09312-008, 2011BAI08B02, 2012ZX09303, and 200902004), and Program for New Century Excellent Talents in University (NCET-13-0917).
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.117.016864/-/DC1.
- Received November 30, 2016.
- Revision received March 6, 2017.
- Accepted March 8, 2017.
- © 2017 American Heart Association, Inc.
- Lozano R,
- Naghavi M,
- Foreman K,
- Lim S,
- Shibuya K,
- Aboyans V,
- et al
- Murray CJ,
- Vos T,
- Lozano R,
- Naghavi M,
- Flaxman AD,
- Michaud C,
- et al
- Lee M,
- Saver JL,
- Chang KH,
- Liao HW,
- Chang SC,
- Ovbiagele B
- 6.↵World Health Organization. A global brief on hypertension: silent killer, global public health crisis. http://apps.who.int/iris/bitstream/10665/79059/1/WHO_DCO_WHD_2013.2_eng.pdf Accessed May 10, 2015.
- Wang X,
- Luo Y,
- Wang Y,
- Wang C,
- Zhao X,
- Wang D,
- et al
- Ninomiya T,
- Kiyohara Y,
- Tokuda Y,
- Doi Y,
- Arima H,
- Harada A,
- et al
- Ovbiagele B,
- Bath PM,
- Cotton D,
- Sha N,
- Diener HC