Change in the Estimated Glomerular Filtration Rate Over Time and Risk of First Stroke in Hypertensive Patients

Abstract

Background The association between changes in estimated glomerular filtration rate (eGFR) over time and the risk of stroke remains inconclusive. We aimed to evaluate the relation of eGFR change during the China Stroke Primary Prevention Trial (CSPPT) with the risk of first stroke during the subsequent post-trial follow-up. Methods A total of 11,742 hypertensive participants with two eGFR measurements (median measure interval, 4.4; interquartile range, 4.2–4.6 years) and without a history of stroke from the CSPPT were included in this analysis. Results Over a median post-trial follow-up of 4.4 years, 729 first strokes were identified, of which 635 were ischemic, 88 were hemorrhagic, and 6 were uncertain types of strokes. Compared with those with 1 to <2% per year increase in eGFR (with the lowest stroke risk), those with an increase in eGFR of ≥4% per year had significantly increased risks of first stroke (adjusted hazard ratio [HR] 1.96; 95% confidence interval [CI], 1.10–3.50) and first ischemic stroke (adjusted HR 2.14; 95% CI, 1.17–3.90). Similarly, those with a decline in eGFR of ≥5% per year also had significantly increased first stroke (adjusted HR 2.13; 95% CI, 1.37–3.31) and first ischemic stroke (adjusted HR 1.89; 95% CI, 1.19–3.02) risk. However, there was no significant association between eGFR change and first hemorrhagic stroke. A similar result was found when the change in eGFR was quantified as an absolute annual change. Conclusion In Chinese hypertensive patients, both the decline and increase of eGFR levels were independently associated with the risks of first stroke or first ischemic stroke.

Risk of recurrent stroke and dementia following acute stroke by changes in kidney function: results from the Perindopril Protection Against Recurrent Stroke Study

“…Previous studies have reported associations of dynamic decline in kidney function and cardiovascular events [7–10] and mortality [8,10,11,14–17]. Our study of large (>30%) or rapid (>5 ml/min/1.73 m 2 /year) eGFR decline being robustly related to major cardiovascular events and all-cause mortality is consistent with prior research [7–11,14–17], but such findings regarding stroke are inconsistent [6–9]. Shlipak et al .…”

“…Another study found that greatest decline of at least 5 ml/min/1.73 m 2 /year was related to 29% increase of stroke risk after adjusting for baseline eGFR [9], while He et al . [6] reported declining eGFR (≥5% per year) was associated with a higher risk of first stroke. To our knowledge, only one article has examined the relationship between change in eGFR and recurrent stroke; that of Vart et al .…”

“…To our knowledge, only one article has examined the relationship between change in eGFR and recurrent stroke; that of Vart et al [29] who reported a 56% higher risk for recurrent stroke in patients with more than 20% decline using within 5% as reference. Consequently, studies have reported a U-shaped relationship of GFR change and CHD [10], stroke [6,29], and mortality [10,14,16,30,31]. There are several possible explanations for the association of decline in GFR and risk of major cardiovascular event and all-cause mortality as reduced kidney function, reflective of CKD, is an established risk factor for cardiovascular disease [2][3][4].…”

“…ata are emerging of the importance of chronic kidney disease (CKD) as risk factor for stroke [1,2], but most studies have examined the association of baseline estimated glomerular filtration rate (eGFR) on incident stroke [2][3][4][5] without considering dynamic changes in eGFR over time [6]. Such an approach may highlight important differences in cardiovascular risk in relation to declining or stable kidney function [7].…”

“…Declining kidney function appears to increase the risk of myocardial infarction (MI) [7][8][9][10], heart failure [7][8][9], end-stage kidney disease (ESKD) [8,[11][12][13], as well as predicting higher rates of all-cause mortality [8,10,11,[14][15][16][17]. Thus, dynamic changes in eGFR, defined by percent or slope of change in eGFR, might be an independent risk factor for incident stroke [6,9]. Prior stroke is a substantial risk for major adverse clinical outcomes [18].…”