Impact and interaction of low estimated GFR and B vitamin therapy on prognosis among ischemic stroke patients: the Vitamin Intervention for Stroke Prevention (VISP) trial

Abstract

Background: Low estimated glomerular filtration rate (eGFR) has been linked to higher risk of primary stroke, but little is known about the relation of low eGFR to recurrent vascular risk after stroke. B Vitamin therapy has been used to lower homocysteine levels, but its interaction with kidney function on future major vascular events has not been assessed. The objective of this study was to conduct a secondary analysis based on the Vitamin Intervention for Stroke Prevention (VISP) trial to clarify these issues.

Study design: In the VISP trial, patients with a prior ischemic stroke were randomly assigned to receive the high- or low-dose B vitamin therapy. The trial did not find a difference between randomly assigned groups. The present study is a secondary analysis of the VISP trial.

Setting & participants: We analyzed the database of a multicenter trial comprising 3,673 patients with recent ischemic stroke who were followed up for 2 years.

Predictor: We subdivided the cohort based on eGFR into 6 groups (≥105, 90-104, 75-89, 60-74, 45-59, and <45 mL/min/1.73 m²) for the analyses and used eGFR of 60-74 mL/min/1.73 m² as the reference category. Low eGFR was defined as <45 mL/min/1.73 m².

Outcomes: The primary end point for this analysis was major vascular events, defined as the composite of nonfatal ischemic stroke, nonfatal myocardial infarction, and vascular death (whichever event came first). The secondary end point was recurrent ischemic stroke. Also, the effects of high-dose B vitamin treatment on future major vascular events according to baseline eGFR categories were analyzed and reported separately.

Results: Mean baseline eGFR was 73.9 ± 21.8 (SD) mL/min/1.73 m². 471 major vascular events during an average of 20 months of follow-up, including 300 recurrent strokes, were recorded. Baseline low eGFR was associated with increased risk of major vascular events (HR, 1.83; 95% CI, 1.32-2.52; P < 0.001) and recurrent stroke (HR, 1.53; 95% CI, 1.01-2.32; P = 0.04) after adjustment for traditional vascular risk factors and homocysteine level. At baseline eGFR <45 mL/min/1.73 m², high-dose B vitamin therapy compared to low dose showed a trend of higher risk of future major vascular events (HR, 1.49; 95% CI, 0.95-2.34; P = 0.08). The overall P value for interaction between B vitamin dose and eGFR was not significant (P = 0.6).

Limitations: No data for albuminuria.

Conclusions: Low eGFR is associated with higher risk of future major vascular events and recurrent stroke after a recent ischemic stroke.