Hypertensive Retinopathy and the Risk of Stroke Among Hypertensive Adults in China

Abstract

Purpose: This study aimed to investigate the association between hypertensive retinopathy and the risk of first stroke, examine possible effect modifiers in hypertensive patients, and test the appropriateness of the Keith-Wagener-Barker (KWB) classification for predicting stroke risk.

Methods: In total, 9793 hypertensive participants (3727 males and 6066 females) without stroke history from the China Stroke Primary Prevention Trial were included in this study. The primary outcome was first stroke.

Results: Over a median follow-up of 4.4 years, 592 participants experienced their first stroke (509 ischemic, 77 hemorrhagic, and six unclassifiable strokes). In total, 5590 participants were diagnosed with grade 1 retinopathy (57.08%), 1466 with grade 2 retinopathy (14.97%), 231 with grade 3 retinopathy (2.36%), and three with grade 4 retinopathy (0.03%). Grades 1 and 2 were merged and classified as mild retinopathy, and grades 3 and 4 were merged and classified as severe retinopathy. There was a significant positive association between hypertensive retinopathy and the risk of first stroke and first ischemic stroke, and no effect modifiers were found. The hazard ratios (HRs) for first stroke were as follows: mild versus no retinopathy, 1.26 (95% confidence interval [CI], 1.01-1.58, P = 0.040), and severe versus no retinopathy, 2.40 (95% CI, 1.49-3.84, P < 0.001). The HRs for ischemic stroke were as follows: severe versus no retinopathy, 2.35 (95% CI, 1.41-3.90, P = 0.001), and nonsignificantly increased HRs for mild versus no retinopathy, 1.26 (95% CI, 0.99-1.60, P = 0.057).

Conclusions: There was a significant positive association between hypertensive retinopathy and the risk of first stroke in patients with hypertension, indicating that hypertensive retinopathy may be a predictor of the risk of stroke. A simplified two-grade classification system based on the KWB classification is recommended for predicting stroke risk.

Figure 1.

Flow chart of participants.

Figure 2.

Survival curves constructed for incident stroke according to sex and hypertensive retinopathy classification (normal; mild retinopathy = Grade 1–2 according to the Keith-Wagener-Barker classification system; severe retinopathy = Grade 3–4 according to the Keith-Wagener-Barker classification system). (A) Total, (B) Male, (C) Female.

Figure 3.

Association between hypertensive retinopathy (mild/grade 1-2 and severe/grade 3-4 vs. normal) and first stroke in subgroups*. *Adjusted for age, sex, BMI, SBP, DBP, diabetes, triglycerides, total cholesterol, high-density lipoprotein, serum folic acid, tHcy, fasting glucose, serum creatinine, treatment group, methylenetetrahydrofolate reductase C677T genotype, and smoking and alcohol consumption status.

Figure 4.

Examples of four grades of hypertensive retinopathy (Keith-Wagener-Barker Classification System). (A) Grade 1 hypertensive retinopathy showing mild generalized retinal arteriolar narrowing and arteriovenous tortuosity (white arrow). (B) Grade 2 hypertensive retinopathy showing focal narrowing and arteriovenous nicking (white arrow). (C) Grade 3 hypertensive retinopathy showing multiple retinal hemorrhages (white arrows), exudates (black arrow) and cotton-wool spots (gray arrow). (D) Grade 4 hypertensive retinopathy showing multiple retinal hemorrhages (white arrows), exudates (black arrow), cotton-wool spots (gray arrow), and swelling of the optic disk.