Synergistic effect of hypertension and smoking on the total small vessel disease score in healthy individuals: the Kashima scan study

The total cerebral small vessel disease (SVD) score is a proposed comprehensive index of SVD severity in the brain. However, data on lifestyle-related risk factors affecting SVD scores are limited. We conducted a cross-sectional study with 858 neurologically healthy adults who underwent brain magnetic resonance imaging (MRI). Information on clinical and lifestyle-related risk factors was obtained from health screenings. The SVD score (0–4) was calculated from the presence of lacunes, cerebral microbleeds, moderate to severe white matter lesions, and basal ganglia perivascular spaces on MRI. Subjects were divided into two groups by SVD score; potential risk factors and their joint effects in the two groups were assessed by logistic regression. Biologic interactions were estimated using the synergy index. After adjustment for possible confounders, the adjusted odds ratio for moderate to severe SVD scores (SVD score ≥ 2) was 1.12 (95% confidence interval (CI) 1.08–1.16) for age per year, 1.33 (95% CI 1.02–1.74) for body mass index per standard deviation, 3.39 (95% CI 1.90–6.03) for hypertension, 2.31 (95% CI 1.14–4.69) for diabetes, and 2.35 (95% CI 1.10–5.02) for smoking. Hypertension and current smoking had a synergistic effect on the risk of moderate to severe SVD (OR 10.59, 95% CI 3.97–28.3; synergy index 4.03, 95% CI 1.17–28.30), and the combination of hypertension and diabetes had an additive effect on the risk of moderate to severe SVD (OR 9.48, 95% CI 3.80–23.66; synergy index 2.12, 95% CI 0.68–6.67). Therefore, combined strategies for managing hypertension, smoking, and diabetes may be effective for preventing SVD.