Cerebral Small Vessel Disease and Risk of Cardiovascular Events and All-Cause Mortality: The Framingham Heart Study

BACKGROUND: The effect of neurovascular health on cardiovascular outcomes is not well-known. Cerebral small vessel disease (CSVD) signals subclinical vascular brain injury and its quantification may serve as a tool to stratify risk in healthy individuals. Studying the relations of CSVD to cardiovascular events and mortality could aid in targeted preventive efforts. METHODS: We included Framingham Heart Study participants free of diagnosed stroke and dementia. CSVD was assessed on brain MRI?considering covert infarcts, cerebral microbleeds, cortical superficial siderosis, high perivascular space burden, and extensive white matter hyperintensities?with 1 point assigned for each marker, to categorize CSVD scores as 0, 1, or 2+. We used a composite outcome and three components: stroke, myocardial infarction, and mortality. Cox regression analysis was used with models adjusted for age, sex, cohort, MRI-exam cycle time interval, and vascular risk factors. RESULTS: In our study, 31% of our 3263 participants (mean age 58.0 years [SD: 13.4], 54% women) had a CSVD score greater than 0, and those with higher scores were generally older and had higher prevalence of vascular risk factors. Over a median follow-up of 8.4 years, 454 participants (13.9%) experienced at least one outcome, with mortality being the most common. Increasing CSVD burden was associated with higher incidence rates of the composite outcome. Compared with participants with CSVD score 0, those with scores of 1 and 2 had significantly higher risk of any event (HR 1.48, 95% CI 1.19?1.85; HR 1.52, 95% CI 1.17?1.97 respectively). CSVD burden showed a dose-response relationship with all-cause mortality and was associated with increased stroke risk, while no significant association with MI was observed. CONCLUSION: Higher subclinical CSVD burden is independently associated with increased risk of adverse cardiovascular events and mortality in community-dwelling individuals. CSVD detected on brain MRI may serve as a valuable imaging biomarker for risk stratification and early prevention of life-threatening outcomes.