Cerebral Small Vessel Disease and Major Adverse Cardiovascular Events: The Framingham Heart Study
Riya Manchanda1, Adlin Pinheiro2, Hugo Javier Aparicio1, Vasileios-Arsenios Lioutas3, Alexa Beiser2, Oluchi Ekenze4, Emelia Benjamin5, Charles DeCarli6, Sudha Seshadri7, Serkalem Demissie2, Jose Romero1
1Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, 2Department of Biostatistics, Boston University School of Public Health, 3Beth Israel Deaconess Medical Center, Department of Neurology, 4Graduate Medical Sciences, Boston University Chobanian & Avedisian School of Medicine, 5Boston University Chobanian & Avedisian School of Medicine, 6Department of Neurology, University of California, 7Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases
Objective:
To investigate the association between cerebral small vessel disease (CSVD) and incidence of major adverse cardiovascular events (MACE) in a healthy, community-dwelling population.
Background:
The effect of neurovascular health on cardiovascular outcomes is not well-known. One neurological risk factor is CSVD, and studying relations to MACE could aid with risk stratification and targeted treatment for disease prevention.
Design/Methods:
We included 3263 Framingham Heart Study participants free of 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, 2, or 3+. MACE consisted of a composite outcome and three components: stroke, myocardial infarction, and cardiovascular death. Cox regression analysis was used with models adjusted for age, sex, cohort, MRI-exam cycle time interval, and vascular risk factors.
Results:
Presence of CSVD was observed in 30.5% of the participants (72.4% CSVD score of 1, 22.2% score of 2, 5.4% score of 3+). Participants with CSVD scores of 1 or 2 had about 1.5 times higher risk of any MACE events (95%CI 1.17-1.81) after multivariable adjusted analyses. There was 1.5-fold increased risk of cardiovascular death (95%CI 1.15-1.93), with risk rising steadily as the CSVD burden increased from 1 to 3+. Similarly, higher stroke risk was seen in patients with CSVD score of 1 (HR 1.57, 95%CI 1.04, 2.35), also increasing as CSVD burden increased. There was numerically higher risk among CSVD patients with scores of 1 or 2 of having a myocardial infarction, but not reaching statistical significance.
Conclusions:
CSVD burden is associated with MACE risk in community-dwelling individuals, suggesting that neurovascular health may be a useful predictor of cardiovascular health and could be a target for MACE prevention.
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