Cerebral Small Vessel Disease and Risk of Cardiovascular Events and All-Cause Mortality: The Framingham Heart Study
- 1Boston University Chobanian & Avedisian School of Medicine
Abstract
O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/26361997v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): [email protected]@aaf8f2org.highwire.dtl.DTLVardef@be10a1org.highwire.dtl.DTLVardef@35c7be_HPS_FORMAT_FIGEXP M_FIG C_FIG BACKGROUNDThe 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.
METHODSWe 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.
RESULTSIn 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.
CONCLUSIONHigher 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.
Indexing Terms: Stroke, Mortality, Myocardial Infarction, Cerebral Small Vessel Disease, Vascular Disease, Brain MRI
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BibTeX
@misc{manchanda2026cerebral,
title = {{Cerebral Small Vessel Disease and Risk of Cardiovascular Events and All-Cause Mortality: The Framingham Heart Study}},
author = {R. Manchanda and A. Pinheiro and H. J. Aparicio and V.-A. Lioutas and A. S. Beiser and J. Sisto and O. Ekenze and E. J. Benjamin and C. DeCarli and S. Seshadri and J. R. Romero},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.26361997},
url = {https://www.medrxiv.org/content/10.64898/2026.09.01.26361997v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cerebral Small Vessel Disease and Risk of Cardiovascular Events and All-Cause Mortality: The Framingham Heart Study
AU - R. Manchanda
AU - A. Pinheiro
AU - H. J. Aparicio
AU - V.-A. Lioutas
AU - A. S. Beiser
AU - J. Sisto
AU - O. Ekenze
AU - E. J. Benjamin
AU - C. DeCarli
AU - S. Seshadri
AU - J. R. Romero
PY - 2026
DA - 2026/09/01
PB - medRxiv
DO - 10.64898/2026.09.01.26361997
UR - https://www.medrxiv.org/content/10.64898/2026.09.01.26361997v1
AB - O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/26361997v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): [email protected]@aaf8f2org.highwire.dtl.DTLVardef@be10a1org.highwire.dtl.DTLVardef@35c7be_HPS_FORMAT_FIGEXP M_FIG C_FIG BACKGROUNDThe 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. METHODSWe 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. RESULTSIn 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. CONCLUSIONHigher 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. Indexing Terms: Stroke, Mortality, Myocardial Infarction, Cerebral Small Vessel Disease, Vascular Disease, Brain MRI
ER -