Sex-specific Associations Of Vascular Risk Factors And Brain Mri Measures In The Framingham Offspring

Aim: To examine if the associations between vascular risk factors (VRF) and brain MRI measures of brain aging and cerebral small vessel disease are different in men and women. Background: Men and women differ in their propensity to develop stroke and this is reflected in sex-specific versions of the widely used Framingham Stroke Risk Prediction (FSRP) index, that provides an estimate of 10-year risk of incident clinical stroke. However, sex-specific associations between the individual risk factor components of FSRP and subclinical vascular brain injury have not been previously explored in our data. Methods/Design: We related levels of blood pressure, diabetes, current smoking and prevalent non-stroke cardiovascular disease (CVD) to brain MRI measures of total cerebral brain, hippocampal and white matter hyperintensity volumes (TCBV, HPV, WMHV) and covert brain infarcts (CBI) in 1,579 stroke- and dementia-free Framingham Offspring who attended their 8th quadrennial examination (53% F; age 66±9 years). We examined age-adjusted, sex-stratified linear or logistic regression analyses for all VRF that suggested a sex-interaction at a p<0.1. Results: Higher blood pressure (assessed as systolic blood pressure (SBP) or as JNC7 defined Stage 1 HTN (≥140/90 mm Hg or use of antihypertensive medication), had a greater adverse impact on WMHV in women compared to men (SBP: β±SE: 0.009±0.002, p<0.001 versus 0.004±0.002, p<0.031; HTN: β 0.176±0.066, p=0.008 versus non-significant association, in women and men respectively), although prevalent CVD, reflecting lifetime vascular risk factor exposure and injury, had a larger adverse effect on WMHV in men (β -0.221±0.087, p=0.012, versus a non-significant association in women). In addition, both Stage 1 HTN and diabetes had larger adverse effects on TCBV in men (β -0.309±0.141, p<0.029 and -0.853±0.177, p<0.001 respectively, versus non-significant associations in women). Conclusions: In our cohort of young-old participants, wherein most women were post-menopausal, current levels of VRF at the time of examination, were associated with a greater burden of vascular brain injury in women than in men of the same age, whereas current VRF levels appeared to have a greater global impact on brain volumes in men. Our data suggest that the greater risk of dementia noted in older women compared to men may be substantially attributable to modifiable vascular risk factors; more aggressively controlling these in women may reduce sex disparities.