Association of aortic valve calcium with dementia and stroke: The Multi-Ethnic Study of Atherosclerosis

Authors: MARRERO, NATALIE - University Of Miami; JHA, KUNAL - Johns Hopkins University School Of Medicine; HUGHES, TIMOTHY - Wake Forest School Of Medicine; RAZAVI, ALEXANDER - Johns Hopkins University School Of Medicine; GRANT, JELANI - Johns Hopkins University School Of Medicine; BOAKYE, ELLEN - Johns Hopkins University School Of Medicine; ANCHOUCHE, KHALIL - McGill University - Canada; DZAYE, OMAR - Johns Hopkins University School Of Medicine; BUDOFF, MATTHEW - Harbor-Ucla Medical Center; ROTTER, JEROME - Harbor-Ucla Medical Center; GUO, XIUQING - Harbor-Ucla Medical Center; YAO, JIA - Harbor-Ucla Medical Center; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); BLUMENTHAL, ROGER - Johns Hopkins University School Of Medicine; MICHOS, ERIN - Johns Hopkins University School Of Medicine; THANASSOULIS, GEORGE - McGill University - Canada; POST, WENDY - Johns Hopkins University School Of Medicine; BLAHA, MICHAEL - Johns Hopkins University School Of Medicine; IBEH, CHINWE - Columbia University - New York; WHELTON, SEAMUS - Johns Hopkins University School Of Medicine

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/22/2024
Publication Date: 5/27/2024
Citation: Marrero, N., Jha, K., Hughes, T.M., Razavi, A.C., Grant, J.K., Boakye, E., Anchouche, K., Dzaye, O., Budoff, M.J., Rotter, J.I., Guo, X., Yao, J., Wood, A.C., Blumenthal, R.S., Michos, E.D., Thanassoulis, G., Post, W.S., Blaha, M.J., Ibeh, C., Whelton, S. 2024. Association of aortic valve calcium with dementia and stroke: The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. https://doi.org/10.1016/j.atherosclerosis.2024.117596.
DOI: https://doi.org/10.1016/j.atherosclerosis.2024.117596

Interpretive Summary: Calcific aortic valve disease is associated increased risk of decreased blood flow to the brain, which can lead to stroke, but it is not recognized as a risk factor for either condition in clinical settings. We examined whether aortic valve calcification (AVC) is associated with dementia and/or stroke, controlling for adiposity – one of the major risk factors for stroke. In a large study of over 6,000 people, spanning 16 years, AVC was associated with an increased risk of newly diagnosed dementia, but not incident stroke. This suggests that AVC may be an important risk factor for the long-term risk of dementia beyond traditional risk factors, but is not a risk factor for stroke over and above obesity.

Technical Abstract: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA). AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, >=300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1,000 person-years) and multivariable adjusted Cox proportional hazards ratios (HR). Overall, 6,812 participants had AVC quantified with a mean age of 62.1 years old, 52.9% were women, and the median 10-year estimated atherosclerotic cardiovascular disease (ASCVD) risk was 13.5%. Participants with AVC >0 were older and less likely to be women compared to those with AVC=0. Over a median 16-year follow-up, there were 535 cases of dementia and 376 cases of stroke. The absolute risk of newly diagnosed dementia increased in a stepwise pattern with higher AVC scores, and stroke increased in logarithmic pattern. In multivariable analyses, AVC was significantly associated with newly diagnosed dementia as a log-transformed continuous variable (HR 1.09; 95% CI 1.04-1.14) and persons with AVC =300 had nearly a two-fold higher risk (HR 1.77; 95% CI 1.14-2.76) compared to those with AVC=0. AVC was associated with an increased risk of stroke after adjustment for age, sex, and race/ethnicity, but not after adjustment for ASCVD risk factors. After multivariable adjustment, AVC >0 was significantly associated with an increased risk of newly diagnosed dementia, but not incident stroke. This suggests that AVC may be an important risk factor for the long-term risk of dementia beyond traditional ASCVD risk factors.