02440nas a2200193 4500008004100000022001400041245013300055210006900188260001600257520178400273100002302057700002302080700002802103700001602131700002002147700002002167700002302187856003602210 2019 eng d a1473-559800aThe role of functional status on the relationship between blood pressure and cognitive decline: the Cardiovascular Health Study.0 arole of functional status on the relationship between blood pres c2019 May 013 a

OBJECTIVE: To examine whether self-reported functional status modified the association between blood pressure (BP) and cognitive decline among older adults.

METHODS: The study included 2097 US adults aged 75 years and older from the Cardiovascular Health Study, followed for up to 6 years. Functional status was ascertained by self-reported limitation in activities of daily living (ADL; none vs. any). Cognitive function was assessed by the Modified Mini Mental State Exam (3MSE). We used linear mixed models to examine whether the presence of at least one ADL limitation modified the association between BP and cognitive decline. Potential confounders included demographics, physiologic measures, antihypertensive medication use and apolipoprotein E ε4 allele. We conducted stratified analyses for significant interactions between BP and ADL.

RESULTS: The association between BP and change in 3MSE differed by baseline ADL limitation. Among participants without ADL limitation, elevated systolic BP (≥140 mmHg) was associated with a 0.15 decrease (95% CI -0.24 to -0.07); P value for interaction less than 0.001, whereas in those with an ADL limitation, elevated systolic BP was independently associated with a 0.30 increase in 3MSE scores per year (95% CI 0.06-0.55). Elevated diastolic BP (≥80 mmHg) was associated with an increase in cognitive function in both groups, although the increase was greater in those with ADL limitation (0.47 points per year vs. 0.18 points per year, P value for interaction = 0.01).

CONCLUSION: Elevated BP appears to be associated with a decrease in cognitive scores among functioning older adults, and modest improvements in cognitive function among poorly functioning elders.

1 aMiller, Lindsay, M1 aPeralta, Carmen, A1 aFitzpatrick, Annette, L1 aWu, Chenkai1 aPsaty, Bruce, M1 aNewman, Anne, B1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/804802354nas a2200217 4500008004100000022001400041245011500055210006900170260001600239300001400255490000700269520166400276100002301940700002001963700002501983700002102008700002802029700002002057700002302077856003602100 2020 eng d a1758-535X00aSex Differences in the Association Between Pentraxin 3 and Cognitive Decline: The Cardiovascular Health Study.0 aSex Differences in the Association Between Pentraxin 3 and Cogni c2020 Jul 13 a1523-15290 v753 a

BACKGROUND: The importance of systemic inflammation, measured by C-reactive protein, in cognitive decline has been demonstrated; however, the role of vascular inflammation is less understood. Pentraxin 3 (PTX3) is a novel marker of vascular inflammation.

METHODS: We followed adults 65 and older, free of cardiovascular disease (CVD) for up to 9 years (n = 1,547) in the Cardiovascular Health Study. We evaluated the relationship between PTX3 and change in cognitive function, measured using the Modified Mini-Mental State Examination (3MSE), and incident cognitive impairment (3MSE < 80). Mediation by CVD events, and effect modification by sex and apolipoprotein E ɛ4 allele (APOE4) were also examined.

RESULTS: The average decline in 3MSE was 0.77 points per year. The association between PTX3 and change in 3MSE differed between women and men (p = .02). In the adjusted model, each standard deviation higher in PTX3 was associated with a 0.20 greater decline in 3MSE score per year in women over follow-up (95% CI: -0. 37, -0.03; p = .02), compared to no change in men (β = 0.07; 95% CI: -0.08, 0.22). CVD events had a minor effect on the associations. No effect modification by APOE4 was found, although we observed the association of PTX3 and cognitive impairment in women was attenuated and nonsignificant after adjustment for APOE4. There was a paradoxical protective association between PTX3 and reduced cognitive impairment in men, even after adjustment for APOE4.

CONCLUSIONS: We found that vascular inflammation was significantly associated with cognitive decline in older women, but not men.

1 aMiller, Lindsay, M1 aJenny, Nancy, S1 aRawlings, Andreea, M1 aArnold, Alice, M1 aFitzpatrick, Annette, L1 aLopez, Oscar, L1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/839902499nas a2200205 4500008004100000022001400041245008600055210006900141260001600210300001000226490000700236520189200243100002302135700001602158700002202174700002002196700001802216700002302234856003602257 2021 eng d a1873-258500aCardiovascular damage phenotypes and all-cause and CVD mortality in older adults.0 aCardiovascular damage phenotypes and allcause and CVD mortality  c2021 Jul 30 a35-400 v633 a

PURPOSE: The association between CVD risk factors and mortality is well established, however, current tools for addressing subgroups have focused on the overall burden of disease. The identification of risky combinations of characteristics may lead to a better understanding of physiologic pathways that underlie morbidity and mortality in older adults.

METHODS: Participants included 5067 older adults from the Cardiovascular Health Study, followed for up to 6 years. Using latent class analysis (LCA), we created CV damage phenotypes based on probabilities of abnormal brain infarctions, major echocardiogram abnormalities, N-terminal probrain natriuretic peptide, troponin T, interleukin-6, c reactive-protein, galectin-3, cystatin C. We assigned class descriptions based on the probability of having an abnormality among risk factors, such that a healthy phenotype would have low probabilities in all risk factors. Participants were assigned to phenotypes based on the maximum probability of membership. We used Cox-proportional hazards regression to evaluate the association between the categorical CV damage phenotype and all-cause and CVD-mortality.

RESULTS: The analysis yielded 5 CV damage phenotypes consistent with the following descriptions: healthy (59%), cardio-renal (11%), cardiac (15%), multisystem morbidity (6%), and inflammatory (9%). All four phenotypes were statistically associated with a greater risk of all-cause mortality when compared with the healthy phenotype. The multisystem morbidity phenotype had the greatest risk of all-cause death (HR: 4.02; 95% CI: 3.44, 4.70), and CVD-mortality (HR: 4.90, 95% CI: 3.95, 6.06).

CONCLUSIONS: Five CV damage phenotypes emerged from CVD risk factor measures. CV damage across multiple systems confers a greater mortality risk compared to damage in any single domain.

1 aMiller, Lindsay, M1 aWu, Chenkai1 aHirsch, Calvin, H1 aLopez, Oscar, L1 aCushman, Mary1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/883403335nas a2200337 4500008004100000022001400041245015100055210006900206260001300275300001000288490000700298520234000305653000902645653002102654653001202675653001802687653001102705653002402716653001702740653001702757100002102774700002102795700001502816700002202831700002002853700002402873700002102897700002302918700002002941856003602961 2023 eng d a1433-296500aAssociation of covert brain infarcts and white matter hyperintensities with risk of hip fracture in older adults: the Cardiovascular Health Study.0 aAssociation of covert brain infarcts and white matter hyperinten c2023 Jan a91-990 v343 a

UNLABELLED: Covert brain infarcts and white matter hyperintensities (WMHs), incidental markers of brain microvascular disease commonly seen on brain MRIs in older adults, have been associated with falls and lower bone mineral density. We found covert infarcts and WMHs may also be associated with an increased risk of future hip fracture.

INTRODUCTION: To determine whether covert infarcts and white matter hyperintensities (WMHs) are associated with increased risk of incident hip fracture.

METHODS: A prospective cohort of 3373 community-dwelling adults aged ≥ 65 years enrolled in the Cardiovascular Health Study with a brain MRI (1992-1993) was analyzed. Covert infarcts were categorized by number of infarcts and largest infarct size. WMH burden was assessed by radiologists and graded qualitatively from 0 (no WMHs) to 9 (extensive).

RESULTS: Participants had 465 incident hip fractures during a mean follow-up of 12.8 years. The demographic-adjusted hazard of incident hip fracture was 32% higher among participants with ≥ 1 covert infarct compared to those without infarcts (hazard ratio (HR) 1.32; 95% CI, 1.08-1.62). The hazard of incident hip fracture was similar after further adjustment for medications and medical history (HR = 1.34; 95% CI, 1.08-1.65), but attenuated following additional adjustment for functional status, frailty, and falls (HR = 1.25; 95% CI, 0.99-1.57). Fully adjusted hazard of incident hip fracture per increase in infarct number was 1.10 (95% CI, 0.98-1.23); risk in individuals whose largest infarct was ≥ 20 mm versus 3 to < 20 mm was similar. Compared with WMH grades 0-1, the demographic-adjusted hazard of hip fracture was 1.34 (95% CI, 1.09-1.66) and 1.83 (95% CI, 1.37-2.46), respectively, for WMH grades 2-3 and 4-9. The hazard was similar following adjustment for medications and medical history (grades 2-3: HR = 1.32; 95% CI, 1.05-1.64; grades 4-9: HR = 1.69; 95% CI, 1.23-2.30), but attenuated following additional adjustment for functional status, frailty, and falls (grades 2-3: HR = 1.24; 95% CI, 0.98-1.56; grades 4-9: HR = 1.34; 95% CI, 0.95-1.90).

CONCLUSION: Older, community-dwelling adults with covert infarcts or WMHs may be at increased risk of hip fracture.

10aAged10aBrain Infarction10aFrailty10aHip Fractures10aHumans10aProspective Studies10aRisk Factors10aWhite Matter1 aSheets, Kerry, M1 aBůzková, Petra1 aChen, Zhao1 aCarbone, Laura, D1 aCauley, Jane, A1 aBarzilay, Joshua, I1 aStarks, Jamie, L1 aMiller, Lindsay, M1 aFink, Howard, A uhttps://chs-nhlbi.org/node/9242