02598nas a2200205 4500008004100000022001400041245017200055210006900227260001600296520186400312100002502176700002502201700002202226700001702248700002702265700002102292700002302313700002002336856003602356 2017 eng d a1545-721400aLate-Life Depressive Symptoms as Partial Mediators in the Associations between Subclinical Cardiovascular Disease with Onset of Mild Cognitive Impairment and Dementia.0 aLateLife Depressive Symptoms as Partial Mediators in the Associa c2017 Nov 203 a

OBJECTIVE: To study whether depression contributes to the association between subclinical cardiovascular disease (CVD) and dementia, and identify the contribution's magnitude.

METHODS: Among participants from the Cardiovascular Health Study Cognition Study who did not have baseline CVD-related events (N = 2,450), causal mediation methodology was implemented to examine whether late-life depressive symptoms, defined as 10-item Center for Epidemiologic Studies-Depression (mCES-D) Scale scores ≥8 from 2 to 3 years after baseline, partially mediated the association of baseline subclinical CVD (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) with mild cognitive impairment (MCI)/dementia onset occurring between 5 and 10 years from baseline. The total effect was decomposed into direct and indirect effects (via late-life depressive symptoms), obtained from an accelerated failure time model with weights derived from multivariable logistic regression of late-life depressive symptoms on subclinical CVD. Analyses were adjusted by baseline covariates: age, race, sex, poverty status, marital status, body mass index, smoking status, ApoE4 status, and mCES-D.

RESULTS: Participants contributed 20,994 person-years of follow-up with a median follow-up time of 9.4 years. Subclinical CVD was associated with 12% faster time to MCI/dementia (time ratio [TR]: 0.88; 95% CI: 0.83, 0.93). The total effect of subclinical CVD on MCI/dementia onset was decomposed into a direct effect (TR: 0.95, 95% CI: 0.92, 0.98) and indirect effect (TR: 0.92, 95% CI: 0.88, 0.97); 64.5% of the total effect was mediated by late-life depressive symptoms.

CONCLUSIONS: These data suggest late-life depressive symptoms partially mediate the association of subclinical CVD with MCI/dementia onset.

1 aArmstrong, Nicole, M1 aCarlson, Michelle, C1 aSchrack, Jennifer1 aXue, Qian-Li1 aCarnethon, Mercedes, R1 aRosano, Caterina1 aChaves, Paulo, H M1 aGross, Alden, L uhttps://chs-nhlbi.org/node/754401869nas a2200205 4500008004100000022001400041245014500055210006900200260001600269300002000285520116300305100002501468700002501493700001701518700002201535700002701557700002301584700002001607856003601627 2017 eng d a1552-688700aRole of Late-Life Depression in the Association of Subclinical Cardiovascular Disease With All-Cause Mortality: Cardiovascular Health Study.0 aRole of LateLife Depression in the Association of Subclinical Ca c2017 Nov 01 a8982643177449213 a

OBJECTIVES: To evaluate whether late-life depression mediates the association of subclinical cardiovascular disease (CVD) with all-cause mortality.

METHOD: Using data from 3,473 Cardiovascular Health Study participants, the Cox proportional hazards model was used to examine the direct and indirect (via late-life depression) effects of the association between baseline subclinical CVD and all-cause mortality with weights derived from multivariable logistic regression of late-life depression on subclinical CVD.

RESULTS: Subclinical CVD led to a higher risk of all-cause mortality (hazard ratio [HR] = 1.51, 95% confidence interval, [CI] = [1.42, 1.94]). Total effect of subclinical CVD on all-cause mortality was decomposed into direct (HR = 1.41, 95% CI = [1.37, 1.58]) and indirect (HR = 1.07, 95% CI = [1.01, 1.23]) effects; 16.3% of the total effect of subclinical CVD on all-cause mortality was mediated by late-life depression.

DISCUSSION: Late-life depression accounts for little, if any, of the association between subclinical CVD, a risk factor of all-cause mortality, and all-cause mortality.

1 aArmstrong, Nicole, M1 aCarlson, Michelle, C1 aXue, Qian-Li1 aSchrack, Jennifer1 aCarnethon, Mercedes, R1 aChaves, Paulo, H M1 aGross, Alden, L uhttps://chs-nhlbi.org/node/754504295nas a2200529 4500008004100000022001400041245009000055210006900145260001600214300001200230490000600242520289400248653000903142653001503151653001103166653001203177653001803189653001103207653001403218653000903232653001603241653001503257653001703272100002103289700002003310700002103330700001603351700002303367700002303390700002203413700001903435700002303454700002003477700003103497700001903528700002003547700002003567700002003587700002203607700001603629700001803645700001703663700001803680700001303698700001803711856003603729 2024 eng d a2380-659100aHigh Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life.0 aHigh Throughput Plasma Proteomics and Risk of Heart Failure and  c2024 Jul 01 a649-6580 v93 a

IMPORTANCE: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions.

OBJECTIVE: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023.

EXPOSURES: Protein aptamers, measured at study V3 and V5.

MAIN OUTCOMES AND MEASURES: Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty.

RESULTS: A total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF.

CONCLUSIONS AND RELEVANCE: In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.

10aAged10aBiomarkers10aFemale10aFrailty10aHeart Failure10aHumans10aIncidence10aMale10aMiddle Aged10aProteomics10aRisk Factors1 aRamonfaur, Diego1 aBuckley, Leo, F1 aArthur, Victoria1 aYang, Yimin1 aClaggett, Brian, L1 aNdumele, Chiadi, E1 aWalker, Keenan, A1 aAustin, Thomas1 aOdden, Michelle, C1 aFloyd, James, S1 avan Wijk, Sandra, Sanders-1 aNjoroge, Joyce1 aKizer, Jorge, R1 aKitzman, Dalane1 aKonety, Suma, H1 aSchrack, Jennifer1 aLiu, Fangyu1 aWindham, Gwen1 aPalta, Priya1 aCoresh, Josef1 aYu, Bing1 aShah, Amil, M uhttps://chs-nhlbi.org/node/9705