scholarly journals Unbiased Proteomics and Targeted Biomarkers Associated With Exceptional Longevity and Multimorbidity in Humans

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 348-348
Author(s):  
Jason Sanders
Keyword(s):  
Primary Outcome ◽  
Cardiovascular Health ◽  
A Priori ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Survival Outcomes ◽  
Exceptional Longevity

Abstract Biomarkers ideal for geroscience trials could be those simultaneously identified using targeted and discovery assays and which strongly associate with complementary disease (multimorbidity) and longevity (exceptional survival) outcomes. To identify a tractable set of biomarkers for use in geroscience trials, we used the Cardiovascular Health Study (CHS), whose participant makeup closely aligns with the Targeting Aging with MEtformin (TAME) trial. In ~4800 CHS participants, quantitative assays of nine a priori-identified biomarkers were used to construct a biomarker index which strongly associated with the TAME primary outcome of mortality and multimorbidity over 6 and 10 years of follow-up. In ~3000 CHS participants, 1300 proteins were measured with unbiased aptamer proteomics and associated with survival to age 90 over 25 years of follow-up. Proteins in the biomarker index were identified as some of the strongest associated with survival to 90. This convergent evidence suggests these biomarkers may be well-suited for geroscience trials.

Abstract 2568: Cerebral Infarcts in Blacks vs Whites: the Southall and Brent REvisited (SABRE) Multi-ethnic Cohort Study

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Dean Shibata ◽  
Therese Tillin ◽  
Norman Beauchamp ◽  
John Heasman ◽  
Wadyslaw Gedroyc ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Health ◽  
African Descent ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Stroke Mortality ◽  
Black African ◽  
Cerebral Mri ◽  
Mri Scans

Introduction: Stroke mortality is doubled in people of Black African descent compared with Whites, but factors responsible for this excess are unclear. We wished to compare infarct like lesions (ILL) on MRI by ethnicity and the role of risk factors. Methods: SABRE is a UK community based multi-ethnic cohort of men and women aged 40-69 years at baseline (1988-1990), and 58-86 years at follow up (2008-2011). At follow up, a questionnaire was completed and investigations performed including resting and ambulatory BP, anthropometry, and bloods for glucose and lipids. Cerebral MRI scans were scored for infarcts independently by two readers according to the Cardiovascular Health Study protocol. Results: Of 2346 Whites, 684 attended follow up, and 590 completed cerebral MRI. Of 801 Blacks (first generation migrants of Black African descent to the UK), 232 attended clinic and 207 completed MRI. Mortality loss was greater in Whites (605, 25%) than Blacks (121, 15%)(p<0.0001), although stroke was more likely the underlying cause in Blacks (23, 19%), than Whites (43, 7%)(p<0.0001) . Baseline systolic/diastolic BP was similarly higher in Blacks than Whites in attendees (8/5 mmHg), non-responders (7/6 mm Hg), and those who died (8/5 mmHg). At follow up stroke risk factors were adverse in Blacks, apart from smoking ( table ). Prevalence of ILL was similar by ethnicity, not differing when those <65 years were analysed separately, or when those with stroke/TIA history were excluded. Associations between ILL and risk factors did not differ by ethnicity. But prescribed treatment in those with elevated clinic BP (≥140 mmHg systolic, or ≥90 mmHg diastolic) was 83% in Blacks, 63% in Whites (p<0.0001). Further, in those with an ILL, 95% of Blacks, and 69% (p<0.0001) of Whites were on treatment. Conclusion: Equivalence of ILL rates in Blacks and Whites was unanticipated, given the greater stroke mortality in Blacks. Mitigating against selective mortality as the explanation of our findings is the similar ethnic differential in baseline BP in survivors and non-survivors, the lower overall mortality in Blacks, and overall small numbers of stroke deaths. A more likely explanation is that better targeted more aggressive treatment is now occurring in Blacks than Whites, reducing their potential burden of ILL.

scholarly journals Trends in Blood Pressure and High-Sensitivity Cardiac Troponin-T With Cardiovascular Disease: The Cardiovascular Health Study

2019 ◽  
Vol 32 (10) ◽  
pp. 1013-1020 ◽  
Author(s):  
David M Tehrani ◽  
Wenjun Fan ◽  
Vijay Nambi ◽  
Julius Gardin ◽  
Calvin H Hirsch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Troponin ◽  
Cardiovascular Health ◽  
Troponin T ◽  
High Sensitivity ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Cvd Risk ◽  
Over Time

AbstractBackgroundHigh-sensitivity cardiac troponin T (hs-cTnT) is individually associated with incident hypertension (HTN) and cardiovascular disease (CVD) events. We hypothesize that the increases in hs-cTnT with increases in blood pressure will be related to higher incidence of CVD.METHODSThe Cardiovascular Health Study is a longitudinal cohort of older adults. Those with hs-cTnT data and CVD risk factors at baseline and follow-up (2–3 years later) were stratified based on systolic blood pressure (SBP; optimal: <120 mm Hg, intermediate: 120–139 mm Hg, elevated: ≥140 mm Hg) and hs-cTnT (undetectable: <5 ng/l, detectable: 5–13 ng/l, elevated: ≥14 ng/l) categories. SBP and hs-cTnT were classified as increased or decreased if they changed categories between exams, and stable if they did not. Cox regression evaluated incident CVD events over an average 9-year follow-up.RESULTSAmong 2,219 adults, 510 (23.0 %) had decreased hs-cTnT, 1,279 (57.6 %) had stable hs-cTnT, and 430 (19.4 %) had increased hs-cTnT. Those with increased hs-cTnT had a higher CVD risk with stable SBP (hazard ratio [HR]: 1.28 [1.04–1.57], P = 0.02) or decreased SBP (HR: 1.57 [1.08–2.28], P = 0.02) compared to those within the same SBP group but a stable hs-cTnT. In those with lower SBP at follow-up, there was an inverse relation between diastolic blood pressure (DBP) and risk of CVD events in those with increased hs-cTnT (HR: 0.44 per 10 mm Hg increase, P < 0.01).CONCLUSIONAn increase in hs-cTnT over time is associated with a higher risk of CVD even when the blood pressure is stable or decreases over time.

scholarly journals Risk of dementia and death in the long-term follow-up of the Pittsburgh Cardiovascular Health Study-Cognition Study

2015 ◽  
Vol 12 (2) ◽  
pp. 170-183 ◽  
Author(s):  
Lewis H. Kuller ◽  
Oscar L. Lopez ◽  
James T. Becker ◽  
Yuefang Chang ◽  
Anne B. Newman
Keyword(s):  
Cardiovascular Health ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Long Term Follow Up

scholarly journals Competing risk of mortality in association studies of non-fatal events

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255313
Author(s):  
Petra Buzkova
Keyword(s):  
Cardiovascular Health ◽  
Association Studies ◽  
Population Based ◽  
Competing Risk ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Subdistribution Hazard ◽  
Hazard Regression ◽  
Risk Of Mortality

In geriatric research of non-fatal events, participants often die during the study follow-up without having the non-fatal event of interest. Cause-specific (CS) hazard regression and Fine-Gray (FG) subdistribution hazard regression are the two most common estimation approaches addressing such competing risk. We explain how the conventional CS approach and the FG approach differ and why many FG estimates of associations are counter-intuitive. Additionally, we clarify the indirect link between models for hazard and models for cumulative incidence. The methodologies are contrasted on data from the Cardiovascular Health Study, a population-based study in adults aged 65 years and older.

scholarly journals Risk Factors for Incident Carotid Artery Revascularization among Older Adults: The Cardiovascular Health Study

2016 ◽  
Vol 6 (3) ◽  
pp. 129-139 ◽  
Author(s):  
Parveen K. Garg ◽  
Willam J.H. Koh ◽  
Joseph A. Delaney ◽  
Ethan A. Halm ◽  
Calvin H. Hirsch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Carotid Artery ◽  
Cardiovascular Health ◽  
Multivariable Analysis ◽  
Population Based ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Increased Risk

Background: Population-based risk factors for carotid artery revascularization are not known. We investigated the association between demographic and clinical characteristics and incident carotid artery revascularization in a cohort of older adults. Methods: Among Cardiovascular Health Study participants, a population-based cohort of 5,888 adults aged 65 years or older enrolled in two waves (1989-1990 and 1992-1993), 5,107 participants without a prior history of carotid endarterectomy (CEA) or cerebrovascular disease had a carotid ultrasound at baseline and were included in these analyses. Cox proportional hazards multivariable analysis was used to determine independent risk factors for incident carotid artery revascularization. Results: Over a mean follow-up of 13.5 years, 141 participants underwent carotid artery revascularization, 97% were CEA. Baseline degree of stenosis and incident ischemic cerebral events occurring during follow-up were the strongest predictors of incident revascularization. After adjustment for these, factors independently associated with an increased risk of incident revascularization were: hypertension (HR 1.53; 95% CI: 1.05-2.23), peripheral arterial disease (HR 2.57; 95% CI: 1.34-4.93), and low-density lipoprotein cholesterol (HR 1.23 per standard deviation [SD] increment [35.4 mg/dL]; 95% CI: 1.04-1.46). Factors independently associated with a lower risk of incident revascularization were: female gender (HR 0.51; 95% CI: 0.34-0.77) and older age (HR 0.69 per SD increment [5.5 years]; 95% CI: 0.56-0.86). Conclusions: Even after accounting for carotid stenosis and incident cerebral ischemic events, carotid revascularization is related to age, gender, and cardiovascular risk factors. Further study of these demographic disparities and the role of risk factor control is warranted.

scholarly journals Serum Individual Nonesterified Fatty Acids and Risk of Heart Failure in Older Adults

Cardiology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Luc Djousse ◽  
Mary L. Biggs ◽  
Nirupa R. Matthan ◽  
Joachim H. Ix ◽  
Annette L. Fitzpatrick ◽  
...  
Keyword(s):  
Heart Failure ◽  
Older Adults ◽  
Fatty Acids ◽  
Cardiovascular Health ◽  
Cox Regression ◽  
Hormone Replacement ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Nonesterified Fatty Acids

Background: Heart failure (HF) is highly prevalent among older adults and is associated with high costs. Although serum total nonesterified fatty acids (NEFAs) have been positively associated with HF risk, the contribution of each individual NEFA to HF risk has not been examined. Objective: The aim of this study was to examine the association of individual fasting NEFAs with HF risk in older adults. Methods: In this prospective cohort study of older adults, we measured 35 individual NEFAs in 2,140 participants of the Cardiovascular Health Study using gas chromatography. HF was ascertained using review of medical records by an endpoint committee. Results: The mean age was 77.7 ± 4.4 years, and 38.8% were male. During a median follow-up of 9.7 (maximum 19.0) years, 655 new cases of HF occurred. In a multivariable Cox regression model controlling for demographic and anthropometric variables, field center, education, serum albumin, glomerular filtration rate, physical activity, alcohol consumption, smoking, hormone replacement therapy, unintentional weight loss, and all other measured NEFAs, we observed inverse associations (HR [95% CI] per standard deviation) of nonesterified pentadecanoic (15:0) (0.73 [0.57–0.94]), γ-linolenic acid (GLA) (0.87 [0.75–1.00]), and docosahexaenoic acid (DHA) (0.73 [0.61–0.88]) acids with HF, and positive associations of nonesterified stearic (18:0) (1.30 [1.04–1.63]) and nervonic (24:1n-9) (1.17 [1.06–1.29]) acids with HF. Conclusion: Our data are consistent with a higher risk of HF with nonesterified stearic and nervonic acids and a lower risk with nonesterified 15:0, GLA, and DHA in older adults. If confirmed in other studies, specific NEFAs may provide new targets for HF prevention.

Abstract 5010: Determining the Plasticity of Cardiovascular Risk in the Elderly: A role for serial NT-proBNP measurement

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Christopher Defilippi ◽  
Robert Christenson ◽  
John Gottdiener ◽  
Willem J Kop ◽  
Stephen L Seliger
Keyword(s):  
Risk Factors ◽  
Cardiovascular Health ◽  
The Elderly ◽  
Cardiovascular Death ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Continuous Measure ◽  
Cox Models ◽  
Low Levels

In the elderly, with decades of exposure to cardiovascular (CV) risk factors, CV prognosis is often considered static. We hypothesized that CV risk is dynamic reflected by changes in NTproBNP over time. We measured NTproBNP at baseline and after 2–3 years in the Cardiovascular Health Study. Long-term risk of CV death according to change in NTproBNP was estimated with the Kaplan-Meier method. We used Cox models to test if effect of change in NTproBNP was independent of demographic and CV risk factors, baseline NTproBNP, renal function, coronary disease, and CV medications. Participants were categorized at baseline as < (low) or >=190pg/mL (high) levels, based on an observed increase in risk above this level. A significant change in NTproBNP category was defined as a change of >25% to a level above or below this cut-point, based on the reported biological variability of NTproBNP. Change in NTproBNP was also evaluated as a continuous measure. Serial NTproBNP levels were measured in 2,975 (86%) of 3,469 participants (age 75±5 years) without heart failure and who had a follow-up visit. CV death was different between those with low levels that remained low (n=1,774) vs. those with low levels that became high (n=468) (1.1 vs. 2.7 per 100 person-yrs, p<.001) and those with high levels that remained high (n=621) vs. those with high levels that became low (n=112) (4.2 vs. 1.6 per 100 person-yrs, p<.001) (figure ). As a continuous measure, change in NTproBNP was linearly associated with CV mortality risk after adjustment (per Ln-fold increment: RR=1.47, p<.001). Dynamic changes in NTproBNP levels reflect dramatic change in CV prognosis in the elderly. Proportion without Cardiovascular death, by initial and follow-up NT-proBNP

Abstract 16017: Atrial Fibrillation is Associated With Increased Risk for Myocardial Infarction in the Cardiovascular Health Study (CHS)

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Matthew C Tattersall ◽  
James H Stein ◽  
Traci Bartz ◽  
Adam D Gepner ◽  
Susan R Heckbert ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Cardiovascular Health ◽  
Cox Regression ◽  
Protein Body ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Public Health Burden ◽  
Increased Risk

Background: Atrial fibrillation (AF) is highly prevalent and poses a significant public health burden on the aging population. We hypothesized that AF independently predicts myocardial infarction (MI) in the Cardiovascular Health Study (CHS). Methods: AF was evaluated longitudinally in participants free of cardiovascular disease at baseline in the CHS. Participants were followed for a mean (standard deviation, SD) 12.7 (5.8) years for development of fatal or nonfatal MI. Cox regression models were utilized to assess the associations of time-updated AF and MI in fully adjusted models and models with gender interaction. Results: Of the 5888 participants in the CHS, 4158 met the inclusion criteria. The mean (SD) age was 72.3 (5.4) years old (38.3% male, 14.3% African-American). Eighty-two had prevalent AF; 1005 developed incident AF during follow up (AF group, n=1087). To avoid bias, participants diagnosed with AF at the same time as their MI were not included in the AF group. Baseline total cholesterol (212.4 [38.6] mg/dL), systolic blood pressure (SBP, 136.1 [21.4] mmHg), and diabetes mellitus prevalence (13.6%) were similar between groups. AF updated as a time-varying exposure was associated with a higher risk of MI: hazard ratio (HR) 1.61, [95% CI 1.32-1.96], after adjusting for age, gender, race, SBP, total and high-density lipoprotein cholesterol, current smoking, fasting glucose, education, alcohol use, C-reactive protein, body-mass index, diabetes, anti-arrhythmic use, and time-updated use of aspirin, anti-hypertensive and lipid medications. Women were at higher risk (HR 2.00 [95% CI 1.53-2.62]) than men (HR 1.33 [95% CI 0.99-1.77]) (p for interaction=0.02). Conclusion: In a large cohort study with over a decade of follow-up, AF was associated with an increased risk for MI. This association was more pronounced in women.

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