Subclinical Atherosclerosis, Cardiac and Kidney Function, Heart Failure, and Dementia in the Very Elderly

Abstract

Background: Heart failure (HF) and dementia are major causes of disability and death among older individuals. Risk factors and biomarkers of HF may be determinants of dementia in the elderly. We evaluated the relationship between biomarkers of cardiovascular disease and HF and risk of dementia and death. Three hypotheses were tested: (1) higher levels of high-sensitivity cardiac troponin T, N-terminal of prohormone brain natriuretic peptide, and cystatin C predict risk of death, cardiovascular disease, HF, and dementia; (2) higher levels of cardiovascular disease biomarkers are associated with increased risk of HF and then secondary increased risk of dementia; and (3) risk of dementia is lower among participants with a combination of lower coronary artery calcium, atherosclerosis, and lower high-sensitivity cardiac troponin T (myocardial injury).

Methods and results: The Cardiovascular Health Study Cognition Study was a continuation of the Cardiovascular Health Study limited to the Pittsburgh, PA, center from 1998-1999 to 2014. In 1992-1994, 924 participants underwent magnetic resonance imaging of the brain. There were 199 deaths and 116 developed dementia before 1998-1999. Of the 609 participants eligible for the Pittsburgh Cardiovascular Health Study Cognition Study, 87.5% (n=532) were included in the study. There were 120 incident HF cases and 72% had dementia. In 80 of 87, dementia preceded HF. A combination of low coronary artery calcium score and low high-sensitivity cardiac troponin T was significantly associated with reduced risk of dementia and HF.

Conclusions: Most participants with HF had dementia but with onset before HF. Lower high-sensitivity cardiac troponin T and coronary artery calcium was associated with low risk of dementia based on a small number of events.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.

Keywords: coronary artery calcium; dementia; epidemiology; heart failure; risk factors.

Figure 1

Sample for CHS (Cardiovascular Health Study) Cognition Study 1998–2014 (n=532). *Participants were classified by prevalence of cardiovascular disease (CVD) and dementia in 1998–1999. *Fifteen later refusal; ^†1 man without race information. Criteria: Pittsburgh CHS center only, magnetic resonance imaging (MRI) in 1992–1994, free of dementia, alive, and either or both cognitive testing or MRI in 1998–1999 (609 eligible, 532 participated [87%]).

Figure 2

Age‐adjusted mortality 1998–1999 to 2014 in white men and women only in the Cardiovascular Health Study Cognition Study by levels of high‐sensitivity cardiac troponin (hs‐cTnT), NT‐proBNP (N‐terminal of prohormone brain natriuretic peptide), and cystatin C (excluding cardiovascular disease in 1998–1999). hs‐cTnT, NT‐proBNP, and cystatin C were directly related to total mortality. PY indicates person‐years.

Figure 3

Age‐adjusted incidence of dementia in 1998–1999 to 2014 in white women only in the Cardiovascular Health Study Cognition Study by levels of high‐sensitivity cardiac troponin (hs‐cTnT), NT‐proBNP (N‐terminal of prohormone brain natriuretic peptide), and cystatin C (excluding cardiovascular disease in 1998–1999). There was only a weak nonsignificant relationship between hs‐cTnT, NT‐proBNP, cystatin C, and risk of dementia for women. PY indicates person‐years.

Figure 4

Age‐adjusted incidence of dementia in 1998–1999 to 2014 in white men only in the Cardiovascular Health Study Cognition Study by levels of high‐sensitivity cardiac troponin (hs‐cTnT), NT‐proBNP (N‐terminal of prohormone brain natriuretic peptide), and cystatin C (excluding cardiovascular disease at 1998–1999). There was only a weak nonsignificant relationship between hs‐cTnT, NT‐proBNP, cystatin C, and risk of dementia for men. PY indicates person‐years.

Figure 5

Kaplan–Meier curve for dementia and high‐sensitivity cardiac troponin (hs‐cTnT), NT‐proBNP (N‐terminal of prohormone brain natriuretic peptide), and cystatin C among white men and women—Cardiovascular Health Study Cognition Study. hs‐cTnT and NT‐proBNP but not cystatin C were related to time to dementia.

Figure 6

Kaplan–Meier curve for dementia in 2013–2014 among white women in the Cardiovascular Health Study Cognition Study. Low coronary artery calcium (CAC) and high‐sensitivity cardiac troponin (hs‐cTnT) were associated with significantly low risk of dementia for white women.