While anemia is associated with poor functional and mortality outcomes in the elderly, the impact of hemoglobin decline is less studied.
We evaluated the determinants and consequences of hemoglobin decline in 3.758 non-anemic participants from the Cardiovascular Health Study, a prospective cohort of community-dwelling elderly ≥65 years old at baseline and followed for up to 16 years. Hemoglobin was measured at baseline and 3 years later and anemia defined by World Health Organization (WHO) criteria. We modeled hemoglobin decline in two ways: 1) per each 1g/dL decrease in hemoglobin and 2) development of anemia by the WHO criteria.
Among participants without baseline anemia, hemoglobin decreased by 0.4g/dL and 9% developed anemia over 3 years. Baseline increasing age, female sex, diabetes, and kidney disease predicted hemoglobin decline over 3 years. Baseline increasing age, being African-American, and kidney disease predicted anemia development over 3 years. Hemoglobin decline was associated with subsequent worse cognitive function in men and anemia development with subsequent worse cognitive function in women. Both anemia development (HR 1.39, 95% CI 1.15, 1.69) and hemoglobin decline (HR 1.11, 95% CI 1.04, 1.18 per 1g/dL decrease) predicted subsequent mortality in men and women.
Hemoglobin decreases identified a large group of elderly individuals at risk for subsequent adverse outcomes who would not be identified using the WHO anemia criteria. These data may allow clinicians to identify at-risk elderly individuals for early intervention to improve the quality and quantity of life.
Anemia; Hemoglobin; Elderly; Mortality; Function; Epidemiology
Associations of inflammation with age-related pathologies are documented; however, it is not understood how changes in inflammation over time impact healthy aging.
We examined associations of long-term change in C-reactive protein (CRP) and interleukin-6 (IL-6) with concurrent onset of physical and cognitive impairment, subsequent cardiovascular disease (CVD), and mortality in 1,051 participants in the Cardiovascular Health Study All Stars Study. Biomarkers were measured in 1996–1997 and 2005–2006.
In 2005–2006, median age was 84.9 years, 63% were women and 17% non-white; 21% had at least a doubling in CRP over time and 23% had at least a doubling in IL-6. Adjusting for demographics, CVD risk factors, and 1996–1997 CRP level, each doubling in CRP change over 9 years was associated with higher risk of physical or cognitive impairment (odds ratio 1.29; 95% confidence interval 1.15, 1.45). Results were similar for IL-6 (1.45; 1.20, 1.76). A doubling in IL-6 change over time, but not CRP, was associated with incident CVD events; hazard ratio (95% confidence interval) 1.34 (1.03, 1.75). Doubling in change in each biomarker was individually associated with mortality (CRP: 1.12 [1.03, 1.22]; IL-6 1.39 [1.16, 1.65]). In models containing both change and 2005–2006 level, only level was associated with CVD events and mortality.
Although increases in inflammation markers over 9 years were associated with higher concurrent risk of functional impairment and subsequent CVD events and mortality, final levels of each biomarker appeared to be more important in determining risk of subsequent events than change over time.
Inflammation; Aging; Physical function; Cognitive function
To examine whether lipid lowering medications (LLMs) and especially statin drugs can delay cognitive decline and dementia onset in individuals with and without Mild Cognitive Impairment (MCI) at baseline.
Longitudinal, observational study of 3,069 cognitively healthy elderly, ages 75 years and older, who were enrolled in the Ginkgo Evaluation of Memory Study. Primary outcome measure was the time to adjudicated all-cause dementia and Alzheimer dementia (AD). Secondary outcome measure was the change in global cognitive function over time measured by 3MSE and ADAS-cog scores.
Among participants without MCI at baseline current use of statins was consistently associated with a reduced risk of all cause dementia (HR 0. 79, 95% confidence interval, 0.65–0.96, p=0.021) and AD (HR 0.57, 95% confidence interval, 0.39–0.85, p= 0.005). In participants who initiated statin therapy lipophilic statins tended to reduce dementia risk more than nonlipophilic agents. In contrast there was no significant association between LLM use (including statins), dementia onset or cognitive decline in individuals with baseline MCI. However, in individuals without MCI at baseline there was a trend for a neuroprotective effect of statins on cognitive decline.
Statins may slow the rate of cognitive decline and delay the onset of AD and all cause dementia in cognitively healthy elderly individuals whereas individuals with MCI may not have comparable cognitive protection from these agents. However, the results from this observational study need to be interpreted with caution and will require confirmation by randomized clinical trials stratifying treatment groups based on MCI status at baseline.
Cognitive function; 3HMG-ACoA reductase inhibitors; Mild Cognitive Impairment; dementia
Most studies of leukocyte telomere length (LTL) focus on diagnosed disease in one system. A more encompassing depiction of health is disease burden, defined here as the sum of noninvasively measured markers of structure or function in different organ systems. We determined if (a) shorter LTL is associated with greater age-related disease burden and (b) shorter LTL is less strongly associated with disease in individual systems or diagnosed chronic conditions (cardiovascular disease, stroke, pulmonary disease, diabetes, kidney disease, arthritis, or depression).
LTL was measured by Southern blots of terminal restriction fragment length. Age-related disease was measured noninvasively and included carotid intima–media thickness, lung vital capacity, white matter grade, cystatin-C, and fasting glucose; each graded 0 (best tertile), 1 (middle tertile), or 2 (worst tertile) and summed (0 to 10) to estimate disease burden. Of 419 participants randomly selected for LTL measurement, 236 had disease burden assessed (mean [SD] age 74.2 [4.9] years, 42.4% male, 86.8% white, and 13.2% black).
Mean (SD) LTL was 6,312 (615) bp, and disease score was 4.7 (2.1) points. An SD higher disease score (β [SE] = −132  bp, p < .01), age (β [SE] = −107 , p = .02) or carotid thickness (β [SE] = −95  bp, p = .02) was associated with shorter LTL, but diagnosed conditions or number of conditions were not associated with LTL. Disease score attenuated the effect of age on LTL by 35%.
LTL was associated with a characterization of age-related disease burden across multiple physiologic systems, which was comparable to, but independent of, its association with age.
Leukocyte telomere length; Disease burden; Noninvasive measurements; Aging
To delineate the associations of total adiponectin, high-molecular-weight (HMW) adiponectin, and the HMW-to-total adiponectin ratio with diabetes in older adults.
RESEARCH DESIGN AND METHODS
Total and HMW adiponectin were measured in a population-based study of older adults. The relations of total adiponectin, HMW adiponectin, and their ratio with incident diabetes (n = 309) were assessed in 3,802 individuals.
Total and HMW adiponectin were highly correlated (r = 0.94). Analysis using cubic splines revealed that the associations between total and HMW adiponectin and new-onset diabetes were not linear. Specifically, after adjustment for confounders, there were similar inverse relationships for total (hazard ratio per SD 0.49 [95% CI 0.39–0.63]) and HMW adiponectin (0.42 [0.32–0.56]) with diabetes up to values of 20 and 10 mg/L, respectively, above which the associations plateaued. These associations persisted after adjustment for potential mediators (blood pressure, lipids, C-reactive protein, and homeostasis model assessment of insulin resistance [HOMA-IR]). There was, however, evidence of interaction by HOMA-IR in the lower range of adiponectin, with stronger inverse associations among insulin-sensitive than insulin-resistant participants. HMW-to-total adiponectin ratio showed a linear adjusted association with outcome, but this was abolished by inclusion of mediating variables.
In this older cohort, increasing concentrations of total and HMW adiponectin were associated with comparably lower risks of diabetes, but these associations leveled off with further increases above concentrations of 20 and 10 mg/L, respectively. The more pronounced risk decreases at the lower range among participants without insulin resistance support a role for adiponectin that is independent of baseline hyperinsulinemia, but this will require further investigation.
Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined.
We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2–9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176).
Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95% CI] = 0.72 [0.52–0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61–3.44] per SD for levels ≥20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78–4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20–2.92]) (p = .043), but not inflammatory markers alone (HR = 2.48 [1.67–3.67]) (p = .55), as compared with smaller changes for both.
Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin–outcome associations reported previously.
Adiponectin; C-reactive protein; Interleukin 6; Aging; Mortality
Background and Purpose
Does progression of MRI-defined vascular disease predict subsequent vascular events in the elderly?
The Cardiovascular Health Study, a longitudinal cohort study of vascular disease in the elderly, allows the question to be answered because its participants had two MRI scans about five years apart and have been followed for about 9 years since the follow-up scan for incident vascular events.
Both MRI-defined incident infarcts and worsened white matter grade (WMG) were significantly associated with heart failure (HF), stroke and death but not transient ischemic attacks, angina, or myocardial infarction. Strongest associations occurred when both incident infarcts and worsened WMG were present: for HF, hazard ratio 1.79 (95% confidence interval 1.18–2.73); for stroke, 2.58 (1.53–4.36); for death, 1.69 (1.28–2.24); and for cardiovascular death 1.97 (1.24–3.14).
Progression of MRI-defined vascular disease identifies elderly people at increased risk of subsequent HF, stroke, and death. Whether aggressive risk factor management would reduce risk is unknown.
MRI; brain infarction; leukoaraiosis; stroke; death
To examine the association between 25-hydroxyvitamin D (25[OH]D) and physical function in adults of advanced age.
Cross-sectional and longitudinal analysis of physical function over 3 years of follow-up in the Cardiovascular Health Study All Stars.
Forsyth County, NC; Sacramento County, CA; Washington County, MD; and Allegheny County, PA.
Community-dwelling adults aged 77–100 years (n=988).
Serum 25(OH)D, short physical performance battery (SPPB) and grip and knee extensor strength assessed at baseline. Mobility disability (difficulty walking half a mile or up 10 steps) and activities of daily living (ADL) disability were assessed at baseline and every 6 months over 3 years of follow-up.
30.8% of participants had deficient 25(OH)D (<20 ng/mL). SPPB scores were lower among those with deficient 25(OH)D compared to those with sufficient 25(OH)D (≥30 ng/mL) after adjusting for sociodemographic characteristics, season, health behaviors and chronic conditions (mean±SE: 6.53±0.24 vs. 7.15±0.25, p <0.01). Grip strength adjusted for body size was also lower among those with deficient versus sufficient 25(OH)D (mean±SE: 24.7±0.6 vs. 26.0±0.6 kg, p <0.05). Participants with deficient 25(OH)D were more likely to have prevalent mobility and ADL disability at baseline (OR (95% CI): 1.44 (0.96–2.14) and 1.51 (1.01–2.25), respectively) compared to those with sufficient 25(OH)D. Furthermore, participants with deficient 25(OH)D were at increased risk of incident mobility disability over 3 years of follow-up (HR (95% CI): 1.56 (1.06–2.30)).
Vitamin D deficiency was common and was associated with poorer physical performance, lower muscle strength, and prevalent mobility and ADL disability among community-dwelling adults of advanced age. Moreover, vitamin D deficiency predicted incident mobility disability.
vitamin D; physical performance; muscle strength; mobility disability; ADL disability
Individual measures and previous composite measures of subclinical vascular disease defined high risk for cardiovascular events, but did not detect low and modest risk. A different approach might better describe the spectrum from low to high risk.
Methods and Results.
In the Cardiovascular Health Study, 3,252 participants without history of clinical cardiovascular disease (M ± SD 74.3 years ± 5.1, 63% women, 17% African Americans) had noninvasive vascular assessments in 1992–1993. We assigned a score of 0, 1, or 2 (no, mild, or severe abnormalities) to ankle–arm index, electrocardiogram, and common carotid intima-media thickness, based on clinical cutoffs. A summary index (range 0–6, absent to severe disease) summed individual scores. Abdominal aortic ultrasound and brain magnetic resonance imaging were collected in a subsample. Mortality and incident cardiovascular events were identified through June 2008. Event and death rates increased across index grades. Comparing grades 1 to 5+ with absent disease, and adjusting for demographics, hazard ratios for cardiovascular events within 8 years ranged from 1.1 (95% confidence interval 0.8–1.6) to 4.7 (3.4–6.9) and, for mortality, from 1.5 (1.0–2.3) to 5.0 (3.3–7.7) (p for trend across grades <.001 for both outcomes). Adjustment for cardiovascular risk factors did not substantially change the associations. The index improved mortality risk classification over demographics and risk factors in participants who did not die during the follow-up. Including in the index the aortic ultrasound and the brain magnetic resonance imaging further improved risk classification.
Older adults with minimal subclinical vascular disease had low cardiovascular events risk and mortality. This approach might more fully account for vascular burden.
Epidemiology; Aging; Atherosclerosis; Cardiovascular disease; Mortality
Despite widespread use, there are no data on initiation of thyroid hormone use in older people. We report the prevalence of thyroid hormone use and predictors of thyroid hormone initiation in a population of older men and women.
Thyroid hormone medication data were collected annually from 1989 to 2006 in community-dwelling individuals aged 65 years and older enrolled in the Cardiovascular Health Study (N = 5,888). Associations of age, sex, race, body mass index, education, and coronary heart disease with initiation were evaluated using discrete-time survival analysis.
In 1989–1990, 8.9% (95% confidence interval 8.1%–9.7%) of participants were taking a thyroid hormone preparation, increasing to 20.0% (95% confidence interval 8.2%–21.8%) over 16 years. The average initiation rate was 1% per year. The initiation rate was nonlinear with age, and those aged 85 years and older initiated thyroid hormone more than twice as frequently as those aged 65–69 years (hazard ratio = 2.34; 95% confidence interval 1.43–3.85). White women were more likely to initiate thyroid hormone than any other race and sex group. Higher body mass index was independently associated with higher risk for initiation (p = .002) as was greater education (p = .02) and prevalent coronary heart disease (p = .03).
Thyroid hormone use is common in older people. The indications and benefits of thyroid hormone use in older individuals with the highest rate of thyroid hormone initiation—the oldest old, overweight and obese individuals, and those with coronary heart disease—should be investigated.
Thyroid hormone; Levothyroxine; Elderly population
Cross-sectional studies show that adiponectin is higher in older than in younger adults but long-term change in adiponectin, its determinants, and its relationship to functional decline or survival in the elderly population have not been evaluated.
We investigated predictors of longitudinal change in adiponectin, and the association of this adipokine or its antecedent change with physical deterioration and all-cause mortality in 988 participants in a population-based study who completed examinations in 1996–1997 and 2005–2006, had serial adiponectin measurements and underwent follow-up through June 2009.
Adiponectin level rose significantly during follow-up, but the increase was smaller in blacks, was associated with declining weight or fasting glucose and, in men, lower albumin, and was affected by medications. Adiponectin was independently associated with greater physical decline, but the relationship for adiponectin change was driven by concomitant weight decrease. Both adiponectin and its change independently predicted mortality, even after adjustment for weight change. The association for adiponectin and mortality was observed in whites but not in blacks and only for levels in the upper range (hazard ratio = 1.85, 95% confidence interval = 1.36–2.52 per SD ≥ 20 mg/L), whereas that for adiponectin change was linear throughout in both racial groups (hazard ratio = 1.30, 95% confidence interval = 1.10–1.52 per SD).
Adiponectin levels increase over time in long-lived adults and are associated with greater physical disability and mortality. Such increases may occur in response to age-related homeostatic dysregulation. Additional investigation is required to define the underlying mechanisms and whether this represents a marker or causal factor for mortality in this age group.
Adiponectin; Aging; Mortality; Physical Function
Genome-wide association studies (GWAS) may yield insights into longevity.
We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort.
There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 × 10−8. Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 × 10−7 for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage.
Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings.
Longevity; Genome-wide association study; Meta-analysis
To estimate the associations of weight dynamics with physical functioning and mortality in older adults.
Longitudinal cohort study using prospectively collected data on weight, physical function, and health status in four U.S. Communities in the Cardiovascular Health Study. Included were 3,278 participants (2,013 women and 541 African Americans), aged 65 or older at enrollment, who had at least five weight measurements. Weight was measured at annual clinic visits between 1992 and 1999, and summary measures of mean weight, coefficient of variation, average annual weight change, and episodes of loss and gain (cycling) were calculated. Participants were followed from 1999 to 2006 for activities of daily living (ADL) difficulty, incident mobility limitations, and mortality.
Higher mean weight, weight variability, and weight cycling increased the risk of new onset of ADL difficulties and mobility limitations. After adjustment for risk factors, the hazard ratio (95% confidence interval) for weight cycling for incident ADL impairment was 1.28 (1.12, 1.47), similar to that for several comorbidities in our model, including cancer and diabetes. Lower weight, weight loss, higher variability, and weight cycling were all risk factors for mortality, after adjustment for demographic risk factors, height, self-report health status, and comorbidities.
Variations in weight are important indicators of future physical limitations and mortality in the elderly and may reflect difficulties in maintaining homeostasis throughout older ages. Monitoring the weight of an older person for fluctuations or episodes of both loss and gain is an important aspect of geriatric care.
Weight change; ADL; Mortality
The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning.
To determine whether G biloba slows the rates of global or domain-specific cognitive decline in older adults.
Design, Setting, and Participants
The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years.
Twice-daily dose of 120-mg extract of G biloba (n=1545) or identical-appearing placebo (n=1524).
Main Outcome Measures
Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.
Annual rates of decline in z scores did not differ between G biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P=.71; for ADAS-Cog, P=.97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P>.05).
Compared with placebo, the use of G biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.
clinicaltrials.gov Identifier: NCT00010803
Few cohort studies have adequate numbers of carefully reviewed deaths to allow an analysis of unique and shared risk factors for cause-specific mortality. Shared risk factors could be targeted for prevention of premature death and the study of longevity.
A total of 5,888 community-dwelling persons aged 65 years or older living in four communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to 1990; an additional 687 black participants were recruited in 1992–1993. The average length of follow-up was 16 years. Total and cause-specific mortality, including cardiovascular disease, stroke, cancer, dementia, pulmonary disease, infection, and other cause, were examined as outcomes. Variables previously associated with total mortality were examined for each cause of death using Cox proportional hazard models.
Multiple risk factors were related to total mortality. When examining specific causes, many factors were related to cardiovascular death, whereas fewer were related to other causes. For most causes, risk factors were specific for that cause. For example, apolipoprotein E ϵ4 was strongly associated for dementia death and forced vital capacity with pulmonary death. Age, male sex, markers of inflammation, and cognitive function were related to multiple causes of death.
In these older adults, associations of risk factors with a given cause of death were related to specific deficits in that same organ system. Inflammation may represent a common pathway to all causes of death.
Mortality risk; Cause of death; Elderly participants
Accumulating evidence suggests that ginkgo biloba is cardioprotective, in part, through its vasodilatory and antihypertensive properties. However, definitive data on its blood pressure-lowering effects in humans is lacking.
We determined the effects of ginkgo biloba extract (240 mg/day) on blood pressure and incident hypertension in 3,069 participants (mean age, 79 yrs; 46% female; 96% White) from the Ginkgo Evaluation of Memory study. We also examined whether the treatment effects are modified by baseline hypertension status.
At baseline 54% of the study participants were hypertensive, 28% were pre-hypertensive, and 17% were normotensive. Over a median follow-up of 6.1 years, there were similar changes in blood pressure and pulse pressure in the ginkgo biloba and placebo groups. Although baseline hypertension status did not modify the antihypertensive effects of ginkgo biloba, it did influence the changes in blood pressure variables observed during follow-up, with decreases in hypertensives, increases in normotensives, and no changes in pre-hypertensives. Among participants who were not on antihypertensive medications at baseline, there was no difference between treatment groups in medication use over time, as the OR (95% CI) for being a never-user in the ginkgo biloba group was 0.75 (0.48–1.16). The rate of incident hypertension also did not differ between participants assigned to ginkgo biloba vs. placebo (HR, 0.99, 95% CI, 0.84–1.15).
Our data indicate that ginkgo biloba does not reduce blood pressure or the incidence of hypertension in elderly men and women.
gingko biloba; blood pressure; hypertension; elderly
To describe retention by age and visit type (clinic, home, phone) and to determine characteristics associated with visit types for a longitudinal epidemiologic study in older adults.
DESIGN, SETTING, PARTICIPANTS
Cardiovascular Health Study (CHS) participants (N=5888; aged 65–100 years at 1989–90 or 1992–93 enrollment; 58% women; 16% black) were contacted every 6 months, with annual assessments through 1999 and in 2005–06 for the All Stars Study visit of the CHS cohort (aged 77–102 years; 67% women; 17% black).
All annual contacts through 1999 (N=43,772) and for the 2005–06 visit (N=1942).
From 1989–99, CHS had 79% clinic, 4% home, 10% phone, and 2% other visits. In 2005–06, the All Stars participants of the CHS cohort had 36.6% clinic, 22.3% home, and 41.1% phone visits. Compared to 65–69 year olds, the odds (95% CI) of not attending a CHS clinic visit were 1.82 (1.54–2.13), 2.94 (2.45–3.57), 4.55 (3.70–5.56) and 9.09 (CI: 7.69–11.11) for ages 70–74, 75–79, 80–84 and 85+ years, respectively in sex-adjusted regression. In multivariable regression, participants with a 2005–06 clinic visit were younger, more likely men, in good health, with better cognitive and physical function 7 years prior compared to participants with other visit types. Participants with home, phone and missing visits were similar on characteristics measured 7 years prior.
Offering home, phone and proxy visits are essential to optimize follow-up of aging cohorts. Home visits increased in-person retention from 37% to 59% and diversified the cohort with respect to age, health and physical functioning.
epidemiology; retention; aging; longitudinal cohort
To describe cross-sectional and longitudinal associations with dehydroepiandrosterone sulfate (DHEAS) and change in DHEAS with age.
Longitudinal cohort study.
Cardiovascular Health Study All Stars study participants assessed in 2005/06 (N =989, mean age 85.2, 63.5% women, 16.5% African American).
Health characteristics were assessed in 2005/06 according to DHEAS level, mean DHEAS and DHEAS change across age categories were tested, and linear and logistic regression was used to identify factors present in 1996/97 associated with continuous and categorical DHEAS change.
Mean ± standard deviation DHEAS was 0.555 ± 0.414 μg/mL in 1996/97 and 0.482 ± 0.449 μg/mL in 2005/06 for women and 0.845 ± 0.520 μg/mL in 1996/97 and 0.658 ± 0.516 μg/mL in 2005/06 for men. In 2005/06, DHEAS was lower in women and subjects with cardiovascular disease (CVD) and chronic pulmonary disease and higher for African Americans and subjects with hypertension and high cholesterol. Mean DHEAS change was greater in men (− 0.200 μg/mL) than in women (− 0.078 μg/mL) (P<.001). Each 1-year increase in age attenuated the effect of male sex by 0.01 μg/mL (P =.009), abolishing the sex difference in DHEAS change by age 79. Presence of CVD before the study period was associated with greater absolute DHEAS change (β = − 0.04 μg/mL, P =.04) and with the fourth quartile of DHEAS change versus the first to third quartiles (odds ratio =1.46, 95% confidence interval =1.03–2.05).
DHEAS change continues into very old age, is not homogenous, is affected by sex, and is associated with prevalent CVD. Future studies should investigate factors that might accelerate DHEAS decline.
dehydroepiandrosterone sulfate; cardiovascular disease; gender; aging
To estimate an equivalent to the Modified Mini-Mental State Exam (3MSE), and to compare changes in the 3MSE with and without the estimated scores.
Comparability study on a subset of 405 participants, aged ≥70 years, from the Cardiovascular Health Study (CHS), a longitudinal study in 4 United States communities. The 3MSE, the Telephone Interview for Cognitive Status (TICS) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were administered within 30 days of one another. Regression models were developed to predict the 3MSE score from the TICS and/or IQCODE, and the predicted values were used to estimate missing 3MSE scores in longitudinal follow-up of 4,274 CHS participants.
The TICS explained 67% of the variability in 3MSE scores, with a correlation of 0.82 between predicted and observed scores. The IQCODE alone was not a good estimate of 3MSE score, but improved the model fit when added to the TICS model. Using estimated 3MSE scores classified more participants with low cognition, and rates of decline were greater than when only the observed 3MSE scores were considered.
3MSE scores can be reliably estimated from the TICS, with or without the IQCODE. Incorporating these estimates captured more cognitive decline in older adults.
Cognitive function; Cognitive decline; Telephone interview; Proxy
We examined associations of pentraxin 3 (PTX3), a vascular inflammation marker, with incident cardiovascular disease (CVD) and all cause death.
Methods and Results
1,583 Cardiovascular Health Study participants free of prevalent CVD were included. Non-exclusive case groups were angina (n=476), myocardial infarction (MI; n=237), stroke (n=310), CVD death (n=282) and all cause death (n=772). 535 participants had no events. PTX3 levels were higher in those with subclinical CVD (1.90 ± 1.89 ng/ml) than those without (1.71 ± 1.88 ng/ml; p=0.001). Using Cox regression adjusted for age, sex and ethnicity, a standard deviation increase in PTX3 (1.89 ng/ml) was associated with CVD death (hazard ratio 1.11; 95% confidence interval 1.02–1.21) and all cause death (1.08; 1.02–1.15). PTX3 was not associated with angina (1.09; 0.98–1.20), MI (0.96; 0.81–1.12) or stroke (1.06; 0.95–1.18). Adding C-reactive protein (CRP) or CVD risk factors to the models had no significant effects on associations.
In these older adults, PTX3 was associated with CVD and all cause death independent of CRP and CVD risk factors. PTX3 likely reflects different aspects of inflammation than CRP and may provide insight into vascular health in aging and chronic diseases of aging that lead to death.
Cardiovascular Diseases; Epidemiology; Inflammation; Mortality; Pentraxin 3
To evaluate both shared and unique risk factors for maintaining physical and cognitive function into the 9th decade and beyond.
Longitudinal cohort study.
Four US communities.
1677 participants in the Cardiovascular Health Study All Stars Study, assessed in 2005/06. Median age: 85 (range 77-102), 66.5% women, 16.6% black.
Intact function was defined as no difficulty with any activities of daily living and a score >=80 on the Modified Mini-Mental Exam. Baseline characteristics assessed in 1992/93 included demographics, behavioral health factors, chronic disease history, subclinical disease markers, cardiovascular risk factors and inflammatory markers. Multinomial logistic regression was used to compare risk for physical disability, cognitive impairment, combined impairments vs. no functional impairment.
Of the 1677 participants evaluated in both domains, 891 (53%) were functionally intact. Continuous measures of function, including the Digit Symbol Substitution Test and gait speed showed that all groups, including the most functional, had declined over time. The functional group had less decline, but also tended to have higher starting values. Functional individuals had a very high baseline health profile compared to those with either physical or cognitive impairment or both impairments combined. Women and individuals with higher weight had higher rates of physical impairment but not cognitive impairment. Risk factors common to both types of impairment included cardiovascular disease and hypertension.
Intact function was found in only about half of these older adults in the 9th decade and beyond. High baseline function and low vascular disease risk characterized functional aging.
(3-5) epidemiology; physical function; cognitive function; aging; extreme old age
The prevalence and prognostic significance of isolated minor non-specific ST- segment and T-wave abnormalities (NSSTTA) in older adults are poorly understood.
Methods and Results
Cardiovascular Health Study participants free of both clinical cardiovascular disease (CVD) and major electrocardiographic abnormalities were included. We examined the prospective association of isolated minor NSSTTA (defined by Minnesota codes 4-3, 4-4, 5-3 and 5-4) with total, cardiovascular and coronary mortality, and incident non-fatal myocardial infarction (NFMI). Among 3224 participants (61.9% women, mean age 72 years), 233 (7.2%) had isolated NSSTTA at baseline. Covariates associated with isolated NSSTTA included older age, non-white race (20.5% of blacks vs. 4.8% of whites; P<0.001), diabetes, higher blood pressure and body mass index, but not presence of subclinical CVD. After 39,518 person-years of follow-up, presence of isolated NSSTTA was associated with significantly increased risk for coronary heart disease mortality (multivariable-adjusted hazards ratio 1.76; 95% confidence interval, 1.18-2.61) but not with incident NFMI (0.71; 0.43-1.17). The association of isolated NSSTTA with coronary death was independent of subclinical atherosclerosis and left ventricular mass measures. In secondary analyses among those with cardiac death, there was a significantly higher rate of primary arrhythmic death (32.3% vs. 15.4%; P=0.02) in participants with isolated NSSTTA versus those without NSSTTA.
Isolated NSSTTA are common in older Americans, and they are associated with significantly increased risk for coronary death. However, isolated NSSTTA are not associated with incident NFMI, suggesting the hypothesis that they are associated particularly with increased risk for primary arrhythmic death.
electrocardiogram; risk; coronary death
Ethnic differences in non-invasive measures of atherosclerosis are increasingly being reported, but the relationship of these measures to each other has not been widely explored. Carotid ultrasonographic and computed cardiac tomographic findings were compared in 6,814 participants of White, Black, Hispanic, and Chinese ethnicities free of overt cardiovascular disease. Coronary calcium and carotid atherosclerosis were strongly related to each other in all ethnic groups. Associations of coronary calcium prevalence and common carotid intimal-medial thickness (IMT) differed by ethnicity in women, being weakest among Black women (0.07 mm IMT difference between those with and without coronary calcium) compared to the other three groups (0.10–0.12 mm difference, p = 0.007). Estimated percent increments in internal carotid IMT per 10% increment in coronary calcium score were highest in Hispanics (18.5%) and lowest in Blacks (6.1%, p < 0.01).
Coronary calcium may be less strongly associated with carotid atherosclerosis in Blacks, particularly Black women, than in other ethnic groups. These differences should be pursued for relationships to coronary events to determine whether coronary calcium carries the same risk information in other ethnic groups as it does in Whites.
atherosclerosis; calcium; carotid arteries; epidemiology
Previous studies have suggested that subclinical abnormalities in TSH levels are associated with detrimental effects on the cardiovascular system.
To determine the relationship between baseline thyroid status and incident atrial fibrillation, incident cardiovascular disease, and mortality in older men and women not taking thyroid medication.
Design, Setting, and Patients
Participants were 3,233 US community-dwelling individuals aged 65 or over with baseline serum TSH levels who were enrolled in 1989–1990 in the Cardiovascular Health Study (CHS), a large, prospective cohort study.
Main Outcome Measures
Incident atrial fibrillation, coronary heart disease, cerebrovascular disease, cardiovascular death, and all-cause death assessed through June, 2002.
Analyses are reported for four groups defined according to thyroid function test results: subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism. Individuals with overt thyrotoxicosis were excluded due to small numbers. Eighty-two percent of participants were euthyroid, 15% had subclinical hypothyroidism, 1.6% were overtly hypothyroid, and 1.5% had subclinical hyperthyroidism. After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared to the euthyroid group (67 events vs. 31 events per 1,000 person-years; p<.001, and an adjusted hazard ratio [AHR] of 1.98; 95% confidence interval [CI] 1.29–3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroid group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroid group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an AHR of 1.07 (95% CI, 0.90–1.28) for incident coronary heart disease.
Our data show an association between subclinical hyperthyroidism and the development of atrial fibrillation, but do not support the hypothesis that unrecognized subclinical hyperthyroidism or subclinical hypothyroidism is associated with other cardiovascular disorders or mortality.
Thyroid disease; cardiovascular disease; subclinical hyperthyroidism; subclinical hypothyroidism; cholesterol; atrial fibrillation; myocardial infarction; mortality; elderly; Cardiovascular Health Study
To characterize longitudinal patterns of musculoskeletal pain in a community sample of older adults over a 6-year period and to identify factors associated with persistence of pain.
Secondary analysis of the Cardiovascular Health Study.
Community-based cohort drawn from four U.S. counties.
Five thousand ninety-three men and women aged 65 and older.
Over a 6-year period, pain was assessed each year using a single question about the presence of pain in any bones or joints during the last year. If affirmative, participants were queried about pain in seven locations (hands, shoulders, neck, back, hips, knees, feet). Participants were categorized according to the percentage of time that pain was present and according to the intermittent or chronic pattern of pain. Factors associated with persistent pain during five remaining years of the study were identified.
Over 6 years, 32% of participants reported pain for three or more consecutive years, and 32% reported pain intermittently. Of those who reported pain the first year, 54% were pain free at least once during the follow-up period. Most of the pain at specific body locations was intermittent. Factors associated with remission of pain over 5 years included older age, male sex, better self-rated health, not being obese, taking fewer medications, and having fewer depressive symptoms. Approximately half of those with pain reported fewer pain locations the following year.
Musculoskeletal pain in older adults, despite high prevalence, is often intermittent. The findings refute the notion that pain is an inevitable, unremitting, or progressive consequence of aging.
pain; musculoskeletal; longitudinal analysis; remission; persistence; symptoms