Showing papers by "Anne B. Newman published in 2004"

The Metabolic Syndrome, Inflammation, and Risk of Cognitive Decline

Abstract: ContextSeveral studies have reported an association between the metabolic syndrome and cardiovascular disease Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there are few data on the metabolic syndrome and cognitionObjectiveTo determine if the metabolic syndrome is a risk factor for cognitive decline and if this association is modified by inflammationDesign and SettingA 5-year prospective observational study conducted from 1997 to 2002 at community clinics at 2 sitesParticipantsA total of 2632 black and white elders (mean age, 74 years)Main Outcome MeasuresAssociation of the metabolic syndrome (measured using National Cholesterol Education Program guidelines) and high inflammation (defined as above median serum level of interleukin 6 and C-reactive protein) with change in cognition (Modified Mini-Mental State Examination [3MS]) at 3 and 5 years Cognitive impairment was defined as at least a 5-point declineResultsCompared with those without the metabolic syndrome (n = 1616), elders with the metabolic syndrome (n = 1016) were more likely to have cognitive impairment (26% vs 21%, multivariate adjusted relative risk [RR], 120; 95% confidence interval [CI], 102-141) There was a statistically significant interaction with inflammation and the metabolic syndrome (P = 03) on cognitive impairment After stratifying for inflammation, those with the metabolic syndrome and high inflammation (n = 348) had an increased likelihood of cognitive impairment compared with those without the metabolic syndrome (multivariate adjusted RR, 166; 95% CI, 119-232) Those with the metabolic syndrome and low inflammation (n = 668) did not exhibit an increased likelihood of impairment (multivariate adjusted RR, 108; 95% CI, 089-130) Stratified multivariate random-effects models demonstrated that participants with the metabolic syndrome and high inflammation had greater 4-year decline on 3MS (P = 04) compared with those without the metabolic syndrome, whereas those with the metabolic syndrome and low inflammation did not (P = 44)ConclusionThese findings support the hypothesis that the metabolic syndrome contributes to cognitive impairment in elders, but primarily in those with high level of inflammation

The Effects of Age, Sex, Ethnicity, and Sleep-Disordered Breathing on Sleep Architecture

Abstract: Background Polysomnography is used to assess sleep quality and to gauge the functional effect of sleep disorders. Few population-based data are available to estimate the variation in sleep architecture across the population and the extent to which sleep-disordered breathing (SDB), a common health condition, contributes to poor sleep independent of other factors. The objective of this study was to describe the population variability in sleep quality and to quantify the independent associations with SDB. Methods Cross-sectional analyses were performed on data from 2685 participants, aged 37 to 92 years, in a community-based multicenter cohort study. Dependent measures included the percentage time in each sleep stage, the arousal index, and sleep efficiency. Independent measures were age, sex, ethnicity, comorbidity status, and the respiratory disturbance index. Results Lighter sleep was found in men relative to women and in American Indians and blacks relative to other ethnic groups. Increasing age was associated with impaired sleep in men, with less consistent associations in women. Notably, women had, on average, 106% more slow wave sleep. Sleep-disordered breathing was associated with poorer sleep; however, these associations were generally smaller than associations with sex, ethnicity, and age. Current smokers had lighter sleep than ex-smokers or never smokers. Obesity had little effect on sleep. Conclusions Sleep architecture varies with sex, age, ethnicity, and SDB. Individual assessment of the effect of SDB on sleep quality needs to account for other host characteristics. Men, but not women, show evidence of poorer sleep with aging, suggesting important sex differences in sleep physiology.

Physical activity, exercise, and inflammatory markers in older adults: findings from the Health, Aging and Body Composition Study.

Abstract: OBJECTIVES: To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use. DESIGN: Cross-sectional study, using baseline data from the Health, Aging and Body Composition Study. SETTING: Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Black and white, well-functioning men and women (N=3,075), aged 70 to 79. MEASUREMENTS: Interviewer-administered questionnaires of previous-week household, walking, exercise, and occupational/volunteer physical activities. Analysis of covariance was used to examine the association between activity level and serum C-reactive protein (CRP), interleukin-6 (IL-6), and plasma tumor necrosis factor alpha (TNFalpha) with covariate adjustment. Antioxidant supplement use (multivitamin, vitamins E or C, beta carotene) was evaluated as an effect modifier of the association. RESULTS: Higher levels of exercise were associated with lower levels of CRP (P 180 min/wk). Adjustment for body fatness attenuated the associations somewhat. Use of antioxidant supplements modified the CRP (P-interaction=.01) and IL-6 (P-interaction=.08) associations such that concentrations were low in those taking supplements (e.g., CRP=1.79-1.84 across exercise levels) and higher in nonsupplement users who did no exercise (2.03) than in those who did the most (1.72). Among nonexercisers, higher levels of other physical activity were related to lower levels of CRP (P<.01) and IL-6 (P=.02) but not TNFalpha (P=.36), even after accounting for body fat. CONCLUSION: Inflammatory markers are lower in older adults with higher levels of exercise and nonexercise activity and in antioxidant supplement users regardless of exercise level.

Inflammatory markers and incident mobility limitation in the elderly.

Abstract: OBJECTIVES: To examine the relationship between indicators of inflammation and the incidence of mobility limitation in older persons. DESIGN: Prospective cohort study: the Health, Aging and Body Composition Study. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: A total of 2,979 men and women, aged 70 to 79, without mobility limitation at baseline. MEASUREMENTS: Serum levels of interleukin (IL)-6, tumor necrosis factor alpha (TNFa), and C-reactive protein (CRP) and soluble cytokine receptors (IL-2sR, IL-6sR, TNFsR1, TNFsR2) were measured. Mobility limitation was assessed and defined as reporting difficulty or inability to walk one-quarter of a mile or to climb 10 steps during two consecutive semiannual assessments over 30 months. RESULTS: Of the 2,979 participants, 30.1% developed incident mobility limitation. After adjustment for confounders (demographics, prevalent conditions at baseline, body composition), the relative risk (RR) of incident mobility limitation per standard deviation (SD) increase was 1.19 (95% confidence interval (CI) 51.10‐1.28) for IL-6, 1.20 (95% CI 51.12‐1.29) for TNFa, and 1.40 (95% CI 51.18‐1.68) for CRP. The association between inflammation and incident mobility limitation was especially strong for the onset of more severe mobility limitation and when the levels of multiple inflammatory markers were high. When persons with baseline or incident cardiovascular disease events or persons who were hospitalized during study follow-up were excluded, findings remained similar. In a subset (n 5499), high levels of the soluble receptors IL2sR and TNFsR1 (per SD increase: RR 51.23 (95% CI 51.04‐1.46) and RR 51.28 (95% CI 51.04‐ 1.57), respectively) were also associated with incident mobility limitation. CONCLUSION: Findings suggest that inflammation is prognostic for incident mobility limitation over 30 months, independent of cardiovascular disease events and incident severe illness. J Am Geriatr Soc 52:1105‐1113, 2004.

Inflammatory and Prothrombotic Markers and the Progression of Renal Disease in Elderly Individuals

Abstract: Inflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers-serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.

Diabetes Is Associated Independently of Body Composition With BMD and Bone Volume in Older White and Black Men and Women: The Health, Aging, and Body Composition Study

Abstract: The association between type 2 diabetes, BMD, and bone volume was examined to determine the effect of lean and fat mass and fasting insulin in the Health, Aging, and Body Composition Study, which included white and black well-functioning men and women 70-79 years of age (N = 2979). Diabetes predicted higher hip, whole body, and volumetric spine BMD, and lower spine bone volume, independent of body composition and fasting insulin. Introduction: The purpose of this study was to determine if the association between type 2 diabetes and higher BMD observed in older white women is seen in elderly white men and blacks and to evaluate if higher BMD in diabetic individuals is accounted for by lean mass, fat mass, or fasting insulin differences. Materials and Methods: In the Health, Aging, and Body Composition Study, which included white and black well-functioning men and women 70-79 years of age (N = 2979), 19% of participants had diabetes at baseline. Of those with diabetes, 57% were men, and 62% were black. Multivariate linear regression models examined independent effects of diabetes, lean mass, fat mass, visceral fat, and fasting insulin on BMD and bone volume while adjusting for relevant covariates. Results and Conclusions: Fasting insulin, visceral fat, and volumetric spine BMD, assessed by CT, and lean mass, fat mass, and total hip and whole body BMD, assessed by DXA, were higher (p ≤ 0.05 for all) for those with diabetes. Hip BMD was higher in white men (0.99 ± 0.14 versus 0.93 ± 0.14 g/cm2, p < 0.001), black men (1.06 ± 0.17 versus 1.00 ± 0.15 g/cm2, p < 0.001), white women (0.83 ± 0.13 versus 0.76 ± 0.13 g/cm2, p < 0.001), and black women (0.90 ± 0.15 versus 0.85 ± 0.15 g/cm2, p < 0.001) with diabetes compared with those without diabetes, although the relationship was attenuated by body composition. In multiple regression models, diabetes was an independent predictor of higher hip, whole body, and volumetric spine BMD in all participants (p ≤ 0.001), but lower spine volume (p = 0.01) and higher hip BMD for each race-gender group (p ≤ 0.01). Type 2 diabetes was associated with a 4-5% higher total hip BMD in all race-gender groups of elderly adults, independent of body composition and fasting insulin levels.

Preclinical Alzheimer disease Neuropsychological test performance 1.5 to 8 years prior to onset

Abstract: Objective: To determine if individuals ultimately diagnosed with Alzheimer disease (AD) exhibited evidence of cognitive impairment on neuropsychological tests administered between 1.5 years and 8.1 years before dementia onset. Methods: A total of 693 community-dwelling individuals, part of the Cardiovascular Health Study, completed a neuropsychological test battery in 1991/92. Subjects were followed annually over the next 8 years (median follow-up = 7.4 years). Seventy-two individuals were ultimately diagnosed with AD (median follow-up = 4.5 years): 24 with AD onset 1.5 to 3.4 years after baseline neuropsychological testing, 20 with AD onset 3.5 to 5.0 years after testing, and 28 with onset 5.1 to 8.1 years after testing. A total of 621 individuals remained nondemented throughout the 8 years of follow-up (median follow-up = 7.5 years). Results: Subjects ultimately diagnosed with AD had poorer scores on baseline neuropsychological measures than subjects who remained nondemented. Although individuals closest to AD onset (i.e., 1.5 to 3.4 years) performed the most poorly, cognitive impairment was detected in individuals who did not develop AD until 5 to 8 years later. Conclusions: Cognitive changes can be detected well before onset of Alzheimer disease.

Insulin‐Like Growth Factor‐1

Abstract: To the Editor: It is well known that insulin-like growth factor (IGF)-1 levels decrease with age, but in the absence of a true deficiency, it is not clear why so much variability exists in circulating levels of serum IGF-1 nor what contributes to this variability, aside from growth hormone levels. Cross-sectional studies are inconsistent regarding the associations between serum IGF-1 and lean tissue mass and bone mineral density (BMD) in the elderly, and there are few longitudinal studies addressing this issue in healthier older adults. Serum levels of IGF-1 in a well-functioning cohort of black and white men and women from the Memphis and Pittsburgh areas, aged 70 to 79 at baseline, were examined. A random sample (n5 625) of participants was selected from the Health, Aging, and Body Composition Study, and IGF-1 in serum that had been frozen at 801C after a fasting blood draw was measured. IGF-1 was separated from its binding proteins using acid-ethanol cryoprecipitation and measured using an IGF-binding protein-blocked radioimmunoassay (ALPCO, Windham, NH). The mean intra-assay coefficient of variation (CV) for the 20 batches run was 2.3% (range50.43–5.87%), and the interassay CV was 3.2%. Total lean and fat mass and regional BMD were measured using dual-energy x-ray absorptiometry (DXA) at baseline and again 2 years later. Abdominal visceral fat and thigh muscle and fat areas were measured using computed tomography (CT) scanning. Thigh intermuscular fat was calculated using the deep fascial plane and muscle areas as guidelines. Thigh muscle density, as an indicator of fatty infiltration into muscle, was calculated using mean attenuation values in Hounsfield Units excluding intermuscular fat. Participants were divided into sex-specific groups by 25th and 75th percentile cutpoints for IGF1. Those cutpoints were 94 ng/L and 148 ng/L for men and 77 ng/L and 127 ng/L for women, respectively. Analysis of covariance was used to examine the cross-sectional relationship between various body composition components and IGF-1 levels in 609 participants with valid IGF-1, CT, and BMD measurements (Table 1). Linear regression was then used to examine the association between baseline IGF-1 (log-transformed) and the prospective 2-year change in total lean body mass (n5514), total fat mass (n5528), and total hip BMD (n5526) from DXA with adjustment for age, sex, race, study site, thigh length (from CT), and baseline levels of lean body mass, total fat mass, and hip BMD for the respective analyses. IGF-1 was not associated with change in lean body mass (P5.12), fat mass (P5.27), or hip BMD (P5.56). Further adjustment for smoking, alcohol consumption, exercise level, or prevalent diseases at baseline did not affect these results, nor did further modeling using the 25th and 75th percentile cutpoints for IGF-1. With the exception of higher indices of thigh muscle mass and muscle density, variations in IGF-1 were not

Water turnover in 458 American adults 40-79 yr of age

Abstract: Despite recent interest in water intake, few data are available on water metabolism in adults. To determine the average and range of usual water intake, urine output, and total body water, we admin...

Respiratory muscle strength and the risk of incident cardiovascular events

Abstract: Background: Maximal inspiratory pressure (MIP) is a measure of inspiratory muscle strength. The prognostic importance of MIP for cardiovascular events among elderly community dwelling individuals is unknown. Diminished forced vital capacity (FVC) is a risk factor for cardiovascular events which remains largely unexplained. Methods: MIP was measured at the baseline examination of the Cardiovascular Health Study. Participants had to be free of prevalent congestive heart failure (CHF), myocardial infarction (MI), and stroke. Results: Subjects in the lowest quintile of MIP had a 1.5-fold increased risk of MI (HR 1.48, 95% CI 1.07 to 2.06) and cardiovascular disease (CVD) death (HR 1.54, 95% CI 1.09 to 2.15) after adjustment for non-pulmonary function covariates. There was a potential inverse relationship with stroke (HR 1.36, 95% CI 0.97 to 1.90), but there was little evidence of an association between MIP and CHF (HR 1.22, 95% CI 0.93 to 1.60). The addition of FVC to models attenuated the HR associated with MIP only modestly; similarly, addition of MIP attenuated the HR associated with FVC only modestly. Conclusions: A reduced MIP is an independent risk factor for MI and CVD death, and a suggestion of an increased risk for stroke. This association with MIP appeared to be mediated through mechanisms other than inflammation.

Lipoprotein levels are associated with incident hypertension in older adults.

Abstract: Objectives: To determine the relationship between baseline measures of serum lipoproteins and incident hypertension in older adults. Design: Prospective cohort study. Setting: Pittsburgh, Pennsylvania, site of Systolic Hypertension in the Elderly Program (SHEP). Participants: One hundred eighty-seven men and women (mean age 71.3), normotensive (systolic blood pressure (SBP) <160 mmHg, diastolic blood pressure (DBP) <90 mmHg) at baseline, were followed annually over 8 years as an ancillary study to the SHEP. Measurements: Hypertension development, defined as initiation of antihypertensive therapy or SBP greater than 160 mmHg or DBP greater than 90 mmHg. Lipoprotein measures included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, and apolipoproteins 1, 2, and B. Results: Over 8 years, 44 participants developed hypertension, for a Kaplan-Meier cumulative incidence rate of 31% (95% confidence interval (CI)=23–39%). Cumulative incidence rates were highly associated with baseline SBP, ranging from 8% in those with baseline SBP less than 120 mmHg to 70% in those with SBP of 140 to 159 mmHg. Other univariate associations included higher DBP, pulse pressure (P < .01 for both), triglycerides (P=.03), apolipoprotein B (P=.03), and lower HDL-C (P=.04) and HDL3-C (P=.02). In multivariate Cox regression analysis, higher baseline SBP (relative risk (RR)=1.8 per 10 mmHg, 95% CI=1.5–2.3) and lower HDL3-C (RR=0.8 per 5 mg/dL, 95% CI=0.42–1.0) remained significant independent predictors of time to hypertension. Conclusion: Older adults with abnormal serum lipoproteins are at increased risk of developing hypertension. Clinical trials exploring the effects of the modification of lipoprotein levels on hypertension incidence rates are needed.

Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: The Health Aging and Body Composition Study (Health ABC)

Abstract: The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68–80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index <0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [ORintegral] = 1.34, 95% confidence interval [CI] 1.10–1.63; ORtrabecular = 1.25, 95% CI 1.02–1.53; ORcortical = 1.36, 95% CI 1.11–1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03–1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-α). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.