Anne B Newman

Pennsylvania Department of Health, Harrisburg, Pennsylvania, United States

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Publications (696)4075.62 Total impact

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    ABSTRACT: Step length variability (SLV) increases with age in those without overt neurologic disease, is higher in neurologic patients, is associated with falls, and predicts dementia. Whether higher SLV in older adults without neurologic disease indicates presence of neurologic abnormalities is unknown. Our objective was to identify whether SLV in older adults without overt disease is associated with findings from multimodal neuroimaging. A well-characterized cohort of 265 adults (79-90 years) was concurrently assessed by gait mat, magnetic resonance imaging with diffusion tensor, and neurological exam. Linear regression models adjusted for gait speed, demographic, health, and functional covariates assessed associations of MRI measures (grey matter volume, white matter hyperintensity volume, mean diffusivity, fractional anisotropy) with SLV. Regional distribution of associations was assessed by sparse partial least squares analyses. Higher SLV (mean: 8.4, SD: 3.3) was significantly associated with older age, slower gait speed, and poorer executive function and also with lower grey matter integrity measured by mean diffusivity (standardized beta = 0.16; p = 0.02). Associations between SLV and grey matter integrity were strongest for the hippocampus and anterior cingulate gyrus (both β = 0.18) as compared to other regions. Associations of SLV with other neuroimaging markers were not significant. Lower integrity of normal-appearing grey matter may underlie higher SLV in older adults. Our results highlighted the hippocampus and anterior cingulate gyrus, regions involved in memory and executive function. These findings support previous research indicating a role for cognitive function in motor control. Higher SLV may indicate focal neuropathology in those without diagnosed neurologic disease.
    Gait & posture 01/2014; · 2.58 Impact Factor
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    ABSTRACT: Background In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and CKD progression among community-living persons with predominantly preserved kidney function is unknown. Study Design Longitudinal observational cohort study. Setting & Participants Well-functioning community-living elders aged 70-79 years at inception. Predictor Serum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. Outcomes Change in eGFR over 7 years, and new eGFR < 60 mL/min/1.73 m2 with a rate of loss of at least 1 mL/min/1.73 m2 per year. Measurements Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR < 60 mL/min/1.73 m2. Results At baseline, mean eGFR was 84 ± 16 (SD) mL/min/1.73 m2, and serum bicarbonate level was 25.2 ± 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n = 85 [8%]) lost eGFR 0.55 (95% CI, 0.13-0.97) mL/min/1.73 m2 per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFRs > 60 mL/min/1.73 m2, 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m2 at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFRs < 60 mL/min/1.73 m2 (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations. Limitations Only 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population. Conclusions Lower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m2 in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development.
    American Journal of Kidney Diseases 01/2014; · 5.29 Impact Factor
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    ABSTRACT: Objectives Because they are potentially modifiable and may coexist, we evaluated the combined occurrence of a reduced forced expiratory volume in 1 second (FEV1) and peripheral artery disease (PAD), including its association with exertional symptoms, physical inactivity, and impaired mobility, in sedentary elders with functional limitations. Design Cross sectional. Setting Lifestyle Interventions and Independence in Elder (LIFE) Study. Participants A total of 1307 sedentary community-dwelling persons, mean age 78.9, with functional limitations (Short Physical Performance Battery [SPPB] <10). Measurements A reduced FEV1 was defined by a z-score less than −1.64 (<lower limit of normal), whereas PAD was defined by an ankle-brachial index less than 1.00. Exertional dyspnea was defined as moderate to severe (modified Borg index) immediately after a 400-meter walk test (400MWT). Exertional leg symptoms were established by the San Diego Claudication Questionnaire. Physical inactivity was evaluated by percent of accelerometry wear-time with activity less than 100 counts per minute (top quartile established high sedentary time). Mobility was evaluated by the 400MWT (gait speed <0.8 m/s defined as slow) and SPPB (≤7 defined moderate-to-severe mobility impairment). Results A combined reduced FEV1 and PAD was established in 6.0% (78/1307) of participants. However, among those who had a reduced FEV1, 34.2% (78/228) also had PAD, whereas 20.8% (78/375) of those who had PAD also had a reduced FEV1. The 2 combined conditions were associated with exertional dyspnea (adjusted odds ratio [adjOR] 2.59 [1.20–5.60]) and slow gait speed (adjOR 3.15 [1.72–5.75]) but not with exertional leg symptoms, high sedentary time, and moderate-to-severe mobility impairment. Conclusions In sedentary community-dwelling elders with functional limitations, a reduced FEV1 and PAD frequently coexisted and, in combination, were strongly associated with exertional dyspnea and slow gait speed (a frailty indicator that increases the risk of deleterious outcomes).
    Journal of the American Medical Directors Association. 01/2014;
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    ABSTRACT: Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 x 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
    Nat Genet. 01/2014; 46(7):669-77.
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    ABSTRACT: The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse relationship to the risks of atherosclerosis and cardiovascular disease (CVD), and have also been associated with longevity. We sought to identify novel loci for HDL that could potentially provide new insights into biological regulation of HDL metabolism in healthy-longevous subjects. We performed a genome-wide association (GWA) scan on HDL using a mixed model approach to account for family structure using kinship coefficients. A total of 4114 subjects of European descent (480 families) were genotyped at ~2.3 million SNPs and ~38 million SNPs were imputed using the 1000 Genome Cosmopolitan reference panel in MACH. We identified novel variants near-NLRP1 (17p13) associated with an increase of HDL levels at genome-wide significant level (p < 5.0E-08). Additionally, several CETP (16q21) and ZNF259-APOA5-A4-C3-A1 (11q23.3) variants associated with HDL were found, replicating those previously reported in the literature. A possible regulatory variant upstream of NLRP1 that is associated with HDL in these elderly Long Life Family Study (LLFS) subjects may also contribute to their longevity and health. Our NLRP1 intergenic SNPs show a potential regulatory function in Encyclopedia of DNA Elements (ENCODE); however, it is not clear whether they regulate NLRP1 or other more remote gene. NLRP1 plays an important role in the induction of apoptosis, and its inflammasome is critical for mediating innate immune responses. Nlrp1a (a mouse ortholog of human NLRP1) interacts with SREBP-1a (17p11) which has a fundamental role in lipid concentration and composition, and is involved in innate immune response in macrophages. The NLRP1 region is conserved in mammals, but also has evolved adaptively showing signals of positive selection in European populations that might confer an advantage. NLRP1 intergenic SNPs have also been associated with immunity/inflammasome disorders which highlights the biological importance of this chromosomal region.
    Frontiers in Genetics 01/2014; 5:159.
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    ABSTRACT: Sarcopenia and visceral obesity have been suggested to aggravate each other, resulting in a vicious cycle. However, evidence based on prospective study is very limited. Our purpose was to investigate whether visceral fat promotes a decrease in skeletal muscle mass and vice versa. We observed changes in anthropometric and body composition data during a follow-up period of 27.6±2.8 months in 379 Korean men and women (mean age 51.9±14.6 years) from the Korean Sarcopenic Obesity Study (KSOS). Appendicular lean soft tissue (ALST) mass was calculated using dual-energy X-ray absorptiometry, and visceral fat area (VFA) was measured using computed tomography at baseline and follow-up examination. ALST mass significantly decreased, whereas trunk and total fat mass increased in both men and women despite no significant change in weight and body mass index. In particular, women with visceral obesity at baseline had a greater decrease in ALST mass than those without visceral obesity (P = 0.001). In multiple linear regression analysis, baseline VFA was an independent negative predictor of the changes in ALST after adjusting for confounding factors including age, gender, life style and body composition parameters, insulin resistance, high sensitivity C-reactive protein and vitamin D levels (P = 0.001), whereas the association between baseline ALST mass and changes in VFA was not statistically significant (P = 0.555). This longitudinal study showed that visceral obesity was associated with future loss of skeletal muscle mass in Korean adults. These results may provide novel insight into sarcopenic obesity in an aging society.
    PLoS ONE 01/2014; 9(12):e115407. · 3.53 Impact Factor
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    ABSTRACT: Background Unless effective preventive strategies are implemented, aging of the population will result in a significant worsening of the heart failure (HF) epidemic. Few data exist on whether baseline ECG abnormalities can refine risk prediction for HF. Methods We examined a prospective cohort of 2915 participants aged 70-79 years without preexisting HF, enrolled between April 1997-June 1998 in the Health Aging and Body Composition (Health ABC) study. Minnesota Code was used to define major and minor ECG abnormalities at baseline and at year 4 follow-up. Using Cox models, we assessed (1) the association between ECG abnormalities and incident HF and (2) the incremental value of adding ECG to the Health ABC HF Risk Score using the net reclassification index (NRI). Results At baseline, 380 participants (13.0%) had minor and 620 (21.3%) had major ECG abnormalities. During a median follow-up of 11.4 years, 485 (16.6%) participants developed incident HF. After adjusting for the Health ABC HF Risk Score variables, the hazard ratio (HR) was 1.27 (95% confidence interval [CI] 0.96-1.68) for minor and 1.99 (95% CI 1.61-2.44) for major ECG abnormalities. At year 4, 263 participants developed new and 549 had persistent abnormalities; both were associated with increased subsequent HF risk (HR = 1.94, 95% CI 1.38-2.72 for new and HR = 2.35, 95% CI 1.82-3.02 for persistent ECG abnormalities). Baseline ECG correctly reclassified 10.5% of patients with HF events, 0.8% of those without HF events and 1.4% of the overall population. The NRI across the Health ABC HF risk categories was 0.11 (95% CI 0.03-0.19). Conclusions Among older adults, baseline and new ECG abnormalities are independently associated with increased risk for HF. The contribution of ECG screening for targeted prevention of HF should be evaluated in clinical trials.
    American Heart Journal. 01/2014;
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    ABSTRACT: To examine whether observed differences in dementia rates between black and white older people living in the community could be explained by measures of socioeconomic status (income, financial adequacy, education, and literacy) and health related factors. Prospective cohort study. General community from two clinic sites in the United States (Pittsburgh, Pennsylvania and Memphis, Tennessee). 2457 older people (mean age 73.6 years; 1019 (41.5%) black; 1233 (50.2%) women), dementia-free at baseline, in the Health, Aging, and Body Composition study. Dementia was determined over 12 years (ending January 2011) by prescribed dementia drugs, hospital records, and decline in global cognitive scores. The influence of socioeconomic status and health related factors on dementia rates was examined in a series of Cox proportional hazard models in which these variables were added sequentially in covariate blocks. Over follow-up, 449 (18.3%) participants developed dementia. Black participants were more likely than white participants to develop dementia (211 (20.7%) v 238 (16.6%), P<0.001; unadjusted hazard ratio 1.44, 95% confidence interval 1.20 to 1.74). The hazard ratio lessened somewhat after adjustment for demographics, apolipoprotein E e4, comorbidities, and lifestyle factors (1.37, 1.12 to 1.67) but was greatly reduced and no longer statistically significant when socioeconomic status was added (1.09, 0.87 to 1.37). These findings suggest that differences in the burden of risk factors, especially socioeconomic status, may contribute to the higher rates of dementia seen among black compared with white older people. Strategies aimed at reducing these disparities may favorably affect the incidence of dementia.
    BMJ (online) 12/2013; 347:f7051. · 17.22 Impact Factor
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    ABSTRACT: -Tumor necrosis factor (TNF) levels are associated with risk for heart failure (HF). The soluble TNF type-1 (sTNF-R1) and type-2 (sTNF-R2) receptors are elevated in patients with manifest HF, but whether they are associated with risk for incident HF is unclear. -Using Cox proportional hazard models, we examined the association between baseline levels of sTNF-R1 and sTNF-R2 with incident HF risk among 1285 participants of the Health, Aging, and Body Composition Study (age 74.0±2.9 years; 51.4% women; 41.1% black). At baseline, median (interquartile range) of TNF, sTNF-R1, and sTNF-R2 levels were 3.14 (2.42-4.06) pg/ml, 1.46 (1.25-1.76) ng/ml, and 3.43 (2.95-4.02) ng/ml, respectively. During a median follow-up of 11.4 (6.9, 11.7) years, 233 (18.1%) participants developed HF. In models controlling for other HF risk factors, TNF (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.02-1.61 per log2 increase), and sTNF-R1 (HR, 1.68; 95%CI, 1.15-2.46 per log2 increase), but not sTNF-R2 (HR, 1.15; 95%CI, 0.80-1.63 per log2 increase), were associated with a higher risk for HF. These associations were consistent across whites and blacks (TNF, sTNF-R1, sTNF-R2, interaction P=0.531, 0.091 and 0.795, respectively), and in both genders (TNF, sTNF-R1, sTNF-R2, interaction P=0.491, 0.672 and 0.999, respectively). TNF-R1 was associated with a higher risk for HF with preserved versus reduced ejection fraction (HR, 1.81; 95%CI, 1.03, 3.18; P=0.038 for preserved vs. HR, 0.90; 95%CI, 0.56, 1.44; P=0.667 for reduced ejection fraction, interaction P=0.05). -In older adults, elevated levels of sTNF-R1 are associated with an increased risk for incident HF. However, addition of TNF-R1 to the previously validated Health ABC HF risk model did not demonstrate material improvement in net discrimination or reclassification.
    Circulation Heart Failure 12/2013; · 6.68 Impact Factor
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    ABSTRACT: Obesity is associated with increased risk of many types of cancer. Less is known regarding associations between adipose depots and cancer risk. We aimed to explore relationships between adipose depots, risk of cancer, and obesity-related cancer (per NCI definition) in participants initially aged 70-79 years without prevalent cancer (1179 men, 1340 women), and followed for incident cancer for 13 years. Measures included body mass index (BMI), total adipose tissue from dual-energy X-ray absorptiometry, and computed tomography measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, thigh intermuscular adipose tissue, and thigh muscle attenuation (Hounsfield unit, HU), where low HU indicates fatty infiltration. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models adjusted for demographics, lifestyle variables, and medical conditions. During follow-up, 617 participants developed cancer of which 224 were obesity-related cancers. Total adipose tissue and VAT were positively associated with cancer risk among women (HR 1.14, 95% CI 1.01-1.30 per SD increase; HR 1.15, 95% CI 1.02-1.30 per SD increase). There were no associations with cancer risk among men. Total adipose tissue was positively associated with obesity-related cancer risk among women (HR 1.23, 95% CI 1.03-1.46 per SD increase). VAT was positively associated with obesity-related cancer risk among men (HR 1.30, 95% CI 1.06-1.60 per SD increase) and remained associated even with adjustment for BMI (HR 1.40, 95% CI 1.08-1.82 per SD increase). These findings provide insight into relationships between specific adipose depots and cancer risk and suggest differential relationships among men and women.
    Applied Physiology Nutrition and Metabolism 12/2013; · 2.01 Impact Factor
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    ABSTRACT: Background: To promote healthy aging, the University of Pittsburgh Prevention Research Center (PRC) developed the 10 KeysTM to Healthy Aging, a bundled health promotion program. The PRC partnered with the Arthritis Foundation (AF) to combine the 10 KeysTM with the AF Exercise Program (AFEP). The program was designed for older adults with arthritis or joint pain because they are at higher risk for other chronic conditions. Methods: A cluster randomized trial was implemented to compare the combined 10 Keys TM and AFEP program compared to AFEP alone, and to build sustainability of the program in the community. The collaboration involved combining content, training instructors, and recruiting host sites, instructors, and participants. Sites were matched on key characteristics for stratified randomization. Results: To date, 18 sites have been randomized to the integrated program (7 programs) or AFEP alone (11) with a goal of 40. Sessions have been held twice weekly for 10 weeks with 467 program participants. Of these, 122 consented to a detailed assessment of preventive health behaviors at baseline and follow-up. Research participants were on average 72.4 ( 9.2) years; 84.4% were women, and 98% Caucasian. Feedback was positive with 92% rating the program as excellent or very good. 50% of the sites continued to offer the program after the initial ten weeks. Conclusions: This program delivers bundled health promotion targeting multiple co-morbid conditions to at-risk older adults in the community. Program continuation suggests that it will be sustainable. Impact on preventive health behaviors remains to be tested.
    141st APHA Annual Meeting and Exposition 2013; 11/2013
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    ABSTRACT: Prior studies evaluating metabolic syndrome (MetS) and incident peripheral artery disease (PAD) have been limited by use of modified MetS criteria and restriction to clinical PAD end points. We investigated MetS and risk of developing a low ankle-brachial index (ABI) and clinical PAD in the Cardiovascular Health Study, a population-based cohort of adults aged ≥65 years. Participants with MetS met at least 3 of 5 Adult Treatment Panel III criteria. Baseline C-reactive protein-MetS or fibrinogen-MetS were defined as presence of 3 of 6 components, with elevated C-reactive protein (>3 mg/L) or fibrinogen (>341 mg/dL) as a sixth component. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among a subset of 1899 individuals with 2 ABI measurements 6 years apart. Over a median follow-up of 13.7 years, 4632 individuals were followed up for clinical PAD, defined as revascularization or diagnosed claudication. Adult Treatment Panel III MetS was associated with both incident low ABI (risk ratio, 1.26; 95% confidence interval [CI], 1.00-1.58) and clinical PAD (hazard ratio, 1.47; 95% CI, 1.11-1.94). Incorporating C-reactive protein or fibrinogen into Adult Treatment Panel III criteria identified an additional 16% to 20% of individuals as having MetS, and both C-reactive protein-MetS and fibrinogen-MetS were associated with incident low ABI (risk ratio, 1.36; 95% CI, 1.07-1.72 and risk ratio, 1.43; 95% CI, 1.13-1.81, respectively) and clinical PAD (hazard ratio, 1.56; 95% CI, 1.17-2.08 and hazard ratio, 1.55; 95% CI, 1.17-2.07, respectively). Among Adult Treatment Panel III MetS criteria, risk of PAD was most strongly associated with hypertension.
    Hypertension 11/2013; · 6.87 Impact Factor
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    ABSTRACT: To determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular (CVD) events beyond conventional risk factors. Several studies have shown that aPWV may be a useful risk factor for predicting CVD but have been underpowered to examine whether this is true for different sub-groups. We undertook a systematic review and obtained individual participant data from 16 studies. Study-specific associations of aPWV with cardiovascular outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects. Of 17,635 participants, 1,785 (10%) had a cardiovascular (CVD) event. The pooled age- and sex-adjusted hazard ratio [95% CI] per SD change in loge aPWV was 1.35 [1.22, 1.50, p<0.001] for coronary heart disease (CHD), 1.54 [1.34, 1.78, p<0.001] for stroke, and 1.45 [1.30, 1.61, p<0.001) for CVD. Associations stratified by sex, diabetes and hypertension were similar, but decreased with age (1.89, 1.77, 1.36 and 1.23 for ≤50, 51-60, 61-70 and >70 years respectively, pinteraction <0.001). After adjusting for conventional risk factors, aPWV remained a predictor: CHD 1.23, [1.11, 1.35 p<0.001]; stroke 1.28, [1.16, 1.42 p<0.001]; cardiovascular events 1.30 [1.18, 1.43, p<0.001]. Reclassification indices showed the addition of aPWV improved risk prediction (13% for 10 year CVD risk for intermediate risk) for some sub-groups. Consideration of aPWV improves model fit and reclassifies risk for future cardiovascular events in models that include standard risk factors. aPWV may enable better identification of high-risk populations who may benefit from more aggressive cardiovascular risk factor management.
    Journal of the American College of Cardiology 11/2013; · 14.09 Impact Factor
  • Journal of the American Geriatrics Society 11/2013; 61(11):2060. · 4.22 Impact Factor
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    ABSTRACT: The aim of this study was to assess the association between frailty and risk for heart failure (HF) in older adults. Frailty is common in the elderly and is associated with adverse health outcomes. Impact of frailty on HF risk is not known. We assessed the association between frailty, using the Health ABC Short Physical Performance Battery (HABC Battery) and the Gill index, and incident HF in 2825 participants aged 70 to 79 years. Mean age of participants was 74 ± 3 years; 48% were men and 59% were white. During a median follow up of 11.4 (7.1-11.7) years, 466 participants developed HF. Compared to non-frail participants, moderate (HR 1.36, 95% CI 1.08-1.71) and severe frailty (HR 1.88, 95% CI 1.02-3.47) by Gill index was associated with a higher risk for HF. HABC Battery score was linearly associated with HF risk after adjusting for the Health ABC HF Model (HR 1.24, 95% CI 1.13-1.36 per SD decrease in score) and remained significant when controlled for death as a competing risk (HR 1.30; 95% CI 1.00-1.55). Results were comparable across age, sex, and race, and in sub-groups based on diabetes mellitus or cardiovascular disease at baseline. Addition of HABC Battery scores to the Health ABC HF Risk Model improved discrimination (change in C-index, 0.014; 95% CI 0.018-0.010) and appropriately reclassified 13.4% (net-reclassification-improvement 0.073, 95% CI 0.021-0.125; P = .006) of participants (8.3% who developed HF and 5.1% who did not). Frailty is independently associated with risk of HF in older adults.
    American heart journal 11/2013; 166(5):887-94. · 4.65 Impact Factor
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    ABSTRACT: Intima-media thickness, adventitial diameter and lumen diameter are indicators of cardiovascular disease risk. The influence of genetic factors on these measures in African ancestry populations is not well defined. Therefore, we estimated heritability and performed genome-wide linkage analysis of carotid ultrasound traits in 7 multigenerational families of African ancestry. A total of 395 individuals (7 pedigrees; mean family size = 56; 2392 relative pairs) aged ≥18 years had a common carotid artery ultrasound scan. Statistical analyses were conducted using pedigree-based maximum likelihood methods. Significant covariates included age, sex, body mass index or height and waist, and systolic blood pressure. Residual heritabilities ranged from 0.35 ± 0.10 to 0.64 ± 0.12 (P < 0.0001). We identified a novel quantitative trait locus for adventitial and lumen diameters on chromosome 11 (max LOD = 4.09, 133 cm). Further fine mapping of this region may identify specific mutations predisposing to subclinical vascular disease among African ancestry individuals.
    Atherosclerosis 11/2013; 231(1):120-123. · 3.71 Impact Factor
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    ABSTRACT: Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants. CHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFRcys). Secondary analyses examined eGFR using serum creatinine (eGFRSCr). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity. The mean age was 75 years and the median eGFRcys was 73 ml/min per 1.73 m(2). Among participants with an eGFRcys <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFRcys ≥90 ml/min per 1.73 m(2), eGFRcys categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFRcys categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFRSCr were not associated with higher risk of prevalent or incident frailty. In community-dwelling elders, lower eGFRcys was associated with a higher risk of prevalent and incident frailty whereas lower eGFRSCr was not. These findings highlight the importance of considering non-GFR determinants of kidney function.
    Clinical Journal of the American Society of Nephrology 10/2013; · 5.07 Impact Factor
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    ABSTRACT: The cerebellum plays an important role in mobility and cognition. However, it is unclear which regions of the cerebellum are associated with gait speed and information-processing ability in older adults without overt brain damage. Cross-sectional associations between cerebellar gray matter volumes (GMV), gait speed, and information-processing ability were explored in 231 community-dwelling adults (mean age: 83 years, 48% black, 58% female). We measured gait speed on an automated walkway and information-processing ability on the Digit Symbol Substitution test (DSST). Total and regional cerebellar GMV was measured on 3T-magnetic resonance imaging. Lobar GMV of the cerebellum, obtained by an automated parcellation process, were aggregated based on the cognitive (lobules VI, VII, VIII and crus I, II), sensorimotor (lobules II, IV, V), and vestibular (lobules IX and X) functions ascribed to the cerebellar regions. Larger cerebellar GMV correlated with faster gait speed and superior DSST scores (both p < .001) independent of age, gender, atrophy, and small vessel disease. After adjusting for age, gender, and atrophy, larger cognitive cerebellar GMV correlated with both faster gait speed (p = .04) and higher DSST scores (p < .001), larger sensorimotor cerebellar GMV correlated significantly with DSST alone (p = .02), and the vestibular cerebellar GMV with neither. The association between cognitive cerebellar GMV and gait speed was no longer significant after adjusting for DSST score in the linear regression models. The relationship between gait speed and cerebellar GMV is influenced by information-processing ability, and this relationship is stronger in subregions ascribed to cognitive than vestibular or sensorimotor functions.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 10/2013; · 4.31 Impact Factor
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    ABSTRACT: Advanced glycation endproducts are biologically active compounds that accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML), a ubiquitous human advanced glycation endproduct, has been associated with age-related conditions and mortality. Our objective was to ascertain the relationship between CML and geriatric outcomes (disability and frailty) in a large cohort of older men and women. In 1996-1997, serum CML was measured in 3,373 Cardiovascular Health Study participants (mean age 78.1 ± 4.8 years). Disability, defined as difficulty in any of six activities of daily living, was assessed every 6-12 months for 14 years. Frailty was defined according to five standard criteria at the 1996-1997 visit. Cox proportional hazard models estimated the relationship between CML and incident disability (N = 2,643). Logistic regression models estimated the relationship between CML and prevalent frailty. Adjusting for multiple potential confounders, higher CML was associated with incident disability (hazard ratio per standard deviation [225 ng/mL] increase: 1.05, 95% CI 1.01-1.11). In men, odds of frailty increased with higher CML values (odds ratio = 1.30 per standard deviation, 95% CI 1.14-1.48), but the relationship was attenuated by adjustment for cognitive status, kidney function, and arthritis. CML was not associated with frailty in women. Higher serum CML levels in late life are associated with incident disability and prevalent frailty. Further work is needed to understand CML's value as a risk stratifier, biomarker, or target for interventions that promote healthy aging.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 10/2013; · 4.31 Impact Factor
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    ABSTRACT: To evaluate race-related differences in depression onset and recovery in older persons, overall and by sex, and examine race-related differences in mortality according to depression. Prospective cohort study. General community in pre-designated zip code areas in Memphis, Tennessee, and Pittsburgh, Pennsylvania. 3,075 persons aged 70-79 years at baseline in the Health, Aging, and Body Composition study. Depression was assessed at eight time points over 10 years using the 10-item Center for Epidemiologic Studies-Depression scale; patients were categorized as nondepressed (score less than 8) or depressed (score of 8 or higher). We created variables for transitions across each 18-month time interval, namely, from nondepressed or depressed to nondepressed, depressed, or death, and determined the association between race and the average likelihood of these transitions over time. A higher percentage of blacks than whites were depressed at nearly all time points. Adjusting for demographics, common chronic conditions, and body mass index, blacks had a higher likelihood of experiencing depression onset than whites (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.03-1.43); among men, blacks were more likely to experience depression onset than whites (OR: 1.44; 95% CI: 1.24-2.89). Blacks also had a higher likelihood of transitioning from nondepressed to death (OR: 1.79; 95% CI: 1.30-2.46). Overall and in sex-stratified analyses, race was not associated with recovery from depression or with the transition from depression to death. Our findings highlight race differences in depression in older persons and encourage further research on the course of depression in older black patients.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 10/2013; · 3.35 Impact Factor

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35k Citations
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Institutions

  • 2007–2014
    • Pennsylvania Department of Health
      Harrisburg, Pennsylvania, United States
  • 2003–2014
    • Columbia University
      • College of Physicians and Surgeons
      New York City, New York, United States
    • University of Leuven
      Louvain, Flanders, Belgium
  • 1991–2014
    • University of Pittsburgh
      • • Division of Geriatric Medicine
      • • Department of Epidemiology
      • • UPMC - Comprehensive Lung Center
      • • Department of Obstetrics, Gynecology and Reproductive Sciences
      • • Division of Renal-Electrolyte
      • • School of Medicine
      • • Department of Psychiatry
      Pittsburgh, Pennsylvania, United States
  • 2013
    • Northwestern University
      • Feinberg School of Medicine
      Evanston, Illinois, United States
    • Oregon State University
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    • University of Cambridge
      • Department of Public Health and Primary Care
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    • King's College London
      • Institute of Psychiatry
      London, ENG, United Kingdom
    • University of Connecticut
      • UConn Center on Aging
      Storrs, Connecticut, United States
    • Uppsala University
      Uppsala, Uppsala, Sweden
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Maryland, United States
  • 2006–2013
    • Emory University
      • • Division of Cardiology
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      • • Division of Endocrinology
      Atlanta, Georgia, United States
    • University of San Francisco
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    • St. Francis Hospital
      Roslyn, New York, United States
  • 2004–2013
    • University of California, San Francisco
      • • Division of Hospital Medicine
      • • Department of Psychiatry
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      • • Veterans Affairs Medical Center
      • • Department of Epidemiology and Biostatistics
      San Francisco, CA, United States
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    • University of Florence
      • Dipartimento di Medicina Sperimentale e Clinica
      Florence, Tuscany, Italy
  • 2001–2013
    • National Institute on Aging
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      Baltimore, Maryland, United States
  • 2012
    • University of Texas Southwestern Medical Center
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      Amiun, Liban-Nord, Lebanon
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      Tolosa de Llenguadoc, Midi-Pyrénées, France
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      New York City, New York, United States
    • Inselspital, Universitätsspital Bern
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      Bern, BE, Switzerland
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      Syracuse, New York, United States
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      • Pulmonary Center
      Boston, Massachusetts, United States
    • Hospital of the University of Pennsylvania
      • Department of Medicine
      Philadelphia, Pennsylvania, United States
    • Instituto Nacional de Cardiología
      Ciudad de México, The Federal District, Mexico
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      Davis, California, United States
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      Columbia, South Carolina, United States
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      Durham, North Carolina, United States
    • University of California, Berkeley
      • Division of Epidemiology
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  • 2008–2012
    • University of Lausanne
      • Faculté de biologie et de médecine (FBM)
      Lausanne, VD, Switzerland
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York City, NY, United States
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      Kansas, United States
    • University of Exeter
      • Peninsula College of Medicine and Dentistry
      Exeter, ENG, United Kingdom
    • Pennington Biomedical Research Center
      Baton Rouge, Louisiana, United States
  • 2005–2012
    • University of Vermont
      • • Department of Pathology
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    • University of Washington Seattle
      • • Department of Biostatistics
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      Seattle, WA, United States
    • Fletcher Allen Health Care
      Burlington, Vermont, United States
    • University of Queensland 
      • School of Human Movement Studies
      Brisbane, Queensland, Australia
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      • Department of Health Sciences
      Columbia, MO, United States
  • 2011
    • Kaiser Permanente
      Oakland, California, United States
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      San Diego, California, United States
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      • Sektion für Genetische Epidemiologie
      Innsbruck, Tyrol, Austria
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      San Francisco, CA, United States
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      • Center for the Study of Aging and Human Development
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    • United States Department of Agriculture
      Washington, Washington, D.C., United States
    • State University of New York Downstate Medical Center
      • Department of Epidemiology and Biostatistics (EPID, BIOS)
      Brooklyn, NY, United States
    • Autonomous University of Barcelona
      Cerdanyola del Vallès, Catalonia, Spain
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    • Weill Cornell Medical College
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      Be'er Sheva`, Southern District, Israel
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    • California State University, Sacramento
      Sacramento, California, United States
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      • Department of Aging and Geriatric Research
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      Winston-Salem, NC, United States
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      Boston, Massachusetts, United States
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      • • Division of Gerontology
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      • • Division of General Medicine and Primary Care
      Boston, MA, United States
  • 2003–2011
    • Wake Forest School of Medicine
      • • Department of Internal Medicine
      • • Sticht Center on Aging
      • • Department of Biostatistical Sciences
      Winston-Salem, NC, United States
  • 2009–2010
    • University of Pennsylvania
      • • Department of Medicine
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      • Department of Internal Medicine
      Seoul, Seoul, South Korea
  • 2006–2009
    • University of Georgia
      • Department of Foods and Nutrition
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  • 2002–2009
    • VU University Medical Center
      • Department of Psychiatry
      Amsterdam, North Holland, Netherlands
  • 2007–2008
    • University of Colorado
      • • Department of Health and Behavioral Sciences
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      Denver, CO, United States
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      • • Department of Neurology
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  • 2006–2007
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      • Department of Preventive Medicine
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  • 2005–2007
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
    • Maastricht University
      Maestricht, Limburg, Netherlands
  • 2004–2007
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2003–2005
    • The University of Arizona
      • Department of Medicine
      Tucson, AZ, United States
  • 2001–2005
    • University of Tennessee
      • • Department of Periodontology
      • • Department of Preventive Medicine
      Knoxville, TN, United States
  • 2000–2005
    • VU University Amsterdam
      • • Faculty of Earth and Life Sciences
      • • Faculty of Medicine/VU University Medical Center
      Amsterdam, North Holland, Netherlands
    • Georgetown University
      • Division of Cardiology
      Washington, D. C., DC, United States
  • 1991–2005
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, Maryland, United States