Anne B Newman

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (686)4170.85 Total impact

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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 10/2014; 64(4). DOI:10.1053/j.ajkd.2014.05.009 · 5.76 Impact Factor
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    ABSTRACT: Objective: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age. Methods: Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP). Results: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45). Conclusions: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.
    Atherosclerosis 09/2014; 237(1):336-342. DOI:10.1016/j.atherosclerosis.2014.09.012 · 3.97 Impact Factor
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    ABSTRACT: The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2014; DOI:10.1093/gerona/glu166 · 4.98 Impact Factor
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    ABSTRACT: Background. Meaningful change criteria help determine if function has improved or declined, but their magnitudes may vary across clinically relevant subgroups. We estimate meaningful decline in four common measures of physical performance in subgroups of older adults based on initial performance, demographics, chronic conditions, and health status. Methods. We used baseline (Year 1) and Year 4 data from the Health, Aging and Body Composition (Health ABC) study, a well-functioning cohort at baseline of white and black men and women (age 70-79), to evaluate the magnitude of meaningful decline in performance (6 m gait speed, 400-m walk time (400MWT), Short Physical Performance Battery, and Health ABC Physical Performance Battery (PPB), based on self-reported perceived mobility anchors (climbing 10 steps and walking 1/4 mile). Estimates were stratified by initial performance, demographics, health status, chronic conditions, and body mass index, and compared across strata. Results. For all four measures, small and substantial decline estimates were generally consistent among subgroups based on initial performance, demographics, health status, and chronic conditions. The only exception was for 400MWT, where men had greater estimates than women. For PPB, small change was 0.12 points, and substantial change was 0.22 points. Conclusions. Estimates of small and substantial meaningful decline resemble those previously reported for gait speed, 400MWT, and SPPB. Magnitudes of meaningful performance decline appear to be generally consistent across strata of initial performance, demographics, health status, body mass index, and chronic conditions.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2014; 69(10):1260-1268. DOI:10.1093/gerona/glu033 · 4.98 Impact Factor
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    ABSTRACT: A positive association between cardiorespiratory fitness (CRF) and white matter integrity has been consistently reported in older adults. However, it is unknown whether this association exists in adults over 80 with a range of chronic disease conditions and low physical activity participation, which can influence both CRF and brain health. This study examined whether higher CRF was associated with greater microstructural integrity of gray and white matter in areas related to memory and information processing in adults over 80 and examined moderating effects of chronic diseases and physical activity. CRF was measured as time to walk 400 m as quickly as possible with concurrent 3Telsa diffusion tensor imaging in 164 participants (57.1%female, 40.3%black). Fractional anisotropy (FA) was computed for cingulum, uncinate and superior longitudinal fasciculi. Mean diffusivity (MD) was computed for dorsolateral prefrontal cortex, hippocampus, parahippocampus, and entorhinal cortex. Moderating effects were tested using hierarchical regression models. Higher CRF was associated with higher FA in cingulum and lower MD in hippocampus and entorhinal cortex (β, sex-adjusted p: -0.182, 0.019; 0.165, 0.035; and 0.220, 0.006, respectively). Hypertension attenuated the association with MD in entorhinal cortex. Moderating effects of chronic diseases and physical activity in walking and climbing stairs on these associations were not significant. The association of higher CRF with greater microstructural integrity in selected subcortical areas appears robust, even among very old adults with a range of chronic diseases. Intervention studies should investigate whether increasing CRF can preserve memory and information processing by improving microstructure and potential effects of hypertension management.
    Brain Research 09/2014; DOI:10.1016/j.brainres.2014.09.003 · 2.83 Impact Factor
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    ABSTRACT: Objectives To determine the contribution of gradations of subclinical vascular disease (SVD) to the likelihood of longer survival and to determine what allows some individuals with SVD to live longer.DesignCohort study.SettingCardiovascular Health Study.ParticipantsIndividuals born between June 30, 1918, and June 30, 1921 (N = 2,082; aged 70–75 at baseline (1992–93)).MeasurementsA SVD index was scored as 0 for no abnormalities, 1 for mild abnormalities, and 2 for severe abnormalities on ankle–arm index, electrocardiogram, and common carotid intima-media thickness measured at baseline. Survival groups were categorized as 80 and younger, 81 to 84, 85 to 89, and 90 and older.ResultsA 1-point lower SVD score was associated with 1.22 greater odds (95% confidence interval = 1.14–1.31) of longer survival, independent of potential confounders. This association was unchanged after adjustment for intermediate incident cardiovascular events. There was suggestion of an interaction between kidney function, smoking, and C-reactive protein and SVD; the association between SVD and longer survival appeared to be modestly greater in persons with poor kidney function, inflammation, or a history of smoking.ConclusionA lower burden of SVD is associated with longer survival, independent of intermediate cardiovascular events. Abstinence from smoking, better kidney function, and lower inflammation may attenuate the effects of higher SVD and promote longer survival.
    Journal of the American Geriatrics Society 09/2014; 62(9). DOI:10.1111/jgs.13018 · 4.22 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 09/2014; 15(9). DOI:10.1016/j.jamda.2014.05.008 · 4.78 Impact Factor
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    ABSTRACT: Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2014; DOI:10.1093/gerona/glu134 · 4.98 Impact Factor
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    ABSTRACT: We sought to determine which systolic blood pressure (SBP) characteristics are associated with reduced brain integrity and whether these associations are stronger for white or gray matter. We hypothesized that exposure to higher and variable SBP will be associated with lower structural integrity of both gray and white matter.
    American Journal of Hypertension 08/2014; 28(3). DOI:10.1093/ajh/hpu134 · 3.40 Impact Factor
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    ABSTRACT: In older adults, depressive symptoms are associated with lower quality of life, high morbidity and mortality. This study aims to identify brain magnetic resonance imaging (MRI) features associated with late-life depressive symptoms in the population. Older community-dwelling adults (n=314) from the Health ABC study underwent brain MRI. Logistic regression was used to characterize the relationships between depressive symptoms (Center for Epidemiologic Studies of Depression scale, CES-D) and the following whole-brain variables: white matter hyperintensity (WMH) burden, fractional anisotropy (FA), and gray matter volume (GMV). Analyses examining possible regional differences between the CES-D groups controlled for Modified Mini-Mental State Examination score and diabetes status. The relative importance of localization of the markers was examined by comparing the distribution of significant peaks across the brain. Each whole-brain variable showed loss of integrity associated with high CES-D. For GMV, the odds ratio (OR)=0.84 (95% confidence interval (CI) 0.74, 0.96); for FA, OR=0.714 (95% CI 0.57, 0.88); for WMH, OR=1.89 (95%CI 1.33, 2.69). Voxel-wise analyses and patterns of peak significance showed non-specific patterns for white matter measures. Loss of GMV was most significant in the bilateral insula and anterior cingulate cortex. This study supports a cerebrovascular pattern for depressive symptoms in older adults. The localization of gray matter changes to the insula, a watershed area and a hub of affective circuits, suggests an etiological pathway from ischemia to increased depressive burden.
    Psychiatry Research Neuroimaging 08/2014; 224(2). DOI:10.1016/j.pscychresns.2014.08.009 · 2.83 Impact Factor
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    ABSTRACT: Background Kidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure. Study Design Retrospective cohort study. Setting & Participants 2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort. Predictors Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively). Outcomes Incident heart failure over a median follow-up of 12 years. Results Median values of each marker at baseline were 812 (IQR, 497-1,235) pg/mg for KIM-1:Cr, 31 (IQR, 19-56) pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51). Limitations Generalizability to other populations is uncertain. Conclusions Higher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude.
    American Journal of Kidney Diseases 07/2014; 64(1). DOI:10.1053/j.ajkd.2014.01.432 · 5.76 Impact Factor
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    ABSTRACT: Objectives To examine associations between weight change, body composition, risk of mobility disability, and mortality in older adults.DesignProspective, longitudinal, population-based cohort.SettingThe Health, Aging, and Body Composition Study.ParticipantsWomen (n = 1,044) and men (n = 931) aged 70 to 79.MeasurementsWeight and lean and fat mass from dual-energy X-ray absorptiometry measured annually over 5 years. Weight was defined as stable (n = 664, reference), loss (n = 662), gain (n = 321), or cycling (gain and loss, n = 328) using change of 5% from year to year or from Year 1 to 6. Mobility disability (two consecutive reports of difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 8 years after the weight change period. Associations were analyzed using Cox proportional hazards regression adjusted for covariates.ResultsDuring follow-up, 313 women and 375 men developed mobility disability, and 322 women and 378 men died. There was no risk of mobility disability or mortality with weight gain. Weight loss (hazard ratio (HR) = 1.88, 95% confidence interval (CI) = 1.40–2.53) and weight cycling (HR = 1.59, 95% CI = 1.11–2.29) were associated with mobility disability in women, and weight loss was associated with mobility disability in men (HR = 1.30, 95% CI = 1.01–1.69). Weight loss and weight cycling were associated with mortality risk in women (weight loss: HR = 1.47, 95% CI = 1.07–2.01; weight cycling: HR = 1.62, 95% CI = 1.15–2.30) and in men (weight loss: HR = 1.41, 95% CI = 1.09–1.83; weight cycling: HR = 1.50, 95% CI = 1.08–2.08). Adjustment for lean and fat mass and change in lean and fat mass from Year 1 to 6 attenuated the relationships between weight loss and mobility disability in men and between weight loss and mortality in men and women.Conclusion Weight cycling and weight loss predict impending mobility disability and mortality in old age, underscoring the prognostic importance of weight history.
    Journal of the American Geriatrics Society 07/2014; 62(8). DOI:10.1111/jgs.12954 · 4.22 Impact Factor
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    ABSTRACT: Importance In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability.Objective To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.Design, Setting, and Participants The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban, and rural communities at 8 centers throughout the United States. We randomized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m.Interventions Participants were randomized to a structured, moderate-intensity physical activity program (n = 818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included aerobic, resistance, and flexibility training activities or to a health education program (n = 817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises.Main Outcomes and Measures The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m.Results Incident major mobility disability occurred in 30.1% (246 participants) of the physical activity group and 35.5% (290 participants) of the health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P = .03).Persistent mobility disability was experienced by 120 participants (14.7%) in the physical activity group and 162 participants (19.8%) in the health education group (HR, 0.72 [95% CI, 0.57-0.91]; P = .006). Serious adverse events were reported by 404 participants (49.4%) in the physical activity group and 373 participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI, 0.98-1.20]).Conclusions and Relevance A structured, moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability. These findings suggest mobility benefit from such a program in vulnerable older adults.Trial Registration Identifier: NCT01072500
    JAMA The Journal of the American Medical Association 06/2014; 311(23):2387. DOI:10.1001/jama.2014.5616 · 30.39 Impact Factor
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    ABSTRACT: Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78±5 and 21% reported limitation in ≥1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP ≤65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of ≤65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders.
    Hypertension 06/2014; 64(3). DOI:10.1161/HYPERTENSIONAHA.114.03831 · 7.63 Impact Factor
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    ABSTRACT: Context: Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk. Objective: The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs). Data Sources and Study Selection: A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes. Data Extraction: Individual data of 38 274 participants from six cohorts for CHD mortality, followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events. Data Synthesis: Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87-1.53 vs HR 1.26, CI 1.01-1.58, P for interaction 0.62], as were risks of CHD events (HR 1.16, CI 0.87-1.56 vs HR 1.26, CI 1.02-1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status. Conclusions: CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.
    Journal of Clinical Endocrinology &amp Metabolism 06/2014; 99(9):jc20141250. DOI:10.1210/jc.2014-1250 · 6.31 Impact Factor
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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 06/2014; 5:159. DOI:10.3389/fgene.2014.00159
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    ABSTRACT: Microvascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 05/2014; DOI:10.1093/gerona/glu074 · 4.98 Impact Factor
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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 05/2014; 40(1). DOI:10.1016/j.gaitpost.2014.03.192 · 2.30 Impact Factor
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    ABSTRACT: Objectives To evaluate sleep–wake disturbances in sedentary community-dwelling elderly adults with functional limitations.DesignCross-sectional.SettingLifestyle Interventions and Independence in Elder (LIFE) Study.ParticipantsCommunity-dwelling persons (mean age 78.9) who spent fewer than 20 min/wk in the previous month engaged in regular physical activity and fewer than 125 min/wk of moderate physical activity, and had a Short Physical Performance Battery (SPPB) score of <10 (N = 1,635).MeasurementsMobility was evaluated according to 400-m walk time (slow gait speed defined as <0.8 m/s) and SPPB score (≤7 defined moderate to severe mobility impairment). Physical inactivity was defined according to sedentary time, as a percentage of accelerometry wear time with activity of <100 counts/min; participants in the top quartile of sedentary time were classified as having a high sedentary time. Sleep–wake disturbances were evaluated using the Insomnia Severity Index (ISI) (range 0–28; ≥8 defined insomnia), Epworth Sleepiness Scale (ESS) (range 0–24; ≥10 defined daytime drowsiness), Pittsburgh Sleep Quality Index (PSQI) (range 0–21; >5 defined poor sleep quality), and Berlin Questionnaire (high risk of sleep apnea).ResultsPrevalence rates were 43.5% for slow gait speed and 44.7% for moderate to severe mobility impairment, with 77.0% of accelerometry wear time spent as sedentary time. Prevalence rates were 33.0% for insomnia, 18.1% for daytime drowsiness, 47.8% for poor sleep quality, and 32.9% for high risk of sleep apnea. Participants with insomnia had a mean ISI score of 12.1, those with daytime drowsiness had a mean ESS score of 12.5, and those with poor sleep quality had a mean PSQI score of 9.2. In adjusted models, measures of mobility and physical inactivity were generally not associated with sleep–wake disturbances, using continuous or categorical variables.Conclusion In a large sample of sedentary community-dwelling elderly adults with functional limitations, sleep–wake disturbances were prevalent but only mildly severe and were generally not associated with mobility impairment or physical inactivity.
    Journal of the American Geriatrics Society 05/2014; 62(6). DOI:10.1111/jgs.12845 · 4.22 Impact Factor
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    ABSTRACT: The contribution of heart failure (HF) unrelated to vascular disease to the overall HF burden in older adults is not well characterized. This was investigated in this study. We assessed HF incidence and outcomes in 2895 participants of the Health ABC Study (age 74 ± 3 years, 48.4% men, 41.4% black) in relation to vascular disease (coronary, peripheral, or cerebrovascular disease) either present at baseline or developed prior to HF. During 11.4 years follow-up, 493 participants developed HF; 134 (27.2%) in participants without any prior vascular disease and 177 (36.8%) without coronary disease. Both baseline [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.9-2.8] and incident vascular disease (HR 4.3, 95% CI 3.6-5.2) were associated with HF. During a median follow-up of 2.1 years after HF onset, 67.5% participants died. Annual mortality after HF development was 21.3% in those with compared with 24.6% in those without vascular disease (HR 1.11, 95% CI 0.87-1.43; P = 0.399). There were 658 all-cause (436.3/1000 person-years) and 523 HF-related (346.4/1000 person-years) hospitalizations after HF development. There was no significant difference in hospitalizations between those with and without vascular disease [rate ratio (RR) 1.04, 95% CI 0.86-1.24 for all-cause, and RR 0.84 95% CI 0.69-1.02 for HF hospitalization]. HF with preserved EF was more common in participants without vascular disease (67.0% vs. 55.0%, P = 0.040). A significant proportion of HF in older adults develops without prior vascular disease. Outcomes for these patients are poor compared with those with preceding vascular disease. These data suggest the need for more targeted HF prediction and prevention efforts.
    European Journal of Heart Failure 05/2014; 16(5). DOI:10.1002/ejhf.69 · 6.58 Impact Factor

Publication Stats

41k Citations
4,170.85 Total Impact Points


  • 1991–2015
    • University of Pittsburgh
      • • Department of Epidemiology
      • • Department of Medicine
      Pittsburgh, Pennsylvania, United States
  • 2014
    • Columbia University
      New York City, New York, United States
  • 2007–2014
    • Pennsylvania Department of Health
      Harrisburg, Pennsylvania, United States
  • 2013
    • Pittsburg State University
      Питсбург, Kansas, United States
    • Bristol-Myers Squibb
      New York, New York, United States
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, England, United Kingdom
    • Cary Orthopaedics
      Кэри, North Carolina, United States
    • University of Pennsylvania
      Philadelphia, Pennsylvania, United States
    • Uppsala University
      Uppsala, Uppsala, Sweden
    • Beverly Hospital, Boston MA
      BVY, Massachusetts, United States
  • 2006–2013
    • The University of Tennessee Health Science Center
      • • Department of Medicine
      • • Department of Preventive Medicine
      Memphis, Tennessee, United States
    • Magee-Womens Hospital
      Pittsburgh, Pennsylvania, United States
  • 2002–2013
    • Boston University
      • • Section of Cardiovascular Medicine
      • • Pulmonary Center
      Boston, Massachusetts, United States
  • 2001–2013
    • National Institute on Aging
      • • Clinical Research Branch (CRB)
      • • Laboratory of Epidemiology, Demography and Biometry (LEDB)
      Baltimore, Maryland, United States
  • 2012
    • University of Vermont
      • Department of Pathology
      Burlington, VT, United States
  • 2011
    • Beth Israel Deaconess Medical Center
      • Division of Gerontology
      Boston, MA, United States
    • National University (California)
      San Diego, California, United States
    • Kaiser Permanente
      Oakland, California, United States
  • 2010
    • The University of Memphis
      Memphis, Tennessee, United States
    • Ben-Gurion University of the Negev
      Be'er Sheva`, Southern District, Israel
    • Yale University
      New Haven, Connecticut, United States
  • 2006–2010
    • University of Lausanne
      • Faculté de biologie et de médecine (FBM)
      Lausanne, VD, Switzerland
  • 2009
    • University of South Carolina
      Columbia, South Carolina, United States
    • Hospital of the University of Pennsylvania
      • Department of Medicine
      Philadelphia, Pennsylvania, United States
    • University of Georgia
      • Department of Foods and Nutrition
      Athens, GA, United States
  • 2007–2009
    • VU University Medical Center
      • Department of Psychiatry
      Amsterdam, North Holland, Netherlands
  • 2005–2009
    • University of Florida
      • Department of Aging and Geriatric Research
      Gainesville, FL, United States
    • Fletcher Allen Health Care
      Burlington, Vermont, United States
    • University of Queensland 
      • School of Human Movement Studies
      Brisbane, Queensland, Australia
    • Tufts Medical Center
      • Division of Nephrology
      Boston, Massachusetts, United States
  • 2008
    • Vanderbilt University
      • Department of Neurology
      Nashville, MI, United States
    • Pennington Biomedical Research Center
      Baton Rouge, Louisiana, United States
  • 2004–2008
    • Wake Forest School of Medicine
      • • Sticht Center on Aging
      • • Section on Gerontology and Geriatric Medicine
      Winston-Salem, NC, United States
  • 2005–2006
    • Maastricht University
      Maestricht, Limburg, Netherlands
  • 2004–2006
    • University of California, San Francisco
      • • Veterans Affairs Medical Center
      • • Department of Epidemiology and Biostatistics
      • • Department of Psychiatry
      San Francisco, CA, United States
    • Kent State University
      Кент, Ohio, United States
  • 2003–2006
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • VU University Amsterdam
      • IHS-Institute of Health Sciences
      Amsterdamo, North Holland, Netherlands
    • University of Leuven
      Louvain, Flanders, Belgium
  • 2004–2005
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2001–2005
    • University of Tennessee
      • • Department of Periodontology
      • • Department of Preventive Medicine
      Knoxville, TN, United States
  • 2000
    • Georgetown University
      • Division of Cardiology
      Washington, D. C., DC, United States
  • 1996
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 1993
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States