Publications by authors named "Anne B Newman"

754 Publications

Estimating cardiorespiratory fitness in older adults using a usual-paced 400-m long-distance corridor walk.

J Am Geriatr Soc 2021 Jul 16. Epub 2021 Jul 16.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.1111/jgs.17360DOI Listing
July 2021

Association of fatigue, inflammation, and physical activity on gait speed: the Long Life Family Study.

Aging Clin Exp Res 2021 Jul 1. Epub 2021 Jul 1.

Graduate School of Public Health, Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15261, USA.

Background: Fatigue, inflammation, and physical activity (PA) are all independently associated with gait speed, but their directionality is not fully elucidated.

Aims: Evaluate the bidirectional associations amongst fatigue, inflammation, and PA on gait speed.

Methods: This cross sectional study included probands (n = 1280, aged 49-105) and offspring (n = 2772, aged 24-88) in the Long Life Family Study. We assessed gait speed, fatigue with the question "I could not get going", inflammation using fasting interleukin-6 (IL-6) and high sensitivity C-reactive protein (CRP), and self-reported PA as walking frequency in the past two weeks. The two generations were examined separately using linear mixed modeling.

Results: Lower fatigue, lower IL-6, and greater PA were all associated with faster gait speed in both generations (all p < 0.05); lower CRP was only associated with faster gait speed in the offspring. PA explained the association of fatigue and gait speed via a 16.1% (95% CI 9.7%, 26.7%) attenuation of the direct associations for the probands and 9.9% (95% CI 6.3%, 18.8%) in the offspring. In addition, IL-6 explained more of the association of fatigue and gait speed than the association between PA and gait speed, via a 14.9% (95% CI 9.2%, 23.4%) attenuation of the direct association in the offspring only.

Discussion: Results revealed a potential directionality from fatigue to IL-6 to PA that may lead to faster gait speed. Future work should examine these relationships longitudinally to establish temporality and causality.

Conclusions: Our findings support a signal that lowering fatigue and inflammation and increasing physical activity may delay functional decline.
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http://dx.doi.org/10.1007/s40520-021-01923-xDOI Listing
July 2021

What cut-point in gait speed best discriminates community dwelling older adults with mobility complaints from those without? A pooled analysis from the Sarcopenia Definitions and Outcomes Consortium.

J Gerontol A Biol Sci Med Sci 2021 Jun 24. Epub 2021 Jun 24.

University of Florida, Gainesville, FL.

Background: Cut-points to define slow walking speed have largely been derived from expert opinion.

Methods: Study participants (13,589 men and 5,043 women aged ≥65years) had walking speed (m/s) measured over 4-6 meters (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as self-reported any difficulty with walking ~1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not.

Results: Among 5,043 women, CART analysis identified two cut-points, classifying 4,144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13,589 men, CART analysis identified three cut-points, classifying 10,001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2,901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the two slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants.

Conclusions: Cut-points in walking speed of ~0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.
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http://dx.doi.org/10.1093/gerona/glab183DOI Listing
June 2021

Association Between Myocardial Strain and Frailty in CHS.

Circ Cardiovasc Imaging 2021 May 17;14(5):e012116. Epub 2021 May 17.

Department of Epidemiology and Population Health, Stanford University, CA (A.X.T., M.C.O.).

Background: Myocardial strain, measured by speckle-tracking echocardiography, is a novel measure of subclinical cardiovascular disease and may reflect myocardial aging. We evaluated the association between myocardial strain and frailty-a clinical syndrome of lack of physiological reserve.

Methods: Frailty was defined in participants of the CHS (Cardiovascular Health Study) as having ≥3 of the following clinical criteria: weakness, slowness, weight loss, exhaustion, and inactivity. Using speckle-tracking echocardiography data, we examined the cross-sectional (n=3206) and longitudinal (n=1431) associations with frailty among participants who had at least 1 measure of myocardial strain, left ventricular longitudinal strain (LVLS), left ventricular early diastolic strain rate and left atrial reservoir strain, and no history of cardiovascular disease or heart failure at the time of echocardiography.

Results: In cross-sectional analyses, lower (worse) LVLS was associated with prevalent frailty; this association was robust to adjustment for left ventricular ejection fraction (adjusted odds ratio, 1.32 [95% CI, 1.07-1.61] per 1-SD lower strain; =0.007) and left ventricular stroke volume (adjusted OR, 1.32 [95% CI, 1.08-1.61] per 1-SD lower strain; =0.007). In longitudinal analyses, adjusted associations of LVLS and left ventricular early diastolic strain with incident frailty were 1.35 ([95% CI, 0.96-1.89] =0.086) and 1.58 ([95% CI, 1.11-2.27] =0.013, respectively). Participants who were frail and had the worst LVLS had a 2.2-fold increased risk of death (hazard ratio, 2.20 [95% CI, 1.81-2.66]; <0.0001).

Conclusions: In community-dwelling older adults without prevalent cardiovascular disease, worse LVLS by speckle-tracking echocardiography, reflective of subclinical myocardial dysfunction, was associated with frailty. Frailty and LVLS have an additive effect on mortality risk.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.012116DOI Listing
May 2021

Using lipid profiling to better characterize metabolic differences in apolipoprotein E (APOE) genotype among community-dwelling older Black men.

Geroscience 2021 May 15. Epub 2021 May 15.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 North Bellefield Avenue, Room 327, Pittsburgh, PA, 15213, USA.

Apolipoprotein E (APOE) allelic variation is associated with differences in overall circulating lipids and risks of major health outcomes. Lipid profiling provides the opportunity for a more detailed description of lipids that differ by APOE, to potentially inform therapeutic targets for mitigating higher morbidity and mortality associated with certain APOE genotypes. Here, we sought to identify lipids, lipid-like molecules, and important mediators of fatty acid metabolism that differ by APOE among 278 Black men ages 70-81. Using liquid chromatography-mass spectrometry methods, 222 plasma metabolites classified as lipids, lipid-like molecules, or essential in fatty acid metabolism were detected. We applied principal factor analyses to calculate a factor score for each main lipid category. APOE was categorized as ε4 carriers (n = 83; ε3ε4 or ε4ε4), ε2 carriers (n = 58; ε2ε3 or ε2ε2), or ε3 homozygotes (n = 137; ε3ε3). Using analysis of variance, the monoacylglycerol factor, cholesterol ester factor, the factor for triacylglycerols that consist mostly of polyunsaturated fatty acids, sphingosine, and free carnitine significantly differed by APOE (p < 0.05, false discovery rate < 0.30). The monoacylglycerol factor, cholesterol ester factor, and sphingosine were lower, whereas the factor for triacylglycerols that consisted mostly of polyunsaturated fatty acids was higher among ε2 carriers than remaining participants. Free carnitine was lower among ε4 carriers than ε3 homozygotes. Lower monoacylglycerols and cholesteryl esters and higher triacylglycerols that consist mostly of polyunsaturated fatty acids may be protective metabolic characteristics of APOE ε2 carriers, whereas lower carnitine may reflect altered mitochondrial functioning among ε4 carriers in this cohort of older Black men.
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http://dx.doi.org/10.1007/s11357-021-00382-6DOI Listing
May 2021

Estimating Systolic Blood Pressure Intervention Trial Participant Posttrial Survival Using Pooled Epidemiologic Cohort Data.

J Am Heart Assoc 2021 May 6;10(10):e020361. Epub 2021 May 6.

MedStar Washington Hospital Center Washington DC.

Background Intensive systolic blood pressure treatment (<120 mm Hg) in SPRINT (Systolic Blood Pressure Intervention Trial) improved survival compared with standard treatment (<140 mm Hg) over a median follow-up of 3.3 years. We projected life expectancy after observed follow-up in SPRINT using SPRINT-eligible participants in the NHLBI-PCS (National Heart, Lung, and Blood Institute Pooled Cohorts Study). Methods and Results We used propensity scores to weight SPRINT-eligible NHLBI-PCS participants to resemble SPRINT participants. In SPRINT participants, we estimated in-trial survival (<4 years) using a time-based flexible parametric survival model. In SPRINT-eligible NHLBI-PCS participants, we estimated posttrial survival (≥4 years) using an age-based flexible parametric survival model and applied the formula to SPRINT participants to predict posttrial survival. We projected overall life expectancy for each SPRINT participant and compared it to parametric regression (eg, Gompertz) projections based on SPRINT data alone. We included 8584 SPRINT and 10 593 SPRINT-eligible NHLBI-PCS participants. After propensity weighting, mean (SD) age was 67.9 (9.4) and 68.2 (8.8) years, and 35.5% and 37.6% were women in SPRINT and NHLBI-PCS, respectively. Using the NHLBI-PCS-based method, projected mean life expectancy from randomization was 21.0 (7.4) years with intensive and 19.1 (7.2) years with standard treatment. Using the Gompertz regression, life expectancy was 11.2 (2.3) years with intensive and 10.5 (2.2) years with standard treatment. Conclusions Combining SPRINT and NHLBI-PCS observed data likely offers a more realistic estimate of life expectancy than parametrically extrapolating SPRINT data alone. These results offer insight into the potential long-term effectiveness of intensive SBP goals.
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http://dx.doi.org/10.1161/JAHA.120.020361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200698PMC
May 2021

Metabolic Markers Demonstrate the Heterogeneity of Myosteatosis in Community-Dwelling Older Black Men from the Health ABC Study.

Metabolites 2021 Apr 7;11(4). Epub 2021 Apr 7.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Myosteatosis is a complex condition, associated with aging and diverse pathological conditions (e.g., diabetes), that contributes to mobility disability. Improved characterization of myosteatosis is required to develop targeted interventions to maintain muscle health in aging. We first determined the associations between plasma metabolites and intermuscular fat (IMF) in a cross-sectional analysis of 313 older Black men from Health ABC Study. Using partial correlation analysis, 34/350 metabolites were associated with IMF, the majority of which were lipids and organic acids. Next, we used Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), as an indicator of metabolic health to delineate the anthropometric, functional, and metabolic heterogeneity of myosteatosis in a case-control matching analysis. We categorized participants based on their IMF and HOMA-IR levels into: Low-IMF with Low- versus High-HOMA, as well as High-IMF with Low- versus High-HOMA. Among participants with similar levels of IMF, those who were metabolically unhealthy, i.e., with High HOMA-IR, had higher fat and lean mass, muscle strength, and had hyperglycemia, hypertriglyceridemia, hyperinsulinemia, and higher levels of plasma metabolites belonging to diacylglycerols, triacylglycerols, fatty acid and aminoacyl-tRNA biosynthesis pathways versus those with Low HOMA-IR. In summary, HOMA-IR delineates the heterogeneity of myosteatosis by distinguishing metabolically healthy versus unhealthy individuals.
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http://dx.doi.org/10.3390/metabo11040224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067743PMC
April 2021

Remote Research and Clinical Trial Integrity During and After the Coronavirus Pandemic.

JAMA 2021 05;325(19):1935-1936

Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1001/jama.2021.4609DOI Listing
May 2021

Heterogeneity of the Predictive Polygenic Risk Scores for Coronary Heart Disease Age-at-Onset in Three Different Coronary Heart Disease Family-Based Ascertainments.

Circ Genom Precis Med 2021 Jun 12;14(3):e003201. Epub 2021 Apr 12.

Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO (M.F.F., M.K.W., L.W., M.A.P.).

Background: Polygenic risk scores (PRS) for coronary heart disease (CHD) may contribute to assess the overall risk of CHD. We evaluated how PRS may influence CHD risk when the distribution of age-at-onset, sex, and family health history differ significantly.

Methods: Our study included 3 family-based ascertainments: LLFS (Long Life Family Study, N=4572), which represents a low CHD risk, and Family Heart Study, which consists of randomly selected families (FamHS-random, N=1806), and high CHD risk families (FamHS-high risk, N=2301). We examined the effects of PRS, sex, family ascertainment, PRS interaction with sex (PRS*sex) and with family ascertainment (PRS*LLFS and PRS*FamHS-high risk) on CHD, corrected for traditional cardiovascular risk factors using Cox proportional hazard regression models.

Results: Healthy-aging LLFS presented ≈17 years delayed for CHD age-at-onset compared with FamHS-high risk (1.0×10). Sex-specific association (<1.0×10) and PRS*sex (=2.7×10) predicted prevalent CHD. CHD age-at-onset was associated with PRS (hazard ratio [HR], 1.57; =1.3×10), LLFS (HR, 0.54; =2.6×10), and FamHS-high risk (HR, 2.86; =6.70x10) in men, and with PRS (HR, 1.76; =7.70×10), FamHS-high risk (HR, 4.88; =8.70×10), and PRS×FamHS-high risk (HR, 0.61; =3.60×10) in women. In the PRS extreme quartile distributions, CHD age-at-onset was associated (<0.05) with PRS, FamHS-high risk, and PRS interactions with both low and high CHD risk families for women. For men, the PRS quartile results remained similar to the whole distribution.

Conclusions: Differences in CHD family-based ascertainments show evidence of PRS interacting with sex to predict CHD risk. In women, CHD age-at-onset was associated with PRS, CHD family history, and interactions of PRS with family history. In men, PRS and CHD family history were the major effects on the CHD age-at-onset. Understanding the heterogeneity of risks associated with CHD end points at both the personal and familial levels may shed light on the underlying genetic effects influencing CHD and lead to more personalized risk prediction.
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http://dx.doi.org/10.1161/CIRCGEN.120.003201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214825PMC
June 2021

Body composition by computed tomography vs. dual energy x-ray absorptiometry: Long-term prediction of all-cause mortality in the Health ABC cohort.

J Gerontol A Biol Sci Med Sci 2021 Apr 9. Epub 2021 Apr 9.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.

Background: Body composition assessment by computed tomography (CT) predicts health outcomes in diverse populations. However, its performance in predicting mortality has not been directly compared to dual-energy-X-ray-absorptiometry (DXA). Additionally, the association between different body compartments and mortality, acknowledging the compositional nature of human body, is not well-studied. Compositional Data Analysis, that is applied to multivariate proportion-type dataset, may help to account for the inter-relationships of body compartments by constructing log-ratios of components. Here, we determined the associations of baseline CT-based measures of mid-thigh cross-sectional areas vs. DXA measures of body composition with all-cause mortality in Health ABC cohort, using both traditional (individual body compartments) and Compositional Data Analysis (using ratios of body compartments) approaches.

Methods: The Health ABC study assessed body composition in 2911 older adults in 1996-97. We investigated the individual and ratios of (by Compositional Analysis) body compartments assessed by DXA (lean, fat, and bone-mass) and CT (muscle, subcutaneous fat area, intermuscular fat (IMF), and bone) on mortality, using Cox proportional hazard models.

Results: Lower baseline muscle area by CT (HRmen=0.56 [95%CI: 0.48-0.67], HRwomen=0.60 [0.48-0.74]), fat-mass by DXA (HRmen=0.48 [0.24-0.95]) were predictors of mortality in traditional Cox-regression analysis. Consistently, Compositional Data Analysis revealed that lower muscle area vs. IMF, muscle area vs. bone area, and lower fat-mass vs. lean-mass were associated with higher mortality in both sexes.

Conclusion: Both CT measure of muscle area and DXA fat-mass (either individually or relative to other body compartments) were strong predictors of mortality in both sexes in a community research setting.
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http://dx.doi.org/10.1093/gerona/glab105DOI Listing
April 2021

Low protein intake, physical activity, and physical function in European and North American community-dwelling older adults: a pooled analysis of four longitudinal aging cohorts.

Am J Clin Nutr 2021 Jul;114(1):29-41

Population Health Sciences Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom.

Background: Dietary protein may slow the decline in muscle mass and function with aging, making it a sensible candidate to prevent or modulate disability progression. At present, studies providing reliable estimates of the association between protein intake and physical function, and its interaction with physical activity (PA), in community-dwelling older adults are lacking.

Objectives: We investigated the longitudinal relation between protein intake and physical function, and the interaction with PA.

Methods: We undertook a pooled analysis of individual participant data from cohorts in the PROMISS (PRevention Of Malnutrition In Senior Subjects in the European Union) consortium (the Health Aging and Body Composition Study, Quebec Longitudinal Study on Nutrition and Successful Aging, Longitudinal Aging Study Amsterdam, and Newcastle 85+) in which 5725 community-dwelling older adults were followed up to 8.5 y. The relation between protein intake and walking speed was determined using joint models (linear mixed-effects and Cox proportional hazards models) and the relation with mobility limitation was investigated using multistate models.

Results: Higher protein intake was modestly protective of decline in walking speed in a dose-dependent manner [e.g., protein intake ≥1.2 compared with 0.8 g/kg adjusted body weight (aBW)/d: β = 0.024, 95% CI: 0.009, 0.032 SD/y], with no clear indication of interaction with PA. Participants with protein intake ≥0.8 g/kg aBW/d had also a lower likelihood of incident mobility limitation, which was observed for each level of PA. This association seemed to be dose-dependent for difficulty walking but not for difficulty climbing stairs. No associations between protein intake and other mobility limitations transitions were observed.

Conclusions: Higher daily protein intake can reduce physical function decline not only in older adults with protein intake below the current RDA of 0.8 g/kg BW/d, but also in those with a protein intake that is already considered sufficient. This dose-dependent association was observed for each level of PA, suggesting no clear synergistic association between protein intake and PA in relation to physical function.
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http://dx.doi.org/10.1093/ajcn/nqab051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246618PMC
July 2021

Elevated IL-6 and CRP levels are associated with incident self-reported major mobility disability: A pooled analysis of older adults with slow gait speed.

J Gerontol A Biol Sci Med Sci 2021 Apr 5. Epub 2021 Apr 5.

University of Florida, Gainesville, FL.

Background: Elevated Interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter-mile.

Methods: We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (≥68 years; 59% female) with slow gait speed (<1.0m/s). Participants were MMD-free at baseline. IL-6 and CRP were assessed using a central laboratory. The study combined a cohort of community dwelling high-functioning older adults (Health ABC) with two trials of low-functioning adults at risk of MMD (LIFE-P, LIFE). Analyses utilized Poisson regression for absolute MMD incidence and proportional hazards models for relative risk.

Results: We found higher MMD risk per unit increase in log IL-6 [HR=1.26 (95% CI 1.13 to 1.41)]. IL-6 meeting pre-determined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD [HR=1.31 (95% CI: 1.12 to 1.54)]. Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk [HR=1.38 (95% CI: 1.10 to 1.74)]. The CRP effect was more pronounced among participants with elevated IL-6 [HR=1.62 (95% CI: 1.12 to 2.33)] compared to lower IL-6 levels [HR=1.19 (95% CI: 0.85 to 1.66)].

Conclusions: High baseline IL-6 and CRP were associated with increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated.
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http://dx.doi.org/10.1093/gerona/glab093DOI Listing
April 2021

Weight Loss through Lifestyle Intervention Improves Mobility in Older Adults.

Gerontologist 2021 Apr 5. Epub 2021 Apr 5.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background And Objectives: The high prevalence of overweight or obesity in older adults is a public health concern because obesity affects health, including risk of mobility disability.

Research Design And Methods: The Mobility and Vitality Lifestyle Program (MOVE UP), delivered by community health workers (CHW), enrolled 303 community-dwelling adults to assess the impact of a 32-session behavioral weight management intervention. Participants completed the program at 26 sites led by 22 CHWs. Participation was limited to people aged 60-75 who had a BMI 27-45 kg/m 2. The primary outcome was performance on the Short Physical Performance Battery (SPPB) over 12 months.

Results: Participants were age (sd) 67.7 (4.1) and mostly female (87%); 22.7% were racial minorities. The mean (sd) BMI at baseline was 34.7 (4.7). Participants attended a median of 24 of 32 sessions; 240 (80.3%) completed the 9- or 13-month outcome assessment. Median weight loss in the sample was 5% of baseline body weight. SPPB total scores improved by +0.31 units (p < .006), gait speed by +0.04 m/sec (p < .0001), and time to complete chair stands by -0.95 sec (p < .0001). Weight loss ≥ 5% was associated with a gain of +0.73 in SPPB score. Increases in activity (by self-report or device) were not independently associated with SPPB outcomes but did reduce the effect of weight loss.

Discussion And Implications: Promoting weight management in a community group setting may be an effective strategy for reducing risk of disability in older adults.
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http://dx.doi.org/10.1093/geront/gnab048DOI Listing
April 2021

Snoring severity is associated with carotid vascular remodeling in young adults with overweight and obesity.

Sleep Health 2021 Apr 2;7(2):161-167. Epub 2021 Jan 2.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address:

Background: Snoring is often used as a surrogate measure for obstructive sleep apnea (OSA), a sleep disorder associated with cardiovascular disease (CVD) risk. Whether snoring is linked to CVD independent of OSA remains unclear. We aimed to explore the snoring and subclinical CVD association in adults with and without OSA.

Methods: We conducted a cross-sectional study in 122 overweight/obese participants (24% male; mean age 40.1 years) attending the 24-month follow-up visit of a lifestyle intervention. Using home-based objective measures of sleep-disordered breathing, we stratified participants into 3 snoring/OSA categories using the snoring index (SI), a measure of snoring vibration, and oxygen desaturation index (ODI): (1) OSA (ODI ≥ 5), (2) non-OSA heavy snorer (ODI <5, above-median SI), and (3) non-OSA low snorer (ODI <5, below-median SI). Vascular measures including pulse wave velocity ([PWV]; carotid-femoral [cf], femoral-ankle [fa], brachial-ankle [ba]), carotid intima-media thickness (IMT), and carotid interadventitial diameter (IAD) were compared across snoring/OSA categories. Linear regressions assessed the association between snoring and subclinical CVD independent of traditional CVD risk factors.

Results: Compared to non-OSA low snorers, common carotid IMT and IAD were higher in non-OSA heavy snorers, and faPWV, IMT, and IAD were higher among those with OSA. The difference between non-OSA heavy snorers and low snorers persisted after adjusting for age, race, sex, blood pressure, body mass index, lipids, and insulin resistance (P < .05 for IMT and IAD).

Conclusions: In overweight/obese young to middle-aged adults, objectively measured snoring was related to vascular remodeling in those without OSA. Snoring may contribute to CVD risk but warrants further examination in larger prospective cohorts.
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http://dx.doi.org/10.1016/j.sleh.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084936PMC
April 2021

Effect of Aspirin on Activities of Daily Living Disability in Community-Dwelling Older Adults.

J Gerontol A Biol Sci Med Sci 2020 Dec 26. Epub 2020 Dec 26.

Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, PA, U.S.

Background: Cerebrovascular events, dementia and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults.

Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100mg aspirin versus placebo recruited 19,114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the U.S. Six basic ADLs were assessed every six months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after six months. Proportional hazards modelling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk.

Results: Over a median 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 versus 5.3 events/1000py; HR=0.81, 95% CI:0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability there were more deaths in the aspirin group (24 versus 12).

Discussion: Low-dose aspirin in initially healthy older people did not reduce risk of incident ADL disability, although there was evidence of reduced persistent ADL disability.
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http://dx.doi.org/10.1093/gerona/glaa316DOI Listing
December 2020

Chronic kidney disease as a risk factor for peripheral nerve impairment in older adults: A longitudinal analysis of Health, Aging and Body Composition (Health ABC) study.

PLoS One 2020 15;15(12):e0242406. Epub 2020 Dec 15.

University of Pittsburgh, Pittsburgh, PA, United States of America.

Introduction: Sensory and motor nerve deficits are prevalent in older adults and are associated with loss of functional independence. We hypothesize that chronic kidney disease predisposes to worsening sensorimotor nerve function over time.

Materials And Methods: Participants were from the Health, Aging and Body Composition Study (N = 1121) with longitudinal data between 2000-01 (initial visit) and 2007-08 (follow-up visit). Only participants with non-impaired nerve function at the initial visit were included. The predictor was presence of CKD (estimated GFR ≤ 60 ml/min/1.73m2) from the 1999-2000 visit. Peripheral nerve function outcomes at 7-year follow-up were 1) Motor: "new" impairments in motor parameters (nerve conduction velocity NCV < 40 m/s or peroneal compound motor action potential < 1 mv) at follow-up, and 2) Sensory: "new" impairment defined as insensitivity to standard 10-g monofilament or light 1.4-g monofilament at the great toe and "worsening" as a change from light to standard touch insensitivity over time. The association between CKD and "new" or "worsening" peripheral nerve impairment was studied using logistic regression.

Results: The study population was 45.9% male, 34.3% Black and median age 75 y. CKD participants (15.6%) were older, more hypertensive, higher in BMI and had 2.37 (95% CI 1.30-4.34) fold higher adjusted odds of developing new motor nerve impairments in NCV. CKD was associated with a 2.02 (95% CI 1.01-4.03) fold higher odds of worsening monofilament insensitivity. CKD was not associated with development of new monofilament insensitivity.

Conclusions: Pre-existing CKD leads to new and worsening sensorimotor nerve impairments over a 7-year time period in community-dwelling older adults.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242406PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737903PMC
January 2021

Fibroblast growth factor 23 and cognitive impairment: The health, aging, and body composition study.

PLoS One 2020 11;15(12):e0243872. Epub 2020 Dec 11.

Tufts Medical Center, Boston, MA, United States of America.

Background: Concentrations of fibroblast growth factor 23 (FGF-23), a hormone that regulates phosphorus and vitamin D metabolism, increase as kidney function declines. Excess fibroblast growth factor 23 may impact brain function through promotion of vascular disease or through direct effects on neuronal tissue.

Methods: In the Healthy Aging and Body Composition Study, a longitudinal observational cohort of well-functioning older adults, intact serum FGF-23 was assayed in 2,738 individuals. Cognitive function was assessed at baseline and longitudinally at years 3, 5, and 8 by administration of the Modified Mini Mental State Examination (3MSE), a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a test primarily of executive function. The associations between FGF-23 and baseline cognitive function and incident cognitive impairment were evaluated using logistic and Poisson regression respectively, and were adjusted for demographics, baseline estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, comorbidity, and other measures of mineral metabolism including soluble klotho.

Results: The mean (SD) age was 74(3) years, with 51% female, and 39% black. The median (25th, 75th) FGF-23 concentration was 47 pg/mL (37, 60). Three hundred ninety-two individuals had prevalent cognitive impairment by the 3MSE and 461 by the DSST. There was no observed association between FGF-23 and baseline cognitive function for either cognitive test. There were 277 persons with incident cognitive impairment by 3MSE, and 333 persons with incident cognitive impairment by DSST. In fully adjusted models, each two-fold higher concentration of baseline FGF-23 was not associated with incident cognitive impairment by the 3MSE (IRR = 1.02[0.88, 1.19] fully adjusted model) or by the DSST (IRR = 0.98 [0.84, 1.15]. We saw no difference when analyses were stratified by eGFR greater than or less than 60 ml/min/1.73m2.

Conclusion: Intact FGF-23 was not associated with baseline cognitive function or incident cognitive impairment in this cohort well-functioning older adults.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243872PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732072PMC
February 2021

Association of Non-Steroidal Anti-Inflammatory Drugs with Kidney Health in Ambulatory Older Adults.

J Am Geriatr Soc 2021 Mar 10;69(3):726-734. Epub 2020 Dec 10.

Kidney Health Research Collaborative, San Francisco VA Medical Center & University of California, San Francisco, San Francisco, California, USA.

Background/objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) can cause kidney injury, especially in older adults. However, previously reported associations between NSAID use and kidney health outcomes are inconsistent and limited by reliance on serum creatinine-based GFR estimates. This analysis investigated the association of NSAID use with kidney damage in older adults using multiple kidney health measures.

Design: Cross-sectional and longitudinal analyses.

Setting: Multicenter, community-based cohort.

Participants: Two thousand nine hundred and ninty nine older adults in the Health ABC Study. A subcohort (n = 500) was randomly selected for additional biomarker measurements.

Exposure: Prescription and over-the-counter NSAID use ascertained by self-report.

Measurements: Baseline estimated glomerular filtration rate (eGFR) by cystatin C (cysC), urine albumin-to-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) were measured in 2,999 participants; alpha-1 microglobulin (α1m), neutrophil gelatinase-associated lipocalin (NGAL), propeptide type III procollagen (PIIINP), and uromodulin (UMOD) were measured in 500 participants. GFR was estimated three times over 10 years and expressed as percent change per year.

Results: Participants had a mean age of 74 years, 51% were female, and 41% African-American. No eGFR differences were detected between NSAID users (n = 655) and non-users (n = 2,344) at baseline (72 ml/min/1.73 m in both groups). Compared to non-users, NSAID users had lower adjusted odds of having ACR greater than 30 mg/g (0.67; 95% confidence interval (CI) = 0.51-0.89) and lower mean urine IL-18 concentration at baseline (-11%; 95% CI = -4% to -18%), but similar mean KIM-1 (5%; 95% CI = -5% to 14%). No significant differences in baseline concentrations of the remaining urine biomarkers were detected. NSAID users and non-users did not differ significantly in the rate of eGFR decline (-2.2% vs -2.3% per year).

Conclusion: Self-reported NSAID use was not associated with kidney dysfunction or injury based on multiple measures, raising the possibility of NSAID use without kidney harm in ambulatory older adults. More research is needed to define safe patterns of NSAID consumption.
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http://dx.doi.org/10.1111/jgs.16961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021485PMC
March 2021

Association of Midlife Cardiovascular Risk Factors With the Risk of Heart Failure Subtypes Later in Life.

J Card Fail 2021 Apr 22;27(4):435-444. Epub 2020 Nov 22.

Columbia University Irving Medical Center, Columbia University, New York, New York. Electronic address:

Background: Independent associations between cardiovascular risk factor exposures during midlife and later life development of heart failure (HF) with preserved ejection fraction (HFpEF) versus reduced EF (HFrEF) have not been previously studied.

Methods: We pooled data from 4 US cohort studies (Atherosclerosis Risk in Communities, Cardiovascular Health, Health , Aging and Body Composition, and Multi-Ethnic Study of Atherosclerosis) and imputed annual risk factor trajectories for body mass index, systolic and diastolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, and glucose starting from age 40 years. Time-weighted average exposures to each risk factor during midlife and later life were calculated and analyzed for associations with the development of HFpEF or HFrEF.

Results: A total of 23,861 participants were included (mean age at first in-person visit, 61.8 ±1 0.2 years; 56.6% female). During a median follow-up of 12 years, there were 3666 incident HF events, of which 51% had EF measured, including 934 with HFpEF and 739 with HFrEF. A high midlife systolic blood pressure and low midlife high-density lipoprotein cholesterol were associated with HFrEF, and a high midlife body mass index, systolic blood pressure, pulse pressure, and glucose were associated with HFpEF. After adjusting for later life exposures, only midlife pulse pressure remained independently associated with HFpEF.

Conclusions: Midlife exposure to cardiovascular risk factors are differentially associated with HFrEF and HFpEF later in life. Having a higher pulse pressure during midlife is associated with a greater risk for HFpEF but not HFrEF, independent of later life exposures.
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http://dx.doi.org/10.1016/j.cardfail.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987686PMC
April 2021

Relationships Between Level and Change in Sarcopenia and Other Body Composition Components and Adverse Health Outcomes: Findings from the Health, Aging, and Body Composition Study.

Calcif Tissue Int 2021 03 15;108(3):302-313. Epub 2020 Nov 15.

MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.

We investigated how baseline values and rates of decline in components of sarcopenia and other body composition parameters relate to adverse clinical outcomes using the Health, Aging, and Body Composition Study. 2689 participants aged 70-79 years were studied. Appendicular lean mass, whole body fat mass, and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. Baseline values and 2-3 year conditional changes (independent of baseline) in each characteristic were examined as predictors of mortality, hospital admission, low trauma fracture, and recurrent falls in the subsequent 10-14 years using Cox regression (generalized estimating equations used for recurrent falls) with adjustment for sex, ethnicity, age, and potential confounders. Lower levels and greater declines in all parameters (excluding hip BMD level) were associated (p < 0.05) with increased rates of mortality; fully-adjusted hazard ratios per SD lower gait speed and grip strength were 1.27 (95% CI 1.19, 1.36) and 1.14 (1.07, 1.21), respectively. Risk factors of hospital admission included lower levels and greater declines in gait speed and grip strength, and greater declines in hip BMD. Lower levels and greater declines in fat mass and hip BMD were associated with low trauma fracture. Lower gait speed, higher fat mass, and both lower levels and greater declines in grip strength were related to recurrent falls. Lower baseline levels and greater declines in musculoskeletal parameters were related to adverse outcomes. Interventions to maximize peak levels in earlier life and reduce rates of age-related decline may reduce the burden of disease in this age group.
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http://dx.doi.org/10.1007/s00223-020-00775-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881954PMC
March 2021

Total carotenoid intake is associated with reduced loss of grip strength and gait speed over time in adults: The Framingham Offspring Study.

Am J Clin Nutr 2021 02;113(2):437-445

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.

Background: Lower antioxidant serum concentrations have been linked to declines in lean mass and physical function in older adults. Yet population data on the effect of dietary antioxidants on loss of muscle strength and physical function are lacking.

Objective: We sought to determine the association of antioxidant intake [vitamin C, vitamin E, and total and individual carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin)] with annualized change in grip strength and gait speed in adults from the Framingham Offspring study.

Methods: This prospective cohort study included participants with a valid FFQ at the index examination and up to 2 prior examinations and at ≥2 measures of primary outcomes: grip strength (n = 2452) and/or gait speed (n = 2422) measured over 3 subsequent examinations. Annualized change in grip strength (kg/y) and change in gait speed (m/s/y) over the follow-up period were used. Linear regression was used to calculate β coefficients and P values, adjusting for covariates.

Results: Mean ± SD age of participants was 61 ± 9 y (range: 33-88 y). Median intakes (IQR, mg/d) of vitamin C, vitamin E, and total carotenoid across available examinations were 209.2 (133.1-394.2), 27.1 (7.4-199.0), and 15.3 (10.4-21.3), respectively. The mean follow-up time was ∼12 ± 2 y (range: 4.5-15.4 y). In the sex-combined sample, higher intakes of total carotenoids, lycopene, and lutein + zeaxanthin were associated with increased annualized change in grip strength [β (SE) per 10-mg higher intake/d, range: 0.0316 (0.0146) to 0.1223 (0.0603) kg/y)]. All antioxidants except for vitamin C were associated with faster gait speed [β (SE) per 10-mg higher intake/d, range: 0.00008 (0.00004) to 0.0187 (0.0081) m/s/y].

Conclusions: Higher antioxidant intake was associated with increase in grip strength and faster gait speed in this cohort of adults. This finding highlights the need for a randomized controlled trial of dietary antioxidants and their effect on muscle strength and physical function.
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http://dx.doi.org/10.1093/ajcn/nqaa288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851823PMC
February 2021

Reply to: Say What?! Ableist Logic Used in Misguided Attempt to Combat Ageism During COVID-19.

J Am Geriatr Soc 2021 01 17;69(1):48. Epub 2020 Nov 17.

Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida, USA.

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http://dx.doi.org/10.1111/jgs.16934DOI Listing
January 2021

Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients.

BMJ Open 2020 09 29;10(9):e037690. Epub 2020 Sep 29.

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Introduction: As the population ages, there is interest in strategies to promote resiliency, especially for frail patients at risk of its complications. The physiological stress of surgery in high-risk individuals has been proposed both as an important cause of accelerated age-related decline in health and as a model testing the effectiveness of strategies to improve resiliency to age-related health decline. We describe a randomised, embedded, multifactorial, adaptative platform (REMAP) trial to investigate multiple perioperative interventions, the first of which is metformin and selected for its anti-inflammatory and anti-ageing properties beyond its traditional blood glucose control features.

Methods And Analysis: Within a multihospital, single healthcare system, the Core Protocol for Strategies to Promote ResiliencY (SPRY) will be embedded within both the electronic health record (EHR) and the healthcare culture generating a continuously self-learning healthcare system. Embedding reduces the administrative burden of a traditional trial while accessing and rapidly analysing routine patient care EHR data. SPRY-Metformin is a placebo-controlled trial and is the first SPRY domain evaluating the effectiveness of three metformin dosages across three preoperative durations within a heterogeneous set of major surgical procedures. The primary outcome is 90-day hospital-free days. Bayesian posterior probabilities guide interim decision-making with predefined rules to determine stopping for futility or superior dosing selection. Using response adaptative randomisation, a maximum of 2500 patients allows 77%-92% power, detecting >15% primary outcome improvement. Secondary outcomes include mortality, readmission and postoperative complications. A subset of patients will be selected for substudies evaluating the microbiome, cognition, postoperative delirium and strength.

Ethics And Dissemination: The Core Protocol of SPRY REMAP and associated SPRY-Metformin Domain-Specific Appendix have been ethically approved by the Institutional Review Board and are publicly registered. Results will be publicly available to healthcare providers, patients and trial participants following achieving predetermined platform conclusions.

Trial Registration Number: NCT03861767.
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http://dx.doi.org/10.1136/bmjopen-2020-037690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526307PMC
September 2020

Identification of Sarcopenia Components That Discriminate Slow Walking Speed: A Pooled Data Analysis.

J Am Geriatr Soc 2020 07 7;68(7):1419-1428. Epub 2020 Jul 7.

California Pacific Medical Research Institute, San Francisco, California, USA.

Background: The Sarcopenia Definitions and Outcomes Consortium (SDOC) sought to identify cut points for muscle strength and body composition measures derived from dual-energy x-ray absorptiometry (DXA) that discriminate older adults with slow walking speed. This article presents the core analyses used to guide the SDOC position statements.

Design: Cross-sectional data analyses of pooled data.

Setting: University-based research assessment centers.

Participants: Community-dwelling men (n = 13,652) and women: (n = 5,115) with information on lean mass by DXA, grip strength (GR), and walking speed.

Measurements: Thirty-five candidate sarcopenia variables were entered into sex-stratified classification and regression tree (CART) models to agnostically choose variables and cut points that discriminate slow walkers (<0.80 m/s). Models with alternative walking speed outcomes were also evaluated (<0.60 and <1.0 m/s and walking speed treated continuously).

Results: CART models identified GR/body mass index (GRBMI) and GR/total body fat (GRTBF) as the primary discriminating variables for slowness in men and women, respectively. Men with GRBMI of 1.05 kg/kg/m or less were approximately four times more likely to be slow walkers than those with GRBMI of greater than 1.05 kg/kg/m . Women with GRTBF of less than 0.65 kg/kg were twice as likely to be slow walkers than women with GRTBF of 0.65 kg/kg or greater. Models with alternative walking speed outcomes selected only functions of GR as primary discriminators of slowness in both men and women. DXA-derived lean mass measures did not consistently discriminate slow walkers.

Conclusion: GR with and without adjustments for body size and composition consistently discriminated older adults with slowness. CART models did not select DXA-based lean mass as a primary discriminator of slowness. These results were presented to an SDOC Consensus Panel, who used them and other information to develop the SDOC Position Statements. J Am Geriatr Soc 68:1419-1428, 2020.
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http://dx.doi.org/10.1111/jgs.16524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018524PMC
July 2020