Health ABC Research Articles

Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOME® trial

Empagliflozin reduced the risk of cardiovascular (CV) death and heart failure (HF) hospitalizations in patients with type 2 diabetes (T2D) and established CV disease (CVD) in the EMPA-REG OUTCOME® trial. We investigated whether the benefit of empagliflozin was observed across the spectrum of HF risk. Seven thousand and twenty patients with T2D (HbA1c 7-10% and eGFR > 30 mL/min/1.73 m2) were treated with empagliflozin 10 or 25 mg, or placebo once daily and followed for median 3.1 years. In patients without HF at baseline (89.9%), we derived the 5-year risk for incident HF using the 9-variable Health ABC HF Risk score [classified as low-to-average (<10%), high (10-20%), and very high (≥ 20%)]. Overall, 67.2% of the population had low-to-average, 24.2% high, and 5.1% very high 5-year HF risk. Across these groups, the effect on CV death and HF hospitalization with empagliflozin was consistent [hazard ratio 0.71 (95% confidence interval: 0.52, 0.96), 0.52 (0.36, 0.75), and 0.55 (0.30, 1.00), respectively]. Effects on CV death in the ostensibly highest HF risk group (HF at baseline and/or incident HF during the trial) in whom 37.9% of the overall CV deaths occurred, was also beneficial [0.67 (0.47, 0.97)], yet, similar benefits were seen in the lower risk patients. In patients with T2D and established CVD, a sizeable proportion without HF at baseline are at high or very high risk for HF outcomes, indicating the need for active case finding in this patient population. Empagliflozin consistently improved HF outcomes both in patients at low or high HF risk.

AMPLITUDE AND LATENCY OF AUDITORY BRAINSTEM RESPONSES CORRELATE WITH IMPAIRMENT IN ACTIVITIES OF DAILY LIVING IN HEALTHY ELDERS

There is increasing epidemiological evidence showing an association between presbycusis or age-related hearing loss and cognitive decline in elderly people. The Health ABC Study has shown that presbycusis subjects with audiometric hearing thresholds (PTA) worse than 40 dB are more likely to develop cognitive decline. Before the development of audiometric hearing loss, aged subjects could have communication problems, a clinical entity known as hidden hearing loss (HHL). The amplitudes and latencies of auditory brainstem responses (ABR) at supra-thresholds levels have been used as objective measures to detect HHL. Objective: To study whether supra-thresholds ABR responses are associated with impairment in activities of daily living (ADL) in healthy elders. 52 Persons from the ANDES study ≥65 years without dementia (MMSE>24) with normal hearing thresholds (PTA<20dB, n=13), with mild (PTA 20–39dB, n=29) or moderate presbycusis (PTA≥40dB, n=10), were evaluated with a comprehensive neuropsychological assessment, questionnaires of ADL and with auditory measurements including: PTA, and amplitudes and latencies of ABR waves I and V obtained at supra-thresholds levels. Neuropsychological and ADL data were compared between groups of hearing impairment, and lineal regressions between these data and different auditory assessment were performed. Those with moderate presbycusis (n=10) had more perseverative errors in the Wisconsin card sorting task (ANOVA, F(2)=3.4, p=0.04) than the other groups, without any other differences in the neuropsychological or ADL assessment (Table 1). Instrumental ADL impairments were correlated with latencies of bilateral ABR waves V: shopping (right: r=0.44, p=0.001; left: r=0.63, p<0.001), work (right: r=0.33, p=0.02; left: r=0.3, p<0.03) and house hold (right: r=0.29, p=0.04; left: r=0.39, p<0.006). Once excluding those with moderate presbycusis, we found significant correlations in the latencies of left wave V for house hold (r=0.38, p=0.013) and for communication (r=0.36, p=0.019). In addition, the amplitudes of wave I from the left ear were correlated with impairment in traveling (r=-0.40, p=0.013) and technology (r=-0.45, p=0.005). Supra-thresholds ABRs are good predictors of ADL impairments in elderlies without evident cognitive or hearing impairment. These results reinforce the study of other risk factors for cognitive decline in the elderly. Funded by Anillo ACT1403, Fondecyt 1140423, Fondecyt 1161155.

Abstract 2277: Adherence to cancer prevention guidelines and risk of cancer among older white and black adults in the Health ABC Study

Abstract Background: About one-third of cancers can be prevented by healthy lifestyle behaviors. The American Cancer Society (ACS) have guidelines for reducing the risk of cancer by maintaining a healthy body weight, being physically active, eating well and limiting alcohol. Few studies have examined adherence to cancer preventive behavior and subsequent cancer risk in older populations that are inclusive of men, women and minorities. Methods: We evaluated adherence to ACS cancer prevention guidelines and subsequent risk of all incident cancer in the Health, Aging and Body Composition Study. The population included 2,124 white and black men and women aged 71-80 years who were initially free of cancer at baseline (1998-1999). Adherence to ACS guidelines was scored from 0 (lowest adherence) to 8 (greatest adherence). Maintenance of healthy body weight was determined from body mass index at ages 25 and 50 (recalled at baseline) and measured height and weight at baseline. Physical activity and alcohol intake were assessed by questionnaire. Diet was assessed by food frequency questionnaire (servings of fruits and vegetables, the ratio of whole grains to refined grains and intake of red meat and processed meats). Incident cancer (all types except non-melanoma skin cancer) was confirmed from pathology reports when available, or medical records and death certificates. Risk of cancer was determined with cox regression adjusted for gender, age and study site. Participants with the lowest adherence to ACS guidelines were the referent. Results: The lowest adherence category (scores 0-2) had 297 participants (14% of all participants), 1,316 (62%) were in the moderate adherence category (scores 3-5), and 511 (24%) were in the highest adherence category (scores 6-8). Adherence was lower among men (P&amp;lt;0.001), black (P&amp;lt;0.001) and older participants (P&amp;lt;0.01). After a median follow-up of 12.5 years, 517 people developed incident cancer. Participants with moderate adherence had a 23% lower risk of cancer [HR=0.77, 95% CI=0.60-0.97]. Participants with the greatest adherence had a 26% lower risk of cancer [HR=0.74, 95% CI=0.56-0.98]. Conclusions: Only 1 in 4 older adults closely followed healthy lifestyle behaviors outlined by the ACS for cancer prevention. Greater adherence to recommendations was associated with lower likelihood of total cancer in older white and black adults. Public health efforts to increase preventive lifestyle behaviors may be particularly needed among men, black and older individuals. Citation Format: Audrey Y. Jung, Christina Gu, Iva Milijkovic, Susan Rubin, Suzanne Satterfield, Stephen B. Kritschevsky, Heidi Klepin, Anne B. Newman, Jane Cauley, Hilsa Ayonayon, Tamara B. Harris, Rachel A. Murphy. Adherence to cancer prevention guidelines and risk of cancer among older white and black adults in the Health ABC Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2277. doi:10.1158/1538-7445.AM2017-2277

FALL INJURIES IN OLDER MEN AND WOMEN: NOVEL ASSESSMENTS AND PREDICTORS

AbstractFalls are associated with reduced physical function in older adults. However few large epidemiologic cohort studies have characterized fall injuries that were self-treated or all injuries treated in outpatient and inpatient settings. The Study of Osteoporotic Fractures in Men (MrOS) is an ongoing cohort of ambulatory men (N=5,994; 10% minorities; 2000–02 enrollment) aged ≥65 years at 6 U.S. sites. The Study of Women’s Health Across the Nation (SWAN; N=3,302; 53% minority; 1996 enrollment) is an ongoing multi-racial/ethnic cohort of women from 7 U.S. sites followed through menopausal transition for 20 years and now in early old age. The Health, Aging and Body Composition (Health ABC) Study enrolled well-functioning, ambulatory Medicare beneficiaries, aged 70–79 years (N=3,075; 52% women, 42% black) at 2 U.S. sites in 1997–98. Each study collected self-reported falls and fall injuries, including non-fracture and fracture injuries. Additionally Health ABC linked Medicare Fee-For-Service claims from denominator, inpatient, outpatient, physician/supplier, and carrier files to treated fall injuries and fractures over 8 years. Perceived fatigue levels will be associated with fall risk in MrOS men (Welburn). Sensory peripheral nerve impairments will be described as fall and fall injury risk factors in SWAN women (Ylitalo). Quadriceps strength will be related to incident fall injuries in Health ABC (Winger). Medicare payments will be compared pre- vs. post-injury for non-fracture and fracture fall injuries in Health ABC (Strotmeyer). The Discussant (Buchner) will focus on the importance of all fall injuries, including self- or outpatient-treated, as these may be early signs of late life decline.

DIABETES, IMPAIRED FASTING GLUCOSE, AND FALL INJURY RISK IN OLDER ADULTS: THE HEALTH ABC STUDY

Diabetes increases fall and fracture risk, but the association of impaired fasting glucose (IFG) with treated fall injuries is unknown. We assessed diabetes (diagnosed/treated and/or FG≥126 mg/dl) and IFG (FG≥100 mg/dl) in Cox Proportional Hazard models for fall injury from linked Medicare Fee-For-Service claims over 8.6 ± 3.3 years in Health ABC (n=2363, age 73.5 ± 2.8 years, 52% women, 38% black, 18% IFG, 17% diabetes). Fall injuries (n=680; 29%) were 76% fractures and 24% non-fracture fall injuries. After adjusting for demographic/lifestyle, medication and comorbidity factors, IFG had lower non-fracture fall injury risk vs. normal glycemia (HR 0.59, 95%CI: 0.35–0.97). Diabetes had higher non-fracture fall injury risk vs. IFG (HR 2.06, 1.15–3.68), though no association existed vs. normal glycemia. No association existed for glycemic status and total fall injury or fracture risk. Non-fracture fall injury risk differs by glycemic status. Further investigation is necessary to understand the mechanism of IFG and fall injury risk.

MYOSTATIN IN OLDER ADULTS: THE HEALTH, AGING, AND BODY COMPOSITION (HEALTH ABC) STUDY

Myostatin (also known as GDF8) is a negative regulator of muscle development and size. We tested the hypothesis that higher myostatin levels are associated with reduced lean mass, deceased muscle density, lower strength and slower walking speed in older adults. We used data from 399 randomly selected men and women (mean±SD age: 78.3 ± 2.8 years) participating in the Year 6 visit of Health ABC Study. Myostatin was detected in previously frozen serum using a validated sandwich ELISA with proprietary antibodies specific to myostatin (Eli Lilly). Muscle and function variables included appendicular lean mass assessed by whole body DXA; thigh cross-sectional area and muscle density by QCT; walking speed by usual pace over 6 meters; and grip strength by Jamar dynamometers. Ordinary least squares regression models (adjusted for age, BMI, race, sex and self-rated health) were used to calculate adjusted mean levels of the muscle and function variables across quartiles of myostatin. We tested for interactions between myostatin and sex, and myostatin and race using linear regression. In adjusted models, mean muscle density values increased as myostatin quartile increased (p for trend 0.10 for all). There was no evidence for any interaction tested (p for interaction >0.10 for all). In conclusion, myostatin levels were unrelated to measures of muscle size and physical function; the association between myostatin levels and muscle density was modest and opposite of the hypothesized direction.

Associations of Musculoskeletal Pain With Mobility in Older Adults: Potential Cerebral Mechanisms.

Musculoskeletal pain is highly prevalent and limits mobility in older adults. A potential mechanism by which pain affects mobility could be through its negative impact on the brain. We examined whether structural integrity of cerebral gray and white matter (WM) mediated the relationship between pain and mobility in community-dwelling older adults. Musculoskeletal pain, gait speed, and neuroimaging data were obtained concurrently from the Health ABC study (mean age = 83/56% female, n = 212). Microstructural gray matter integrity was measured by mean diffusivity (MD), WM microstructure and macrostructure were measured by fractional anisotropy (FA) and WM hyperintensities (WMH), respectively. Regression models were adjusted for gray matter atrophy, age, gender, medication use, and obesity. Bootstrapped mediation methods were used (1,000 bootstrapped samples, 95% confidence intervals). The associations of musculoskeletal pain with WMH (β = .19, p < .05) and FA (β = -.18, p < .05) were robust to adjustment for gender, medication use, age, body mass index (BMI), and brain atrophy. Participants who experienced both knee and back pain had a significantly slower gait speed (~0.11 m/s) than those without knee or back pain (p < .05) independent of gender, medication, age, and BMI. WMH and FA significantly mediated the pain-gait speed relationship. Associations between pain and MD were not significant, and MD did not modify the association between pain and gait speed. Cerebral WM integrity may contribute to the detrimental effects of musculoskeletal pain on mobility, although pre-existing WM integrity may also simultaneously amplify pain and decrease mobility. Future studies are needed to further understand whether successful pain management may significantly improve both brain health and mobility.

The Prevalence of Anosmia and Associated Factors Among U.S. Black and White Older Adults.

Olfactory impairment is common among older adults; however, data are largely limited to whites. We conducted pooled analyses of two community-based studies: the Atherosclerosis Risk in Communities study (ARIC, 1,398 blacks and 4,665 whites), and the Health, Aging, and Body Composition study (Health ABC, 958 blacks and 1,536 whites) to determine the prevalence of anosmia and associated factors for black and white older adults in the United States. The overall prevalence of anosmia was 22.3% among blacks and 10.4% among whites. Blacks had a markedly higher odds of anosmia compared to whites in age and sex adjusted analyses (odds ratio [OR] 2.96, 95% confidence interval [CI] = 2.59-3.38). In both blacks and whites, higher anosmia prevalence was associated with older age and male sex. The highest prevalence was found in black men 85 years or older (58.3%), and the lowest in white women aged 65-69 years (2.4%). Higher education level, lower cognitive score, ApoE ε4, daytime sleepiness, poorer general health status, lower body mass index, and Parkinson disease were associated with higher prevalence of anosmia in one or both races. However, the racial difference in anosmia remained statistically significant after adjusting for these factors (fully adjusted OR = 1.76, 95%CI: 1.50-2.07). Results were comparable between the two cohorts. Anosmia is common in older adults, particularly among blacks. Further studies are needed to identify risk factors for anosmia and to investigate racial disparities in this sensory deficit.

Risk for Incident Heart Failure: A Subject-Level Meta-Analysis From the Heart "OMics" in AGEing (HOMAGE) Study.

BackgroundTo address the need for personalized prevention, we conducted a subject‐level meta‐analysis within the framework of the Heart “OMics” in AGEing (HOMAGE) study to develop a risk prediction model for heart failure (HF) based on routinely available clinical measurements.Methods and ResultsThree studies with elderly persons (Health Aging and Body Composition [Health ABC], Valutazione della PREvalenza di DIsfunzione Cardiaca asinTOmatica e di scompenso cardiaco [PREDICTOR], and Prospective Study of Pravastatin in the Elderly at Risk [PROSPER]) were included to develop the HF risk function, while a fourth study (Anglo‐Scandinavian Cardiac Outcomes Trial [ASCOT]) was used as a validation cohort. Time‐to‐event analysis was conducted using the Cox proportional hazard model. Incident HF was defined as HF hospitalization. The Cox regression model was evaluated for its discriminatory performance (area under the receiver operating characteristic curve) and calibration (Grønnesby‐Borgan χ2 statistic). During a follow‐up of 3.5 years, 470 of 10 236 elderly persons (mean age, 74.5 years; 51.3% women) developed HF. Higher age, BMI, systolic blood pressure, heart rate, serum creatinine, smoking, diabetes mellitus, history of coronary artery disease, and use of antihypertensive medication were associated with increased HF risk. The area under the receiver operating characteristic curve of the model was 0.71, with a good calibration (χ2 7.9, P=0.54). A web‐based calculator was developed to allow easy calculations of the HF risk.ConclusionsSimple measurements allow reliable estimation of the short‐term HF risk in populations and patients. The risk model may aid in risk stratification and future HF prevention strategies.

Circulating Vitamin K Is Inversely Associated with Incident Cardiovascular Disease Risk among Those Treated for Hypertension in the Health, Aging, and Body Composition Study (Health ABC)

Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational studies found that low circulating phylloquinone (vitamin K-1) was associated with increased CAC progression, especially in persons treated for hypertension. It is unknown whether hypertension treatment modifies this putative role of vitamin K in clinical CVD risk.Objective: We determined the association between vitamin K status and incident clinical CVD in older adults in the Health ABC (Health, Aging, and Body Composition Study) and whether the association differed by hypertension treatment status.Methods: Plasma phylloquinone was measured in 1061 participants free of CVD (70-79 y of age, 58% women, 39% black). Plasma uncarboxylated MGP [(dp)ucMGP] was measured in a subset of 635 participants. Multivariate Cox models estimated the HR for incident CVD over 12.1 follow-up years. Effect modification by hypertension was tested with the use of interaction terms.Results: Neither low plasma phylloquinone (<0.2 nmol/L) nor elevated (dp)ucMGP (≥574 pmol/L) was significantly associated with incident CVD [respective HRs (95% CIs): 1.27 (0.75, 2.13) and 1.02 (0.72, 1.45)]. In participants treated for hypertension (n = 489; 135 events), low plasma phylloquinone was associated with higher CVD risk overall (HR: 2.94; 95% CI: 1.41, 6.13). In those with untreated hypertension (n = 153; 48 events) and without hypertension (n = 418; 92 events), low plasma phylloquinone was not associated with incident CVD. The association between high (dp)ucMGP did not differ by hypertension treatment status (P-interaction = 0.72).Conclusions: Vitamin K status was not significantly associated with CVD risk overall, but low plasma phylloquinone was associated with a higher CVD risk in older adults treated for hypertension. Additional evidence from larger clinical studies is needed to clarify the importance of vitamin K to CVD in persons treated for hypertension, a segment of the population at high risk of clinical CVD events.

Modeling the shape and composition of the human body using dual energy X-ray absorptiometry images.

There is growing evidence that body shape and regional body composition are strong indicators of metabolic health. The purpose of this study was to develop statistical models that accurately describe holistic body shape, thickness, and leanness. We hypothesized that there are unique body shape features that are predictive of mortality beyond standard clinical measures. We developed algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans into body thickness and leanness images. We performed statistical appearance modeling (SAM) and principal component analysis (PCA) to efficiently encode the variance of body shape, leanness, and thickness across sample of 400 older Americans from the Health ABC study. The sample included 200 cases and 200 controls based on 6-year mortality status, matched on sex, race and BMI. The final model contained 52 points outlining the torso, upper arms, thighs, and bony landmarks. Correlation analyses were performed on the PCA parameters to identify body shape features that vary across groups and with metabolic risk. Stepwise logistic regression was performed to identify sex and race, and predict mortality risk as a function of body shape parameters. These parameters are novel body composition features that uniquely identify body phenotypes of different groups and predict mortality risk. Three parameters from a SAM of body leanness and thickness accurately identified sex (training AUC = 0.99) and six accurately identified race (training AUC = 0.91) in the sample dataset. Three parameters from a SAM of only body thickness predicted mortality (training AUC = 0.66, validation AUC = 0.62). Further study is warranted to identify specific shape/composition features that predict other health outcomes.

Association of Holter-Derived Heart Rate Variability Parameters With the Development of Congestive Heart Failure in the Cardiovascular Health Study

ObjectivesThis study sought to determine whether Holter-based parameters of heart rate variability (HRV) are independently associated with incident heart failure among older adults in the CHS (Cardiovascular Health Study) as evidenced by an improvement in the predictive power of the Health Aging and Body Composition Heart Failure (Health ABC) score. BackgroundAbnormal HRV, a marker of autonomic dysfunction, has been associated with multiple adverse cardiovascular outcomes but not the development of congestive heart failure (CHF). MethodsAsymptomatic CHS participants with interpretable 24-h baseline Holter recordings were included (n = 1,401). HRV measures and premature ventricular contraction (PVC) counts were compared between participants with (n = 260) and without (n = 1,141) incident CHF on follow-up. Significantly different parameters between groups were added to the components of the Health ABC score, a validated CHF prediction tool, using stepwise Cox regression. ResultsThe final model included components of the Health ABC score, In PVC counts (adjusted hazard ratio [aHR]: 1.12; 95% confidence interval [CI]: 1.07 to 1.19; p < 0.001) and the following HRV measures: abnormal heart rate turbulence onset (aHR: 1.52; 95% CI: 1.11 to 2.08; p = 0.009), short-term fractal scaling exponent (aHR: 0.27; 95% CI: 0.14 to 0.53; p < 0.001), in very low frequency power (aHR: 1.28; 95% CI: 1.02 to 1.60; p = 0.037), and coefficient of variance of N-N intervals (aHR: 0.94; 95% CI: 0.90 to 0.99; p = 0.009). The C-statistic for the final model was significantly improved over the Health ABC model alone (0.77 vs. 0.73; p = 0.0002). ConclusionsAbnormal HRV parameters were significantly and independently associated with incident CHF in asymptomatic, older adults. When combined with increased PVCs, HRV improved the predictive power of the Health ABC score.

Predictors of Cardiovascular Health in Older Adults: a Regression Tree Analysis

BackgroundCardiovascular health is central to overall health. Studies on predictors of cardiovascular health in older adults have not fully considered potential interactions among predictor variables.ObjectiveThe purpose of this study was to determine the relationships of lifestyle behaviors and body composition with cardiovascular health in older adults while accounting for potential interactions among lifestyle behaviors, measures of body composition and socio demographic characteristics.MethodsThe Health, Aging and Body Composition (Health ABC)Study is a prospective cohort study of 3,075 adults aged 70 to 79 at baseline. The Generalized, Unbiased, Interaction Detection and Estimation (GUIDE) algorithm for regression tree analysis was used to predict measures of cardiovascular health, including high‐density lipoprotein (HDL) cholesterol, interleukin‐6 (IL‐6), homeostasis model assessment of insulin resistance (HOMA‐IR), and systolic blood pressure (SBP), of Health ABC participants based on their lifestyle behaviors, measures of body composition and socio demographic characteristics.ResultsParticipants with the highest mean HDL cholesterol had trunk lean mass ≤21.6 kg and abdominal visceral fat ≤96.2 cm2, while those with the lowest HDL cholesterol had trunk lean mass &gt;27.8 kg. Persons with the lowest IL‐6 had a sagittal diameter ≤24.7 cm (or had missing values for sagittal diameter) and flossed their teeth at least 3 times per week, while those with the highest IL‐6 had a sagittal diameter &gt;24.7 cm. Persons with the lowest HOMA‐IR had a BMI ≤27.4 kg/m2 (or had missing values for BMI), while those with the highest HOMA‐IR had a BMI &gt;27.4 kg/m2 and a sagittal diameter &gt;27.1 cm. Participants with the lowest SBP were those who were not on (or had missing data on) blood pressure medication, were from the Memphis clinical site and were white, while those with the highest SBP were those on high blood pressure medication from the Pittsburgh site.ConclusionThis study provides further evidence that abdominal adiposity is strongly linked to cardiovascular risk in older adults and supports the use of sagittal diameter as an indicator of cardiovascular health. It also suggests a strong inverse relationship between lean body mass and HDL cholesterol, which warrants further investigation.Support or Funding InformationThis research is supported by USDA‐ARS Specific Cooperative Agreement 8040‐53000‐018‐08. This study is also supported in part by National Institute on Aging (NIA) Contracts N01‐AG‐6‐2101;N01‐AG‐6‐2103; N01‐AG‐6‐2106; NIA grant R01‐AG028050, NINR grant R01‐NR012459, and by the Intramural Research Program of the NIH, NIA.

(439) Pain and Function in Older Black and White Adults: a Secondary Analysis of the Health ABC Study

(439) Pain and Function in Older Black and White Adults: a Secondary Analysis of the Health ABC Study

Are Preferences for Aggressive Medical Treatment Associated with Healthcare Utilization in the Very Old?

Objectives: To examine the relationship between end-of-life (EOL) treatment preferences and recent hospitalization or emergency department (ED) care in the very old. Design: Quarterly telephone follow-up of participants in the EOL in the Very Old cohort. Setting: The EOL in the Very Old Age cohort drew from 1403 participants in the Health, Aging, and Body Composition (Health ABC) study who were alive in year 15 of follow-up. 87.5% (n = 1227) were successfully recontacted and enrolled. Participants: Preferences for treatment at the EOL and reported hospital and ED use were examined for 1118 participants (18% involving proxy reports) over 6 months, 1021 (16% with proxy reports) over 12 months, and 945 (23% with proxy reports) over 18 months in 6-month intervals. Measurements: Preferences for eight EOL treatments, elicited once each year; hospitalization and ED use reported every six months. Results: Preferences for more aggressive treatment (endorsing ≥5 of 8 options) were not significantly associated with inpatient or ED treatment. Inpatient and ED treatment were not associated with changes in preferences for aggressive EOL treatment over 12 months. Conclusion: Alternative measures that tap attitudes toward routine care, rather than EOL treatment preferences, may be more highly associated with healthcare utilization.

Protein Intake and Mobility Limitation in Community-Dwelling Older Adults: the Health ABC Study.

The current Recommended Dietary Allowance (RDA) for protein is based on short-term nitrogen balance studies in young adults and may underestimate the amount needed to optimally preserve physical function in older adults. We examined the association between protein intake and the onset of mobility limitation over 6 years of follow-up in older adults in the Health ABC study. Prospective cohort study. Memphis, Tennessee and Pittsburgh, Pennsylvania. Community-dwelling, initially well-functioning adults aged 70-79 years (n = 1998). Protein intake (g/kg body weight/d) was calculated using an interviewer-administered 108-item food frequency questionnaire at baseline. Mobility limitation was assessed semi-annually and defined as reporting any difficulty walking one-quarter of a mile or climbing 10 steps on 2 consecutive 6-month contacts. The association between protein intake and incident mobility limitation was examined using Cox proportional hazard regression models adjusting for demographics, behavioral characteristics, chronic conditions, total energy intake, and height. Mean (SD) protein intake was 0.91 (0.38) g/kg body weight/d, with 43% reporting intakes less than the RDA (0.8 g/kg body weight/d). During 6 years of follow-up, 705 participants (35.3%) developed mobility limitations. Compared to participants in the upper tertile of protein intake (≥1.0 g/kg body weight/d), participants in the lower two tertiles of protein intake (<0.7 and 0.7 -<1.0 g/kg body weight/d) were at greater risk of developing mobility limitation over 6 years of follow-up (RR (95% CI): 1.86 (1.41-2.44) and 1.49 (1.20-1.84), respectively). Lower protein intake was associated with increased risk of mobility limitation in community-dwelling, initially well-functioning older adults. These results suggest that protein intakes of ≥1.0 g/kg body weight/d may be optimal for maintaining physical function in older adults.

Genetic association analysis of polymorphisms in PSD3 gene with obesity, type 2 diabetes, and HDL cholesterol.

The pleckstrin and Sec7 domain-containing 3 (PSD3) gene has been linked to immune diseases. We examined whether the genetic variants within the PSD3 gene are associated with obesity, type 2 diabetes (T2D), and high-density lipoprotein (HDL) cholesterol level. Multiple logistic regression model and linear regression model were used to examine the associations of 259 single nucleotide polymorphisms (SNPs) within the PSD3 gene with obesity and T2D as binary traits, and HDL level as a continuous trait using the Marshfield data, respectively. A replication study of obesity was conducted using the Health Aging and Body Composition (Health ABC) sample. 23SNPs were associated with obesity (p<0.05) in the Marshfield sample and rs4921966 revealed the strongest association (p=3.97×10-6). Of the 23SNPs, 20 were significantly associated with obesity in the meta-analysis of two samples (p<0.05). Furthermore, 6SNPs revealed associations with T2D in the Marshfield data (top SNP rs12156368 with p=3.05×10-3); while two SNPs (rs6983992 and rs7843239) were associated with both obesity and T2D (p=0.0188 and 0.023 for obesity and p=8.47×10-3 and 0.0128 for T2D, respectively). Furthermore, 11SNPs revealed associations with HDL level (top SNP rs13254772 with p=2.79×10-3) in the Marshfield data; meanwhile rs7009615 was associated with both T2D (p=0.038) and HDL level (p=4.44×10-3). In addition, haplotype analyses further supported the results of single SNP analysis. Common variants in PSD3 were associated with obesity, T2D and HDL level. These findings add important new insights into the pathogenesis of obesity, T2D and HDL cholesterol.

Information for CME Credit— Exercise Capacity, Heart Failure Risk, and Mortality in Older Adults: The Health ABC Study

Information for CME Credit— Exercise Capacity, Heart Failure Risk, and Mortality in Older Adults: The Health ABC Study

Clinical Implications

HomeHypertensionVol. 69, No. 2Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Feb 2017https://doi.org/10.1161/HYPERTENSIONAHA.116.08941Hypertension. 2017;69:197Arterial Stiffness and Risk of Heart Failure Subtypes (p 267)Download figureDownload PowerPointHigher measures of arterial stiffness are associated with increased risk of atherosclerotic cardiovascular disease and mortality. However, the contribution of higher arterial stiffness toward risk of heart failure (HF) and its subtypes, HF with preserved ejection fraction and HF with reduced ejection fraction, independent of other established risk factors, is not well studied. In this study, we evaluated the association between arterial stiffness measured as carotid-femoral pulse wave velocity and risk of HF outcomes among participants of the Health ABC study (Health, Aging, and Body Composition). We observed that higher carotid-femoral pulse wave velocity was associated with greater risk of overall HF and its subtypes, HF with preserved ejection fraction and HF with reduced ejection fraction. However, these associations were attenuated substantially and not significant after adjustment for prevalent cardiovascular disease and its risk factors. These findings suggest that the higher incidence of HF outcomes among patients with higher carotid-femoral pulse wave velocity seems to be related to the greater burden of cardiovascular disease and its risk factors. Thus, higher carotid-femoral pulse wave velocity is an intermediate phenotype observed in at-risk individuals, but it may not contribute to the development of HF independent of other risk factors. Future studies are needed to determine if aggressive risk factor modification may lower the risk of HF among individuals with higher carotid-femoral pulse wave velocity.Uric Acid Lowering and Endothelial Function (p 243)Hypertension represents a staggering public health burden. Elevated serum uric acid levels (≥5.0 mg/dL) have been associated with endothelial dysfunction, a precursor mechanism in the development of hypertension. Lowering uric acid in a population at a higher risk of developing hypertension could potentially improve endothelial function and thereby prevent the development of hypertension. We conducted a randomized, double-blind, placebo-controlled trial in which 47, 49, and 53 overweight/obese, nonhypertensive participants received probenecid, allopurinol, and matching placebo, respectively. Neither probenecid nor allopurinol improved endothelial-dependent vasodilation (a measure of endothelial function) by brachial artery ultrasound (endothelial-dependent vasodilation 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks with probenecid; 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks with allopurinol; 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks with placebo; Figure), despite effective uric acid lowering. Our findings do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for the development of hypertension.Download figureDownload PowerPoint(Pro)Renin Receptor and Fructose-Induced Salt Sensitivity (p 339)Download figureDownload PowerPointFructose is a principal source of added sugar in our diet, such as in sugar-sweetened beverages. The consumption of fructose in the human diet has dramatically increased, coinciding with the epidemics of obesity and metabolic syndrome. Experimental evidence demonstrates that high fructose (HF) intake induces salt-sensitive hypertension, but the underlying mechanism largely remains elusive. The goal of the present study was to examine the role of (pro)renin receptor in HF-induced salt-sensitive hypertension. We tested whether a xanthine oxidase inhibitor allopurinol and a (pro)renin receptor decoy inhibitor PRO20 attenuated the development of salt-sensitive hypertension after HF intake. Radiotelemetry demonstrated that mean arterial pressure was 10 mm Hg higher in rats from HF-fed group receiving high salt diet that contained 8% NaCl compared with the control group rats, and this increase was completely blocked by allopurinol or PRO20 treatment (Figure). HF intake induced urinary renin activity and renal expression of Na+ transporters such as NKCC2 and NHE3, all of which were blunted by allopurinol or PRO20. We conclude that (1) (pro)renin receptor–dependent activation of intrarenal renin–angiotensin system and renal Na+ transporters underlies enhanced salt sensitivity induced by HF intake, (2) the activity of intrarenal renin–angiotensin system may predict the development of hypertension in patients with HF intake, and (3) our study calls for future clinical evaluation of allopurinol and PRO20 for their antihypertensive action in patients with HF-induced salt-sensitive hypertension. Previous Back to top Next FiguresReferencesRelatedDetails February 2017Vol 69, Issue 2 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.116.08941 Originally publishedFebruary 1, 2017 PDF download Advertisement

Arterial Stiffness and Risk of Overall Heart Failure, Heart Failure With Preserved Ejection Fraction, and Heart Failure With Reduced Ejection Fraction: The Health ABC Study (Health, Aging, and Body Composition).

Higher arterial stiffness is associated with increased risk of atherosclerotic events. However, its contribution toward risk of heart failure (HF) and its subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), independent of other risk factors is not well established. In this study, we included Health ABC study (Health, Aging, and Body Composition) participants without prevalent HF who had arterial stiffness measured as carotid-femoral pulse wave velocity (cf-PWV) at baseline (n=2290). Adjusted Cox-proportional hazards models were constructed to determine the association between continuous and data-derived categorical measures (tertiles) of cf-PWV and incidence of HF and its subtypes (HFpEF [ejection fraction >45%] and HFrEF [ejection fraction ≤45%]). We observed 390 HF events (162 HFpEF and 145 HFrEF events) over 11.4 years of follow-up. In adjusted analysis, higher cf-PWV was associated with greater risk of HF after adjustment for age, sex, ethnicity, mean arterial pressure, and heart rate (hazard ratio [95% confidence interval] for cf-PWV tertile 3 versus tertile 1 [ref] =1.35 [1.05-1.73]). However, this association was not significant after additional adjustment for other cardiovascular risk factors (hazard ratio [95% confidence interval], 1.14 [0.88-1.47]). cf-PWV velocity was also not associated with risk of HFpEF and HFrEF after adjustment for potential confounders (most adjusted hazard ratio [95% confidence interval] for cf-PWV tertile 3 versus tertile 1 [ref]: HFpEF, 1.06 [0.72-1.56]; HFrEF, 1.28 [0.83-1.97]). In conclusion, arterial stiffness, as measured by cf-PWV, is not independently associated with risk of HF or its subtypes after adjustment for traditional cardiovascular risk factors.