The association of peripheral neuropathy detected by monofilament testing with risk of falls and fractures in older adults.

BACKGROUND: In persons with diabetes, annual screening for peripheral neuropathy (PN) using monofilament testing is the standard of care. However, PN detected by monofilament testing is common in older adults, even in the absence of diabetes. We aimed to assess the association of PN with risk of falls and fractures in older adults. METHODS: We included participants in the Atherosclerosis Risk in Communities (ARIC) Study who underwent monofilament testing at visit 6 (2016-2017). Incident falls and fractures were identified based on ICD-9 and ICD-10 codes from active surveillance of all hospitalizations and linkage to Medicare claims. We used Cox models to assess the association of PN with falls and fractures (combined and as separate outcomes) after adjusting for demographics and risk factors for falls. RESULTS: There were 3617 ARIC participants (mean age 79.4 [SD 4.7] years, 40.8% male, and 21.4% Black adults), of whom 1242 (34.3%) had PN based on monofilament testing. During a median follow-up of 2.5 years, 371 participants had a documented fall, and 475 participants had a documented fracture. The incidence rate (per 1000 person-years) for falls or fractures for participants with PN versus those without PN was 111.1 versus 74.3 (p < 0.001). The age-, sex-, and race-adjusted 3-year cumulative incidence of incident fall or fracture was significantly higher for participants with PN versus those without PN (26.5% vs. 18.4%, p < 0.001). After adjusting for demographics, PN remained independently associated with falls and fractures (HR 1.48, 95% CI 1.26, 1.74). Results were similar for models including traditional risk factors for falls, when falls and fractures were analyzed as separate outcomes, and after adjustment for competing risk of death. CONCLUSIONS: PN, as measured by monofilament testing, is common in older adults and associated with risk of falls and fracture. Screening with monofilament testing may be warranted to identify older adults at high risk for falls.

Performance of High-Sensitivity Cardiac Troponin Assays to Reflect Comorbidity Burden and Improve Mortality Risk Stratification in Older Adults With Diabetes.

OBJECTIVE: Incorporation of comorbidity burden to inform diabetes management in older adults remains challenging. High-sensitivity cardiac troponins are objective, quantifiable biomarkers that may improve risk monitoring in older adults. We assessed the associations of elevations in high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) with comorbidities and improvements in mortality risk stratification. RESEARCH DESIGN AND METHODS: We used logistic regression to examine associations of comorbidities with elevations in either troponin (≥85th percentile) among 1,835 participants in the Atherosclerosis Risk in Communities (ARIC) Study with diabetes (ages 67-89 years, 43% male, 31% black) at visit 5 (2011-2013). We used Cox models to compare associations of high cardiac troponins with mortality across comorbidity levels. RESULTS: Elevations in either troponin (≥9.4 ng/L for hs-cTnI, ≥25 ng/L for hs-cTnT) were associated with prevalent coronary heart disease, heart failure, chronic kidney disease, pulmonary disease, hypoglycemia, hypertension, dementia, and frailty. Over a median follow-up of 6.2 years (418 deaths), both high hs-cTnI and high hs-cTnT further stratified mortality risk beyond comorbidity levels; those with a high hs-cTnI or hs-cTnT and high comorbidity were at highest mortality risk. Even among those with low comorbidity, a high hs-cTnI (hazard ratio 3.0 [95% CI 1.7, 5.4]) or hs-cTnT (hazard ratio 3.3 [95% CI 1.8, 6.2]) was associated with elevated mortality. CONCLUSIONS: Many comorbidities were reflected by both hs-cTnI and hs-cTnT; elevations in either of the troponins were associated with higher mortality risk beyond comorbidity burden. High-sensitivity cardiac troponins may identify older adults at high mortality risk and be useful in guiding clinical care of older adults with diabetes.

Epigenetic Age Acceleration and Cognitive Function in African American Adults in Midlife: The Atherosclerosis Risk in Communities Study.

Methylation levels measured at defined sites across the genome have recently been shown to be correlated with an individual's chronological age. Age acceleration, or the difference between age estimated from DNA methylation status and chronological age, has been proposed as a novel biomarker of aging. In this study, the cross-sectional association between two different measures of age acceleration and cognitive function was investigated using whole blood samples from 2,157 African American participants 47-70 years of age in the population-based Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using three domain-specific tests. A significant inverse association between a 1-year increase in age acceleration calculated using a blood-based age predictor and scores on the Word Fluency Test was found using a general linear model adjusted for chronological age, gender, and years of education (ß = -0.140 words; p = .001) and after adding other potential confounding variables (ß = -0.104 words, p = .023). The results were replicated in 1,670 European participants in the Generation Scotland: Scottish Family Health Study (fully adjusted model: ß = -0.199 words; p = .034). A significant association was also identified in a trans-ethnic meta-analysis across cohorts that included an additional 708 European American ARIC study participants (fully adjusted model: ß = -0.110 words, p = .003). There were no associations found using an estimate of age acceleration derived from multiple tissues. These findings provide evidence that age acceleration is a correlate of performance on a test of verbal fluency in middle-aged adults.

Subclinical Cardiovascular Disease and Fall Risk in Older Adults: Results From the Atherosclerosis Risk in Communities Study.

BACKGROUND/OBJECTIVES: Falls are frequent and often devastating events among older adults. Cardiovascular disease (CVD) is associated with greater fall risk; however, it is unknown if pathways that contribute to CVD, such as subclinical myocardial damage or wall strain, are related to future falls. We hypothesized that elevations in high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), measured in older adults, would be associated with greater fall risk. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Atherosclerosis Risk in Communities Study participants without known coronary heart disease, heart failure, or stroke. MEASUREMENTS: We measured hs-cTnT or NT-proBNP in 2011 to 2013. Falls were identified from hospital discharge International Classification of Diseases, Ninth Revision (ICD-9), codes or Centers for Medicare and Medicaid Services claims. We used Poisson models adjusted for age, sex, and race/study center to quantify fall rates across approximate quartiles of hs-cTnT (less than 8, 8-10, 11-16, and 17 or greater ng/L) and NT-proBNP (less than 75, 75-124, 125-274, and 275 or greater pg/mL). We used Cox models to determine the association of cardiac markers with fall risk, adjusted for age, sex, race/center, and multiple fall risk factors. RESULTS: Among 3973 participants (mean age = 76 ± 5 years, 62% women, 22% black), 457 had a subsequent fall during a median follow-up of 4.5 years. Incidence rates across quartiles of hs-cTnT and NT-proBNP were 17.1, 20.0, 26.2, and 36.4 per 1000 person-years and 12.8, 22.2, 28.7, and 48.4 per 1000 person-years, respectively. Comparing highest vs lowest quartiles of either hs-cTnT or NT-proBNP demonstrated a greater than two-fold higher fall risk, with hazard ratios of 2.17 (95% confidence interval {CI} = 1.60-2.95) and 2.34 (95% CI = 1.73-3.16), respectively. In a joint model, the relationships of hs-cTnT and NT-proBNP with falls were significant and independent. CONCLUSION: Subclinical elevations of cardiac damage and wall strain were each associated with a higher fall risk in older adults. Further research is needed to determine whether interventions that lower hs-cTnT or NT-proBNP also lower fall risk. J Am Geriatr Soc 67:1795-1802, 2019.

Association of sickle cell trait with measures of cognitive function and dementia in African Americans.

OBJECTIVE: The incidence and prevalence of cognitive decline and dementia are significantly higher among African Americans compared with non-Hispanic Whites. The aim of this study was to determine whether inheritance of the sickle cell trait (SCT) i.e. heterozygosity for the sickle cell mutation increases the risk of cognitive decline or dementia Among African Americans. METHODS: We studied African American participants enrolled in the Atherosclerosis Risk in Communities study. SCT genotype at baseline and outcome data from cognitive assessments at visits 2, 4 and 5, and an MRI performed at visit 5 were analyzed for the association between SCT and risk of cognitive impairment and/or dementia. RESULTS: There was no significant difference in risk factors profile between participants with SCT (N = 176) and those without SCT (N = 2532). SCT was not independently associated with a higher prevalence of global or domain-specific cognitive impairment at baseline or with more rapid cognitive decline. Participants with SCT had slightly lower incidence of dementia (HR = 0.63 [0.38, 1.05]). On the other hand, SCT seems to interact with the apolipoprotein E ε4 risk allele resulting in poor performance on digit symbol substitution test at baseline (z-score = -0.08, Pinteraction = 0.05) and over time (z-score = -0.12, Pinteraction = 0.04); and with diabetes mellitus leading to a moderately increased risk of dementia (HR = 2.06 [0.89, 4.78], Pinteraction = 0.01). CONCLUSIONS: SCT was not an independent risk factor for prevalence or incidence of cognitive decline or dementia, although it may interact with and modify other putative risk factors for cognitive decline and dementia.

Controlling for Frailty in Pharmacoepidemiologic Studies of Older Adults: Validation of an Existing Medicare Claims-based Algorithm.

BACKGROUND: Frailty is a geriatric syndrome characterized by weakness and weight loss and is associated with adverse health outcomes. It is often an unmeasured confounder in pharmacoepidemiologic and comparative effectiveness studies using administrative claims data. METHODS: Among the Atherosclerosis Risk in Communities (ARIC) Study Visit 5 participants (2011-2013; n = 3,146), we conducted a validation study to compare a Medicare claims-based algorithm of dependency in activities of daily living (or dependency) developed as a proxy for frailty with a reference standard measure of phenotypic frailty. We applied the algorithm to the ARIC participants' claims data to generate a predicted probability of dependency. Using the claims-based algorithm, we estimated the C-statistic for predicting phenotypic frailty. We further categorized participants by their predicted probability of dependency (<5%, 5% to <20%, and ≥20%) and estimated associations with difficulties in physical abilities, falls, and mortality. RESULTS: The claims-based algorithm showed good discrimination of phenotypic frailty (C-statistic = 0.71; 95% confidence interval [CI] = 0.67, 0.74). Participants classified with a high predicted probability of dependency (≥20%) had higher prevalence of falls and difficulty in physical ability, and a greater risk of 1-year all-cause mortality (hazard ratio = 5.7 [95% CI = 2.5, 13]) than participants classified with a low predicted probability (<5%). Sensitivity and specificity varied across predicted probability of dependency thresholds. CONCLUSIONS: The Medicare claims-based algorithm showed good discrimination of phenotypic frailty and high predictive ability with adverse health outcomes. This algorithm can be used in future Medicare claims analyses to reduce confounding by frailty and improve study validity.

Association of History of Dizziness and Long-term Adverse Outcomes With Early vs Later Orthostatic Hypotension Assessment Times in Middle-aged Adults.

Importance: Guidelines recommend assessing orthostatic hypotension (OH) 3 minutes after rising from supine to standing positions. It is not known whether measurements performed immediately after standing predict adverse events as strongly as measurements performed closer to 3 minutes. Objective: To compare early vs later OH measurements and their association with history of dizziness and longitudinal adverse outcomes. Design, Setting, and Participants: This was a prospective cohort study of middle-aged (range, 44-66 years) participants in the Atherosclerosis Risk in Communities Study (1987-1989). Exposures: Orthostatic hypotension, defined as a drop in blood pressure (BP) (systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg) from the supine to standing position, was measured up to 5 times at 25-second intervals. Main Outcomes and Measures: We determined the association of each of the 5 OH measurements with history of dizziness on standing (logistic regression) and risk of fall, fracture, syncope, motor vehicle crashes, and all-cause mortality (Cox regression) over a median of 23 years of follow-up (through December 31, 2013). Results: In 11 429 participants (mean age, 54 years; 6220 [54%] were women; 2934 [26%] were black) with at least 4 OH measurements after standing, after adjustment OH assessed at measurement 1 (mean [SD], 28 [5.4] seconds; range, 21-62 seconds) was the only measurement associated with higher odds of dizziness (odds ratio [OR], 1.49; 95% CI, 1.18-1.89). Measurement 1 was associated with the highest rates of fracture, syncope, and death at 18.9, 17.0, and 31.4 per 1000 person-years. Measurement 2 was associated with the highest rate of falls and motor vehicle crashes at 13.2 and 2.5 per 1000 person-years. Furthermore, after adjustment measurement 1 was significantly associated with risk of fall (hazard ratio [HR], 1.22; 95% CI, 1.03-1.44), fracture (HR, 1.16; 95% CI, 1.01-1.34), syncope (HR, 1.40; 95% CI, 1.20-1.63), and mortality (HR, 1.36; 95% CI, 1.23-1.51). Measurement 2 (mean [SD], 53 [7.5] seconds; range, 43-83 seconds) was associated with all long-term outcomes, including motor vehicle crashes (HR, 1.43; 95% CI, 1.04-1.96). Measurements obtained after 1 minute were not associated with dizziness and were inconsistently associated with individual long-term outcomes. Conclusions and Relevance: In contrast with prevailing recommendations, OH measurements performed within 1 minute of standing were the most strongly related to dizziness and individual adverse outcomes, suggesting that OH be assessed within 1 minute of standing.

Are Trends in Hospitalization Prior to Hospice Use Associated With Hospice Episode Characteristics?

This study expands current knowledge of factors associated with initiation of hospice care by examining prehospice patterns of medical care leading to Medicare hospice use and the relationships to hospice episode characteristics. Data from the Atherosclerosis Risk in Communities (ARIC) study cohort offer the ability to control for measures that are not available in Medicare claims data, including marital status, nursing home residency, and education. For 1248 ARIC participants who used hospice (2006-2012), participant level trends in the number of hospital days per 30-day period over the year prior to hospice initiation were generated using a fixed-effects model. Logistic regression was used to estimate the associations between increasing hospital use over the year prior to hospice enrollment with key patient characteristics (diagnosis, age, and comorbidity) and episode characteristics (short hospice stay ending in death, long hospice stay, and live discharge). Participants with severe comorbidity (measured as a Charlson comorbidity index score greater than 5) had higher odds of increasing hospital use prior to hospice (odds ratio [OR] = 3.28, confidence interval [CI] = 2.25-4.78). Increasing hospital use did not vary by diagnosis but was associated with reduced odds of a live hospice discharge (OR = 0.55, CI = 0.34-0.88) or long stay in hospice (OR = 0.44, CI = 0.24-0.79) and increased odds of a short stay in hospice (OR = 1.92, CI = 1.36-2.71). The evidence that care patterns prior to hospice use are associated with hospice outcomes could facilitate development of interventions to improve timely hospice referral.

Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study.

The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle-brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P = 0.44), but a higher prevalence of ABI 0.9-1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0.9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9-1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53-15.31) and men (3.49, 1.39-8.72). However, ABI 0.9-1.0 was significantly associated with incident clinical PAD (3.33, 1.44-7.70) and incident stroke (2.45, 1.38-4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD.