Introduction: Current physical activity (PA) recommendations support replacing time spent sedentary with PA of any intensity. There is ample evidence that moderate/vigorous intensity PA is beneficially associated with physical function. Light intensity PA may provide an additional opportunity to improve physical function in inactive individuals. However, the longitudinal associations of replacing sedentary time with light intensity PA and physical function are not clear. Hypothesis: We hypothesized that replacing sedentary time with light intensity PA is associated with better physical function. Methods: Participants in the CARDIA study with accelerometer data at the Years 20 ([Y20] 2005-06) and 35 ([Y35] 2020-22) exams and physical performance at Y35 (n=996) were included. Measures of balance, endurance, gait speed, grip strength, and lower extremity strength Y35 were used to create a composite physical performance (CAPP) score; higher scores represent better physical function. We used compositional isotemporal substitution models to estimate predicted differences in CAPP resulting from hypothetical replacement of sedentary time with light intensity PA and whether associations varied by initial time spent sedentary, in moderate/vigorous intensity PA, or age. Secondary analyses evaluated associations with individual CAPP components. Multiple imputation was used to address missing data. Results: Across midlife (mean 45±SD 3.5 [Y20] to 60± 3.6 [Y35] years old), 26% of participants increased daily time in light intensity PA. Mean CAPP score at Y35 was 13.1±SD 3.9. Hypothetical replacement of 3 hours of daily sedentary time with light intensity PA from Y20 to Y35 was associated with 1.0 unit greater CAPP score at Y35 (95% CI: 0.6,1.4) (Figure). This association was similar across initial time spent sedentary, in moderate/vigorous intensity PA, and age. By subcomponent, hypothetical replacement of 3 hours of daily sedentary time with light intensity PA was associated with better balance (6 seconds; 95% CI: 4,8), endurance (86 feet; 95% CI: 49,123), gait speed (0.04 m/s, 95% CI: 0.01,0.06), and lower extremity strength (0.7 sit-stands; 95% CI: 0.2,1.2), but not grip strength (0.6 kg/lbs of force; 95% CI: -0.3,1.4). Conclusions: Replacement of sedentary time with light intensity PA across midlife was associated with better physical function. Interventions to increase light intensity PA may help improve physical function in midlife in active and inactive individuals.

BACKGROUND:Postprandial hypotension (PPH) may contribute to falls among older adults, particularly those taking antihypertensive medication. However, evidence on this association in community-dwelling populations is limited. Since ambulatory blood pressure (BP) monitoring captures BP during daily activities, it may provide accurate assessments of PPH outside the clinic setting. METHODS:This prospective cohort study examined the association between PPH and fall risk among community-dwelling adults aged ≥65 years taking antihypertensive medication. At baseline, participants underwent 24-hour ambulatory BP monitoring; subsequently, they completed monthly fall calendars during a 12-month follow-up. PPH by systolic BP (SBP; systolic PPH) was defined as a postprandial SBP decline, mean SBP during the hour before the meal minus the minimum SBP during the 2 hours after the meal, following any meal of ≥20 mm Hg, or a decrease to SBP ≤90 mm Hg when preprandial SBP was ≥100 mm Hg. RESULTS:Among 626 participants (mean±SD age, 74.6±6.2 years; 56.1% women), 442 (70.6%) experienced systolic PPH. The mean±SD number of meals was 2.6±0.8 during the ambulatory BP monitoring period. During the 12-month follow-up, falls occurred in 169 of 442 (38.2%) participants with systolic PPH and 70 of 184 (38.0%) participants without systolic PPH. Systolic PPH was not associated with fall risk (adjusted hazard ratio, 0.93 [95% CI, 0.69-1.26]). A restricted cubic spline analysis demonstrated no evidence of an association between the largest postprandial SBP decline across all meals and fall risk. CONCLUSIONS:In this cohort study, PPH identified by ambulatory BP monitoring was common but not associated with risk of falls.

Background: Loneliness is a growing public health concern. In 2022, the AHA identified it as a contributor to poor cardiovascular health, followed by a 2023 U.S. Surgeon General advisory declaring an “Epidemic of Loneliness and Isolation”. Although linked to mortality, its independent effect and generalizability across diverse groups remain understudied. With over half of U.S. adults reporting loneliness, understanding its role may be essential to improving cardiovascular outcomes. Research Questions/Hypothesis: We examined the association between loneliness and CVD mortality in a diverse national cohort. We hypothesized that loneliness would be associated with increased CVD mortality. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study is a prospective cohort of 30,239 adults aged ≥45 years recruited from 2003-2007. We included those who completed a baseline loneliness item assessing feelings in the past week. Cox proportional hazards models estimated HRs and 95% CIs for the association between loneliness and time to CVD death. Models were sequentially adjusted for demographics (age, race, gender), SDOH (employment, education, income, insurance, region, poverty, health professional shortage, public health infrastructure), clinical factors (hypertension, diabetes, self-rated physical health, obesity, inflammation, cognition), health behaviors (smoking, activity, diet, medication adherence), and objective social health (partnership, social isolation, social support). Effect modification by age, race, and gender was assessed using interaction terms. Results: We included 29,387 participants with median follow-up of 13.1 years (IQR 7.3-16.1). Mean age was 65.0 years (SD 9.4); 41% identified as Non-Hispanic Black and 55% were women. Overall, 21% of participants reported loneliness in the past week, with 3,643 CVD deaths observed. Loneliness was associated with a 41% increased hazard of CVD mortality in unadjusted models (HR, 1.41; 95% CI, 1.31-1.53). The association attenuated but remained significant in the fully adjusted model (HR, 1.21; 95% CI, 1.03-1.41). No effect modification was observed. Conclusion: Loneliness was associated with increased CVD mortality risk, even after accounting for clinical, behavioral, and social factors. A one-time, self-reported loneliness measure may serve as a practical tool for identifying at-risk patients and inform efforts to reduce cardiovascular risk.

Background: Over-intensification of antihypertensive medication may lead to hypotension and excessive blood pressure (BP) variability and thus increase the risk for falls, a major cause of injury-related hospitalization and death among older adults. Monitoring BP at home may allow for better BP management and avoidance of falls. Objective: To evaluate the associations of home BP, white coat effect (difference between clinic and home BP), and day-to-day variability of BP with falls. Methods: The Ambulatory Blood Pressure in Older Adults Home BP Monitoring (HBPM) (AMBROSIA-HOME) study included 541 participants from Kaiser Permanente Southern California aged ≥65 years taking antihypertensive medication. Participants were instructed in proper HBPM technique and asked to take 2 BP readings each morning and each evening for 7 days. We included 499 participants (92.2%) with ≥4 days with 2 morning and 2 evening HBPM readings. For both systolic BP (SBP) and diastolic BP (DBP), the white coat effect was defined as mean clinic BP minus mean BP from HBPM and the standard deviation independent of the mean (SDIM) of morning and evening BP were calculated as measures of day-to-day variability. Participants reported any fall where their body parts hit a surface, including falls that occured on stairs, monthly for 1 year using falls calendars. We used Cox proportional hazards models to estimate hazard ratios of time to first fall across quartiles of each HBPM metric, separately, adjusting for demographic characteristics and chronic conditions. Results: The mean ± SD age of participants was 74.2±6.1 years, and 57.3% were women. The prevalence of prefrailty and frailty were 50.7% and 3.4%, respectively. Participants in the top quartile of mean SBP from HBPM were older, more frequently male, more frequently Black and Hispanic, and had higher prevalence of diabetes, arthritis, and neuropathy than those in the lowest quartile. There were 187 participants who reported falls (376 falls/1,000 person-years). We did not find evidence of associations between mean, white coat effect, or SDIM of SBP ( Figure ) or DBP from HBPM and falls. Conclusion: In this population of older US adults with treated hypertension, BP measured using HBPM was not associated with falls.

Introduction: Reserve and resilience refer to the degree of robustness prior to, and the subsequent ability to recover from a health stressor. Frailty and nursing facility use (NFU) may characterize varying levels of physical reserve and resilience among individuals hospitalized for a cardiovascular event. Objective: To characterize older US adults who had a CVD hospitalization using novel indicators of reserve and resilience: nursing facility use and a frailty index. Methods: We analyzed data from 1,605 Black and White REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants with Medicare fee-for-service coverage who were age ≥65.5 years and had no NFU before an adjudicated myocardial infarction, heart failure, or stroke hospitalization in 2004-2019. Participants were grouped into mutually exclusive categories based on Medicare claims for NFU and vital status (i.e., alive without NFU, alive with NFU, and death) within 182 days and 183-365 days following discharge. We calculated a claims-based frailty index (index ranges from 0 to 1, with higher values indicating greater deficit accumulation) within 182 days before admission, and within 182 days and 183-365 days following discharge. Results: The mean age at admission was 77.4 years, 43.6% were female, and 30.4% were Black. Most participants were alive without NFU for 365 days post-discharge (64.9%), followed by those who died within 182 days following discharge (11.6%), and those who were alive with NFU within 182 days and alive without NFU in the 183-365 days following discharge (10.3%). Participants who were alive without NFU for 365 days post-discharge had the lowest frailty index in each assessment period (Figure) and were younger (mean age 76.5 years) versus the other groups (range 77.3-80.4 years). There were no substantial differences in subgroups defined by NFU and vital status post-discharge in analyses stratified by sex or race. Conclusion: NFU and frailty index identify older adults with varying levels of apparent reserve and resilience before and after a cardiovascular hospitalization.

Background: Poor physical performance, often measured by gait speed and chair stand tests, has been linked to mortality, but patterns may differ depending on prior history of cardiovascular disease (CVD). Objective: To examine associations between physical performance and death from coronary heart disease (CHD), CVD, and all-cause by history of CVD. Methods: Among 14,137 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants (2013-2016), participants were categorized by quartiles of gait speed and chair stand times or inability to complete the test. Deaths (CHD, CVD, and all-cause) were adjudicated through December 31, 2020. Stratified by history of CVD, we created survival curves and conducted Cox proportional hazards models adjusted for demographics, health behaviors, and medical history. Results: The average age of participants was 72.54±8.5, 56.1% were female, 63.3% were White, 36.7% were Black, and 42.9% had history of CVD; 2,749 participants died. Compared to the fastest quartile, participants with history of CVD and slowest gait speeds had adjusted hazards ratios (HRs) of 1.29 (95% CI: 0.75, 2.23) for CHD, 1.37 (0.92, 2.05) for CVD, and 1.81 (1.47, 2.23) for all-cause mortality; HR for those with incomplete gait speed tests were 1.66 (0.80, 3.44), 3.07 (1.94, 4.86), and 3.19 (2.48, 4.10), respectively. Participants with history of CVD and the slowest quartile of chair stand time had HRs of 1.05 (95% CI: 0.62, 1.78) for CHD, 1.49 (1.08, 2.04) for CVD, and 1.82 (1.48, 2.23) for all-cause mortality; those with incomplete chair stand tests had HR of 1.33 (0.76, 2.33), 2.30 (1.68, 3.16), and 3.18 (2.47, 4.09), respectively. A similar pattern was seen among those without history of CVD, but the magnitude of the associations was lower (p-interaction = 0.345, 0.028, and 0.026 for CHD, CVD, and all-cause mortality, respectively, for gait speed tests and p-interaction = 0.064, 0.084, and 0.034 for CHD, CVD, and all-cause mortality, respectively, for chair stand tests). Conclusions: While physical performance was associated with mortality among individuals with and without CVD, poor physical performance may be a stronger marker for risk of death among those with CVD.

Frailty prevalence in older adults has been reported but is largely unknown in middle-aged adults. We determined the prevalence of frailty indicators among middle-aged and older adults from a general Swiss population characterized by universal health insurance coverage and assessed the determinants of frailty with a special focus on socioeconomic status. Participants aged 50 and more from the population-based 2006–2010 Bus Santé study were included (N = 2,930). Four frailty indicators (weakness, shrinking, exhaustion, and low activity) were measured according to standard definitions. Multivariate logistic regressions were used to determine associations. Overall, 63.5%, 28.7%, and 7.8% participants presented no frailty indicators, one frailty indicator, and two or more frailty indicators, respectively. Among middle-aged participants (50–65 years), 75.1%, 22.2%, and 2.7% presented 0, 1, and 2 or more frailty indicators. The number of frailty indicators was positively associated with age, hypertension, and current smoking and negatively associated with male gender, body mass index, waist-to-hip ratio, and serum total cholesterol level. Lower income level but not education was associated with higher number of frailty indicators. Frailty indicators are frequently encountered in both older and middle-aged adults from the Swiss general population. Despite universal health insurance coverage, household income is independently associated with frailty.

Hypertension requiring treatment with multiple antihypertensive medications is common among individuals with chronic kidney disease (CKD). Small clinic-based studies have reported a high prevalence of treatment resistant hypertension (TRH) among patients with CKD. However, the prevalence of TRH has not been estimated for people with CKD in population-based studies. We hypothesized that lower estimated glomerular filtration rate (eGFR) and higher albumin-to-creatinine ratio (ACR) would be associated with a higher prevalence of TRH. We determined the prevalence of TRH among REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants (n=30,239) by eGFR and ACR and evaluated clinical and demographic correlates of TRH in those with CKD. Blood pressure was measured twice, pill bottles were inspected, and serum creatinine and an ACR were measured during an in-home study visit. TRH was defined as systolic/diastolic blood pressure ≥140/90 mmHg with concurrent use of ≥3 antihypertensive medication classes or use of ≥4 antihypertensive medication classes. CKD was defined as an ACR ≥30 mg/g or a CKD-EPI equation-derived eGFR <60 ml/min/1.73m 2 . The mean age of the 11,285 REGARDS participants treated for hypertension was 66.0 (SD=9.0) years, 56.9% were women and 48.8% were black. The prevalence of TRH was 14.5%, 23.5%, and 31.2% for those with an eGFR ≥60, 45-59, and <45 mL/min/1.73m 2 , respectively. The prevalence of TRH was 11.3%, 18.8%, 25.5%, and 44.5% for ACR <10, 10-29, 30-299, and ≥300 mg/g, respectively. A graded association between lower eGFR and higher ACR with TRH remained present after multivariable adjustment (Table 1). Also, after multivariable adjustment, black race, a larger waist circumference, diabetes, and history of myocardial infarction and stroke were associated with TRH among individuals with CKD. In conclusion, individuals with CKD have a high prevalence of TRH. Strategies are needed to improve blood pressure control in this population and reduce cardiovascular disease risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly recommended for pain treatment in older adults because they aremore effective than acetaminophen and lack the central nervous system side effects of opioids. Although the risks of long-term NSAID use are well known, short-term use of ibuprofen is generally considered to be safe. To our knowledge, this is the first report of acute kidney injury after only 2 days of ibuprofen use. A 73-year-old woman with diabetes and baseline creatinine of 0.94 mg/dL presented to the emergency department with weakness, nausea, and decreased urination after taking ibuprofen for 2 days for her fractured humerus. The patient was found to have a potassium of 8.6 mmol/L and a creatinine of 6.99 mg/dL. The patient was treated with intravenous calcium gluconate and sodium bicarbonate and admitted to the intensive care unit for emergent dialysis. The patient was discharged without long-term sequelae. This case demonstrates the danger of even short courses of NSAIDs in older adults with disease or medications, which predispose them to NSAID-induced acute kidney injury.