Cardiovascular Burden of the V142I Transthyretin Variant.

Importance: Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments. Objectives: To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population. Design, Setting, and Participants: A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024. Exposure: V142I carrier status (n = 754, 3.2%). Main Outcomes and Measures: Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data. Results: Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant. Conclusions and Relevance: Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.

Bicycling over a Lifetime Is Associated with Less Symptomatic Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

INTRODUCTION: To evaluate the relationship between a history of bicycling and symptomatic and structural outcomes of knee osteoarthritis (OA), the most common form of arthritis. METHODS: This was a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), where we investigated OAI participants with complete data on bicycling, knee pain, and radiographic evidence of knee OA. We used a self-administered questionnaire at the 96-month OAI visit to identify participation in bicycling during four time periods throughout a participant's lifetime (ages 12-18, 19-34, 35-49, and > 50 years old). Using logistic regression, we evaluated the influence of prior bicycling status (any history, history for each time period, number of periods cycling) on three outcomes at the 48-month OAI visit: frequent knee pain, radiographic OA (ROA), and symptomatic radiographic OA (SOA), adjusting for age and gender. RESULTS: 2607 participants were included; 44.2% were male; mean age was 64.3 (SD 9.0) years; body mass index was 28.5 (SD 4.9) kg/m 2 . The adjusted risk ratio for the outcome of frequent knee pain, ROA, and SOA among those who reported any history of bicycling compared to non-bicyclers was 0.83 (0.73-0.92), 0.91 (0.85-0.98), and 0.79 (0.68-0.90), respectively. We observed a dose-response among those who participated in bicycling during more time periods. CONCLUSIONS: People who participated in bicycling had a lower prevalence of frequent knee pain, ROA, and SOA. The benefit appeared cumulative. This study indicates that bicycling may be favorable to knee health and should be encouraged.

Gardening/yardwork in people with knee osteoarthritis is not associated with symptom or structural progression over 48 months: data from the Osteoarthritis Initiative.

OBJECTIVE: To evaluate the relationship of gardening/yardwork with symptomatic and structural progression in those with pre-existing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative (OAI), an observational study designed to evaluate potential and known biomarkers and risk factors of knee OA. METHODS: We conducted a cohort study nested within the OAI, including participants ≥ 50 years old with radiographic OA in at least one knee at the time of OAI enrollment. A participant reported the level of gardening/yardwork activity in a self-administered survey. Logistic regression analyses were used to evaluate the association of gardening/yardwork on new frequent knee pain, Kellgren-Lawrence (KL) worsening, medial joint space narrowing (JSN) worsening, and improved frequent knee pain. RESULTS: Of 1808 knees (1203 participants), over 60% of knees had KL grade = 2, 65% had medial JSN, and slightly more than a third had frequent knee symptoms. Gardeners/yardworkers and non-gardners/yardworkers had similar "worsening" outcomes for new knee pain (29% vs. 29%), KL worsening (19% vs. 18%), and medial JSN (23% vs. 24%). The adjusted odds ratio (OR) for the "worsening" outcomes of new knee pain, KL worsening, and medial JSN worsening were 1.0 (0.7-1.3), 1.0 (0.8-1.3), and 1.1 (0.9-1.4), respectively. The gardeners/yardworkers had an adjusted OR of 1.2 (0.9-1.7) for improved knee pain compared with non-gardners/yardworkers. CONCLUSION: Gardening/yardwork is not associated with knee OA progression and should not be discouraged in those with knee OA. Key Points • Gardening/yardwork is not associated with knee OA symptomatic or structural progression. • Gardening/yardwork should not be discouraged in people with knee OA.

Heart Failure Risk Among African-American Women With an ICAM1 Missense Variant.

BACKGROUND: A common genetic variant of ICAM1 among African-American individuals (rs5491; p.K56M) is associated with heart failure (HF) hospitalization, but whether this risk is specific to heart failure with preserved ejection fraction (HFpEF) remains unclear. Older women are at high risk for HFpEF, and the relationship between rs5491 and HFpEF across the age spectrum is unknown. OBJECTIVES: This study assessed risk of HF and its subtypes conferred by ICAM1 p.K56M (rs5491). METHODS: Associations of rs5491 with risk of HF and its subtypes were estimated among African American individuals in WHI (Women's Health Initiative). The study evaluated whether the association between rs5491 and HF hospitalizations was modified by baseline age. Subsequently, African-American women in WHI and MESA (Multi-Ethnic Study of Atherosclerosis) were pooled and analyses were repeated. RESULTS: Among 8,401 women in WHI, the minor allele frequency of rs5491 was 20.7%, and 731 HF hospitalizations occurred over 19.2 years. The rs5491 variant was not associated with HF or its subtypes across WHI. Interaction analyses suggested that age as a continuous variable modified the association of rs5491 with HFpEF hospitalization (interaction P = 0.04). Upon categorizing women into age decades, rs5491 conferred increased risk of HFpEF among women ≥70 years (HR per additional rs5491 allele: 1.82 [95% CI: 1.25-2.65]; P = 0.002) but was not associated with HFpEF risk among women <70 years. Pooling African-American women in WHI (n = 8,401) and MESA (n = 856) demonstrated that the effect modification by age on the association of rs5491 with HFpEF became more significant (interaction P = 0.009), with consistent HFpEF risk effect estimates among women ≥70 years. CONCLUSIONS: ICAM1 p.K56M (rs5491) is associated with HFpEF among African-American women ≥70 years.

Evaluating the association between longitudinal exposure to a PFAS mixture and adolescent cardiometabolic risk in the HOME Study.

Background: Exposure to per- and polyfluoroalkyl substances (PFAS) throughout gestation and childhood may impact cardiometabolic risk. Methods: In 179 HOME Study participants (Cincinnati, OH; recruited 2003-2006), we used latent profile analysis to identify two distinct patterns of PFAS exposure from serum concentrations of four PFAS measured at birth and ages 3, 8, and 12 years. We assessed the homeostatic model of insulin resistance, triglycerides-to-high-density lipoprotein cholesterol ratio, leptin-to-adiponectin ratio, systolic blood pressure, visceral fat, and hemoglobin A1c levels at age 12 years. We used multivariable linear regression to assess the association of membership in the longitudinal PFAS mixture exposure group with a summary measure of overall cardiometabolic risk and individual components. Results: One PFAS exposure profile (n = 66, 39%) had higher geometric means of all PFAS across all visits than the other. Although adjusted associations were null in the full sample, child sex modified the association of longitudinal PFAS mixture exposure group with overall cardiometabolic risk, leptin-to-adiponectin ratio, systolic blood pressure, and visceral fat (interaction term P values: 0.02-0.08). Females in the higher exposure group had higher cardiometabolic risk scores (ß = 0.43; 95% CI = -0.08, 0.94), systolic blood pressures (ß = 0.6; 95% CI = 0.1, 1.1), and visceral fat (ß = 0.44; 95% CI = -0.13, 1.01); males had lower cardiometabolic risk scores (ß = -0.52; 95% CI = -1.06, -0.06), leptin-to-adiponectin ratios (ß = -0.7; 95% CI = -1.29, -0.1), systolic blood pressures (ß = -0.14; 95% CI = -0.7, 0.41), and visceral fat (ß = -0.52; 95% CI = -0.84, -0.19). Conclusions: Exposure to this PFAS mixture throughout childhood may have sex-specific effects on adolescent cardiometabolic risk.

Photosensitizing antihypertensive medication and risk of skin cancer among postmenopausal women.

BACKGROUND: Few prospective studies exist with an evaluation of a dose-response relationship between use of some photosensitizing antihypertensive medications and skin cancer. PATIENT AND METHODS: We used prospective data from the Women's Health Initiative Observational Study to investigate the association between antihypertensive use and risk of non-melanoma skin cancer (NMSC) and melanoma in postmenopausal women aged 50-79 years at baseline (n  =  64,918). Multivariable Cox proportional hazards regression models were used and hazard ratios (HRs) and 95 confidence intervals (CIs) were calculated. RESULTS: 8,777 NMSC and 1,227 melanoma cases were observed. Use of antihypertensives (HR [95% CI]: 1.12 [1.07-1.18]), ACE inhibitors (1.09 [1.01-1.18]), calcium channel blockers (1.13 [1.05-1.22]), diuretics (1.20 [1.12-1.27]), loop diuretics (1.17 [1.07-1.28]), and thiazides (1.17 [1.03-1.33]) were each associated with higher NMSC risk. NMSC risk linearly increased with use of multiple antihypertensives (p-trend  =  0.02) and with longer duration of use (p-trend < 0.01). Antihypertensives (1.15 [1.00-1.31]), angiotensin-II receptor blockers (1.82 [1.05-3.15]), and diuretics (1.34 [1.13-1.59]) were each associated with elevated melanoma risk. Effect modification by solar radiation exposure was found between antihypertensive use and incidence of melanoma (p-interaction  =  0.02). CONCLUSIONS: Use of antihypertensives overall, and several individual classes thereof, were associated with higher incidence of NMSC and melanoma with dose-response relationship.

Accelerometer-Measured Physical Activity, Sedentary Time, and Heart Failure Risk in Women Aged 63 to 99 Years.

Importance: Heart failure (HF) prevention is paramount to public health in the 21st century. Objective: To examine incident HF and its subtypes with preserved ejection fraction (HFpEF) and reduced EF (HFrEF) according to accelerometer-measured physical activity (PA) and sedentary time. Design, Setting, and Participants: This was a prospective cohort study, the Objective Physical Activity and Cardiovascular Health (OPACH) in Older Women study, conducted from March 2012 to April 2014. Included in the analysis were women aged 63 to 99 years without known HF, who completed hip-worn triaxial accelerometry for 7 consecutive days. Follow-up for incident HF occurred through February 2022. Data were analyzed from March to December 2023. Exposure: Daily PA (total, light, moderate to vigorous PA [MVPA], steps) and sedentary (total, mean bout duration) behavior. Main Outcomes and Measures: Adjudicated incident HF, HFpEF, and HFrEF. Results: A total of 5951 women (mean [SD] age, 78.6 [6.8] years) without known HF were included in this analysis. Women self-identified with the following race and ethnicity categories: 2004 non-Hispanic Black (33.7%), 1022 Hispanic (17.2%), and 2925 non-Hispanic White (49.2%). There were 407 HF cases (257 HFpEF; 110 HFrEF) identified through a mean (SD) of 7.5 (2.6) years (range, 0.01-9.9 years) of follow-up. Fully adjusted hazard ratios (HRs) for overall HF, HFpEF, and HFrEF associated with a 1-SD increment were 0.85 (95% CI, 0.75-0.95), 0.78 (95% CI, 0.67-0.91), and 1.02 (95% CI, 0.81-1.28) for minutes per day total PA; 0.74 (95% CI, 0.63-0.88), 0.71 (95% CI, 0.57-0.88), and 0.83 (95% CI, 0.62-1.12) for steps per day; and 1.17 (95% CI, 1.04-1.33), 1.29 (95% CI, 1.10-1.51), and 0.94 (95% CI, 0.75-1.18) for minutes per day total sedentary. Cubic spline curves for overall HF and HFpEF were significant inverse for total PA and steps per day and positive for total sedentary. Light PA and MVPA were inversely associated with overall HF (HR per 1 SD: 0.88; 95% CI, 0.78-0.98 and 0.84; 95% CI, 0.73-0.97) and HFpEF (0.80; 95% CI, 0.70-0.93 and 0.85; 95% CI, 0.72-1.01) but not HFrEF. Associations did not meaningfully differ when stratified by age, race and ethnicity, body mass index, physical function, or comorbidity score. Results for sedentary bout duration were inconsistent. Conclusions and Relevance: Higher accelerometer-measured PA (MVPA, light PA, steps per day) was associated with lower risk (and greater total sedentary time with higher risk) of overall HF and HFpEF in a racially and ethnically diverse cohort of older women. Increasing PA and reducing sedentary time for primary HFpEF prevention may have relevant implications for cardiovascular resilience and healthy aging in later life.

Clonal Hematopoiesis and Incident Heart Failure With Preserved Ejection Fraction.

Importance: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic stem cells with leukemogenic acquired genetic variants, is associated with incident heart failure (HF). Objective: To evaluate the associations of CHIP and key gene-specific CHIP subtypes with incident HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Design, Setting, and Participants: This population-based cohort study included participants from 2 racially diverse prospective cohort studies with uniform HF subtype adjudication: the Jackson Heart Study (JHS) and Women's Health Initiative (WHI). JHS participants were enrolled during 2000 to 2004 and followed up through 2016. WHI participants were enrolled during 1993 to 1998 and followed up through 2022. Participants who underwent whole-genome sequencing, lacked prevalent HF at baseline, and were followed up for HF adjudication were included. Follow-up occurred over a median (IQR) of 12.0 (11.0-12.0) years in the JHS and 15.3 (9.0-22.0) years in the WHI. Statistical analysis was performed from June to December 2023. Exposures: Any CHIP and the most common gene-specific CHIP subtypes (DNMT3A and TET2 CHIP). Main Outcomes and Measures: First incident hospitalized HF events were adjudicated from hospital records and classified as HFpEF (left ventricular ejection fraction ≥50%) or HFrEF (ejection fraction <50%). Results: A total of 8090 participants were included; 2927 from the JHS (median [IQR] age, 56 [46-65] years; 1846 [63.1%] female; 2927 [100.0%] Black or African American) and 5163 from the WHI (median [IQR] age, 67 [62-72] years; 5163 [100.0%] female; 29 [0.6%] American Indian or Alaska Native, 37 [0.7%] Asian or Pacific Islander, 1383 [26.8%] Black or African American, 293 [5.7%] Hispanic or Latinx, 3407 [66.0%] non-Hispanic White, and 14 [0.3%] with other race and ethnicity). The multivariable-adjusted hazard ratio (HR) for composite CHIP and HFpEF was 1.28 (95% CI, 0.93-1.76; P = .13), and for CHIP and HFrEF it was 0.79 (95% CI, 0.49-1.25; P = .31). TET2 CHIP was associated with HFpEF in both cohorts (meta-analyzed HR, 2.35 [95% CI, 1.34 to 4.11]; P = .003) independent of cardiovascular risk factors and coronary artery disease. Analyses stratified by C-reactive protein (CRP) in the WHI found an increased risk of incident HFpEF in individuals with CHIP and CRP greater than or equal to 2 mg/L (HR, 1.94 [95% CI, 1.20-3.15]; P = .007), but not in those with CHIP and CRP less than 2 mg/L or those with CRP greater than or equal to 2 mg/L without CHIP, when compared with participants without CHIP and CRP less than 2 mg/L. Conclusions and Relevance: In this cohort study, TET2 CHIP was an independent risk factor associated with incident HFpEF. This finding may have implications for the prevention and management of HFpEF, including development of targeted therapies.

Knee cartilage change on magnetic resonance imaging: Should we lump or split topographical regions? A 2-year study of data from the osteoarthritis initiative.

OBJECTIVE: We challenge the paradigm that a simplistic approach evaluating anatomic regions (e.g., medial femur or tibia) is ideal for assessing articular cartilage loss on magnetic resonance (MR) imaging. We used a data-driven approach to explore whether specific topographical locations of knee cartilage loss may identify novel patterns of cartilage loss over time that current assessment strategies miss. DESIGN: We assessed 60 location-specific measures of articular cartilage on a sample of 99 knees with baseline and 24-month MR images from the Osteoarthritis Initiative, selected as a group with a high likelihood to change. We performed factor analyses of the change in these measures in two ways: (1) summing the measures to create one measure for each of the six anatomically regional-based summary (anatomic regions; e.g., medial tibia) and (2) treating each location separately for a total of 60 measures (location-specific measures). RESULTS: The first analysis produced three factors accounting for 66% of the variation in the articular cartilage changes that occur over 24 months of follow-up: (1) medial tibiofemoral, (2) medial and lateral patellar, and (3) lateral tibiofemoral. The second produced 20 factors accounting for 75% of the variance in cartilage changes. Twelve factors only involved one anatomic region. Five factors included locations from adjoining regions (defined by the first analysis; e.g., medial tibiofemoral). Three factors included articular cartilage loss from disparate locations. CONCLUSIONS: Novel patterns of cartilage loss occur within each anatomic region and across these regions, including in disparate regions. The traditional anatomic regional approach is simpler to implement and interpret but may obscure meaningful patterns of change.

Strength Training Is Associated With Less Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: We aimed to evaluate the relationship of a history of strength training with symptomatic and structural outcomes of knee osteoarthritis (OA). METHODS: This study was a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), a multicenter prospective longitudinal observational study. Data were collected at four OAI clinical sites: Memorial Hospital of Rhode Island, the Ohio State University, the University of Pittsburgh, and the University of Maryland/Johns Hopkins. The study included 2,607 participants with complete data on strength training, knee pain, and radiographic evidence of knee OA (male, 44.2%; mean ± SD age 64.3 ± 9.0 years; mean ± SD body mass index 28.5 ± 4.9 kg/m2 ). We used a self-administered questionnaire at the 96-month OAI visit to evaluate the exposure of strength training participation during four time periods throughout a participant's lifetime (ages 12-18, 19-34, 35-49, and ≥50 years old). The outcomes (dependent variables) were radiographic OA (ROA), symptomatic radiographic OA (SOA), and frequent knee pain. RESULTS: The fully adjusted odds ratios (95% confidence interval) for frequent knee pain, ROA, and SOA among those who participated in strength training any time in their lives were 0.82 (0.68-0.97), 0.83 (0.70-0.99), and 0.77 (0.63-0.94), respectively. Findings were similar when looking at the specific age ranges. CONCLUSION: Strength training is beneficial for future knee health, counteracting long-held assumptions that strength training has adverse effects.

Association of Weight Loss and Weight Gain With Structural Defects and Pain in Hand Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: Our aim was to define the association of weight change (weight loss or weight gain) with the incidence and progression of hand osteoarthritis (OA), assessed either by radiography or by pain, using data from the Osteoarthritis Initiative. METHODS: Among the 4,796 participants, we selected 4,598 participants, excluding those with cancer or rheumatoid arthritis or a body mass index under 18.5 kg/m2. We investigated the association of weight change with incidence and progression of radiographic hand OA and the development and resolution of hand pain. Using multivariable logistic regression, we investigated the association of weight change from baseline to the 4-year follow-up with the incidence and progression of radiographic hand OA at the 4-year follow-up. Additionally, multivariable repeated-measure mixed-effects logistic regression analyzed the association of weight change with the development and resolution of hand pain across 2-year, 4-year, 6-year, and 8-year follow-ups. RESULTS: No statistically significant associations were observed between weight change and the investigated outcomes. Specifically, for each 5% weight loss, the odds ratios for the incidence and progression of radiographic hand OA were 0.90 (95% confidence interval [95% CI] 0.67-1.23) and 0.92 (95% CI 0.84-1.00), respectively. Similarly, for each 5% weight loss, the odds ratios for the development and resolution of hand pain at the 8-year follow-up were 1.00 (95% CI 0.92-1.09) and 1.07 (95% CI 0.91-1.25), respectively. CONCLUSION: Our study found no evidence of an association between weight change and the odds of incidence or progression of radiographic hand OA over 4 years, nor the development or resolution of hand pain over 8 years.

Radiographic joint space width in individuals with hand osteoarthritis: Are their "healthy" joints really healthy?

OBJECTIVES: We aimed to investigate the systemic nature of hand osteoarthritis (OA). We hypothesized that people who suffer from hand OA would display narrower radiographic joint space width (JSW) - not only in joints with apparent radiographic OA but also in their unaffected "healthy" joints. METHOD: We examined 3394 participants from the Osteoarthritis Initiative with available dominant hand radiographs at baseline. Cases were defined as having interphalangeal OA (IPOA) based on a Kellgren and Lawrence (KL) score of ≥2 in two or more finger joints, whereas controls did not have IPOA. We used custom software to make JSW measurements of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints in fingers 2-5 per hand. In joint-level analyses, we included only KL score=0, allowing us to compare all joints without IPOA in cases and controls. We used generalized estimating equation models to compare JSW between both groups, adjusted for age, gender, metacarpal length, and joint type. RESULTS: Finger joints without radiographic OA had significantly narrower JSW in the IPOA group compared to finger joints in the control group (p < 0.001). The differences were significant across all joint types and for both total JSW measurements as well as for central and lateral sub-regions within each joint group (p < 0.001). CONCLUSION: Unaffected finger joints in people with IPOA had narrower joint space than joints of healthy controls. This implies a systemic nature of hand OA, in which people may have a predisposition for general cartilage deterioration.

Hand joints without radiographic osteoarthritis maintain their joint space width over 4 years despite what's happening elsewhere in the hand.

OBJECTIVES: We aimed to determine if hand osteoarthritis is characterized by systemic cartilage loss by assessing if radiographically normal joints had greater joint space width (JSW) loss during four years in hands with incident or prevalent osteoarthritis elsewhere in the hand compared with hands without osteoarthritis. METHODS: We used semi-automated software to measure JSW in the distal and proximal interphalangeal joints of 3,368 participants in the Osteoarthritis Initiative who had baseline and 48-month hand radiographs. A reader scored 16 hand joints (including the thumb-base) for Kellgren-Lawrence (KL) Grade. A joint had osteoarthritis if scored as KL ≥ 2. We identified three groups based on longitudinal hand osteoarthritis status: 1) no hand osteoarthritis (KL < 2 in all 16 joints) at the baseline and 48-month visits, 2) incident hand osteoarthritis (KL < 2in all 16 joints at baseline and then ≥1 joint with KL ≥ 2 at 48-months), and 3) prevalent hand osteoarthritis (≥1 joint with KL ≥ 2 at baseline and 48-months). We then assessed if JSW in radiographically normal joints (KL = 0) differed across these three groups. We calculated unpooled effect sizes to help interpret the differences between groups. RESULTS: We observed small differences in JSW loss that are unlikely to be clinically important between radiographically normal joints between those without hand osteoarthritis (n = 1054) and those with incident (n = 102) or prevalent hand osteoarthritis (n = 2212) (effect size range: -0.01 to 0.24). These findings were robust when examining JSW loss dichotomized based on meaningful change and in other secondary analyses. CONCLUSIONS: Hand osteoarthritis is not a systemic disease of cartilage.

Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People: Secondary Analysis of a Randomized Clinical Trial.

Importance: Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals. Objective: To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin. Design, Setting, and Participants: This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023. Interventions: Daily 100-mg enteric-coated aspirin or matching placebo. Main Outcomes and Measures: Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records. Results: Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04). Conclusions and Relevance: This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma. Trial Registration: ISRCTN.org Identifier: ISRCTN83772183.

Examining the Relationship Between Multilevel Resilience Resources and Cardiovascular Disease Incidence, Overall and by Psychosocial Risks, Among Participants in the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

We examined relationships between resilience resources (optimism, social support, and neighborhood social cohesion) and cardiovascular disease (CVD) incidence and assessed potential effect-measure modification by psychosocial risk factors (e.g., stress, depression) among adults without CVD in 3 cohort studies (2000-2018): the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study. We fitted adjusted Cox models accounting for within-neighborhood clustering while censoring at dropout or non-CVD death. We assessed for effect-measure modification by psychosocial risks. In secondary analyses, we estimated standardized risk ratios using inverse-probability-weighted Aalen-Johansen estimators to account for confounding, dropout, and competing risks (non-CVD deaths) and obtained 95% confidence intervals (CIs) using cluster bootstrapping. For high and medium (versus low) optimism (n = 6,243), adjusted hazard ratios (HRs) for incident CVD were 0.94 (95% CI: 0.78, 1.13) and 0.90 (95% CI: 0.75, 1.07), respectively. Corresponding HRs were 0.88 (95% CI: 0.74, 1.04) and 0.92 (95% CI: 0.79, 1.06) for social support (n = 7,729) and 1.10 (95% CI: 0.94, 1.29) and 0.99 (95% CI: 0.85, 1.16) for social cohesion (n = 7,557), respectively. Some psychosocial risks modified CVD HRs. Secondary analyses yielded similar findings. For optimism and social support, an inverse relationship was frequently most compatible with the data, but a positive relationship was also compatible. For neighborhood social cohesion, positive and null relationships were most compatible. Thus, specific resilience resources may be potential intervention targets, especially among certain subgroups.

Association of Clonal Hematopoiesis of Indeterminate Potential with Incident Heart Failure with Preserved Ejection Fraction.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) was recently identified as a risk factor for incident heart failure (HF). Whether CHIP is associated selectively with risk of heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) subtypes is unknown. Objectives: To evaluate whether CHIP is associated with incident HF subtypes, HFrEF versus HFpEF. Methods: We obtained CHIP status from whole genome sequencing of blood DNA in participants without prevalent HF from a multi-ethnic sample of post-menopausal women without prevalent HF (N=5,214) from the Women's Health Initiative (WHI). Cox proportional hazards models were performed, adjusting for demographic and clinical risk factors. Results: CHIP was significantly associated with a 42% (95%CI 6%, 91%) increased risk of HFpEF (P=0.02). In contrast, there was no evidence of association between CHIP and risk of incident HFrEF. When the three most common CHIP subtypes were assessed individually, the risk of HFpEF was more strongly associated with TET2 (HR=2.5; 95%CI 1.54, 4.06; P<0.001), than DNMT3A or ASXL1. Conclusion: CHIP, particularly mutations in TET2, represents a potential new risk factor for incident HFpEF.

Racial and Ethnic Differences in Self-Reported COVID-19 Exposure Risks, Concerns, and Behaviors Among Diverse Participants in the Women's Health Initiative Study.

BACKGROUND: Racial and ethnic disparities in coronavirus disease 2019 (COVID-19) risk are well-documented; however, few studies in older adults have examined multiple factors related to COVID-19 exposure, concerns, and behaviors or conducted race- and ethnicity-stratified analyses. The Women's Health Initiative (WHI) provides a unique opportunity to address those gaps. METHODS: We conducted a secondary analysis of WHI data from a supplemental survey of 48 492 older adults (mean age 84 years). In multivariable-adjusted modified Poisson regression analyses, we examined predisposing factors and COVID-19 exposure risk, concerns, and behaviors. We hypothesized that women from minoritized racial or ethnic groups, compared to non-Hispanic White women, would be more likely to report: exposure to COVID-19, a family or friend dying from COVID-19, difficulty getting routine medical care or deciding to forego care to avoid COVID-19 exposure, and having concerns about the COVID-19 pandemic. RESULTS: Asian women and non-Hispanic Black/African American women had a higher risk of being somewhat/very concerned about risk of getting COVID-19 compared to non-Hispanic White women and each was significantly more likely than non-Hispanic White women to report forgoing medical care to avoid COVID-19 exposure. However, Asian women were 35% less likely than non-Hispanic White women to report difficulty getting routine medical care since March 2020 (adjusted relative risk 0.65; 95% confidence interval 0.57, 0.75). CONCLUSIONS: We documented COVID-related racial and ethnic disparities in COVID-19 exposure risk, concerns, and care-related behaviors that disfavored minoritized racial and ethnic groups, particularly non-Hispanic Black/African American women.

The co-occurrence and cumulative prevalence of hypertension, rheumatoid arthritis, and hypothyroidism in preterm-born women in the Women's Health Initiative.

Emerging evidence suggests that preterm-born individuals (<37 weeks gestation) are at increased risk of developing chronic health conditions in adulthood. This study compared the prevalence, co-occurrence, and cumulative prevalence of three female predominant chronic health conditions - hypertension, rheumatoid arthritis [RA], and hypothyroidism - alone and concurrently. Of 82,514 U.S. women aged 50-79 years enrolled in the Women's Health Initiative, 2,303 self-reported being born preterm. Logistic regression was used to analyze the prevalence of each condition at enrollment with birth status (preterm, full term). Multinomial logistic regression models analyzed the association between birth status and each condition alone and concurrently. Outcome variables using the 3 conditions were created to give 8 categories ranging from no disease, each condition alone, two-way combinations, to having all three conditions. The models adjusted for age, race/ethnicity, and sociodemographic, lifestyle, and other health-related risk factors. Women born preterm were significantly more likely to have any one or a combination of the selected conditions. In fully adjusted models for individual conditions, the adjusted odds ratios (aORs) were 1.14 (95% CI, 1.04, 1.26) for hypertension, 1.28 (1.12, 1.47) for RA, and 1.12 (1.01, 1.24) for hypothyroidism. Hypothyroidism and RA were the strongest coexisting conditions [aOR 1.69, 95% CI (1.14, 2.51)], followed by hypertension and RA [aOR 1.48, 95% CI (1.20, 1.82)]. The aOR for all three conditions was 1.69 (1.22, 2.35). Perinatal history is pertinent across the life course. Preventive measures and early identification of risk factors and disease in preterm-born individuals are essential to mitigating adverse health outcomes in adulthood.

Automatic Measuring of Finger Joint Space Width on Hand Radiograph using Deep Learning and Conventional Computer Vision Methods.

Hand osteoarthritis (OA) severity can be assessed visually through radiographs using semi-quantitative grading systems. However, these grading systems are subjective and cannot distinguish minor differences. Joint space width (JSW) compensates for these disadvantages, as it quantifies the severity of OA by accurately measuring the distances between joint bones. Current methods used to assess JSW require users' interaction to identify the joints and delineate initial joint boundary, which is time-consuming. To automate this process and offer a more efficient and robust measurement for JSW, we proposed two novel methods to measure JSW: 1) The segmentation-based (SEG) method, which uses traditional computer vision techniques to calculate JSW; 2) The regression-based (REG) method, which is a deep learning approach employing a modified VGG-19 network to predict JSW. On a dataset with 3,591 hand radiographs, 10,845 DIP joints were cut as regions of interest and served as input to the SEG and REG methods. The bone masks of the ROI images generated by a U-Net model were sent as input in addition to the ROIs. The ground truth of JSW was labeled by a trained research assistant using a semi-automatic tool. Compared with the ground truth, the REG method achieved a correlation coefficient of 0.88 and mean square error (MSE) of 0.02 mm on the testing set; the SEG method achieved a correlation coefficient of 0.42 and MSE of 0.15 mm. Results show the REG method has promising performance in automatic JSW measurement and in general, Deep Learning approaches can facilitate the automatic quantification of distance features in medical images.