Gender and age differences in the associations between cortical thickness and hand osteoarthritis severity: data from the Osteoarthritis Initiative.

OBJECTIVE: To evaluate gender differences in the association between metacarpal cortical thickness (Tcort)-a surrogate for bone density-and severity of radiographic hand osteoarthritis (HOA) in a longitudinal observational study. METHOD: Hand radiographs of 3575 participants (2039 F/1536 M) from the Osteoarthritis Initiative were assessed at baseline and 48 months. A reader used a semi-automated software tool to calculate Tcort, a measurement of the cortical thickness, for metacarpals 2-4. Average Tcort at baseline and change in Tcort from baseline to 48 months was determined and stratified by gender and age for 7 5-year age groups. Spearman's rank correlation coefficients were calculated for the association of baseline Tcort and 2 measures of baseline HOA severity: the sum of Kellgren-Lawrence (KL) grade and total number of joints with radiographic HOA. Longitudinally, logistic regression was used to assess the relationship of Tcort loss to new finger joint radiographic HOA, increase in KL grades, and incident hand pain. RESULTS: Male Tcort was higher than females. Significant correlations between Tcort and radiographic severity were noted for women but not men, with stronger associations among women >60 years (rho = -0.25; 95% confidence interval (CI) = -0.31 to -0.19). Statistically significant associations were seen between Tcort change and radiographic osteoarthritis change among women but not men, with substantial gender differences for Tcort change, particularly ages 50 to 70 years (p < 0.01; e.g., Tcort change ages 55 to <60: males = -0.182 (0.118), females = -0.219 (0.124)). CONCLUSION: We found significant HOA-related gender differences in Tcort, suggesting the involvement of female bone loss during and after menopause.

Associations of inflammatory and metabolic biomarkers with incident erosive hand osteoarthritis in the osteoarthritis initiative cohort.

OBJECTIVE: Erosive hand osteoarthritis (eHOA) is a subtype of hand osteoarthritis (OA) that develops in finger joints with pre-existing OA and is differentiated by clinical characteristics (hand pain/disability, inflammation, and erosions) that suggest inflammatory or metabolic processes. METHOD: This was a longitudinal nested case-cohort design among Osteoarthritis Initiative participants who had hand radiographs at baseline and 48-months, and biospecimens collected at baseline. We classified incident radiographic eHOA in individuals with ≥1 joint with Kellgren-Lawrence ≥2 and a central erosion present at 48-months but not at baseline. We used a random representative sample (n = 1282) for comparison. We measured serum biomarkers of inflammation, insulin resistance and dysglycemia, and adipokines using immunoassays and enzymatic colorimetric procedures, blinded to case status. RESULTS: Eighty-six participants developed incident radiographic eHOA. In the multivariate analyses adjusted for age, gender, race, smoking, and body mass index, and after adjustment for multiple analyses, incident radiographic eHOA was associated with elevated levels of interleukin-7 (risk ratio (RR) per SD = 1.30 [95% confidence interval (CI) 1.09, 1.55] p trend 0.01). CONCLUSION: This exploratory study suggests an association of elevated interleukin-7, an inflammatory cytokine, with incident eHOA, while other cytokines or biomarkers of metabolic inflammation were not associated. Interleukin-7 may mediate inflammation and tissue damage in susceptible osteoarthritic finger joints and participate in erosive progression.

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.

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.

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.

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.

Association of Preterm Birth With Prevalent and Incident Hypertension, Early-Onset Hypertension, and Cardiovascular Disease in the Women's Health Initiative.

Increasing evidence suggests preterm birth is a risk factor for hypertension and cardiovascular disease (CVD) in adulthood. Whether there is effect modification by hypertension on CVD risk is unknown. To investigate the associations between preterm birth, hypertension, and incident CVD, we identified 2,303 women aged 50 to 79 years who self-reported being born preterm from the Women's Health Initiative. Using multivariable logistic regression, prevalent hypertension at enrollment, age at hypertension diagnosis, and antihypertensive medication use were compared by birth status (preterm, full-term). Risk of incident hypertension, coronary heart disease, and CVD were analyzed using multivariable Cox proportional-hazard models. Both models adjusted for age, race/ethnicity, education, smoking, physical activity, body mass index, and diabetes mellitus. Significant associations were found between preterm birth and prevalent hypertension (37% vs 33.1%; adjusted odds ratio 1.26 [95% confidence interval (CI) 1.15 to 1.28] p = <0.0001), early-onset hypertension (<50 years) (14.7% vs 11.7%; adjusted odds ratio 1.31, 95% CI 1.15 to 1.48, p = <0.0001), and incident hypertension (53.2% vs 51%; ajusted hazard ratio 1.10, 95% CI 1.03 to 1.19, p = 0.008). Preterm-born women reported taking more antihypertensive medications (2.9% vs 2.6%, p = 0.04). Preterm birth had a nonsignificant association with CVD risk, but when stratified by prevalent hypertension, women born preterm without hypertension had elevated CVD risk compared with women born full-term without prevalent hypertension. Women with prevalent hypertension, preterm and full-term, had similar magnitudes of elevations in CVD risk. In conclusion, preterm birth increases the risk of hypertension and coronary heart disease. With 10% of the population born preterm, birth history should be assessed as a CVD risk factor.

Bronchopulmonary dysplasia and neurobehavioural outcomes at birth and 2 years in infants born before 30 weeks.

OBJECTIVE: To identify neurobehavioural risks in preterm infants with bronchopulmonary dysplasia (BPD) prior to hospital discharge. DESIGN AND PATIENTS: Longitudinal study of 676 newborns born before 30 weeks of gestation. SETTING: Nine university NICUs affiliated with six universities. All were Vermont Oxford Network (VON) participants. PATIENTS AND INTERVENTIONS: Infants were enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants Study from April 2014 to June 2016. Prospective medical record reviews, VON definitions and criteria, and maternal interviews were used to collect maternal and neonatal medical variables and socioenvironmental data. MAIN OUTCOME MEASURES: NICU Network Neurobehavioral Scale (NNNS) at the time of hospital discharge; Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and Gross Motor Function Classification System at 2 years' corrected age. RESULTS: Infants with moderate/severe BPD were less attentive (Wald χ2 9.68, p=0.008), more lethargic (Wald χ2 9.91, p=0.007), with increased non-optimal reflexes (Wald χ2 7.37, p=0.025). Infants with moderate/severe BPD were more likely to have Bayley-III language and motor scores <85 (adjusted OR (aOR) 1.74, 95% CI 1.06 to 2.85, and aOR 2.06, 95% CI 1.10 to 3.85). Infants with both moderate/severe and mild BPD were more likely to have a cerebral palsy diagnosis (aOR 2.96, 95% CI 1.34 to 6.54, and aOR 2.81, 95% CI 1.32 to 5.99). CONCLUSIONS: BPD severity presents risks for poor neurodevelopment at NICU discharge and at age 2 years. Early identification of poorly regulated behaviour can provide critical information for early preventive and targeted interventions with potential to improve long-term outcomes.

Heart rate variability and the risk of heart failure and its subtypes in post-menopausal women: The Women's Health Initiative study.

BACKGROUND: Low heart rate variability (HRV), a measure of autonomic imbalance, is associated with increased risk of coronary heart disease (CHD) and heart failure (HF). However, its relationship with HF subtypes; heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) has not been studied prior. METHODS AND FINDINGS: We conducted a longitudinal study in Women's Health Initiative study cohort to investigate the association of baseline quartiles of resting heart rate (rHR) and HRV measures; SDNN (SD of normal-to-normal RR interval) and RMSSD (root mean square of successive difference of RR interval) measured by twelve-lead electrocardiogram (ECG) on enrollment, with the risk of hospitalized HF and its subtypes. Total of 28,603 post-menopausal women, predominantly non-Hispanic whites (69%), with a mean (SD) age of 62.6 (7.1) years, free of baseline CHD and HF were included. In a fully adjusted cox-proportional hazards regression model which adjusted for age, race, BMI, alcohol intake, education, physical activity, hyperlipidemia, hypertension, left ventricular hypertrophy, use of beta-blocker, calcium-channel blocker, hormone therapy, and time-varying incident CHD, the hazard ratios of lowest quartile of HRV (Q1) with HF risk were significant (Q1 SDNN compared to Q4 SDNN: 1.22, 95% CI 1.07, 1.39; Q1 RMSSD compared to Q4 RMSSD: 1.17, 95% CI 1.02, 1.33). On subgroup analysis of HF subtypes, low HRV was associated with elevated HFpEF risk (Q1 vs Q4 SDNN: 1.22, 95% CI 1.02, 1.47) but not with HFrEF (Q1 vs Q4 SDNN: 1.19, 95% CI 0.95, 1.50; Q1 RMSSD: 1.13, 95% CI 0.90, 1.43). CONCLUSION: Low HRV is associated with elevated overall hospitalized HF risk and HFpEF risk in post-menopausal women. Whether interventions to increase HRV through healthy lifestyle changes will decrease HF risk warrants further investigation.

From HRSA Grant to Medical Practice: Improving Care for Children and Adolescents in a Family Medicine Residency Clinic.

BACKGROUND: The patient-centered medical home (PCMH) is an ideal primary care model for patients across the lifespan. Family Medicine (FM) practice and training often address adults more than children/adolescents. Few studies describe the efficacy of education programs seeking to enhance PCMH-based care of children/adolescents. METHODS: At the Brown FM Residency in Pawtucket, Rhode Island (RI), from 2015-2020, we aimed to enhance care of children/adolescents through a HRSA-funded program that enhanced PCMH-based care for children/adolescents and related resident education. Our mixed- methods evaluation assessed learner experiences. Vaccination data assessed patient impact. RESULTS: 119/155 (77%) residents completed surveys over four years and learning and performance improved, especially in PCMH principles and behavorial health (BH) competencies. Vaccination rates improved. Qualitative interviews supported quantitative results. CONCLUSIONS: Enhancing care for children/adolescents within a FM residency clinic requires a multi-pronged approach. This initiative improved children/adolescents' care and increased residents' learning and performance.

Nurse practitioners in home-based prepalliative care demonstrate an innovative, value-based approach to end-of-life care planning.

BACKGROUND: Nurse practitioners (NPs) demonstrate value-based, home-based primary health care (HBPC) to home-bound patients with high disease burden at reduced cost. PURPOSE: The research questions were as follows: (a) Does patient-centered, prepalliative care delivered by HBPC NPs decrease number of hospitalizations and emergency department (ED) visits and increase patient satisfaction? and (b) What are the criteria for patients to receive end-of-life (EOL) discussions by NPs? METHODOLOGY: This was a quasi-experimental, retrospective two-group design with a convenience sample of 233 HBPC patients from an academic clinical partnership compared with 234 clinic patients matched on age and Charlson Comorbidity Index (CCI) score over 4 years. Measures included signed advanced directives (ADRs), medical orders of life-sustaining treatment (MOLST) forms, number and length of home visits, hospitalizations, and ED visits after diagnosis. Chi-square analyses and general linear models using a Poisson distribution were conducted. RESULTS: Home-based primary health care patients had higher disease burden, statistically higher CCI scores, and signed ADR and MOLST agreements more often than clinic patients with significantly fewer hospitalizations and ED visits, and longer visits with providers. CONCLUSIONS: Patients receiving HBPC for prepalliative, EOL illness benefit from more time to discuss the difficult factors surrounding access to care for those with life-threatening illnesses. IMPLICATIONS: Recipients of prepalliative HBPC by NPs could require fewer provider visits, hospitalizations and ED visits, patient satisfaction, and a potential decrease in health care spending at EOL.

Racket or Bat Sports: No Association With Thumb-Base Osteoarthritis.

CONTEXT: Repetitive joint use is a risk factor for osteoarthritis, which is a leading cause of disability. Sports requiring a racket or bat to perform repetitive high-velocity impacts may increase the risk of thumb-base osteoarthritis. However, this hypothesis remains untested. OBJECTIVE: To determine if a history of participation in racket or bat sports was associated with the prevalence of thumb-base osteoarthritis. DESIGN: Descriptive epidemiologic study. SETTING: Four US clinical sites associated with the Osteoarthritis Initiative. PATIENTS OR OTHER PARTICIPANTS: We recruited 2309 men and women from the community. Eligible participants had dominant-hand radiographic readings, hand symptom assessments, and historical physical activity survey data. MAIN OUTCOME MEASURE(S): A history of exposure to racket or bat sports (badminton, baseball or softball, racketball or squash, table tennis [or ping pong], tennis [doubles], or tennis [singles]) was based on self-reported recall data covering 3 age ranges (12-18, 19-34, and 35-49 years). Prevalent radiographic thumb-base osteoarthritis was defined as Kellgren-Lawrence grade >2 in the first carpometacarpal joint or scaphotrapezoidal joint at the Osteoarthritis Initiative baseline visit. Symptomatic thumb-base osteoarthritis was defined as radiographic osteoarthritis and hand or finger symptoms. RESULTS: Radiographic or symptomatic thumb-base osteoarthritis was present in 355 (34%) and 56 (5%), respectively, of men (total = 1049) and 535 (42%) and 170 (13%), respectively, of women (total = 1260). After adjusting for age, race, and education level, we found no significant associations between a history of any racket or bat sport participation and thumb-base osteoarthritis (radiographic or symptomatic; odds ratios ranged from 0.82 to 1.34). CONCLUSIONS: In a community-based cohort, a self-reported history of participation in racket or bat sports was not associated with increased odds of having radiographic or symptomatic thumb-base osteoarthritis in the dominant hand.

Associations between maternal pre-pregnancy body mass index and neonatal neurobehavior in infants born before 30 weeks gestation.

OBJECTIVE: To examine the relationship between maternal pre-pregnancy body mass index (BMI) and neonatal neurobehavior in very premature infants. STUDY DESIGN: Multi-center prospective observational study of 664 very preterm infants with 227 born to obese mothers. The NICU Network Neurobehavioral Scale (NNNS) assessed neurobehavior at NICU discharge. RESULTS: Elevated BMI combined with infection increased the odds of having the most poorly regulated NNNS profile by 1.9 times per BMI SD. Infants born to mothers with elevated BMI in combination with: infection had poorer self-regulation, chorioamnionitis had increased asymmetrical reflexes, diabetes had poorer attention, and low SES required more handling. CONCLUSION: Maternal pre-pregnancy BMI alone did not affect short-term neonatal neurobehavior in infants born before 30 weeks gestation. Infants born to mothers with elevated pre-pregnancy weight in addition to infections, diabetes, or socioeconomic adversity demonstrated increased risk of having the most poorly regulated NNNS profile and deficits in multiple domains.

The association of walking pace and incident heart failure and subtypes among postmenopausal women.

BACKGROUND: To investigate the association between walking pace and the risk of heart failure (HF) and HF sub-types. METHODS: We examined associations of self-reported walking pace with risk of incident HF and HF subtypes of preserved (HFpEF) and reduced (HFrEF) ejection fractions, among 25,183 postmenopausal women, ages 50-79 years. At enrollment into the Women's Health Initiative cohort in 1993-1998, this subset of women was free of HF, cancer, or the inability to walk one block, with self-reported information on walking pace and walking duration. Multivariable Cox regression was used to examine associations of walking pace (casual <2 mph [referent], average 2-3 mph, and fast >3 mph) with incident HF. We also examined the joint association of walking pace and duration with incident HF. RESULTS: There were 1455 incident adjudicated acute decompensated HF hospitalization cases during a median of 16.9 years of follow-up. There was a strong inverse association between walking pace and overall risk of HF (HR = 0.73, 95% CI [0.65, 0.83] for average vs. casual walking; HR = 0.66, 95%CI [0.56, 0.78] for fast vs. casual walking). There were similar associations of walking pace with HFpEF (HR = 0.73, 95%CI [0.62, 0.86] average vs. casual; HR = 0.63, 95%CI [0.50, 0.80] for fast vs. casual) and with HFrEF (HR = 0.72, 95%CI [0.57, 0.91] for average vs. casual; HR = 0.74, 95%CI [0.54, 0.99] for fast vs. casual). The risk of HF associated with fast walking with less than 1 h/week walking duration was comparable with the risk of HF among casual and average walkers with more than 2 h/week walking duration. CONCLUSION: Walking pace was inversely associated with risks of overall HF, HFpEF, and HFrEF in postmenopausal women. Whether interventions to increase the walking pace in older adults will reduce HF risk and whether fast pace will compensate for the short duration of walking warrants further study.

Association between race/ethnicity and income on the likelihood of coronary revascularization among postmenopausal women with acute myocardial infarction: Women's health initiative study.

BACKGROUND: Historically, race, income, and gender were associated with likelihood of receipt of coronary revascularization for acute myocardial infarction (AMI). Given public health initiatives such as Healthy People 2010, it is unclear whether race and income remain associated with the likelihood of coronary revascularization among women with AMI. METHODS: Using the Women's Health Initiative Study, hazards ratio (HR) of revascularization for AMI was compared for Black and Hispanic women vs White women and among women with annual income <$20,000/year vs ≥$20,000/year over median 9.5 years follow-up(1993-2019). Proportional hazards models were adjusted for demographics, comorbidities, and AMI type. Results were stratified by revascularization type: percutaneous coronary intervention and coronary artery bypass grafting(CABG). Trends by race and income were compared pre- and post-2010 using time-varying analysis. RESULTS: Among 5,284 individuals with AMI (9.5% Black, 2.8% Hispanic, and 87.7% White; 23.2% <$20,000/year), Black race was associated with lower likelihood of receiving revascularization for AMI compared to White race in fully adjusted analyses [HR:0.79(95% Confidence Interval:[CI]0.66,0.95)]. When further stratified by type of revascularization, Black race was associated with lower likelihood of percutaneous coronary intervention for AMI compared to White race [HR:0.72(95% CI:0.59,0.90)] but not for CABG [HR:0.97(95%CI:0.72,1.32)]. Income was associated with lower likelihood of revascularization [HR:0.90(95%CI:0.82,0.99)] for AMI. No differences were observed for other racial/ethnic groups. Time periods (pre/post-2010) were not associated with change in revascularization rates. CONCLUSION: Black race and income remain associated with lower likelihood of revascularization among patients presenting with AMI. There is a substantial need to disrupt the mechanisms contributing to race, sex, and income disparities in AMI management.

Prevalence, Incidence, and Progression of Radiographic and Symptomatic Hand Osteoarthritis: The Osteoarthritis Initiative.

OBJECTIVE: To describe the prevalence, incidence, and progression of radiographic and symptomatic hand osteoarthritis (OA), and to evaluate differences according to age, sex, race, and other risk factors. METHODS: Participants were assessed for radiographic and symptomatic hand OA at baseline and year 4 to determine incident disease. A modified Poisson regression with a robust variance estimator was used to account for clustering of joints within fingers within persons to estimate the prevalence ratios and relative risk estimates associated with participant characteristics. RESULTS: Among 3,588 participants, the prevalence of radiographic hand OA was 41.4%, and the prevalence of symptomatic hand OA was 12.4%. The incidence over 48 months was 5.6% for radiographic hand OA and 16.9% for symptomatic hand OA. Over 48 months, 27.3% of the participants exhibited OA progression. We found complex differences by age, sex, and race, with increasing rates of prevalent hand OA with older age in both men and women, but with rates of incident disease peaking at ages 55-64 years in women. Women had higher rates of symptomatic hand OA, but only nonsignificantly higher rates of incident radiographic hand OA, than men. Women more frequently had distal interphalangeal joint disease, while men more frequently had metacarpophalangeal joint OA. Black men and women had lower rates of hand OA than White participants, but Black men had higher rates of prevalent hand OA than Black women at younger ages. CONCLUSION: Hand OA is a heterogeneous disease with complex differences by age, sex, race, hand symptoms, and patterns of specific joints affected. Further research investigating the mechanisms behind these differences, whether mechanical, metabolic, hormonal, or constitutional, is warranted.

Maternal Worry About Infant Weight and its Influence on Artificial Milk Supplementation and Breastfeeding Cessation.

BACKGROUND: Maternal worry about infant weight has inconsistently been reported as a breastfeeding barrier. Weight monitoring is a critical tool to assess adequacy of infant feeding. Yet, little is known about the intensity of maternal worry about infant weight or associated breastfeeding outcomes. RESEARCH AIMS: To examine (1) the frequency and intensity of maternal worry about infant weight; (2) the relationship between worry about weight and use of artificial milk; and 3) the relationship between worry about weight and breastfeeding cessation. METHODS: A prospective cross-sectional design was used. A questionnaire was completed by women in the United States (N = 287) from 12 web-based maternal support groups. RESULTS: Sixty-three percent of women (n = 182) had some worry about infant weight. Participants breastfeeding for the first time had more worry (p = .035). Participants still breastfeeding had less worry about weight compared to those who had stopped (67%, n = 147 vs. 41%, n = 28). Exclusive breastfeeding participants had less worry (p < .001) compared to those who supplemented with artificial milk. Increased worry was associated with the use of artificial milk within 1 week of birth (p < .001) and early breastfeeding cessation (p < .001). CONCLUSIONS: Worry about weight is a significant breastfeeding barrier. It is associated with first time breastfeeding, less exclusive breastfeeding, use of artificial milk, and earlier breastfeeding cessation. Lactating mothers need anticipatory guidance about expected neonatal weight changes and interventions to help relieve worry about infant weight.

Supplemental Association of Clonal Hematopoiesis With Incident Heart Failure.

BACKGROUND: Age-related clonal hematopoiesis of indeterminate potential (CHIP), defined as clonally expanded leukemogenic sequence variations (particularly in DNMT3A, TET2, ASXL1, and JAK2) in asymptomatic individuals, is associated with cardiovascular events, including recurrent heart failure (HF). OBJECTIVES: This study sought to evaluate whether CHIP is associated with incident HF. METHODS: CHIP status was obtained from whole exome or genome sequencing of blood DNA in participants without prevalent HF or hematological malignancy from 5 cohorts. Cox proportional hazards models were performed within each cohort, adjusting for demographic and clinical risk factors, followed by fixed-effect meta-analyses. Large CHIP clones (defined as variant allele frequency >10%), HF with or without baseline coronary heart disease, and left ventricular ejection fraction were evaluated in secondary analyses. RESULTS: Of 56,597 individuals (59% women, mean age 58 years at baseline), 3,406 (6%) had CHIP, and 4,694 developed HF (8.3%) over up to 20 years of follow-up. CHIP was prospectively associated with a 25% increased risk of HF in meta-analysis (hazard ratio: 1.25; 95% confidence interval: 1.13-1.38) with consistent associations across cohorts. ASXL1, TET2, and JAK2 sequence variations were each associated with an increased risk of HF, whereas DNMT3A sequence variations were not associated with HF. Secondary analyses suggested large CHIP was associated with a greater risk of HF (hazard ratio: 1.29; 95% confidence interval: 1.15-1.44), and the associations for CHIP on HF with and without prior coronary heart disease were homogenous. ASXL1 sequence variations were associated with reduced left ventricular ejection fraction. CONCLUSIONS: CHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF.

Citrus Consumption and the Risk of Non-Melanoma Skin Cancer in the Women's Health Initiative.

Evidence from animal studies suggests that furocoumarins, compounds present in citrus products, can increase the risk of non-melanoma skin cancer (NMSC) when combined with ultraviolet radiation. The objective of this study was to determine the relationship between citrus intake and NMSC risk among postmenopausal women from the Women's Health Initiative (WHI) Observational Study, who were aged 50-79 years at enrollment (1993-1998). The consumption of citrus fruit, citrus juice, and non-citrus fruit and juice were measured at the baseline of the study using a food frequency questionnaire (FFQ). NMSC cases (basal or squamous cell carcinomas) were self-reported during annual follow-up surveys. The outcome data used for this analysis were collected through March 2020. The relative risk (RR) for incident NMSC by citrus consumption was calculated. Among 49,007 non-Hispanic white participants, there were 8642 cases of incident NMSC. Using less than one serving of citrus juice per week as reference, the RRs and 95% confidence intervals (CI) for incident NMSC by citrus juice intake were 1.03 (0.95, 1.10) for one serving/week, 1.06 (1.00, 1.12) for two to four servings/week, 0.98 (0.90, 1.07) for five to six servings/week, and 1.08 (1.02, 1.13) for one or more serving/day (p-trend = 0.007). Subgroup analyses did not reveal meaningful associations by sun exposure variables. In conclusion, there were indications of a slightly higher risk of incident NMSC among citrus juice consumers; however, further longitudinal and mechanistic studies are needed to confirm the key risk factors.