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.

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 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.

Healthy lifestyle and risk of incident heart failure with preserved and reduced ejection fraction among post-menopausal women: The Women's Health Initiative study.

We examined associations of diet, physical activity, cigarette smoking, and body mass index (BMI), separately and as a cumulative lifestyle score, with incident hospitalized HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). This analysis included 40,095 postmenopausal women in the Women's Health Initiative clinical trial and observational studies, aged 50-79 years and without self-reported HF at baseline. A healthy lifestyle score (HLS) was developed, in which women received 1 point for each healthy lifestyle. A weighted HLS was also created to examine the independent magnitude of each of the lifestyle factors in HF subtypes. Trained adjudicators determined cases of incident hospitalized HF, HFpEF, HFrEF through March 2018. Multiple variable Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up period of 14.5 years, 659 incident HFrEF and 1276 HFpEF cases were documented. Across unweighted HLS of 0 (referent), 1, 2, 3, and 4, multivariable adjusted HRs (95% CI) for HFrEF were 1.00, 0.52 (0.38, 0.71), 0.40 (0.29, 0.56), 0.33 (0.23, 0.48), and 0.33 (0.19, 0.56) (P-trend = 0.03) and for HFpEF were 1.00, 0.47 (0.37, 0.59), 0.39 (0.30, 0.49), 0.26 (0.20, 0.34), and 0.23 (0.15, 0.35) (P-trend < 0.001). Results were similar for the weighted HLS. Our findings suggest that following a healthy lifestyle pattern is associated with lower risks of HFpEF and HFrEF among postmenopausal women.

Traditional serrated adenomas (TSA) and the company they keep: TSA presence predicts advanced neoplasm states.

BACKGROUND: The association of TSAs with metachronous neoplasms is well established and suggests that TSAs would also have an association with synchronous neoplasms. METHODS: We compared odds ratios and rates of synchronous neoplasms found in colonoscopies with and without TSAs. RESULTS: There was a mean of 2.44 neoplasms among TSA cases in comparison with 1.72 in non-TSA cases. The odds ratio for advanced neoplasia was highest among cases with one or more TSAs relative to cases with one or more HPs (7.54 [CI, 4.23-13.44]) when compared with adenomas (1.95 [CI, 1.75-2.17]) and SSPs (2.98 [CI, 2.54-3.5]). CONCLUSIONS: In this study population, there is a 7-fold higher risk of synchronous advanced neoplasms among cases with one or more TSAs.

Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients.

BACKGROUND: "T50," shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant. METHODS: The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORIT) cohort is a completed, large, multiethnic controlled clinical trial cohort of chronic, stable kidney transplant recipients (KTRs). We conducted a longitudinal case-cohort analysis using a randomly selected subcohort of patients, and all individual cases who developed CVD. Serum T50 and fetuin-A were determined in this total of n = 685 FAVORIT trial participants at randomization. RESULTS: During a median surveillance of 2.18-years, 311 incident or recurrent CVD events occurred. Shorter T50 (minutes) or reduced fetuin-A concentrations (g/L) were associated with CVD after adjustment for treatment assignment, systolic blood pressure, age, sex, race, preexisting CVD and diabetes, smoking, body mass index, total cholesterol/HDL cholesterol, kidney allograft vintage and type, calcineurin inhibitor, or lipid-lowering drug use, estimated glomerular filtration rate, and urinary albumin/creatinine: tertile 1 (lowest) to tertile 3 (highest) comparisons, T50, (hazard ratio [HR] 1.86; 95% CI 1.20-2.89); fetuin-A, (HR 2.25; 95% CI 1.38-3.69). Elevated high sensitivity c-reactive protein (hsCRP) was an effect modifier of both these associations. CONCLUSIONS: Shortened T50, as well as reduced fetuin-A levels, ostensible promoters of vascular calcification, remained associated with greater risk for CVD outcomes, after adjustment for major CVD risk factors, measures of kidney function and damage, and KTR clinical characteristics and demographics, in a large, multiethnic cohort of long-term KTRs. Increased hsCRP was an effect modifier of these CVD risk associations.

Serum Uromodulin: A Biomarker of Long-Term Kidney Allograft Failure.

BACKGROUND: Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs). METHODS: The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. RESULTS: The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05-5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06-3.77). CONCLUSIONS: Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs.

The associations between radiographic hand osteoarthritis definitions and hand pain: data from the osteoarthritis initiative.

The goal of our study was to evaluate the associations between various definitions of radiographic hand osteoarthritis (OA) and self-reported hand pain. We conducted a cross-sectional study with 3604 participants from the Osteoarthritis Initiative (OAI). Posteroanterior radiographs of the dominant hand were read using a modified Kellgren-Lawrence (KL) scale. For our primary analysis, hand OA at person level was defined as two or more finger joints with KL grade 2 or higher. In addition, for the purpose of exploratory analyses, we explored more conservative definitions of hand OA as well as different sum scores and digit- and row-based scores. The majority of definitions of radiographic hand OA were statistically significantly associated with self-reported hand pain. In our main analysis, persons with two or more finger joints with KL grade > 2 were approximately two times more likely to self-report hand pain than persons without radiographic hand OA. Increasing KL grades and increasing number of joints affected lead to stronger associations. Almost all definitions of hand OA were related to pain. Individuals with more severely affected joints or with higher number of affected joints are more likely to report hand pain than their peers. Specifically, individuals with hand joints with KL 3 or 4 have the greatest likelihood of hand pain.

Comparing the Validity of Self-Report and Urinalysis for Substance Use among Former Inmates in the Northeastern United States.

BACKGROUND: Problems with self-reported drug use include difficulties with recall and recognition as well as the desire to respond to questions in a socially desirable manner. Various methods have been developed to improve and/or validate estimates based on direct questioning of individuals regarding their substance use. For this study, we were interested in validating self-reported use of: 1) tobacco, 2) marijuana, and 3) other substances (i.e., heroin, cocaine, opiates, oxycodone, benzodiazepines, methamphetamine, phencyclidine, and barbiturates) employing urinalysis among inmates who participated in a randomized controlled trial of a smoking abstinence intervention in a tobacco-free prison located in the northeastern United States. METHODS: Two-hundred and seven men and women with a mean age of 34.9 (standard deviation = 9.0) completed questions regarding their substance use on a 7-day Timeline Follow-Back and provided urine specimens three weeks following prison release. RESULTS: Self-reported tobacco and marijuana use were highly consistent with urine drug testing in terms of overall agreement and Kappa (93.7% and.804 for tobacco, respectively; and 90.3% and.804 for marijuana, respectively); however, consistency was much lower for other drug use grouped together (62.7% and.270). DISCUSSION: Although some former inmates may not accurately report substance use, our findings indicate that they are in the minority, suggesting that self-report is valid for tobacco and marijuana use but much less so for other drugs grouped together. Future research should be conducted with a larger and more diverse sample of former inmates to establish the generalizability of our findings from this study.

Theoretical Effects of Substituting Butter with Margarine on Risk of Cardiovascular Disease.

BACKGROUND: Several recent articles have called into question the deleterious effects of high animal fat diets due to mixed results from epidemiologic studies and the lack of clinical trial evidence in meta-analyses of dietary intervention trials. We were interested in examining the theoretical effects of substituting plant-based fats from different types of margarine for animal-based fat from butter on the risk of atherosclerosis-related cardiovascular disease (CVD). METHODS: We prospectively studied 71,410 women, aged 50-79 years, and evaluated their risk for clinical myocardial infarction (MI), total coronary heart disease (CHD), ischemic stroke, and atherosclerosis-related CVD with an average of 13.2 years of follow-up. Butter and margarine intakes were obtained at baseline and year 3 by means of a validated food frequency questionnaire. Cox proportional hazards regression using a cumulative average diet method was used to estimate the theoretical effect of substituting 1 teaspoon/day of three types of margarine for the same amount of butter. RESULTS: Substituting butter or stick margarine with tub margarine was associated with lower risk of MI (HRs = 0.95 and 0.91). Subgroup analyses, which evaluated these substitutions among participants with a single source of spreadable fat, showed stronger associations for MI (HRs = 0.92 and 0.87). Outcomes of total CHD, ischemic stroke, and atherosclerosis-related CVD showed wide confidence intervals but the same trends as the MI results. CONCLUSIONS: This theoretical dietary substitution analysis suggests that substituting butter and stick margarine with tub margarine when spreadable fats are eaten may be associated with reduced risk of myocardial infarction.

A Randomized Clinical Trial of a Tailored Lifestyle Intervention for Obese, Sedentary, Primary Care Patients.

PURPOSE: The aim of the study was to test a tailored lifestyle intervention for helping obese primary care patients achieve weight loss and increase physical activity. METHODS: We conducted a 24-month randomized clinical trial in Rhode Island. Primary care physicians identified obese, sedentary patients motivated to lose weight and increase their moderate to vigorous physical activity. These patients were randomized to 1 of 2 experimental groups: enhanced intervention (EI) or standard intervention (SI). Both groups received 3 face-to-face weight loss meetings. The enhanced intervention group also received telephone counseling calls, individually tailored print materials, and DVDs focused on diet and physical activity. Active intervention occurred in year 1 with a tapered maintenance phase in year 2. RESULTS: Two hundred eleven obese, sedentary patients were recruited from 24 primary care practices. Participants were 79% women and 16% minorities. They averaged 48.6 years of age, with a mean body mass index (BMI) of 37.8 kg/m(2), and 21.2 minutes/week of moderate to vigorous physical activity. Significantly more EI participants lost 5% of their baseline weight than SI participants (group by visit, P <.001). The difference was significant during active treatment at 6 months (37.2% EI vs 12.9% SI) and 12 months (47.8% vs 11.6%), but was no longer significant during the maintenance phase at 18 months (31.4% vs 26.7%,) or 24 months (33.3% vs 24.6%). The EI group reported significantly more minutes of moderate to vigorous physical activity over time than the SI group (group by visit, P = 0.04). The differences in minutes per week at 6 months was 95.7 for the EI group vs 68.3 minutes for the SI group; at 12 months, it was 126.1 vs 73.7; at 18 months, 103.7 vs 63.7, and at 24 months, 101.3 vs 75.4. Similar trends were found for absolute weight loss and the percentage reaching national guidelines for physical activity. CONCLUSION: A home-based tailored lifestyle intervention in obese, sedentary primary care patients was effective in promoting weight loss and increasing moderate to vigorous physical activity, with the effects peaking at 12 months but waning at 24 months.

Exploration of Incarcerated Men's and Women's Attitudes of Smoking in the Presence of Children and Pregnant Women: Is There a Disparity Between Smoking Attitudes and Smoking Behavior?

INTRODUCTION: A major health challenge facing persons who are incarcerated is tobacco smoking. Upon reentry to the community, concerns regarding smoking cessation may be less likely to receive needed attention. Many individuals have partners who are pregnant and/or reside in households where children and pregnant women live. We explored incarcerated adults' attitudes of smoking in the presence of children and pregnant women and how post-release smoking behaviors are influenced by their attitudes. METHODS: Two hundred forty-seven incarcerated adults participated in a smoking cessation randomized clinical trial in a tobacco-free prison. An instrument was developed to examine smoking attitudes and behaviors around children and pregnant women. Moderating effects of smoking factors on post-release abstinence were examined by evaluating interactions between smoking factors and treatment group. RESULTS: Four factors were defined using factor analysis: smoking around children; impact of smoking on child's health; awareness of environmental tobacco smoke (ETS) risk for pregnant women; and importance of smoking avoidance during pregnancy. We found moderation effects of smoking factors on smoking outcomes which included: treatment group by smoking behavior around children (ß = 0.8085; standard error [SE] = 0.4002; P = .04); treatment group by impact of smoking on child's health (ß = 1.2390; SE = 0.5632; P = .03) and for those smoking 50% fewer cigarettes post-release, treatment group by smoking impact on child's health (ß = 1.2356; SE = 0.4436; P < .01). CONCLUSIONS: Concern for smoking around children and pregnant women and awareness of ETS risk for pregnant women was not found to be significantly associated with smoking outcomes and requires additional investigation. Among individuals who continue to smoke post-release, effective ETS interventions are needed aimed at protecting children and pregnant women with whom they live.

Prematurity, Birth Weight, and Socioeconomic Status Are Linked to Atypical Diurnal Hypothalamic-Pituitary-Adrenal Axis Activity in Young Adults.

In a prospective, case-controlled longitudinal design, 180 preterm and fullterm infants who had been enrolled at birth participated in a comprehensive assessment battery at age 23. Of these, 149 young adults, 34 formerly full-term and 115 formerly preterm (22 healthy preterm, 48 with medical complications, 21 with neurological complications, and 24 small for gestational age) donated five saliva samples from a single day that were assayed for cortisol to assess diurnal variation of the hypothalamic-pituitary-adrenal (HPA) axis. Analyses were conducted to determine whether prematurity category, birth weight, and socioeconomic status were associated with differences in HPA axis function. Pre- and perinatal circumstances associated with prematurity influenced the activity of this environmentally sensitive physiological system. Results are consistent with the theory of Developmental Origins of Health and Disease and highlight a possible mechanism for the link between prematurity and health disparities later in life.

Cigarette smoking as an expression of independence and freedom among inmates in a tobacco-free prison in the United States.

INTRODUCTION: Most adults report initiation of cigarette smoking during adolescence, a time also marked by developmental striving for independence and freedom. Tobacco use may retain its association with independence and/or freedom into adulthood. This association may contribute to continued tobacco use and/or increased risk of relapse to smoking among some individuals. This study examines the relationship between cigarette smoking and perceptions of independence and freedom among inmates in a tobacco-free prison in the northeastern United States. METHODS: Questionnaires administered to 247 male and female inmates 6 weeks prior to scheduled prison release assessed demographics, smoking history, nicotine dependence, attitudes toward smoking, and plans for tobacco use or abstinence after prison release. Perceptions of smoking as an expression of independence and freedom were measured using 2 items. Smoking was assessed 3 weeks postrelease. RESULTS: Constructs of freedom and independence were correlated but did not overlap completely. Both constructs were negatively associated with plans for smoking abstinence after prison release, and with perceived costs of continued smoking. Number of cigarettes smoked postrelease and perception of the pros of smoking were associated with freedom, but not independence. CONCLUSIONS: Associations of smoking as an expression of freedom and independence may negatively influence plans for renewed smoking after a forced abstinence. Additional research is needed to determine the degree to which these 2 constructs predict smoking behavior and whether they can be used to improve interventions for incarcerated smokers.

Is inflammatory chronic obstructive pulmonary disease a coronary heart disease risk equivalent? A longitudinal analysis of the third National Health and Nutrition Examination Survey (NHANES III), 1988-1994.

BACKGROUND: Evidence suggests that there is an association between chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD). An important etiological link between COPD and CHD may be an underlying systemic inflammatory process. Given that COPD patients are at greater risk of cardiovascular mortality, understanding the burden of CHD on COPD patients could permit future risk attenuation. METHODS: Longitudinal cohort analyses of the Third National Health and Nutrition Examination Survey from 1988-1994 were performed. 3,681 individuals ≥40 years of age with good quality spirometry data were included. Participants were divided into 5 groups: 1) no COPD, no CHD; 2) COPD without inflammation, no CHD; 3) COPD with inflammation, no CHD; 4) CHD only, and 5) CHD + COPD. A novel "inflammatory" COPD designation included those with COPD and clinical evidence of inflammation (i.e., CRP ≥95.24 nmol/L). RESULTS: The risk for CHD mortality was significant only for the CHD group (HR 5.56, 95% CI 3.24-9.55) and the COPD + CHD group (HR 5.02, 95% CI 2.83-8.90). Similarly, the risk for cardiovascular disease (CVD) mortality was significant only for the CHD group (HR 4.25, 95% CI 2.70-6.69) and the CHD + COPD group (HR 4.12, 95% CI 2.60-6.54) after adjusting for nonmodifiable CHD risk factors (age, gender, race/ethnicity, family history of CHD). After adjusting for modifiable CHD risk factors (diabetes, BMI, physical activity, systolic blood pressure, cholesterol, and smoking), hazard ratios of the two groups remained similar but attenuated. For total mortality, the risk was significant for the four groups: the non-inflammatory COPD group; the COPD with inflammation group, the CHD group, and the COPD + CHD group. CONCLUSIONS: Our study did not confirm that inflammatory COPD may be a CHD risk equivalent. However, due to the small size of the "inflammatory" COPD group, further prospective replication and validation is needed. Moreover, given that COPD results from inflammation, the systemic inflammation associated with COPD may have worsened comorbid conditions and may have lead to the increased total mortality found in the COPD with inflammation and COPD + CHD groups which requires further investigation.

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.

Methacholine-induced airway hyper-reactivity phenotypes.

OBJECTIVE: The incorporation of airways conductance/resistance is a rare feature in clinical methacholine challenge test (MCT) protocols, and the majority of pulmonary laboratories rely solely on the spirometric parameters. The importance and interpretation of an MCT demonstrating a significant decline in specific airway conductance specific airway conductance (sGaw), but not forced expiratory volume in one second (FEV(1)), remains undefined. This study sought to elucidate the clinical and physiologic phenotypes of individuals with a ≥40% sGaw decline but <20% FEV(1) change. METHODS: All subjects completed the Asthma Quality of Life Questionnaire (AQLQ), followed by standard MCT, with measurements of sGaw and an additional independent measurement of resistance and reactance by impulse oscillation system (IOS) before and after MCT. RESULTS: Of 201 subjects, 47(23.4%) were in Group 1 (FEV(1) declined by ≥20%), 45(22.4%) were in Group 2 (non-significant FEV(1) drop, sGaw declined ≥40%), and 109(54.2%) were in Group 3 (no significant decline in FEV(1)/sGaw). There was a nearly identical change in all oscillometric parameters and sGaw for Groups 1 and 2 versus Group 3. There were no differences between Groups 1 and 2 in any AQLQ category, and Groups 1 and 2 were statistically different from Group 3. CONCLUSIONS: Our prospective study suggests that patients with a significant sGaw decline alone during MCT are a clinically and physiologically important hyper-reactivity phenotype--whose hyper-reactivity independently was confirmed to be nearly identical to those with an FEV(1) decline. By failing to assess airways conductance/resistance, asthma may be inappropriately "ruled out" in ∼20% of the patients referred for MCT. Based on this, standardized incorporation of body plethysmography and/or IOS to MCT protocols should be considered.

Social support and smoking abstinence among incarcerated adults in the United States: a longitudinal study.

BACKGROUND: In the United States, tobacco use among prisoners is nearly three times that of the general population. While many American prisons and jails are now tobacco-free, nearly all inmates return to smoking as soon as they are released back into the community. METHODS: To better understand the role that personal relationships may play in enabling return to smoking, we enrolled former-smokers who were inmates in a tobacco-free prison. Baseline assessments were conducted six weeks prior to inmates' scheduled release and included measures of smoking prior to incarceration, motivation, confidence and plans for remaining quit after release. We also assessed global social support (ISEL) and a measure of social support specific to quitting smoking (SSQ). Smoking status was assessed three weeks after prison release and included 7-day point-prevalence abstinence validated by urine cotinine, days to first cigarette and smoking rate. RESULTS: A diverse sample comprised of 35% women, 20% Hispanic, and 29% racial minorities (average age 35.5 years) provided baseline data (n = 247). Over 90% of participants provided follow up data at 3-weeks post-release. Prior to incarceration participants had smoked an average of 21.5 (SD = 11.7) cigarettes per day. Only 29.2% had definite plans to remain smoking-abstinent after release. Approximately half of all participants reported that "most" or "all" of their family (42.2%) and friends (68%) smoked, and 58.8% reported their spouse or romantic partner smoked.SSQ scores were not significantly predictive of smoking outcomes at three weeks, however, social support from family and friends were each significantly and positively correlated with motivation, confidence, and plans for remaining abstinent (all p values <0.05). These smoking-related attitudinal variables were significantly predictive of smoking outcomes (all p values <0.01). General social support (ISEL) was not associated with smoking-related attitudinal variables or smoking outcomes. CONCLUSIONS: Inmates of smoke-free prisons have a head-start on being smoke-free for life. They have been abstinent well past the duration of nicotine withdrawal and have great financial incentive not to begin smoking again. However, this advantage may be offset by a lack of non-smoking role models among their family and friends, and perceived lack of support for remaining smoke-free. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01684995.