DXA-derived abdominal fat free mass to predict MRI skeletal muscle mass in postmenopausal women.

Dual-energy X-ray absorptiometry (DXA) is more available than gold-standard magnetic resonance imaging (MRI), but DXA ability to estimate abdominal skeletal muscle mass (SMM) is unknown. DXA-derived abdominal fat-free mass (FFM; Hologic QDR2000 or QDR4500w) was correlated with single-slice MRI SMM at L4 (N = 69; r QDR2000=0.71, QDR4500w=0.69; p<.0001). Linear regression to predict SMM, including DXA FFM, BMI, and age, resulted in an R-squared of 0.72 and 0.65 for QDR2000 and QDR4500. Bland-Altman limits of agreement were ±21g and ±31g for 2-3 standard deviations from the mean difference. DXA predicted abdominal SSM is a moderate proxy for MRI abdominal SMM.

Levels of Sex Hormones and Abdominal Muscle Composition in Men from The Multi-Ethnic Study of Atherosclerosis.

Information on the associations of testosterone levels with abdominal muscle volume and density in men is limited, while the role of estradiol and SHBG on these muscle characteristics are unclear. Therefore, this study aimed to investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Conducted as a cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis, our analyses focused on a community-based sample of 907 men aged 45-84 years, with 878 men having complete data. CT scans of the abdomen were interrogated for muscle characteristics, and multivariable linear regressions were used to test the associations. After adjustment for relevant factors, higher levels of both total testosterone and estradiol were associated with higher abdominal muscle area (1.74, 0.1-3.4, and 1.84, 0.4-3.3, respectively). In the final analyses, levels of total testosterone showed a positive association, while an inverse relationship was observed for SHBG with abdominal muscle radiodensity (0.3, 0.0-0.6, and - 0.33, - 0.6 to - 0.1, respectively). Our results indicate a complex association between sex hormones and abdominal muscle characteristics in men. Specifically, total testosterone and estradiol were associated with abdominal muscle area, while only total testosterone was associated with muscle radiodensity and SHBG was inversely associated with muscle radiodensity.Clinical Trial: NCT00005487.

Association of Diet Quality With Risk of Incident Rheumatoid Arthritis in the Women's Health Initiative.

BACKGROUND: Various foods and nutrients are linked with higher or lower risk of rheumatoid arthritis (RA), yet these associations are inconsistent across studies. Limited research has been done evaluating the association between diet quality and RA in a larger-scale prospective study on postmenopausal women. OBJECTIVE: The objective of this study was to evaluate the association between dietary quality and risk of incident RA in postmenopausal women. DESIGN: This was a prospective cohort study as part of the Women's Health Initiative (WHI), with an average follow-up time of 8.1 years. Baseline diet was measured using a food frequency questionnaire (FFQ). Diet quality was evaluated by the Healthy Eating Index (HEI)-2015 total score. In addition, intake of food groups and nutrients that align with HEI-2015 components was assessed. PARTICIPANTS/SETTING: Postmenopausal women (N = 109 591) were included in this study, which was conducted at various clinical centers across the United States with recruitment from 1993 to 1998. Women's Health Initiative participants who were missing outcome data, had unreliable/missing FFQ data, or had RA at baseline were excluded. MAIN OUTCOME MEASURES: The primary outcome measure was incident RA. Statistical analyses performed Multivariable Cox proportional regression analysis was performed evaluating the association of diet quality with self-reported physician-diagnosed RA after adjusting for age, race, ethnicity, education status, income, and body mass index (BMI). RESULTS: During 857 517 person-years of follow-up, 5823 incident RA cases were identified. After adjustment for multiple comparisons, compared with quartile 1, quartiles 2, 3, and 4 of the HEI-2015 total scores were associated with lower RA risks of 1%, 10%, and 19%, respectively (P-trend < .001). Greater consumption of total fruits (P-trend = .014), whole fruits (P-trend < .0002), total vegetables (P-trend = .008), greens and beans (P-trend < .0002), whole grains (P-trend = .008), and dairy (P-trend = .018) were significantly associated with lower rates of incident RA. Conversely, higher consumption of saturated fat (P-trend = .002) was significantly associated with higher rates of incident RA. CONCLUSION: A higher-quality diet reflected by higher HEI-2015 total scores was inversely associated with incident RA in postmenopausal women.

The association between reproductive history and abdominal adipose tissue among postmenopausal women: results from the Women's Health Initiative.

STUDY QUESTION: What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women? SUMMARY ANSWER: Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity. WHAT IS KNOWN ALREADY: Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI. STUDY DESIGN, SIZE, DURATION: This study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Women who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies. LIMITATIONS, REASONS FOR CAUTION: The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention. STUDY FUNDING/COMPETING INTEREST(S): HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Relationship of apolipoprotein C-III proteoform composition with ankle-brachial index and peripheral artery disease in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Apolipoprotein C-III (apoC-III) proteoform composition shows distinct relationships with plasma lipids and cardiovascular risk. The present study tested whether apoC-III proteoforms are associated with risk of peripheral artery disease (PAD). METHODS: ApoC-III proteoforms, i.e., native (C-III0a), and glycosylated with zero (C-III0b), one (C-III1) or two (C-III2) sialic acids, were measured by mass spectrometry immunoassay on 5,734 Multi-Ethnic Study of Atherosclerosis participants who were subsequently followed for clinical PAD over 17 years. Ankle-brachial index (ABI) was also assessed at baseline and then 3 and 10 years later in 4,830 participants. RESULTS: Higher baseline C-III0b/C-III1 and lower baseline C-III2/C-III1 were associated with slower decline in ABI (follow-up adjusted for baseline) over time, independently of cardiometabolic risk factors, and plasma triglycerides and HDL cholesterol levels (estimated difference per 1 SD was 0.31 % for both, p < 0.01). The associations between C-III2/C-III1 and changes in ABI were stronger in men (-1.21 % vs. -0.27 % in women), and in Black and Chinese participants (-0.83 % and -0.86 % vs. 0.12 % in White). Higher C-III0b/C-III1 was associated with a trend for lower risk of PAD (HR = 0.84 [95%CI: 0.67-1.04]) that became stronger after excluding participants on lipid-lowering medications (0.73 [95%CI: 0.57-0.94]). Neither change in ABI nor clinical PAD was related to total apoC-III levels. CONCLUSIONS: We found associations of apoC-III proteoform composition with changes in ABI that were independent of other risk factors, including plasma lipids. Our data further support unique properties of apoC-III proteoforms in modulating vascular health that go beyond total apoC-III levels.

Arriba por la Vida Estudio: a randomized controlled trial promoting standing behavior to reduce sitting time among postmenopausal Latinas.

Postmenopausal Hispanic/Latina (N = 254) women with a body mass index (BMI) ≥ 25 kg/m2 were randomized to an intervention to reduce sitting time or a comparison condition for 12 weeks. The standing intervention group received three in-person health-counseling sessions, one home visit, and up to eight motivational interviewing calls. The heart healthy lifestyle comparison group (C) received an equal number of contact hours to discuss healthy aging. The primary outcome was 12-week change in sitting time measured via thigh-worn activPAL. Group differences in outcomes were analyzed using linear mixed-effects models. Participants had a mean age of 65 (6.5) years, preferred Spanish language (89%), BMI of 32.4 (4.8) kg/m2, and sat for an average of 540 (86) minutes/day. Significant between-group differences were observed in reductions of sitting time across the 12-week period [Mdifference (SE): C - 7.5 (9.1), SI - 71.0 (9.8), p < 0.01]. Results demonstrate that coaching models to reduce sitting are feasible and effective.

Loneliness, social isolation, and cardiovascular disease among nonveteran and veteran women.

We examined the prospective associations of social isolation and loneliness with incident cardiovascular disease (CVD) among aging nonveteran and veteran women, and effect modification by veteran status. Participants with no history of myocardial infarction (MI), stroke, coronary heart disease (CHD), or coronary heart failure from the Women's Health Initiative Extension Study II self-reported social isolation, loneliness, health behaviors, health status, and veteran status. CVD and CVD subevents were physician adjudicated. Hazard ratios (HR) and 95% confidence intervals (CI) for the Interquartile Range (IQR) in social isolation (IQR = 1) and loneliness (IQR=.33) were calculated using Cox proportional hazard models adjusting for sociodemographic, health behavior, and health status characteristics. Veteran status was tested as an effect modifier. Among 52,442 women (Mean age = 79 ± 6.1; veterans n = 1023; 89.2% non-Hispanic White), 3579 major CVD events occurred over an average 5.8 follow-up years. Compared to nonveterans, veteran women reported higher levels of social isolation (p < .01) and loneliness (p < .01). The CVD HR was 1.07 (95% CI, 1.04-1.10) for the IQR in social isolation and 1.03 (95% CI, 1.10-1.06) for the IQR in loneliness. The HR for the IQR in both social isolation and loneliness was 1.10 (95% CI, 1.05-1.15). Social isolation was associated with CHD (HR = 1.12; 95% CI, 1.03-1.21). The CHD HR for the IQR in social isolation was 1.12 (95% CI, 1.03-1.21). Associations did not differ by veteran status (all p-interactions > 0.08). Findings suggest that the adverse associations of social isolation and loneliness with CVD are similar among veteran and nonveteran women.

Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women with Inflammatory Bowel Disease.

BACKGROUND: Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. METHODS: We conducted a survival analysis of Women's Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). RESULTS: Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). CONCLUSIONS: Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.

Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein.

Hereditary angioedema (HAE), a rare genetic disorder, is associated with uncontrolled plasma kallikrein (PKa) enzyme activity leading to the generation of bradykinin swelling in subcutaneous and submucosal membranes in various locations of the body. Herein, we describe a series of potent α-amidobenzylboronates as potential covalent inhibitors of PKa. These compounds exhibited time-dependent inhibition of PKa (compound 20 IC50 66 nM at 1 min, 70 pM at 24 h). Further compound dissociation studies demonstrated that 20 showed no apparent reversibility comparable to d-Phe-Pro-Arg-chloromethylketone (PPACK) (23), a known nonselective covalent PKa inhibitor.

Cardiovascular risk, social vigilance, and stress profiles of male law enforcement officers versus civilians.

This study examined the cardiovascular disease (CVD) risk profiles of male law enforcement officers (LEOs) and civilians. CVD risk profiles were based on data collected using traditional objective (e.g., resting BP, cholesterol), novel objective (e.g., ambulatory BP) and self-report measures (e.g., EMA social vigilance). A subset of male LEOs (n = 30, M age = 41.47, SD = 8.03) and male civilians (n = 120, M age = 40.73, SD = 13.52) from a larger study were included in analyses. Results indicated LEOs had significantly higher body mass index [BMI], 31.17 kg/m2 versus 28.87 kg/m2, and exhibited significantly higher trait and state social vigilance across multiple measures, whereas perceived stress was higher among civilians. Findings highlight the need for future research examining CVD risk associated with occupational health disparities, including attributes of individuals entering certain professions as well as experiential and environmental demands of the work.

Associations Between Visceral Fat, Abdominal Muscle, and Coronary Artery Calcification: A Cross-Sectional Analysis of the Multi-Ethnic Study of Atherosclerosis.

The associations of body composition components, including muscle and adipose tissue, and markers of subclinical coronary artery disease are unclear. We examined the relation between abdominal computed tomography (CT)-derived measures of the area and density of fat and muscle with coronary artery calcification (CAC), using data from the Multi-Ethnic Study of Atherosclerosis (MESA). A total of 1,974 randomly selected MESA participants free of coronary heart disease underwent abdominal CT scans at examinations 2 or 3, with the resulting images interrogated for abdominal body composition. Using 6 cross-sectional slices spanning L2 to L5, the Medical Imaging Processing Analysis and Visualization software was used to determine abdominal muscle and fat composition using appropriate Hounsfield units ranges. CT chest scans were used to obtain CAC scores, calculated using the Agatston method and spatially weighted calcium score. Multivariable linear and logistic regression analyses were performed to assess the relation between abdominal visceral fat and muscle area and density to prevalent CAC. A total of 1,089 participants had a CAC >0, with an average CAC score of 310. In the fully adjusted model, for every 10-cm2 increase in visceral fat area, the likelihood of having a CAC greater than 0 increased by 0.60% (p <0.001). In the minimally adjusted model, abdominal muscle area was significantly associated with CAC >0, which became nonsignificant in the fully adjusted model. For the density of visceral fat, every 1-Hounsfield unit increase (less lipid-dense fat tissue), the likelihood of having a CAC score >0 decreased by 0.29% (p <0.05). No significant relation was observed between density of abdominal muscle and CAC >0. A greater area and higher lipid density of abdominal visceral fat were associated with an increased likelihood of having CAC, whereas there was no significant relation between abdominal muscle area or density and CAC. The quantity and the quality of fat have associations, with an important marker of subclinical atherosclerosis, CAC, and their significance with respect to cardiovascular outcomes, require further evaluation.

Associations of Circulating Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 With Long-Term Cardiac Function.

BACKGROUND: Although VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) have been associated with incident heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF), the associations of VCAM-1 and ICAM-1 with sensitive measures of cardiac structure/function are unclear. The objective of this study is to evaluate associations between VCAM-1, ICAM-1, and measures of cardiac structure and function as potential pathways through which cellular adhesion molecules promote HFpEF and AF risk. METHODS AND RESULTS: In MESA (Multi-Ethnic Study of Atherosclerosis), we evaluated the associations of circulating VCAM-1 and ICAM-1 at examination 2 (2002-2004) with measures of cardiac structure/function on cardiac magnetic resonance imaging at examination 5 (2010-2011) after multivariable adjustment. Mediation analysis of left atrial (LA) strain on the association between VCAM-1 or ICAM-1 and AF or HFpEF was also performed. Overall, 2304 individuals (63±10 years; 47% men) with VCAM-1 or ICAM-1, cardiac magnetic resonance imaging, and covariate data were included in analysis. Higher VCAM-1 and ICAM-1 were associated with lower LA peak longitudinal strain and worse global circumferential left ventricular strain but were not associated with left ventricular myocardial scar or interstitial fibrosis. Lower LA peak longitudinal strain mediated 8% (95% CI, 2-30) of the relationship between VCAM-1 and HFpEF and 9% (95% CI, 2-21) of the relationship between VCAM-1 and AF. CONCLUSIONS: Higher VCAM-1 and ICAM-1 were associated with lower LA function and left ventricular systolic function but were not associated with myocardial scar or interstitial fibrosis. VCAM-1 and ICAM-1 may promote HFpEF and AF risk through impaired LA reservoir function.

Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: The Multi-Ethnic Study of Atherosclerosis.

Information on the associations of testosterone levels with abdominal muscle volume and quality in men is limited, while the role of estradiol and SHBG on these muscle characteristics are unclear. To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. After adjustment, higher levels of both total testosterone and estradiol were associated with higher abdominal muscle area (1.79, 0.1-3.4, & 1.79, 0.4-3.2, respectively). In the final analyses, levels of total testosterone showed a positive association, while an inverse relationship was observed for SHBG with abdominal muscle radiodensity (0.3, 0.0-0.6, & -0.34, -0.6 - -0.1, respectively). Our results indicate a complex association between sex hormones and abdominal muscle characteristics in men. Specifically, total testosterone and estradiol were associated with abdominal muscle area, while only total testosterone was associated with muscle radiodensity and SHBG was inversely associated with muscle radiodensity.

Associations of Abdominal Muscle Density and Area and Incident Cardiovascular Disease, Coronary Heart Disease, and Stroke: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Muscle density is inversely associated with all-cause mortality, but associations with cardiovascular disease (CVD) risk are not well understood. This study evaluated the association between muscle density and muscle area and incident total CVD, coronary heart disease (CHD), and stroke in diverse men and women. METHODS AND RESULTS: Adult participants (N=1869) in the Multi-Ethnic Study of Atherosclerosis Ancillary Body Composition Study underwent computer tomography scans of the L2-L4 region of the abdomen. Muscle was quantified by density (Hounsfield units) and area in cm2. Sex-stratified Cox proportional hazard models assessed associations between incident total CVD, incident CHD, and incident stroke across sex-specific percentiles of muscle area and density, which were entered simultaneously into the model. Mean age for men and women at baseline were 64.1 and 65.1 years, respectively, and median follow-up time was 10.3 years. For men, associations between muscle density and incident CVD were inverse but not significant in fully adjusted models (P trend=0.15). However, there was an inverse association between density and CHD (P trend=0.02; HR, 0.26 for 95th versus 10th percentile), and no association with stroke (P trend=0.78). Conversely, for men, there was a strong positive association between muscle area and incident CVD (HR, 4.19 for 95th versus 10th percentile; P trend<0.001). Associations were stronger for CHD (HR, 6.18 for 95th versus 10th percentile; P trend<0.001), and null for stroke (P trend=0.67). Associations for women were mostly null. CONCLUSIONS: For men, abdominal muscle density is associated with lower CHD risk, whereas greater muscle area is associated with markedly increased risk of CHD.

Association between Statin use and Incident Peripheral Artery Disease According to Race, Age, and Presence of Depression in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Peripheral artery disease (PAD) is associated with high morbidity and mortality and has been commonly described as a coronary heart disease equivalent. Statin medications are recommended for primary prevention of atherosclerotic cardiovascular disease (CVD) among other indications. Therefore, understanding the longitudinal relationship of incident PAD is necessary to inform future research on how to prevent the disease. Depression complicates CVD patients' ability to properly adhere to their medications, yet the effect of depression on the relationship between statin use and incident PAD is understudied. People with PAD have a higher incidence of depressive symptoms than people without PAD. Black American and Hispanic populations are disproportionately affected by both PAD and depression yet research on the modifying effect of either race or depression on the relationship between statin use and onset of PAD is minimal. While statin utilization is highest for ages 75-84 years, there is minimal evidence of favorable risk-benefit balance. Consequently, in this project, we examined the relationship between statin use and incident PAD and whether this relationship is modified by race/ethnicity, depressive symptoms, or age. METHODS: We used data on participants from the Multi-Ethnic Study of Atherosclerosis from visit 1 (2000) through study visit 6 (2020) who had three separate measurements of the ankle-brachial index (ABI) taken at visit 1, visit 3, and visit 5. Incident PAD was defined as 1) incident lower extremity amputation or revascularization or 2) ABI less than 0.90 coupled with ABI decrease greater than 0.15 over the follow-up period. Statin use was noted on the study visit prior to incident PAD diagnosis while depressive symptoms were measured at exam 1, visit 3, and visit 5. Propensity score matching was implemented to create balance between the participants in the two treatment groups, that is, statin-treated and statin-untreated groups, to reduce the problem of confounding by indication. Propensity scores were calculated using multivariate logistic regression model to estimate the probability of receiving statin treatment. We used Cox proportional hazards regression to investigate the relationship between time-dependent statin use as well as other risk factors with incident PAD, overall and stratified by 1) race, 2) depression status, and 3) age. RESULTS: A total of 4,210 participants were included in the final matched analytic cohort. There were 810 incident cases (19.3%) of PAD that occurred over an average (mean) of 11.3 years (SD = 5.7) of follow-up time. In the statin-treated group, and with an average follow-up time of 12.5 years (SD = 5.6), there were 281 cases (13.4%) of incident PAD with the average follow-up time of 10.1 years (SD = 5.5), whereas in the statin-untreated group, there were 531 cases (25.2%) (P < 0.001). Results demonstrate a lower risk of PAD event in the statin-treated group compared to the untreated group (hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.33-0.62) over the span of 18.5 years. The interactions between 1) depression and 2) race with statin use for incident PAD were not significant. However, other risk factors which were significant included Black American race that had approximately 30% lower hazard of PAD compared to non-Hispanic White (HR = 0.70, 95% CI: 0.58-0.84); age-stratified models were also fitted, and stain use was still a significant treatment factor for ages 45-54 (HR = 0.45, 95% CI: 0.33-0.63), 55-64 (HR = 0.61, 95% CI: 0.46-0.79), and 65-74 years (HR = 0.61, 95% CI: 0.48-0.78) but not for ages 75-84 years. CONCLUSIONS: Statin use was associated with a decreased risk of incident PAD for those under the age of 75 years. Neither race nor depression significantly modified the relationship between statin use and incident PAD; however, the risk of incident PAD was lower among Black Americans. These findings highlight that the benefit of statin may wane for those over the age of 75 years. Findings also suggest that statin use may not be compromised in those living with depression.

Coarse Particulate Matter and Markers of Inflammation and Coagulation in the Multi-Ethnic Study of Atherosclerosis (MESA) Population: A Repeat Measures Analysis.

BACKGROUND: In contrast to fine particles, less is known of the inflammatory and coagulation impacts of coarse particulate matter (PM10-2.5, particulate matter with aerodynamic diameter ≤10µm and>2.5µm). Toxicological research suggests that these pathways might be important processes by which PM10-2.5 impacts health, but there are relatively few epidemiological studies due to a lack of a national PM10-2.5 monitoring network. OBJECTIVES: We used new spatiotemporal exposure models to examine associations of both 1-y and 1-month average PM10-2.5 concentrations with markers of inflammation and coagulation. METHODS: We leveraged data from 7,071 Multi-Ethnic Study of Atherosclerosis and ancillary study participants 45-84 y of age who had repeated plasma measures of inflammatory and coagulation biomarkers. We estimated PM10-2.5 at participant addresses 1 y and 1 month before each of up to four exams (2000-2012) using spatiotemporal models that incorporated satellite, regulatory monitoring, and local geographic data and accounted for spatial correlation. We used random effects models to estimate associations with interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and D-dimer, controlling for potential confounders. RESULTS: Increases in PM10-2.5 were not associated with greater levels of inflammation or coagulation. A 10-µg/m3 increase in annual average PM10-2.5 was associated with a 2.5% decrease in CRP [95% confidence interval (CI): -5.5, 0.6]. We saw no association between annual average PM10-2.5 and the other markers (IL-6: -0.7%, 95% CI: -2.6, 1.2; fibrinogen: -0.3%, 95% CI: -0.9, 0.3; D-dimer: -0.2%, 95% CI: -2.6, 2.4). Associations consistently showed that a 10-µg/m3 increase in 1-month average PM10-2.5 was associated with reduced inflammation and coagulation, though none were distinguishable from no association (IL-6: -1.2%, 95% CI: -3.0 , 0.5; CRP: -2.5%, 95% CI: -5.3, 0.4; fibrinogen: -0.4%, 95% CI: -1.0, 0.1; D-dimer: -2.0%, 95% CI: -4.3, 0.3). DISCUSSION: We found no evidence that PM10-2.5 is associated with higher inflammation or coagulation levels. More research is needed to determine whether the inflammation and coagulation pathways are as important in explaining observed PM10-2.5 health impacts in humans as they have been shown to be in toxicology studies or whether PM10-2.5 might impact human health through alternative biological mechanisms. https://doi.org/10.1289/EHP12972.

Association of circulating fibroblast growth factor 21 levels with all-cause and cardiovascular mortality: The multi-ethnic study of atherosclerosis.

BACKGROUND: Fibroblast growth factor 21 (FGF21) levels are often elevated in cardiovascular disease (CVD). However, no study has assessed its association with cardiovascular and all-cause mortality in a population free of clinically evident CVD. METHODS: A total of 5543 Multi-Ethnic Study of Atherosclerosis (MESA) participants (mean age 62.7 years, 47.5 % male), free of clinically evident CVD at baseline, were studied. From baseline (2000-2002), 1606 deaths (including 387 CVD deaths) were observed over a median follow-up of 17.7 years. Multivariable Cox regression analysis was performed to assess the association of plasma FGF21 levels with mortality. RESULTS: FGF21 levels at baseline were associated with all-cause mortality, even after adjustment for traditional risk factors, including demographic, socioeconomic and cardiovascular risk factors (adjusted hazard ratio 1.08 [95% confidence interval 1.01, 1.16] per 1 SD increase in ln-transformed levels; 1.27 for the highest vs, lowest quartile). Baseline FGF21 levels were significantly associated with both CVD and non-CVD mortality in unadjusted models. However, the association with non-CVD mortality, but not CVD mortality, remained statistically significant after adjusting for covariates. Similar results were obtained in FGF21 quartile analyses and also when using competing risk regression or matched case-control cohort in sensitivity analyses. CONCLUSIONS: In subjects without clinically-evident CVD at baseline, over 17.7 years follow-up there is a modest association of baseline FGF21 levels with all-cause mortality. The finding that this is driven primarily by a significant association with non-CVD mortality over almost two decades merits further investigation.

Adipokines and adiposity among postmenopausal women of the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: We investigated whether the associations of serum adiponectin, leptin, and resistin with adiposity differ with menopausal age. METHODS: In this cross-sectional study, we included 751 postmenopausal women from the Multi-Ethnic Study of Atherosclerosis (MESA) who reported their menopausal age (<45, 45-49, 50-54 and ≥55 y) and had anthropometrics, serum adipokines, and abdominal computed tomography measures of visceral and subcutaneous adipose tissue (VAT and SAT) obtained at MESA exam 2 or 3. Linear regression models were used for analysis. RESULTS: The mean ± SD age was 65.1 ± 9.0 years for all participants. The median (interquartile range) values for serum adiponectin, leptin and resistin, VAT, and SAT were 21.9 (14.8-31.7) ng/L, 24.3 (12.5-42.4) pg/L, 15.3 (11.8-19.5) pg/L, 183.9 (130.8-251.1) cm2, and 103.7 (65.6-151.5) cm2, respectively. The mean ± SD values for body mass index, waist circumference, and waist-to-hip ratio were 28.3 ± 5.81 kg/m2, 96.6 ± 15.9 cm, and 0.91 ± 0.078, respectively. Adiponectin was inversely associated with all adiposity measures, with similar patterns across menopausal age categories. Leptin was positively associated with all adiposity measures, and the strength of associations varied across menopausal age categories for body mass index, waist circumference, and SAT (Pinteraction ≤ 0.01 for all). The associations of resistin with adiposity measures were mostly nonsignificant except in the 45- to 49-year menopausal age category. CONCLUSIONS: Menopausal age category had no influence on the association of serum adiponectin with adiposity. The association of serum leptin and resistin differed according to menopausal age category for generalized adiposity but was inconsistent for measures of abdominal adiposity.

Nonlinear associations between computed tomography-measures of adiposity and long pentraxin-3 in the Multi-Ethnic Study of Atherosclerosis.

Objective: Long pentraxin-3 (PTX-3) is an acute phase protein associated with cardiovascular disease, lung injury, and mortality. We evaluated the association between computed tomography (CT)-measurements of adipose tissue and plasma levels of PTX-3. Methods: We performed a cross-sectional analysis of community-dwelling adults enrolled in the multi-center Multiethnic Study of Atherosclerosis who underwent cardiac or abdominal CT and had available PTX-3 measurements. Results: There was a U-shaped association between pericardial adipose tissue volume (PAT), abdominal visceral adipose tissue area (VAT), hepatic attenuation, and PTX-3 levels, with extremes of adiposity associated with greater PTX-3 levels. Using multivariable-adjusted piecewise regression models, among participants with low PAT, every 1% increase in PAT volume was associated with a 13.8% decrease in PTX-3 (95% confidence interval [CI] -21.6 to -6.0); among participants with high PAT, every 1% increase in PAT volume was associated with a 6.0% increase in PTX-3 (95% CI -0.4 to 12.5). Results were similar for abdominal VAT and hepatic attenuation. Conclusions: In a cohort of community-dwelling adults, we demonstrated a "U-shaped" association between pericardial, abdominal visceral, and hepatic adiposity with PTX3 levels, suggesting that extreme adiposity is associated with greater circulating levels of PTX3. Further work is required to identify the mechanisms linking adiposity and PTX-3.