A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

Assessment of Subclinical Atherosclerosis in Asymptomatic People In Vivo: Measurements Suitable for Biomarker and Mendelian Randomization Studies.

BACKGROUND: One strategy to reduce the burden of cardiovascular disease is the early detection and treatment of atherosclerosis. This has led to significant interest in studies of subclinical atherosclerosis, using different phenotypes, not all of which are accurate reflections of the presence of asymptomatic atherosclerotic plaques. The aim of part 2 of this series is to provide a review of the existing literature on purported measures of subclinical disease and recommendations concerning which tests may be appropriate in the prevention of incident cardiovascular disease. METHODS: We conducted a critical review of measurements used to infer the presence of subclinical atherosclerosis in the major conduit arteries and focused on the predictive value of these tests for future cardiovascular events, independent of conventional cardiovascular risk factors, in asymptomatic people. The emphasis was on studies with >10 000 person-years of follow-up, with meta-analysis of results reporting adjusted hazard ratios (HRs) with 95% CIs. The arterial territories were limited to carotid, coronary, aorta, and lower limb arteries. RESULTS: In the carotid arteries, the presence of plaque (8 studies) was independently associated with future stroke (pooled HR, 1.89 [1.04-3.44]) and cardiac events (7 studies), with a pooled HR, 1.77 (1.19-2.62). Increased coronary artery calcium (5 studies) was associated with the risk of coronary heart disease events, pooled HR, 1.54 (1.07-2.07) and increasing severity of calcification (by Agaston score) was associated with escalation of risk (13 studies). An ankle/brachial index (ABI) of <0.9, the pooled HR for cardiovascular death from 7 studies was 2.01 (1.43-2.81). There were insufficient studies of either, thoracic or aortic calcium, aortic diameter, or femoral plaque to synthesize the data based on consistent reporting of these measures. CONCLUSIONS: The presence of carotid plaque, coronary artery calcium, or abnormal ankle pressures seems to be a valid indicator of the presence of subclinical atherosclerosis and may be considered for use in biomarker, Mendelian randomization and similar studies.

Associations Between Flavonoid Intake and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Flavonoids may play a role in mitigating atherosclerotic cardiovascular diseases, with evidence suggesting effects may differ between vascular beds. Studies examining associations with subclinical markers of atherosclerosis between subpopulations with different underlying risks of atherosclerosis are lacking. METHODS: Among 5599 participants from the MESA (Multi-Ethnic Study of Atherosclerosis), associations between dietary flavonoid intakes (estimated from a food frequency questionnaire) and subclinical measures of atherosclerosis (ankle-brachial index, carotid plaques and intima-media thickness, and coronary artery calcification) were examined using repeated measures models. Exposures and outcomes were measured at exam 1 (2000-2002) and exam 5 (2010-2011). Stratified analyses and interaction terms were used to explore effect modification by time, sex, race/ethnicity, and smoking status. RESULTS: In the analytic population, at baseline, ≈46% were men with a median age of 62 (interquartile range, 53-70) years and total flavonoid intakes of 182 (interquartile range, 98-308) mg/d. After multivariable adjustments, participants with the highest (quartile 4) versus lowest (quartile 1) total flavonoid intakes had 26% lower odds of having an ankle-brachial index <1 (odds ratio, 0.74 [95% CI, 0.60-0.92]) and 18% lower odds of having a carotid plaque (odds ratio, 0.82 [95% CI, 0.69-0.99]), averaged over exams 1 and 5. Moderate (quartile 3) to high (quartile 4) intakes of flavonols, flavanol monomers, and anthocyanins were associated with 19% to 34% lower odds of having an ankle-brachial index <1 and 18% to 20% lower odds of having carotid plaque. Participants with the highest intakes of anthocyanins (quartile 4) at baseline had a marginally slower rate of carotid plaque progression than those with moderate intakes (quartiles 2 and 3). There were no significant associations with intima-media thickness or coronary artery calcification. Observed associations did not differ by sex, race/ethnicity, or smoking status. CONCLUSIONS: In this multi-ethnic population, higher dietary flavonoid intakes were associated with lower odds of peripheral and carotid artery atherosclerosis. Increasing intakes of healthy, flavonoid-rich foods may protect against atherosclerosis in the peripheral and carotid arteries.

Health Disparities in Peripheral Artery Disease: A Scientific Statement From the American Heart Association.

Peripheral artery disease (PAD) affects 200 million individuals worldwide. In the United States, certain demographic groups experience a disproportionately higher prevalence and clinical effect of PAD. The social and clinical effect of PAD includes higher rates of individual disability, depression, minor and major limb amputation along with cardiovascular and cerebrovascular events. The reasons behind the inequitable burden of PAD and inequitable delivery of care are both multifactorial and complex in nature, including systemic and structural inequity that exists within our society. Herein, we present an overview statement of the myriad variables that contribute to PAD disparities and conclude with a summary of potential novel solutions.

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

Regular cannabis smoking and carotid artery calcification in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Studies on cannabis use and adverse cardiovascular outcomes have reported conflicting results. Research on its relationship to calcified arterial plaque remains limited. METHODS: Cross-sectional data from 2152 participants at Exam 6 (2016-2018) in the Multi-Ethnic Study of Atherosclerosis (MESA) were analyzed, including self-reported cannabis smoking patterns and carotid artery calcification (CAC) as measured via computed tomography. Multivariable relative and absolute risk regression models were used to estimate adjusted prevalence ratios (PRs) and prevalence differences, respectively, for the presence of calcified plaque. Multivariable linear regression was then used to compare group differences in the extent of CAC in those with calcified plaque. RESULTS: A minority of participants (n = 159, 7.4%) reported a history of regular cannabis smoking. Among all participants, 36.1% (n = 777) had detectable CAC. In models adjusted for demographics, behavioral, and clinical cardiovascular disease factors, a history of regular cannabis smoking was not associated with the prevalence of CAC in either common carotid artery (PR: 1.14, 95% CI: 0.88 to 1.49). In the subset of participants with calcified plaque, and in separate fully adjusted multivariable linear regression models, a history of regular cannabis smoking was not associated with increased calcium volume (difference = 7.7%, 95% CI: -21.8 to 48.5), calcium density (difference = 0.4%, 95% CI: -6.6 to 7.9), or Agatston score (difference = 32.1%, 95% CI: -31.8 to 155.8) in either carotid artery. Models exploring potential effect modification by age, race/ethnicity, and tobacco smoking status showed no significant association, except for higher CAC prevalence in men with a history of regular cannabis smoking. CONCLUSIONS: In a racially and ethnically diverse cohort of older adults with a moderately high prevalence of CAC, no associations were found between a history of regular cannabis smoking, duration, or recency of cannabis smoking, and the prevalence of carotid calcified plaque. These findings were consistent across age, race/ethnicity, and cigarette smoking, except for an increased prevalence in men with a history of regular cannabis smoking. Similarly, in a subgroup with CAC, no association was found between a history of regular cannabis smoking and extent of calcification as measured by volume, density, and Agatston score.

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.

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.

Neighborhood environments and psychological distress 6-years later: results from the San Diego HCHS/SOL community and surrounding areas study.

PURPOSE: The current study examined associations of social and built features of neighborhood environments with psychological distress 6 years later and whether these associations were explained by stress and social factors, among Hispanic/Latino adults from the HCHS/SOL and SOL CASAS Ancillary Study. METHODS: In the SOL CASAS Ancillary Study, HCHS/SOL San Diego participants' baseline (2008-2011) home addresses were geocoded, neighborhoods were defined using 800 m radial buffers, and variables representing neighborhood socioeconomic deprivation, social disorder, walkability, and greenness were created. Psychological distress (anxiety and depression symptoms) and proposed pathway variables chronic stress, social support, and family cohesion were assessed at HCHS/SOL Visit 2 (2014-2017). RESULTS: On average, the population (n = 2785) was 39.47 years old, 53.3% were women, and 92.3% were of Mexican heritage. In complex survey regression analyses that accounted for sociodemographic covariates, the complex sampling design, and sample weights, greater baseline neighborhood socioeconomic deprivation predicted lower family cohesion at Visit 2 (B = -0.99, 95% CI [-1.97, -0.06]). Path models showed indirect associations of baseline neighborhood socioeconomic deprivation with Visit 2 psychological distress through family cohesion (MacKinnon's 95% CI depression [0.001, 0.026]; 3.9% of the variance accounted for; anxiety [0.00071, 0.019] 3.0% of the variance accounted for). CONCLUSIONS: Among adults of mostly Mexican heritage from the San Diego, CA area, neighborhood deprivation indirectly predicted later psychological distress through family cohesion. No other effects of neighborhood variables were observed.

Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL.

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban and Dominican) background residing in the USA. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), 22 for waist circumference adjusted for body mass index (WCadjBMI) and 28 for hip circumference adjusted for body mass index (HIPadjBMI), which reached suggestive significance (P < 1 × 10-6). Many loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in cohorts (N = 34 161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (P < 0.05 and consistent direction of effect, and P < 5 × 10-8 after meta-analysis), including two for WHRadjBMI (rs13301996, rs79478137); one for WCadjBMI (rs3168072) and one for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI, 10 for WCadjBMI and 12 for HIPadjBMI). Our study highlights the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity susceptibility that may be ancestry-specific.

Allele-specific variation at APOE increases nonalcoholic fatty liver disease and obesity but decreases risk of Alzheimer's disease and myocardial infarction.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is highly correlated with metabolic disease. NAFLD results from environmental exposures acting on a susceptible polygenic background. This study performed the largest multiethnic investigation of exonic variation associated with NAFLD and correlated metabolic traits and diseases. An exome array meta-analysis was carried out among eight multiethnic population-based cohorts (n = 16 492) with computed tomography (CT) measured hepatic steatosis. A fixed effects meta-analysis identified five exome-wide significant loci (P < 5.30 × 10-7); including a novel signal near TOMM40/APOE. Joint analysis of TOMM40/APOE variants revealed the TOMM40 signal was attributed to APOE rs429358-T; APOE rs7412 was not associated with liver attenuation. Moreover, rs429358-T was associated with higher serum alanine aminotransferase, liver steatosis, cirrhosis, triglycerides and obesity; as well as, lower cholesterol and decreased risk of myocardial infarction and Alzheimer's disease (AD) in phenome-wide association analyses in the Michigan Genomics Initiative, United Kingdom Biobank and/or public datasets. These results implicate APOE in imaging-based identification of NAFLD. This association may or may not translate to nonalcoholic steatohepatitis; however, these results indicate a significant association with advanced liver disease and hepatic cirrhosis. These findings highlight allelic heterogeneity at the APOE locus and demonstrate an inverse link between NAFLD and AD at the exome level in the largest analysis to date.

Associations between Metabolomic Biomarkers of Avocado Intake and Glycemia in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Avocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes. OBJECTIVES: To identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia. METHODS: Baseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an ∼18 y follow-up period. A metabolome-wide association study of avocado consumption status (consumer compared with nonconsumer) was conducted, and the relationship of these features with glycemia via cross-sectional associations with fasting insulin and glucose and longitudinal associations with incident T2D was examined. RESULTS: Three highly-correlated spectral features were associated with avocado intake at metabolome-wide significance levels (P < 5.3 ∗ 10-7) and combined into a single biomarker. We did not find evidence that these features were additionally associated with overall dietary quality, nor with any of 47 other food groups (all P > 0.001), supporting their suitability as a biomarker of avocado intake. Avocado intake showed a modest association only with lower fasting insulin (ß = -0.07 +/- 0.03, P = 0.03), an association that was attenuated to nonsignificance when additionally controlling for body mass index (kg/m2). However, our biomarker of avocado intake was strongly associated with lower fasting glucose (ß = -0.22 +/- 0.02, P < 2.0 ∗ 10-16), lower fasting insulin (ß = -0.17 +/- 0.02, P < 2.0 ∗ 10-16), and a lower incidence of T2D (hazard ratio: 0.68; 0.63-074, P < 2.0 ∗ 10-16), even when adjusting for BMI. CONCLUSIONS: Highly significant associations between glycemia and avocado-related metabolomic features, which serve as biomarkers of the physiological impact of dietary intake after digestion and absorption, compared to modest relationships between glycemia and avocado consumption, highlights the importance of considering individual differences in metabolism when considering diet-health relationships.

Mean affect and affect variability may interact to predict inflammation.

INTRODUCTION: Individuals with greater affect variability (i.e., moment-to-moment fluctuations possibly reflecting emotional dysregulation) are at risk for greater systemic inflammation, which is associated with cardiovascular disease. Some evidence suggests that affect variability is linked with poorer health indicators only among those with higher average levels of affect, particularly for positive affect (PA), and that associations may be non-linear. The present study sought to examine whether links between both PA and negative affect (NA) variability and inflammation are moderated by average level of affect. METHODS: Participants (N = 300, 50 % female, ages 21-70, 60 % non-Hispanic White, 19 % Hispanic, 15 % non-Hispanic Black) completed a lab assessment and provided a blood sample to measure systemic inflammation (i.e., TNF-α, IL-6, CRP). Affect was collected via a two-day ecological momentary assessment protocol where reports were collected about every 45-min during waking hours. Momentary affect ratings were averaged across both days (i.e., iM), separately for PA and NA, for each participant. Affect variability was calculated as the person-specific SD (i.e., iSD) of affect reports, separately for PA and NA. Linear and quadratic interactions were tested. Models included covariates for sex, race, and body mass index. RESULTS: There were significant interactions between NA iM and NA iSD predicting TNF-α (b = 6.54; p < 0.05) and between PA iM and PA iSD predicting IL-6 (b = 0.45; p < 0.05). Specifically, the association between these affect variability indicators and inflammatory markers were suggestive of a positive association among those with higher average affect but a negative association among those with lower average affect. There was no evidence of non-linear associations between affect and inflammation. DISCUSSION: Incorporating interactive effects between affect variability and average affect may be an important consideration in understanding affective-inflammatory associations.

Associations between avocado intake and measures of glucose and insulin homeostasis in Hispanic individuals with and without type 2 diabetes: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND AND AIMS: To investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry. METHODS AND RESULTS: The associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%ß), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by dysglycemia status. In those with normoglycemia, avocado intake was associated with a higher insulinogenic index (ß = 0.17 ± 0.07, P = 0.02). In those with T2D (treated and untreated), avocado intake was associated with lower hemoglobin A1c (HbA1c; ß = -0.36 ± 0.21, P = 0.02), and lower fasting glucose (ß = -0.27 ± 0.12, P = 0.02). In the those with untreated T2D, avocado intake was additionally associated with HOMA-%ß (ß = 0.39 ± 0.19, P = 0.04), higher insulin values 2-h after an oral glucose load (ß = 0.62 ± 0.23, P = 0.01), and a higher insulinogenic index (ß = 0.42 ± 0.18, P = 0.02). No associations were observed in participants with prediabetes. CONCLUSIONS: We observed an association of avocado intake with better glucose/insulin homeostasis, especially in those with T2D.

Evaluation of the Value of Waist Circumference and Metabolomics in the Estimation of Visceral Adipose Tissue.

Visceral adipose tissue (VAT) is a strong prognostic factor for cardiovascular disease and a potential target for cardiovascular risk stratification. Because VAT is difficult to measure in clinical practice, we estimated prediction models with predictors routinely measured in general practice and VAT as outcome using ridge regression in 2,501 middle-aged participants from the Netherlands Epidemiology of Obesity study, 2008-2012. Adding waist circumference and other anthropometric measurements on top of the routinely measured variables improved the optimism-adjusted R2 from 0.50 to 0.58 with a decrease in the root-mean-square error (RMSE) from 45.6 to 41.5 cm2 and with overall good calibration. Further addition of predominantly lipoprotein-related metabolites from the Nightingale platform did not improve the optimism-corrected R2 and RMSE. The models were externally validated in 370 participants from the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS, 2006-2009) and 1,901 participants from the Multi-Ethnic Study of Atherosclerosis (MESA, 2000-2007). Performance was comparable to the development setting in PIVUS (R2 = 0.63, RMSE = 42.4 cm2, calibration slope = 0.94) but lower in MESA (R2 = 0.44, RMSE = 60.7 cm2, calibration slope = 0.75). Our findings indicate that the estimation of VAT with routine clinical measurements can be substantially improved by incorporating waist circumference but not by metabolite measurements.

Association of Premature Menopause With Risk of Abdominal Aortic Aneurysm in the Women's Health Initiative.

OBJECTIVE: To determine if premature menopause and early menarche are associated with increased risk of AAA, and to explore potential effect modification by smoking history. SUMMARY OF BACKGROUND DATA: Despite worse outcomes for women with AAA, no studies have prospectively examined sex-specific risk factors, such as premature menopause and early menarche, with risk of AAA in a large, ethnically diverse cohort of women. METHODS: This was a post-hoc analysis of Women's Health Initiative participants who were beneficiaries of Medicare Parts A&B fee-for-service. AAA cases and interventions were identified from claims data. Follow-up period included Medicare coverage until death, end of follow-up or end of coverage inclusive of 2017. RESULTS: Of 101,119 participants included in the analysis, the mean age was 63 years and median follow-up was 11.3 years. Just under 10,000 (9.4%) women experienced premature menopause and 22,240 (22%) experienced early men-arche. Women with premature menopause were more likely to be overweight, Black, have >20 pack years of smoking, history of cardiovascular disease, hypertension, and early menarche. During 1,091,840 person-years of follow-up, 1125 women were diagnosed with AAA, 134 had premature menopause (11.9%), 93 underwent surgical intervention and 45 (48%) required intervention for ruptured AAA. Premature menopause was associated with increased risk of AAA [hazard ratio 1.37 (1.14, 1.66)], but the association was no longer significant after multivariable adjustment for demographics and cardiovascular disease risk factors. Amongst women with ≥20 pack year smoking history (n = 19,286), 2148 (11.1%) had premature menopause, which was associated with greater risk of AAA in all models [hazard ratio 1.63 (1.24, 2.23)]. Early menarche was not associated with increased risk of AAA. CONCLUSIONS: This study finds that premature menopause may be an important risk factor for AAA in women with significant smoking history. There was no significant association between premature menopause and risk of AAA amongst women who have never smoked. These results suggest an opportunity to develop strategies for better screening, risk reduction and stratification, and outcome improvement in the comprehensive vascular care of women.

Association of abdominal muscle area and density with glucose regulation: The multi-ethnic study of atherosclerosis (MESA).

AIMS: Previous characterisation of body composition as a type 2 diabetes mellitus (T2DM) risk factor has largely focused on adiposity, but less is known about the independent role of skeletal muscle. We examined associations between abdominal muscle and measures of glucose regulation. MATERIALS AND METHODS: Cross-sectional analysis of 1,891 adults enrolled in the Multi-Ethnic Study of Atherosclerosis. Multivariable regression assessed associations between abdominal muscle area and density (measured by computed tomography) with fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), and prevalent T2DM (fasting glucose ≥126 mg/dL or medication use). RESULTS: In minimally adjusted models (age, sex, race/ethnicity, income), a 1-SD increment in abdominal muscle area was associated with higher HOMA-IR (ß = 0.20 ± SE 0.03; 95%CI: 0.15, 0.25; P < 0.01) and odds of T2DM (OR = 1.47; 95%CI: 1.18, 1.84; P < 0.01), while higher density was associated with lower fasting glucose (-4.49 ± 0.90; -6.26, -2.72; P < 0.01), HOMA-IR (-0.16 ± 0.02; -0.20, -0.12; P < 0.01), and odds of T2DM (0.64; 0.52, 0.77; P < 0.01). All associations persisted after adjustment for comorbidities and health behaviours. However, after controlling for height, BMI, and visceral adiposity, increasing muscle area became negatively associated with fasting glucose (-2.23 ± 1.01; -4.22, -0.24; P = 0.03), while density became positively associated with HOMA-IR (0.09 ± 0.02; 0.05, 0.13; P < 0.01). CONCLUSIONS: Increasing muscle density was associated with salutary markers of glucose regulation, but associations inverted with further adjustment for body size and visceral adiposity. Conversely, after full adjustment, increasing muscle area was associated with lower fasting glucose, suggesting some patients may benefit from muscle-building interventions.

Neighborhood built environments and Hispanic/Latino adults' physical activity in the U.S.: The Hispanic community health study/study of Latinos community and surrounding areas study.

Despite experiencing health inequities, less is known about neighborhood environments and physical activity among Hispanic/Latino adults compared to other populations. We investigated this topic in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanic/Latino adults in the San Diego, California area of the U.S. completed measures of overall moderate-to-vigorous physical activity (MVPA) via accelerometry and domain-specific MVPA via questionnaire at Visits 1 (2008-2011; n = 4086) and 2 (2014-2017; n = 1776), ~6 years apart. 800-m home neighborhood buffers were used to create objective measures of residential, intersection, and retail density, bus/trolley stops, greenness, parks, and recreation area at Visit 1. Regression models tested the association of each neighborhood feature with MVPA at Visit 1 and over 6 years, adjusting for individual characteristics and neighborhood socioeconomic deprivation. At Visit 1, those in neighborhoods with higher vs. lower retail density or recreation area (+1 vs. -1 standard deviation from the mean) engaged in 10% more overall MVPA and 12-22% more active transportation. Those in neighborhoods with higher vs. lower residential density engaged in 22% more active transportation. Those in neighborhoods with higher vs. lower greenness and park count engaged in 14-16% more recreational MVPA. Neighborhood features were unassociated with changes in MVPA over 6 years. Although changes in MVPA over time were similar across neighborhoods, Hispanic/Latino adults living in neighborhoods with design features supportive of walking and recreational activity (e.g., greater residential and retail density, more parks and recreation facilities) were consistently more active. Improving neighborhood environments appears important for supporting physical activity among Hispanic/Latino adults.

Coronary calcium density in relation to coronary heart disease and cardiovascular disease in adults with diabetes or metabolic syndrome: the Multi-ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Coronary artery calcium (CAC) density is inversely associated with coronary heart disease (CHD) and cardiovascular disease (CVD) risk. We examined this relation in those with diabetes mellitus (DM) or metabolic syndrome (MetS). METHODS: We studied 3,818 participants with non-zero CAC scores from the Multiethnic Study of Atherosclerosis and classified them as DM, MetS (without DM) or neither DM/MetS. Risk factor-adjusted CAC density was calculated and examined in relation to incident CHD and CVD events over a median follow-up of 15 years among these three disease groups. RESULTS: Adjusted CAC density was 2.54, 2.61 and 2.69 among those with DM, MetS or neither DM/MetS. Hazard ratios (HRs) for CHD per 1 SD increase of CAC density was 0.91 (95% CI: 0.72-1.16), 0.70 (95% CI: 0.56-0.87) and 0.79 (95% CI: 0.66-0.95) for those with DM, MetS or neither DM/MetS groups and were 0.77 (95% CI: 0.64-0.94), 0.83 (95% CI: 0.70-0.99) and 0.82 (95% CI: 0.71-0.95) for CVD, respectively. Adjustment for CAC density increased the HRs of CAC volume for CHD/CVD events. Compared to prediction models with or without single CAC measures, c-statistics of models with CAC volume and density were the highest ranging 0.67-0.72. CONCLUSION: CAC density is lower among patients with DM or MetS than those with neither DM/MetS and is inversely associated with future CHD/CVD risk among them. Including CAC density in risk assessment among those with MetS may improve prediction of CHD and CVD.

Associations between adherence to the dietary approaches to stop hypertension (DASH) diet and six glucose homeostasis traits in the Microbiome and Insulin Longitudinal Evaluation Study (MILES).

BACKGROUND AND AIMS: The DASH diet conveys protection against type 2 diabetes mellitus (T2D) Via plant-based and non-plant-based recommendations. Research has not identified which glucose homeostasis pathways are improved. We examined associations between adherence to a DASH diet and six glucose homeostasis traits, probing whether associations could be attributed to the plant-based (DASH-P) and/or non-plant based (DASH-NP) components. METHODS AND RESULTS: We included data from 295 adults without T2D (age 59.3 ± 9.00 years; 63.46% non-Hispanic White and 36.54% African American, self-reported race ancestry) participating in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). An oral glucose tolerance test (OGTT) yielded fasting plasma glucose, insulin, C-peptide, and insulin secretion, sensitivity, and disposition index. Habitual dietary intake was assessed by food frequency questionnaire (FFQ). Associations between DASH components and glucose homeostasis traits were examined, controlling for demographics, body mass index (BMI), physical activity, and energy intake. For significant associations, the models were repeated with scores for DASH-P and DASH-NP as predictors in the same model. DASH and DASH-P scores were inversely associated with fasting plasma glucose (DASH:ß = -0.036 ± 0.012,P = 0.005; DASH-P: ß = -0.04 ± 0.017,P = 0.002), and positively associated with insulin sensitivity (DASH:ß = 0.022 ± 0.012,P = 0.042; DASH-P: = 0.036 ± 0.015,P = 0.014). The DASH score was also associated with disposition index (ß = 0.026 ± 0.013,P = 0.038), but this association did not reach significance with DASH-P (ß = 0.035 ± 0.018,P = 0.051). No associations were observed with DASH-NP score (all P > 0.05). CONCLUSIONS: DASH diet is associated with improvement in specific glucose homeostasis traits, likely arising from increased plant-based foods. Such research may help tailor future dietary advice to specific metabolic risk, and to food groups most effective at improving these.