Publications by authors named "Matthew A Allison"

300 Publications

Predicting incident heart failure in women with machine learning: The Women's Health Initiative Cohort.

Can J Cardiol 2021 Aug 13. Epub 2021 Aug 13.

Division of Cardiology, Department of Medicine, University of California, San Francisco, Cardiology (San Francisco, California, United States).

Background: Heart failure (HF) is a leading cause of cardiac morbidity among women, whose risk factors differ from those in men. We used machine learning approaches to develop risk prediction models for incident HF in a cohort of postmenopausal women from the Women's Health Initiative (WHI).

Methods And Results: We used two machine learning methods, Least Absolute Shrinkage and Selection Operator (LASSO) and Classification and Regression Trees (CART), to perform variable selection on 1,227 baseline WHI variables for the primary outcome of incident HF. These variables were then used to construct separate Cox proportional hazard models, and we compared these results, using receiver operating characteristic (ROC) curve analysis, against a comparator model built using variables from the Atherosclerosis Risk in Communities (ARIC) HF prediction model. We analyzed 43,709 women who had 2,222 incident HF events; median follow-up was 14.3 years. LASSO selected 10 predictors and CART selected 11 predictors. The highest correlation between selected variables was 0.46. In addition to selecting well-established predictors such as age, myocardial infarction, and smoking, novel predictors included physical function, number of pregnancies, number of prior live births and age at menopause. In ROC analysis, the CART-derived model had the highest c-statistic of 0.83 (95% CI 0.81-0.85), followed by LASSO 0.82 (95% CI 0.81-0.84) and ARIC 0.73 (95% 0.70-0.76).

Conclusions: Machine learning approaches can be used to develop HF risk prediction models that can have better discrimination compared to an established HF risk model, and may provide a basis for investigating novel HF predictors.
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http://dx.doi.org/10.1016/j.cjca.2021.08.006DOI Listing
August 2021

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

Diabetes Metab Res Rev 2021 Jul 30:e3488. Epub 2021 Jul 30.

Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California, USA.

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 (β = 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.
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http://dx.doi.org/10.1002/dmrr.3488DOI Listing
July 2021

Chronic Stress Burden, Visceral Adipose Tissue, and Adiposity-Related Inflammation: The Multi-Ethnic Study of Atherosclerosis.

Psychosom Med 2021 Jul 21. Epub 2021 Jul 21.

Joint Doctoral Program in Epidemiology, San Diego State University and University of California San Diego, San Diego CA, USA School of Medicine, University of California San Diego, San Diego CA, USA Department of Psychology, San Diego State University, San Diego CA, USA Department of Psychology, University of Arizona, Tucson AZ, USA Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA Family Medicine and Public Health, University of California San Diego, San Diego CA, USA.

Objective: We investigated the role of chronic stress burden on adiposity and adiposity-related inflammation with two hypotheses: (1) greater chronic stress is associated with higher central adiposity and selective accumulation of visceral adipose tissue (VAT) compared to subcutaneous adipose tissue (SAT); and (2) associations between VAT and inflammatory biomarkers are exacerbated when chronic stress is high.

Methods: Data come from 1,809 participants included in a Multi-Ethnic Study of Atherosclerosis ancillary study of body composition and adiposity-related inflammation. Chronic psychosocial stress was measured with a 5-item version of the Chronic Stress Burden Scale. First, we tested associations between chronic stress (3-level categorical variable) and VAT, SAT, and VAT/SAT ratio. Second, we tested whether associations between VAT and inflammatory biomarkers varied by level of chronic stress.

Results: Participants were approximately 65 years, 50% female, and 40.5% White, 25.6% Hispanic, 21.2% African American, and 12.8% Chinese American. About half of the sample reported little to no stress, and a quarter and a fifth of the sample reported medium and high levels of stress. Higher levels of chronic stress were associated with greater VAT and SAT, but not VAT/SAT ratio. Greater levels of VAT were associated with increased levels of adiposity-related inflammation in a graded pattern. These associations did not vary by stress level.

Conclusions: Greater chronic stress burden is associated with both central and subcutaneous adiposity. We found no evidence that the associations between VAT and inflammatory biomarkers are exacerbated by chronic stress. Findings contribute to ongoing literature untangling pathways in which psychosocial stress contributes to adiposity-related inflammation.
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http://dx.doi.org/10.1097/PSY.0000000000000983DOI Listing
July 2021

Adipose tissue biomarkers and type 2 diabetes incidence in normoglycemic participants in the MESArthritis Ancillary Study: A cohort study.

PLoS Med 2021 Jul 9;18(7):e1003700. Epub 2021 Jul 9.

Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Background: Given the central role of skeletal muscles in glucose homeostasis, deposition of adipose depots beneath the fascia of muscles (versus subcutaneous adipose tissue [SAT]) may precede insulin resistance and type 2 diabetes (T2D) incidence. This study was aimed to investigate the associations between computed tomography (CT)-derived biomarkers for adipose tissue and T2D incidence in normoglycemic adults.

Methods And Findings: This study was a population-based multiethnic retrospective cohort of 1,744 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with normoglycemia (baseline fasting plasma glucose [FPG] less than 100 mg/dL) from 6 United States of America communities. Participants were followed from April 2010 and January 2012 to December 2017, for a median of 7 years. The intermuscular adipose tissue (IMAT) and SAT areas were measured in baseline chest CT exams and were corrected by height squared (SAT and IMAT indices) using a predefined measurement protocol. T2D incidence, as the main outcome, was based on follow-up FPG, review of hospital records, or self-reported physician diagnoses. Participants' mean age was 69 ± 9 years at baseline, and 977 (56.0%) were women. Over a median of 7 years, 103 (5.9%) participants were diagnosed with T2D, and 147 (8.4%) participants died. The IMAT index (hazard ratio [HR]: 1.27 [95% confidence interval [CI]: 1.15-1.41] per 1-standard deviation [SD] increment) and the SAT index (HR: 1.43 [95% CI: 1.16-1.77] per 1-SD increment) at baseline were associated with T2D incidence over the follow-up. The associations of the IMAT and SAT indices with T2D incidence were attenuated after adjustment for body mass index (BMI) and waist circumference, with HRs of 1.23 (95% CI: 1.09-1.38) and 1.29 (95% CI: 0.96-1.74) per 1-SD increment, respectively. The limitations of this study include unmeasured residual confounders and one-time measurement of adipose tissue biomarkers.

Conclusions: In this study, we observed an association between IMAT at baseline and T2D incidence over the follow-up. This study suggests the potential role of intermuscular adipose depots in the pathophysiology of T2D.

Trial Registration: ClinicalTrials.gov NCT00005487.
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http://dx.doi.org/10.1371/journal.pmed.1003700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337053PMC
July 2021

Temporal change in inflammatory biomarkers and risk of cardiovascular events: the Multi-ethnic Study of Atherosclerosis.

ESC Heart Fail 2021 Jul 9. Epub 2021 Jul 9.

Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-0409, USA.

Aims: Little is known about the association of temporal changes in inflammatory biomarkers and the risk of death and cardiovascular diseases. We aimed to evaluate the association between temporal changes in C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6) and risk of heart failure (HF), cardiovascular disease (CVD), and all-cause mortality in individuals without a history of prior CVD.

Methods And Results: Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort with repeated measures of inflammatory biomarkers and no CVD event prior to the second measure were included. Quantitative measures, annual change, and biomarker change categories were used as main predictors in Cox proportional hazard models stratified based on sex and statin use. A total of 2258 subjects (50.6% female, mean age of 62 years) were studied over an average of 8.1 years of follow-up. The median annual decrease in CRP levels was 0.08 mg/L. Fibrinogen and IL-6 levels increased by a median of 30 mg/dL and 0.24 pg/mL annually. Temporal changes in CRP were positively associated with HF risk among females (HR: 1.18 per each standard deviation increase, P < 0.001) and other CVD in both female (HR: 1.12, P = 0.004) and male participants (HR: 1.24, P = 0.003). The association of CRP change with HF and other CVD was consistently observed in statin users (HR: 1.23 per SD increase, P = 0.001 for HF and HR: 1.19 per SD increase, P < 0.001 for other CVD). There were no significant associations between temporal changes of fibrinogen or IL-6 with HF or other CVD. Men with sustained high values of IL-6 had a 2.3-fold higher risk of all-cause mortality (P < 0.001) compared with those with sustained low values.

Conclusions: Temporal change in CRP is associated with HF only in women and statin users, and other CVD in both women and men, and statin users. Annual changes in fibrinogen and IL-6 were not predictive of cardiovascular outcomes in either sex.
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http://dx.doi.org/10.1002/ehf2.13445DOI Listing
July 2021

Neighborhood Socioeconomic Deprivation and Depression Symptoms in Adults From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Am J Community Psychol 2021 Jun 25. Epub 2021 Jun 25.

University of California San Diego, La Jolla, CA, USA.

Socioeconomic factors appear to impact mental health conditions such as depression, but little is known about the relative and combined role of neighborhood and personal socioeconomic deprivation among Hispanics/Latinos. This study examined cross-sectional associations of neighborhood and personal socioeconomic deprivation with depression symptoms in a US Hispanic/Latino population from the San Diego Field Center of the Hispanic Community Health Study/Study of Latinos (n = 3,851). Depression symptoms were assessed with the ten-item Centers for Epidemiological Studies in Depression Scale. Neighborhood socioeconomic deprivation was a composite of eleven variables (e.g., neighborhood income, education, employment, household crowding). Greater personal socioeconomic deprivation based on education, income, and employment was generally associated with higher depression symptoms, including after adjusting for neighborhood socioeconomic deprivation. Greater neighborhood socioeconomic deprivation was associated with higher depression symptoms in females but not males, but the association in females became non-significant when adjusting for personal socioeconomic deprivation. Neighborhood socioeconomic deprivation did not significantly interact with personal socioeconomic deprivation in relation to depression symptoms. The present findings support the association of personal socioeconomic status with mental health (indicated by depression symptoms) among Hispanic/Latino populations, whereas neighborhood socioeconomic deprivation did not relate to depression beyond the impact of personal indicators.
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http://dx.doi.org/10.1002/ajcp.12525DOI Listing
June 2021

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

Hum Mol Genet 2021 Jun 24. Epub 2021 Jun 24.

Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, 91101, USA.

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 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), 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 US. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for WHRadjBMI, 22 for WCadjBMI, and 28 for HIPadjBMI that reached suggestive significance (P < 1x10-6). 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 4 novel loci (P < 0.05 and consistent direction of effect, and P < 5x10-8 after meta-analysis), including 2 for WHRadjBMI (rs13301996, rs79478137); 1 for WCadjBMI (rs3168072); and 1 for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI; 10 for WCadjBMI; 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.
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http://dx.doi.org/10.1093/hmg/ddab166DOI Listing
June 2021

Endothelial-derived cardiovascular disease-related microRNAs elevated with prolonged sitting pattern among postmenopausal women.

Sci Rep 2021 Jun 3;11(1):11766. Epub 2021 Jun 3.

Department of Family Medicine, UC San Diego, La Jolla, CA, USA.

Time spent sitting is positively correlated with endothelial dysfunction and cardiovascular disease risk. The underlying molecular mechanisms are unknown. MicroRNAs contained in extracellular vesicles (EVs) reflect cell/tissue status and mediate intercellular communication. We explored the association between sitting patterns and microRNAs isolated from endothelial cell (EC)-derived EVs. Using extant actigraphy based sitting behavior data on a cohort of 518 postmenopausal overweight/obese women, we grouped the woman as Interrupted Sitters (IS; N = 18) or Super Sitters (SS; N = 53) if they were in the shortest or longest sitting pattern quartile, respectively. The cargo microRNA in EC-EVs from the IS and SS women were compared. MicroRNA data were weighted by age, physical functioning, MVPA, device wear days, device wear time, waist circumference, and body mass index. Screening of CVD-related microRNAs demonstrated that miR-199a-5p, let-7d-5p, miR-140-5p, miR-142-3p, miR-133b level were significantly elevated in SS compared to IS groups. Group differences in let-7d-5p, miR-133b, and miR-142-3p were validated in expanded groups. Pathway enrichment analyses show that mucin-type O-glycan biosynthesis and cardiomyocyte adrenergic signaling (P < 0.001) are downstream of the three validated microRNAs. This proof-of-concept study supports the possibility that CVD-related microRNAs in EC-EVs may be molecular transducers of sitting pattern-associated CVD risk in overweight postmenopausal women.
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http://dx.doi.org/10.1038/s41598-021-90154-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175392PMC
June 2021

Pericardial Fat and the Risk of Heart Failure.

J Am Coll Cardiol 2021 Jun;77(21):2638-2652

Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

Background: Obesity is a well-established risk factor for heart failure (HF). However, implications of pericardial fat on incident HF is unclear.

Objectives: This study sought to examine the association between pericardial fat volume (PFV) and newly diagnosed HF.

Methods: This study ascertained PFV using cardiac computed tomography in 6,785 participants (3,584 women and 3,201 men) without pre-existing cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis). Cox proportional hazards regression was used to evaluate PFV as continuous and dichotomous variable, maximizing the J-statistic: (Sensitivity + Specificity - 1).

Results: In 90,686 person-years (median: 15.7 years; interquartile range: 11.7 to 16.5 years), 385 participants (5.7%; 164 women and 221 men) developed newly diagnosed HF. PFV was lower in women than in men (69 ± 33 cm vs. 92 ± 47 cm; p < 0.001). In multivariable analyses, every 1-SD (42 cm) increase in PFV was associated with a higher risk of HF in women (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.21 to 1.71; p < 0.001) than in men (HR: 1.13; 95% CI: 1.01 to 1.27; p = 0.03) (interaction p = 0.01). High PFV (≥70 cm in women; ≥120 cm in men) conferred a 2-fold greater risk of HF in women (HR: 2.06; 95% CI: 1.48 to 2.87; p < 0.001) and a 53% higher risk in men (HR: 1.53; 95% CI: 1.13 to 2.07; p = 0.006). In sex-stratified analyses, greater risk of HF remained robust with additional adjustment for anthropometric indicators of obesity (p ≤ 0.008), abdominal subcutaneous or visceral fat (p ≤ 0.03) or biomarkers of inflammation and hemodynamic stress (p < 0.001) and was similar among Whites, Blacks, Hispanics, and Chinese (interaction p = 0.24). Elevated PFV predominantly augmented the risk of HF with preserved ejection fraction (p < 0.001) rather than reduced ejection fraction (p = 0.31).

Conclusions: In this large, community-based, ethnically diverse, prospective cohort study, pericardial fat was associated with an increased risk of HF, particularly HF with preserved ejection fraction, in women and men.
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http://dx.doi.org/10.1016/j.jacc.2021.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218602PMC
June 2021

Occupations Associated With Poor Cardiovascular Health in Women: The Women's Health Initiative Observational Study.

J Occup Environ Med 2021 05;63(5):387-394

Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania (Nriagu, Ako, Wang, Michael); Department of Environmental and Occupational Health, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania (De Roos); Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa (Wallace); Department of Family Medicine and Public Health University of California, San Diego, La Jolla, California (Allison); Texas A&M AgriLife Research, Texas A&M University System, College Station, Texas (Seguin).

Introduction: Research on the effect of occupation on cardiovascular health (CVH) among older women is limited.

Methods: Each of the seven American Heart Association's CVH metrics was scored as ideal (1) or non-ideal (0) and summed. Multivariable logistic regression was used to estimate the odds of poor overall CVH (CVH score of 0 to 2) comparing women employed in each of the top 20 occupational categories to those not employed in that category, adjusting for age, marital status, and race/ethnicity.

Results: (1) Bookkeeping, accounting, and auditing clerks; (2) first-line supervisors of sales workers; (3) first-line supervisors of office and administrative support workers; and (4) nursing, psychiatric, and home health aides were more likely to have poor overall CVH compared to women who did not work in these occupations.

Conclusions: Several commonly held occupations among women were associated with poor CVH.
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http://dx.doi.org/10.1097/JOM.0000000000002135DOI Listing
May 2021

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

Hum Mol Genet 2021 Jul;30(15):1443-1456

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.

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.
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http://dx.doi.org/10.1093/hmg/ddab096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283205PMC
July 2021

Quantitative Analysis of Adipose Depots by Using Chest CT and Associations with All-Cause Mortality in Chronic Obstructive Pulmonary Disease: Longitudinal Analysis from MESArthritis Ancillary Study.

Radiology 2021 06 6;299(3):703-711. Epub 2021 Apr 6.

From the Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N Caroline St, JHOC 3171c, Baltimore, MD 21287 (F.P., S.D.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (M.S., T.Q.A.C.S., W.S.P., J.A.C.L.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (D.A.B.); Lundquist Institute at Harbor-University of California Los Angeles School of Medicine, Torrance, Calif (M.B.); Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); and Division of Preventive Medicine, Department of Family Medicine and Public Health, University of Calif San Diego, La Jolla, Calif (M.A.A.).

Background Obesity and sarcopenia are associated with mortality in chronic obstructive pulmonary disease (COPD). Routine chest CT examinations may allow assessment of obesity and sarcopenia by soft-tissue markers for predicting risks of mortality. Purpose To investigate associations between soft-tissue markers subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and pectoralis muscle (PM) index from chest CT with mortality in participants with COPD. Materials and Methods In this secondary analysis of a prospectively enrolled cohort from the Multi-Ethnic Study of Atherosclerosis, participants with available chest CT in 2010-2012 were included. CT examinations were analyzed to determine SAT, IMAT (within PM), and PM areas. The spirometry evaluations were used to establish COPD diagnosis. Mortality data were extracted from the National Death Index (April 2010 to December 2017). The correlations of the soft-tissue markers with fat mass index were studied. The associations of these markers and risks of mortality in participants with COPD were assessed by using Cox proportional-hazard models adjusted for confounders. Results Among 2994 participants who were included (mean age, 69 years ± 9 [standard deviation]; 1551 women), 265 had COPD (9%; mean age, 72 years ± 9; 162 men) and 49 participants with COPD (18%) died during follow-up. The SAT, IMAT, and PM areas had moderate-to-excellent reliabilities (intraclass correlation coefficient, 0.88-0.99). In the 2994 participants, the SAT (ρ = 0.80; 95% CI: 0.78, 0.81; < .001) and IMAT indexes (ρ = 0.37; 95% CI: 0.34, 0.41; < .001) were correlated with fat mass index. Those with COPD and higher SAT index had lower risks of mortality (hazard ratio, 0.2; 95% CI: 0.1, 0.4; < .001, per doubling), whereas a higher IMAT index was associated with a higher risk of mortality (hazard ratio, 1.4; 95% CI: 1.0, 1.9; = .04, per doubling). Conclusion Soft-tissue markers were reliably obtained by using chest CT performed for lung assessment. In participants with chronic obstructive pulmonary disease, a high intermuscular adipose tissue index was associated with a higher risk of mortality than was a high subcutaneous adipose tissue index. © RSNA, 2021 See also the editorial by Sverzellati and Cademartiri in this issue.
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http://dx.doi.org/10.1148/radiol.2021203959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165946PMC
June 2021

Hemostatic factors, inflammatory markers, and risk of incident venous thromboembolism: The Multi-Ethnic Study of Atherosclerosis.

J Thromb Haemost 2021 07 7;19(7):1718-1728. Epub 2021 May 7.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

Background: Several hemostatic factors and inflammatory markers are associated with the risk of incident venous thromboembolism (VTE), however, most existing data are from case-control studies in Caucasian populations.

Objectives: We aimed to prospectively confirm previous findings and explore less studied biomarkers in relation to VTE risk in a multi-racial/multi-ethnic cohort.

Methods: Circulating levels of factor VIII, fibrinogen, D-dimer, plasmin-antiplasmin complex (PAP), C-reactive protein (CRP), and interleukin-6 (IL-6) were measured at baseline (2000-2002) in 6706 participants of the Multi-Ethnic Study of Atherosclerosis. Incident VTE was identified using hospitalization discharge codes from baseline to December 31, 2015. Hazard ratios (HRs) of VTE were estimated in Cox regression models.

Results: There were 227 events during a median of 14 years of follow-up. Compared with participants in the lowest quartile, the HRs for those above the 95th percentile and p for trend across categories were 3.50 (95% confidence interval [CI] 1.98-6.19; p < .001) for D-dimer, 1.49 (95% CI 0.84-2.63; p = .02) for factor VIII, 1.32 (95% CI 0.76-2.28; p = .99) for fibrinogen, 1.92 (95% CI 1.08-3.42; p = .15) for PAP, 1.68 (95% CI 0.81-3.48; p = .08) for CRP, and 2.55 (95% CI 1.15-5.66; p = .07) for IL-6, after adjustment for demographics and body mass index. For CRP and IL-6, follow-up was restricted to 10 years because of violations of the proportional hazards assumption. No significant interactions by age/ethnicity were observed.

Conclusions: We demonstrated a fairly novel association between PAP and risk of incident VTE, and contributed further prospective confirmation regarding the associations of D-dimer, factor VIII, and IL-6 with VTE.
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http://dx.doi.org/10.1111/jth.15315DOI Listing
July 2021

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

Am J Hum Genet 2021 04 12;108(4):564-582. Epub 2021 Mar 12.

The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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.
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http://dx.doi.org/10.1016/j.ajhg.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059339PMC
April 2021

Stroke Risk Factor Status and Use of Stroke Prevention Medications Among Hispanic/Latino Adults in HCHS/SOL.

Stroke 2021 Apr 4;52(4):1339-1346. Epub 2021 Mar 4.

Department of Neurology and Rehabilitation (F.B., D.P., F.D.T.), University of Illinois at Chicago.

Background And Purpose: We investigated the prevalence, awareness, and control of vascular risk factors (VRFs) and the use of antithrombotic and statin agents in HCHS (Hispanic Community Health Study)/SOL (Study of Latinos) participants with self-reported history of stroke or transient ischemic attack.

Methods: Sociodemographic characteristics, medications, and prevalence of different VRFs were recorded. VRF diagnoses and goals were based on the recommendations of professional organizations. Factors associated with optimal VRF control and use of antithrombotic and statin agents were investigated using multivariate logistic regression.

Results: The analysis included 404 participants (39% men). The prevalences of hypertension, dyslipidemia, and diabetes were 59%, 65%, and 39%, respectively. Among those who met the diagnostic criteria for these diagnoses, the frequencies of awareness were 90%, 75%, and 83%, respectively. In participants who were aware of their VRFs, the prevalences of controlled hypertension, dyslipidemia, and diabetes were 46%, 32%, and 54%. Approximately 46% of the participants were on antithrombotics, 39% on statins, and 26% on both. Only 38% of those with atrial fibrillation received anticoagulation. In multivariate analyses adjusted for baseline sociodemographic characteristics, older age was associated with uncontrolled hypertension and diabetes. Residing in the United States for ≥10 years and born in the United States were associated with uncontrolled diabetes, female sex with uncontrolled dyslipidemia, and lack of health insurance with decreased use of statins and hyperlipidemia.

Conclusions: Hispanic/Latino adults in the United States have high prevalence and awareness of VRFs but low adherence to secondary stroke prevention strategies. Older adults, women, and uninsured people are vulnerable groups that may benefit from targeted interventions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060344.
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http://dx.doi.org/10.1161/STROKEAHA.120.031216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988300PMC
April 2021

Go Red for Women Strategically Focused Research Network: Summary of Findings and Network Outcomes.

J Am Heart Assoc 2021 02 23;10(5):e019519. Epub 2021 Feb 23.

General Internal Medicine Department of Medicine Johns Hopkins University School of Medicine Baltimore MD.

The Go Red for Women movement was initiated by the American Heart Association (AHA) in the early 2000s to raise awareness concerning cardiovascular disease (CVD) risk in women. In 2016, the AHA funded 5 research centers across the United States to advance our knowledge of the risks and presentation of CVD that are specific to women. This report highlights the findings of the centers, showing how insufficient sleep, sedentariness, and pregnancy-related complications may increase CVD risk in women, as well as presentation and factors associated with myocardial infarction with nonobstructive coronary arteries and heart failure with preserved ejection fraction in women. These projects were augmented by collaborative ancillary studies assessing the relationships between various lifestyle behaviors, including nightly fasting duration, mindfulness, and behavioral and anthropometric risk factors and CVD risk, as well as metabolomic profiling of heart failure with preserved ejection fraction in women. The Go Red for Women Strategically Focused Research Network enhanced the evidence base related to heart disease in women, promoting awareness of the female-specific factors that influence CVD.
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http://dx.doi.org/10.1161/JAHA.120.019519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174263PMC
February 2021

Long-Term Exposure to Ambient Air Pollution and Cognitive Function Among Hispanic/Latino Adults in San Diego, California.

J Alzheimers Dis 2021 ;79(4):1489-1496

Department of Family Medicine and Public Health, UC San Diego, La Jolla, CA, USA.

Background: Hispanics/Latinos in the United States are more likely to live in neighborhoods with greater exposure to air pollution and are projected to have the largest increase in dementia among race/ethnic minority groups.

Objective: We examined the associations of air pollution with performance on cognitive function tests in Hispanic/Latino adults.

Methods: We used data from the San Diego site of the Hispanic Community Health Study/Study of Latinos, an ongoing cohort of Hispanics/Latinos. This analysis focused on individuals ≥45 years of age who completed a neurocognitive battery examining overall mental status, verbal learning, memory, verbal fluency, and executive function (n = 2,089). Air pollution (PM2.5 and O3) before study baseline was assigned to participants' zip code. Logistic and linear regression were used to estimate the associations of air pollution on overall mental status and domain-specific standardized test scores. Models accounted for complex survey design, demographic, and socioeconomic characteristics.

Results: We found that for every 10μg/m3 increase in PM2.5, verbal fluency worsened (β: -0.21 [95%CI: -0.68, 0.25]). For every 10 ppb increase in O3, verbal fluency and executive function worsened (β: -0.19 [95%CI: -0.34, -0.03]; β: -0.01 [95%CI: -0.01, 0.09], respectively). We did not identify any detrimental effect of pollutants on other domains.

Conclusion: Although we found suggestions that air pollution may impact verbal fluency and executive function, we observed no consistent or precise evidence to suggest an adverse impact of air pollution on cognitive level among this cohort of Hispanic/Latino adults.
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http://dx.doi.org/10.3233/JAD-200766DOI Listing
September 2021

Lipoprotein (a) and coronary artery calcification: prospective study assessing interactions with other risk factors.

Metabolism 2021 03 7;116:154706. Epub 2021 Jan 7.

Lipid Research Group, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. Electronic address:

Background: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship.

Methods: We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline.

Results: Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm/year in quartile 4, compared to -3.44, -0.59 and 1.91 mm/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL.

Conclusions: Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression.
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http://dx.doi.org/10.1016/j.metabol.2021.154706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853621PMC
March 2021

Occupations Associated with Poor Cardiovascular Health in Women: The Women's Health Initiative Observational Study.

J Occup Environ Med 2021 Jan 6;Publish Ahead of Print. Epub 2021 Jan 6.

Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania (Nriagu, Ako, Wang, Michael), Department of Environmental and Occupational Health, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania (Roos), Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa (Wallace), Department of Family Medicine and Public Health University of California, San Diego, La Jolla (Allison), Texas A&M AgriLife Research, Texas A&M University System (Seguin).

Introduction: Research on the effect of occupation on cardiovascular health (CVH) among older women is limited.

Methods: Each of the 7 American Heart Association's CVH metrics was scored as ideal (1) or non-ideal (0) and summed. Multivariable logistic regression was used to estimate the odds of poor overall CVH (CVH score of 0-2) comparing women employed in each of the top 20 occupational categories to those not employed in that category, adjusting for age, marital status, and race/ethnicity.

Results: 1) Bookkeeping, accounting, and auditing clerks; 2) first-line supervisors of sales workers; 3) first-line supervisors of office and administrative support workers; and 4) nursing, psychiatric, and home health aides were more likely to have poor overall CVH compared to women who did not work in these occupations.

Conclusions: Several commonly held occupations among women were associated with poor CVH.
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http://dx.doi.org/10.1097/JOM.00000000000021DOI Listing
January 2021

Diet quality indices and risk of metabolic syndrome among postmenopausal women of Mexican ethnic descent in the Women's Health Initiative Observational Study.

Nutr Healthy Aging 2020 Nov 3;5(4):261-272. Epub 2020 Nov 3.

Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: The prevalence of metabolic syndrome is higher among minority populations, including individuals of Mexican ethnic descent. Whether alignment to healthy dietary patterns is associated with lower risk of metabolic syndrome in this population is largely unknown.

Objective: To prospectively evaluate the associations between diet quality scores and risk of metabolic syndrome and its components among postmenopausal women of Mexican ethnic descent.

Methods: A total of 334 women of Mexican ethnic descent who participated in the Women's Health Initiative (WHI) observational study without metabolic syndrome or diabetes at baseline (1993-1998) were included. Baseline diets were scored with the Alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH), the Healthy Eating Index (HEI-2010), the Mediterranean Diet Score (MDS), and the traditional Mexican Diet (MexD) score. Multivariable linear and logistic regression models were used to test the associations between baseline diet quality and risk of metabolic syndrome and its individual components at follow-up (2012-2013).

Results: Approximately 16% of women met the criteria for metabolic syndrome at follow-up. None of the diet quality indices were associated with risk of metabolic syndrome. However, higher vs lower DASH scores were associated with lower waist circumference (85.2 vs 88.0 cm) and glucose concentrations (90.0 vs 95.1 mg/dL), and higher HDL cholesterol (62.6 vs 59.0 mg/dL), while higher vs lower HEI-2010 scores were associated with lower waist circumference (83.9 vs 88.1 cm), triglycerides (103 vs 117 mg/dL) and glucose concentrations (89.5 vs 94.4 mg/dL), and higher HDL cholesterol levels (63.9 vs 58.5 mg/dL).

Conclusions: Diet quality was not associated with risk of metabolic syndrome in this population. However, the results suggest that alignment to DASH and HEI-2010 recommendations may be beneficial for reducing some individual components of metabolic syndrome among postmenopausal women of Mexican descent.
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http://dx.doi.org/10.3233/NHA-190076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745721PMC
November 2020

Lipoprotein (a) and the risk of elevated depressive symptoms: The Multi-Ethnic Study of Atherosclerosis.

J Psychiatr Res 2021 01 13;133:119-124. Epub 2020 Dec 13.

Lipid Research Group, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. Electronic address:

Previous studies suggested a potential relationship between plasma lipoprotein (a) [Lp(a)] and elevated depressive symptoms. We aimed to investigate any such relationship in the Multi-Ethnic Study of Atherosclerosis participants who were free of cardiovascular events. Analysis included 4938 participants without elevated depressive symptoms and with Lp(a) levels measured at baseline. Participants were examined at four clinic visits over a 10-year period. Elevated depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D) and were defined as a CES-D score ≥16 or use of anti-depressants. Lp(a) level was measured with a latex-enhanced turbidimetric immunoassay. After adjusting for demographics, socioeconomic factors and other confounding factors in Cox regression analyses, a higher ln-transformed Lp(a) level was associated with new elevated depressive symptoms since baseline (hazard ratio [95% CI] = 1.09 [1.02-1.16] per SD increment in ln-transformed level, P = 0.01). However, no association was found when elevated Lp(a) levels were assessed using clinical cut-off point (≥30 or 50 mg/dL), nor in sensitivity analyses using alternative definitions of elevated depressive symptoms. No significant interaction with race/ethnicity was found for all the above analyses. Also, no significant association was found between baseline Lp(a) levels and absolute or relative changes in CES-D score between baseline and last follow-up visits. Our study suggests a potential association between Lp(a) level and new elevated depressive symptoms, but such association was not robust in the sensitivity analyses. Future studies are warranted to investigate the role of Lp(a) in depressive symptoms in other cohorts.
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http://dx.doi.org/10.1016/j.jpsychires.2020.12.022DOI Listing
January 2021

Dietary cholesterol and egg intake in relation to incident cardiovascular disease and all-cause and cause-specific mortality in postmenopausal women.

Am J Clin Nutr 2021 04;113(4):948-959

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Background: The potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades.

Objectives: We aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality.

Methods: We included 96,831 US postmenopausal women aged 50-79 y without known CVD or cancer during baseline enrollment (1993-1998) of the Women's Health Initiative. Dietary information was collected using a validated FFQ. Incident CVD [i.e., ischemic heart disease (IHD) and stroke] and all-cause and cause-specific mortality were ascertained and adjudicated through February 2018.

Results: A total of 9808 incident CVD cases and 19,508 all-cause deaths occurred during a median follow-up of 17.8 y and 18.9 y, respectively. After multivariable adjustment for traditional risk factors and key dietary nutrients including dietary saturated fat, there were modest associations of dietary cholesterol intake with incident CVD (HRQ5versusQ1: 1.12; 95% CI: 1.03, 1.21; P-trend < 0.001) and all-cause mortality (HRQ5versusQ1: 1.09; 95% CI: 1.02, 1.15; P-trend < 0.001). Significant positive associations were also observed between dietary cholesterol and incident IHD (P-trend = 0.007), incident ischemic stroke (P-trend = 0.002), and CVD mortality (P-trend = 0.002), whereas there was an inverse association for incident hemorrhagic stroke (P-trend = 0.037) and no association for mortality from cancer, Alzheimer disease/dementia, respiratory diseases, or other causes (P-trend > 0.05). Higher egg consumption was also associated with modestly higher risk of incident CVD (P-trend = 0.004) and all-cause mortality (P-trend < 0.001), with HRs of 1.14 (95% CI: 1.04, 1.25) and 1.14 (95% CI: 1.07, 1.22), respectively, when comparing ≥1 egg/d with <1 egg/wk.

Conclusions: Both higher dietary cholesterol intake and higher egg consumption appeared to be associated with modestly elevated risk of incident CVD and all-cause mortality in US postmenopausal women.
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http://dx.doi.org/10.1093/ajcn/nqaa353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023834PMC
April 2021

Health insurance status and type associated with varying levels of glycemic control in the US: The multi-ethnic study of atherosclerosis (MESA).

Prim Care Diabetes 2021 04 9;15(2):378-384. Epub 2020 Dec 9.

Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California, USA.

Aims: To investigate associations of health insurance with measures of glucose metabolism, and whether associations vary by diabetes status or insurance type.

Methods: Cross-sectional analysis of baseline data from the Multi-Ethnic Study of Atherosclerosis. Cohort a priori stratified by age <65 (N = 3,665) and ≥65 years (N = 2,924). Multivariable linear and logistic regression assessed associations between insurance and fasting glucose, HOMA-IR, and prevalent diabetes, controlling for relevant confounders, including age, sex, race/ethnicity, income, and education.

Results: In participants <65, compared to uninsured, having any insurance was associated with lower fasting glucose in participants with diabetes (Mean Difference = -20.4 mg/dL, P = 0.01), but not in participants without diabetes. Compared to Private insurance, uninsured participants had higher fasting glucose (Mean Difference = 3.8 mg/dL, P = 0.03), while participants with Medicaid had higher HOMA-IR (Mean Difference = 3.5 mg/dL, P < 0.01). In participants ≥65, compared to Private insurance, uninsured participants (Mean Difference = 7.5 mg/dL, P = 0.02), and participants with Medicaid only (Mean Difference = 19.9 mg/dL, P < 0.01) or Medicare + Medicaid (Mean Difference = 5.2 mg/dL, P = 0.03) had higher fasting glucose.

Conclusions: In this large multiethnic cohort, having any insurance was associated with significantly lower fasting glucose for individuals with diabetes. Levels of fasting glucose and insulin resistance varied across different insurance types.
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http://dx.doi.org/10.1016/j.pcd.2020.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936947PMC
April 2021

Association between dairy product intake and body composition among South Asian adults from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study.

Br J Nutr 2021 Oct 14;126(7):1100-1109. Epub 2020 Dec 14.

Public Health Nutrition, School of Global Public Health, New York University, New York, NY, USA.

South Asians, who are at a disproportionately greater risk of atherosclerotic CVD (ASCVD), represent a rapidly growing population in the USA. The relationship between dairy products, a major component of South Asian diets, and body composition - an established risk factor for ASCVD, is unclear. The aim of the present study was to examine associations between dairy intake and multiple measures of body composition (BMI, waist and hip circumference, waist:hip ratio, abdominal lean mass, subcutaneous, visceral, and intermuscular fat areas) among South Asian adults in the USA. A baseline analysis was conducted using existing data from the Mediators of Atherosclerosis in South Asians Living in America cohort. In women, the highest (>1·9 servings/d) v. lowest (<1 serving/d) tertile of dairy intake was associated with 53 % lower odds of a waist circumference >80 cm (95 % CI 0·25, 0·89, Pfor trend<0·05). No associations were observed between dairy intake and measures of body composition. However, >3 servings of low-fat yogurt/week was associated with a 9·9 cm2 lower visceral fat area (95 % CI -19·07, -0·72, P<0·05) and 2·3 cm2 lower intermuscular fat area (95 % CI -3·76, -0·79, P<0·05) as compared with those with three servings/week. Milk and cheese were not associated with body composition measures. These analyses suggest that higher consumption of low-fat yogurt is associated with lower visceral and intermuscular fat in the whole sample, and women with higher dairy intake have lower waist circumference. Our study supports dietary incorporation of dairy products, and recognises the utility of multidimensional measures of central adiposity.
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http://dx.doi.org/10.1017/S0007114520005061DOI Listing
October 2021

Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement From the American Heart Association.

Circulation 2020 Dec 30;142(25):e506-e532. Epub 2020 Nov 30.

Cardiovascular disease (CVD) is the leading cause of death in women, who have a notable increase in the risk for this disease after menopause and typically develop coronary heart disease several years later than men. This observation led to the hypothesis that the menopause transition (MT) contributes to the increase in coronary heart disease risk. Over the past 20 years, longitudinal studies of women traversing menopause have contributed significantly to our understanding of the relationship between the MT and CVD risk. By following women over this period, researchers have been able to disentangle chronological and ovarian aging with respect to CVD risk. These studies have documented distinct patterns of sex hormone changes, as well as adverse alterations in body composition, lipids and lipoproteins, and measures of vascular health over the MT, which can increase a woman's risk of developing CVD postmenopausally. The reported findings underline the significance of the MT as a time of accelerating CVD risk, thereby emphasizing the importance of monitoring women's health during midlife, a critical window for implementing early intervention strategies to reduce CVD risk. Notably, the 2011 American Heart Association guidelines for CVD prevention in women (the latest sex-specific guidelines to date) did not include information now available about the contribution of the MT to increased CVD in women. Therefore, there is a crucial need to discuss the contemporary literature on menopause and CVD risk with the intent of increasing awareness of the significant adverse cardiometabolic health-related changes accompanying midlife and the MT. This scientific statement provides an up-to-date synthesis of the existing data on the MT and how it relates to CVD.
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http://dx.doi.org/10.1161/CIR.0000000000000912DOI Listing
December 2020

The association between indices of blood pressure waveforms (PTC1 and PTC2) and incident heart failure.

J Hypertens 2021 04;39(4):661-666

Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.

Objectives: The radial artery pulse waveform is a continuous measure of pressure throughout the cardiac cycle, and thus can provide more information than just systolic and diastolic blood pressures. New indices based on a Windkessel model of the waveform, PTC1 and PTC2, are related to arterial compliance and add information for prediction of incident cardiovascular disease (coronary heart disease, stroke, myocardial infarction) but their association with heart failure is unknown.

Methods: Among 6229 adults (mean age 62 years) from four race/ethnic groups who were initially free of clinical cardiovascular disease and heart failure in 2000-2002, we evaluated the associations of baseline PTC1 and PTC2 with incident heart failure.

Results: Mean ± standard deviation PTC1 and PTC2 were 394 ± 334 and 94 ± 46 ms, respectively. During a median of 15.7 years follow-up, there were 357 heart failure events (148 with reduced, 150 with preserved, and 59 with unknown ejection fraction). After adjustment for traditional risk factors, the hazard ratio for heart failure per 1 standard deviation higher PTC2 was 0.73 (95% confidence interval: 0.63--0.85). Higher PTC2 was also significantly associated with lower risk of heart failure with reduced ejection fraction (hazard ratio = 0.67; 95% confidence interval: 0.56--0.80). There was no evidence of a significant association between PTC2 and heart failure with preserved ejection fraction or between PTC1 and heart failure.

Conclusion: The PTC2 measure of the radial artery pulse waveform may represent a novel phenotype related to heart failure, especially heart failure with reduced ejection fraction.
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http://dx.doi.org/10.1097/HJH.0000000000002707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177733PMC
April 2021

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

Ann Surg 2020 Nov 4. Epub 2020 Nov 4.

Departments of Epidemiology, Surgery, and Medicine, Brown University, Providence, Rhode Island.

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 menarche. 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.
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http://dx.doi.org/10.1097/SLA.0000000000004581DOI Listing
November 2020

Sex-Specific Associations of Cardiovascular Risk Factors and Biomarkers With Incident Heart Failure.

J Am Coll Cardiol 2020 09;76(12):1455-1465

Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address:

Background: Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear.

Objectives: The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF.

Methods: The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio.

Results: Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001).

Conclusions: CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.
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http://dx.doi.org/10.1016/j.jacc.2020.07.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493711PMC
September 2020

Lipoprotein(a) levels and risk of abdominal aortic aneurysm in the Women's Health Initiative.

J Vasc Surg 2021 Apr 31;73(4):1245-1252.e3. Epub 2020 Aug 31.

Department of Epidemiology and Medicine, Brown University, Providence, RI.

Objective: Few studies have prospectively examined the associations of lipoprotein(a) [Lp(a)] levels with the risk of abdominal aortic aneurysm (AAA), especially in women. Accounting for commonly recognized risk factors, we investigated the baseline Lp(a) levels and the risk of AAA among postmenopausal women participating in the ongoing national Women's Health Initiative.

Methods: Women's Health Initiative participants with baseline Lp(a) levels available who were beneficiaries of Medicare parts A and B fee-for-service at study enrollment or who had aged into Medicare at any point were included. Participants with missing covariate data or known AAA at baseline were excluded. Thoracic aneurysms were excluded owing to the different pathophysiology. The AAA cases and interventions were identified using the International Classification of Diseases, 9th and 10th revision, codes and Current Procedural Terminology codes from claims data. Hazard ratios were computed using Cox proportional hazard models according to the quintiles of Lp(a).

Results: The mean age of the 6615 participants included in the analysis was 65.3 years. Of the 6615 participants, 66.6% were non-Hispanic white, 18.9% were black, 7% were Hispanic and 4.7% were Asian/Pacific Islander. Compared with the participants in the lowest Lp(a) quintile, those in higher quintiles were more likely to be overweight, black, and former or current smokers, to have hypertension, hyperlipidemia, and a history of cardiovascular disease, and to use menopausal hormone therapy and statins. During 65,476 person-years of follow-up, with a median of 10.4 years, 415 women had been diagnosed with an AAA and 36 had required intervention. More than one half had required intervention for a ruptured AAA. We failed to find a statistically significant association between Lp(a) levels and incident AAA. Additional sensitivity analyses stratified by race, with exclusion of statin users and alternative categorizations of Lp(a) using log-transformed levels, tertiles, and a cutoff of >50 mg/dL, were conducted, which did not reveal any significant associations.

Conclusions: We found no statistically significant association between Lp(a) levels and the risk of AAA in a large and well-phenotyped sample of postmenopausal women. Women with high Lp(a) levels were more likely to be overweight, black, and former or current smokers, and to have hypertension, hyperlipidemia, and a history of cardiovascular disease, or to use hormone therapy and statins compared with those with lower Lp(a) levels. These findings differ from previous prospective, case-control, and meta-analysis studies that had supported a significant relationship between higher Lp(a) levels and an increased risk of AAA. Differences in the association could have resulted from study limitations or sex differences.
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http://dx.doi.org/10.1016/j.jvs.2020.07.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914280PMC
April 2021
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