Multi-Ethnic Study Of Atherosclerosis Participants Research Articles

The Association between Proteomic Aging Clocks and the Risk of Cancer in Midlife Individuals.

To measure the aging process before a cancer diagnosis, we developed the first cancer-specific proteomic aging clock (CaPAC) and examined its association with cancer risk in the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis (MESA) studies. Using the SomaScan assay, ARIC measured 4,712 proteins in plasma samples collected in 1990-92 from 3,347 participants who developed cancer over follow-up until 2015 and 7,487 who remained cancer-free, all aged 46-70. We constructed CaPAC0 using elastic net regression among two-thirds randomly selected cancer-free participants (N=4,991, training set) and calculated age acceleration for CaPAC0 (CaPAA0) as residuals of CaPAC0 on chronological age in all remaining ARIC participants. We used multivariable-adjusted Cox proportional hazards regression to calculate hazard ratios (HRs) for the risk of overall, obesity-related, smoking-related, and the most common cancers (prostate, lung, breast, colorectal) with CaPAA0 using a case-cohort design. We replicated the analysis in 3,893 MESA participants aged 46-70 at Exam 1 (456 incident cancer). CaPAC0 was correlated with chronological age in ARIC and MESA (r=0.82 and 0.86, respectively). In both ARIC and MESA, CaPAA0 was significantly (p<0.05) associated with the risk of overall [HRs per 5-years=1.08 and 1.23, respectively], smoking-related [HRs=1.30 and 1.54, respectively], and lung cancers [HRs=1.54 and 1.94, respectively]. CaPAA0 was also significantly associated with colorectal cancer risk in ARIC [HR=1.31], but not in MESA. CaPAA0 was not associated with obesity-related, breast, or prostate cancers. CaPAA0 was associated with several types of cancer with the strongest association observed for lung cancer risk.

Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis.

Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited. To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4). The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024. Urine samples were collected at baseline (2000-2002), and arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc levels were measured in 2020-2022. Digit Symbol Coding (DSC) (n = 3819) (possible score range, 0-133), Cognitive Abilities Screening Instrument (CASI) (n = 3918) (possible score range, 0-100), and Digit Span (DS) (n = 4176) (possible score range, 0-30) cognitive tests were administered in 2010-2012; higher scores of each test indicate increasing levels of positive response. A total of 6303 participants were followed up for dementia diagnosis through 2018. The median age at baseline was 60 (IQR, 53-70) years, and 3303 participants (52.4%) were female. The median cognitive scores were 51 (IQR, 38-64) for DSC, 90 (IQR, 84-95) for CASI, and 15 (IQR, 12-18) for DS. There were 559 cases of dementia through the follow-up period. Inverse associations with DSC were identified: mean differences in z scores per IQR increase in metal levels were -0.03 (95% CI, -0.07 to 0.00) for arsenic, -0.05 (95% CI, -0.09 to -0.004) for cobalt, -0.05 (95% CI, -0.07 to -0.02) for copper, -0.04 (95% CI, -0.08 to -0.001) for uranium, and -0.03 (95% CI, -0.06 to -0.01) for zinc. Among 1058 APOE4 carriers, manganese was also inversely associated with DSC. The joint mean difference of DSC comparing percentile 95th with the 25th of the 9-metal mixture was -0.30 (95% CI, -0.47 to -0.14) for APOE4 carriers and -0.10 (95% CI, -0.19 to -0.01) for noncarriers. Arsenic, cadmium, cobalt, copper, tungsten, uranium, and zinc were individually associated with dementia, with hazard ratios per IQR of metal ranging from 1.15 (95% CI, 1.03-1.29) for tungsten to 1.46 (95% CI, 1.06-2.02) for uranium. The joint hazard ratio of dementia comparing percentiles 95th with the 25th of the 9-metal mixture was 1.71 (95% CI, 1.24-3.89), with no significant difference by APOE4 status. In this study, participants with higher concentrations of metals in their urine, compared with those with lower concentrations, had worse performance on cognitive tests and greater likelihood of developing dementia. The findings of this multicenter multiethnic cohort study might inform screening and potential interventions for prevention of dementia based on individuals' metal exposure levels and genetic profiles.

Plasma Proteomic Determinants of Small Vessel Disease of the Brain: the Multi‐Ethnic Study of Atherosclerosis

AbstractBackgroundThe identification of novel blood‐based biomarkers of small vessel disease of the brain (SVD) may improve pathophysiologic understanding and inform the development of new therapeutic strategies for prevention. We evaluated plasma proteomic associations of white matter fractional anisotropy (WMFA), white matter hyperintensity (WMH) volume, enlarged perivascular space (ePVS) volume, and the presence of microbleeds (MB) on brain magnetic resonance imaging (MRI) in the population‐based Multi‐Ethnic Study of Atherosclerosis (MESA).MethodsEligible MESA participants had 2941 plasma proteins measured from stored blood samples (collected in 2016‐2018) using the antibody‐based Olink proteomics platform, and completed brain MRI scans in 2018‐2019. Participants with quality control exclusion of protein measurements, missing covariate data, and poor quality or missing MRI outcome variables were excluded. The cross‐sectional association between the abundance of each plasma protein (normalized protein expression – a relative protein quantification unit measured on a log2 scale) was modeled separately with WMFA, WMH volume, total ePVS volume, and the presence of MBs using multivariable linear or modified Poisson regression, adjusting for demographic variables, estimated glomerular filtration rate (eGFR), and SVD risk factors. The Benjamini‐Hochberg procedure was used to control the false discovery rate (FDR) &lt;0.05 to account for multiple hypothesis testing. For proteins independently associated with the SVD markers on MRI, penalized regression with least absolute shrinkage and selection operator (LASSO) was used to create a parsimonious proteomic model.ResultsEligible participants (total N=709) had a mean age of 73 years, 53% were women, 25% were Black, 17% were Chinese, 19% were Hispanic or Latino, and 39% were White (Table 1). After adjustment for demographics, eGFR, and SVD risk factors, 769 plasma proteins were associated with WMFA (FDR &lt;0.05) (Figure). LASSO regression identified a 37‐protein model predictive of WMFA (Table 2). We did not find plasma proteins to be independently associated with WMH volume, ePVS volume, or the presence of MBs.ConclusionMultiple circulating proteins – implicated in central nervous system myelination, lipid metabolism, angiogenesis, coagulation, cellular adhesion and migration, appetite regulation, energy homeostasis, systemic inflammation, and immune regulation – were independently associated with WMFA in a multi‐ethnic cohort of older adults.

Factors associated with lipid lowering therapy in the multi-ethnic study of atherosclerosis

BackgroundLipid-lowering therapy (LLT) plays a central role in managing atherosclerotic cardiovascular disease (ASCVD) risk, but its underuse is reported in over 40% of the qualified population in the United States. Studies on factors, particularly actionable factors associated with guideline-directed LLT are limited.MethodsThis study evaluated participants from the Multi-Ethnic Study of Atherosclerosis (MESA) on their qualification for LLT at exam 5 (2010–2012) according to the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on cholesterol management. Participants were categorized as on-LLT or off-LLT at the following exam (2016–2018). Multi-variable relative risk (RR) models were used to analyze between LLT usage and factors prior to 2013, including age, gender, race/ethnicity, education level and medical insurance, income, smoking, body mass index (BMI), diabetes, hypertension, and presence of coronary artery calcium (CAC).ResultsAmong the 2114 participants qualified for LLT at exam 5 with an average age of 70.7, 1,129 (53.4%) were on LLT while 985 (46.6%) were off LLT at exam 6. Black participants were less likely to be on LLT compared to the reference white participants (RR 0.80, 95% confidence interval CI 0.71–0.90). Higher BMI showed borderline significant association with LLT. Comorbidities of diabetes and hypertension were positively associated with LLT use (RR 1.39 and 1.23, 95% CI 1.27–1.52 and 1.10–1.36, respectively). CAC score > 0 as an indicator of subclinical ASCVD was strongly associated with LLT too, independent of other demographic or comorbidity factors (RR 1.38, 95% CI 1.21–1.56).ConclusionsThis study identifies key factors influencing LLT use among MESA participants. Black participants were less likely to be on LLT, highlighting healthcare disparities. CAC presence was strongly associated with LLT use, suggesting that CAC measurement could be an actionable factor to improve adherence to LLT guidelines.

Abstract 4137155: Relationship between Subclinical Myocardial Injury and Global Cognitive Performance: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: With demographic trends transitioning towards older adults, dementia and cognitive impairment are predicted to increase dramatically. We aim to elucidate the relationship between subclinical myocardial injury, as indicated by asymptomatic increased levels of high-sensitivity cardiac Troponin (hs-cTnT), and cognitive performance. Methods: We studied MESA participants from Exam 1 (2000-02) to Exam 6 (2016-18), categorizing them based on baseline hs-cTnT at Exam 1. Cognitive decline was defined as a decrease of ≥5 units in CASI between Exam 5&amp;6. We used Pearson correlation and linear regression to analyze the association of hs-cTnT levels with CASI scores, and logistic regression to examine the association with cognitive decline. We also explored the relationship between different hs-cTnT categories and cognitive measures. Models were adjusted for demographics, lifestyle, APOE status, comorbidities, and medication use ( Figure ). Results: 4445 participants had both baseline hs-cTnT and valid Exam 5 CASI scores while only 1776 participants had valid Exam 6 CASI scores. Cohort was predominantly female (53%), mean age of 60 years, and 27% had at least one APOE e4 allele. Median hs-cTnT was 6.32 ng/L, and median CASI scores were 89 at Exam 5 and 91.5 at Exam 6. We found a negative correlation between the log-hs-cTnT at Exam 1 and Exam 5 with CASI scores at Exam 5. An increase of one unit in log-hs-cTnT level was associated with a decrease of 0.67 (CI -1.17, -0.17) in CASI and corresponded to higher odds (OR: 1.44; CI 1.05-1.95) of cognitive decline, after adjusting for covariates. When comparing various categories of hs-cTnT with category 1, we observe that the odd of cognitive decline increases as the category increases. However, this trend does not hold for category 5 with significantly lower sample size ( Figure ). Conclusion: Our findings indicate an inverse relationship between hs-cTnT and cognitive function years later, which is significantly attenuated by known risk factors for cognitive decline. Further research is needed to determine hs-cTnT as a predictor of future global cognitive functions.

Abstract 4124606: Disparities in statin use following identification of Coronary Artery Calcium

Introduction: Coronary artery calcium (CAC) scoring is a useful tool for risk stratification in asymptomatic individuals, and guidelines recommend statin use in individuals with CAC. A growing body of research has aimed to identify and mitigate health disparities and their relation to CVD risk. Likewise, studies have highlighted social determinants of health (SDOH) that contribute to health disparities in CVD. We sought to extend this work by evaluating whether disparities exist with regards to statin use after identification of CAC within the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The sample consisted of all MESA participants with baseline CAC &gt;0, not already on statin therapy, and without prior CVD events (n=2665). The association between race/ethnicity, age, sex, primary language, and an aggregate SDOH score with statin prescription at short (exam 2, median 1.6 year) and long (exam 5, median 9.4 year) term follow-up was evaluated in logistic regression models with adjustment for traditional CVD risk factors. The SDOH score was created from 14 components which covered the 5 general domains described in the Healthy People 2030 initiative (Figure 1). Results: Rates of statin prescription after CAC identification by race/ethnicity, language, and SDOH score tertile are shown in Figure 2. At short-term follow up, those with a higher SDOH score (worse burden) (OR 0.39, 95% CI 0.16-0.91), Hispanic / Latino participants (OR 0.59, 95% CI 0.40-0.85) and Spanish speaking participants (OR 0.51, 95% CI 0.30-0.83) were less likely to report statin use following CAC identification. At long-term follow up, Black participants (OR 0.71, 95% CI 0.52-0.96), Chinese participants (OR 0.58, 95% CI 0.39-0.86) and Chinese speaking participants (OR 0.50, 95% CI 0.33-0.76) were also less likely to report statin use following CAC identification, and a trend was noted for SDOH score (OR 0.53, 95% CI 0.26-1.09). Conclusion: This study identifies disparities in statin use after identification of CAC by race/ethnicity, language and social determinants of health. Future studies should investigate underlying reasons for these disparities and potential interventions to reduce disparities in cardiovascular care.

Metagenomic Study of the MESA: Detection of Gemella Morbillorum and Association With Coronary Heart Disease.

Inflammation is a feature of coronary heart disease (CHD), but the role of proinflammatory microbial infection in CHD remains understudied. CHD was defined in the MESA (Multi-Ethnic Study of Atherosclerosis) as myocardial infarction (251 participants), resuscitated arrest (2 participants), and CHD death (80 participants). We analyzed sequencing reads from 4421 MESA participants in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program using the PathSeq workflow of the Genome Analysis Tool Kit and a 65-gigabase microbial reference. Paired reads aligning to 840 microbes were detected in >1% of participants. The association of the presence of microbe reads with incident CHD (follow-up, ~18 years) was examined. First, important variables were ascertained using a single regularized Cox proportional hazard model, examining change of risk as a function of presence of microbe with age, sex, education level, Life's Simple 7, and inflammation. For variables of importance, the hazard ratio (HR) was estimated in separate (unregularized) Cox proportional hazard models including the same covariates (significance threshold Bonferroni corrected P<6×10-5, 0.05/840). Reads from 2 microbes were significantly associated with CHD: Gemella morbillorum (HR, 3.14 [95% CI, 1.92-5.12]; P=4.86×10-6) and Pseudomonas species NFACC19-2 (HR, 3.22 [95% CI, 2.03-5.41]; P=1.58×10-6). Metagenomics of whole-genome sequence reads opens a possible frontier for detection of pathogens for chronic diseases. The association of G morbillorum and Pseudomonas species reads with CHD raises the possibilities that microbes may drive atherosclerotic inflammation and that treatments for specific pathogens may provide clinical utility for CHD reduction.

Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis

BackgroundExposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression. ObjectivesThe authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis). MethodsWe analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (μg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. ResultsAt baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%, 74%) higher at baseline and 75% (95% CI: 47%, 107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%, 71%), 39% (95% CI: 17%, 64%), and 47% (95% CI: 25%, 74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors. ConclusionsExposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression.

Associations of Adipokine Levels With Levels of Remnant Cholesterol: The Multi-Ethnic Study of Atherosclerosis.

The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. We studied 1791 MESA (Multi-Ethnic Study of Atherosclerosis) participants who took part in an ancillary study on body composition with adipokine levels measured (leptin, adiponectin, and resistin) at either visit 2 or visit 3. RC was calculated as non-high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol, measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed-effects models were used to assess the cross-sectional and longitudinal associations between adipokines and log-transformed levels of RC. Mean±SD age was 64.5±9.6 years; mean±SD body mass index was 29.9±5.0 kg/m2; and 52.0% were women. In fully adjusted cross-sectional models that included body mass index, diabetes, low-density lipoprotein cholesterol, and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.6% (95% CI, 12.2-16.9) lower RC. With each 1-unit increment in leptin and resistin, there was 4.8% (95% CI, 2.7-7.0) and 4.0% (95% CI, 0.2-8.1) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5 (interquartile range, 4-8) years. Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for body mass index and low-density lipoprotein cholesterol.

Racial and ethnic differences in the risk of dementia diagnosis under hypothetical blood pressure-lowering interventions: The Multi-Ethnic Study of Atherosclerosis.

Substantial racial and ethnic disparities in hypertension and dementia exist in the United States. We evaluated the effect of maintaining systolic blood pressure (SBP) below clinical thresholds on dementia incidence. We included 6806 Multi-Ethnic Study of Atherosclerosis participants (44 to 84 years old). We implemented the parametric g-formula to simulate the hypothetical interventions to reduce SBP below 120 and 140mmHg over time, accounting for time-varying confounding. We estimated risk ratios (RRs) and risk differences for dementia incidence at 19 years. The RRs (95% confidence intervals [CIs]) comparing an intervention reducing SBP below 120mmHg to no intervention were 0.93 (0.87 to 0.99) for total sample, 0.95 (0.88 to 1.02) for White, 0.90 (0.79 to 1.02) for Black, 0.90 (0.78 to 1.05) for Latino, and 1.16 (0.83 to 1.55) for Chinese American participants. Results for lowering SBP below 140mmHg and with death as competing event were attenuated. The reduction of SBP below 120mmHg over time has modest effects on reducing dementia incidence. More work is needed to understand the heterogeneity across racial and ethnic groups. There is a potential beneficial effect in lowering SBP to reduce the risk of dementia, which may vary by race and ethnicity. The percentage of participants who would need intervention on blood pressure to meet clinical thresholds is greater for Black and Latino communities. Results are sensitive to the way that death is specified in the research question and analysis.

Association of social determinants of health (SDH), allostatic load (AL) and incident cancers in the multi-ethnic study of atherosclerosis (MESA).

10562 Background: AL may represent accumulated physiologic stress from adverse SDH. We assess the relationship of AL and incident cancer risk in MESA, a cohort free of cardiovascular disease (CVD) at baseline. Methods: MESA participants at Exam 1 (July 2000-August 2002) were included, except those with prevalent cancers other than non-melanoma skin, median follow-up, 16.5 years. We assigned the composite AL measure 1 point for each individual biomarker in the worst quartile for total cholesterol, high density lipoprotein cholesterol, C-reactive protein, and IL-6. One point each was assigned for BMI&gt;25 or &lt;18kg/m2; creatinine&gt;1.2mg/dL (women) or &gt;1.4mg/dL(men), systolic (≥140mmHg), diastolic (≥90mmHg) blood pressure; heart rate&gt;100bpm; coronary artery calcium score&gt;0 and history of diabetes. AL score (mean=3.09, SD=1.76) ranged 0-12. Other covariates included sociodemographic variables. Where missing, data for individual biomarkers were imputed using Multivariate Imputation by Chained Equations in R prior to calculating AL score. Cox regression models assessed AL in the whole population and stratified by race/ethnicity. Results: 6808 participants comprised the analytic sample; 1022 (15%) were diagnosed with new cancer during follow-up. Chinese (adjusted hazard ratio [aHR], 95% confidence interval [95%CI], 0.46,0.36-0.60) and Hispanic/Latino (aHR,95%CI 0.60,0.50-0.72) participants were less likely to develop new cancers compared with White participants. Each AL point increase was associated with increased new cancer risk (aHR,95%CI 1.07,1.03-1.11). In models stratified by race/ethnicity, AL association with new cancer risk persisted only for Black (aHR,95%CI 1.07, 1.00-1.14, p=0.04) and Hispanic/Latino (aHR,95%CI 1.17, 1.07-1.28, p=0.001) participants. Conclusions: AL as a composite measure of physiologic stress and self-reported Chinese and Hispanic/Latino race/ethnicity independently correlated with incident cancer risk in a cohort free of CVD at baseline. Race/ethnicity may moderate the effects of AL. [Table: see text]

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

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

Optimal Method for Assessing Right Ventricular to Pulmonary Arterial Coupling in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis

Right ventricular (RV) to pulmonary arterial (PA) coupling describes the ability of the RV to augment contractility in response to increased afterload. Several echocardiographic indexes of RV-PA coupling have been defined; however, the optimal numerator in the coupling ratio is unclear. We sought to establish which of these ratios is best for assessing RV-PA coupling based on their relations with 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the Kansas City Cardiomyopathy Questionnaire (KCCQ) in aging adults. In this study of 1,611 Multi-Ethnic Study of Atherosclerosis participants who underwent echocardiography at Exam 6, we evaluated the association between different numerators, including tricuspid annular planar systolic excursion (TAPSE), fractional area change (FAC), RV free wall strain, and tissue Doppler imaging S' velocity to pulmonary artery systolic pressure (PASP) with 6MWD, NT-proBNP, and KCCQ score, adjusted for socioeconomic and cardiovascular disease risk factors. Our cohort had a mean age of 73 ± 8 years, 54% female, 17% Chinese American, 22% African American, 22% Hispanic, and 39% White participants. The mean ( ± SD) TAPSE/PASP, FAC/PASP, tissue Doppler imaging S' velocity/PASP, and RV free wall strain:PASP ratios were 0.7 ± 0.2, 1.3 ± 0.3, 0.5 ± 0.1, and 0.8 ± 0.2, respectively. All RV-PA coupling indices decreased with age (p <0.0001 for all). TAPSE:PASP ratio was lower in older (³85 years) female (0.59 ± 0.14) versus male (0.65 ± 0.17) participants (p = 0.01), whereas FAC/PASP ratio was higher in the same female versus male participants (p <0.01). TAPSE/PASP and FAC/PASP ratios were significantly and strongly associated with all NT-proBNP, 6MWD, and KCCQ scores in fully adjusted and receiver operating characteristic analysis. In older community-dwelling adults free of heart failure and pulmonary hypertension, both FAC/PASP and TAPSE:PASP ratios are optimal for assessment of RV-PA coupling based on its association with 6MWD, NT-proBNP, and KCCQ score. FAC/PASP ratio has the additional benefit of reflecting age and gender-related geometric and functional changes.

Abstract MP73: The Association of Urinary Metals With Cardiovascular Disease Incidence and All-Cause Mortality in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Environmental exposure to metals is widespread yet preventable and has been associated with cardiovascular disease (CVD) endpoints, although evidence from prospective studies with racial and ethnic diversity is limited. Objective: We assessed the prospective association of urinary metals with incident coronary heart disease (CHD) and CVD and all-cause mortality in a diverse population of adults from the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: We included 6,638 MESA participants (mean (SD) age 62.1(10.2) years, 53% female, 39% non-Hispanic white, 27% non-Hispanic Black, 22% Hispanic/Latino, 12% Chinese). Urinary non-essential metals (cadmium, tungsten, and uranium), and essential metals (cobalt, copper, and zinc) were assessed at baseline (2000-2001). We used Cox proportional hazards regression to estimate adjusted (table footnote) hazard ratios (HR) for the association between urine metals with incident CHD, CVD, and all-cause mortality through 2019. Results: Over 17.7 years median follow up (IQR: 12.4, 18.5), 749 (11%) participants developed CHD, 1,162 (17%) developed CVD, and 1,844 (28%) died. In the models adjusted by sociodemographic and behavioral factors (Table 1, [Model 1]), one IQR increase in urinary cadmium, tungsten, cobalt, copper, and zinc at baseline was significantly associated with higher risk of incident CHD, incident CVD and all-cause mortality. Uranium levels were significantly associated with all-cause mortality and incident CVD, but not CHD. The magnitude of the association was attenuated when adjusting the models for clinical risk factors (Table 1, [Model 2]). A linear trend was identified for cadmium and copper and all endpoints. Conclusion: Our findings among a large and ethnically diverse US population support that metal exposure is associated with incident CVD and premature mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health.

Abstract P187: Associations of Body Composition, Inflammation, and Lipids: The Multi-Ethnic Study of Atherosclerosis

Background: Prior evidence has linked inflammation with myopenic obesity (MO), a high cardiometabolic risk body composition phenotype characterized by low muscle and high fat mass. Inflammation may also alter lipid metabolism. This study aimed to examine the association between MO and lipids and whether inflammation is one potential mediator of their complex relationship. Methods: We conducted a cross-sectional analysis of 1,421 Multi-Ethnic Study of Atherosclerosis participants with abdominal computed tomography body composition, lipid, and inflammatory marker measurements. The ratio of total skeletal muscle area to total adipose tissue area (SM/AT) at L3-4 was used to identify MO (lowest sex-stratified tertiles of &lt;0.52 in men and &lt;0.44 in women). Principal component analysis was used to reduce six inflammatory markers by patterns of covariation. Parallel mediation analysis was conducted to examine whether the inflammatory components mediated the relationship between SM/AT and lipids, acknowledging the limitations of cross-sectional data. Results: The sample’s mean age was 64±10 years, 52.4% were female, and 42.1% were Caucasian. Participants with MO (n=474), compared to those without (n=947), had lower high-density lipoprotein cholesterol (HDL-C; 49±13 vs. 54±16, p&lt;0.001), higher remnant cholesterol (RC; 28±13 vs. 24±13, p&lt;0.001), and similar low-density lipoprotein cholesterol (LDL-C; 110±32 vs. 113±30, p=0.073). All inflammatory markers were higher in MO (p≤0.002). Parallel mediation analysis showed significant direct effects between SM/AT and both HDL-C and RC, which were mediated by component 1 but not component 2. There was no significant direct or indirect effect between SM/AT and LDL-C (Table 1). Conclusion: Participants with MO exhibited elevated levels of inflammation and unfavorable lipid profiles. Two inflammatory components were identified, one of which (IL-6, CRP, fibrinogen, and leptin) partially mediated the relationship of SM/AT with HDL-C and RC.

Abstract P368: Differences in Perceived General Health and Health Care Utilization by Race and Ethnicity During the COVID Pandemic: The C4R-MESA Study

Background: The COVID-19 pandemic reshaped individuals' lives with potential impacts on perceptions of their general health and healthcare utilization. Objective: Examine patterns of self-reported general health perceptions and routine healthcare utilization during the pandemic, and assess differences by race and ethnicity, in a community-based sample of US adults. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) assessed the impact of the pandemic on participants via questionnaires designed by the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study. For the question, “How does your general health compare to before the pandemic?”, responses of “worse” were compared to “about the same” or “better.” For the question, “Since March 2020, did you have to delay or miss out on any healthcare services?”; “yes” responses were compared to “no.” Associations with race and ethnicity were tested using logistic regression models, adjusting for covariates. Results: Of 1929 MESA participants (age 75±8 years; 55% female; 40% White; 23% Hispanic; 22% Black; 15% Chinese), worse general health during the pandemic was reported by 15% of participants and 32% reported missed or delayed healthcare services. Race and ethnicity were not associated with worse general health ( Table ). Black (vs White) participants were less likely to report having missed or delayed healthcare (aOR:0.56;95%CI:0.37-0.84). There were no significant differences in missed or delayed healthcare for Chinese and Hispanic participants compared to White participants. Conclusion: These findings suggest that 1 in 7 adults experienced worsening general health and 1 in 3 missed or delayed healthcare during the pandemic. However, race and ethnicity were not associated with perceived general health and associations with missed/delayed healthcare were limited. Longer-term effects of the pandemic on general health and utilization, and related health disparities, are being evaluated in this prospective cohort.

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

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

Method validation for (ultra)-trace element concentrations in urine for small sample volumes in large epidemiological studies: application to the population-based epidemiological multi-ethnic study of atherosclerosis (MESA).

Analysis of essential and non-essential trace elements in urine has emerged as a valuable tool for assessing occupational and environmental exposures, diagnosing nutritional status and guiding public health and health care intervention. Our study focused on the analysis of trace elements in urine samples from the Multi-Ethnic Study of Atherosclerosis (MESA), a precious resource for health research with limited sample volumes. Here we provide a comprehensive and sensitive method for the analysis of 18 elements using only 100 μL of urine. Method sensitivity, accuracy, and precision were assessed. The analysis by inductively coupled plasma mass spectrometry (ICP-MS) included the measurement of antimony (Sb), arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), cobalt (Co), copper (Cu), gadolinium (Gd), lead (Pb), manganese (Mn), molybdenum (Mo), nickel (Ni), selenium (Se), strontium (Sr), thallium (Tl), tungsten (W), uranium (U), and zinc (Zn). Further, we reported urinary trace element concentrations by covariates including gender, ethnicity/race, smoking and location. The results showed good accuracy and sensitivity of the ICP-MS method with the limit of detections rangings between 0.001 μg L-1 for U to 6.2 μg L-1 for Zn. Intra-day precision for MESA urine analysis varied between 1.4% for Mo and 26% for Mn (average 6.4% for all elements). The average inter-day precision for most elements was <8.5% except for Gd (20%), U (16%) and Mn (19%) due to very low urinary concentrations. Urinary mean concentrations of non-essential elements followed the order of Sr > As > Cs > Ni > Ba > Pb > Cd > Gd > Tl > W > U. The order of urinary mean concentrations for essential trace elements was Zn > Se > Mo > Cu > Co > Mn. Non-adjusted mean concentration of non-essential trace elements in urine from MESA participants follow the order Sr > As > Cs > Ni > Ba > Pb > Cd > Gd > Tl > W > U. The unadjusted urinary mean concentrations of essential trace elements decrease from Zn > Se > Mo > Cu > Co > Mn.

Nontraditional Risk Markers for Incident Coronary Artery Calcium Among Persons ≥65 Years of Age

BackgroundThe initiation of coronary artery calcium (CAC) is an important physiologic milestone associated with increased cardiovascular disease risk. However, traditional risk factors (RF) do not perform well for predicting incident CAC among the 54 million older U.S. adults. ObjectivesThe authors sought to assess the association between nontraditional cardiovascular disease RF and incident CAC in older persons. MethodsThere were 815 MESA (Multi-Ethnic Study of Atherosclerosis) participants ≥65 years of age who had CAC = 0 at Visit 1 and a follow-up CAC scan. Multivariable adjusted Cox hazards ratios (aHR) and C-statistics were calculated to examine the association of nontraditional RF with incident CAC. ResultsThe mean age was 70.2 years and 67% were women. The median follow-up time to repeat CAC scan was 3.6 years (IQR: 2.6-9.2 years) and 45% of participants developed incident CAC. Albuminuria (aHR: 1.50, 95% CI: 1.07-2.09), carotid plaque (aHR: 1.32, 95% CI: 1.04-1.66), and thoracic aortic calcification (TAC) (aHR: 1.38, 95% CI: 1.10-1.75) were significantly associated with incident CAC, while higher levels of nontraditional RF including apolipoprotein-B, lipoprotein(a), high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide were not. When added to demographics, albuminuria, carotid plaque, and TAC provided a greater C-statistic improvement (+0.047, P = 0.004) vs all traditional RF combined (+0.033, P = 0.05). ConclusionsAmong nontraditional RF and measures of subclinical atherosclerosis, only albuminuria, carotid plaque, and TAC were significantly associated with incident CAC in persons ≥65 years of age. Identification of albuminuria or extracoronary atherosclerosis may help guide the timing of repeat CAC scoring in older persons with baseline CAC = 0.

Prevalence of Subclinical Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction

BackgroundAtrial fibrillation (AF) is common in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with poorer clinical outcomes. The prevalence of subclinical AF in patients with HFpEF remains unknown. ObjectivesThe aim of this study was to determine whether subclinical AF was more prevalent in individuals with HFpEF than in individuals without histories of heart failure (HF). MethodsPatients with HFpEF with no prior diagnoses of AF were screened for subclinical AF, and the prevalence of subclinical AF was compared with that among control subjects without HF drawn from MESA (Multi-Ethnic Study of Atherosclerosis) who underwent the same electrocardiographic monitoring. Multivariable logistic regression was used to adjust for demographic and clinical comorbidities. ResultsNinety patients with HFpEF and 1,230 MESA participants were included. Patients with HFpEF were younger (median age 69 years [Q1-Q3: 63-76 years] vs 72 years [Q1-Q3: 66-80 years]; P = 0.02), more obese (median body mass index 36 kg/m2 [Q1-Q3: 30-45 kg/m2] vs 27 kg/m2 [Q1-Q3: 24-30 kg/m2]; P < 0.001), and more likely to have diabetes (34% vs 21%; P = 0.01). The prevalence of subclinical AF was 8.9% in patients with HFpEF and 4.1% in non-HF participants. After multivariable adjustment for age, sex, race, body mass index, diabetes, smoking, and total analyzable time on electrocardiographic monitor, there was a significantly higher odds of subclinical AF in patients with HFpEF compared with MESA (OR: 3.01; 95% CI: 1.13-7.99; P = 0.03). ConclusionsPatients with HFpEF had a higher prevalence of subclinical AF than participants without HF from a community-based study. Screening for atrial arrhythmias may be appropriate among patients with HFpEF for timely initiation of thromboembolic prophylaxis and may identify individuals at greater risk for clinical decompensation.