Multi-Ethnic Study Of Atherosclerosis Participants Research Articles

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>25 or <18kg/m2; creatinine>1.2mg/dL (women) or >1.4mg/dL(men), systolic (≥140mmHg), diastolic (≥90mmHg) blood pressure; heart rate>100bpm; coronary artery calcium score>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.

Abstract 13405: Cardiac Computed Tomography Variables for Prediction of New-Onset Heart Failure: Multi-Ethnic Study of Atherosclerosis

Introduction: Heart failure (HF) prediction models utilize clinical variables. The purpose of this study was to determine if addition of cardiac computed tomography (CT) variables could improve discrimination of HF prediction scores. Methods: Participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort between 45 to 84 years old and free of clinical cardiovascular disease at baseline, with complete clinical data and cardiac CT were included to evaluate new-onset HF during the follow-up period. Cardiac CT variables analyzed included left ventricular size index (LVSi) and calcification of the coronary arteries (CAC), aortic valve (AVC), mitral valve (MVC), and thoracic aorta (TAC). We evaluated if CT variables improved the Pooled Cohort equations to Prevent HF (PCP-HF) score (an internally and externally validated model of 33,010 patients predicting 10-year risk of new-onset HF). Results: Among 6,667 MESA participants (52.7% female), 426 events of new-onset HF occurred during the follow-up period. After the Cox model was adjusted for cardiac CT and PCP-HF score variables, CAC (HR 1.10; 95% CI 1.05-1.15; p&lt;0.001), AVC (HR 1.08; 95% CI 1.03-1.13; p=0.002), MVC (HR 1.06; 95% CI 1.01-1.12; p=0.015), and LVSi (HR 1.14; 95% CI 1.10-1.18; p&lt;0.001) were all significantly associated with new-onset HF. After using time-dependent ROC and stratifying by sex, AUC discrimination of new-onset HF with the PCP-HF score was improved by the inclusion of cardiac CT variables. In females, the AUC for 10-year risk of new-onset HF improved from 0.80 to 0.86 with the addition of cardiac CT variables. In males, the AUC for 10-year risk of new-onset HF improved from 0.77 to 0.84 with the addition of cardiac CT variables. Conclusions: In addition to traditional clinical risk factors, cardiac CT variables provide anatomic risk factors that improve the prediction of new-onset HF. Coronary and valvular calcification may signal poorly controlled clinical risk factors that are often associated with HF. LVSi may reflect left ventricular remodeling associated with HF. More studies are needed to further elucidate the relationship between cardiac CT anatomic risk factors and HF.

Omega-3 Polyunsaturated Fatty Acids are not associated with Peripheral Artery Disease in a Meta-Analysis from the Multi-Ethnic Study of Atherosclerosis and Atherosclerosis Risk in Communities Study Cohorts

BackgroundResearch suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce. ObjectivesWe evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts. MethodsOmega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined. ResultsIn the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y. ConclusionThis study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk.

Abstract 12439: Abdominal Visceral Fat Area and Density Are Associated With Coronary Artery Calcification: A Cross-Sectional Analysis of the Multi-Ethnic Study of Atherosclerosis

Introduction: The associations of body composition components, including muscle and adipose tissue, and markers of subclinical coronary artery disease are unclear. We examined the relationship between abdominal 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). Methods: A randomly selected total of 1,974 MESA participants free of coronary heart disease underwent abdominal CT scans at exams 2 or 3, with the resulting images interrogated for abdominal body composition. Using six cross-sectional slices spanning L2-L5, Medical Imaging Processing Analysis and Visualization (MIPAV) software was used to determine abdominal muscle and fat composition by utilizing appropriate Hounsfield units (HU) ranges. CT chest scans obtained during the exam 1 were used to obtain CAC scores, calculated using the Agatston method and spatially weighted calcium score (SWCS). Multivariable linear regression analysis was performed to assess the relationship between both abdominal visceral fat and muscle area and density to prevalent CAC. Results: A total of 1,089 participants had a CAC&gt;0, with an average CAC score of 310. In the fully adjusted model, for every 10 cm 2 increase in visceral fat area, the likelihood of having a CAC &gt;0 increased by 0.60% (p&lt;0.001). In the minimally adjusted model, abdominal muscle area was significantly associated with CAC&gt;0, which became non-significant in the fully adjusted model. For density of visceral fat , every 1 HU increase (less lipid dense fat tissue), the likelihood of having a CAC score&gt;0 decreased by 0.29% (p&lt;0.05). No significant relationship was observed between density of abdominal muscle and CAC&gt;0. Conclusion: Greater area and higher lipid density of abdominal visceral fat was associated with an increased likelihood of having CAC, while there was no significant relationship between abdominal muscle area or density and CAC. Both 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 requires further evaluation.

Serum reactivity to citrullinated protein/peptide antigens and left ventricular structure and function in the Multi-Ethnic Study of Atherosclerosis (MESA).

Antibodies to citrullinated protein antigens have been linked to altered left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA). Serum reactivity to several citrullinated protein/peptide antigens has been identified in RA, which are detectable years before RA onset and in individuals who may never develop RA. Among community-living individuals without heart failure (HF) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated associations between serum reactivity to citrullinated protein/peptide antigens, LV mass, LV ejection fraction (LVEF), and incident HF. Among 1232 MESA participants, we measured serum reactivity to 28 different citrullinated proteins/peptides using a multiplex bead-based array. Each antibody was defined as having extremely high reactivity (EHR) if >95th percentile cut-off in MESA. Number of EHR antibody responses to citrullinated protein/peptide antigens were summed for each participant (range 0-28). LV mass(g) and LVEF(%) were measured on cardiac MRI. Associations between EHR antibodies and LV mass and LVEF were evaluated using linear regression. Cox proportional hazards models were used to evaluate associations between EHR antibodies and incident HF during 11 years of follow-up, adjusting for age, gender, race/ethnicity, smoking status, systolic blood pressure, use of anti-hypertensive medications, self-reported arthritis, IL-6, body surface area, and estimated glomerular filtration rate. Mean age was 65±10, 50% were female, 40% were White, 21% were Black, 26% were Hispanic/Latino, and 14% were Chinese. Twenty-seven percent of MESA participants had extremely high reactivity to ≥ 1 citrullinated protein/peptide antigen. In fully adjusted analysis, every additional EHR antibody was significantly associated with 0.1% lower LVEF (95% CI: -0.17%, -0.02%). No association was observed with LV mass (β per additional EHR antibody) = 0.13±0.15 (p = 0.37)). Neither the presence nor number of EHR antibodies was associated with incident HF during follow-up (HR per additional EHR antibody = 1.008 (95% CI: 0.97, 1.05)). Greater number of extremely highly reactive antibodies was associated with lower LVEF, but not with LV mass or incident HF. Thus, serum reactivity to citrullinated protein/peptide antigens was associated with subtle subclinical changes in myocardial contractility, but the significance in relation to clinically apparent HF is uncertain.

Personal Health Literacy and Life Simple 7: The Multi-Ethnic Study of Atherosclerosis

ABSTRACT Background Personal Health literacy (PHL) is essential in cardiovascular risk management. Hindrances in PHL can lead to poor cardiovascular outcomes. Purpose To investigate whether limited PHL is associated with lower likelihoods of i) overall cardiovascular health and ii) individual cardiovascular health components as defined by the American Heart Association’s Life Simple (LS7). Methods Multi-Ethnic Study of Atherosclerosis participants (N = 3719; median age[range]: 59[45–84]) completed a PHL questionnaire in 2016–2018. PHL was classified as limited (score ≥10) or adequate (score <10). LS7 components were measured in 2000–2002. Robust Poisson regression was employed to compute prevalence ratios and 95% confidence intervals (PR[95%CI]) of LS7 measures. Results 14.7% of participants had limited PHL. Limited PHL was associated with lower likelihoods of optimal LS7 (0.69[0.50, 0.95], p = .02) and average LS7 (0.95[0.88, 1.02], p = .15) after adjustment. Limited PHL was significantly associated with a 7% lower likelihood of ideal fasting blood glucose level after adjustment (0.93[0.89, 0.98], p < .01). Discussion Limited PHL was modestly associated with suboptimal cardiovascular health and elevated blood glucose, independent of income and education. Translation to Health Education Practice Health educators and providers should equitably address PHL barriers to improve cardiovascular management and quality of care for patients and communities.

Modifiable kidney disease risk factors among nondiabetic adults with obesity from the Multi-Ethnic Study of Atherosclerosis.

It is unknown whether weight change or physical fitness is associated with chronic kidney disease (CKD) risk among nondiabetic adults with obesity. This was a prospective, longitudinal cohort study of adults with obesity without baseline CKD or diabetes enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Linear mixed-effects and multistate models were adjusted for demographics, time-varying covariates including blood pressure, and comorbidities these were used to examine associations of weight change and slow walking pace (<2 miles/h) with (i) rate of annual estimated glomerular filtration rate (eGFR) decline and (ii) incident CKD, defined as eGFRCr-Cys < 60 mL/min/1.73 m2 , and tested for interaction by baseline hypertension status. Among 1208 included MESA participants (median BMI 33.0 kg/m2 [interquartile range 31.2-35.9]), 15% developed CKD. Slow walking pace was associated with eGFR decline (-0.27 mL/min/1.73 m2 /year; 95% CI: -0.42 to -0.12) and CKD risk (adjusted hazard ratio 1.48; 95% CI: 1.08 to 2.01). Weight gain was associated with CKD risk (adjusted hazard ratio 1.34; 95% CI: 1.02 to 1.78 per 5 kg weight gain from baseline). There was no significant interaction by baseline hypertension status. Slow walking pace and weight gain were associated with CKD risk among adults with obesity who did not have diabetes at baseline.

Association Between Alcohol Consumption and Ectopic Fat in the Multi-Ethnic Study of Atherosclerosis.

Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 (light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Using multivariable linear regression, we examined the associations between categories ofalcohol consumption and natural log-transformed fat in ectopic depots. We included 6756 MESA participants (62.1±10.2 years; 47.2% women), of whom 6734 and 1934 had chest computed tomography (pericardial and hepatic fat) and abdominal computed tomography (subcutaneous, intermuscular, and visceral fat), respectively. In adjusted analysis, heavy drinking, relative to lifetime abstention, was associated with a higher (relative percent difference) pericardial 15.1 [95% CI, 7.1-27.7], hepatic 3.4 [95% CI, 0.1-6.8], visceral 2.5 [95% CI, -10.4 to 17.2], and intermuscular 5.2 [95% CI, -6.6 to 18.4] fat but lower subcutaneous fat -3.5 [95% CI, -15.5 to 10.2]). The associations between alcohol consumption and ectopic adiposity exhibited a J-shaped pattern. Binge drinking, relative to light-to-moderate drinking, was also associated with higher ectopic fat. Conclusions Alcohol consumption had a J-shaped association with ectopic adiposity. Both heavy alcohol intake and binge alcohol drinking were associated with higher ectopic fat.

Myocardial Fibrosis and Cardiomyopathy Risk: A Genetic Link in the MESA.

Common genetic variants are associated with risk for hypertrophic cardiomyopathy and dilated cardiomyopathy and with left ventricular (LV) traits. Whether these variants are associated with myocardial fibrosis, an important pathophysiological mediator of cardiomyopathy, is unknown. Multi-Ethnic Study of Atherosclerosis participants with T1-mapping cardiac magnetic resonance imaging in-whom extracellular volume was assessed, and genotyping information was available were included (N=1255). Log extracellular volume (%) was regressed on 50 candidate single nucleotide polymorphisms (previously identified to be associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and LV traits) adjusting for age, sex, diabetes, blood pressure, and principal components of ancestry. Ancestry-specific results were pooled by fixed-effect meta-analyses. Gene knockdown experiments were performed in human cardiac fibroblasts. The SMARCB1 rs2186370 intronic variant (minor allele frequency: 0.18 in White and 0.50 in Black participants), previously identified as a risk variant for dilated cardiomyopathy and hypertrophic cardiomyopathy, was significantly associated with increased extracellular volume (P=0.0002) after adjusting for confounding clinical variables. The SMARCB1 rs2070458 locus previously associated with increased LV wall thickness and mass was similarly significantly associated with increased extracellular volume (P=0.0002). The direction of effect was similar in all 4 ancestry groups, but the effect was strongest in Black participants. The variants are strong expression quantitative loci in human LV tissue and associated with genotype-dependent decreased expression of SMARCB1 (P=7.3×10-22). SMARCB1 knockdown in human cardiac fibroblasts resulted in increased TGF (transforming growth factor)-β1-mediated α-smooth muscle actin and collagen expression. Common genetic variation in SMARCB1 previously associated with risk for cardiomyopathies and increased LV wall thickness is associated with increased cardiac magnetic resonance imaging-based myocardial fibrosis and increased TGF-β1 mediated myocardial fibrosis in vitro. Whether these findings suggest a pathophysiologic link between myocardial fibrosis and cardiomyopathy risk remains to be proven.

Visit-to-Visit Glucose Variability, Cognition, and Global Cognitive Decline: The Multi-Ethnic Study of Atherosclerosis.

Higher visit-to-visit glucose variability (GV) is associated with dysglycemia and type 2 diabetes (T2D), key risk factors for cognitive decline. Evaluate the association of GV with cognitive performance and decline in racially/ethnically diverse older populations with and without T2D. We calculated the standard deviation of glucose (SDG), average real variability (ARV), and variability independent of the mean (VIM) among 4367 Multi-Ethnic Study of Atherosclerosis participants over 6 clinical examinations. Participants completed a cognitive assessment at the fifth examination, and a subset completed a second assessment 6 years later. We used multivariable linear regression to estimate the association of intraindividual GV with cognitive test scores after adjustments for cardiovascular risk factors and mean glucose level over the study period. Two-fold increments in the VIM and SDG were associated with worse Cognitive Abilities Screening Instrument (CASI) performance, while two-fold increments in VIM and ARV were associated with worse Digit Symbol Coding test score. GV measures were not associated with change in CASI performance among 1834 participants with repeat CASI data 6 years later. However, among 229 participants with incident T2D, the SDG and VIM were associated with decline in CASI (-1.7 [95% CI: -3.1, -0.3] and -2.1 [-3.7, -0.5] points, respectively). In contrast, single-timepoint glucose and HbA1c were not associated with CASI decline among participants with or without incident T2D. Higher visit-to-visit GV over 16 to 18 years is associated with worse cognitive performance in the general population, and with modest global cognitive decline in participants with T2D.