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Objective: To examine inpatient COVID-19-related outcomes among patients with and without diabetes alone or with a history of established heart failure (HF) or established atherosclerotic cardiovascular disease (ASCVD)., Design: Observational study; longitudinal analysis of registry data., Setting: Hospitals in the USA reporting to the American Heart Association (AHA) COVID-19 Registry from January 2020 to May 2021., Participants: 20 796 individuals with diabetes (11 244 men; mean age 64.2) and 30 798 without diabetes (15 980 men; mean age 59.0) hospitalised for COVID-19 in the USA., Primary and Secondary Outcome Measures: Primary outcome measures were all-cause mortality, inpatient major adverse cardiovascular events (MACE) and/or inpatient mechanical ventilation. Secondary outcome measures included the association with diabetes and these outcomes among those with and without pre-existing ASCVD and HF and the association with insulin use and these outcomes in patients hospitalised for COVID-19., Results: After adjustment for relevant covariates diabetes increased the risk of mortality (HR 1.12, 95% CI: 1.03 to 1.21), MACE (HR 1.32, 95% CI: 1.17 to 1.48) and mechanical ventilation (HR 1.33, 95% CI: 1.26 to 1.42). Among patients with established ASCVD or HF, diabetes did not modify the risk of adverse outcomes. There was a significant difference in the risk of mortality between patients taking insulin compared with those who were not (HR 1.32, 95% CI: 1.01 to 1.26); however, there was no difference in the risk of MACE or mechanical ventilation., Conclusions: Diabetes was associated with a higher risk of in-hospital all-cause mortality, MACE and need for mechanical ventilation in patients hospitalised for COVID-19. Diabetes was independently associated with adverse outcomes, particularly among those without pre-existing cardiovascular disease., Competing Interests: Competing interests: FP reports research support (to Emory University) from Insulet, Dexcom, Novo Nordisk, Tandem and Ideal Medical Technologies and consulting for Dexcom and Medscape. UG, LTV, AG, AQ, CA and SD have no interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Among Black adults, high-sensitivity cardiac troponin I (hs-cTnI) is associated with heart failure (HF) risk. The association of longitudinal changes in hs-cTnI with risk of incident HF, HF with reduced and preserved ejection fraction (HFrEF and HFpEF, respectively), among Black adults is not well-established., Methods and Results: This study included Black participants from the Jackson Heart Study with available hs-cTnI data at visits 1 (2000-2004) and 2 (2005-2008) and no history of cardiovascular disease. Cox models were used to evaluate associations of categories of longitudinal change in hs-cTnI with incident HF risk. Among 2423 participants, 11.6% had incident elevation in hs-cTnI at visit 2, and 16.9% had stable or improved elevation (≤50% increase in hs-cTnI), and 4.0% had worsened hs-cTnI elevation (>50% increase). Over a median follow-up of 12.0 years, there were 139 incident HF hospitalizations (64 HFrEF, 58 HFpEF). Compared with participants without an elevated hs-cTnI, those with incident, stable or improved, or worsened hs-cTnI elevation had higher HF risk (adjusted hazard ratio 3.20 [95% confidence interval, 1.92-5.33]; adjusted hazard ratio 2.40, [95% confidence interval, 1.47-3.92]; and adjusted hazard ratio 8.10, [95% confidence interval, 4.74-13.83], respectively). Similar patterns of association were observed for risk of HFrEF and HFpEF., Conclusions: Among Black adults, an increase in hs-cTnI levels on follow-up was associated with a higher HF risk., Lay Summary: The present study included 2423 Black adults from the Jackson Heart Study with available biomarkers of cardiac injury and no history of cardiovascular disease at visits 1 and 2. The majority of participants did not have evidence of cardiac injury at both visits (67.5%), 11.6% had evidence of cardiac injury only on follow-up, 14.5% had stable elevations, 4.0% had worsened elevations, and 2.4% had improved elevations of cardiac injury biomarkers during follow-up. Compared with participants without evidence of cardiac injury, those with new, stable, and worsened levels of cardiac injury had a higher risk of developing heart failure., Tweet: Among Black adults, persistent or worsening subclinical myocardial injury is associated with an elevated risk of HF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Recognizing bipolar disorder as a multi-system metabolic condition driven, in part, by binge eating behavior and atypical depressive symptoms, this study aimed to quantify diet quality and evaluate clinical correlates in a bipolar disorder cohort., Methods: Participants from the Mayo Clinic Bipolar Disorder Biobank (n = 734) completed the Rapid Eating Assessment for Participants - Shortened version (REAP-S) to determine diet quality. The average REAP-S score for a U.S. omnivorous diet is 32 (range 13 to 39) with higher scores indicating healthier diet. Demographic variables were collected in a standardized clinical questionnaire. Depressive symptoms were assessed by the Bipolar Inventory of Symptoms Scale. Cardiometabolic variables were retrieved from the electronic health record. Associations between continuous variables and REAP-S scores (total, 'healthy foods' and 'avoidance of unhealthy foods') were assessed using linear regression., Results: Overall, our sample had a mean REAP-S score of 27.6 (4.9), suggestive of a lower diet quality than the average general population in the US. There was a significant inverse relationship between mean REAP-S lower scores with increased BMI, waist circumference, disordered eating and depression. All these associations were significantly stronger in female participants., Limitations: EHR cross-sectional data., Conclusions: Our data suggest unhealthy diet quality in bipolar disorder is associated with depression, obesity and cardiometabolic abnormalities. Additional work is encouraged to prospectively track mood and diet quality to further understand the bidirectional relationship and clarify if dietary interventions can positively impact mood. Further delineating potential sex differences in diet quality and depression may provide greater appreciation of modifiable risk factors for future cardiometabolic burden., (Copyright © 2022. Published by Elsevier B.V.)

Background: Supranormal ejection fraction by echocardiography in clinically referred patient populations has been associated with an increased risk of cardiovascular disease (CVD). The prognostic implication of supranormal left ventricular ejection fraction (LVEF)-assessed by cardiac magnetic resonance (CMR)-in healthy, community-dwelling individuals is unknown., Objectives: The purpose of this study is to investigate the prognostic implication of supranormal LVEF as assessed by CMR and its inter-relationship with stroke volume among community-dwelling adults without CVD., Methods: Participants from the MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) cohorts free of CVD who underwent CMR with LVEF above the normal CMR cutoff (≥57%) were included. The association between cohort-specific LVEF categories and risk of clinically adjudicated major adverse cardiovascular events (MACE) was assessed using adjusted Cox models. Subgroup analysis was also performed to evaluate the association of LVEF and risk of MACE among individuals stratified by left ventricular stroke volume index., Results: The study included 4,703 participants from MESA and 2,287 from DHS with 727 and 151 MACE events, respectively. In adjusted Cox models, the risk of MACE was highest among individuals in LVEF Q4 (vs Q1) in both cohorts after accounting for potential confounders (MESA: HR = 1.27 [95% CI: 1.01-1.60], P = 0.04; DHS: HR = 1.72 [95% CI: 1.05-2.79], P = 0.03). A significant interaction was found between the continuous measures of LVEF and left ventricular stroke volume index (P interaction = 0.02) such that higher LVEF was significantly associated with an increased risk of MACE among individuals with low but not high stroke volume., Conclusions: Among community-dwelling adults without CVD, LVEF in the supranormal range is associated with a higher risk of adverse cardiovascular outcomes, particularly in those with lower stroke volume., Competing Interests: Funding Support and Author Disclosures The MESA study was supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute; and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). The Dallas Heart Study was supported by a grant from the Donald W. Reynolds Foundation and the National Center for Advancing Translational Sciences (UL1TR001105). Dr Segar has received nonfinancial support from Pfizer and Merck. Dr Pandey has received research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute of Aging GEMSSTAR Grant (1R03AG067960-01), and Applied Therapeutics; has served on the advisory board of Roche Diagnostics; serves as a consultant to Tricog Health, Rivus, and Lilly USA; and has received nonfinancial support from Pfizer and Merck. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Early repolarization pattern (ERP) is associated with increased mortality in case-control studies, but the mechanism and role of left ventricular mass (LVM) remain unclear. Our objectives were to understand (1) whether ERP associates with adverse outcomes in a multiethnic population and (2) to explore the role of LVM in these associations. Participants from the Dallas Heart Study with an electrocardiogram interpretable for ERP, defined as J point elevation ≥1 mm in 2 contiguous leads, were included. Combined all-cause mortality and nonfatal cardiovascular disease (CVD) events and individual components were assessed using Cox proportional hazards modeling after adjustment for demographics, traditional CVD risk factors, electrocardiogram intervals, and cardiac magnetic resonance imaging-derived factors. Cardiac magnetic resonance imaging-defined LVM was then added to the most fully adjusted model. Of the 2,686 participants, 240 (8.9%) demonstrated ERP. Participants with ERP were more likely to be male and Black, with lower body mass index, greater left ventricular end-diastolic volumes, and LVM. Over a median follow-up of 11 years, the combined end point occurred in 326 patients. Multivariable modeling demonstrated ERP was associated with the combined end point (HR [95% CI] 1.61 [1.14 to 2.26]), all-cause mortality (1.67 [1.00 to 2.80]). However, further adjusting for LVM attenuated the associations of ERP with the primary end point (HR [95% CI] 1.22 [0.85 to 1.77]) and secondary end points of mortality (1.39 [0.80 to 2.41]) and nonfatal CVD (1.05 [0.68 to 1.64]). ERP was associated with increased mortality and nonfatal CVD events, which was attenuated after adjusting for LVM, a previously under-recognized clinical phenotype. Previous associations of ERP with adverse cardiovascular outcomes may be partially explained by greater LVM in those with ERP., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Cardiovascular (CV) mortality has declined for more than 3 decades in the US. However, differences in declines among residents at a US county level are not well characterized., Objective: To identify unique county-level trajectories of CV mortality in the US during a 35-year study period and explore county-level factors that are associated with CV mortality trajectories., Design, Setting, and Participants: This longitudinal cross-sectional analysis of CV mortality trends used data from 3133 US counties from 1980 to 2014. County-level demographic, socioeconomic, environmental, and health-related risk factors were compiled. Data were analyzed from December 2019 to September 2021., Exposures: County-level characteristics, collected from 5 county-level data sets., Main Outcomes and Measures: Cardiovascular mortality data were obtained for 3133 US counties from 1980 to 2014 using age-standardized county-level mortality rates from the Global Burden of Disease study. The longitudinal K-means approach was used to identify 3 distinct clusters based on underlying mortality trajectory. Multinomial logistic regression models were constructed to evaluate associations between county characteristics and cluster membership., Results: Among 3133 US counties (median, 49.5% [IQR, 48.9%-50.5%] men; 30.7% [IQR, 27.1%-34.4%] older than 55 years; 9.9% [IQR, 4.5%-22.7%] racial minority group [individuals self-identifying as Black or African American, American Indian or Alaska Native, Asian, Native Hawaiian, Pacific Islander, other, or multiple races/ethnicities]), CV mortality declined by 45.5% overall and by 38.4% in high-mortality strata (694 counties), by 45.0% in intermediate-mortality strata (1382 counties), and by 48.3% in low-mortality strata (1057 counties). Counties with the highest mortality in 1980 continued to demonstrate the highest mortality in 2014. Trajectory groups were regionally distributed, with high-mortality trajectory counties focused in the South and in portions of Appalachia. Low- vs high-mortality groups varied significantly in demographic (racial minority group proportion, 7.6% [IQR, 4.1%-14.5%]) vs 23.9% [IQR, 6.5%-40.8%]) and socioeconomic characteristics such as high-school education (9.4% [IQR, 7.3%-12.6%] vs 20.1% [IQR, 16.1%-23.2%]), poverty rates (11.4% [IQR, 8.8%-14.6%] vs 20.6% [IQR, 17.1%-24.4%]), and violent crime rates (161.5 [IQR, 89.0-262.4] vs 272.8 [IQR, 155.3-431.3] per 100 000 population). In multinomial logistic regression, a model incorporating demographic, socioeconomic, environmental, and health characteristics accounted for 60% of the variance in the CV mortality trajectory (R2 = 0.60). Sociodemographic factors such as racial minority group proportion (odds ratio [OR], 1.70 [95% CI, 1.35-2.14]) and educational attainment (OR, 6.17 [95% CI, 4.55-8.36]) and health behaviors such as smoking (OR for high vs low, 2.04 [95% CI, 1.58-2.64]) and physical inactivity (OR, 3.74 [95% CI, 2.83-4.93]) were associated with the high-mortality trajectory., Conclusions and Relevance: Cardiovascular mortality declined in all subgroups during the 35-year study period; however, disparities remained unchanged during that time. Disparate trajectories were associated with social and behavioral risks. Health policy efforts across multiple domains, including structural and public health targets, may be needed to reduce existing county-level cardiovascular mortality disparities.

Background Emerging evidence links acute kidney injury (AKI) in patients with COVID-19 with higher mortality and respiratory morbidity, but the relationship of AKI with cardiovascular disease outcomes has not been reported in this population. We sought to evaluate associations between chronic kidney disease (CKD), AKI, and mortality and cardiovascular outcomes in patients hospitalized with COVID-19. Methods and Results In a large multicenter registry including 8574 patients with COVID-19 from 88 US hospitals, data were collected on baseline characteristics and serial laboratory data during index hospitalization. Primary exposure variables were CKD (categorized as no CKD, CKD, and end-stage kidney disease) and AKI (classified into no AKI or stages 1, 2, or 3 using a modification of the Kidney Disease Improving Global Outcomes guideline definition). The primary outcome was all-cause mortality. The key secondary outcome was major adverse cardiac events, defined as cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, new-onset nonfatal heart failure, and nonfatal cardiogenic shock. CKD and end-stage kidney disease were not associated with mortality or major adverse cardiac events after multivariate adjustment. In contrast, AKI was significantly associated with mortality (stage 1 hazard ratio [HR], 1.72 [95% CI, 1.46-2.03]; stage 2 HR, 1.83 [95% CI, 1.52-2.20]; stage 3 HR, 1.69 [95% CI, 1.44-1.98]; versus no AKI) and major adverse cardiac events (stage 1 HR, 2.17 [95% CI, 1.74-2.71]; stage 2 HR, 2.70 [95% CI, 2.07-3.51]; stage 3 HR, 3.06 [95% CI, 2.52-3.72]; versus no AKI). Conclusions This large study demonstrates a significant association between AKI and all-cause mortality and, for the first time, major adverse cardiovascular events in patients hospitalized with COVID-19.

Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored., Objective: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population., Data Sources and Selection: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points., Data Extraction and Synthesis: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses., Main Outcomes and Measures: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes)., Results: The meta-analysis included 7 cohort studies involving 21 401 individuals (mean [SD] age, 53.7 [10.2] years; 10 012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326 392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P = .01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P = .02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P < .001). In analyses comparing MCP-1 quartiles, these associations followed dose-response patterns. After additionally adjusting for vascular risk factors, the risk estimates were attenuated, but the associations of MCP-1 levels with cardiovascular death remained statistically significant, as did the association of MCP-1 levels in the upper quartile with coronary heart disease. There was no significant heterogeneity; the results did not change in sensitivity analyses excluding events occurring in the first 5 years after MCP-1 measurement, and the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein., Conclusions and Relevance: Higher circulating MCP-1 levels are associated with higher long-term cardiovascular mortality in community-dwelling individuals free of overt cardiovascular disease. These findings provide further support for a key role of MCP-1-signaling in cardiovascular disease.

The contribution of genome structural variation (SV) to quantitative traits associated with cardiometabolic diseases remains largely unknown. Here, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. We used sensitive methods to identify and genotype 129,166 high-confidence SVs from deep whole-genome sequencing (WGS) data of 4,848 individuals. We tested the 64,572 common and low-frequency SVs for association with 116 quantitative traits and tested candidate associations using exome sequencing and array genotype data from an additional 15,205 individuals. We discovered 31 genome-wide significant associations at 15 loci, including 2 loci at which SVs have strong phenotypic effects: (1) a deletion of the ALB promoter that is greatly enriched in the Finnish population and causes decreased serum albumin level in carriers (p = 1.47 × 10 -54 ) and is also associated with increased levels of total cholesterol (p = 1.22 × 10 -28 ) and 14 additional cholesterol-related traits, and (2) a multi-allelic copy number variant (CNV) at PDPR that is strongly associated with pyruvate (p = 4.81 × 10 -21 ) and alanine (p = 6.14 × 10 -12 ) levels and resides within a structurally complex genomic region that has accumulated many rearrangements over evolutionary time. We also confirmed six previously reported associations, including five led by stronger signals in single nucleotide variants (SNVs) and one linking recurrent HP gene deletion and cholesterol levels (p = 6.24 × 10 -10 ), which was also found to be strongly associated with increased glycoprotein level (p = 3.53 × 10 -35 ). Our study confirms that integrating SVs in trait-mapping studies will expand our knowledge of genetic factors underlying disease risk., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To evaluate the association between cardiometabolic markers and bipolar disorder (BD), examining the impact of sex and cardiometabolic medication use, from a large case-control biorepository of more than 1300 participants., Patients and Methods: Recruited from July 2009 through September 2017, cardiometabolic markers were harvested from electronic health records (EHR) of participants (n=661) from the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder and Mayo Clinic Biobank age-sex-matched controls (n=706). Markers were compared between cases and controls using logistic regression, stratified by sex, adjusting for cardiometabolic medications and current smoking status. We studied the effect of psychotropics in case-only analyses., Results: The mean age of the sample was 52.5 ± 11.6 years and 55% were female. BD patients had higher rates of smoking, but lower utilization of lipid-lowering medication compared with controls. After adjustment, BD was associated with obesity [Odds ratio (CI) 1.62 (1.22-2.15)], elevated systolic blood pressure (SBP) [2.18 (1.55-3.06)] and elevated triglycerides [1.58 (1.13-2.2)]. When stratified by sex, obesity [1.8 (1.23-2.66)] and systolic blood pressure [2.32 (1.46-3.7)] were associated with BD females compared to female controls; however, only systolic blood pressure [2.04 (1.23-3.42)] was associated with male bipolars compared to male controls. Psychotropics were marginally associated with mean BMI, abnormal triglycerides, and HbA1c., Limitations: EHR cross-sectional data CONCLUSION: To our knowledge, this is the largest case controlled study to date to explore the association between cardiometabolic markers and bipolar disorder adjusting for utilization of cardiometabolic medication. Identification of significant, non-laboratory based cardiometabolic markers that are associated with increased risk of major cardiovascular adverse events in patients with bipolar disorder, underscores, both the utility and importance of risk monitoring that can be easily done in community mental health centers., (Copyright © 2020. Published by Elsevier B.V.)

Aims: Thirty-day risk standardized readmission and mortality rates (RSRR, RSMR) are key determinants for hospital performance for cardiovascular conditions such as acute myocardial infarction (AMI) and heart failure (HF). We evaluated whether individual hospitals in the USA perform similarly for HF and AMI over time based on readmission and mortality metrics., Methods and Results: A total of 1950 hospitals in the USA with continuous participation in the Centers for Medicare and Medicaid Services (CMS) public reporting programme between 2010 and 2016 were identified. Latent mixture modelling was used to define performance trajectory groups. Overall, there were consistent declines in the RSMR (16.1-14.0%) and RSRR (20.3-16.6%) for AMI from 2010 to 2016. For HF, RSRR declined over time (25.1-21.7%), while there was a modest increase in RSMR (11.3-12.0%); parallel findings were observed across performance trajectory groups. The proportion of best performing centres for HF care that were also best performers for AMI care based on the 30-day RSMR and 30-day RSRR metric was 54% and 35%, respectively. Furthermore, the discordance rate between the best and worst performers for both conditions was low (<2% for both 30-day outcomes)., Conclusion: In the USA, despite variation in baseline hospital-level outcomes, hospitals had consistent longitudinal trajectories (worsening or improvement) across conditions and metrics. Hospitals identified as high performing were frequently similar across target conditions and over time, suggesting that performance may be driven by systems of care influencing different disease states in a comparable manner., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Context: Galectin-3 is a biomarker associated with inflammation and fibrosis in cardiac, liver, and renal disease. Galectin-3 is higher in overweight and obese individuals; whether an association with diabetes exists independent of weight is unknown., Objective: To evaluate if galectin-3 is associated with diabetes mellitus., Design: We performed measurements of galectin-3 among participants in the Dallas Heart Study (DHS) Phases 1 and 2 (DHS-1 and DHS-2; n = 3392, and n = 3194, respectively). Of these, 1989 participants were evaluated longitudinally in both studies. Associations of galectin-3 with prevalent and incident type 2 diabetes were determined using logistic regression models. Associations of galectin-3 with relevant biomarkers and fat compartments were evaluated using Spearman correlation coefficients and multivariable linear regression models, respectively., Setting and Participants: DHS is a population-based, single-site, multiethnic study conducted in Dallas County, Texas, with oversampling to comprise 50% blacks., Results: Galectin-3 levels were associated with diabetes prevalence in DHS-1 [OR 1.56 per SD change in log-galectin (95% CI 1.41 to 1.73)] and DHS-2 [OR 1.86 (95% CI 1.67 to 2.06)]. Galectin-3 levels in DHS-1 also associated with incident diabetes mellitus over the 7.1 (interquartile range 6.6 to 7.6)-year follow-up period [OR 1.34 (95% CI 1.14 to 1.58)]. These associations maintained significance in models adjusted for traditional metabolic risk factors (age, sex, race, body mass index, and hypertension) and renal function. Galectin-3 levels correlated with levels of biomarkers implicated in inflammation (high-sensitivity C-reactive peptide, IL-18, monocyte chemoattractant protein 1, soluble TNF receptor 1A, myeloperoxidase), insulin secretion (C-peptide and C-peptide/homeostatic model assessment for insulin resistance), and subcutaneous adiposity., Conclusions: Galectin-3 is associated with diabetes prevalence and incidence, possibly through the inflammatory pathway contributing to β-cell fibrosis and impaired insulin secretion., (Copyright © 2019 Endocrine Society.)

Inflammation has been shown to play an increasingly important role in the pathogenesis of atherosclerosis and in precipitating thrombotic events. Inflammatory bowel disease (IBD) is a systemic inflammatory disorder with a wide range of extraintestinal manifestations including a clinically significant increase in the risk of venous thromboembolism compared to matched controls in several studies. The data for the association between IBD and ischemic heart disease are less clear; multiple population-based studies have shown both positive and negative associations between the 2 conditions. While the systemic inflammation should theoretically increase the risk for cardiovascular disease, inflammatory bowel also potentially provides a cardioprotective effect in several ways. Patients with IBD typically enter the healthcare system at an earlier age and experience a lower incidence of obesity, hypercholesterolemia, and hyperlipidemia. Given the complex interplay among the proatherogenic, prothrombogenic, and cardioprotective effects, IBD should be taken into consideration as a nontraditional risk factor for cardiovascular disease in specific subsets of patients.

Objectives: Patients with clinically evident autoimmune disease are at increased risk for premature cardiovascular disease (CVD). Markers of serological autoimmunity such as anti-nuclear antibodies (ANA) are found in approximately 25% of the general population. Yet, the vast majority will not develop clinical autoimmune disease. Serological autoimmunity is a risk factor for CVD death in individuals without autoimmune disease; however, the mechanisms mediating this excess CVD risk have not been elucidated., Methods: We examined associations of ANA with traditional cardiovascular risk factors, inflammatory mediators, and vascular biomarkers in the Dallas Heart Study - a large, representative multiethnic population-based cohort. Plasma ANA were measured by enzyme linked immunosorbent assay in 3,488 Dallas Heart Study participants aged 30 to 65 years who do not have known rheumatologic disease. Associations of ANA with demographic characteristics, cardiovascular risk factors, and biomarkers were assessed using univariable and multivariable linear regression., Results: Factors independently associated with higher ANA include female sex, African-American race/ethnicity, soluble intracellular adhesion molecule-1, soluble CD40 ligand, chemokine CXCL-2, and Cystatin C (p<0.05 for each). ANA was not associated with traditional cardiovascular risk factors, high sensitivity C-reactive protein, coronary artery calcium scores, or aortic wall thickness., Conclusion: ANA are associated with inflammatory mediators and biomarkers of vascular activation, but not with traditional cardiovascular risk factors in a multiethnic population-based cohort. These findings suggest that the cardiovascular risk associated with ANA may involve pathways distinct from traditional risk factors and include dysregulation of endothelial cells and the immune system.

To evaluate aortic stiffness in patients with ankylosing spondylitis (AS) using cardiovascular magnetic resonance (CMR) and to assess its association with AS characteristics and left ventricular (LV) remodeling. In this prospective study, 14 consecutive AS patients were each matched to two controls without cardiovascular symptoms or known cardiovascular disease who underwent CMR imaging for the assessment of aortic arch pulse wave velocity (PWV) at 1.5 Tesla. To enhance comparability of the samples, matching was done with replacement resulting in 20 unique controls. Only AS patients with abnormal findings on screening echocardiography were included in this exploratory study. Cine CMR was used to assess LV geometry and systolic function, and late gadolinium enhancement was performed to determine the presence of myocardial hyperenhancement (i.e., fibrosis). Aortic arch PWV was significantly higher in the AS group compared with the control group (median 9.7 m/s, interquartile range [IQR] 7.1 to 11.8 vs. 6.1 m/s, IQR 4.6 to 7.6 m/s; p < 0.001). PWV was positively associated with functional disability as measured by BASFI (R: 0.62; p = 0.018). Three patients (21%) with a non-ischemic pattern of hyperenhancement showed increased PWV (11.7, 12.3, and 16.5 m/s) as compared to the 11 patients without hyperenhancement (9.0 m/s, IQR 6.6 to 10.5 m/s; p = 0.022). PWV was inversely associated with LV ejection fraction (R: - 0.63; p = 0.015), but was not found to be statistically correlated to LV volumes or mass. Aortic arch PWV was increased in our cohort of patients with AS. Higher PWV in the aortic arch was associated with functional disability, the presence of non-ischemic hyperenhancement, and reduced LV systolic function.

Importance: Prior studies suggest that higher sedentary time is associated with a greater risk for cardiovascular disease (CVD). However, the quantitative, dose-response association between sedentary time and CVD risk is not known., Objective: To determine the categorical and quantitative dose-response association between sedentary time and CVD risk., Data Sources: Two independent investigators searched the MEDLINE and EMBASE databases for all studies published before July 6, 2015, that evaluated the association between sedentary time and incident CVD., Study Selection: Prospective cohort studies with participants 18 years or older that reported the association between sedentary time and incident CVD were included., Data Extraction and Synthesis: Two independent investigators performed the data extraction and collection using a standardized form. The study quality was assessed using the Newcastle-Ottawa Scale. The categorical dose-response association was evaluated by comparing the pooled hazard ratio (HR) for incident CVD associated with different levels of sedentary time (vs lowest sedentary time) across studies. The continuous dose-response association was assessed using random-effects generalized least squares spline models. Data were collected from April 5 to July 6, 2015., Main Outcomes and Measures: Incident CVD (coronary heart disease, including nonfatal myocardial infarction, stroke, and cardiovascular mortality)., Results: Nine prospective cohort studies with 720 425 unique participants (57.1% women; 42.9% men; mean age, 54.5 years) and 25 769 unique cardiovascular events and a median follow-up of 11 years were included. In categorical analyses, compared with the lowest sedentary time category (median, 2.5 h/d), participants in the highest sedentary time category (median, 12.5 h/d) had an increased risk for CVD (HR, 1.14; 95% CI, 1.09-1.19). However, no apparent risk associated with intermediate levels of sedentary time (HR for 7.5 h/d, 1.02; 95% CI, 0.96-1.08) was found. In continuous analyses, a nonlinear association between sedentary time and incident CVD was found (P for nonlinearity < .001), with an increased risk observed for more than 10 hours of sedentary time per day (pooled HR, 1.08; 95% CI, 1.00-1.14)., Conclusions and Relevance: The association between sedentary time and the risk for CVD is nonlinear with an increased risk only at very high levels. These findings could have implications for guideline recommendations regarding the risks related to sedentary behavior.

Objective: Polycystic ovarian syndrome (PCOS) is estimated to affect up to 20% of women. PCOS is associated with insulin resistance and cardiovascular (CV) risk factors. We aimed to evaluate the impact of race/ethnicity on the prevalence of CV risk factors and subclinical predictors of CV events., Design: Cross-sectional analysis of data collected by the Dallas Heart Study, an urban, population-based cohort oversampled for blacks., Patients: A previously described cohort of women with PCOS and control subjects of the same racial/ethnic group, matched for age and body mass index., Measurements: Hormonal and clinical measures associated with PCOS and CV risk factors., Results: The study included 117 women with PCOS and 204 controls. Women with PCOS had significant differences across racial/ethnic groups in the prevalence of hypertension, hypercholesterolaemia, hypertriglyceridaemia and impaired fasting glucose (P < 0·05). Controls showed significant racial/ethnic differences in the prevalence of hypertension and impaired fasting glucose (P < 0·05). The odds of hypertension were significantly greater among women with PCOS than controls after adjusting for race/ethnicity (odds ratio, 1·50 [95% CI, 1·03-2·30]; P = 0·04). However, we did not see an interaction of race/ethnicity that significantly changed CV risk factor prevalence between PCOS and controls. In addition, subclinical measures of CV disease were not different between women with PCOS vs controls, even among hypertensive women., Conclusions: Race/ethnicity affects the prevalence of CV risk factors for women with and without PCOS. However, race/ethnicity does not interact with PCOS to additionally increase CV risk factor prevalence or subclinical CV disease., (© 2015 John Wiley & Sons Ltd.)

Objective: Noninvasive blood pressure (BP) measurement often triggers a transient rise in BP, known as an alerting reaction. However, the prevalence and prognostic significance of the alerting reaction has never been assessed in the general population., Methods: We evaluated the association between the alerting reaction and left ventricular mass by MRI and urinary albumin-to-creatinine ratio in the Dallas Heart Study, a large population sample of 3069 individuals. Participants were categorized into four groups based on levels of consecutive BP: first, normal first BP and average third to fifth (avg3-5) BP of less than 140/90 mmHg (control group); second, high first BP of at least 140/90 mmHg and normal (avg3-5) BP (alerting reaction group); third, normal first BP and high (avg3-5) BP; and fourth, high first to fifth BP. Then, associations between BP categories with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9.4 years were assessed., Results: The sample-weighted prevalence of isolated hypertension during the first BP measurement was 9.6%. Presence of an alerting reaction was independently associated with increased left ventricular mass, urinary albumin-to-creatinine ratio, cardiovascular events after adjustment for traditional cardiovascular risk factors, and baseline BP (adjusted hazard ratio 1.24, 95% confidence interval 1.07-1.43)., Conclusion: Our study indicated that the alerting reaction is independently associated with increased cardiovascular and renal complications., Competing Interests: None

Background: Little is known about the association between cardiovascular (CV) health and health insurance status. We hypothesized that U.S. adults without health insurance coverage would have a lower likelihood of ideal cardiovascular health., Methods and Results: Using National Health and Nutrition Examination Survey (NHANES) data from 2007-2010, we examined the relationship between health insurance status and ideal CV health in U.S. adults aged ≥19 years and <65 (N = 3304). Ideal CV health was defined by the American Heart Association (AHA) as the absence of clinically manifested CV disease and the simultaneous presence of 6-7 "ideal" CV health factors and behaviors. Logistic regression modeling was used to determine the relationship between health insurance status and the odds of ideal CV health. Of the U.S. adult population, 5.4% attained ideal CV health, and 23.5% were without health insurance coverage. Those without health insurance coverage were more likely to be young (p<0.0001), male (p<0.0001), non-white (p<0.0001), with less than a high school degree (p<0.0001), have a poverty-to-income ratio less than 1 (p<0.0001) and unemployed (p<0.0001) compared to those with coverage. Lack of health insurance coverage was associated with a lower likelihood of ideal CV health; however, this relationship was attenuated by socioeconomic status., Conclusions: U.S. adults without health insurance coverage are less likely to have ideal CV health. Population-based strategies and interventions directed at the community-level may be one way to improve overall CV health and reach this at-risk group.

Background: Cardiovascular magnetic resonance (CMR) has been validated for the noninvasive assessment of total arterial compliance and aortic stiffness, but their associations with cardiovascular outcomes is unknown. The purpose of this study was to evaluate associations of CMR measures of total arterial compliance and two CMR measures of aortic stiffness with respect to future cardiovascular events., Methods: The study consisted of 2122 Dallas Heart Study participants without cardiovascular disease who underwent CMR at 1.5 Tesla. Aortic stiffness was measured by CMR-derived ascending aortic distensibility and aortic arch pulse wave velocity. Total arterial compliance was calculated by dividing left ventricular stroke volume by pulse pressure. Participants were monitored for cardiovascular death, non-fatal cardiac events, and non-fatal extra-cardiac vascular events over 7.8 ± 1.5 years. Cox proportional hazards regression was used to assess for associations between CMR measures and cardiovascular events., Results: Age, systolic blood pressure, and resting heart rate were independently associated with changes in ascending aortic distensibility, arch pulse wave velocity, and total arterial compliance (all p < .0001). A total of 153 participants (6.9%) experienced a cardiovascular event. After adjusting for traditional risk factors, total arterial compliance was modestly associated with increased risk for composite events (HR 1.07 per 1SD, p = 0.03) while the association between ascending aortic distensibility and composite events trended towards significance (HR 1.18 per 1SD, p = 0.08). Total arterial compliance and aortic distensibility were independently associated with nonfatal cardiac events (HR 1.11 per 1SD, p = 0.001 and HR 1.45 per 1SD, p = 0.0005, respectively), but not with cardiovascular death or nonfatal extra-cardiac vascular events. Arch pulse wave velocity was independently associated with nonfatal extra-cardiac vascular events (HR 1.18 per 1SD, p = 0.04) but not with cardiovascular death or nonfatal cardiac events., Conclusions: In a multiethnic population free of cardiovascular disease, CMR measures of arterial stiffness are associated with future cardiovascular events. Total arterial compliance and aortic distensibility may be stronger predictors of nonfatal cardiac events, while pulse wave velocity may be a stronger predictor of nonfatal extra-cardiac vascular events.

Purpose: To determine the value of two abdominal aortic atherosclerosis measurements at magnetic resonance (MR) imaging for predicting future cardiovascular events., Materials and Methods: This study was approved by the institutional review board and complied with HIPAA regulations. The study consisted of 2122 participants from the multiethnic, population-based Dallas Heart Study who underwent abdominal aortic MR imaging at 1.5 T. Aortic atherosclerosis was measured by quantifying mean aortic wall thickness (MAWT) and aortic plaque burden. Participants were monitored for cardiovascular death, nonfatal cardiac events, and nonfatal extracardiac vascular events over a mean period of 7.8 years ± 1.5 (standard deviation [SD]). Cox proportional hazards regression was used to assess independent associations of aortic atherosclerosis and cardiovascular events., Results: Increasing MAWT was positively associated with male sex (odds ratio, 3.66; P < .0001), current smoking (odds ratio, 2.53; P < .0001), 10-year increase in age (odds ratio, 2.24; P < .0001), and hypertension (odds ratio, 1.66; P = .0001). A total of 143 participants (6.7%) experienced a cardiovascular event. MAWT conferred an increased risk for composite events (hazard ratio, 1.28 per 1 SD; P = .001). Aortic plaque was not associated with increased risk for composite events. Increasing MAWT and aortic plaque burden both conferred an increased risk for nonfatal extracardiac events (hazard ratio of 1.52 per 1 SD [P < .001] and hazard ratio of 1.46 per 1 SD [P = .03], respectively)., Conclusion: MR imaging measures of aortic atherosclerosis are predictive of future adverse cardiovascular events., (© RSNA, 2013.)

The Global Vascular Risk Management (GVRM) Study is a 5-year prospective observational study of 87,863 patients (61% females) with hypertension and associated cardiovascular risk factors began January 1, 2010. Data are gathered electronically and cardiovascular risk is evaluated using the Consortium for Southeastern Hypertension Control™ (COSEHC™)-11 risk score. Here, we report the results obtained at the completion of 33 months since study initiation. De-identified electronic medical records of enrolled patients were used to compare clinical indicators, antihypertensive medication usage, and COSEHC™ risk scores across sex and diabetic status subgroups. The results from each subgroup, assessed at baseline and at regular follow-up periods, are reported since the project initiation. Inference testing was performed to look for statistically significant differences between goal attainments rates between sexes. At-goal rates for systolic blood pressure (SBP) were improved during the 33 months of the study, with females achieving higher goal rates when compared to males. On the other hand, at-goal control rates for total and low-density lipoprotein (LDL) cholesterol (chol) were better in males compared to females. Diabetic patients had lower at-goal rates for SBP and triglycerides but higher rates for LDL-chol. The LDL-chol at-goal rates were higher for males, while high-density lipoprotein (HDL)-chol rates were higher for females. Utilization of antihypertensive medications was similar during and after the baseline period for both men and women. Patients taking two or more antihypertensive medications had higher mean COSEHC™-11 scores compared to those on monotherapy. With treatment, hypertensive patients can reach SBP and cholesterol goals; however, population-wide improvement in treatment goal adherence continues to be a challenge for physicians. The COSEHC™ GVRM Study shows, however, that continuous monitoring and feedback to physicians of accurate longitudinal data is an effective tool in achieving better control rates of cardiovascular risk factors.

Background: The inverse, dose-dependent association between cardiorespiratory fitness and mortality is well-established; however, the pattern of the association between low fitness and mortality across short- (0 to 10 years), intermediate- (10 to 20 years), and long-term (>20 years) follow-up has not been studied., Methods and Results: We included 46 575 men and 16 151 women (mean age 44 years) from the Cooper Center Longitudinal Study. Participants were categorized as either "low fit" or "not low fit," based on age- and sex- adjusted treadmill times, and were followed for mortality, determined from the National Death Index. Multivariable-adjusted Cox proportional hazards models were constructed to compare the association between fitness and traditional risk factors, with mortality outcomes across short-, intermediate-, and long-term follow-up. After a median follow-up of 16 years, there were 1295 cardiovascular disease and 2840 noncardiovascular disease deaths. Low fitness was associated with all-cause mortality across all periods in men [0 to 10 years: hazard ratios (HR), 1.99 (95% confidence interval [CI], 1.66 to 2.40); 10 to 20 years: HR, 1.61 (95% CI, 1.41 to 1.84); and >20 years: HR, 1.42 (95% CI, 1.27 to 1.60)] and in women [0 to 10 years: HR, 1.98 (95% CI, 1.27 to 3.10); 10 to 20 years: HR, 1.90 (95% CI, 1.40 to 2.56); and >20 years: HR, 1.54 (95% CI, 1.15 to 2.07)]. Similar results were seen for both cardiovascular disease and noncardiovascular disease mortality. Although these associations were also consistent across most subgroups, low fitness appeared to be most strongly associated with mortality in the short term among individuals at highest short-term risk (ie, older age, abnormal exercise test)., Conclusions: Similar to traditional risk factors, fitness is associated with mortality across short-, intermediate-, and long-term follow-up.

Background: The Consortium for Southeastern Hypertension Control (COSEHC) promotes global risk factor management in patients with metabolic syndrome. The COSEHC Global Vascular Risk Management Study (GVRM) intends to quantify these efforts on long-term patient outcomes. The objectives of this study were to present baseline demographics of patients enrolled in the GVRM, calculate a modified COSEHC risk score using 11 variables (COSEHC-11), and compare it with the original COSEHC-17 and Framingham, Prospective Cardiovascular Münster (PROCAM), and Systemic Coronary Risk Evaluation (SCORE) risk scores., Methods: Deidentified electronic medical records of enrolled patients were used to calculate the risk scores. The ability of the COSEHC-11 score to predict the COSEHC-17 score was assessed by regression analysis. Raw risk scores were converted to probability estimates of fatal coronary heart disease (CHD) and compared with predicted risks from other algorithms., Results: Of the 177,404 patients enrolled, 43,676 had data for all 11 variables. The COSEHC-11 score (mean ± standard deviation) of these 43,676 patients was 31.75 ± 11.66, implying a five-year fatal CHD risk of 1.4%. The COSEHC-11 score was highly predictive of the COSEHC-17 score (R(2) = 0.93; P < 0.0001) and correlated well with the SCORE algorithm., Conclusion: The COSEHC-11 risk score is statistically similar to the COSEHC-17 risk score and should be a viable tool for evaluating its ability to predict five-year cardiovascular mortality in the coming years.