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Background and Aims: Identifying the association of novel plasma biomarkers with coronary artery calcium (CAC) incidence or progression may provide insights into the pathophysiology of atherogenesis and plaque formation., Methods: Participants of the Dallas Heart Study (DHS), a multi-ethnic cohort of ambulatory individuals at low-intermediate risk for future atherosclerotic cardiovascular disease (ASCVD), who had their blood tested for 31 biomarkers reflecting multiple pathophysiological pathways, underwent 2 serial non-contrast computed tomography assessments for CAC a median ∼7 years apart. The collected biomarkers were explored for association with CAC incidence or progression using univariate and multivariate analysis., Results: A total of 1424 participants were included; mean age 43 years, 39 % male, and nearly half African-American. Over a 7-year interval between the two CAC measurements, 340 participants (23.9 %) had CAC incidence or progression, 105 (7.4 %) with incident CAC, and 309 (21.7 %) with CAC progression. Although several plasma biomarkers were associated with CAC incidence or progression in a univariate model, only soluble intercellular adhesion molecule-1 (sICAM-1), related to atherosclerosis by the inflammatory pathway, remained independently associated in a multivariate model adjusted for traditional risk factors., Conclusions: Further studies are needed to characterize the role of sICAM-1 in CAC evolvement to establish whether it has a pivotal mechanistic contribution or is rather an innocent bystander. Alternate measures of coronary atherosclerosis may be needed to elucidate contributors to atherosclerosis incidence or progression., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Neeland has been a speaker/consultant for Boehringer-Ingelheim/Lilly Alliance and Bayer Pharmaceuticals and has been an advisory board member for AMRA Medical, Boehringer Ingelheim, Bayer, and Lilly. Dr. Eisen has been a speaker/consultant/ Advisory board member for Boehringer-Ingelheim, Bayer, Novo Nordisk, AstraZeneca, Pfizer, Neopharm, Medison Pharma, and Sanofi. Dr. de Lemos reports grant support from Roche Diagnostics and Abbott Diagnostics, consulting fees from Quidel Cardiovascular, Inc., Cytokinetics and Glaxo Smith Kline, honoraria for participation in endpoint committees from Beckman Coulter and Siemens Health Care Diagnostics, and fees for participation in Data Monitoring Committees from Astra Zeneca, Novo Nordisk, Eli Lilly, Regeneron, Amgen, and Verve Therapeutics., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: The effects of weight loss with a partial or total meal replacement programme (MRP) on atherosclerotic cardiovascular disease (ASCVD) risk factors are not fully understood, in particular in people at higher CV risk. In the 52-week randomized controlled OPTIWIN study in men and women with obesity, meal replacement programme (total for first 26 weeks, partial for the ensuing 26 weeks) with OPTIFAST (OP) resulted in significantly greater weight loss compared with a low-calorie food-based (FB) dietary plan, both as part of a comprehensive lifestyle intervention [OP (n = 135)/FB (n = 138) week 26: -12.4%/-6.0%, p < .001; week 52: -10.5%/-5.5%, p < .001]. Here, we examined effects on ASCVD risk factors and 10-year ASCVD risk., Materials and Methods: Participants with body mass index 30-55 kg/m 2 and age 18-70 years, and not on anti-obesity medications, were recruited. The effects on systolic and diastolic blood pressure (SBP, DBP), lipid parameters and 10-year ASCVD risk were analysed as changes over time using linear mixed models. Subgroup analyses were conducted for changes in SBP, DBP and ASCVD risk by categories of age (<40, 40-59, ≥60 years), baseline SBP (2 , 10-year ASCVD risk <5% 87%/74%, dysglycaemia 52%/50%). At week 26, SBP/DBP were significantly reduced with OP versus FB, and a greater proportion achieved BP ≤130/80 mmHg [odds ratio 2.11 (95% confidence interval 1.10, 4.03), p = .024]. All lipid parameters as well as 10-year ASCVD risk were significantly improved with OP versus FB. A similar, but slightly attenuated pattern was observed at 52 weeks. Across subgroups, greater reductions for SBP, DBP and ASCVD risk were generally seen with OP versus FB with quantitatively higher baseline SBP and age, and in men., Conclusions: In people with obesity at low ASCVD risk, OP significantly reduced cardiovascular risk factors and 10-year predicted risk for ASCVD., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD., Methods: The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular filtration rate. Models were sex-specific, race-free, developed on the age scale, and adjusted for competing risk of non-CVD death. Analyses were conducted in each data set and meta-analyzed. Discrimination was assessed using the Harrell C-statistic. Calibration was calculated as the slope of the observed versus predicted risk by decile. Additional equations to predict each CVD subtype (atherosclerotic CVD and heart failure) and include optional predictors (urine albumin-to-creatinine ratio and hemoglobin A1c), and social deprivation index were also developed. External validation was performed in 3 330 085 participants from 21 additional data sets., Results: Among 6 612 004 adults included, mean±SD age was 53±12 years, and 56% were women. Over a mean±SD follow-up of 4.8±3.1 years, there were 211 515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval, 0.763-0.809) in female and 0.757 (0.727-0.778) in male participants. The calibration slopes were 1.03 (interquartile interval, 0.81-1.16) and 0.94 (0.81-1.13) among female and male participants, respectively. Similar estimates for discrimination and calibration were observed for atherosclerotic CVD- and heart failure-specific models. The improvement in discrimination was small but statistically significant when urine albumin-to-creatinine ratio, hemoglobin A1c, and social deprivation index were added together to the base model to total CVD (ΔC-statistic [interquartile interval] 0.004 [0.004-0.005] and 0.005 [0.004-0.007] among female and male participants, respectively). Calibration improved significantly when the urine albumin-to-creatinine ratio was added to the base model among those with marked albuminuria (>300 mg/g; 1.05 [0.84-1.20] versus 1.39 [1.14-1.65]; P =0.01)., Conclusions: PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults by using routinely available clinical variables., Competing Interests: Disclosures Dr Coresh reports grants from the National Institutes of Health (NIH) and from the National Kidney Foundation during the conduct of the study and personal fees and other support from Healthy.io outside the submitted work. Dr Khan reports grants from NIH during the conduct of the study (R21 HL165376). Dr Chang reports consulting fees from Novartis, Reata, and Amgen, and grants from Novartis, Novo Nordisk, NIH, and the National Kidney Foundation. Dr Palaniappan reports grants from NIH during the conduct of the study (K24 HL150476). Dr Tuttle reports unpaid support from the American Heart Association and grant support from NIH (01MD014712, OT2OD032581, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, and UM1AI109568); the Centers for Disease Control and Prevention (75D301-21-P-12254), as well as Bayer and Travere, paid to the institution; consulting fees from Eli Lilly, Boehringer Ingelheim, AstraZeneca, Goldfinch Bio, Novo Nordisk, Bayer, and Travere Therapeutics Inc; honoraria from Eli Lilly, AstraZeneca, Novo Nordisk, and Bayer; unpaid participation as a Data Safety and Monitoring Board chair for National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)/NIH and George Clinical Institute; and unpaid participation as a Diabetic Kidney Disease collaborative chair for the American Society of Nephrology. Dr Neeland reports speaker and consulting fees from Boehringer Ingelheim, Eli Lilly and Co, Nestle Health Science, and Bayer Pharmaceuticals. Dr Virani reports grants from NIH, US Department of Veterans Affairs, Tahir and Jooma Family. The views expressed in this article 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 US Department of Health and Human Services. All other coauthors have nothing to disclose.

Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed.

Background: Inflammatory bowel disease (IBD) is associated with higher incidence of atherosclerotic cardiovascular disease (ASCVD). Data investigating the role of coronary artery calcium (CAC) scoring in identifying subclinical atherosclerotic disease in IBD patients is scarce., Methods: Using data obtained from the CLARIFY registry, a prospective study of no-charge coronary artery calcium (CAC) testing at University Hospitals, we reviewed patients with ulcerative colitis (UC) or Crohn's disease (CD) who underwent CAC scoring from 2014 to 2020. We investigated the concordance between CAC risk and 10-year estimated ASCVD risk by AHA/ACC pooled cohort equation using pre-established thresholds for statin prescription (CAC≥100, 10-year ASCVD risk ≥7.5%). We additionally investigated the association between CAC, preventive therapy initiation and Major Adverse Cardiovascular Events (MACE)., Results: A total of 369 patients with IBD were included (174 UC, 195 CD), with median age of 60 years. The median CAC score was 14.9 with no significant difference between UC and CD (P = .76). Overall, 151 (41%) had CAC of 0, 108 (29%) had CAC 1-99, 61 (17%) had CAC 100 to 399, and 49 (13%) had CAC ≥400 with no difference in CAC distribution between CD and UC (P = .17). There was no difference in median CAC between IBD or age/sex-matched controls (P = .34). Approximately half of the patients (52%) with IBD had 10-year estimated ASCVD risk of 7.5% or higher. Among patients with ASCVD risk <7.5% (n = 163), 29 (18%) had CAC≥100 and among patients with ASCVD risk ≥7.5% (n = 178), 102 (57%) had CAC <100. There was no difference between CAC<100 vs CAC≥100 with respect to CRP, use of immunosuppressive or amino-salicylate therapy, IBD severity or complications. CAC score (AUROC 0.67 [0.56-0.78]), but not PCE ASCVD risk (AUROC 0.60 [0.48-0.73]), was predictive of MACE. The best cut-off for CAC score was 76 (sensitivity = 60%, specificity = 69%), and was associated with 4-fold increase in MACE (Hazard Ratio 4.0 [2.0-8.1], P < .001)., Conclusion: Subclinical atherosclerosis, as evaluated by CAC scoring, is prevalent in patients with IBD, and is associated with cardiovascular events. Further studies are needed to understand underlying biological processes of increased atherosclerotic disease risk among adults with IBD., Competing Interests: Conflict of interest None to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Cardiovascular disease (CVD) risk amongst those with type 2 diabetes (T2D) is heterogenous. The role of imaging-based cardiometabolic biomarkers (e.g., coronary artery calcium [CAC] score, and hepatic triglyceride content [HTC]) in CVD risk stratification in T2D is unclear. To better understand this, we sought to evaluate the individual and joint associations between CAC and hepatic steatosis (HS) with clinical atherosclerotic CVD (ASCVD) in Dallas Heart Study (DHS) participants with and without T2D., Methods: We examined participants in the DHS, a multi-ethnic cohort study, without self-reported ASCVD. CAC scoring was performed via computed tomography with the mean of two consecutive scores used. HTC was measured using magnetic resonance spectroscopy, and HS was defined as HTC >5.5% The primary outcome was incident ASCVD, defined as coronary heart disease (CHD; myocardial infarction, percutaneous coronary intervention, or coronary artery bypass graft surgery), ischemic stroke, transient ischemic attack, or CVD death. Cox regression analyses, and interaction testing was performed to evaluate the individual and joint associations between CAC and HS with ASCVD. The association between HS and coronary heart disease was validated in the UK Biobank (UKB)., Results: A total of 1252 DHS participants were included with mean age 44.8 ± 9.3 years, mean body mass index 28.7 ± 5.9 kg/m 2 , 55% female, and 59% black with an overall prevalence of T2D of 9.7%. CAC scores were significantly higher (p < 0.01) and HS was significantly more prevalent in those with T2D (p < 0.01). Over a median of 12.3 years, 8.3% of participants experienced ASCVD events. The ASCVD event rate was significantly higher in participants with T2D (20.5% vs 7.0%, p < 0.01). Continuous CAC was associated with ASCVD events in the overall cohort regardless of T2D status with a significant interaction present between CAC and T2D status on ASCVD, P interaction  = 0.02. HTC was not associated with ASCVD risk in participants without T2D but was inversely associated with risk in participants with T2D (HR 0.91, 95% CI 0.83-0.99 per 1% increase in HTC, p = 0.02), P interaction  = 0.02. Amongst 37,266 UKB participants, 4.5% had T2D. CHD events occurred in 2.2% of participants, with 10.2% of events occurring amongst those with T2D. An inverse relationship between HTC and CHD was also found amongst those with T2D in UKB with a significant interaction between T2D status and HTC on CHD (HR per 1% increase in HTC 0.95, 95% CI 0.91-0.99, p = 0.01, P interaction  = 0.02)., Conclusions: In the DHS, we found that CAC was associated with ASCVD risk independent of T2D status. We did not observe an association between HTC and ASCVD in participants without T2D, but there was an inverse association between HTC and ASCVD in those with T2D that was replicated in the UKB cohort. Further investigation is warranted to understand the possible protective association of HS in participants with T2D., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Adults with diabetes are at an increased risk of atherosclerotic cardiovascular disease (ASCVD), and food insecurity may be a major and underappreciated risk compounder in this population. We sought to analyze the prevalence of food insecurity and its association with ASCVD in adults with diabetes., Methods: A total of 6424 participants with diabetes were included from the 2019 and 2020 National Health Interview Survey. Food insecurity was determined with a 10-question U.S. Adult Food Security Survey Module, and classified as high, marginal, low, and very low. ASCVD was defined as a self-reported history of coronary artery disease, myocardial infarction, or stroke., Results: Of the 6424 included participants (weighted: n = 21 690 217), 5 405 543 (24.4%) reported a history of ASCVD and 2 946 061 (13.3%) were identified as food insecure (low or very low food security). Adults with food insecurity were more likely to have ASCVD than adults who were food secure (28.9% vs 23.7%; P = 0.008). In the multivariate analyses adjusted for traditional cardiovascular risk factors, all levels of food insecurity were associated with ASCVD compared with food-secure adults (marginal security: odds ratio [OR]: 1.60; 95% confidence interval [CI], 1.18-2.18]; P = 0.003; low security: OR: 2.09; 95% CI, 1.58-2.74]; P < 0.001; very low security: OR: 1.69; 95% CI, 1.22-2.34]; P = 0.001). The association persisted when adjusted for income, location, education, and insurance status. In adults with diabetes and ASCVD, income was a negative factor for food insecurity (OR: 0.71; 95% CI, 0.62-0.80; P < 0.001), but female sex and smoking were positive factors (OR: 1.90; 95% CI, 1.29-2.80; P = 0.001; and OR: 1.97; 95% CI, 1.23-3.18; P = 0.005; respectively). At younger ages, the prevalence of food insecurity increased, especially in adults with ASCVD., Conclusions: We showed that 13% of U.S. adults with diabetes are food insecure, which was associated with ASCVD independent of traditional and socioeconomic risk factors. Our findings emphasize the importance of recognizing food insecurity as a driver of ASCVD in adults with diabetes, and encourage future efforts at reducing this disparity., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Coronary artery calcium (CAC) scoring is not routinely performed in patients with diabetes based on an existing class I indication for statin therapy in these patients. However, CAC scoring may improve risk classification and prediction of atherosclerotic cardiovascular disease (ASCVD) events beyond risk scores in asymptomatic individuals with prediabetes and diabetes, warranting CAC assessment in this population. The routine availability through provision of no-charge CAC as an alternative to routine probabilistic risk scores may improve utilization of preventive therapies especially in traditionally underserved populations., Methods: Prospective observational study in a large health system offering no-charge CAC scoring for primary prevention risk prediction with available glycosylated hemoglobin (HbA1c) measurements between June 2015 and March 2019 were divided according to no diabetes (HbA1c <5.7 %), prediabetes (HbA1c 5.7 %-6.4 %), or diabetes (HbA1c ≥ 6.5 % or charted history) and followed for major adverse cardiovascular events [myocardial infarction, stroke, death (MACE) or coronary revascularization]. Patient characteristics, health history, laboratory data, and statin prescription rates were measured at baseline and at one year after CAC scoring., Results: A total of 12,194 subjects with available HbA1c underwent CAC scoring during the study period (6462 diabetes, 2062 prediabetes, and 3670 without diabetes). At a median follow-up of 1.2 years, there were 458 MACE events (71 patients without diabetes, 66 patients with prediabetes, and 321 patients with diabetes). Among patients with diabetes or prediabetes, increased CAC was associated with MACE (HR 1.38 [1.26-1.51], p < 0.001) and MACE or revascularization (HR 1.70 [1.57-1.85], p < 0.001). In patients with diabetes, CAC category was associated with greater statin initiation (89.6 % for CAC≥400 vs 60.1 % for CAC = 0, p < 0.001) and high intensity statin initiation (42.2 % for CAC≥400 vs 16.8 % for CAC = 0, p < 0.001) at one year post CAC scoring. Patients with diabetes had greater reductions in systolic blood pressure, LDL-C, total cholesterol, and triglycerides from baseline with a CAC ≥400 compared to a lower CAC category (p = 0.007)., Conclusions: CAC burden is associated with ASCVD risk in patients with diabetes. CAC scoring increases statin prescriptions and reduces ASCVD risk in patients with diabetes, potentially warranting routine CAC assessment in this population., (Copyright © 2022. Published by Elsevier Inc.)

Findings from epidemiological studies over the past 30 years have shown that visceral adipose tissue, accurately measured by CT or MRI, is an independent risk marker of cardiovascular and metabolic morbidity and mortality. Emerging evidence also suggests that ectopic fat deposition, including hepatic and epicardial fat, might contribute to increased atherosclerosis and cardiometabolic risk. This joint position statement from the International Atherosclerosis Society and the International Chair on Cardiometabolic Risk Working Group on Visceral Obesity summarises the evidence for visceral adiposity and ectopic fat as emerging risk factors for type 2 diabetes, atherosclerosis, and cardiovascular disease, with a focus on practical recommendations for health professionals and future directions for research and clinical practice. We discuss the measurement of visceral and ectopic fat, pathophysiology and contribution to adverse health outcomes, response to treatment, and lessons from a public health programme targeting visceral and ectopic fat. We identify knowledge gaps and note the need to develop simple, clinically applicable tools to be able to monitor changes in visceral and ectopic fat over time. Finally, we recognise the need for public health messaging to focus on visceral and ectopic fat in addition to excess bodyweight to better combat the growing epidemic of obesity worldwide., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aims: Metabolic syndrome (MetS) increases atherosclerotic cardiovascular disease (ASCVD) risk. Low HDL cholesterol (HDL-C) is a diagnostic criterion of MetS and a major ASCVD risk factor. HDL particle concentration (HDL-P) associates with incident ASCVD independent of HDL-C, but its association with incident MetS has not been studied. We hypothesized that HDL-P would be inversely associated with incident metabolic syndrome independent of HDL-C and markers of adiposity and insulin resistance., Materials and Methods: HDL-P was measured by NMR and visceral fat by MRI in participants of the Dallas Heart Study, a probability-based population sample of adults age 30-65. Participants with prevalent MetS, DM, CVD, and any systemic illlness were excluded. Incident MetS as defined by NCEP ATPIII criteria was determined in all participants after median follow-up period of 7.0 years., Results: Among 1120 participants without DM or MetS at baseline (57% women, 45% Black, mean age 43), 22.8% had incident MetS at follow-up. HDL-P and HDL-C were modestly correlated (r=0.54, p<0.0001). In models adjusted for traditional risk factors and MetS risk factors including visceral fat, HS-CRP, triglyceride to HDL-C ratio, and HOMA-IR, the lowest quartile of HDL-P was associated with a 2-fold increased risk of incident MetS (OR 2.1, 95%CI 1.4-3.1; p=0.0003)., Conclusions: Low HDL-P is independently associated with incident MetS after adjustment for traditional risk factors, lipid parameters, adiposity, inflammation, and markers of insulin resistance. Further studies are warranted to validate these findings and elucidate the mechanisms underpinning this association., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Excess adipose tissue has been implicated in the pathogenesis of insulin resistance and atherosclerosis and is a key risk factor for blood pressure (BP) elevation. However, circulating levels of adiponectin, a protein produced by adipose tissue and widely implicated in the pathogenesis of insulin resistance and atherosclerosis, are inversely proportional to adiposity. The relationship between adiponectin and incident hypertension has not been determined in the general US population., Methods: Normotensive participants (n = 1233) enrolled in the Dallas Heart Study, a multiethnic, probability-based population sample of Dallas County adults were followed for median of 7 years. Retroperitoneal, intraperitoneal, visceral, and subcutaneous adipose tissue were measured at baseline by magnetic resonance imaging. Liver fat content was measured by 1 H-magnetic resonance spectroscopy. Relative risk regression was used to determine the association of adiponectin with incident hypertension after adjustment for age, race, sex, BMI, smoking, diabetes, baseline systolic BP, total cholesterol, and regional fat depot., Results: Of the 1233 study participants (median age 40 years, 40% black, and 56% women), 391 (32%) had developed hypertension over a median follow-up of 7 years. Adiponectin levels were associated with reduced risk of incident hypertension (RR 0.81, 95% CI [0.68-0.96]) in the fully adjusted model, which included liver fat. Similar results were observed after adjustment for subcutaneous or visceral fat depots when tested individually or simultaneously in the model., Conclusion: Our study suggested a protective role of adiponectin against incident hypertension independent of body fat distribution., (Copyright © 2016 John Wiley & Sons, Ltd.)

Therapies targeting high-density lipoprotein cholesterol content (HDL-C) have not improved coronary heart disease (CHD) outcomes. High-density lipoprotein particle concentration (HDL-P) may better predict CHD. However, the impact of race/ethnicity on the relations between HDL-P and subclinical atherosclerosis and incident CHD events has not been described. Participants from the Dallas Heart Study (DHS), a multiethnic, probability-based, population cohort of Dallas County adults, underwent the following baseline measurements: HDL-C, HDL-P by nuclear magnetic resonance imaging, and coronary artery calcium by electron-beam computed tomography. Participants were followed for a median of 9.3 years for incident CHD events (composite of first myocardial infarction, stroke, coronary revascularization, or cardiovascular death). The study comprised 1,977 participants free of CHD (51% women, 46% black). In adjusted models, HDL-C was not associated with prevalent coronary artery calcium (p = 0.13) or incident CHD overall (hazard ratio [HR] per 1 SD 0.89, 95% confidence interval [CI] 0.76 to 1.05). However, HDL-C was inversely associated with incident CHD among nonblack (adjusted HR per 1 SD 0.67, 95% CI 0.46 to 0.97) but not black participants (HR 0.94, 95% CI 0.78 to 1.13, pinteraction = 0.05). Conversely, HDL-P, adjusted for risk factors and HDL-C, was inversely associated with prevalent coronary artery calcium (p = 0.009) and with incident CHD overall (adjusted HR per 1 SD 0.73, 95% CI 0.62 to 0.86), with no interaction by black race/ethnicity (pinteraction = 0.57). In conclusion, in contrast to HDL-C, the inverse relation between HDL-P and incident CHD events is consistent across ethnicities. These findings suggest that HDL-P is superior to HDL-C in predicting prevalent atherosclerosis as well as incident CHD events across a diverse population and should be considered as a therapeutic target., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Prediabetes defined by fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1c) predicts incident diabetes, but their individual and joint associations with micro- and macro-vascular risk remain poorly defined., Methods: FPG, HbA1c, coronary artery calcium (CAC), carotid wall thickness, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) were measured in adults free from prior diabetes or cardiovascular disease (CVD) in the Dallas Heart Study 2 (DHS-2), a population-based cohort study. Prediabetes was defined by FPG 100-125 mg/dL and/or HbA1c 5.7%-6.4%. Multivariable logistic regression was used to analyse associations of HbA1c and/or FPG in the prediabetes range with subclinical atherosclerosis and renal measures., Results: The study comprised 2340 participants, median age = 49 years; 60% women and 50% black. Those with prediabetes were older (52 vs 48 years), more often men (63% vs 53%), black (53% vs 47%) and obese (58% vs 40%; p < 0.001 for each). Prediabetes was captured by FPG alone (43%), HbA1c alone (30%) or both (27%). Those with prediabetes by HbA1c or FPG versus normal HbA1c/FPG had more CAC [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.5-2.2], higher carotid wall thickness (1.32 vs 1.29 mm, p < 0.001), eGFR < 60 mL/min [OR = 1.6 (95% CI = 1.1-2.4)], UACR > 30 mg/dL [OR = 1.8 (95% CI = 1.2-2.7)] and a higher odds for the composite eGFR + UACR [chronic kidney disease (CKD) ≥ 2] [OR = 1.9 (95% CI = 1.5-2.6)]. After multivariable adjustment, none of these associations remained significant., Conclusion: Prediabetes defined by HbA1c and/or FPG criteria is crudely associated with markers of diabetic macro- and micro-vascular disease, but not after statistical adjustment, suggesting the relationships are attributable to other characteristics of the prediabetes population.

Objective: Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population-based cohort of obese adults., Design and Methods: Among obese participants in the Dallas Heart Study, we examined the cross-sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation (n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography (n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index., Results: In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA-IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number (p < 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque (p < 0.001 for each). VAT independently associated with C-reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA-IR were significant in univariable analyses but attenuated after multivariable adjustment., Conclusion: VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub-phenotypes with heterogeneous metabolic and atherosclerosis risk., (Copyright © 2012 The Obesity Society.)

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

Aims We tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores. Methods and results The rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67%). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as ‘progressors’ or ‘non-progressors’ based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group. Conclusion The 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression. [ABSTRACT FROM PUBLISHER]

Background and aims Inflammatory biomarkers and adipocytokines (IBA) may contribute to atherosclerosis by promoting vascular inflammation. The association between IBA and coronary artery calcium (CAC), a marker of subclinical atherosclerosis, is not well defined in South Asians (SA). We hypothesized that IBA (high sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TNF-α], adiponectin, and leptin) were independently associated with and improved discrimination of CAC among SA. Methods We analyzed IBA and CAC among participants in the prospective Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. We used logistic regression models to examine cross-sectional associations of IBA with CAC presence (CAC >0) and severity (CAC >100), and C-statistics to assess the incremental contribution of each IBA to traditional risk factors (TRF) from the AHA/ACC Pooled Cohort Equations (PCE) for discrimination of CAC. Results Among 906 participants in the MASALA study, women (n = 420) had significantly higher levels of hsCRP, adiponectin, and leptin but lower levels of TNF-α than men ( p  < .01 for all). There was no significant association between any of the four IBA and either CAC category in multivariable-adjusted models, respectively. Lastly, none of the four IBA improved discrimination of CAC presence or severity when added to elements of the PCE. Conclusions IBA were not associated with CAC presence or severity in the MASALA population. IBA did not help identify SA at risk of subclinical atherosclerosis, although associations with ASCVD events remain unclear. In SA, CAC may have a distinct pathophysiology independent of inflammation as measured by IBA. [ABSTRACT FROM AUTHOR]

The article presents a study on the epidemiology of cholesterol efflux capacity and its connection to incident atherosclerotic cardiovascular disease outcomes. Topics covered include high-density lipoprotein (HDL) cholesterol concentration, the ability to assess the clinical relevance of reverse cholesterol transport in humans, and the use of the National Death Index to determine vital status for trial participants.

Background: Longitudinal increases in metabolic syndrome (MS) components are associated with increased heart failure (HF) risk, but the association of MS change over time with subclinical myocardial injury is unknown. Hypothesis: Greater progression and duration of MS is associated with subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin T (hs-cTnT). Methods: We studied 8,170 participants (mean age 63, 59% female) without coronary heart disease, HF or diabetes at ARIC Visit 4 (1996-1998) with available data on MS components from the first four ARIC visits and hs-cTnT data at Visit 4. We defined MS using AHA/NHLBI criteria for high waist circumference (WC), hyperglycemia, elevated blood pressure (BP), low HDL-C and hypertriglyceridemia, with a diagnosis of MS made by ≥ 3 components. Using data on MS components from Visit 1 (1987-89) through 4, we used logistic regression models adjusted for demographics and cardiovascular risk factors to evaluate associations of changes in MS components over time and duration of MS with elevated hs-cTnT (≥ 14 ng/L) at Visit 4. Results: 3,644 (45%) of Visit 4 participants had MS. Greater number of MS components at Visit 4 was associated with a higher likelihood of elevated hs-cTnT, with the highest odds seen for those with 5 MS components (OR 2.32; 95%CI: 1.39-3.87) compared to those with none. Among MS components, the strongest associations were seen for elevated BP and high WC. Among participants without MS at V1, those with no MS components at both Visits 1 and 4 had the lowest odds of elevated hs-cTnT (reference), with progressively higher likelihood of elevated hs-cTnT for those increasing to 1-2 (OR 1.12; 95%CI 0.61-2.06), 3 (OR 1.90; 95%CI 1.04-3.45) and 4-5 (OR 2.64; 95%CI 1.41-4.92) MS components by Visit 4. MS duration was also significantly associated with elevated hs-cTnT, with an OR of 1.08 (95%CI: 1.06-1.11) per year of MS duration. Conclusions: Greater MS severity and progression, and longer duration of MS, are associated with a higher likelihood of subclinical myocardial injury. This may have mechanistic implications for the association between MS and HF, and underscores the need to refine strategies to prevent MS onset and progression. [ABSTRACT FROM AUTHOR]