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• Increasing alcohol consumption leads to increased HDL markers. • Moderate drinkers have higher HDL values compared to light drinkers. • Race and sex can modify the relationship between HDL and cholesterol efflux. • Unable to evaluate impact of HDL markers due to low number of cardiovascular events. Small studies have suggested that moderate alcohol consumption increases HDL cholesterol (HDL-C) levels and cholesterol efflux capacity (CEC), a main anti-atherosclerotic HDL function. This study aimed to understand the degree to which alcohol intake is associated with various HDL markers in a large, multiethnic population cohort, the Dallas Heart Study (DHS), and whether alcohol modifies the link between HDL markers and atherosclerotic cardiovascular disease (ASCVD). Participants of the DHS were included if they had self-reported alcohol intake and CEC measurements (N=2,919). Alcohol intake was analyzed continuously (grams/week) and as an ordered categorical variable (never, past, light, moderate, heavy, and binge drinkers). HDL-C, CEC, HDL particle number (HDL-P), HDL particle size (HDL-size), and ApoA-I were the primary HDL measures. After adjustment for confounding variables, increasing continuous measure of alcohol intake was associated with increased levels of all HDL markers. Moreover, as compared to moderate drinkers, light drinkers had decreased levels of the HDL markers. In a large, multiethnic cohort, increased alcohol intake was associated with increased levels of multiple markers of HDL metabolism. However, the association of HDL markers with ASCVD risk as modified by alcohol consumption is unable to be determined in this low-risk cohort. [ABSTRACT FROM AUTHOR]

Background: Cell adhesion molecules are key regulators of atherosclerotic plaque development, but circulating levels of soluble fragments, such as intercellular adhesion molecule (sICAM-1) and vascular cell adhesion molecule (sVCAM-1), have yielded conflicting associations with atherosclerotic cardiovascular disease (ASCVD). Endothelial cell-selective adhesion molecule (ESAM) is expressed exclusively in platelets and endothelial cells, and soluble ESAM (sESAM) levels have been associated with prevalent subclinical atherosclerosis. We therefore hypothesized that sESAM would be associated with incident ASCVD.Methods: sESAM, sICAM-1, and sVCAM-1 were measured in 2,442 participants without CVD in the Dallas Heart Study, a probability-based population sample aged 30-65 years enrolled between 2000 and 2002. ASCVD was defined as first myocardial infarction, stroke, coronary revascularization, or CV death. A total of 162 ASCVD events were analyzed over 10.4 years.Results: Increasing sESAM was associated with ASCVD, independent of risk factors (HR Q4 vs Q1: 2.7, 95% CI 1.6-4.6). Serial adjustment for renal function, sICAM-1, VCAM-1, and prevalent coronary calcium did not attenuate these associations. Continuous ESAM demonstrated similar findings (HR 1.31, 95% CI 1.2-1.4). Addition of sESAM to traditional risk factors improved discrimination and reclassification (delta c-index: P = .009; integrated-discrimination-improvement index P = .001; net reclassification index = 0.42, 95% CI 0.15-0.68). Neither sICAM-1 nor sVCAM-1 was independently associated with ASCVD.Conclusions: sESAM but not sICAM-1 or sVCAM-1 levels are associated with incident ASCVD. Further studies are warranted to investigate the role of sESAM in ASCVD. [ABSTRACT FROM AUTHOR]

Objectives This study sought to assess the effect of coronary artery calcium (CAC) on coronary heart disease (CHD) risk prediction in a younger population. Background CAC measured by computed tomography improves CHD risk classification in older adults, but the effectiveness of CAC in younger populations has not been fully assessed. Methods In the DHS (Dallas Heart Study), a multiethnic probability-based population sample, traditional CHD risk factors and CAC were measured in participants without baseline cardiovascular disease or diabetes. Incident CHD—defined as CHD death, myocardial infarction, or coronary revascularization—was assessed over a median follow-up of 9.2 years. Predicted CHD risk was assessed with a Weibull model inclusive of traditional risk factors before and after the addition of CAC as ln(CAC + 1). Participants were divided into 3 10-year risk categories, <6%, 6% to <20%, and ≥20%, and the net reclassification improvement (NRI) was calculated. We also performed a random-effects meta-analysis of NRI from previous studies inclusive of older individuals. Results The analysis comprised 2,084 participants; mean age was 44.4 ± 9.0 years. CAC was independently associated with incident CHD (hazard ratio per SD: 1.90, 95% confidence interval [CI] 1.51 to 2.38; p < 0.001). The addition of CAC to the traditional risk factor model resulted in significant improvement in the C-statistic (delta = 0.03; p = 0.003). Among participants with CHD events, the addition of CAC resulted in net correct upward reclassification of 21%, and among those without CHD, a net correct downward reclassification of 0.5% (NRI: 0.216, p = 0.012). Results remained significant when the outcome was restricted to CHD death and myocardial infarction and when individuals with diabetes were included. The NRI observed in this study was similar to the pooled estimate from previous studies (0.200, 95% CI: 0.140 to 0.258) and the addition of our study to the meta-analysis did not result in significant heterogeneity (I 2 = 0%). Conclusions CAC scoring also improves CHD risk classification in younger adults. [ABSTRACT FROM AUTHOR]

A low plasma level of high-density lipoprotein (HDL) cholesterol (HDL-C) is a major risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, several observations have highlighted the shortcomings of using cholesterol content as the sole reflection of HDL metabolism. In particular, several large randomized controlled trials of extended release niacin and cholesteryl-ester transfer protein (CETP) inhibitors on background statin therapy have failed to show improvement in ASCVD outcomes despite significant increases in HDL-C. Reverse cholesterol transport (RCT) is the principal HDL function that impacts macrophage foam cell formation and other functions such as endothelial activation of endothelial nitric oxide synthase, monocyte adhesion, and platelet aggregation. Cholesterol efflux from macrophages to plasma/serum reflects the first critical step of RCT and is considered a key anti-atherosclerotic function of HDL. Whether this function is operative in humans remains to be seen, but recent studies assessing cholesterol efflux in humans suggest that the cholesterol efflux capacity (CEC) of human plasma or serum is a potent marker of ASCVD risk. This review describes the methodology of measuring CEC ex vivo from human samples and the findings to date linking CEC to human disease. Studies to date confirm that CEC can be reliably measured using stored human blood samples as cholesterol acceptors and suggest that CEC may be a promising new biomarker for atherosclerotic and metabolic diseases. Further studies are needed to standardize measurements and clarify the role CEC may play in predicting risk of developing disease and response to therapies. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to investigate the independent and joint associations between family history of myocardial infarction (FH) and coronary artery calcification (CAC) with incident coronary heart disease (CHD). Background FH and CAC are associated with each other and with incident CHD. It is not known whether FH retains its predictive value after CAC results are accounted for. Methods Among 2,390 participants without cardiovascular disease enrolled in the Dallas Heart Study, we assessed FH (myocardial infarction in a first-degree relative) and prevalent CAC by electron-beam computed tomography. The primary outcome, a composite of CHD-related death, myocardial infarction, and percutaneous or surgical coronary revascularization, was assessed over a mean follow-up of 8.0 ± 1.2 years. The individual and joint associations with the CHD composite outcome were determined for FH and CAC. Results The mean age of the population was 44 ± 9 years; 32% had FH and 47% had a CAC score of 0. In multivariate models adjusted for traditional risk factors, FH was independently associated with CHD (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). Further adjustment for prevalent CAC did not diminish this association (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). FH and CAC were additive: CHD event rates in those with both FH and CAC were 8.8% vs. 3.3% in those with prevalent CAC alone (p < 0.001). CHD rates were 1.9% in those with FH alone compared with 0.4% in those with neither FH nor CAC (p < 0.017). Among subjects without CAC, FH characterized a group with a more unfavorable cardiometabolic profile. Conclusions FH provided prognostic information that was independent of and additive to CAC. Among those with CAC, FH identified subjects at particularly high short-term risk, and, among those without it, selected a group with an adverse risk-factor profile. [ABSTRACT FROM AUTHOR]

Background: Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin β receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP). Methods: Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo. Results: Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin β receptor (1.7 vs 2.4 ng/mL, P = .002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P = .01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P = .02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P = .003) and hs-CRP (0.42 vs 0.31 ng/mL, P = .02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P = .046). Conclusion: Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation. [Copyright &y& Elsevier]

Background: Although chronic lung disease (CLD) is common among patients with myocardial infarction (MI), little is known about the influence of CLD on patient management and outcomes following MI. Methods: Using the National Cardiovascular Data Registry''s ACTION Registry-GWTG, demographics, clinical characteristics, treatments, processes of care, and in-hospital adverse events after acute MI were compared between patients with (n = 22,624) and without (n = 136,266) CLD. Multivariable adjustment was performed to determine the independent association of CLD with treatments and adverse events. Results: CLD (17.0% of non–ST-elevation MI [NSTEMI] and 10.1% of ST-elevation MI [STEMI] patients) was associated with older age, female sex, and a greater burden of comorbidities. Among NSTEMI patients, those with CLD were less likely to undergo cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft compared to those without; in contrast, no differences were seen in invasive therapies for STEMI patients with or without CLD. Multivariable-adjusted risk of major bleeding was significantly increased in CLD patients with NSTEMI (13.0% vs 8.1%, ORadj = 1.27, 95% CI = 1.20-1.34, P < .001) and STEMI (16.0% vs 10.5%, ORadj = 1.19, 95% CI = 1.10-1.29, P < .001). In NSTEMI, CLD was associated with a higher risk of inhospital mortality (ORadj = 1.21, 95% CI = 1.11-1.33); in STEMI no association between CLD and mortality was seen (ORadj = 1.05, 95% CI = 0.95-1.17). Conclusions: CLD is common among patients with MI and is independently associated with an increased risk for major bleeding. In NSTEMI, CLD is also associated with receiving less revascularization and with increased in-hospital mortality. Special attention should be given to this high-risk subgroup for the prevention and management of complications after MI. [Copyright &y& Elsevier]

Abstract: Objective: Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population. Methods and results: Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08–1.84), APB (beta coefficient 0.23, p =0.02), and AWT (beta coefficient 0.04, p =0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61–1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (p interaction =0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23–2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68–1.44). Conclusion: Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease. [Copyright &y& Elsevier]

Abstract: Background: Peptidoglycan recognition protein-1 (PGLYRP-1) is part of the innate immune system and binds to peptidoglycan, a component of bacterial cell walls that has been found in human atherosclerotic lesions. Chronic exposure to bacterial antigens may cause or exacerbate the inflammatory response to lipid deposition within arterial walls. We hypothesized that PGLYRP-1 is associated with subclinical atherosclerosis as measured by computed tomography and magnetic resonance imaging. Methods and results: PGLYRP-1 was measured in 3222 subjects in the Dallas Heart Study, a probability-based population sample age 30–65 including 50% African-Americans and 56% women. Coronary artery calcium (CAC) was measured by electron beam computed tomography (n =2467), abdominal aortic wall thickness (AWT) by magnetic resonance imaging (MRI) (n =2270), and abdominal aortic plaque burden (APB) by MRI (n =2256). In univariable analyses, increasing levels of PGLYRP-1 were associated with all major cardiovascular risk factors, with inflammatory markers such as C-reactive protein, and with CAC, AWT, and APB (p <0.0001 for each). In multivariable models adjusted for traditional risk factors, logPGLYRP-1 remained significantly associated with CAC (OR 1.1, 95% CI 1.01–1.3 per S.D.; p =0.04) and AWT (p =0.009) but not APB (p =0.09). Further adjustment for novel biomarkers associated with PGLYRP-1 and atherosclerosis attenuated the association with CAC (p =0.18) but not with AWT (p =0.01) or APB (p =0.037). Conclusion: In this first reported clinical study of PGLYRP-1 in humans, PGLYRP-1 levels were independently associated with atherosclerosis phenotypes that represent different vascular beds and stages of atherosclerosis. [Copyright &y& Elsevier]

Abstract: Numerous epidemiological studies have identified high-density lipoprotein cholesterol (HDL) to be an independent risk factor for coronary heart disease (CHD). HDL is an emerging therapeutic target that could rival the impact of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) on LDL and CHD risk reduction. HDL metabolism, HDL kinetics, the concentration of various HDL subclasses, and other genetic factors affecting HDL functionality may all contribute to the anti-atherogenic properties of HDL; thus, standard plasma measurement may not capture the full range of HDL effects. Algorithms have been suggested to treat low HDL levels in subgroups of patients; however, no formal HDL target goals or treatment guidelines have been implemented as there is a lack of strong clinical evidence to support effective pharmacologic therapy for primary risk reduction. Available therapies have a modest impact on serum HDL levels; however, emerging therapies could have a more significant influence. [Copyright &y& Elsevier]

Coronary artery calcium (CAC) scoring is a powerful tool for atherosclerotic cardiovascular disease risk stratification. The nongated, noncontrast chest computed tomography scan (NCCT) has emerged as a source of CAC characterization with tremendous potential due to the high volume of NCCT scans. Application of incidental CAC characterization from NCCT has raised questions around score accuracy, standardization of methodology including the possibility of deep learning to automate the process, and the risk stratification potential of an NCCT-derived score. In this review, the authors aim to summarize the role of NCCT-derived CAC in preventive cardiovascular health today as well as explore future avenues for eventual clinical applicability in specific patient populations and broader health systems. [Display omitted] • CAC detected incidentally on NCCT scans is strongly correlated with gated CT Agatston scores and cardiovascular disease outcomes. • Challenges include standardizing quantification of CAC detected by NCCT, validating its prospective power, and avoiding unnecessary downstream testing based solely on the findings. • Interdisciplinary collaboration and integration into health care delivery could improve atherosclerotic risk stratification. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Identifying asymptomatic individuals with American Heart Association/American College of Cardiology stage B heart failure (HF) in the population is an important step to prevent the development of symptomatic HF. The comparative utility of 2 screening strategies (biomarkers vs risk scores) in identifying prevalent stage B HF is unknown. Methods: Participants 30 to 65 years old without symptomatic HF in the Dallas Heart Study who had a cardiac magnetic resonance imaging were included (n = 2,277). Stage B HF (n = 284) was defined by left ventricular (LV) hypertrophy, reduced LV ejection fraction, or prior myocardial infarction. We compared the utility of 2 risk scores (Health Aging and Body Composition HF risk score and the Framingham Heart Failure risk score) with B-type natriuretic peptide (BNP) and N-terminal pro-BNP in identifying stage B HF using logistic regression. Results: Depending upon the method of indexing LV mass (body surface area, fat-free mass, or height2.7), the c-statistic for the Health Aging and Body Composition HF risk score (0.73, 0.75, and 0.64, respectively) was greater than that for BNP (0.62, 0.70, and 0.57, respectively) and N-terminal pro-BNP (0.62, 0.69, and 0.56, respectively) (P < .01 for all). These findings were similar for the Framingham Heart Failure risk score except when LV mass was indexed to fat-free mass. Addition of natriuretic peptide levels to the risk scores resulted in a modest but significant improvement in discrimination of stage B HF (Δ c-statistic, 0.01-0.03, P < .05 for all). Conclusions: Screening for stage B HF in the population is enhanced when natriuretic peptides are measured in addition to, rather than in place of, traditional risk scores. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor superfamily, binds ligands expressed by activated lymphocytes. Interruption of LTβR signaling improves autoimmune diseases and alters lipid homeostasis. We assayed circulating LTβR and examined its association with atherosclerosis phenotypes in a population-based sample. Methods and results: Plasma LTβR was measured by ELISA in 3215 subjects enrolled in the Dallas Heart Study. Atherosclerosis was assessed using CT measurements of coronary calcium (CAC) and abdominal MRI measurements of aortic plaque (AP) (n =2252) and aortic wall thickness (AWT) (n =2265). We analyzed associations between LTβR and atherosclerosis using multivariable logistic and linear regression methods. Higher levels of LTβR associated with most traditional cardiovascular risk factors, multiple inflammatory markers, and markers of cardiac injury. Univariable analyses demonstrated significant associations of LTβR with CAC, AP, and AWT (p <0.0001 for each). In multivariable models adjusted for traditional risk factors, the 4th vs. the 1st quartile of LTβR remained associated with prevalent CAC, AP, and increased AWT (all p <0.05). Similar associations were observed when LTβR was modeled as a log-transformed continuous variable. Conclusion: LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Elevated lipoprotein(a) (Lp[a]) and family history (FHx) of coronary heart disease (CHD) are individually associated with cardiovascular risk, and Lp(a) is commonly measured in those with FHx.Objectives: The aim of this study was to determine independent and joint associations of Lp(a) and FHx with atherosclerotic cardiovascular disease (ASCVD) and CHD among asymptomatic subjects.Methods: Plasma Lp(a) was measured and FHx was ascertained in 2 cohorts. Elevated Lp(a) was defined as the highest race-specific quintile. Independent and joint associations of Lp(a) and FHx with cardiovascular risk were determined using Cox regression models adjusted for cardiovascular risk factors.Results: Among 12,149 ARIC (Atherosclerosis Risk In Communities) participants (54 years, 56% women, 23% black, 44% with FHx), 3,114 ASCVD events were observed during 21 years of follow-up. FHx and elevated Lp(a) were independently associated with ASCVD (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.09 to 1.26, and HR: 1.25; 95% CI: 1.12 to 1.40, respectively), and no Lp(a)-by-FHx interaction was noted (p = 0.75). Compared with subjects without FHx and nonelevated Lp(a), those with either elevated Lp(a) or FHx were at a higher ASCVD risk, while those with both had the highest risk (HR: 1.43; 95% CI: 1.27 to 1.62). Similar findings were observed for CHD risk in ARIC, in analyses stratified by premature FHx, and in an independent cohort, the DHS (Dallas Heart Study). Presence of both elevated Lp(a) and FHx resulted in greater improvement in ASCVD and CHD risk reclassification and discrimination indexes than either marker alone.Conclusions: Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions. [ABSTRACT FROM AUTHOR]

Background: Cholesterol efflux capacity (CEC), which is a key step in the reverse cholesterol transport pathway, is independently associated with atherosclerotic cardiovascular disease (ASCVD). However, whether it predicts ASCVD beyond validated novel risk markers is unknown.Objectives: This study assessed if CEC improved ACSVD risk prediction beyond using coronary artery calcium (CAC), family history (FH), and high-sensitivity C-reactive protein (hs-CRP).Methods: CEC, CAC, self-reported FH, and hs-CRP were assessed among participants without baseline ASCVD who were enrolled in the Dallas Heart Study (DHS). ASCVD was defined as a first nonfatal myocardial infarction (MI) or stroke, coronary revascularization, or cardiovascular death, assessed over a median 9.4 years. Risk prediction was assessed using various modeling techniques and improvements in the c-statistic, the integrated discrimination index (IDI), and the net reclassification index (NRI).Results: The mean age of the population (N = 1,972) was 45 years, 52% had CAC (>0), 31% had FH, and 58% had elevated hs-CRP (≥2 mg/l). CEC greater than the median was associated with a 50% reduced incidence of ASCVD in those with CAC (5.4% vs. 10.5%; p = 0.003), FH (5.8% vs. 10%; p = 0.05), and elevated hs-CRP (3.8% vs. 7.9%; p = 0.004). CEC improved all metrics of discrimination and reclassification when added to CAC (c-statistic, p = 0.004; IDI, p = 0.02; NRI: 0.38; 95% confidence interval [CI]: 0.13 to 0.53), FH (c-statistic, p = 0.006; IDI, p = 0.008; NRI: 0.38; 95% CI: 0.13 to 0.55), or elevated hs-CRP (c-statistic p = 0.008; IDI p = 0.02; NRI: 0.36; 95% CI 0.12 to 0.52).Conclusions: CEC improves ASCVD risk prediction beyond using CAC, FH, and hs-CRP and warrants consideration as a novel ASCVD risk marker. [ABSTRACT FROM AUTHOR]

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, probabilitybased, 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. [ABSTRACT FROM AUTHOR]

Background Obesity has been linked to the development of hypertension, but whether total adiposity or site-specific fat accumulation underpins this relationship is unclear. Objectives This study sought to determine the relationship between adipose tissue distribution and incident hypertension. Methods Normotensive participants enrolled in the Dallas Heart Study were followed for a median of 7 years for the development of hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of blood pressure medications). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was quantified by magnetic resonance imaging and proton-spectroscopic imaging, and lower body fat (LBF) was imaged by dual-energy x-ray absorptiometry. Multivariable relative risk regression was performed to test the association between individual fat depots and incident hypertension, adjusting for age, sex, race/ethnicity, diabetes, smoking, SBP, and body mass index (BMI). Results Among 903 participants (median age, 40 years; 57% women; 60% nonwhite; median BMI 27.5 kg/m 2 ), 230 (25%) developed incident hypertension. In multivariable analyses, higher BMI was significantly associated with incident hypertension (relative risk: 1.24; 95% confidence interval: 1.12 to 1.36, per 1-SD increase). However, when VAT, SAT, and LBF were added to the model, only VAT remained independently associated with incident hypertension (relative risk: 1.22; 95% confidence interval: 1.06 to 1.39, per 1-SD increase). Conclusions Increased visceral adiposity, but not total or subcutaneous adiposity, was robustly associated with incident hypertension. Additional studies will be needed to elucidate the mechanisms behind this association. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to determine the association between fitness and lifetime risk for cardiovascular disease (CVD).Background: Higher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD.Methods: We followed up 11,049 men who underwent clinical examination at the Cooper Institute in Dallas, Texas, before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 years (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by the Balke protocol and categorized according to treadmill time into low, moderate, and high fitness, with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45, 55, and 65 years, with non-CVD death as the competing event.Results: Differences in fitness levels (low fitness vs. high fitness) were associated with marked differences in the lifetime risks for CVD death at each index age: age 45 years, 13.7% versus 3.4%; age 55 years, 34.2% versus 15.3%; and age 65 years, 35.6% versus 17.1%. These associations were strongest among persons with CVD risk factors.Conclusions: A single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among persons with a high burden of CVD risk factors. [ABSTRACT FROM AUTHOR]