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Arterial stiffness, echolucency and texture features are altered with hypertension and associated with increased cardiovascular disease risk. The relationship between these markers and structural and load-dependent artery wall changes in hypertension are poorly understood. The Multi-ethnic Study of Atherosclerosis (MESA) is a longitudinal study of 6814 adults from six communities across the United States designed to study subclinical cardiovascular disease. From B-mode imaging of the right common carotid artery at the baseline MESA examination, we calculated carotid artery Young's elastic modulus (YEM, n = 5894) and carotid artery gray-scale texture features (n = 1403). The standard YEM calculation represented total arterial stiffness. Structural stiffness was calculated by adjusting YEM to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. We found that load-dependent YEM was elevated in hypertensive individuals compared with normotensive individuals (35.7 ± 105.5 vs. -62.0 ± 112.4 kPa, p < 0.001) but that structural YEM was similar (425.3 ± 274.8 vs. 428.4 ± 293.0 kPa, p = 0.60). Gray-scale measures of heterogeneity in carotid artery wall texture (gray-level difference statistic contrast) had small but statistically signification correlations with carotid artery stiffness mechanisms. This association was positive for structural YEM (0.107, p < 0.001), while for load-dependent YEM, the association was negative (-0.064, p = 0.02). In conclusion, increased arterial stiffness in hypertension was owing solely to the non-linear mechanics of having higher blood pressure, not structural changes in the artery wall, and high load-dependent stiffness was associated with a more homogenous carotid artery wall texture. This is potentially related to arterial remodeling associated with subclinical atherosclerosis and future cardiovascular disease development. These results also indicate that gray-scale texture features from ultrasound imaging had a small but statistically significant association with load-dependent arterial stiffness and that gray-scale texture features may be partially load dependent. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is a dynamic process. There is little evidence regarding whether quantification of atherosclerosis extent and progression, particularly in the carotid artery, in asymptomatic individuals predicts all-cause mortality., Objectives: This study sought to evaluate the independent predictive value (beyond cardiovascular risk factors) of subclinical atherosclerosis burden and progression and all-cause mortality., Methods: A population of 5,716 asymptomatic U.S. adults (mean age 68.9 years, 56.7% female) enrolled between 2008 and 2009 in the BioImage (A Clinical Study of Burden of Atherosclerotic Disease in an At Risk Population) study underwent examination by vascular ultrasound to quantify carotid plaque burden (cPB) (the sum of right and left carotid plaque areas) and by computed tomography for coronary artery calcium (CAC). Follow-up carotid vascular ultrasound was performed on 732 participants a median of 8.9 years after the baseline exam. All participants were followed up for all-cause mortality, the primary outcome. Trend HRs are the per-tertile increase in each variable., Results: Over a median 12.4 years' follow-up, 901 (16%) participants died. After adjustment for cardiovascular risk factors and background medication, baseline cPB and CAC score were both significantly associated with all-cause mortality (fully adjusted trend HR: 1.23; 95% CI: 1.16-1.32; and HR: 1.15; 95% CI: 1.08-1.23), respectively (both P < 0.001), thus providing additional prognostic value. cPB performed better than CAC score. In participants with a second vascular ultrasound evaluation, median cPB progressed from 29.2 to 91.3 mm 3 . cPB progression was significantly associated with all-cause mortality after adjusting for cardiovascular risk factors and baseline cPB (HR: 1.03; 95% CI: 1.01-1.04 per absolute 10-mm 3 change; P = 0.01)., Conclusions: Subclinical atherosclerosis burden (cPB and CAC) in asymptomatic individuals was independently associated with all-cause mortality. Moreover, atherosclerosis progression was independently associated with all-cause mortality., Competing Interests: Funding Support and Author Disclosures The High-Risk Plaque BioImage initiative was a precompetitive industry collaboration funded by BG Medicine, Abbott Vascular, AstraZeneca, Merck & Co., Philips, and Takeda. These funders had no role in the present study. Dr Ibanez was supported by the European Commission (grant numbers H2020-HEALTH 945118 and ERC-CoG 819775), La Caixa Foundation (HR22-00533, DIREQT2Heart), the Spanish Ministry of Science and Innovation (PID2022-140176OB-I00), and the Red Madrileña de Nanomedicina en Imagen Molecular–Comunidad de Madrid (2022/BMD-7403 RENIM-CM). Dr García-Álvarez was supported by the Instituto de Salud Carlos III (PI20/00742 and PI23/01341) and La Fundació la Marató TV3 (202314-30/31). Dr Devesa is an Alfonso Martin Escudero fellow and was scientifically supported by la La Caixa Foundation. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MICIU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIU/AEI/10.13039/501100011033). Dr Sánchez-González is an employee of Philips. Dr Muntendam is CEO of SQ innovation. Philips and SQ innovation had no role in the present study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study investigated the association of American Heart Association's cardiovascular health guidelines Life's Essential 8 (LE8) and Life's Simple 7 (LS7) with carotid artery outcomes among young adults., Methods and Results: This cross-sectional study included 240 young adults (age 24.2±1.6 years) who underwent a carotid ultrasound between 2018 and 2022. LE8 score was calculated from 4 health factors (body mass index, non-high-density lipoprotein cholesterol, fasting glucose, and blood pressure), and 4 health behaviors (dietary intake, physical activity, tobacco use, and sleep). LS7 was calculated from 7 metrics (all LE8 metrics, except for sleep) with a simpler algorithm. Higher LE8 and LS7 scores both indicate better health and better adherence to American Heart Association guidelines. Carotid artery outcomes included carotid artery intima-media thickness, arterial stiffness (eg, distensibility), and echogenicity determined by grayscale median of the intima media complex. Results of linear regression analyses, adjusting for age, sex, ethnicity, and parents' highest degree, indicated that a 1-SD increase in LE8 score was associated with 12.14 μm lower carotid artery intima-media thickness (95% CI, -20.93 to 3.35), 1.17 (10 -6 ×m 2 /N) greater distensibility (95% CI, 0.09-2.24), suggesting less arterial stiffness, and 2.66 μm greater grayscale median of the intima media complex (95% CI, 0.58-4.75), suggesting less lipid deposition. Analyses using LS7 score demonstrated comparable findings. Health factor metrics demonstrated stronger association with carotid artery outcomes, as compared with behavior metrics., Conclusions: Greater adherence to the American Heart Association's cardiovascular health guidelines is associated with lower risk for subclinical atherosclerosis in young adults. LE8 and LS7 demonstrated comparable associations with carotid artery outcomes.

Background and Aims: We aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs)., Methods: A total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32-46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL., Results: 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30-1.36), incidence (1.30-1.32), and progression (1.31-1.35) of coronary artery calcium (CAC) and a 42-44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 μm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures., Conclusions: Among adults aged 32-46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.D.S. is on the scientific advisory boards of Amgen, Agepha, Ionis, New Amsterdam, Novartis, Precision BioScience, and Novo Nordisk, and is a consultant for Ionis, Novartis, Regeneron, Aidoc, and Shanghai Pharma Biotherapeutics. All other authors declare that they have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Effects of more than one-year exposure to air pollution on atherosclerosis is seldom studied. This paper aims to examine the association between five-year exposure to particulate matter ≤2.5 μm (PM2.5), ozone (O3) and atherosclerosis observed about seven years later in late midlife women.Material and Methods: This study was conducted among 1188 women of the Study of Women's Health Across the Nation (SWAN) from five sites, Detroit, MI; Oakland, CA; Pittsburgh, PA; Chicago, IL; and Newark, NJ, with available data on both air pollutant exposure and carotid ultrasound scans. Five-year mean annualized exposure levels of two air pollutants, PM2.5 and ozone (O3), were collected during 5 SWAN visits (1999-2005) from monitors 20 km within the participant's residential address. Linear regression models were used to estimate the association of prior five-year mean annualized exposure to PM2.5 and O3 with common carotid intima-media thickness (cIMT) and inter-adventitial diameter (IAD) examined approximately seven years later (2009-2013). Logistic and multinomial logistic regressions were applied to assess the associations of air pollutants with plaque presence and plaque index, respectively.Results: At time of carotid ultrasound scan, women were on average 59.6 (±2.7) years old and a majority was postmenopausal (88.4%). The women were White (48.4%), Black (31.2%), Chinese (13.3%) and Hispanic (7.1%). A 1 μg/m3 higher 5-year mean annualized exposure to PM2.5 was associated with an 8.0 μm (95% CI: 1.0-15.1) greater maximum cIMT at a later mid-life, adjusting for cardiovascular disease risk factors; but was only related to IAD after adjusting for site. No association was found between either pollutant and plaque presence or plaque index.Conclusions: Long-term exposure to PM2.5 may contribute to elevated risk of atherosclerosis in the post-menopausal period. [ABSTRACT FROM AUTHOR]

Background and Aims: While the association of potato consumption with risk factors for coronary artery disease has been inconsistent, no data are available in the literature on the influence of potato consumption on subclinical disease. Thus, we sought to examine whether baked/mashed potato consumption is associated with calcified atherosclerotic plaques in the coronary arteries., Methods and Results: In a cross-sectional design, we studied 2208 participants of the NHLBI Family Heart Study. These subjects were selected based on their elevated cardiovascular disease risk compared to the general population. Potato consumption was assessed by a semi-quantitative food frequency questionnaire. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age at initial clinic visit was 58.2 years and 55% were female. Median consumption of potatoes was 2-4/week. There was no statistically significant association between frequency of potato consumption and prevalent CAC: odds ratios (95% CI) for CAC were 1.0 (reference), 0.85 (0.56-1.30), 0.85 (0.58-1.26), and 0.95 (0.60-1.53) among subjects reporting potato consumption of <1/week, 1/week, 2-4/week, and 5+/week, respectively (p for linear trend 0.83), adjusting for age, sex, BMI, smoking, exercise, diabetes, hypertension, total calories, prevalent coronary heart disease, income, education, and daily red meat intake., Conclusions: We found no significant association between baked/mashed potato consumption and CAC in older adults., Study Registration Number: NCT00005136. Study registration date: 5/25/2000., Competing Interests: Conflicts of interest Dr. Djousse received investigator-initiated funding from the Alliance of Potato Research and Education (APRE) for a different ongoing project. Other authors declare that they have no conflict of interest., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Introduction: The risk factors for cardiovascular disease (CVD) are associated with coronary atherosclerosis and having multiple risk factors potentiates atherosclerosis. This study examined the prevalence of multiple biological and lifestyle/behavioral risk factors and their association with coronary artery calcium (CAC), a marker for subclinical coronary atherosclerosis.Methods: This is a cross-sectional study of 1607 community-dwelling asymptomatic individuals from central Appalachia who participated in CAC screening between January 2011 and December 2012. Data on demographics (sex and age) and 7 traditional risk factors for coronary artery disease (CAD) were collected and categorized into 5 groups (0-1, 2, 3, 4, and ≥5). Prevalence of these risk factors and CAC scores (0, 1-99, 100-399, ≥400) were assessed, and the impact of the number of risk factors on CAC scores were delineated using multiple logistic regression.Results: Over 98% of participants had ≥1 risk factor. While obesity, diabetes, hypertension, and family history of CAD significantly increased the odds of having CAC, CAC scores significantly increased with number of risk factors. After adjusting for demographic factors, having 3, 4, and ≥5 risk factors was significantly associated with increased odds of having higher CAC scores when compared to zero CAC score by more than one and half times [OR=1.65, CI (1.20-2.25)], two times [OR=2.32, CI (1.67-3.23)] and three times [OR=3.45, CI (2.42-4.92)], respectively.Conclusion: The high prevalence of multiple risk factors in the study population suggests the need for aggressive multiple risk factors interventions for primary prevention of CAD, which could address CVD health disparities. [ABSTRACT FROM AUTHOR]

Central obesity is a known cardiovascular risk factor and measures of visceral obesity are known to predict atherosclerosis. This study sought to explore the association between various anthropometric measures and markers of subclinical atherosclerosis (MoSCA) among low risk healthy individuals. Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of Caucasian (38%), Afro-American (28%), Chinese (22%) and Hispanic (12%) subjects, aged 45–84 years, free from clinical cardiovascular disease. We performed a post hoc analysis of the limited access dataset of MESA subjects to evaluate the association between carotid intima media thickness and coronary artery calcium score (CACS), as MoSCA and various measures of obesity. Multivariable regression analyses adjusted for traditional cardiovascular risk factors, ethnicity and C-reactive protein were performed. Each unit increase in waist–hip ratio was strongly associated with increase in both common and internal carotid intima media thickness (beta: 0.12, 95% confidence interval (CI): 0.06 to 0.18, p < 0.001 and beta: 0.23, 95% CI: 0.03 to 0.43, p = 0.021, respectively). Measures of central obesity were superior to body mass index as demonstrated by their consistent association with each category of CACS when compared to the reference category (CACS = 0). Compared to body mass index, measures of visceral obesity were significantly associated with MoSCA in this multiethnic healthy population. Waist–hip ratio seems to be more consistent in its association with various MoSCA compared to other anthropometric measures. [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: South Asians (individuals from India, Pakistan, Bangladesh, Nepal, and Sri Lanka) have high rates of cardiovascular disease which cannot be explained by traditional risk factors. Few studies have examined coronary artery calcium (CAC) in South Asians. Methods: We created a community-based cohort of South Asians in the United States and compared the prevalence and distribution of CAC to four racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA). We compared 803 asymptomatic South Asians free of cardiovascular disease to the four MESA racial/ethnic groups (2622 Whites, 1893 African Americans, 1496 Latinos and 803 Chinese Americans). Results: The age-adjusted prevalence of any CAC was similar between White and South Asian men, but was lower in South Asian women compared to White women. After adjusting for all covariates associated with CAC, South Asian men were similar to White men and had higher CAC scores compared to African Americans, Latinos and Chinese Americans. In fully adjusted models, CAC scores were similar for South Asian women compared to all women enrolled in MESA. However, South Asian women ≥70 years had a higher prevalence of any CAC than most other racial/ethnic groups. Conclusions: South Asian men have similarly high CAC burden as White men, but higher CAC than other racial/ethnic groups. South Asian women appear to have similar CAC burden compared to other women, but have somewhat higher CAC burden in older age. The high burden of subclinical coronary atherosclerosis in South Asians may partly explain higher rates of cardiovascular disease in South Asians. [Copyright &y& Elsevier]

Abstract: Background: A number of genetic variants have been discovered by recent genome-wide association studies for their associations with clinical coronary heart disease (CHD). However, it is unclear whether these variants are also associated with the development of CHD as measured by subclinical atherosclerosis phenotypes, ankle brachial index (ABI), carotid artery intima-media thickness (cIMT) and carotid plaque. Methods: Ten CHD risk single nucleotide polymorphisms (SNPs) were genotyped in individuals of European American (EA), African American (AA), American Indian (AI), and Mexican American (MA) ancestry in the Population Architecture using Genomics and Epidemiology (PAGE) study. In each individual study, we performed linear or logistic regression to examine population-specific associations between SNPs and ABI, common and internal cIMT, and plaque. The results from individual studies were meta-analyzed using a fixed effect inverse variance weighted model. Results: None of the ten SNPs was significantly associated with ABI and common or internal cIMT, after Bonferroni correction. In the sample of 13,337 EA, 3809 AA, and 5353 AI individuals with carotid plaque measurement, the GCKR SNP rs780094 was significantly associated with the presence of plaque in AI only (OR = 1.32, 95% confidence interval: 1.17, 1.49, P = 1.08 × 10−5), but not in the other populations (P = 0.90 in EA and P = 0.99 in AA). A 9p21 region SNP, rs1333049, was nominally associated with plaque in EA (OR = 1.07, P = 0.02) and in AI (OR = 1.10, P = 0.05). Conclusions: We identified a significant association between rs780094 and plaque in AI populations, which needs to be replicated in future studies. There was little evidence that the index CHD risk variants identified through genome-wide association studies in EA influence the development of CHD through subclinical atherosclerosis as assessed by cIMT and ABI across ancestries. [Copyright &y& Elsevier]

Introduction: South Asians are the second fastest growing ethnic group in the United States and have high rates of cardiovascular disease (CVD) that is not explained by widely known risk factors. Moderate alcohol consumption has been associated with lower risk of CVD in some race/ethnic groups, but the association of alcohol consumption and atherosclerosis in South Asians has not been investigated. Methods: We used data from 906 South Asian participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort. Alcohol consumption was ascertained via questionnaire, coronary artery calcium (CAC) was measured with computed tomography and expressed as Agatston units, and common carotid artery intima-media thickness (cIMT) was measured using B-mode ultrasonography. We used logistic regression models to examine cross-sectional associations of alcohol consumption with CAC prevalence (CAC>0) and used linear regression model for cIMT. Models were adjusted for age, sex, income, and cardiovascular risk factors. Results: The mean age of MASALA participants was 55.3 (±9.4) years, and 46% of participants were women. Family history of MI, mean LDL and HDL concentrations, BMI and use of lipid-lowering medications did not differ by alcohol consumption. Compared with non-drinkers, participants consuming 4-6 drinks/week had statistically significant 48% decreased odds of any CAC prevalence. After adjusting for potential confounders and mediators, participants consuming 4-6 drinks/week showed 58% and 63% decreased CAC prevalence. Alcohol consumption of >7 drinks/week was associated with 0.09 mm (95% CI, 0.02-0.16) increase in common-cIMT compared to no alcohol intake. Conclusion: The association between alcohol intake and subclinical atherosclerosis varied by the amount of intake among South Asians. Long-term follow-up of the MASALA cohort will examine prospective associations of alcohol intake with incident CVD events. [ABSTRACT FROM AUTHOR]

In the absence of clinically recognized cardiovascular disease, increased carotid artery intimal medial thickness was associated with higher hip fracture risk in older adults, despite its association with higher bone mineral density (BMD). Low ankle brachial index and aortic wall thickness were not associated with fracture risk or BMD., Introduction: Clinically recognized cardiovascular disease (CVD) is associated with osteoporosis and hip fracture risk, but the relationship of subclinical atherosclerosis to bone health is not certain., Methods: We followed 3385 participants from the Cardiovascular Health Study (mean age 74.7 ± 5.3 years) with a median time to fracture of 12.1 years who underwent baseline carotid artery and aortic wall ultrasound scanning and ankle brachial blood pressure index (ABI) determinations. A subset underwent bone mineral density (BMD) testing., Results: There were 494 hip fractures during follow-up. Among persons without clinical CVD, an average standard-deviation increase in a composite score of maximal common and internal carotid artery intimal medial thickness (cIMT) was associated with increased risk of hip fracture [(HR 1.18 [1.04, 1.35]), even though cIMT was positively associated with BMD. Neither aortic wall thickness nor ABI were associated with hip fracture risk or BMD. Among participants with clinical CVD, cIMT and aortic wall thickness, but not ABI, were associated with increased hip fracture risk., Conclusion: Subclinical cIMT is associated with an increased risk of hip fractures despite being associated with increased BMD. This finding suggests that vascular health, even in its early stages, is linked to bone health, by pathways other than BMD.

Objective: Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker of early atherosclerosis. Glucocorticoid receptor gene (NR3C1) regulates many biological processes, including stress response, behavioral, cardiometabolic and immunologic functions. Genetic variants in NR3C1 have been associated with atherosclerosis and related risk factors. This study investigated the association of NR3C1 promoter methylation with FMD, independent of genetic and family-level environmental factors., Methods: We studied 84 middle-aged, male-male monozygotic twin pairs recruited from the Vietnam Era Twin Registry. Brachial artery FMD was measured by ultrasound. DNA methylation levels at 22 CpG residues in the NR3C1 exon 1F promoter region were quantified by bisulfite pyrosequencing in genomic DNA isolated from peripheral blood leukocytes. Co-twin control analyses were conducted to examine the association of methylation variation with FMD, adjusting for smoking, physical activity, body mass index, lipids, blood pressure, fasting glucose, and depressive symptoms. Multiple testing was corrected using the false discovery rate., Results: Mean methylation level across the 22 studied CpG sites was 2.02%. Methylation alterations at 12 out of the 22 CpG residues were significantly associated with FMD. On average, a 1% increase in the intra-pair difference in mean DNA methylation was associated with 2.83% increase in the intra-pair difference in FMD (95% CI: 1.46-4.20; P < 0.0001) after adjusting for risk factors and multiple testing., Conclusion: Methylation variation in NR3C1 exon 1F promoter significantly influences subclinical atherosclerosis, independent of genetic, early family environmental and other risk factors., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Pericardial fat and lipoprotein abnormalities contribute to increased risk of cardiovascular disease (CVD). We investigated the relationship between pericardial fat volume and lipoprotein distribution, and whether the association of pericardial fat volume with subclinical atherosclerosis and incident CVD events differs according to lipoprotein distribution., Methods: We analyzed data from 5407 participants from the Multi-Ethnic Study of Atherosclerosis who had measurements of pericardial fat volume, lipoprotein distribution, carotid intima-media thickness (IMT), and coronary artery calcium (CAC). All participants were free of clinically apparent CVD at baseline. Incident CVD was defined as any adjudicated CVD event., Results: After adjusting for demographic factors, traditional risk factors, and biomarkers of inflammation and hemostasis, a larger pericardial fat volume was associated with higher large VLDL particle (VLDL-P) concentration and small HDL particle (HDL-P) concentration, and smaller HDL-P size (regression coefficients = 0.585 nmol/L, 0.366 μmol/L, and -0.025 nm per SD increase in pericardial fat volume respectively, all P < 0.05). The association of pericardial fat volume with large VLDL-P concentration and HDL-P size, but not small HDL-P concentration, remained significant after further adjusting for each other as well as LDL cholesterol, HDL cholesterol, and triglycerides. The relationship of pericardial fat volume with incident CVD events, carotid IMT, and prevalence and severity of CAC did not differ by quartiles of large VLDL-P concentration, small HDL-P concentration, or HDL-P size (P for interaction>0.05)., Conclusion: Pericardial fat is associated with atherogenic lipoprotein abnormalities. However, its relationship with subclinical atherosclerosis and incident CVD events does not differ according to lipoprotein distribution., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Ten-year and lifetime cardiovascular risk assessment algorithms have been adopted into atherosclerotic cardiovascular disease (ASCVD) prevention guidelines, but these prediction models are not based on South Asian populations and may underestimate the risk in Indians, Pakistanis, Bangladeshis, Nepali, and Sri Lankans in the United States. Little is known about ASCVD risk prediction and intermediate endpoints such as subclinical atherosclerosis in US individuals of South Asian ancestry., Methods and Results: South Asians (n=893) from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study who were 40 to 79 years and free of ASCVD were included. Ten-year ASCVD predicted risk was calculated using the 2013 Pooled Cohort Equations. Lifetime predicted risk was based on risk factor burden. Baseline levels of subclinical atherosclerosis (coronary artery calcium [CAC] and carotid intima media thickness [CIMT]) were compared across 10-year and lifetime risk strata: (1) high (≥7.5%) 10-year and low (<7.5%) 10-year risk; (2) high (≥39%) lifetime and low (<39%) lifetime risk. South Asian men and women with high 10-year predicted risk had a significantly greater CAC burden than those with low 10-year risk. South Asians with high lifetime predicted risk had a significantly increased odds for CAC higher than 0 (odds ratio: men 1.97; 95% CI, 1.2 to 3.2; women 3.14; 95% CI, 1.5, 6.6). Associations between risk strata and CIMT were also present., Conclusion: This study is the first to provide evidence that contemporary ASCVD risk assessment algorithms derived from non-Hispanic white and African-American samples can successfully identify substantial differences in atherosclerotic burden in US South Asians., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Increased carotid intima-media thickness (IMT) is associated with subclinical left ventricular myocardial dysfunction, suggesting a possible role of carotid IMT in heart failure (HF) risk determination., Methods and Results: Mean far wall carotid IMT, measured by B-mode ultrasound, was available for 13 590 Atherosclerosis Risk in Communities study participants aged 45 to 64 years and free of HF at baseline. HF was defined using ICD-9 428 and ICD-10 I-50 codes from hospitalization records and death certificates. The association between carotid IMT and incident HF was assessed using Cox proportional hazards analysis with models adjusted for demographic variables, major CVD risk factors, and interim CHD. There were 2008 incident HF cases over a median follow-up of 20.6 years (8.1 cases per 1000 person-years). Mean IMT was higher in those with HF than in those without (0.81 mm ± 0.23 versus 0.71 mm ± 0.17, P<0.001). Unadjusted rate of HF for the fourth compared with the first quartile of IMT was 15.4 versus 3.9 per 1000 person-years; P<0.001. In multivariable analysis, after adjustment, each standard deviation increase in IMT was associated with incident HF (HR 1.20 [95% CI: 1.16 to 1.25]). After adjustment, the top quartile of IMT was associated with HF (HR 1.60 [95% CI: 1.37 to 1.87]). Results were similar across race and gender groups., Conclusions: Increasing carotid IMT is associated with incident HF in middle-aged whites and blacks, beyond risks explained by major CVD risk factors and CHD. This suggests that carotid IMT may be associated with HF through mechanisms different from myocardial ischemia or infarction.

Background: Single nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3 (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT) in HIV-infected men. We evaluated SNPs in the RYR3 gene among HIV-infected women participating in Women's Interagency HIV Study (WIHS)., Methods: CCA cIMT was measured using B-mode ultrasound and the 838 SNPs in the RYR3 gene region were genotyped using the Illumina HumanOmni2.5-quad beadchip. The CCA cIMT genetic association was assessed using linear regression analyses among 1213 women and also separately among White (n=139), Black (n=720) and Hispanic (n=354) women after adjusting for confounders. A summary measure of pooled association was estimated using a meta-analytic approach by combining the effect estimates from the three races. Haploblocks were inferred using Gabriel's method and haplotype association analyses were conducted among the three races separately., Results: SNP rs62012610 was associated with CCA cIMT among the Hispanics (p=4.41×10(-5)), rs11856930 among Whites (p=5.62×10(-4)), and rs2572204 among Blacks (p=2.45×10(-3)). Meta-analysis revealed several associations of SNPs in the same direction and of similar magnitude, particularly among Blacks and Hispanics. Additionally, several haplotypes within three haploblocks containing SNPs previously related with CCA cIMT were also associated in Whites and Hispanics., Discussion: Consistent with previous research among HIV-infected men, SNPs within the RYR3 region were associated with subclinical atherosclerosis among HIV-infected women. Allelic heterogeneity observed across the three races suggests that the contribution of the RYR3 gene to CCA cIMT is complex, and warrants future studies to better understand regional SNP function., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study examines whether the coronary artery calcium (CAC) score can be used to define the target population to treat with a polypill., Background: Prior studies have suggested a single polypill to reduce cardiovascular disease (CVD) at the population level., Methods: Participants from MESA (Multi-Ethnic Study of Atherosclerosis) were stratified using the criteria of 4 polypill studies (TIPS [The Indian Polycap Study], Poly-Iran, Wald, and the PILL [Program to Improve Life and Longevity] Collaboration). We compared coronary heart disease (CHD) and CVD event rates and calculated the 5-year number needed to treat (NNT) after stratification based on the CAC score., Results: Among MESA participants eligible for TIPS, Poly-Iran, Wald, and the PILL Collaboration, CAC = 0 was observed in 58.6%, 54.5%, 38.9%, and 40.8%, respectively. The rate of CHD events among those with CAC = 0 varied from 1.2 to 1.9 events per 1,000 person-years, those with CAC scores from 1 to 100 had event rates ranging from 4.1 to 5.5, and in those with CAC scores >100 the event rate ranged from 11.6 to 13.3. The estimated 5-year NNT to prevent 1 CVD event ranged from 81-130 for patients with CAC = 0, 38-54 for those with CAC scores from 1 to 100, and 18-20 for those with CAC scores >100., Conclusions: In MESA, among individuals eligible for treatment with the polypill, the majority of CHD and CVD events occurred in those with CAC scores >100. The group with CAC = 0 had a very low event rate and a high projected NNT. The avoidance of treatment in individuals with CAC = 0 could allow for significant reductions in the population considered for treatment, with a more selective use of the polypill and, as a result, avoidance of treatment in those who are unlikely to benefit., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)