Search

AimsPatients with a low lifetime risk of coronary heart disease (CHD) are not completely free of events over 10 years. We evaluated predictors for CHD among "low lifetime risk" participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA).MethodsMESA enrolled 6814 men and women aged 45-84 years who were free of baseline cardiovascular disease. Using established criteria of non-diabetic, non-smokers with total cholesterol ≤ 200 mg/dL, systolic BP ≤ 139 mmHg, and diastolic BP ≤ 89 mmHg at baseline, we identified 1391 participants with a low lifetime risk for cardiovascular disease. Baseline covariates were age, gender, ethnicity, HDL-C, C-reactive protein, family history of CHD, carotid intima-media thickness and coronary artery calcium (CAC). We calculated event rates and the number needed to scan (NNS) to identify one participant with CAC>0 and > 100.ResultsOver 10.4 years median follow-up, there were 33 events (2.4%) in participants with low lifetime risk. There were 479 participants (34%) with CAC>0 including 183 (13%) with CAC>100. CAC was present in 25 (76%) participants who experienced an event. In multivariable analyses, only CAC>100 remained predictive of CHD (HR 4.6; 95% CI: 1.6-13.6; p = 0.005). The event rates for CAC = 0, CAC>0 and CAC>100 were 0.9/1,000, 5.7/1,000, and 11.0/1000 person-years, respectively. The NNS to identify one participant with CAC>0 and > 100 were 3 and 7.6, respectively.ConclusionsWhile 10-year event rates were low in those with low lifetime risk, CAC was the strongest predictor of incident CHD. Identification of individuals with CAC = 0 and CAC>100 carries significant potential therapeutic implications.

ObjectiveMinimal data are available regarding the long-term mortality risk of subclinical atherosclerosis using coronary artery calcium (CAC) scoring among patients with a family history (FH) of coronary artery disease (CAD). The aim of the present analysis was to assess the prognostic utility of CAC scoring among cohorts of young and older patients with and without a FH of CAD.MethodsA total of 9715 consecutive asymptomatic patients, free of known CAD, underwent CAC scoring for cardiovascular risk assessment. The primary end point was all-cause mortality, with a median follow-up of 14.6 years. Unadjusted and risk-factor adjusted Cox proportional hazard modelling was employed. We calculated the area under the curve (AUC) from receiver operating characteristics analysis.Results15-year all-cause mortality rates ranged from 4.7% to 25.0% for FH patients and from 5.0% to 38.0% for non-FH patients with CAC scores of 0 to >400 (p60 years with FH of CAD, there was a significant improvement in the AUC with CAC over CAD risk factors (AUC: 0.539 vs 0.725, p

ObjectivesThis study sought to determine the predictors of healthy arterial aging.BackgroundLong-term nondevelopment of coronary artery calcification (persistent CAC = 0) is a marker of healthy arterial aging. The predictors of this phenotype are not known.MethodsWe analyzed 1,850 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with baseline CAC = 0 who underwent a follow-up CAC scan at visit 5 (median 9.6 years after baseline). We examined the proportion with persistent CAC = 0 and calculated multivariable relative risks and area under the receiver operating characteristic curve for prediction of this healthy arterial aging phenotype.ResultsWe found that 55% of participants (n = 1,000) had persistent CAC = 0, and these individuals were significantly more likely to be younger, female, and have fewer traditional risk factors (RF). Participants with an ASCVD (Atherosclerotic Cardiovascular Disease Risk Score) risk score

BackgroundThe American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines have significantly broadened the scope of candidates eligible for statin therapy.ObjectivesThis study evaluated the implications of the absence of coronary artery calcium (CAC) in reclassifying patients from a risk stratum in which statins are recommended to one in which they are not.MethodsMESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6,814 men and women 45 to 84 years of age without clinical atherosclerotic cardiovascular disease (ASCVD) risk at enrollment. We excluded 1,100 participants (16%) on lipid-lowering medication, 87 (1.3%) without low-density lipoprotein levels, 26 (0.4%) with missing risk factors for calculation of 10-year risk of ASCVD, 633 (9%) >75 years of age, and 209 (3%) with low-density lipoprotein

BackgroundSeveral studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed.ObjectivesThe goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors.MethodsAlgorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study).ResultsInclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell's C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate.ConclusionsAn accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.

BackgroundCardiovascular calcification outside of the coronary tree, known as extracoronary calcification (ECC), is highly prevalent, often occurs concurrently in multiple sites, and yet its prognostic value is unclear.ObjectiveTo determine whether multisite ECC is associated with coronary heart disease (CHD) events, CHD mortality, and all-cause mortality.MethodsWe evaluated 5903 participants from the Multi-Ethnic Study of Atherosclerosis without diabetes who underwent CT imaging for calcification of the aortic valve, aortic root, mitral valve, and thoracic aorta. Participants were followed for 10.3 years. Multivariable adjusted hazard ratios estimated risk of outcomes for increasing numbers of ECC sites (0, 1, 2, 3, and 4), and receiver operator characteristic analysis assessed model discrimination.ResultsPrevalence of any ECC was 45%; median age was 62 years. Compared with those without ECC, those with ECC in 4 sites had increased hazards of 4.5, 7.1 and 2.3 for CHD events, CHD mortality, and all-cause mortality, respectively, independent of traditional risk factors (TRF; all P ≤ .05), and had ≥2-fold increased hazards for outcomes independent of coronary artery calcification (CAC). Each additional site of ECC was positively associated with each outcome in a graded fashion. When added to TRF, ECC significantly increased the area under the receiver operator characteristic curve for all outcomes and modestly increased the area under the curve for mortality beyond TRF + CAC (0.799 to 0.802; P = .03).ConclusionIncreasing multisite ECC has a graded association with higher CHD and mortality risk, contributing information beyond TRF. Multisite ECC incidentally identified on imaging can be used to improve individualized risk prediction.

BackgroundCoronary artery calcium (CAC) detected by noncontrast cardiac computed tomography scanning is a measure of coronary atherosclerosis burden. Increasing CAC levels have been strongly associated with increased coronary events. Prior studies of cardiovascular disease risk factors and CAC progression have been limited by short follow-up or restricted to patients with advanced disease.Methods and resultsWe examined cardiovascular disease risk factors and CAC progression in a prospective multiethnic cohort study. CAC was measured 1 to 4 times (mean 2.5 scans) over 10 years in 6810 adults without preexisting cardiovascular disease. Mean CAC progression was 23.9 Agatston units/year. An innovative application of mixed-effects models investigated associations between cardiovascular disease risk factors and CAC progression. This approach adjusted for time-varying factors, was flexible with respect to follow-up time and number of observations per participant, and allowed simultaneous control of factors associated with both baseline CAC and CAC progression. Models included age, sex, study site, scanner type, and race/ethnicity. Associations were observed between CAC progression and age (14.2 Agatston units/year per 10 years [95% CI 13.0 to 15.5]), male sex (17.8 Agatston units/year [95% CI 15.3 to 20.3]), hypertension (13.8 Agatston units/year [95% CI 11.2 to 16.5]), diabetes (31.3 Agatston units/year [95% CI 27.4 to 35.3]), and other factors.ConclusionsCAC progression analyzed over 10 years of follow-up, with a novel analytical approach, demonstrated strong relationships with risk factors for incident cardiovascular events. Longitudinal CAC progression analyzed in this framework can be used to evaluate novel cardiovascular risk factors.

We hypothesized that anthropometric measures of abdominal obesity would have a stronger positive association with nonalcoholic fatty liver disease (NAFLD) measured by noncontrast computed tomography versus general measures of obesity. The Multiethnic Study of Atherosclerosis comprised participants aged 45 to 84 years free of known cardiovascular disease. We studied 4,088 participants with adequate liver and spleen computed tomography imaging and no previous use of oral steroids, class 3 antiarrhythmics, moderately heavy alcohol use, or cirrhosis. Prevalent NAFLD was defined as a liver:spleen Hounsfield attenuation ratio of

BackgroundThe transition from no coronary artery calcium (CAC) to detectable CAC is important, as even mild CAC is associated with increased cardiovascular events. We sought to characterize the anatomic distribution and burden of newly detectable CAC over 10-year follow-up.MethodsWe evaluated 3112 participants (mean age, 58 years; 64% female) with baseline CAC = 0 from the Multi-Ethnic Study of Atherosclerosis. Participants underwent repeat CAC testing at different time intervals (between 2-10 years after baseline) per the Multi-Ethnic Study of Atherosclerosis protocol. Among participants who developed CAC on a follow-up scan, we used logistic regression and marginal probability modeling to describe the coronary distribution and burden of new CAC by age, sex, and race after adjustment for cardiovascular risk factors and time to detection.ResultsA total of 1125 participants developed detectable CAC during follow-up with a mean time to detection of 6.1 ± 3 years. New CAC was most commonly isolated to 1 vessel (72% of participants), with the left anterior descending artery (44% of total) most commonly affected followed by the right coronary (12%), left circumflex (10%), and left main (6%). These patterns were similar across age, sex, and race. In multivariate models, residual predictors of multivessel CAC (28% of total) included male sex, African American or Hispanic race, hypertension, obesity, and diabetes. At the first detection of CAC >0, burden was usually low with median Agatston CAC score of 7.1 and 100.ConclusionNew-onset CAC most commonly involves just 1 vessel, occurs in the left anterior descending artery, and has low CAC burden. New CAC can be detected at an early stage when aggressive preventive strategies may provide benefit.

BackgroundThe prognostic value of coronary artery calcium (CAC) or carotid intima-media thickness (CIMT) among asymptomatic adults with a family history (FH) of premature coronary heart disease is unclear.Methods and resultsMultiethnic Study of Atherosclerosis enrolled 6814 adults without known atherosclerotic cardiovascular disease (ASCVD). Hard ASCVD events were ascertained over a median follow-up of 10.2 years. We estimated adjusted-hazard ratios for CAC and CIMT categories using Cox regression, both within and across FH status groups. Improvement in discrimination with CAC or CIMT added to variables from the ASCVD pooled cohort equation was also evaluated using receiver-operating characteristic curve and likelihood ratio analysis. Of 6125 individuals (62±10 years; 47% men) who reported information on FH, 1262 (21%) had an FH of premature coronary heart disease. Among these, 104 hard ASCVD events occurred. Crude incidence rates (per 1000 person-years) for hard ASCVD were 4.4 for CAC, 0 (n=574; 46% of the sample); 8.8 for CAC, 1 to 99 (n=368); 14.9 for CAC, 100 to 399 (n=178); and 20.8 for CAC, ≥400 (n=142). Relative to CAC=0, adjusted hard ASCVD hazard ratios for each CAC category among persons with an FH were 1.64 (95% confidence interval, 0.94-2.87), 2.45 (1.31-4.58), and 2.80 (1.44-5.43), respectively. However, there was no increased adjusted hazard for hard ASCVD in high versus low CIMT categories. In participants with an FH of premature coronary heart disease, CAC improved discrimination of hard ASCVD events (P

Although the traditional Agatston coronary artery calcium (CAC) score is a powerful predictor of mortality, it is unknown if the regional distribution of CAC further improves cardiovascular risk prediction. We retrospectively studied 23,058 patients referred for Agatston CAC scoring, of whom 61% had CAC (n=14,084). CAC distribution was defined as the number of vessels with CAC (0 to 4, including left main). For multivessel CAC, "diffuse" CAC was defined by decreasing percentage of CAC in the single most affected vessel and by ≤75% total Agatston CAC score in the most calcified vessel. All-cause mortality was ascertained through the social security death index. The mean age was 55±11 years, with 69% men. There were 584 deaths (2.5%) over 6.6±1.7 years. Considerable heterogeneity existed between the Agatston CAC score group and the number of vessels with CAC. In each CAC group, increasing number of vessels with CAC was associated with an increased mortality rate. After adjusting for age, gender, Agatston CAC score, and cardiovascular risk factors, increasing number of vessels with CAC was associated with higher mortality risk compared with single-vessel CAC (2-vessel: HR 1.61 [95% CI 1.14 to 2.25], 3-vessel: 1.99 [1.44 to 2.77], and 4-vessel: 2.22 [1.53 to 3.23]). "Diffuse" CAC was associated with a higher mortality rate in the CAC 101 to 400 and >400 groups. Left main CAC was associated with increased mortality risk. In conclusion, increasing number of vessels with CAC and left main CAC predict increased all-cause mortality and improve the prognostic power of the traditional Agatston CAC score.

BackgroundCoronary artery calcium (CAC) is strongly predictive of all-cause mortality in intermediate-risk groups, but this relationship is not well defined in very low-risk individuals. We investigated the relationship between CAC scoring and the long-term all-cause mortality among patients with ≤ 1 cardiovascular disease (CVD) risk factor.MethodsWe analyzed a retrospective cohort of 5584 asymptomatic patients with no known CVD (mean 56.6 ± 11.6 years, 69%men) and ≤ 1 risk factor who were physician referred for a CAC scan. Mortality was ascertained through linkage with the Social Security Death Index. We calculated the prevalence of CAC stratified by age and risk factors. We also examined the association between CAC and mortality using multivariable Cox Proportional hazards models.ResultsDuring a mean follow-up of 10.4 ± 3.1 years, 168 individuals (3.0%) died. Overall, 54.5% of patients had a CAC >0 and 9.8% had CAC ≥ 400. There was a greater risk of mortality with increasing CAC 1-99 (HR 1.9, 95% CI 1.2-3.1), 100-399 (HR 2.1, 95% CI 1.2-3.6) and ≥ 400 (HR 2.8, 95% CI 1.6-4.8) compared to CAC=0 (p

ObjectiveWe sought to assess the impact of smoking status, cumulative pack-years, and time since cessation (the latter in former smokers only) on 3 important domains of cardiovascular disease: inflammation, vascular dynamics and function, and subclinical atherosclerosis.Approach and resultsThe Multi-Ethnic Study of Atherosclerosis (MESA) cohort enrolled 6814 adults without prior cardiovascular disease. Smoking variables were determined by self-report and confirmed with urinary cotinine. We examined cross-sectional associations between smoking parameters and (1) inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], interleukin-6, and fibrinogen); (2) vascular dynamics and function (brachial flow-mediated dilation and carotid distensibility by ultrasound, as well as aortic distensibility by MRI); and (3) subclinical atherosclerosis (coronary artery calcification, carotid intima-media thickness, and ankle-brachial index). We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Mean age was 62 years and 47% were male. There was no consistent association between smoking and vascular distensibility or flow-mediated dilation outcomes. However, compared with never smokers, the adjusted association between current smoking and measures of either inflammation or subclinical atherosclerosis was consistently stronger than for former smoking (eg, odds ratio for hsCRP>2 mg/L of 1.7 [95% confidence interval, 1.5-2.1] versus 1.2 [1.1-1.4], odds ratio for coronary artery calcification>0 of 1.8 [1.5-2.1] versus 1.4 [1.2-1.6], respectively). Similar associations were seen for interleukin-6, fibrinogen, carotid intima-media thickness, and ankle-brachial index. A monotonic association was also found between higher pack-year quartiles and increasing inflammatory markers. Furthermore, current smokers with hsCRP>2 mg/L were more likely to have increased carotid intima-media thickness, abnormal ankle-brachial index, and coronary artery calcification>75th percentile for age, sex, and race (relative to smokers with hsCRP2 mg/L of 0.91 [0.88-0.95] and odds ratio for coronary artery calcification>0 of 0.94 [0.90-0.97] for every 5-year cessation interval).ConclusionsThese findings expand our understanding of the harmful effects of smoking and help explain the cardiovascular benefits of smoking cessation.

IntroductionWe characterized the association of 3 metabolic conditions - obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) - with increased inflammation and subclinical atherosclerosis.MethodsWe conducted cross-sectional analysis of 3976 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with adequate CT imaging to diagnose NAFLD. Obesity was defined as BMI ≥ 30 kg/m(2), metabolic syndrome by AHA/NHLBI criteria, and NAFLD using non-contrast cardiac CT and a liver/spleen attenuation ratio (L/S)  0. We studied the association of a stepwise increase in number of these metabolic conditions (0-3) with increased inflammation and CAC, stratifying results by gender and ethnicity.ResultsMean age of participants was 63 (±10) years, 45% were male, 37% white, 10% Chinese, 30% African American, and 23% were Hispanic. Adjusting for obesity, metabolic syndrome and traditional risk factors, NAFLD was associated with a prevalence odds ratio for hsCRP ≥2 mg/L and CAC >0 of 1.47 (1.20-1.79) and 1.37 (1.11-1.68) respectively. There was a positive interaction between female gender and NAFLD in the association with hsCRP ≥2 mg/L (p = 0.006), with no interaction by race. With increasing number of metabolic conditions, there was a graded increase in prevalence odds ratios of hsCRP ≥2 mg/L and CAC >0.ConclusionNAFLD is associated with increased inflammation and CAC independent of traditional risk factors, obesity and metabolic syndrome. There is a graded association between obesity, metabolic syndrome, and NAFLD with inflammation and CAC.

ObjectiveTo describe the relationship between circulating resistin levels and cardiovascular diseases (CVD) and all-cause death in a multi-ethnic cohort.Methods and resultsWe studied 1913 participants from the Multi-Ethnic Study of Atherosclerosis with measurements of plasma resistin levels. Absolute proportions experiencing new-onset atrial fibrillation (AF), atherosclerotic CVD (myocardial infarction, angina, resuscitated cardiac arrest, stroke), heart failure (HF), and all-cause death were calculated for each quartile of resistin. We used adjusted Cox proportional regression modeling resistin as a continuous variable per standard deviation of log-transformed resistin and secondarily as a categorical variable using resistin quartiles. Results were stratified by sex and race/ethnicity. The mean age of the population was 64.5 ± 10 years with half being female and a median resistin concentration of 15.1 ng/mL (11.9-19.1). Mean follow-up time was 7.2 ± 1.8 years. There was a graded increase in the occurrence of all outcomes across increasing quartiles of resistin. Modeled as a continuous variable, after adjustment for anthropomorphic measures, traditional risk factors, markers of inflammation, and other adipokines, significant associations were noted for HF (HR 1.4, CI 1.0-2.0), hard and all CVD (HR 1.3, 1.1-1.7 and 1.3, 1.1-1.6, respectively), and CHD (HR 1.31, 1.0-1.6), but not for AF or death. Significant interaction terms were noted between resistin and race, with Hispanic race/ethnicity showing the strongest relationship between resistin and outcomes.ConclusionsIn an ethnically diverse population without known CVD at baseline, there was a strong, independent association between higher resistin levels and incident CVD, CHD and HF.

ObjectivesTo examine the contemporary effect of smoking in a multiethnic sample, and to explore the respective contributions of inflammation and subclinical atherosclerosis to the cardiovascular consequences of smoking.Approach and resultsWe studied 6814 participants free of cardiovascular disease and coronary heart disease (CHD) from the Multiethnic Study of Atherosclerosis. Smoking status and cumulative exposure were determined by self-report and confirmed by urinary cotinine. Multivariable Cox regression was used to estimate the association between smoking parameters and all-cause cardiovascular disease, all-cause CHD, and hard CHD events. We further adjusted for high-sensitivity C-reactive protein and coronary artery calcium (CAC) in hierarchical Cox models. We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Median follow-up was 10.2 years. Compared with never smokers, adjusted hazard ratios in current smokers were 1.7 (95% confidence interval, 1.3-2.2) for all-cause cardiovascular disease, 1.6 (1.1-2.1) for all-cause CHD, and 1.7 (1.2-2.4) for hard CHD. Similarly, among current smokers, hazard ratios were higher in the 4th versus 1st quartile of pack-years (eg, all-cause CHD hazard ratio=2.7 [1.1-6.6]). Both CAC>100 and high-sensitivity C-reactive protein ≥3 mg/L identified higher relative risk among current smokers (eg, all-cause CHD hazard ratio of 3.0 [1.5-6.0, compared with CAC=0] and 2.6 [1.4-4.8, compared with high-sensitivity C-reactive protein 100 identified high-risk smokers who may benefit from more intensive smoking-cessation efforts.

ObjectiveHigher serum leptin levels have been associated with a modestly higher incidence of cardiovascular disease in studies involving mostly Caucasian men. We aimed to assess the hypothesis that higher baseline levels of serum leptin are associated with higher risk of future cardiovascular disease in a diverse cohort.MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a modern, community-based, ethnically-diverse, and sex-balanced prospective cohort study of US adults free from cardiovascular disease. Serum leptin was measured in an ancillary study in 2002-2005. This analysis included 1905 MESA participants with baseline leptin and incident cardiovascular event data. Leptin levels were modeled as a log-transformed continuous variable and multivariable-adjusted Cox regression was performed for the primary outcome of hard cardiovascular disease, including coronary heart disease and stroke.ResultsThe median follow-up was 7.6 years (25th-75th 7.1-8.3) with 7051 and 6738 person-years of follow-up in women and men. A hard cardiovascular disease event occurred in 47 women and 63 men. The age- and ethnicity-adjusted hazard ratio estimates for a 1 standard deviation increase in ln(leptin) were 1.16 in women (95% CI 0.78-1.73, p = 0.46) and 0.91 (95% CI 0.69-1.20, p = 0.51) in men. Pooling sexes, and adjusting for sex in addition to age and ethnicity, estimates were 0.98 (95% CI 0.78-1.23, p = 0.89). With additional adjustment for cardiovascular risk factors, the results remained nonsignificant: 0.87 (95% CI 0.68-1.11, p = 0.26).ConclusionIn conclusion, in a modern, US prospective cohort study of multi-ethnic women and men of multi-ethnic backgrounds, leptin levels are not associated with incident cardiovascular events.

BackgroundAccurate risk assessment of atherosclerotic cardiovascular disease (ASCVD) is essential to effectively balance the risks and benefits of therapy for primary prevention.ObjectiveTo compare the calibration and discrimination of the new American Heart Association (AHA) and American College of Cardiology (ACC) ASCVD risk score with alternative risk scores and to explore preventive therapy as a cause of the reported risk overestimation using the AHA-ACC-ASCVD score.DesignProspective epidemiologic study of ASCVD.SettingMESA (Multi-Ethnic Study of Atherosclerosis), a community-based, sex-balanced, multiethnic cohort.Patients4227 MESA participants aged 50 to 74 years and without diabetes at baseline.MeasurementsObserved and expected events for the AHA-ACC-ASCVD score were compared with 4 commonly used risk scores-and their respective end points-in MESA after a 10.2-year follow-up.ResultsThe new AHA-ACC-ASCVD and 3 older Framingham-based risk scores overestimated cardiovascular events by 37% to 154% in men and 8% to 67% in women. Overestimation was noted throughout the continuum of risk. In contrast, the Reynolds Risk Score overestimated risk by 9% in men but underestimated risk by 21% in women. Aspirin, lipid-lowering or antihypertensive therapy, and interim revascularization did not explain the overestimation.LimitationComparability of MESA with target populations for primary prevention and possibility of missed events in MESA.ConclusionOf the 5 risk scores, 4, including the new AHA-ACC-ASCVD score, showed overestimation of risk (25% to 115%) in a modern, multiethnic cohort without baseline clinical ASCVD. If validated, overestimation of ASCVD risk may have substantial implications for individual patients and the health care system.Primary funding sourceNational Heart, Lung, and Blood Institute.

Presence of coronary artery calcium (CAC), carotid plaque, and increased carotid intima-media thickness (IMT) may indicate elevated cardiovascular disease (CVD) risk; however, no large studies have compared them directly. This study compares predictive uses of CAC presence, carotid artery plaque presence, and high IMT for incident CVD events. Participants were from the Multi-Ethnic Study of Atherosclerosis (MESA). Predictive values of carotid plaque, IMT, and CAC presence were compared using Cox proportional hazards models, c-statistics, and net reclassification indices. The 6779 participants were mean (SD) 62.2 (10.2) years old; 49.9% had CAC, and 46.7% had carotid plaque. The mean left and right IMT were 0.754 (0.210) mm and 0.751 (0.187) mm, respectively. After 9.5 years (mean), 538 CVD events, 388 coronary heart disease (CHD) events, and 196 stroke/transient ischemic attacks were observed. CAC presence was a stronger predictor of incident CVD and CHD than carotid ultrasound measures. Mean IMT≥75th percentile (for age, sex, and race) alone did not predict events. Compared with traditional risk factors, c-statistics for CVD (c=0.756) and CHD (c=0.752) increased the most by the addition of CAC presence (CVD, 0.776; CHD, 0.784; P

BackgroundThe Multi-Ethnic Study of Atherosclerosis (MESA) showed that the addition of coronary artery calcium (CAC) to traditional risk factors improves risk classification, particularly in intermediate risk asymptomatic patients with LDL cholesterol levels

BackgroundA subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population.MethodsPubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or subclinical CVD.ResultsA total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define "metabolically healthy", while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study (14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts.ConclusionsMHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.