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BackgroundUrinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis.MethodsUrinary levels of 8-isoprostane and 2,3-dinor-8-F2-isoprostane were measured in 1089 participants (mean±SD 62±8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors.ResultsIn adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F2-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline.ConclusionsHigher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD.Trial registrationThe MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.

Objectives This study assessed the association of diabetes duration with incident heart failure (HF). Background Diabetes increases HF risk. However, the independent effect of diabetes duration on incident HF is unknown. Methods We included 9,734 participants (mean age 63 years, 58% women, 22% Black) at ARIC (Atherosclerosis Risk In Communities) Visit 4 (1996-1998) without HF or coronary heart disease. We calculated diabetes duration at Visit 4 (baseline), utilizing diabetes status at the first 4 ARIC visits spaced 3 years apart, and self-reported diagnosis date for those with diabetes diagnosed before Visit 1. We used Cox regression to estimate associations of diabetes duration with incident HF, accounting for intercurrent coronary heart disease and other risk factors. We performed analyses stratified by age ( Results Over 22.5 years of follow-up, there were 1,968 HF events. Compared to those without diabetes, HF risk rose with longer diabetes duration, with the highest risk among those with ≥15 y diabetes duration (HR: 2.82; 95% CI: 2.25-3.63). Each 5-year increase in diabetes duration was associated with a 17% (95% CI: 11-22) relative increase in HF risk. Similar results were observed across HF subtypes. The HF and diabetes duration associations were stronger among those aged Conclusions Delaying diabetes onset may augment HF prevention efforts, and therapies to improve HF outcomes might target those with long diabetes duration.

Background Lower exercise capacity, as measured by 6-minute walk distance (6MWD), is associated with incident heart failure (HF). Among those without HF, the associations of measures of cardiac function with 6MWD are unclear, and may provide insight regarding the risk of incident HF. Objectives The purpose of this study was to understand the relationships between cardiac function and exercise capacity. Methods This study evaluated the associations of cardiac mechanics with 6MWD in the sixth examination of the Multi-Ethnic Study of Atherosclerosis. Echocardiography (2-dimensional, Doppler, and speckle-tracking) was performed at rest and after passive leg raise to evaluate functional reserve after intravascular volume challenge. Results Of 2,096 participants without HF (mean age 73 years, 48% men, 58% non-White), individuals with lower (worse) left atrial (LA) reservoir strain were older and had higher blood pressure. Lower resting LA reservoir strain (β coefficient per SD decrease: −5.0; 95% confidence interval [CI]: −8.8 to −1.3 m; p = 0.009), inability to augment LA reservoir strain after passive leg raise (β coefficient per SD decrease: −5.8; 95% CI: −9.1 to −2.5 m; p Conclusions Among individuals without HF, worse biatrial function, lack of LA functional reserve, and worse LV diastolic function were associated with reduced submaximal exercise capacity. Therapies aimed to improve these functional domains may increase exercise capacity and prevent HF.

The 2017 American blood pressure (BP) guidelines recommended a personalized risk-based approach to treatment in stage 1 hypertension. We sought to establish the utility of coronary artery or thoracic aortic calcium (CAC or TAC) as additional risk modifiers in this setting. We included 1859 Multiethnic Study of Atherosclerosis participants with stage 1 hypertension. We compared adjusted HR for the composite outcome of incident atherosclerotic cardiovascular disease or heart failure across predefined categories of either CAC or TAC (0, 1 to 100, or >100) in: (1) the full sample; (2) 4 high-risk subgroups recommended for pharmacotherapy to a BP goal 100. CAC >100 was independently associated with a higher relative risk of events compared with CAC = 0 (e.g., adjusted HR [9.5 (1.8 to 18.7)] in the low-risk subgroup). NNT10 for CAC = 0 were 3 to 5 times higher than those for CAC >100 in all analyses. TAC was not a reliable risk modifier in our study. In conclusion, CAC, but not TAC, can further guide risk-based allocation of treatment in stage 1 hypertension and should be considered as a risk modifier in future guidelines.

Background The purpose of this study is to determine if a new score calculated with coronary artery calcium (CAC) density and volume is associated with total coronary artery plaque burden and composition on coronary CT angiography (CCTA) compared to the Agatston score (AS). Methods We identified 347 men enrolled in the Multicenter AIDS cohort study who underwent contrast and non-contrast CCTs, and had CAC>0. CAC densities (mean Hounsfield Units [HU]) per plaque) and volumes on non-contrast CCT were measured. A Density-Volume Calcium score was calculated by multiplying the plaque volume by a factor based on the mean HU of the plaque (4, 3, 2 and 1 for 130–199, 200–299, 300–399, and ≥400HU). Total Density-Volume Calcium score was determined by the sum of these individual scores. The semi-quantitative partially calcified and total plaque scores (PCPS and TPS) on CCTA were calculated. The associations between Density-Volume Calcium score, PCPS and TPS were examined. Results Overall, 2879 CAC plaques were assessed. Multivariable linear regression models demonstrated a stronger association between the log Density-Volume Calcium score and both the PCPS (β 0.99, 95%CI 0.80–1.19) and TPS (β 2.15, 95%CI 1.88–2.42) compared to the log of AS (PCPS: β 0.77, 95%CI 0.61–0.94; TPS: β 1.70, 95%CI 1.48–1.94). Similar results were observed for numbers of PC or TP segments. Conclusion The new CAC score weighted towards lower density demonstrated improved correlation with semi-quantitative PC and TP burden on CCTA compared to the traditional AS, which suggests it has utility as an alternative measure of atherosclerotic burden.

Longitudinal trajectories of cardiovascular health (CVH) may reflect vascular risk burden due to prolonged cumulative exposure to non-ideal CVH levels. Identifying individuals who have a higher risk CVH trajectory may facilitate treatment, screening, and prevention. We aimed to characterize 10-year trajectories of CVH and examine the associations between CVH trajectories and subsequent cardiovascular disease (CVD) and mortality.We analyzed 3674 MESA participants who completed four exams and remained CVD-free from 2000 to 2011. A 12-point CVH score was calculated based on physical activity, smoking status, body mass index, cholesterol, blood pressure, and glucose. Ideal CVH was defined as a score ≥ 9. Group-based trajectory modeling was used to identify trajectories of ideal CVH. Cox models were used to examine the association of CVH trajectories with incident CVD and death from 2011 to 2018, adjusting for age, sex, race/ethnicity, income, education, and marital status.Three trajectories were identified based on the probability of achieving ideal CVH: high (Persistently nonideal CVH is a common trajectory. Targeted prevention programs might benefit individuals with persistently nonideal CVH given their elevated risk of subsequent CVD and mortality.

Background Sex differences in the incidence and manifestation of cardiovascular disease (CVD) suggest the involvement of sex hormones in disease pathogenesis. Coronary artery calcium (CAC) and its progression, measured by non-contrast cardiac computed tomography, are markers of subclinical atherosclerosis and predict CVD, even among low-risk women. We hypothesized that sex hormone levels were associated with CAC progression among women in the Multi-Ethnic Study of Atherosclerosis. Methods We studied 2759 post-menopausal women (age 65 ± 9 years), free of baseline CVD, with baseline serum sex hormones and CAC measured at Exam 1 (2000–2002). Of this sample, 2427 had ≥1 follow-up CAC measurement through Exam 5 (2010–2012). Using mixed effects linear regression methods, we tested change in log[CAC+1] score by log[sex hormone] levels (continuous, comparing the 90th versus 10th percentiles). Models adjusted for demographics, lifestyle factors, cardiovascular risk factors, hormone therapy, and years since menopause. Results At baseline, we found no associations between sex hormones and prevalent CAC. Over a median of 4.7 years, in fully-adjusted models, women with higher free testosterone levels had relatively greater CAC progression [Ratio 1.26 (95% CI 1.01–1.56)], whereas higher sex hormone binding globulin (SHBG) was associated with lower progression risk [0.80 (0.64–0.99). No associations were seen for total testosterone, estradiol, or dehydroepiandrosterone. Conclusion A more androgenic hormone profile of higher free testosterone and lower SHBG is associated with a greater CAC progression up to 10-years in post-menopausal women. Sex hormone levels may help identify women at increased risk for CVD who may benefit from additional risk-reducing strategies.

Background and aims It is not known if ultrasound carotid plaque features are associated with cardiovascular disease (CVD) risk factors or if they predict future CVD events. Methods We measured total carotid plaque area (TPA) and grayscale plaque features (grayscale median, black areas, and discrete white areas) by B-mode carotid ultrasound among 2205 participants who participated in the first (baseline) visit of the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used to examine relationships between ultrasound plaque features and CVD risk factors at baseline. Cox proportional hazards models were used to assess if TPA, grayscale features, and carotid plaque score (number of arterial segments with a plaque) could predict incident coronary heart disease and cerebrovascular disease events over a mean follow-up of 13.3 years. Results Participants were mean (standard deviation [SD]) 65.4 (9.6) years, 49% male, 39% White, 11% Chinese, 28% Black, and 22% Hispanic. Mean TPA 27.7 (24.7) mm2, but no grayscale plaque features, was associated with CVD risk factors. In fully adjusted models, TPA but no grayscale features predicted incident coronary heart disease (CHD) events (HR 1.23; 95%CI 1.11–1.36; p Conclusions In middle-aged adults free of known cardiovascular disease, TPA but not grayscale plaque features was associated with CVD risk factors and predicted incident CHD events. For CHD, prediction indices for TPA were similar to carotid plaque score but less than for CAC.

BACKGROUND AND AIMS: Coronary artery calcification (CAC) is common among patients with chronic kidney disease (CKD) and predicts the risk for cardiovascular disease (CVD). We examined the associations of novel risk factors with CAC progression among patients with CKD. METHODS: Among 1,123 CKD patients in the Chronic Renal Insufficiency Cohort (CRIC) Study, CAC was measured in Agatston units at baseline and a follow-up visit using electron beam computed tomography or multidetector computed tomography. RESULTS: Over an average 3.3-year follow-up, 109 (25.1%) participants without CAC at baseline had incident CAC and 124 (18.0%) participants with CAC at baseline had CAC progression, defined as an annual increase of ≥100 Agatston units. After adjustment for established atherosclerotic risk factors, several novel risk factors were associated with changes in CAC over follow-up. Changes in square root transformed CAC score associated with 1 SD greater level of risk factors were −0.20 (95% confidence interval, −0.31 to −0.10; p

Objective Sex hormone (SH) levels may contribute to sex differences in the risk of heart failure with preserved ejection fraction (HFpEF). We examined the associations of SH levels with left ventricular mass (LVM) and mass (M):volume (V) ratio, which are risk markers for HFpEF. Study design We studied 1941 post-menopausal women and 2221 men, aged 45–84 years, participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Serum SH levels, cardiac magnetic resonance imaging (MRI) and ejection fraction (EF) ≥50% had been recorded at baseline (2000–2002). Of these participants, 2810 underwent repeat MRI at Exam 5 (2010–2012). Stratified by sex, linear mixed-effect models were used to test associations between SH and sex hormone binding globulin (SHBG) level [per 1 SD greater log-transformed (SH)] with baseline and change in LV structure. Models were adjusted for age, race/ethnicity, center, height, weight, education, physical activity and smoking, and, in women, for hormone therapy and years since menopause. Main outcome measures LVM and M:V ratio. Results After a median of 9.1 years, higher free testosterone levels were independently associated with a modest increase in LVM (g/yr) in women [0.05 (95% CI 0.01, 0.10)] and men [0.16 (0.03, 0.28)], while higher SHBG levels were associated with less LVM change (g/yr) in women [−0.07 (−0.13, −0.01)] and men [−0.15 (−0.27, −0.02)]. In men, higher dehydroepiandrosterone and estradiol levels were associated with increased LVM. Among women, free testosterone levels were positively and SHBG levels inversely associated with change in M:V ratio. Conclusion A more androgenic profile (higher free testosterone and lower SHBG levels) is associated with a greater increase in LVM in men and women and greater increase in M:V ratio in women over the course of 9 years.

Background Despite the rising incidence of heart failure (HF), there is no validated prediction model for incident HF. Each of the LA and LV parameters taken separately has a prognostic value to predict incident HF. Based on the close physiological interaction between LA and LV, the simultaneous assessment of the left atrioventricular coupling could be even more accurate to predict incident HF. However, no data has been described on the existence of such an atrioventricular index. Purpose This study aimed to investigate the prognostic value of a novel left atrioventricular functional coupling index(LAFCI) and to assess its predictive value for incident HF occurrence. Methods A total of 4,124 participants in the Multi-Ethnic Study of Atherosclerosis underwent a cardiac MRI study. The LAFCI by cardiac MRI was defined by the ratio of the indexed LA end-diastolic volume divided by the LV global function index(LVGFI) already described. Cox proportional hazard models were constructed to predict the occurrence of HF. In univariable and multivariable Cox analysis, the association between LAFCI or all other LA and LV variables and time-to-event was analyzed, adjusting for traditional HF risk factors and biomarkers. Results A total of 231(5.6%) patients experienced HF during a median(IQR) follow-up period of 15.6(12.7–16.3) years. In univariable analysis, LAFCI was associated with incident HF (HR 2.23, 95%CI [2.02–2.34] P Fig. 1 ). Conclusions The LAFCI is an independent predictor of incident HF in this large multi-ethnic cohort.

Diastolic blood pressure has a J-curve relationship with coronary heart disease and death. Because this association is thought to reflect reduced coronary perfusion at low diastolic blood pressure, we hypothesized that the J-curve would be most pronounced among persons with coronary artery calcium. Among 6,811 participants from the Multi-Ethnic Study of Atherosclerosis, we used Cox models to examine if diastolic blood pressure category is associated with coronary heart disease events, stroke, and mortality. Analyses were conducted in the sample overall and after stratification by coronary artery calcium score. In multivariable-adjusted analyses, compared with diastolic blood pressure of 80 to 89 mmHg (reference), persons with diastolic blood pressure 0. Diastolic blood pressure

Background Studies in chronic kidney disease populations suggest that the non–glomerular filtration rate (GFR) determinants of serum levels of the low-molecular-weight protein filtration markers cystatin C, β 2 -microglobulin (B2M), and beta-trace protein (BTP) are less affected by age, sex, and ethnicity than those of creatinine. Study Design Cross-sectional study. Setting & Participants Predominantly elderly participants selected from the Age, Gene/Environment Susceptibility Kidney Study (AGES-Kidney; N=683; mean [SD] age, 79 [4] years; GFR, 62 [17]mL/min/1.73 m 2 ) and from the Multi-Ethnic Study of Atherosclerosis Kidney Study (MESA-Kidney; N=273; mean [SD] age, 70.5 [9] years; GFR, 73 [19]mL/min/1.73 m 2 ). Predictors Demographic and clinical factors hypothesized to be associated with conditions affecting non-GFR determinants of the filtration markers. Outcomes Measured GFRs and estimated GFRs (eGFRs) based on creatinine, cystatin C, B2M, and BTP levels (eGFR cr, eGFR cys , eGFR B2M , and eGFR BTP , respectively). Residual associations of factors with eGFR after accounting for measured GFR as the parameter of interest. Results eGFR cys , eGFR B2M , and eGFR BTP had significantly less strong residual associations with age and sex than eGFR cr in both AGES-Kidney and MESA-Kidney and were not associated with ethnicity (black vs white) in MESA-Kidney. After adjusting for age, sex, and ethnicity, residual associations with most clinical factors were smaller than observed with age and sex. eGFR cys and eGFR B2M , but not eGFR BTP , had significant residual associations with C-reactive protein levels in both studies. Limitations Small sample size may limit power to detect associations. Participants may be healthier than the general population. Conclusions Similar to previous studies in chronic kidney disease, in community-dwelling elders, cystatin C, B2M, and BTP levels are less affected than creatinine level by age and sex and are not affected by ethnicity. Both cystatin C and B2M levels may be affected by inflammation. These findings are important for the development and use of GFR estimating equations based on low-molecular-weight serum proteins throughout the range in GFRs.

Funding Acknowledgements Type of funding sources: None. BACKGROUND Although left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic value as predictors of HF, the close physiological relationship between LA and LV suggest that the assessment of LA/LV coupling could better reflect left atrioventricular dysfunction and be a better predictor of heart failure (HF). PURPOSE We investigated the prognostic value of a left atrioventricular coupling index (LACI), measured by cardiovascular magnetic resonance (CMR), as well as change in LACI to predict incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS In the MESA, 2,250 study participants, free of clinically recognized HF and cardiovascular disease at baseline, had LACI assessed by CMR imaging at baseline (Exam 1, 2000–2002), and ten years later (Exam 5, 2010–2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident HF after adjustment on traditional HF risk factors. The incremental risk prediction was calculated using C-statistic, categorical net reclassification index (NRI) and integrative discrimination index (IDI). RESULTS Among the 2,250 participants (mean age 59.3 ± 9.3 years and 47.6% male participants), 50 incident HF events occurred over 6.8 ± 1.3 years after the second CMR exam. After adjustment, greater LACI and ΔLACI were independently associated with HF (adjusted HR 1.44, 95% CI [1.25-1.66] and adjusted HR 1.55, 95% CI [1.30-1.85], respectively; both p CONCLUSIONS In a multi-ethnic population, atrioventricular coupling (LACI) and coupling change (ΔLACI) are independently associated with incident HF. Both have incremental prognostic value for predicting HF over traditional HF risk factors.

25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low testosterone levels in men, but there are conflicting reports of its associations with sex hormones in women. Less is known about whether these associations are independent of adiposity and lifestyle factors, and whether they differ by race/ethnicity.To examine associations of 25(OH)D concentrations with sex hormone levels.Cross-sectional analysis of 3017 men and 2929 women in a multi-ethnic cohort.Testosterone, estradiol, dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and free testosterone.The mean (SD) levels of 25(OH)D in men and women were 25.7(10.4) and 26.1(12.0)ng/ml, respectively. In men, after adjusting for demographic and lifestyle variables, a 10ng/ml [25nmol/L] decrease in 25(OH)D was associated with an average difference of -0.70nmol/L (95%CI -1.36, -0.05) in SHBG and 0.02 percent (0.01, 0.04) in free testosterone, but was not associated with low total testosterone level (10.41nmol/L). In women, a 10ng/ml decrease in 25(OH)D levels was associated with an average difference of -0.01nmol/L (-0.01, -0.00) for estradiol, -8.29nmol/L (-10.13, -6.45) for SHBG, 0.06 percent (0.04, 0.07) for free testosterone, and 0.40nmol/L (0.19, 0.62) for DHEA. There was no significant interaction by race/ethnicity.Lower 25(OH)D concentrations were associated with lower SHBG levels and higher free testosterone levels in both men and women, and lower estradiol and higher DHEA levels in women, independent of adiposity and lifestyle. We observed no significant association of 25(OH)D with total testosterone in men. Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels.

Objectives The aim of this study was to investigate whether inclusion of simple measures of calcified plaque distribution might improve the ability of the traditional Agatston coronary artery calcium (CAC) score to predict cardiovascular events. Background Agatston CAC scoring does not include information on the location and distributional pattern of detectable calcified plaque. Methods We studied 3,262 (50%) individuals with baseline CAC >0 from MESA (Multi-Ethnic Study of Atherosclerosis). Multivessel CAC was defined by the number of coronary vessels with CAC (scored 1 to 4, including the left main). The “diffusivity index” was calculated as: 1 − (CAC in most affected vessel/total CAC), and was used to group participants into concentrated and diffuse CAC patterns. Multivariable Cox proportional hazards regression, area under the curve, and net reclassification improvement analyses were performed for both coronary heart disease (CHD) and cardiovascular disease (CVD) events to assess whether measures of regional CAC distribution add to the traditional Agatston CAC score. Results Mean age of the population was 66 ± 10 years, with 42% women. Median follow-up was 10.0 (9.5 to 10.7) years and there were 368 CHD and 493 CVD events during follow-up. Considerable heterogeneity existed between CAC score group and number of vessels with CAC (p Conclusions The number of coronary arteries with calcified plaque, indicating increasingly “diffuse” multivessel subclinical atherosclerosis, adds significantly to the traditional Agatston CAC score for the prediction of CHD and CVD events.

Background Elevated parathyroid hormone (PTH) levels have been associated with cardiovascular disease risk factors and events. We hypothesized that elevated PTH levels would also be associated with subclinical cerebrovascular disease. We examined the relationship between elevated PTH level and white matter hyperintensities (WMHs) and subclinical infarcts measured on brain magnetic resonance imaging (MRI). Methods PTH was measured at baseline (1993-1994) among participants free of prior clinical stroke who underwent a brain MRI at baseline (n = 1703) and a second brain MRI 10 years later (n = 948). PTH levels of 65 pg/mL or higher were considered elevated (n = 204). Participants who did not return for a follow-up MRI had, at baseline, higher PTH and a greater prevalence of cardiovascular risk factors ( P Results At baseline, the participants had a mean age of 62 years and were 60% female and 49% black. Cross-sectionally, after adjusting for demographic and lifestyle factors, elevated PTH level was associated with higher WMH score (β = .19, 95% confidence interval [CI] .04-.35) and increased odds of prevalent infarcts (odds ratio 1.56, 95% CI 1.02-2.36). Results were attenuated after adjustment for potential mediators of this association (i.e., hypertension). No prospective associations were found between PTH and incident infarcts or change in estimated WMH volume, although estimates were imprecise. Conclusions Although associated cross-sectionally, we did not confirm any association between elevated PTH level and progression of cerebrovascular changes on brain MRIs obtained 10 years apart. The relationship of PTH with subclinical brain disease warrants further study.

Background Atrial fibrillation (AF) is the most common sustained arrhythmia. LA and LV parameters have both a prognostic value to predict AF occurrence when taken separately. Based on the close physiological interaction between LA and LV, the simultaneous assessment of the left atrioventricular coupling could be even more accurate to predict AF. However, no data has been described on the existence of such an atrioventricular index. Purpose This study aimed to investigate the prognostic value of a novel left atrioventricular coupling index (LACI) that integrates LA and LV parameters and to assess its predictive value for AF occurrence throughout adult life in a large population without a history of CV diseases. Methods A total of 4124 participants in the multi-ethnic study of atherosclerosis (MESA) underwent a cardiac MRI study. The LACI by cardiac MRI was defined by the ratio of the indexed LA end-diastolic volume divided by the indexed LV end-diastolic volume. Cox proportional hazard models were constructed to predict the occurrence of AF. In univariable and multivariable Cox analysis, the association between LACI or all other LA and LV variables and time-to-event was analysed, adjusting for traditional AF factors. Results A total of 237 (5.7%) patients experienced AF during a median (IQR) follow-up period of 10.8 (7.8–11.4) years. In univariate analysis, LACI was associated with incident AF (HR: 2.13, 95% CI [1.97–2.31] P Fig. 1 ). Conclusions The LACI was an independent predictor of incident AF.

Background The left atrium (LA) and left ventricle (LV) parameters have both a good prognostic value for CV events when they are taken separately. Based on the close physiological interactions between LA and LV, we hypothesise the simultaneous assessment of the left atrioventricular coupling could be even more accurate to predict CV events. Purpose This study aimed to investigate the prognostic value of a novel left atrioventricular coupling index (LACI) and to assess its predictive value for CV events. Methods A total of 4124 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) underwent a cardiac MRI study. The LACI by cardiac MRI was defined by the ratio of the indexed LA end-diastolic volume divided by the indexed LV end-diastolic volume. Cox proportional hazard models were constructed to predict the endpoints of atrial fibrillation (AF), heart failure (HF), hard CV events, and CV death. In univariable and multivariable Cox analyses, the association between LACI or all other LA and LV variables and time-to-event was analysed, adjusting for after adjustment for established risk factors and biomarkers. Results A total of 1151 (27.9%) CV events were observed during a median (IQR) follow-up period of 15.9 (12.9–16.6) years. In univariate analysis, LACI was associated with AF (HR: 2.13, 95% CI [1.97–2.31]), heart failure (HR: 1.70, 95% CI [1.56–1.86]), hard CV events (HR: 1.35, 95% CI [1.25–1.46]) ( Fig. 1 ), and CV death (HR: 1.53, 95% CI [1.38–1.70]; for all P Fig. 1 ). Conclusions The LACI is a powerful predictor of incident HF, AF, hard CV events, and CV death.

South Asians (SAs) are at increased risk for atherosclerotic cardiovascular disease (ASCVD). Aortic valve calcium (AVC) is associated with risk for both ASCVD and aortic stenosis. Elevated Lp(a) is heritable and an independent risk factor for ASCVD. Genetic variations in the LPA gene are associated

Oxidized phospholipids (OxPL) are carried by lipoprotein(a) (Lp(a)) and may contribute to Lp(a)-mediated aortic valve calcification (AVC). Plasma Lp(a) and OxPL were measured in the Multi-Ethnic Study of Atherosclerosis (n=4108) and the Framingham Heart Study (n=1143). AVC was quantified by cardiac

Electrocardiography (ECG) is a practical and cost-effective clinical tool. Machine learning may enable identification of novel ECG variables for predicting incident atrial fibrillation (AF). We included 3151 participants from MESA with 568 baseline ECG variables each in addition to demographic

Background Several 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. Objectives The 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. Methods Algorithm 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). Results Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p Conclusions An 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.

Background Familial hypercholesterolemia (FH) is an autosomal dominant dyslipidemia characterized by defective low-density lipoprotein (LDL) clearance. The aim of this study was to compare Friedewald-estimated LDL cholesterol (LDL-C) to biologic LDL-C in individuals screening positive for FH and then further characterize FH phenotypes. Methods We studied 1,320,581 individuals from the Very Large Database of Lipids, referred from 2009 to 2011 for Vertical Auto Profile ultracentrifugation testing. Friedewald LDL-C was defined as the cholesterol content of LDL-C, intermediate-density lipoprotein cholesterol, and lipoprotein(a) cholesterol (Lp(a)-C), with LDL-C representing biologic LDL-C. Using Friedewald LDL-C, we phenotypically categorized patients by the National Lipid Association guideline age-based screening thresholds for FH. In those meeting criteria, we categorized patients using population percentile-equivalent biologic LDL-C cutpoints and explored Lp(a)-C and remnant lipoprotein cholesterol (RLP-C) levels. Results Overall, 3829 patients met phenotypic criteria for FH by Friedewald LDL-C screening (FH+). Of those screening FH+, 78.8% were above and 21.2% were below the population percentile-equivalent biologic LDL-C. The mean difference in Friedewald biologic LDL-C percentiles was −0.01 (standard deviation, 0.17) for those above, and 1.92 (standard deviation, 9.16) for those below, respectively. Over 1 of 3 were found to have an elevated Lp(a)-C and over 50% had RLP-C greater than 95th percentile of the entire VLDL population. Conclusions Of those who screened FH+, Friedewald and biologic LDL-C levels were closely correlated. Large proportions of the FH+ group had excess levels of Lp(a)-C and RLP-C. Future studies are warranted to study these mixed phenotypic groups and determine the role for further risk stratification and treatment algorithms.

Rationale and Objectives Pilot study to determine whether among subjects receiving coronary computed tomography angiography (CTA), the combination of high-sensitivity troponin I (hsTnI) and coronary artery calcium score (CACS) identifies a low-risk population in whom CTA might be avoided. Materials and Methods A cross-sectional study of 314 symptomatic patients receiving CTA as part of their acute coronary syndrome evaluation was conducted. hsTnI was measured with Abbott Laboratories' hsTnI assay. CACSs were calculated via the Agatston method. Patients were followed for at least 30 days after discharge for the occurrence of major adverse cardiac events (MACEs; all-cause mortality, acute coronary syndrome, and revascularization). Results Of 314 subjects studied, 213 (67.8%) had no coronary artery stenosis, and 67 (21.3%), 28 (8.9%), and 6 (1.9%) had maximal coronary artery stenosis of 1%–49%, 50%–69%, and 70% or greater, respectively. All MACEs occurred during index hospitalization and include one myocardial infarction and four revascularizations. Sixty-two percent (189/307) of subjects had zero CACS, and 24% (76/314) of subjects had undetected hsTnI. No subjects with undetectable hsTnI or zero CACS had an MACE. A strategy of avoiding further testing in subjects with undetectable initial hsTnI, performing CACS on subjects with detectable initial hsTnI but nonincreased hsTnI (less than 99th percentile), and obtaining CTA in subjects with Agatston greater than 0 will have a negative predictive value of 100.0% (95% confidence interval, 98.2%–100.0%). This strategy will avoid CTA in 63% (198/314) of subjects. Conclusions In this pilot study, the addition of CACS to hsTnI improves the identification of low-risk subjects in whom CTA might be avoided.

Objective Positive remodeling (PR), a coronary artery characteristic associated with risk for myocardial infarction (MI), may be more prevalent in HIV-infected (HIV+) people. We evaluated the prevalence of PR using coronary CT angiography (CCTA) in HIV+ and HIV-uninfected (HIV−) men.

Background Prolonged heart rate–corrected QT interval on electrocardiograms (ECGs) is associated with increased risk of myocardial infarction and cardiovascular disease (CVD)–related deaths in patients with prevalent coronary heart disease. Objectives This study sought to examine the prognostic association between the baseline QT interval and incident cardiovascular events in individuals without prior known CVD. Methods The corrected baseline 12-lead ECG QT interval duration (QTcorr) was determined by adjustment for age, sex, race/ethnicity, and RR interval duration in 6,273 participants in MESA (Multi-Ethnic Study of Atherosclerosis). Cox proportional hazards models adjusting for demographic and clinical risk factors were used to examine the association of baseline QTcorr with incident cardiovascular events. Results The mean age at enrollment was 61.7 ± 10 years, and 53.4% of participants were women. Cardiovascular events occurred in 291 participants over a mean follow-up of 8.0 ± 1.7 years. Each 10-ms increase in the baseline QTcorr was associated with incident heart failure (hazard ratio [HR]: 1.25; 95% CI: 1.14 to 1.37), CVD events (HR: 1.12; 95% CI: 1.05 to 1.20), and stroke (HR: 1.19; 95% CI: 1.07 to 1.32) after adjustment for CVD risk factors and potential confounders. There was no evidence of interaction with sex or ethnicity. Conclusions The QT interval was associated with incident cardiovascular events in middle-aged and older adults without prior CVD.

Insulin resistance may be related to vascular calcification as both are associated with abdominal obesity. We investigated the association of insulin resistance with abdominal aortic calcium (AAC), coronary artery calcium (CAC) and thoracic aortic calcium (TAC), and whether it differs according to different levels of subcutaneous fat area (SFA) and visceral fat area (VFA) in a cross-sectional study design.We investigated 1632 participants without diabetes from the Multi-Ethnic Study of Atherosclerosis with valid data on homeostasis model assessment index (HOMA-IR), AAC, CAC, and TAC. Adipocytokines, SFA, and VFA were also determined.HOMA-IR was associated with the presence of CAC, but not AAC and TAC, and the association remained significant after adjusting for traditional risk factors, adipocytokines, abdominal muscle mass, SFA, and VFA (prevalence ratio = 1.04 per one interquartile range [IQR] increase, P = 0.01). As the strength of the association of HOMA-IR with vascular calcification may differ by abdominal fat composition, subgroup analysis was performed among participants with different tertiles of SFA and VFA. Significant interactions between HOMA-IR with SFA and VFA separately were observed for the presence of TAC, but not AAC and CAC, even after adjusting for confounding factors. The association of HOMA-IR with TAC tended to be stronger in participants with more SFA and VFA.Atherosclerotic calcification, especially in the coronary arteries, is related to insulin resistance. Further studies are needed to delineate the mechanisms by which visceral obesity can lead to vascular calcification.

Background Common carotid artery (CCA) intima-media thickness (IMT) can be measured using ultrasound near to or below the carotid bulb. This might affect associations of IMT with coronary heart disease (CHD) risk factors and events. Methods IMT measurements were performed near and below the divergence of the CCA bulb in 279 white individuals aged 45 to 54 years free of CHD at baseline and a subset of the Multi-Ethnic Study of Atherosclerosis, a cohort composed of whites, blacks, Chinese, and Hispanic subjects. Participants were followed for an average of 8.2 years. Far wall mean of the maximum IMT (MMaxIMT) and mean of the mean IMT of the right and left CCAs were averaged. Framingham risk factors were used in multivariate linear regression models. Parsimonious Cox proportional regression models included first-time CHD as outcome. Results Mean of the mean IMT below the bulb was smaller than near the bulb (0.51 ± 0.078 vs 0.56 ± 0.088 mm, P R 2 = 0.215 vs 0.186). MMaxIMT below the bulb was associated with risk factors (model R 2 = 0.211), but MMaxIMT near to the bulb was not ( R 2 = 0.025). Mean of the mean IMT and MMaxIMT below the bulb were associated with CHD events (hazard ratios, 1.67 [ P = .047] and 1.72 [ P = .037], respectively) but not when measured near the bulb. Conclusions CCA IMT measurements made below the bulb are smaller but have more consistent associations with CHD risk factors and outcomes compared with IMT measured near the bulb.

Previous studies demonstrated that blacks have less coronary artery calcification (CAC) than whites. We evaluated racial differences in plaque composition and stenosis in the Multicenter AIDS Cohort Study. HIV-positive and HIV-negative men underwent noncontrast cardiac computed tomography (CT) if they were aged 40 to 70 years, weighed136 kg, and had no history of cardiac surgery or revascularization and, if eligible, coronary CT angiography (CTA). There were 1,001 men who underwent CT scans and 759 men CTA. We measured CAC on noncontrast CT and identified total plaque, noncalcified plaque, calcified plaque, mixed plaque, and coronary stenosis50% on CTA. The association of presence and extent of plaque with race was determined after adjustment for HIV serostatus, cardiovascular risk factors, and measures of socioeconomic status. The prevalences of any plaque on CTA and noncalcified plaque were not different between black and white men; however, black men had lower prevalences of CAC (prevalence ratio [PR] 0.79, p = 0.01), calcified plaque (PR 0.69, p = 0.002), and stenosis50% (PR 0.59, p = 0.009). There were no associations between black race and extent of plaque in fully adjusted models. Using log-linear regression, black race was associated with a lower extent of any plaque on CTA in HIV-positive men (estimate = -0.24, p = 0.051) but not in HIV-negative men (0.12, p = 0.50, HIV interaction p = 0.005). In conclusion, a lower prevalence of CAC in black compared with white men appears to reflect less calcification of plaque and stenosis rather than a lower overall prevalence of plaque.

Objectives The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. Background CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. Methods We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. Results A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression. Conclusions Progression of CAC is associated with an increased risk for future hard and total CHD events.