Background 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 utilities of CAC presence, carotid artery plaque presence, and high IMT for incident CVD events. Methods and Results Participants were from the Multi-Ethnic Study of Atherosclerosis. Predictive values of carotid plaque, IMT and CAC presence were compared using Cox proportional hazards models, c-statistics, and net reclassification indices. The 6,779 participants were mean (standard deviation) 62.2 (10.2) years old; 49.9% had CAC, 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 (TIA) 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 to traditional risk factors, c-statistics for CVD (c=0.756) and CHD (c=0.752) increased most by adding of CAC presence (CVD 0.776, CHD, 0.784; p<0.001) followed by carotid plaque presence (CVD c=0.760, CHD 0.757; p<0.05). Compared to risk factors (c=0.782), carotid plaque presence (c=0.787, p=0.045) but not CAC (c=0.785, p=0.438) improved prediction of stroke/TIA. Conclusions In adults without CVD, CAC presence improves prediction of CVD and CHD more than carotid plaque presence or high IMT. CAC and carotid ultrasound parameters performed similarly for stroke/TIA event prediction.

Background and Purpose Carotid artery intima-media thickness (IMT) and plaque are non-invasive markers of subclinical arterial injury that predict incident cardiovascular disease. We evaluated predictors of longitudinal changes in IMT and new plaque over a decade in a longitudinal multiethnic cohort. Methods Carotid IMT and plaque were evaluated in Multi-Ethnic Study of Atherosclerosis participants at exams 1 and 5, a mean (standard deviation) of 9.4 (0.5) years later. Far wall carotid IMT was measured in both common (CCA) and internal carotid arteries. A plaque score was calculated from all carotid segments. Mixed effects longitudinal and multivariate regression models evaluated associations of baseline risk factors and time-updated medication use with IMT progression and plaque formation. Results The 3,441 MESA participants were 60.3 (9.4) years old (53% female; 26% African-American, 22% Hispanic, 13% Chinese); 1,620 (47%) had carotid plaque. Mean CCA IMT progression was 11.8 (12.8) μm/year. 1,923 (56%) of subjects developed new plaque. IMT progressed more slowly in Chinese (β=−2.89, p=0.001) and Hispanic participants (β=−1.81, p=0.02), and with higher baseline high-density lipoprotein cholesterol (per 5 mg/dL, β=−0.22, p=0.03), antihypertensive use (β=−2.06, p=0.0004), and time on antihypertensive medications (years) (β=−0.29, p<0.0001). Traditional risk factors were associated with new plaque formation, with strong associations for cigarette use (odds ratio 2.31, p<0.0001) and protection by African-American ethnicity (odds ratio 0.68, p<0.0001). Conclusions In a large, multi-ethnic cohort with a decade of follow-up, ethnicity is a strong, independent predictor of carotid IMT and plaque progression. Anti-hypertensive medication use was associated with less subclinical disease progression.

Background and Purpose Arterial stiffening is associated with hypertension, stroke, and cognitive decline; however, the effects of aging and cardiovascular disease risk factors on carotid artery stiffening have not been assessed prospectively in a large multi-ethnic, longitudinal study. Methods Distensibility coefficient and Young’s elastic modulus of the right common carotid artery were calculated at baseline and after a mean (standard deviation) of 9.4 (0.5) years in 2,650 participants. Effects of age and cardiovascular disease risk factors were evaluated by multivariable mixed regression and analysis of covariance models. Results At baseline, participants were 59.9 (9.4) years old (53% female; 25% Black, 22% Hispanic, 14% Chinese). Young’s elastic modulus increased from 1,581 (927) to 1,749 (1,306) mmHg (p<0.0001) and distensibility coefficient decreased from 3.1 (1.3) to 2.7 (1.1) x 10−3 mmHg−1 (p<0.001), indicating progressive arterial stiffening. Young’s elastic modulus increased more among participants who were >75 years old at baseline (p<0.0001). In multivariable analyses, older age and less education independently predicted worsening Young’s elastic modulus and distensibility coefficient. Stopping antihypertensive medication during the study period predicted more severe worsening of Young’s elastic modulus (β=360.2 mmHg, p=0.008). Starting antihypertensive medication after exam 1 was predictive of improvements in distensibility coefficient (β =1.1 x 10−4, mmHg−1; p=0.024). Conclusions Arterial stiffening accelerates with advanced age. Older individuals experience greater increases in Young’s elastic modulus than do younger adults, even after considering the effects of traditional risk factors. Treating hypertension may slow the progressive decline in carotid artery distensibility observed with aging and improve cerebrovascular health.

Key PointsQuestionAmong patients with recent myocardial infarction or hospitalization for heart failure, is high-dose trivalent inactivated influenza vaccine more effective than standard-dose quadrivalent inactivated influenza vaccine for reducing all-cause mortality or hospitalizations for cardiac or pulmonary causes?FindingsIn this randomized clinical trial that involved 5260 adults and was conducted over 3 influenza seasons, there was no significant difference in the time to first occurrence of all-cause death or cardiopulmonary hospitalization during each enrolling season for those in the high-dose group vs the standard-dose group (hazard ratio, 1.06).MeaningIn patients with high-risk cardiovascular disease, high-dose trivalent influenza vaccine, compared with standard-dose quadrivalent vaccine, did not significantly reduce all-cause mortality or hospitalizations for cardiac or pulmonary causes; influenza vaccination remains strongly recommended in this population.

In the COMPANION trial, a machine learning algorithm produced a model that predicted clinical outcomes after CRT. Applied before device implant, this model may better differentiate outcomes over current clinical discriminators and improve shared decision-making with patients.

Objectives To identify and characterize an association between persistent asthma and cardiovascular disease (CVD) risk in the Multi-Ethnic Study of Atherosclerosis (MESA). Approach and Results MESA is a longitudinal prospective study of an ethnically diverse cohort of individuals free of known CVD at its inception. Presence and severity of asthma were assessed in the MESA at Exam 1. Persistent asthma was defined as asthmatics using controller medications (inhaled corticosteroids, leukotriene inhibitors, oral corticosteroids) and intermittent asthma as asthmatics not using controller medications. Participants were followed for a mean (standard deviation) 9.1 (2.8) years for development of incident CVD (coronary death, myocardial infarction, angina, stroke, and CVD death). Multivariable Cox regression models were used to assess associations of asthma and CVD. The 6,792 participants were 62.2 (standard deviation 10.2) years old: 47% male (28% African-American, 22% Hispanic, 12% Chinese). Persistent asthmatics (N=156), compared to intermittent (N=511) and non-asthmatics (N=6125), respectively had higher C-reactive protein (1.2 [1.2] vs 0.9 [1.2] vs 0.6 [1.2] mg/L) and fibrinogen (379 [88] vs 356 [80] vs 345 [73] mg/dL) levels. Persistent asthmatics had the lowest unadjusted CVD-free survival rate of 84.1%, 95% confidence interval (78.9–90.3%) compared with intermittent asthmatics 91.1% (88.5–93.8%) and non-asthmatics 90.2% (89.4–91%). Persistent asthmatics had greater risk of CVD events than non-asthmatics (HR 1.6 [95% 1.01–2.5, p=0.040]), even after adjustment for age, sex, race, CVD risk factors, and anti-hypertensive and lipid medication use. Conclusions In this large multi-ethnic cohort, persistent asthmatics had a higher CVD event rate than non-asthmatics.

Objective- HDL-C (high-density lipoprotein cholesterol) may not always be cardioprotective in postmenopausal women. HDL particles (HDL-P) via ion-mobility may better reflect the antiatherogenicity of HDL. Objectives were (1) to evaluate associations of HDL-C and ion-mobility HDL-P with carotid intima-media thickness (cIMT) and carotid plaque separately and jointly in women; and (2) to assess interactions by age at and time since menopause. Approach and Results- Analysis included 1380 females from the MESA (Multi-Ethnic Study of Atherosclerosis; age: 61.8±10.3; 61% natural-, 21% surgical-, and 18% peri-menopause). Women with unknown or early menopause (age at nonsurgical menopause ≤45 years) were excluded. Adjusting for each other, higher HDL-P but not HDL-C was associated with lower cIMT ( P=0.001), whereas higher HDL-C but not HDL-P was associated with greater risk of carotid plaque presence ( P=0.04). Time since menopause significantly modified the association of large but not small HDL-P with cIMT; higher large HDL-P was associated with higher cIMT close to menopause but with lower cIMT later in life. The proatherogenic association reported for HDL-C with carotid plaque was most evident in women with later age at menopause who were >10 years postmenopausal. Conclusions- Elevated HDL-C may not always be cardioprotective in postmenopausal women. The cardioprotective capacity of large HDL-P may adversely compromise close to menopause supporting the importance of assessing how the menopause transition might impact HDL quality and related cardiovascular disease risk later in life.

These findings support the potential use of the ultrasound texture contrast for evaluating arterial injury and CVD risk. Advances in knowledge: This paper contributes to the literature in that it describes how the greyscale texture feature "contrast" is related to CVD risk factors.