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1.  Associations of cardiovascular risk factors, carotid intima-media thickness and left ventricular mass with inter-adventitial diameters of the common carotid artery: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2011;218(2):344-349.
Common carotid artery inter-adventitial diameter (IAD) and intima-media thickness (IMT) are measurable by ultrasound. IAD may be associated with left ventricular mass (LV mass) while IMT is a marker of subclinical atherosclerosis. It is not clear if IAD is associated with LV mass after accounting for IMT and traditional cardiovascular risk factors.
IAD and IMT were measured on participants of the Multi-Ethnic Study of Atherosclerosis (MESA) IMT progression study. A total of 5641 of the originally enrolled 6814 MESA participants were studied. LV mass was measured by magnetic resonance imaging. Multivariable linear regression was used with IAD as the outcome and adjustment for risk factors, as well as IMT and LV mass.
Traditional cardiovascular risk factors, height, weight and ethnicity were significantly associated with IAD. After adjustment for risk factors, a one mm difference in IMT was associated with a 1.802 mm (95% CI: 1.553, 2.051) higher mean IAD. A one gm difference in LV mass was associated with a 0.006 mm (95% CI: 0.005, 0.007) higher mean IAD. LV mass was independently associated with IAD after adjusting for cardiovascular risk factors and IMT. These associations were slightly different for men and women.
Inter-adventitial diameters are associated with left ventricular mass after adjusting for cardiovascular risk factors and IMT. IAD might serve as a surrogate for left ventricular mass and have predictive value for cardiovascular outcomes.
PMCID: PMC3186064  PMID: 21726862
carotid arteries; ultrasonics; hypertrophy; magnetic resonance imaging; remodeling; risk factors; left ventricle
2.  Relation of Leptin to Left Ventricular Hypertrophy (From the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2013;112(5):726-730.
Increasing adiposity increases the risk for left ventricular hypertrophy. Adipokines are hormone-like substances from adipose tissue that influence several metabolic pathways relevant to LV hypertrophy. Data was from participants enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent magnetic resonance imaging of the heart and who also had fasting venous blood assayed for 4 distinct adipokines (adiponectin, leptin, tumor necrosis factor – alpha and resistin). 1,464 MESA participants had complete data. The mean age was 61.5 years, the mean body mass index was 27.6 kg/m2 and 49% were female. With adjustment for age, sex, race, height and weight, multivariable linear regression modeling revealed that a 1-SD increment in leptin was significantly associated with smaller LV mass (ß: −4.66 % predicted, p-value: < 0.01), LV volume (−5.87 % predicted, < 0.01), stroke volume (−3.23 ml, p < 0.01) and cardiac output (−120 mL/min, p = 0.01) as well as a lower odds ratio for the presence of LV hypertrophy (OR: 0.65, p < 0.01), but a higher ejection fraction (0.44%, p = 0.05). Additional adjustment for the traditional cardiovascular disease (CVD) risk factors, insulin resistance, physical activity, education, income, inflammatory biomarkers, other selected adipokines and pericardial fat did not materially change the magnitude or significance of the associations. The associations between the other adipokines and LV structure and function were inconsistent and largely non-significant. In conclusion, the results indicate that higher levels of leptin are associated with more favorable values of several measures of LV structure and function.
PMCID: PMC3745795  PMID: 23711806
leptin; left ventricle; hypertrophy; mass
3.  Association of resting heart rate with carotid and aortic arterial stiffness: Multi-Ethnic Study of Atherosclerosis (MESA) 
Hypertension  2013;62(3):10.1161/HYPERTENSIONAHA.113.01605.
Resting heart rate is an easily measured, non-invasive vital sign that is associated with cardiovascular disease events. The pathophysiology of this association is not known. We investigated the relationship between resting heart rate and stiffness of the carotid (a peripheral artery) and the aorta (a central artery) in an asymptomatic multi-ethnic population. Resting heart rate was recorded at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Distensibility was used as a measure of arterial elasticity, with a lower distensibility indicating an increase in arterial stiffness. Carotid distensibility was measured in 6,484 participants (98% of participants) using B-mode ultrasound and aortic distensibility was measured in 3,512 participants (53% of participants) using cardiac MRI. Heart rate was divided into quintiles and we used progressively adjusted models that included terms for physical activity and AV-nodal blocking agents. Mean resting heart rate of participants (mean age 62 years, 47% male) was 63 beats per minute (SD 9.6 beats per minute). In unadjusted and fully adjusted models, carotid distensibility and aortic distensibility decreased monotonically with increasing resting heart rate (p for trend <0.001 and 0.009 respectively). The relationship was stronger for carotid versus aortic distensibility. Similar results were seen using the resting heart rate taken at the time of MRI scanning. Our results suggest that a higher resting heart rate is associated with an increased arterial stiffness independent of AV-nodal blocker use and physical activity level, with a stronger association for a peripheral (carotid) compared to a central (aorta) artery.
PMCID: PMC3838105  PMID: 23836802
heart rate; cardiovascular disease; stiffness; ultrasound; cardiac magnetic resonance imaging
4.  Association of Small Artery Elasticity With Incident Cardiovascular Disease in Older Adults 
American Journal of Epidemiology  2011;174(5):528-536.
Functional biomarkers like large artery elasticity (LAE) and small artery elasticity (SAE) may predict cardiovascular disease (CVD) events beyond blood pressure. The authors examined the prognostic value of LAE and SAE for clinical CVD events among 6,235 Multi-Ethnic Study of Atherosclerosis participants who were initially aged 45–84 years and without symptomatic CVD. LAE and SAE were derived from diastolic pulse contour analysis. During a median 5.8 years of follow-up between 2000 and 2008, 454 adjudicated CVD events occurred, including 256 cases of coronary heart disease (CHD), 93 strokes, and 126 heart failures (multiple diagnoses were possible). After adjustment for age, race/ethnicity, sex, clinic, height, heart rate, body mass index, systolic and diastolic blood pressure, use of antihypertensive and cholesterol-lowering medications, smoking, total cholesterol, high density lipoprotein cholesterol, triglycerides, diabetes, and high-sensitivity C-reactive protein, the hazard ratio for any CVD per standard-deviation increase in SAE was 0.71 (95% confidence interval: 0.61, 0.83; P < 0.0001). The lowest (stiffest) SAE quartile had a hazard ratio of 2.28 (95% confidence interval: 1.55, 3.36) versus the highest (most elastic) quartile. The net reclassification index, conditional on base risk, was 0.11. SAE was significantly associated with future CHD, stroke, and heart failure. After adjustment, LAE was not significantly related to CVD. In asymptomatic participants free of overt CVD, lower SAE added prognostic information for CVD, CHD, stroke, and heart failure events.
PMCID: PMC3202150  PMID: 21709134
arteries; cardiovascular diseases; elasticity; risk factors
5.  Pericardial Fat is Associated with Carotid Stiffness in the Multi-Ethnic Study of Atherosclerosis 
Background and Aims
Arterial stiffness is a prominent feature of vascular aging and a risk factor for cardiovascular disease (CVD). Fat around the heart and blood vessels (i.e. pericardial fat, Pfat) may contribute to arterial stiffness via a local paracrine effect of adipose tissue on the surrounding vasculature. Thus, we determined the association between Pfat and carotid stiffness in 5,770 participants (mean age 62 yrs, 53% female, 25% African American, 24% Hispanic, and 13% Chinese) from the Multi-Ethnic Study of Atherosclerosis.
Methods and Results
Pfat was measured by computed tomography, and ultrasonography of the common carotid artery was used to calculate the distensibility coefficient (DC) and young’s modulus (YM). Lower DC and higher YM values indicate stiffer arteries. Pfat quartile was highly associated with demographic, behavioral, anthropometric, hemodynamic, metabolic, and disease variables in both men and women. After adjusting for height, clinical site, CVD risk factors, and medications, a 1-standard deviation (41.91 cm3) increment in Pfat was associated with a 0.00007±0.00002 1/mmHg lower DC (p=0.0002) in men and a 48.1±15.1 mmHg/mm higher YM in women (p=0.002). Additional adjustment for C-reactive protein, coronary artery calcification, and carotid intima-media thickness had only modest effects. More importantly, adjusting for body mass index and waist circumference did not significantly change the overall results.
Higher Pfat is associated with higher carotid stiffness, independent of traditional CVD risk factors and obesity.
PMCID: PMC2929306  PMID: 20153618
pericardial fat; arterial stiffness; distensibility; carotid artery
6.  Cardiovascular Imaging for Assessing Cardiovascular Risk in Asymptomatic Men Versus Women 
Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD.
Methods and Results
The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62±10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05).
There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.
PMCID: PMC3037859  PMID: 21068189
imaging; cardiovascular diseases; sex

Results 1-6 (6)