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1.  Relation of Left Ventricular Mass at Age 23 to 35 years to Global Left Ventricular Systolic Function 20 Years Later (From the Coronary Artery Risk Development in Young Adults Study) 
The American journal of cardiology  2013;113(2):377-383.
Left ventricular (LV) mass and LV ejection fraction (EF) are major independent predictors of future cardiovascular disease. The association of LV mass with future LVEF in younger populations has not been studied. We investigated the relation of LV mass index (LVMI) at age 23 to 35 years to LV function after 20 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA is a longitudinal study that enrolled young adults in 1985–1986. We included participants with echocardiographic examinations at both years-5 and -25. LVMI and LVEF were assessed using M-mode echocardiography at year-5 and using both M-mode and 2-dimensional images at year-25. Statistical analytic models assessed the correlation between LVMI and LV functional parameters both cross-sectionally and longitudinally. A total of 2,339 participants were included. The mean LVEF at year-25 was 62%. Although there was no cross-sectional correlation between LVMI and LVEF at year-5, there was a small, but statistically significant negative correlation between LVMI at year-5 and LVEF 20 years later (r = −0.10, p < 0.0001); this inverse association persisted for LVMI in the multivariable model. High LVMI was an independent predictor of systolic dysfunction (LVEF < 50%) 20 years later (odds ratio 1.46, p = 0.0018). In conclusion, we have shown that LVMI in young adulthood in association with chronic risk exposure impacts systolic function in middle age; the antecedents of heart failure may occur at younger ages than previously thought.
PMCID: PMC3901209  PMID: 24176073
left ventricular mass; left ventricular ejection fraction; echocardiography; left ventricular remodeling
2.  Longitudinal Determinants of Left Ventricular Mass and Geometry: The CARDIA Study 
Circulation. Cardiovascular imaging  2013;6(5):10.1161/CIRCIMAGING.112.000450.
The purpose of this study was to identify determinants of 20 year change in left ventricular (LV) mass (LVM) and LV geometry in black and white young adults in the CARDIA Study.
Methods and Results
We studied 2426 black and white men and women (54.7% Caucasian) aged 43-55 years with cardiovascular (CV) risk factor data and echocardiograms from CARDIA year 5 and 25 examinations. In regression models, year 25 LVM or relative wall thickness was the dependent variable and with year 5 echo values, age, gender, race, body mass index (BMI), change in BMI, mean arterial blood pressure, change in mean blood pressure, heart rate (HR), change in HR, tobacco use, presence of diabetes, alcohol use, and physical activity score as independent variables. LVM and relative wall thickness increased while prevalence of normal geometry declined from 84.2% to 69.7%. Significant determinants of year 25 LVM/m2.7 were year 5 LVM, year 5 and change in BMI, year 5 and change in mean arterial pressure, year 5 and change in HR, baseline diabetes, and year 5 tobacco and/or alcohol use (overall r2 = 0.40). Significant determinants of year 25 relative LV wall thickness were year 5 value, black race, change in BMI, year 5 and change in mean arterial pressure, starting smoking, and year 5 diabetes. (overall r2 = 0.11).
Prevalence of abnormal LV hypertrophy and geometry increased from young adulthood to middle age. Both young adult CV risk traits and change in these traits predicted change in LV mass/geometry.
PMCID: PMC3873157  PMID: 23922005
echocardiography; left ventricular mass; blood pressure; obesity; risk assessment
3.  Better Population Health Through Behavior Change in Adults A Call to Action 
Circulation  2013;128(19):2169-2176.
PMCID: PMC4074536  PMID: 24100544
AHA Scientific Statements; behavior; population health; prevention
4.  Associations Between a Parental History of Premature Cardiovascular Disease and Coronary Calcium and Carotid Intima-Media Thickness: The Coronary Artery Risk Development In Young Adults (CARDIA) Study 
It is unclear if associations between a parental history of premature CVD (pCVD) and subclinical atherosclerosis are attenuated by adjustment for long-term risk factors levels through middle adulthood.
Prospective community-based cohort study
CARDIA participants who attended the year 20 exam (N=2283, mean age 45 years) were grouped by pCVD status: maternal only, paternal only, any parental, and no parental history (referent). We used separate logistic regression models, adjusted for average risk factor levels over 20 years' follow-up to assess associations of parental pCVD and subclinical atherosclerosis in offspring.
White participants with any parental history of pCVD had a higher odds of CAC>0 than participants with no parental history (OR 1.55; 95% CI, 1.01-2.37). This was largely driven by the association of a paternal history of pCVD with CAC>0 (OR 2.15; 95% CI, 1.42-3.23), which was minimally attenuated by multivariable adjustment (OR 2.09; 95% CI, 1.31-3.32). Similarly, adjusted associations between parental pCVD and IMT > 90%tile were observed in white participants with a paternal history of pCVD (OR=1.93; 95% CI, 1.10-3.39) and any parental history pCVD (OR 1.67; 95% CI, 1.02-2.74). No significant associations between a parental history of pCVD and the odds of subclinical atherosclerosis were observed in black participants.
Parental pCVD is independently associated with early development of subclinical atherosclerosis; these associations may be race-specific for participants in their 5th decade of life.
PMCID: PMC3779512  PMID: 23027592
Family History of Premature Cardiovascular Disease; Coronary Artery Calcium; Carotid Intima-Media Thickness
5.  Association of early adult modifiable cardiovascular risk factors with left atrial size over a 20-year follow-up period: the CARDIA study 
BMJ Open  2014;4(1):e004001.
We investigate how early adult and 20-year changes in modifiable cardiovascular risk factors (MRF) predict left atrial dimension (LAD) at age 43–55 years.
The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled black and white adults (1985–1986). We included 2903 participants with echocardiography and MRF assessment in follow-up years 5 and 25. At years 5 and 25, LAD was assessed by M-mode echocardiography, then indexed to body surface area (BSA) or height. Blood pressure (BP), body mass index (BMI), heart rate (HR), smoking, alcohol use, diabetes and physical activity were defined as MRF. Associations of MRF with LAD were assessed using multivariable regression adjusted for age, ethnicity, gender and year-5 left atrial (LA) size.
The participants were 30±4 years; 55% white; 44% men. LAD and LAD/height were modest but significantly higher over the follow-up period, but LAD/BSA decreased slightly. Increased baseline and 20-year changes in BP were related to enlargement of LAD and indices. Higher baseline and changes in BMI were also related to higher LAD and LAD/height, but the opposite direction was found for LAD/BSA. Increase in baseline HR was related to lower LAD but not LAD indices, when only baseline covariates were included in the model. However, baseline and 20-year changes in HR were significantly associated to LA size.
In a biracial cohort of young adults, the most robust predictors for LA enlargement over a 20-year follow-up period were higher BP and BMI. However, an inverse direction was found for the relationship between BMI and LAD/BSA. HR showed an inverse relation to LA size.
PMCID: PMC3902509  PMID: 24384901
Cardiology; Epidemiology
6.  High Risk Blood Pressure and Obesity Increase the Risk for Left Ventricular Hypertrophy in African-American Adolescents 
The Journal of pediatrics  2012;162(1):94-100.
To examine the relative effects of high blood pressure (BP) and obesity on left ventricular mass (LVM) among African-American adolescents; and if metabolic or inflammatory factors contribute to LVM.
Study design
Using a 2×2 design, AA adolescents, were stratified by body mass index (BMI) percentile (BMI <95th %=non-obese; ≥95th %=obese) and average BP (normal <120/80 mm Hg; high BP ≥120/80). Glucose, insulin, insulin resistance, lipids, and inflammatory cytokines were measured. From echocardiography measures of LVM, calculated LVM index (LVMI) ≥95th % defined left ventricular hypertrophy (LVH).
Data included 301 adolescents (48% female), mean age 16.2 years, 51% obese, and 29% high BP. LVMI was highest among adolescents with both obesity and high BP. The multiplicative interaction of obesity and high BP on LVH was not significant (OR= 2.35, p=0.20) but the independent additive associations of obesity and high BP with log-odds of LVH were significant; obesity OR = 3.26, p<0.001; high BP OR = 2.92, p<0.001. Metabolic and inflammatory risk factors were associated with obesity, but had no independent association with LVMI. Compared with those with average systolic BP <75th %, adolescents with systolic BP from the 75th to 90th % had higher LVMI (33.2 vs 38.7 gm/m2.7, p<0.001) and greater LVH (18% vs 43%, p<0.001), independent of obesity.
Prevalence of LVH is highest among AA adolescents with average BP ≥120/80 mm Hg and obesity. There also is an independent association of LVMI with BP, beginning at the 75th systolic BP percentile.
PMCID: PMC3480988  PMID: 22817908
Adolescents; Blood Pressure; Obesity; Cardiac Hypertrophy; Minority Children
7.  Integrated wall stress: a new methodological approach to assess ventricular workload and myocardial contractile reserve 
Wall stress is a useful concept to understand the progression of ventricular remodeling. We measured cumulative LV wall stress throughout the cardiac cycle over unit time and tested whether this “integrated wall stress (IWS)” would provide a reliable marker of total ventricular workload.
Methods and results
We applied IWS to mice after experimental myocardial infarction (MI) and sham-operated mice, both at rest and under dobutamine stimulation. Small infarcts were created so as not to cause subsequent overt hemodynamic decompensation. IWS was calculated over one minute through simultaneous measurement of LV internal diameter and wall thickness by echocardiography and LV pressure by LV catheterization. At rest, the MI group showed concentric LV hypertrophy pattern with preserved LV cavity size, LV systolic function, and IWS comparable with the sham group. Dobutamine stimulation induced a dose-dependent increase in IWS in MI mice, but not in sham mice; MI mice mainly increased heart rate, whereas sham mice increased LV systolic and diastolic function. IWS showed good correlation with a product of peak-systolic wall stress and heart rate. We postulate that this increase in IWS in post-MI mice represents limited myocardial contractile reserve.
We hereby propose that IWS provides a useful estimate of total ventricular workload in the mouse model and that increased IWS indicates limited LV myocardial contractile reserve.
PMCID: PMC3750700  PMID: 23919327
Wall stress; Ventricular workload; Myocardial contractile reserve; Ventricular remodeling
9.  LVM Assessed by Echocardiography and Cardiac Magnetic Resonance, Cardiovascular Outcomes, and Medical Practice 
JACC. Cardiovascular imaging  2012;5(8):837-848.
We investigate three important areas related to the clinical use of LVM (LVM): accuracy of assessments by echocardiography and cardiac magnetic resonance (CMR), the ability to predict cardiovascular outcomes, and the comparative value of different indexing methods. The recommended formula for echocardiographic estimation of LVM uses linear measurements and is based on the assumption of the left ventricle as a prolate ellipsoid of revolution. CMR permits a modeling of the left ventricle free of cardiac geometric assumptions or acoustic window dependency, showing better accuracy and reproducibility. However, echocardiography has lower cost, easier availability, and better tolerability. From the Medline database, 26 longitudinal echocardiographic studies and 5 CMR studies, investigating LVM or LV hypertrophy as predictors of death or major cardiovascular outcomes, were identified. LVM and LV hypertrophy were reliable cardiovascular risk predictors using both modalities. However, no study directly compared the methods for the ability to predict events, agreement in hypertrophy classification, or performance in cardiovascular risk reclassification. Indexing LVM to BSA was the earliest normalization process used, but it seems to underestimate the prevalence of hypertrophy in obese and overweight subjects. Dividing LVM by height to 1.7 or 2.7 as allometric powers are the most promising normalization methods in terms of practicality and usefulness from a clinical ans scientific standpoints for scaling myocardial mass to body size. The measurement of LVM, calculation of LVMi, and classification for LVH should be standardized by scientific societies across measurement techniques and adopted by clinicians in risk stratification and therapeutic decision.
PMCID: PMC3501209  PMID: 22897998
LVM; LVH; cardiovascular events; cardiac magnetic resonance; echocardiography
11.  Childhood Obesity and Blood Pressure: Back to the Future? 
Hypertension  2011;58(5):754-755.
PMCID: PMC3287055  PMID: 21968756
This cross sectional study was conducted to test reproducibility of analysis of MRI parameters in carotids and thoracic descending aorta (TOA), evaluate the correlation of plaque burden and associations with subject age and gender.
Three hundred subjects, with cardiovascular risk factors, underwent a black blood MRI of both carotids and TOA. Mean wall area, wall thickness, lumen area, total vessel area and wall area/total vessel area (WA/TVA) ratio were manually measured. Inter-reader and intra-reader-reproducibility was tested on 187 and 20 randomly chosen subjects respectively.
The intra-observer-reproducibility for the analysis was high (Intraclass-Correlation-Coefficients (ICC’s >0.8), except mean WA/TVA ratio of TOA. Similarly, the inter-observer reproducibility was acceptable (ICC’s >0.7 for mean wall area, lumen area and total vessel area). MRI parameters in aorta and carotids increased with age for both sexes (p<0.001). Except for mean wall thickness of TOA and WA/TVA ratio, MRI parameters were significantly higher in males than in females. All MRI measurements except the mean wall thickness and WA/TVA ratio were highly reproducible. There was good correlation for mean wall area between carotids and aorta compatible with the systemic nature of atherosclerosis. Similar to clinical presentation of cardiovascular diseases we found greater values in most MRI parameters (except for WA/TVA ratio) in males than in females and with increasing age.
These data suggest that analysis of most MRI measurements of plaque burden is reproducible and that there is correlation between plaque burden between carotids and aorta validating the systemic distribution of the disease.
PMCID: PMC3338149  PMID: 19174763
13.  Serum Non-high-density lipoprotein cholesterol concentration and risk of death from cardiovascular diseases among U.S. adults with diagnosed diabetes: the Third National Health and Nutrition Examination Survey linked mortality study 
Non-high-density lipoprotein cholesterol (non-HDL-C) measures all atherogenic apolipoprotein B-containing lipoproteins and predicts risk of cardiovascular diseases (CVD). The association of non-HDL-C with risk of death from CVD in diabetes is not well understood. This study assessed the hypothesis that, among adults with diabetes, non-HDL-C may be related to the risk of death from CVD.
We analyzed data from 1,122 adults aged 20 years and older with diagnosed diabetes who participated in the Third National Health and Nutrition Examination Survey linked mortality study (299 deaths from CVD according to underlying cause of death; median follow-up length, 12.4 years).
Compared to participants with serum non-HDL-C concentrations of 35 to 129 mg/dL, those with higher serum levels had a higher risk of death from total CVD: the RRs were 1.34 (95% CI: 0.75-2.39) and 2.25 (95% CI: 1.30-3.91) for non-HDL-C concentrations of 130-189 mg/dL and 190-403 mg/dL, respectively (P = 0.003 for linear trend) after adjustment for demographic characteristics and selected risk factors. In subgroup analyses, significant linear trends were identified for the risk of death from ischemic heart disease: the RRs were 1.59 (95% CI: 0.76-3.32) and 2.50 (95% CI: 1.28-4.89) (P = 0.006 for linear trend), and stroke: the RRs were 3.37 (95% CI: 0.95-11.90) and 5.81 (95% CI: 1.96-17.25) (P = 0.001 for linear trend).
In diabetics, higher serum non-HDL-C concentrations were significantly associated with increased risk of death from CVD. Our prospective data support the notion that reducing serum non-HDL-C concentrations may be beneficial in the prevention of excess death from CVD among affected adults.
PMCID: PMC3127754  PMID: 21605423
lipids; lipoproteins; mortality; diabetes mellitus; cardiovascular diseases
15.  Acute and long term effects of grape and pomegranate juice consumption on endothelial dysfunction in pediatric metabolic syndrome 
This study aimed to determine the short- and long-term effects of consumption of grape and pomegranate juices on markers of endothelial function and inflammation in adolescents with metabolic syndrome (MetS).
In a non-pharmacologic randomized controlled trial, 30 individuals were randomly assigned to two groups of drinking natural grape or pomegranate juice for 1 month. Measurements of inflammatory factors [Hs-CRP, sE-selectin, sICAM-1, sVCAM, and interleukin 6 (IL-6)] and flow-mediated dilation (FMD) were made at baseline, 4 hours after first juice consumption and after one month of juice consumption.
The percent changes of FMD were significant in both groups in the short- and long-term. Hs-CRP had a nonsignificant decrease. sE selectin had a significant decrease after 4 hours in total and in the pomegranate juice group, followed by a significant decrease after 1 month in both groups. After 4 hours, sICAM-1 significantly decreased in the pomegranate juice group, and after 1 month it decreased in total and pomegranate juice group. Interleulkin-6 (IL-6) had a significant constant decrease at 4-hour and 1-month measurements after drinking pomegranate juice, and in both groups after 1 month. Significant negative correlations of changes in sICAM-1 and sE-selectin with changes in FMD were found in both periods of follow-up; and at 1 month for IL-6.
Decline in inflammation was associated with improvement in FMD without changes in conventional risk factors. Daily consumption of natural antioxidants may improve endothelial function in adolescents with MetS.
PMCID: PMC3214329  PMID: 22091240
Endothelium function; metabolic syndrome; antioxidants; inflammation; adolescents
16.  Association of Pathobiological Determinants of Atherosclerosis in Youth Risk Score and 15-year Change in Risk Score with Carotid Artery Intima-Media Thickness in Young Adults (From the Cardiovascular Risk in Young Finns Study) 
The American journal of cardiology  2007;100(7):1124-1129.
The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study of autopsied 15-34 year old young people developed a risk score using the coronary heart disease (CHD) risk factors (sex, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia) to estimate the probability of advanced atherosclerotic lesions in the coronary arteries. The Cardiovascular Risk in Young Finns Study measured CHD risk factors in a population-based cohort in 1986 and 2001 and measured carotid artery intima-media thickness (IMT) with ultrasound in 2001. We computed the PDAY risk score from risk factors measured in 1279 subjects who were 12-24 years old in 1986 and 27-39 years in 2001. The PDAY risk score early in life (1986) and the change in risk score over the following 15 years (between 1986 and 2001) were independent predictors of carotid artery IMT; the multiplicative effect of 1 point in the 1986 risk score was 1.008 (95% CI 1.005-1.012) and the multiplicative effect of a 1 point increase between 1986 and 2001 risk scores was 1.003 (95% CI 1.001-1.006) (multiplicative effect 0.997 for 1 point decrease). In conclusion, the change over time (either a decrease or an increase) in the risk score during adolescence and young adulthood as well as the risk score early in life are important predictors of atherosclerosis.
PMCID: PMC2700359  PMID: 17884375
Prevention; Atherosclerosis; Risk factors; Coronary disease
17.  Cardiovascular magnetic resonance parameters of atherosclerotic plaque burden improve discrimination of prior major adverse cardiovascular events 
Patients with prior major cardiovascular or cerebrovascular events (MACE) are more likely to have future recurrent events independent of traditional cardiovascular disease risk factors. The purpose of this study was to determine if patients with traditional risk factors and prior MACE had increased cardiovascular magnetic resonance (CMR) plaque burden measures compared to patients with risk factors but no prior events.
Methods and Results
Black blood carotid and thoracic aorta images were obtained from 195 patients using a rapid extended coverage turbo spin echo sequence. CMR measures of plaque burden were obtained by tracing lumen and outer vessel wall contours. Patients with prior MACE had significantly higher MR plaque burden (wall thickness, wall area and normalized wall index) in carotids and thoracic aorta compared to those without prior MACE (Wall thickness carotids: 1.03 ± 0.03 vs. 0.93± 0.03, p = 0.001; SD wall thickness carotids: 0.137 ± 0.0008 vs. 0.102 ± 0.0004, p < 0.001; wall thickness aorta: 1.63 ± 0.10 vs. 1.50 ± 0.04, p = 0.009; SD wall thickness aorta: 0.186 ± 0.035 vs. 0.139 ± 0.012, p = 0.009 respectively). Plaque burden (wall thickness) and plaque eccentricity (standard deviation of wall thickness) of carotid arteries were associated with prior MACE after adjustment for age, sex, and traditional risk factors. Area under ROC curve (AUC) for discriminating prior MACE improved by adding plaque eccentricity to models incorporating age, sex, and traditional CVD risk factors as model inputs (AUC = 0.79, p = 0.05).
A greater plaque burden and plaque eccentricity is prevalent among patients with prior MACE.
PMCID: PMC2680849  PMID: 19393089
18.  Plasma Lipid Concentrations in Non-Diabetic, African American Adults 
Despite higher rates of cardiovascular disease, African Americans have a more favorable lipid profile. The purpose of the study was to examine the association between plasma lipid concentrations and insulin resistance in African Americans and to determine if insulin resistance is present at a lower triglyceride (TG) threshold than is used for metabolic syndrome criteria.
Data were examined on 185 non-diabetic African American men (N=61) and women (N=124), mean 39.8 years. Measurements included blood pressure, anthropometrics, oral glucose tolerance test, and insulin sensitivity (M), by insulin clamp. The relationship between lipids and insulin sensitivity was analyzed by correlation analysis and by comparing triglyceride levels among tertiles of M.
Despite relatively low mean TG (87.8 ± 55.2 mg/dL), there were statistically significant correlations of M with TG (r = -.23, P<0.002), high density lipoprotein cholesterol (HDL-C; r =.19, P < 0.01)), and TG/HDL-C ratio (r = -.23, P<0.002). The correlations were strongest in men. Subjects with TG in an intermediate range (110-149 mg/dL) had insulin resistance equivalent to the high TG group (≥ 150 mg/dL).
In African Americans, triglyceride levels below the current metabolic syndrome threshold criterion are associated with insulin resistance.
PMCID: PMC1950893  PMID: 17570258
Insulin; Metabolic Syndrome; Insulin Resistance; Triglycerides; High Density Lipoprotein

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