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1.  Prognostic Value of Frontal QRS-T Angle in Patients without Clinical Evidence of Cardiovascular Disease (From the Multi-Ethnic Study of Atherosclerosis [MESA]) 
The American journal of cardiology  2013;112(12):10.1016/j.amjcard.2013.08.017.
Abnormal frontal QRS-T angle on a 12 lead electrocardiogram (ECG) is associated with incident coronary heart disease and total mortality in a biracial cohort but there have been no studies to date examining QRS-T angle’s prognostic value across multiple ethnicities. We studied 6,814 participants (52.7% women, mean age 62) from MESA; a multi-ethnic cohort aged 45–84 free of clinical cardiovascular disease (CVD) at enrollment. Baseline examination included measurement of traditional risk factors and 12-lead ECG’s. Frontal QRS-T axis was defined as normal (<75th percentile), borderline (75–95th percentile) or abnormal (≥ 95th percentile) and participants were followed for the composite endpoint of incident CVD events: cardiovascular death, myocardial infarction, angina pectoris or heart failure. After 7.6 years of follow up there were 444 total events. Borderline ((HR 1.37 95% Confidence Interval (CI) (1.10,1.70)) and abnormal QRS-T angle (HR 2.2 95% CI (1.63, 2.97)) was associated with incident CVD events in multivariable-adjusted models. However, after adjusting for T wave abnormalities there was no statistically significant association of either borderline (HR 1.12 95% CI (0.90, 1.41)) or abnormal (HR 1.31 95% CI (0.93, 1.84)) QRS-T angle with incident CVD events. Abnormal frontal QRS-T angle predicts incident CVD events in a multiethnic population and this increased risk is primarily mediated through T wave abnormalities. QRS-T angle provides an easily interpretable, continuous marker of abnormal ventricular repolarization that can aid the everyday clinician in risk prediction.
doi:10.1016/j.amjcard.2013.08.017
PMCID: PMC3863114  PMID: 24063831
Electrocardiography; risk assessment; cardiovascular disease
2.  The compensation for asynchronous cardiac quiescence in coronary wall MR imaging 
The aim of the present study was to assess the incremental benefit of compensating asynchronous cardiac quiescence in coronary wall MR imaging. With the approval of IRB, black-blood coronary wall MR imaging was performed on 30 older subjects (90 coronary wall segments). For round 1 coronary wall MR imaging, acquisition windows were traditionally set within rest period 4-chamber. Totally 51 of 90 images were ranked as "good" images and resulted in an interpretability rate of 57%. Then, an additional cine-MR was centered at coronary segments to obtain rest period cross-sectional. The rest period overlap (the intersection between rest period 4-chamber and rest period cross-sectional) was measured for each coronary segments. The "good" images had a longer rest period overlap and higher acquisition coincidence rate (the percentage of acquisition window covered by the rest period overlap) than "poor" images. Coronary wall rescans (round 2) were completed at 39 coronary segments that were judged as having "poor" images in round 1 scans. The acquisition windows was set within the rest period overlap. For the round 2 images, 17 of 39 (44%) coronary segments was ranked as "good" images. The overall interpretability rate (68 of 90, 76%) was significantly higher than that of the round 1 images alone. Our data demonstrated that asynchronous cardiac quiescence adversely affects the performance of coronary wall MR imaging. Individualizing acquisition windows based on multi-plane cine-MR imaging helps to compensate for this motion discrepancy and to improve image quality.
doi:10.1007/s10554-013-0318-3
PMCID: PMC3946801  PMID: 24170261
Coronary wall MR imaging; Asynchronous quiescence; Compensation
3.  Impact of Inflammatory Biomarkers on Relation of High Density Lipoprotein-Cholesterol with Incident Coronary Heart Disease: Cardiovascular Health Study 
Atherosclerosis  2013;231(2):10.1016/j.atherosclerosis.2013.08.036.
Background
Inflammatory factors and low HDL-C relate to CHD risk, but whether inflammation attenuates any protective association of high HDL-C is unknown.
Objective
Investigate inflammatory markers' individual and collective impact on the association of HDL-C with incident coronary heart disease (CHD).
Methods
In 3,888 older adults without known cardiovascular disease (CVD), we examined if the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA2) modify the relation of HDL-C with CHD. HDL-C, CRP, IL-6, and Lp-PLA2 values were grouped as using gender-specific tertiles. Also, an inflammation index of z-score sums for CRP, IL-6, and Lp-PLA2 was categorized into tertiles. We calculated CHD incidence for each HDL-C/inflammation group and performed Cox regression, adjusted for standard CVD risk factors and triglycerides to examine the relationship of combined HDL-C-inflammation groups with incident events.
Results
CHD incidence (per 1,000 person years) was higher for higher levels of CRP, IL-6, and the index, and lower for higher levels of HDL-C. Compared to high HDL-C/low-inflammation categories (referent), adjusted HRs for incident CHD were increased for those with high HDL-C and high CRP (HR=1.50, p<0.01) or highest IL-6 tertile (HR=1.40, p<0.05), but not with highest Lp-PLA2 tertile. Higher CHD incidence was similarly seen for those with intermediate or low HDL-C accompanied by high CRP, high IL-6, or a high inflammatory index.
Conclusion
The protective relation of high HDL-C for incident CHD appears to be attenuated by greater inflammation.
doi:10.1016/j.atherosclerosis.2013.08.036
PMCID: PMC3858257  PMID: 24267235
High Density Lipoprotein; Inflammation; C-Reactive Protein; Coronary Heart Disease
4.  Competing Cardiovascular Outcomes Associated with Subclinical Atherosclerosis (From the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2013;111(11):1541-1546.
Subclinical atherosclerosis measured by coronary artery calcium (CAC) is associated with increased risk for multiple cardiovascular disease (CVD) outcomes and non-CVD death simultaneously, and we sought to determine the competing risks of specific cardiovascular disease (CVD) events and non-CVD death associated with varying burdens of subclinical atherosclerosis. We included 3095 men and 3486 women from the Multi-Ethnic Study of Atherosclerosis, aged 45–84 years, and from 4 ethnic groups. Participants were stratified by CAC scores: 0, 1–99, and ≥ 100. We used competing Cox models to determine competing cumulative incidences and hazards ratios within a group (e.g., among those with CAC ≥ 100) and hazards ratios for specific events between groups (e.g., CAC ≥ 100 vs. CAC = 0). We compared risks for specific CVD events and also compared against non-CVD death. In women, during a mean follow up of 7.1 years, the hazards ratios (HR) for any CVD event compared with a non-CVD death occurring first for CAC = 0 and CAC ≥ 100 were 1.40 (95% CI, 0.97–2.04) and 3.07 (2.02–4.67), respectively. CHD was the most common first CVD event type at all levels of CAC, and CHD rates were 9.5% vs. 1.6% (HR 6.24; 3.99–9.75) for women with CAC ≥100 compared with CAC = 0. We observed similar results in men. In conclusion, at all levels of CAC, CHD was the most common first CVD event and this analysis represents a novel approach to understanding the temporal sequence of cardiovascular events associated with atherosclerosis.
doi:10.1016/j.amjcard.2013.02.003
PMCID: PMC3657323  PMID: 23499272
coronary artery calcium; competing risks
5.  Natural History of the Early Repolarization Pattern in a Biracial Cohort: CARDIA (Coronary Artery Risk Development in Young Adults) Study 
Objectives
The objective of this analysis was to determine the natural history and prospective association of cardiovascular risk factors with early repolarization (ER).
Background
ER is common and has been suggested to increase risk for cardiovascular mortality in middle-aged adults. Data are sparse regarding the natural history of ER from young adulthood to middle age.
Methods
We examined 5,069 participants (mean age 25 years at baseline; 40% black) from the CARDIA (Coronary Artery Risk Development in Young Adults) cohort over 20 years. Electrocardiograms were recorded at years 0 (Y0), 7 (Y7), and 20 (Y20) and coded as either definite, probable, possible, or no ER. Logistic regression was used to determine the association of cardiovascular risk factors with the presence of ER cross-sectionally and prospectively.
Results
A total of 941 of the 5,069 participants (18.6%) had definite ER at baseline, and only 119 of 2,505 participants (4.8%) at the Y20 examination still demonstrated the presence of ER. Younger age, black race, male sex, longer exercise duration and QRS duration, and lower body mass index (BMI), heart rate, QT index, and Cornell voltage were associated cross-sectionally with the presence of ER. Predictors of maintenance of ER from Y0 to Y20 were black race (odds ratio [OR]: 2.62; 95% CI; 1.61 to 4.25), BMI (OR: 0.62 per 1 SD; 95% CI: 0.40 to 0.94), serum triglyceride levels (OR: 0.66 per 1 SD; 95% CI: 0.45 to 0.98), and QRS duration (OR: 1.68 per 1 SD; 95% CI: 1.37 to 2.06) at baseline.
Conclusions
The prevalence of ER was significantly higher than previous estimates among asymptomatic young adults, and the majority of ER regressed by middle age. Black race, lower BMI, lower serum triglyceride levels, and longer QRS duration were independently associated with maintenance of ER over time.
doi:10.1016/j.jacc.2012.11.053
PMCID: PMC3748821  PMID: 23428218
early repolarization; electrocardiography; epidemiology
6.  Cardiovascular Health Behavior and Health Factor Changes (1988 –2008) and Projections to 2020 
Circulation  2012;125(21):2595-2602.
Background
The American Heart Association’s 2020 Strategic Impact Goals target a 20% relative improvement in overall cardiovascular health with the use of 4 health behavior (smoking, diet, physical activity, body mass) and 3 health factor (plasma glucose, cholesterol, blood pressure) metrics. We sought to define current trends and forward projections to 2020 in cardiovascular health.
Methods and Results
We included 35 059 cardiovascular disease–free adults (aged ≥20 years) from the National Health and Nutrition Examination Survey 1988–1994 and subsequent 2-year cycles during 1999–2008. We calculated population prevalence of poor, intermediate, and ideal health behaviors and factors and also computed a composite, individual-level Cardiovascular Health Score for all 7 metrics (poor=0 points; intermediate=1 point; ideal=2 points; total range, 0–14 points). Prevalence of current and former smoking, hypercholesterolemia, and hypertension declined, whereas prevalence of obesity and dysglycemia increased through 2008. Physical activity levels and low diet quality scores changed minimally. Projections to 2020 suggest that obesity and impaired fasting glucose/diabetes mellitus could increase to affect 43% and 77% of US men and 42% and 53% of US women, respectively. Overall, population-level cardiovascular health is projected to improve by 6% overall by 2020 if current trends continue. Individual-level Cardiovascular Health Score projections to 2020 (men=7.4 [95% confidence interval, 5.7–9.1]; women=8.8 [95% confidence interval, 7.6–9.9]) fall well below the level needed to achieve a 20% improvement (men=9.4; women=10.1).
Conclusions
The American Heart Association 2020 target of improving cardiovascular health by 20% by 2020 will not be reached if current trends continue.
doi:10.1161/CIRCULATIONAHA.111.070722
PMCID: PMC3914399  PMID: 22547667
cardiovascular disease risk factors; epidemiology; risk factors; trends
7.  Prevalence, Prospective Risk Markers, and Prognosis Associated With the Presence of Left Ventricular Diastolic Dysfunction in Young Adults 
American Journal of Epidemiology  2012;177(1):20-32.
The authors sought to determine the prevalence, prospective risk markers, and prognosis associated with diastolic dysfunction in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The CARDIA Study cohort includes approximately equal proportions of white and black men and women. The authors collected data on risk markers at year 0 (1985–1986), and echocardiography was done at year 5 when the participants were 23–35 years of age. Participants were followed for 20 years (through 2010) for a composite endpoint of all-cause mortality, myocardial infarction, heart failure, and stroke. Diastolic function was defined according to a validated hierarchical classification algorithm. In the 2,952 participants included in the primary analysis, severe diastolic dysfunction was present in 1.1% and abnormal relaxation was present in 9.3%. Systolic blood pressure at year 0 was associated with both severe diastolic dysfunction and abnormal relaxation 5 years later, whereas exercise capacity and pulmonary function abnormalities were associated only with abnormal relaxation 5 years later. After multivariate adjustment, the hazard ratios for the composite endpoint in participants with severe diastolic dysfunction and abnormal relaxation were 4.3 (95% confidence interval: 2.0, 9.3) and 1.6 (95% confidence interval: 1.1, 2.5), respectively. Diastolic dysfunction in young adults is associated with increased morbidity and mortality, and the identification of prospective risk markers associated with diastolic dysfunction could allow for targeted primary prevention efforts.
doi:10.1093/aje/kws224
PMCID: PMC3590041  PMID: 23211639
CARDIA study; clinical outcomes; diastolic dysfunction; left ventricle
8.  Chicago Healthy Aging Study: Objectives and Design 
American Journal of Epidemiology  2013;178(4):635-644.
Investigators in the Chicago Healthy Aging Study (CHAS) reexamined 1,395 surviving participants aged 65–84 years (28% women) from the Chicago Heart Association Detection Project in Industry (CHA) 1967–1973 cohort whose cardiovascular disease (CVD) risk profiles were originally ascertained at ages 25–44 years. CHAS investigators reexamined 421 participants who were low-risk (LR) at baseline and 974 participants who were non-LR at baseline. LR was defined as having favorable levels of 4 major CVD risk factors: serum total cholesterol level <200 mg/dL and no use of cholesterol-lowering medication; blood pressure 120/≤80 mm Hg and no use of antihypertensive medication; no current smoking; and no history of diabetes or heart attack. While the potential of LR status in overcoming the CVD epidemic is being recognized, the long-term association of LR with objectively measured health in older age has not been examined. It is hypothesized that persons who were LR in 1967–1973 and have survived to older age will have less clinical and subclinical CVD, lower levels of inflammatory markers, and better physical performance/functioning and sleep quality. Here we describe the rationale, objectives, design, and implementation of this longitudinal epidemiologic study, compare baseline and follow-up characteristics of participants and nonparticipants, and highlight the feasibility of reexamining study participants after an extended period postbaseline with minimal interim contact.
doi:10.1093/aje/kwt020
PMCID: PMC3816341  PMID: 23669655
cardiovascular disease; epidemiologic studies; follow-up examination; risk factors
9.  Remaining Lifetime Risk for Cancer Death at Selected Ages by Sex and Smoking status: The Lifetime Risk Pooling Project 
Cancer causes & control : CCC  2012;23(10):1729-1737.
Background
Understanding how sex and tobacco exposure may modify lifetime risks for cancer mortality is important for effective communication of risk in targeted public health messages.
Objective
To determine lifetime risk estimates for cancer death associated with sex and smoking status in the United States.
Methods
A pooled cohort design using ten well-defined epidemiologic cohorts including middle-aged and older individuals was used to estimate the lifetime risk for cancer death at selected index ages, with death from non-cancer causes as the competing risk, by sex and smoking status.
Results
There were a total of 11,317 cancer-related deaths. At age 45 years, the lifetime risk of cancer death for male smokers is 27.7% (95% CI 24.0% to 31.4%) compared to 15.8% (95% CI 12.7% to 18.9%) for male non-smokers. At age 45 years, the lifetime risk of cancer death for female smokers is 21.7% (95% CI 18.8% to 24.6%) compared to 13.2% (95% CI 11.0% to 15.4%) for female non-smokers. Remaining lifetime risk for cancer death declined with age, and men have a greater risk for cancer death compared to women. Adjustment for competing risk of death, particularly representing cardiovascular mortality, yielded a greater change in lifetime risk estimates for men and smokers compared to women and non-smokers.
Conclusions
At the population level the lifetime risk for cancer death remains significantly higher for smokers compared to non-smokers, regardless of sex. These estimates may provide clinicians with useful information for counseling individual patients and highlight the need for continued public health efforts related to smoking cessation.
doi:10.1007/s10552-012-9959-0
PMCID: PMC3542389  PMID: 22825072
Tobacco; Smoking; Cancer; Lifetime Risk; Cancer mortality; Sex
10.  Association of Cardiac Annular / Valvular Calcification with Brain Findings on Magnetic Resonance Imaging in Community Dwelling Older Adults: the Cardiovascular Health Study 
Objective
The objective of this study is to investigate the association of mitral annular calcification (MAC), aortic annular calcification (AAC), and aortic valve sclerosis (AVSc) with covert magnetic resonance imaging (MRI)-defined brain infarcts.
Background
Clinically silent brain infarcts defined by MRI are associated with increased risk of cognitive decline, dementia, and future overt stroke. Left sided cardiac valvular / annular calcifications are suspected as risk factors for clinical ischemic stroke.
Methods
2,680 Cardiovascular Health Study participants without clinical history of stroke or transient ischemic attack underwent both brain MRI (1992–93) and echocardiography (1994–95).
Results
The mean age of the participants was 74.5 years ± 4.8 and 39.3% were men. The presence of any annular / valvular calcification (either MAC or AAC or AVSc), MAC alone, or AAC alone were significantly associated with a higher prevalence of covert brain infarcts in unadjusted analyses (p < 0.01 for all). In models adjusted for age, sex, race, body mass index, physical activity, creatinine, systolic blood pressure, total cholesterol, HDL-cholesterol, smoking, diabetes, coronary heart disease, and congestive heart failure, the presence of any annular / valve calcification remained associated with covert brain infarcts [RR 1.24 (95% CI 1.05, 1.47)]. The degree of annular / valvular calcification severity showed a direct relation with the presence of covert MRI findings.
Conclusion
Left-sided cardiac annular / valvular calcification are associated with covert MRI-defined brain infarcts. Further study is warranted to identify mechanisms and determine whether intervening on the progression of annular / valvular calcification could reduce the incidence of covert brain infarcts as well as the associated risk of cognitive impairment and future stroke.
doi:10.1016/j.jacc.2011.01.034
PMCID: PMC4104125  PMID: 21596233
Covert Brain Infarcts; Aortic Valve; Mitral Valve; Calcification; Epidemiology
11.  Competing cardiovascular outcomes associated with electrocardiographic left ventricular hypertrophy: the Atherosclerosis Risk in Communities study 
Heart (British Cardiac Society)  2011;98(4):330-334.
OBJECTIVE
Individuals with electrocardiographically-determined left ventricular hypertrophy (ECG LVH) are at risk for multiple cardiovascular disease (CVD) outcomes simultaneously. We sought to characterize the competing incidences for subtypes of first CVD events or non-CVD death in those with and without ECG LVH.
DESIGN
We included participants in the Atherosclerosis Risk in Communities (ARIC) study. ECG LVH was defined according to Sokolow-Lyon criteria. We used competing Cox models to compare hazards for diverse outcomes within groups (e.g., among those with ECG LVH) and for a given event between groups (ECG LVH versus no ECG LVH).
RESULTS
After 15 years, men with ECG LVH at baseline (N = 383) had cumulative incidence of first CVD events and non-CVD deaths of 29.2% and 6.1%, respectively (hazard ratio 4.86; 95% CI, 3.04–7.77). In men without ECG LVH (N = 6576) the incidence of any first CVD event and non-CVD death was 18.9% and 6.9%, respectively (hazard ratio 2.67; 2.39–2.98). Similar associations were observed in women (N = 381 with and N = 8187 without ECG LVH). Coronary heart disease (CHD) was the most common first event in men with ECG LVH (15.0%) and heart failure (HF) was the most common first event in women with ECG LVH (10.5%). After adjustment for risk factors including systolic blood pressure, any CVD event remained the most likely first event.
CONCLUSIONS
Among middle-aged individuals with ECG LVH, the most likely first events are CHD in men and HF in women; these results may have implications for preventive approaches.
doi:10.1136/heartjnl-2011-300819
PMCID: PMC3569012  PMID: 22139711
left ventricular hypertrophy; cardiovascular disease; coronary heart disease; stroke; heart failure
12.  Yield of Screening for Coronary Artery Calcium in Early Middle-Age Adults Based on the 10-Year Framingham Risk Score 
JACC. Cardiovascular imaging  2012;5(9):923-930.
OBJECTIVES
The purpose of this study was to assess the prevalence and distribution of coronary artery calcium (CAC) across Framingham Risk Score (FRS) strata and therefore determine FRS levels at which asymptomatic, young to early middle-age individuals could potentially benefit from CAC screening.
BACKGROUND
High CAC burden is associated with increased risk of coronary events beyond the FRS. Expert panel recommendations for CAC screening are based on data obtained in middle-age and older individuals.
METHODS
We included 2,831 CARDIA (Coronary Artery Risk Development in Young Adults) study participants with an age range of 33 to 45 years. The number needed to screen ([NNS] number of people in each FRS stratum who need to be screened to detect 1 person with a CAC score above the specified cut point) was used to assess the yield of screening for CAC. CAC prevalence was compared across FRS strata using a chi-square test.
RESULTS
CAC scores >0 and ≥100 were present in 9.9% and 1.8% of participants, respectively. CAC prevalence and amount increased across higher FRS strata. A CAC score >0 was observed in 7.3%, 20.2%, 19.1%, and 44.8% of individuals with FRSs of 0 to 2.5%, 2.6% to 5%, 5.1% to 10%, and >10%, respectively (NNS = 14, 5, 5, and 2, respectively). A CAC score of ≥100 was observed in 1.3%, 2.4%, and 3.5% of those with FRSs of 0 to 2.5%, 2.6% to 5%, and 5.1% to 10%, respectively (NNS = 79, 41, and 29, respectively), but in 17.2% of those with an FRS >10% (NNS = 6). Similar trends were observed when findings were stratified by sex and race.
CONCLUSIONS
In this young to early middle-age cohort, we observed concordance between CAC prevalence/amount and FRS strata. Within this group, the yield of screening and possibility of identifying those with a high CAC burden (CAC score of ≥100) is low in those with an FRS of ≤10%, but considerable in those with an FRS >10%.
doi:10.1016/j.jcmg.2012.01.022
PMCID: PMC3664953  PMID: 22974805
coronary artery calcium; coronary heart disease; Framingham Risk Score; number needed to screen; risk factors
13.  The Association of Framingham and Reynolds Risk Scores with Incidence and Progression of Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis 
Objectives
To compare the association of the Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) with subclinical atherosclerosis, assessed by incidence and progression of coronary artery calcium (CAC).
Background
The comparative effectiveness of competing risk algorithms for indentifying subclinical atherosclerosis is unknown.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of 6,814 participants free of baseline CVD. All participants underwent risk factor assessment, as well as baseline and follow-up CAC testing. We assessed the performance of the FRS and RRS to predict CAC incidence and progression using relative risk and robust linear regression.
Results
The study population included 5,140 individuals (61±10 years, 47% males, mean follow-up: 3.1±1.3 years). Among 53% of subjects (n=2,729) with no baseline CAC, 18% (n=510) developed incident CAC. Both the FRS and RRS were significantly predictive of incident CAC [RR 1.40 (95% CI 1.29 – 1.52), and RR 1.41 (95% CI 1.30 – 1.54) per 5% increase in risk, respectively] and CAC progression [mean CAC score change 6.92 (95% CI 5.31 – 8.54) and 6.82 (95% CI 5.51 – 8.14) per 5% increase]. Discordance in risk category classification (< or > 10% 10-year CHD risk) occurred in 13.7%, with only the RRS consistently adding predictive value for incidence and progression of CAC. These subclinical atherosclerosis findings are supported by a CHD events analysis over 5.6±0.7 year follow-up.
Conclusion
Both the RRS and FRS predict onset and progression of subclinical atherosclerosis. However, the RRS may provide additional predictive information when discordance between the scoring systems exists.
doi:10.1016/j.jacc.2011.08.022
PMCID: PMC4079464  PMID: 22051329
coronary artery calcium progression; subclinical atherosclerosis; risk prediction; Reynolds Risk Score; Framingham Risk Score
14.  Status of Cardiovascular Health in US Adults: Prevalence Estimates from the National Health and Nutrition Examination Surveys (NHANES) 2003-2008 
Circulation  2011;125(1):45-56.
Background
The American Heart Association's 2020 Strategic Impact Goals define a new concept, “cardiovascular (CV) health”; however, current prevalence estimates of the status of CV health in U.S. adults according to age, sex and race/ethnicity have not been published.
Methods and Results
We included 14,515 adults (≥20 years) from the 2003-2008 National Health and Nutrition Examination Surveys. Participants were stratified by young (20-39 years), middle (40-64 years), and older ages (65+ years). CV health behaviors (diet, physical activity, body mass index, smoking) and CV health factors (blood pressure, total cholesterol, fasting blood glucose, smoking) were defined as poor, intermediate, or ideal. Less than 1% of adults exhibited ideal CV health for all 7 metrics. For CV health behaviors, non-smoking was most prevalent (range:60.2-90.4%) while ideal Healthy Diet Score was least prevalent (range:0.2-2.6%) across groups. Prevalence of ideal BMI (range:36.5-45.3%) and ideal physical activity levels (range:50.2-58.8%) were higher in young adults compared to middle or older ages. Ideal total cholesterol (range:23.7-36.2%), blood pressure (range:11.9-16.3%) and fasting blood glucose (range:31.2-42.9%) were lower in older adults compared with young and middle age adults.Prevalence of poor CV health factors was lowest in young age but higher at middle and older ages. Prevalence estimates by age and sex were consistent across race/ethnic groups.
Conclusions
These prevalence estimates of CV health represent a starting point from which effectiveness of efforts to promote CV health and prevent CV disease can be monitored and compared in U.S. adult populations.
doi:10.1161/CIRCULATIONAHA.111.035733
PMCID: PMC4077723  PMID: 22095826
Cardiovascular Diseases; Diet; Epidemiology; Obesity; Risk Factors
15.  Quantifying Options for Reducing Coronary Heart Disease Mortality By 2020 
Circulation  2013;127(25):2477-2484.
Introduction
The AHA 2020 Strategic Impact Goal proposes a 20% improvement in cardiovascular health of all Americans. We aimed to estimate the potential reduction in coronary heart disease (CHD) deaths.
Methods and Results
We used data on 40,373 CVD-free adults from NHANES (1988–2010). We quantified recent trends for six metrics (total cholesterol [TC]; systolic blood pressure [SBP]; physical inactivity; smoking; diabetes; obesity) and generated linear projections to 2020. We projected the expected number of CHD deaths in 2020 if 2006 age- and sex-specific CHD death rates remained constant, which would result in approximately 480,000 CHD deaths in 2020 (12% increase). We used the previously validated IMPACT CHD model to project numbers of CHD deaths in 2020 under two different scenarios.
A) Assuming a 20% improvement in each CVH metric, we project 365,000 CHD deaths in 2020, (range 327,000–403,000) a 24% decrease reflecting modest reductions in TC (−41,000), SBP (−36,000), physical inactivity (−12,000), smoking (−10,000), diabetes (−10,000), and obesity (−5,000). B) Assuming that recent risk factor trends continue to 2020, we project 335,000 CHD deaths (range 274,000–386,000), a 30% decrease reflecting improvements in TC, SBP, smoking and physical activity (~167,000 fewer deaths), offset by increases in diabetes and BMI (~24,000 more deaths).
Conclusions
Two contrasting scenarios of change in CVH metrics could prevent 24–30% of the CHD deaths expected in 2020, though with differing impacts by age. Unfavorable continuing trends in obesity and diabetes would have substantial adverse effects. This analysis demonstrates the utility of modelling to inform health policy.
doi:10.1161/CIRCULATIONAHA.112.000769
PMCID: PMC3795417  PMID: 23661723
heart disease; American Heart Association; epidemiology; risk factor
16.  Racial Differences in Risks for First Cardiovascular Events and Non-Cardiovascular Death: the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Multi-Ethnic Study of Atherosclerosis (MESA) 
Circulation  2012;126(1):50-59.
Background
No studies have compared first CVD events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously.
Methods and Results
We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in three multi-center, NHLBI-sponsored cohorts. Of 14569 ARIC study participants aged 45–64y with mean follow up of 10.5y, 11.6% had CVD and 5.0% had non-CVD death as first events; among 4237 CHS study participants aged 65–84y and followed for 8.5y, these figures were 43.2% and 15.7%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for MESA participants. Traditional Cox and competing risks models yielded different results for CHD risk. Black men appeared somewhat more likely than white men to experience CHD using a standard Cox model (HR 1.06; 95% CI 0.90, 1.26) whereas they appeared less likely than white men to have a first CHD event using a competing risks model (HR 0.77; 95% CI 0.60, 1.00).
Conclusions
CVD affects blacks at an earlier age than whites; this may be partially attributable to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events.
doi:10.1161/CIRCULATIONAHA.111.057232
PMCID: PMC3437934  PMID: 22693351
cardiovascular diseases; epidemiology; prevention; risk factors; survival
17.  Effects of respiratory motion on coronary wall MR imaging: A quantitative study of older adults 
Purpose
The aim of the present study is to assess the effects of respiratory motion on the image quality of two-dimensional (2D), free-breathing, black-blood coronary wall (magnetic resonance) MR imaging.
Materials and methods
This study was compliance with the HIPPA. With the approval of the institution review board, 230 asymptomatic participants, including 164 male patients (72.9 ± 4.4 years) and 66 female patients (72.4 ± 5.1 years), were recruited. Written informed consent was obtained. A 2D navigator(NAV)-gated, black-blood coronary wall MR imaging sequence was run on the left main artery, the left anterior descending artery and the right coronary artery. The drift of the location of the NAV and scan efficiency were compared between good (scored 2 or 3) and poor images (scored 1). Age, body weight, body weight index (BMI), heart rate, length of the rest period of cardiac motion, diaphragm excursion and breathing frequency were compared using a t-test between the "successful" (having 2 or 3 good images) and "unsuccessful" cases (having 1 or 0 good images). A logistic regression model was applied to identify the contributors to good image quality.
Results
The drift of the NAV location and the scan efficiency were higher in the 411 good images compared with the 279 poor images. Minimal drift of the NAV location and low body weight were identified as independent predictors of good images after using a logistic regression model to adjust for multiple physiological and technical factors.
Conclusions
The stability of respiratory motion significantly influences the image quality of 2D, free-breathing, black-blood coronary wall MR imaging.
doi:10.1007/s10554-013-0187-9
PMCID: PMC3679310  PMID: 23378158
Coronary wall MR imaging; Respiratory motion; Effects
18.  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 
Background
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.
Design
Prospective community-based cohort study
Methods
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.
Results
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.
Conclusions
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.
doi:10.1177/2047487312462801
PMCID: PMC3779512  PMID: 23027592
Family History of Premature Cardiovascular Disease; Coronary Artery Calcium; Carotid Intima-Media Thickness
19.  Minor Isolated Q Waves and Cardiovascular Events in the MESA Study 
The American journal of medicine  2013;126(5):450.e9-450.e16.
BACKGROUND
The significance of minor isolated Q waves in the resting electrocardiograms (ECGs) of apparently healthy individuals is unknown.
OBJECTIVE
To examine the association between minor isolated Q waves and incident cardiovascular disease events in the Multi-Ethnic Study of Atherosclerosis (MESA).
DESIGN
This analysis included 6551 MESA participants (38% white, 28% black, 22% Hispanic, 12% Chinese) who were free of cardiovascular disease at enrollment. Cox proportional hazards models were used to examine the association between minor isolated Q waves defined by the Minnesota ECG Classification with adjudicated incident cardiovascular events.
RESULTS
During up to 7.8 years of follow-up, 423 events occurred, with a rate of 10.7 events per 1000 person-years. A significant interaction between minor isolated Q waves and race/ethnicity was observed (P = .030). In models stratified by race/ethnicity and adjusted for demographics, socioeconomic status, common cardiovascular risk factors, and other ECG abnormalities, presence of isolated minor Q waves was significantly associated with incident cardiovascular events in Hispanics (hazard ratio [HR] 2.62; 95% confidence interval [CI], 1.42-4.82), but not in whites (HR 0.65; 95% CI, 0.32-1.33) or blacks (HR 1.46; 95% CI, 0.74-2.89). Despite the statistically significant association in the Chinese population, the small number of events precluded solid conclusions in this race/ethnicity.
CONCLUSION
The prognostic significance of minor isolated Q waves varies across races/ethnicities; they carry a high risk for future cardiovascular events in apparently healthy Hispanics, but not in whites or blacks.
doi:10.1016/j.amjmed.2012.10.030
PMCID: PMC3741651  PMID: 23582938
Electrocardiography; MESA; Minor isolated Q waves; Race/ethnicity
20.  Prevalence of Electrocardiographic Abnormalities in a Middle-Aged, Biracial Population: Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Journal of electrocardiology  2010;43(5):385.e1-385.e9.
Background
Few studies to date have described the prevalence of electrocardiographic (ECG) abnormalities in a biracial middle-aged cohort.
Methods and Results
Participants underwent measurement of traditional risk factors and 12-lead ECGs coded using both Minnesota Code (MC) and Novacode (NC) criteria. Among 2585 participants, of whom 57% were women and 44% were black (mean age 45 years), the prevalence of major and minor abnormalities were significantly higher (all P<0.001) among black men and women compared to whites. These differences were primarily due to higher QRS voltage and ST/T wave abnormalities among blacks. There was also a higher prevalence of Q waves (MC 1-1, 1-2, 1-3) than described by previous studies. These racial differences remained after multivariate adjustment for traditional cardiovascular (CV) risk factors.
Conclusions
Black men and women have a significantly higher prevalence of ECG abnormalities, independent of traditional CV risk factors, than whites in a contemporary cohort middle-aged participants.
doi:10.1016/j.jelectrocard.2010.02.001
PMCID: PMC3569004  PMID: 20374967
21.  Prediction of Coronary Artery Calcium Progression in Individuals with Low Framingham Risk Score: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Jacc. Cardiovascular Imaging  2012;5(2):144-153.
Objectives
We sought to determine whether novel markers not involving ionizing radiation could predict CAC progression in a low-risk population.
Background
Increase in coronary artery calcium (CAC) scores over time (CAC progression) improves prediction of coronary heart disease (CHD) events. Due to radiation exposure, CAC measurement represents an undesirable method for repeated risk assessment, particularly in low predicted risk individuals (Framingham Risk Score [FRS] <10%).
Methods
From 6814 MESA participants, 2620 individuals were classified as low risk for CHD events (FRS <10%), and had follow-up CAC measurement. In addition to traditional risk factors [(RFs) - base model], various combinations of novel-marker models were selected based on data-driven, clinical, or backward stepwise selection techniques.
Results
Mean follow-up was 2.5 years. CAC progression occurred in 574 participants (22% overall; 214 of 1830 with baseline CAC =0, and 360 of 790 with baseline CAC >0). Addition of various combinations of novel markers to the base model (c-statistic =0.711), showed improvements in discrimination of approximately only 0.005 each (c-statistics 0.7158, 0.7160 and 0.7164) for the best-fit models. All 3 best-fit novel-marker models calibrated well but were similar to the base model in predicting individual risk probabilities for CAC progression. The highest prevalence of CAC progression occurred in the highest compared to the lowest probability quartile groups (39.2–40.3% versus 6.4–7.1%).
Conclusions
In individuals at low predicted risk by FRS, traditional RFs predicted CAC progression in the short term with good discrimination and calibration. Prediction improved minimally when various novel markers were added to the model.
doi:10.1016/j.jcmg.2011.11.008
PMCID: PMC3310187  PMID: 22340820
coronary calcium; Framingham risk score; risk factors; progression
22.  Incident Obesity and Cardiovascular Risk Factors Between Young Adulthood and Middle Age by Religious Involvement: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Preventive Medicine  2011;54(2):117-121.
Background
Religious involvement has been associated with improved health outcomes but greater obesity in older adults. No longitudinal study of young adults has examined the prospective association of religious involvement with incident cardiovascular risk factors (RFs) and subclinical disease (subCVD).
Methods
We included 2433 participants of the CARDIA study, aged 20 to 32 in 1987 when religiosity was assessed, who were followed for 18 years. Multivariable-adjusted regression models were fitted to assess prospective associations of frequency of religious participation at baseline with incidence of RFs and prevalence of subCVD after 18 years’ follow up.
Results
High frequency of religious participation was associated with a significantly greater incidence of obesity in unadjusted models (RR 1.57, 95% CI 1.14 – 1.73) and demographic-adjusted models (RR 1.34, 95% CI 1.09 – 1.65) but not after additional adjustment for baseline RFs (RR 1.17, 95% CI 0.97 – 1.41). When religious participation was treated dichotomously, any religious participation, compared with none, was associated with significantly lower subCVD.
Conclusions
Frequent religious participants are more likely to become obese between young adulthood and middle age; this association is confounded by demographic and other factors. Nonetheless, young adults with frequent participation may represent an opportunity for obesity prevention.
doi:10.1016/j.ypmed.2011.11.004
PMCID: PMC3310238  PMID: 22155479
Religion; Cardiovascular Disease; Obesity; Epidemiology; Prevention
23.  Lifetime Risk for Heart Failure Among White and Black Americans: Cardiovascular Lifetime Risk Pooling Project 
Objective
To estimate lifetime risk for HF by sex and race.
Background
Prior estimates of lifetime risk for developing heart failure (HF) range from 20% to 33% in predominantly white cohorts. Short-term risks for HF appear higher for blacks than whites, but only limited comparisons of lifetime risk for HF have been made.
Methods
Using public-release and internal datasets from NHLBI-sponsored cohorts, we estimated lifetime risks for developing HF to age 95, with death free of HF as the competing event, among participants in Chicago Heart Association Detection Project in Industry (CHA), Atherosclerosis Risk in Communities (ARIC), and Cardiovascular Health Study (CHS) cohorts.
Results
There were 39,578 participants (33,652 [85%] white; 5,926 [15%] black) followed for 716,976 person-years; 5,983 participants developed HF. At age 45 years, lifetime risks for HF through age 95 years in CHA and CHS were 30-42% in white men, 20-29% in black men, 32-39% in white women, and 24-46% in black women. Results for ARIC demonstrated similar lifetime risks for HF in blacks and whites through age 75 years (limit of follow-up). Lifetime risk for HF was higher with higher BP and BMI at all ages in both blacks and whites and did not diminish substantially with advancing index age.
Conclusions
These are among the first data to compare lifetime risks for HF between blacks and whites. Lifetime risks for HF are high and appear similar for black and white women, yet are somewhat lower for black compared with white men due to competing risks.
doi:10.1016/j.jacc.2013.01.022
PMCID: PMC3618527  PMID: 23500287
lifetime risk; heart failure; epidemiology
24.  Electronic Health Record-Based Patient Identification and Individualized Mailed Outreach for Primary Cardiovascular Disease Prevention: A Cluster Randomized Trial 
ABSTRACT
BACKGROUND
Many individuals at higher risk for cardiovascular disease (CVD) do not receive recommended treatments. Prior interventions using personalized risk information to promote prevention did not test clinic-wide effectiveness.
OBJECTIVE AND DESIGN
To perform a 9-month cluster-randomized trial, comparing a strategy of electronic health record-based identification of patients with increased CVD risk and individualized mailed outreach to usual care.
PARTICIPANTS
Patients of participating physicians with a Framingham Risk Score of at least 5 %, low-density lipoprotein (LDL)-cholesterol level above guideline threshold for drug treatment, and not prescribed a lipid-lowering medication were included in the intention-to-treat analysis.
INTERVENTION
Patients of physicians randomized to the intervention group were mailed individualized CVD risk messages that described benefits of using a statin (and controlling hypertension or quitting smoking when relevant).
MAIN MEASURES
The primary outcome was occurrence of a LDL-cholesterol level, repeated in routine practice, that was at least 30 mg/dl lower than prior. A secondary outcome was lipid-lowering drug prescribing. Clinicaltrials.gov identifier: NCT01286311.
KEY RESULTS
Fourteen physicians with 218 patients were randomized to intervention, and 15 physicians with 217 patients to control. The mean patient age was 60.7 years and 77% were male. There was no difference in the primary outcome (11.0 % vs. 11.1 %, OR 0.99, 95 % CI 0.56–1.74, P = 0.96), but intervention group patients were twice as likely to receive a prescription for lipid-lowering medication (11.9 %, vs. 6.0 %, OR 2.13, 95 % CI 1.05–4.32, p = 0.038). In post hoc analysis with extended follow-up to 18 months, the primary outcome occurred more often in the intervention group (22.5 % vs. 16.1 %, OR 1.59, 95 % CI 1.05–2.41, P = 0.029).
CONCLUSIONS
In this effectiveness trial, individualized mailed CVD risk messages increased the frequency of new lipid-lowering drug prescriptions, but we observed no difference in proportions lowering LDL-cholesterol after 9 months. With longer follow-up, the intervention’s effect on LDL-cholesterol levels was apparent.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-2268-1) contains supplementary material, which is available to authorized users.
doi:10.1007/s11606-012-2268-1
PMCID: PMC3599027  PMID: 23143672
cholesterol; primary care; cardiovascular disease prevention; electronic health records; patient outreach
25.  Coronary Heart Disease Risks Associated with High Levels of HDL Cholesterol 
Background
The association between high‐density lipoprotein cholesterol (HDL‐C) and coronary heart disease (CHD) events is not well described in individuals with very high levels of HDL‐C (>80 mg/dL).
Methods and Results
Using pooled data from 6 community‐based cohorts we examined CHD and total mortality risks across a broad range of HDL‐C, including values in excess of 80 mg/dL. We used Cox proportional hazards models with penalized splines to assess multivariable, adjusted, sex‐stratified associations of HDL‐C with the hazard for CHD events and total mortality, using HDL‐C 45 mg/dL and 55 mg/dL as the referent in men and women, respectively. Analyses included 11 515 men and 12 925 women yielding 307 245 person‐years of follow‐up. In men, the association between HDL‐C and CHD events was inverse and linear across most HDL‐C values; however at HDL‐C values >90 mg/dL there was a plateau effect in the pattern of association. In women, the association between HDL‐C and CHD events was inverse and linear across lower values of HDL‐C, however at HDL‐C values >75 mg/dL there were no further reductions in the hazard ratio point estimates for CHD. In unadjusted models there were increased total mortality risks in men with very high HDL‐C, however mortality risks observed in participants with very high HDL‐C were attenuated after adjustment for traditional risk factors.
Conclusions
We did not observe further reductions in CHD risk with HDL‐C values higher than 90 mg/dL in men and 75 mg/dL in women.
doi:10.1161/JAHA.113.000519
PMCID: PMC4187512  PMID: 24627418
CHD events; total mortality; very‐high HDL‐C

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