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1.  Association of Neighborhood Characteristics with Cardiovascular Health in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
The concept of ‘cardiovascular health’ (CVH) was introduced as a global measure of one’s cardiovascular health. Previous studies established the relationship between neighborhood characteristics and individual cardiovascular risk factors. However, the relationship between neighborhood environment and overall CVH remains unknown.
Methods and Results
We analyzed data from the MESA baseline exam (2000–2002). Mean age was 61.6 years and 52% were female. Ideal, intermediate and poor categories of cholesterol, body mass index, diet, physical activity, fasting glucose, blood pressure and smoking were defined according to the AHA 2020 Strategic Goals, assigned an individual score and summed to create an overall score. CVH scores were categorized into ideal (11–14 points), intermediate (9–10) and poor (0–8). Neighborhood exposures included favorable food store and physical activity resources densities (by 1-mile buffer), reported healthy food availability, walking/physical activity environment, safety and social cohesion (by census tract). Multinomial logistic regression was used to determine the association of each characteristic with ideal and intermediate CVH, adjusted for demographics and neighborhood socioeconomic status (SES). Over 20% of MESA participants had an ideal CVH score at baseline. In fully adjusted models, favorable food stores (OR= 1.22, 1.06–1.40), physical activity resources (OR=1.19, 1.08–1.31), walking/physical activity environment (OR=1.20, 1.05–1.37) and neighborhood SES (OR=1.22, 1.11–1.33) were associated with higher odds of having an ideal CVH score.
Conclusions
Neighborhood environment including favorable food stores, physical activity resources, walking/physical activity environment and neighborhood SES are associated with ideal CVH. Further research is needed to investigate the longitudinal associations between neighborhood environment and CVH.
doi:10.1161/CIRCOUTCOMES.113.000698
PMCID: PMC4172357  PMID: 25006187
risk factors; blood pressure; cholesterol; diet; exercise; prevention
2.  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
3.  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
4.  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
5.  The detection of coronary stiffness in cardiac allografts using MR imaging 
European journal of radiology  2014;83(8):1402-1407.
Objective
To test the hypothesis that biomechanical changes are quantitatively related to morphological features of coronary arteries in heart transplant (HTx) recipients.
Materials and methods
With IRB approval, three-dimensional (3D) magnetic resonance (MR) angiography and two-dimensional (2D) black-blood stead-state free precession (SSFP) MR imaging were performed to image coronary arteries of 36 HTx patients. Contours of coronary wall were manually drawn. For each coronary segment, coronary wall thickness, wall area, lumen area (in systole and diastole) were acquired. Coronary distensibility index (CDI) and the percent of the coronary wall occupying the vessel area (PWOV) were calculated.
Results
There are totally 98 coronary segments eligible for quantitative analysis from 27 HTx patients. The CDI is 4.90 ± 2.44 mmHg−1. The mean wall thickness is 1.49 ± 0.24 mm and the PWOV is 74.6% ± 7.5%. CDI has moderate correlations with wall thickness (r = −0.531, P < 0.001) and with PWOV (R = −0.435, P < 0.001).
Conclusions
Detected with coronary MR imaging, CDI is quantitatively correlated with the morphological features of the coronary artery in HTx patients. Coronary stiffness has the potential to become an alternative imaging biomarker for the quantitative assessment of the status of cardiac allografts.
doi:10.1016/j.ejrad.2014.05.028
PMCID: PMC4151319  PMID: 24929442
Heart Transplantation; Magnetic Resonance Imaging; Coronary stiffness
6.  Associations between Nonalcoholic Fatty Liver Disease and Subclinical Atherosclerosis in Middle-Aged Adults: The Coronary Artery Risk Development in Young Adults Study 
Atherosclerosis  2014;235(2):599-605.
Objective
Non-alcoholic fatty liver disease (NAFLD) is an obesity-related condition associated with cardiovascular mortality. Yet, whether or not NAFLD is independently related to atherosclerosis is unclear. In a population-based cross-sectional sample of middle-aged adults free from liver or heart disease, we tested the hypothesis that NAFLD is associated with subclinical atherosclerosis (coronary artery (CAC) and abdominal aortic calcification (AAC)) independent of obesity.
Methods
Participants from the Coronary Artery Risk Development in Young Adults study with CT quantification of liver fat, CAC and AAC were included (n=2,424). NAFLD was defined as liver attenuation ≤ 40 Hounsfield Units after exclusion of other causes of liver fat. CAC and AAC presence was defined as Agatston score > 0.
Results
Mean participant age was 50.1±3.6 years, (42.7% men, 50.0% black) and BMI was 30.6±7.2 kg/m2. The prevalence of NAFLD, CAC, and AAC was 9.6%, 27.1%, and 51.4%. NAFLD participants had increased prevalence of CAC (37.9% vs. 26.0%, p<0.001) and AAC (65.1% vs. 49.9%, p<0.001). NAFLD remained associated with CAC (OR, 1.33; 95% CI, 1.001–1.82) and AAC (OR, 1.74; 95% CI, 1.29–2.35) after adjustment for demographics and health behaviors. However, these associations were attenuated after additional adjustment for visceral adipose tissue (CAC OR, 1.05; 95% CI, 0.74–1.48, AAC OR=1.20; 95% CI, 0.86–1.67). There was no interaction by race or sex.
Conclusion
In contrast to prior research, these findings suggest that obesity attenuates the relationship between NAFLD and subclinical atherosclerosis. Further studies evaluating the role of NAFLD duration on atherosclerotic progression and cardiovascular events are needed.
doi:10.1016/j.atherosclerosis.2014.05.962
PMCID: PMC4124046  PMID: 24956534
calcium; cardiovascular diseases; epidemiology; imaging; liver; obesity; risk factors
7.  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
8.  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
9.  Perceived Lifetime Risk for Cardiovascular Disease (From the Dallas Heart Study) 
Lifetime risk estimation for cardiovascular disease (CVD) has been proposed as a useful strategy to improve risk communication in the primary prevention setting. However, the perception of lifetime risk for CVD is unknown. We included 2,998 individuals from the Dallas Heart Study. Lifetime risk for developing CVD was classified as high (≥39%) vs. low (<39%) according to risk factor burden as described in our previously published algorithm. Perception of lifetime risk for myocardial infarction was assessed via a 5-point scale. Baseline characteristics were compared across levels of perceived lifetime risk. Multivariable logistic regression analyses were performed to determine the association of participant characteristics with level of perceived lifetime risk for CVD and with correctness of perceptions. 64.8% (1942/2998) of participants were classified as high predicted lifetime risk for CVD. There was significant discordance between perceived and predicted lifetime risk. After multivariable adjustment, family history of premature MI, high self-reported stress, and low perceived health were all strongly associated with high perceived lifetime risk (OR [95% CI]: 2.37 [1.72–3.27], 2.17 [1.66–2.83], and 2.71 [2.09–3.53]). However, the association between traditional CVD risk factors and high perceived lifetime risk was more modest. In conclusion, misperception of lifetime risk for CVD is common and frequently reflects the influence of factors other than traditional risk factor levels. These findings highlight the importance of effectively communicating the significance of traditional risk factors in determining the lifetime risk for CVD.
doi:10.1016/j.amjcard.2014.04.006
PMCID: PMC4440865  PMID: 24834788
Lifetime Risk for Cardiovascular Disease; Predicted Lifetime Risk for Cardiovascular Disease; Perceived Lifetime Risk for Cardiovascular Disease
10.  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
11.  Clinical Characteristics and Outcomes Associated with the Natural History of Early Repolarization in a Young, Biracial Cohort Followed to Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study 
Background
Early repolarization (ER), a common electrocardiographic phenotype, has been associated with increased mortality risk in middle-aged adults. Data are sparse on long-term follow-up and outcomes associated with ER in younger adults.
Methods and Results
We prospectively examined 5,039 participants (mean age 25 years at baseline, 40% black) from the CARDIA cohort over 23 years. Twelve-lead electrocardiograms were recorded and analyzed at Years 0, 7 and 20 and coded as definite or probable ER using a standardized algorithm. Cox regression was used, and models were adjusted for important baseline and clinical covariates. Kaplan-Meier curves were created for presence of ER and total mortality and cardiovascular (CV) mortality. Participants with ER were more likely to be black, male, smoke, have higher systolic blood pressure, lower heart rate, and BMI, and also higher exercise duration, and longer PR, QRS and QT intervals. ER was associated with total mortality (HR1.77, 1.38–2.28, p<0.01), and CV mortality (HR 1.59, 1.01–2.50, p=0.04) in unadjusted analyses, but adjustment for age, sex, and race attenuated associations almost completely. Sex-race stratified analyses showed no significant associations between ER and outcome for any of the subgroups except blacks.
Conclusions
The presence of ER at any time point over 23 years of follow-up was not associated with adverse outcomes. Black race and male sex confound the unadjusted association of ER and outcomes, with no race-sex interactions noted. Further studies are necessary to understand the factors associated with heightened risk of death in those who maintain ER into and beyond middle age.
doi:10.1161/CIRCEP.113.000874
PMCID: PMC4136505  PMID: 24759868
ECG; ECG criteria; outcome; mortality; early repolarization
12.  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
14.  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
15.  Heart Disease and Stroke Statistics—2011 Update 
Circulation  2010;123(4):e18-e209.
Summary
Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited more than 8700 times in the literature (including citations of all annual versions). In 2009 alone, the various Statistical Updates were cited ≈1600 times (data from ISI Web of Science). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas. For this year’s edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year and added a new chapter detailing how family history and genetics play a role in cardiovascular disease (CVD) risk. Also, the 2011 Statistical Update is a major source for monitoring both cardiovascular health and disease in the population, with a focus on progress toward achievement of the AHA’s 2020 Impact Goals. Below are a few highlights from this year’s Update.
Death Rates From CVD Have Declined, Yet the Burden of Disease Remains High
The 2007 overall death rate from CVD (International Classification of Diseases 10, I00–I99) was 251.2 per 100 000. The rates were 294.0 per 100 000 for white males, 405.9 per 100 000 for black males, 205.7 per 100 000 for white females, and 286.1 per 100 000 for black females. From 1997 to 2007, the death rate from CVD declined 27.8%. Mortality data for 2007 show that CVD (I00–I99; Q20–Q28) accounted for 33.6% (813 804) of all 2 243 712 deaths in 2007, or 1 of every 2.9 deaths in the United States.
On the basis of 2007 mortality rate data, more than 2200 Americans die of CVD each day, an average of 1 death every 39 seconds. More than 150 000 Americans killed by CVD (I00–I99) in 2007 were <65 years of age. In 2007, nearly 33% of deaths due to CVD occurred before the age of 75 years, which is well before the average life expectancy of 77.9 years.
Coronary heart disease caused ≈1 of every 6 deaths in the United States in 2007. Coronary heart disease mortality in 2007 was 406 351. Each year, an estimated 785 000 Americans will have a new coronary attack, and ≈470 000 will have a recurrent attack. It is estimated that an additional 195 000 silent first myocardial infarctions occur each year. Approximately every 25 seconds, an American will have a coronary event, and approximately every minute, someone will die of one.
Each year, ≈795 000 people experience a new or recurrent stroke. Approximately 610 000 of these are first attacks, and 185 000 are recurrent attacks. Mortality data from 2007 indicate that stroke accounted for ≈1 of every 18 deaths in the United States. On average, every 40 seconds, someone in the United States has a stroke. From 1997 to 2007, the stroke death rate fell 44.8%, and the actual number of stroke deaths declined 14.7%.
In 2007, 1 in 9 death certificates (277 193 deaths) in the United States mentioned heart failure.
Prevalence and Control of Traditional Risk Factors Remains an Issue for Many Americans
Data from the National Health and Nutrition Examination Survey (NHANES) 2005–2008 indicate that 33.5% of US adults ≥20 years of age have hypertension (Table 7-1). This amounts to an estimated 76 400 000 US adults with hypertension. The prevalence of hypertension is nearly equal between men and women. African American adults have among the highest rates of hypertension in the world, at 44%. Among hypertensive adults, ≈80% are aware of their condition, 71% are using antihypertensive medication, and only 48% of those aware that they have hypertension have their condition controlled.
Despite 4 decades of progress, in 2008, among Americans ≥18 years of age, 23.1% of men and 18.3% of women continued to be cigarette smokers. In 2009, 19.5% of students in grades 9 through 12 reported current tobacco use. The percentage of the nonsmoking population with detectable serum cotinine (indicating exposure to secondhand smoke) was 46.4% in 1999 to 2004, with declines occurring, and was highest for those 4 to 11 years of age (60.5%) and those 12 to 19 years of age (55.4%).
An estimated 33 600 000 adults ≥20 years of age have total serum cholesterol levels ≥240 mg/dL, with a prevalence of 15.0% (Table 13-1).
In 2008, an estimated 18 300 000 Americans had diagnosed diabetes mellitus, representing 8.0% of the adult population. An additional 7 100 000 had undiagnosed diabetes mellitus, and 36.8% had prediabetes, with abnormal fasting glucose levels. African Americans, Mexican Americans, Hispanic/Latino individuals, and other ethnic minorities bear a strikingly disproportionate burden of diabetes mellitus in the United States (Table 16-1).
The 2011 Update Expands Data Coverage of the Obesity Epidemic and Its Antecedents and Consequences
The estimated prevalence of overweight and obesity in US adults (≥20 years of age) is 149 300 000, which represents 67.3% of this group in 2008. Fully 33.7% of US adults are obese (body mass index ≥30 kg/m2). Men and women of all race/ethnic groups in the population are affected by the epidemic of overweight and obesity (Table 15-1).
Among children 2 to 19 years of age, 31.9% are overweight and obese (which represents 23 500 000 children), and 16.3% are obese (12 000 000 children). Mexican American boys and girls and African American girls are disproportionately affected. Over the past 3 decades, the prevalence of obesity in children 6 to 11 years of age has increased from ≈4% to more than 20%.
Obesity (body mass index ≥30 kg/m2) is associated with marked excess mortality in the US population. Even more notable is the excess morbidity associated with overweight and obesity in terms of risk factor development and incidence of diabetes mellitus, CVD end points (including coronary heart disease, stroke, and heart failure), and numerous other health conditions, including asthma, cancer, degenerative joint disease, and many others.
The prevalence of diabetes mellitus is increasing dramatically over time, in parallel with the increases in prevalence of overweight and obesity.
On the basis of NHANES 2003–2006 data, the age-adjusted prevalence of metabolic syndrome, a cluster of major cardiovascular risk factors related to overweight/obesity and insulin resistance, is 34% (35.1% among men and 32.6% among women).
The proportion of youth (≤18 years of age) who report engaging in no regular physical activity is high, and the proportion increases with age. In 2007, among adolescents in grades 9 through 12, 29.9% of girls and 17.0% of boys reported that they had not engaged in 60 minutes of moderate-to-vigorous physical activity, defined as any activity that increased heart rate or breathing rate, even once in the previous 7 days, despite recommendations that children engage in such activity ≥5 days per week.
Thirty-six percent of adults reported engaging in no vigorous activity (activity that causes heavy sweating and a large increase in breathing or heart rate).
Data from NHANES indicate that between 1971 and 2004, average total energy consumption among US adults increased by 22% in women (from 1542 to 1886 kcal/d) and by 10% in men (from 2450 to 2693 kcal/d; see Chart 19-1).
The increases in calories consumed during this time period are attributable primarily to greater average carbohydrate intake, in particular, of starches, refined grains, and sugars. Other specific changes related to increased caloric intake in the United States include larger portion sizes, greater food quantity and calories per meal, and increased consumption of sugar-sweetened beverages, snacks, commercially prepared (especially fast food) meals, and higher energy-density foods.
The 2011 Update Provides Critical Data Regarding Cardiovascular Quality of Care, Procedure Utilization, and Costs
In light of the current national focus on healthcare utilization, costs, and quality, it is critical to monitor and understand the magnitude of healthcare delivery and costs, as well as the quality of healthcare delivery, related to CVDs. The Update provides these critical data in several sections.
Quality-of-Care Metrics for CVDs
Chapter 20 reviews many metrics related to the quality of care delivered to patients with CVDs, as well as healthcare disparities. In particular, quality data are available from the AHA’s “Get With The Guidelines” programs for coronary artery disease and heart failure and the American Stroke Association/ AHA’s “Get With the Guidelines” program for acute stroke. Similar data from the Veterans Healthcare Administration, national Medicare and Medicaid data and National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network - “Get With The Guidelines” Registry data are also reviewed. These data show impressive adherence with guideline recommendations for many, but not all, metrics of quality of care for these hospitalized patients. Data are also reviewed on screening for cardiovascular risk factor levels and control.
Cardiovascular Procedure Utilization and Costs
Chapter 21 provides data on trends and current usage of cardiovascular surgical and invasive procedures. For example, the total number of inpatient cardiovascular operations and procedures increased 27%, from 5 382 000 in 1997 to 6 846 000 in 2007 (National Heart, Lung, and Blood Institute computation based on National Center for Health Statistics annual data).
Chapter 22 reviews current estimates of direct and indirect healthcare costs related to CVDs, stroke, and related conditions using Medical Expenditure Panel Survey data. The total direct and indirect cost of CVD and stroke in the United States for 2007 is estimated to be $286 billion. This figure includes health expenditures (direct costs, which include the cost of physicians and other professionals, hospital services, prescribed medications, home health care, and other medical durables) and lost productivity resulting from mortality (indirect costs). By comparison, in 2008, the estimated cost of all cancer and benign neoplasms was $228 billion ($93 billion in direct costs, $19 billion in morbidity indirect costs, and $116 billion in mortality indirect costs). CVD costs more than any other diagnostic group.
The AHA, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current data available in the Statistics Update. The 2007 mortality data have been released. More information can be found at the National Center for Health Statistics Web site, http://www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_01.pdf.
Finally, it must be noted that this annual Statistical Update is the product of an entire year’s worth of effort by dedicated professionals, volunteer physicians and scientists, and outstanding AHA staff members, without whom publication of this valuable resource would be impossible. Their contributions are gratefully acknowledged. Véronique L. Roger, MD, MPH, FAHAMelanie B. Turner, MPHOn behalf of the American Heart Association Heart Disease and Stroke Statistics Writing Group
Note: Population data used in the compilation of NHANES prevalence estimates is for the latest year of the NHANES survey being used. Extrapolations for NHANES prevalence estimates are based on the census resident population for 2008 because this is the most recent year of NHANES data used in the Statistical Update.
doi:10.1161/CIR.0b013e3182009701
PMCID: PMC4418670  PMID: 21160056
AHA Statistical Update; cardiovascular diseases; epidemiology; risk factors; statistics; stroke
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.  Validation of the Atherosclerotic Cardiovascular Disease Pooled Cohort Risk Equations 
JAMA  2014;311(14):1406-1415.
Importance
The American College of Cardiology/American Heart Association Pooled Cohort risk equations were developed to estimate atherosclerotic cardiovascular disease (ASCVD) risk and guide statin initiation.
Objective
Assess calibration and discrimination of the Pooled Cohort risk equations in a contemporary US population.
Design, Setting, and Participants
Adults 45-79 years enrolled in the REasons for Geographic And Racial Differences in Stroke study between January 2003 and October 2007 and followed through December 2010. We studied participants for whom ASCVD risk may trigger a discussion of statin initiation (those without clinical ASCVD or diabetes, LDL-C between 70-189 mg/dL, not taking statins; n=10,997).
Main Outcomes and Measures
Predicted risk and observed adjudicated ASCVD incidence (non-fatal myocardial infarction, coronary heart disease [CHD] death, non-fatal or fatal stroke) at 5 years as REGARDS participants have not been followed 10 years. Additional analyses, limited to Medicare beneficiaries (n=3,333), added ASCVD events identified in claims data.
Results
There were 338 adjudicated events (192 CHD events, 146 strokes). The observed and predicted 5-year ASCVD incidence per 1,000 person-years for participants with 10-year predicted ASCVD risk <5% was 1.9 (95%CI: 1.3 – 2.7) and 1.9, risk 5% to <7.5% was 4.8 (95%CI: 3.4 – 6.7) and 4.8, risk 7.5% to <10% was 6.1 (95%CI: 4.4 – 8.6) and 6.9, and risk ≥10% was 12.0 (95%CI: 10.6 – 13.6) and 15.1 (Hosmer-Lemeshow χ2 19.9 p-value=0.01). The c-index was 0.72 (95%CI: 0.70–0.75). There were 234 ASCVD events (120 CHD events, 114 strokes) among Medicare-linked participants and the observed and predicted 5-year ASCVD incidence per 1,000 person-years for participants with predicted risk <7.5% was 5.3 (95% CI: 2.8 – 10.1) and 4.0, risk 7.5% to <10% was 7.9 (95% CI: 4.6 – 13.5) and 6.4, and risk ≥10% was 17.4 (95% CI: 15.3–19.8) and 16.4 (Hosmer-Lemeshow χ2 5.4 p-value=0.71). The c-index was 0.67 (95%CI: 0.64 – 0.71)
Conclusions and Relevance
In this cohort of US adults for whom statin initiation is considered based on the ACC/AHA Pooled Cohort risk equations, observed and predicted 5-year ASCVD risks were similar, indicating that these risk equations were well calibrated in the population for which they were designed to be used.
doi:10.1001/jama.2014.2630
PMCID: PMC4189930  PMID: 24682252
18.  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
19.  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
20.  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
21.  Impact of Blood Pressure and Blood Pressure Change during Middle Age on the Remaining Lifetime Risk for Cardiovascular Disease: The Cardiovascular Lifetime Risk Pooling Project 
Circulation  2011;125(1):37-44.
Background
Prior estimates of lifetime risk (LTR) for cardiovascular disease (CVD) examined the impact of blood pressure at the index age and did not account for changes in blood pressure over time. We examined how changes in blood pressure during middle-age affect LTR for CVD, coronary heart disease (CHD) and stroke.
Methods and Results
Data from 7 diverse US cohort studies were pooled. Remaining LTR for CVD, CHD and stroke were estimated for White and Black men and women with death free of CVD as a competing event. LTR for CVD by blood pressure (BP) strata and by changes in BP over an average of 14 years were estimated. Starting at age 55, we followed 61,585 men and women for 700,000 person-years. LTR for CVD was 52.5% (95% CI 51.3–53.7) for men and 39.9% (38.7–41.0) for women. LTR for CVD was higher for Blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22–41%, as compared to individuals who had or developed hypertension by the age of 55, 42–69%; suggesting a dose-response effect for the length of time at high BP levels
Conclusions
Individuals who experience increases or decreases in BP in middle age have associated higher and lower remaining LTR for CVD. Prevention efforts should continue to emphasize the importance of lowering BP and avoiding or delaying the incidence of hypertension in order to reduce the LTR for CVD.
doi:10.1161/CIRCULATIONAHA.110.002774
PMCID: PMC3310202  PMID: 22184621
cardiovascular disease; coronary heart disease; stroke; hypertension; risk factors
22.  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
23.  Distribution of Coronary Artery Calcium Scores by Framingham 10-Year Risk Strata in the Multi-Ethnic Study of Atherosclerosis (MESA): Potential Implications for Coronary Risk Assessment 
Objectives
By examining the distribution of CAC across FRS strata in a large, multi-ethnic, community-based sample of men and women, we sought to determine if lower risk persons could potentially benefit from CAC screening.
Background
The 10-year Framingham risk scores (FRS) and coronary artery calcium (CAC) are predictors of coronary heart disease (CHD). CAC ≥300 is associated with the highest risk for CHD even in low risk (FRS <10%) persons; however expert groups have suggested CAC screening only in intermediate risk (FRS 10–20%) groups.
Methods
We included 5660 MESA participants. The number needed to screen [number of people that need to be screened to detect one person with CAC above the specified cut-point (NNS)] was used to assess the yield of screening for CAC. CAC prevalence was compared across FRS strata using chi-square tests.
Results
CAC >0, ≥100 and ≥300 were present in 46.4%, 20.6% and 10.1% of participants, respectively. Prevalence and amount of CAC increased with higher FRS. CAC ≥300 was observed in 1.7% and 4.4% of those with FRS 0–2.5% and 2.6–5%, respectively (NNS =59.7 and 22.7). Likewise, CAC ≥300 was observed in 24% and 30% of those with FRS 15.1–20% and >20%, respectively (NNS =4.2 and 3.3). Trends were similar when stratified by age, gender and race/ethnicity.
Conclusions
Our study suggests that in very low risk individuals (FRS ≤5%), the yield of screening and probability of identifying persons with clinically significant levels of CAC is low, but becomes greater in low and intermediate risk persons (FRS 5.1–20%).
doi:10.1016/j.jacc.2010.11.053
PMCID: PMC3268231  PMID: 21527159
Framingham risk score; coronary calcium; coronary heart disease; number needed to screen; risk factors; population; atherosclerosis; low risk
24.  Factors Associated with Presence and Extent of Coronary Calcium in Individuals Predicted to be at Low Risk Based on Framingham Risk Score (From The Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2011;107(6):879-885.
Even among asymptomatic people at low risk (<10%) by Framingham Risk Score (FRS), high coronary artery calcium (CAC) scores signify higher predicted risk of coronary heart disease (CHD) events. We sought to determine non-invasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3046 participants from MESA at low 10-year predicted risk (FRS <10%) for CHD events. Multivariable logistic regression was used to assess the association of novel markers with presence of any CAC (CAC >0) and advanced CAC (CAC ≥ 300). CAC >0 and CAC ≥ 300 were present in 30% and 3.5% of participants, respectively. Factor VIIIc, fibrinogen and sICAM were each associated with CAC presence (P ≤ 0.02); and C-reactive protein, D-dimer and carotid intima-media thickness (CIMT) with advanced CAC (P ≤ 0.03). The base model combining traditional risk factors had excellent discrimination for advanced CAC (C-statistic, 0.808). Addition of the 2 best-fit models combining biomarkers plus/minus CIMT improved the c-statistics to 0.822 and 0.820, respectively. All 3 models calibrated well, but were similar in estimating individual risk probabilities for advanced CAC (prevalence = 9.97%, 10.63% and 10.10% in the highest quartiles of predicted probabilities versus 0.26%, 0.26% and 0.26% in the lowest quartiles, respectively). In conclusion, in low risk individuals, traditional risk factors alone predicted advanced CAC with high discrimination and calibration. Biomarker combinations +/− CIMT were also significantly associated with advanced CAC, but improvement in prediction and estimation of clinical risk were modest compared to traditional risk factors alone.
doi:10.1016/j.amjcard.2010.10.072
PMCID: PMC3182475  PMID: 21376929
coronary calcium; biomarkers; novel markers; low-risk; risk factors
25.  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

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