Calcium Intake From Diet and Supplements and the Risk of Coronary Artery Calcification and its Progression Among Older Adults: 10-Year Follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (CVD) events. Using a longitudinal cohort study, we assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (CAC). METHODS AND RESULTS: We studied 5448 adults free of clinically diagnosed CVD (52% female; aged 45-84 years) from the Multi-Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles. Baseline CAC was measured by computed tomography, and CAC measurements were repeated in 2742 participants ≈10 years later. At baseline, mean calcium intakes across quintiles were 313.3, 540.3, 783.0, 1168.9, and 2157.4 mg/day. Women had higher calcium intakes than men. After adjustment for potential confounders, among 1567 participants without baseline CAC, the relative risk (RR) of developing incident CAC over 10 years, by quintile 1 to 5 of calcium intake, were 1 (reference), 0.95 (0.79-1.14), 1.02 (0.85-1.23), 0.86 (0.69-1.05), and 0.73 (0.57-0.93). After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident CAC (RR=1.22 [1.07-1.39]). No relation was found between baseline calcium intake and 10-year changes in log-transformed CAC among those participants with baseline CAC >0. CONCLUSIONS: High total calcium intake was associated with a decreased risk of incident atherosclerosis over long-term follow-up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident CAC.

Legacy of MESA.

The MESA (Multi-Ethnic Study of Atherosclerosis) was initiated to address unresolved questions about subclinical cardiovascular disease and its progression to clinically overt cardiovascular disease in a diverse population-based sample, incorporating emerging imaging technologies for better evaluation of subclinical disease and creating a population laboratory for future research. MESA's recruited (from 2000 to 2002) cohort comprised >6,000 adults from 4 racial/ethnic groups, ages 45 to 84 years, who were free of cardiovascular disease at baseline. Extensive cohort data have been collected over 5 exams (through 2011) with additional exam components added through extramurally funded ancillary study grants, and through regular phone follow-up contacts. Over 1,000 MESA papers have been published to date. Exam 6 will incorporate components that use novel wearable, imaging, and other technologies to address new research questions. MESA investigators have and continue to seek opportunities for collaboration with other researchers on a wide variety of topics to further expand the science of MESA.

Prevalence and Correlates of Myocardial Scar in a US Cohort.

IMPORTANCE: Myocardial scarring leads to cardiac dysfunction and poor prognosis. The prevalence of and factors associated with unrecognized myocardial infarction and scar have not been previously defined using contemporary methods in a multiethnic US population. OBJECTIVE: To determine prevalence of and factors associated with myocardial scar in middle- and older-aged individuals in the United States. DESIGN, SETTING, AND PARTICIPANTS: The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease (CVD) at baseline in 2000-2002. In the 10th year examination (2010-2012), 1840 participants underwent cardiac magnetic resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at baseline and year 10. Logistic regression models were used to estimate adjusted odds ratios (ORs) for myocardial scar. EXPOSURES: Cardiovascular risk factors, CAC scores, left ventricle size and function, and carotid intima-media thickness. MAIN OUTCOMES AND MEASURES: Myocardial scar detected by CMR imaging. RESULTS: Of 1840 participants (mean [SD] age, 68 [9] years, 52% men), 146 (7.9%) had myocardial scars, of which 114 (78%) were undetected by electrocardiogram or by clinical adjudication. In adjusted models, age, male sex, body mass index, hypertension, and current smoking at baseline were associated with myocardial scar at year 10. The OR per 8.9-year increment was 1.61 (95% CI, 1.36-1.91; P < .001); for men vs women: OR, 5.76 (95% CI, 3.61-9.17; P < .001); per 4.8-SD body mass index: OR, 1.32 (95% CI, 1.09-1.61, P = .005); for hypertension: OR, 1.61 (95% CI, 1.12-2.30; P = .009); and for current vs never smokers: 2.00 (95% CI, 1.22-3.28; P = .006). Age-, sex-, and ethnicity-adjusted CAC scores at baseline were also associated with myocardial scar at year 10. Compared with a CAC score of 0, the OR for scores from 1 through 99 was 2.4 (95% CI, 1.5-3.9); from 100 through 399, 3.0 (95% CI, 1.7-5.1), and 400 or higher, 3.3 (95% CI, 1.7-6.1) (P ≤ .001). The CAC score significantly added to the association of myocardial scar with age, sex, race/ethnicity, and traditional CVD risk factors (C statistic, 0.81 with CAC vs 0.79 without CAC, P = .01). CONCLUSIONS AND RELEVANCE: The prevalence of myocardial scars in a US community-based multiethnic cohort was 7.9%, of which 78% were unrecognized by electrocardiography or clinical evaluation. Further studies are needed to understand the clinical consequences of these undetected scars.

10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study).

BACKGROUND: Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed. OBJECTIVES: The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. METHODS: Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study). RESULTS: Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrell's C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate. CONCLUSIONS: An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.

Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial.

Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (ß) 0.33) and negatively associated with eGFR (ß -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g.

Ten-year trends in coronary calcification in individuals without clinical cardiovascular disease in the multi-ethnic study of atherosclerosis.

BACKGROUND: Coronary heart disease (CHD) incidence has declined significantly in the US, as have levels of major coronary risk factors, including LDL-cholesterol, hypertension and smoking, but whether trends in subclinical atherosclerosis mirror these trends is not known. METHODS AND FINDINGS: To describe recent secular trends in subclinical atherosclerosis as measured by serial evaluations of coronary artery calcification (CAC) prevalence in a population over 10 years, we measured CAC using computed tomography (CT) and CHD risk factors in five serial cross-sectional samples of men and women from four race/ethnic groups, aged 55-84 and without clinical cardiovascular disease, who were members of Multi-Ethnic Study of Atherosclerosis (MESA) cohort from 2000 to 2012. Sample sizes ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the prevalence of CAC increased across exams among African Americans, whose prevalence of CAC was 52.4% in 2000-02, 50.4% in 2003-04, 60.0% is 2005-06, 57.4% in 2007-08, and 61.3% in 2010-12 (p for trend <0.001). The trend was strongest among African Americans aged 55-64 [prevalence ratio for 2010-12 vs. 2000-02, 1.59 (95% confidence interval 1.06, 2.39); p = 0.005 for trend across exams]. There were no consistent trends in any other ethnic group. Risk factors generally improved in the cohort, and adjustment for risk factors did not change trends in CAC prevalence. CONCLUSIONS: There was a significant secular trend towards increased prevalence of CAC over 10 years among African Americans and no change in three other ethnic groups. Trends did not reflect concurrent general improvement in risk factors. The trend towards a higher prevalence of CAC in African Americans suggests that CHD risk in this population is not improving relative to other groups.

The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men.

Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation. Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant. Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort.

Progression of coronary calcium and incident coronary heart disease events: MESA (Multi-Ethnic Study of Atherosclerosis).

OBJECTIVES: The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. BACKGROUND: CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. METHODS: We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. RESULTS: A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression. CONCLUSIONS: Progression of CAC is associated with an increased risk for future hard and total CHD events.

Cardiovascular epidemiology in a changing world--challenges to investigators and the National Heart, Lung, and Blood Institute.

Over the past 60 years, revolutionary discoveries made by epidemiologists have contributed to marked declines in cardiovascular disease morbidity and mortality. Now, in an era of increasingly constrained resources, researchers in cardiovascular epidemiology face a number of challenges that call for novel, paradigm-shifting approaches. In this paper, the authors pose to the community 4 critical questions: 1) How can we avoid wasting resources on studies that provide little incremental knowledge? 2) How can we assure that we direct our resources as economically as possible towards innovative science? 3) How can we be nimble, responding quickly to new opportunities? 4) How can we identify prospectively the most meritorious research questions? Senior program staff at the National Heart, Lung, and Blood Institute invite the epidemiology community to join them in an ongoing Web-based blog conversation so that together we might develop novel approaches that will facilitate the next generation of high-impact discoveries.

Distribution of coronary artery calcium scores by Framingham 10-year risk strata in the MESA (Multi-Ethnic Study of Atherosclerosis) potential implications for coronary risk assessment.

OBJECTIVES: By examining the distribution of coronary artery calcium (CAC) levels across Framingham risk score (FRS) strata in a large, multiethnic, community-based sample of men and women, we sought to determine if lower-risk persons could benefit from CAC screening. BACKGROUND: The 10-year FRS and CAC levels are predictors of coronary heart disease. A CAC level of 300 or more is associated with the highest risk for coronary heart disease even in low-risk persons (FRS, <10%); however, expert groups have suggested CAC screening only in intermediate-risk groups (FRS, 10% to 20%). METHODS: We included 5,660 Multi-Ethnic Study of Atherosclerosis participants. The number needed to screen (number of people that need to be screened to detect 1 person with CAC level above the specified cutoff point) was used to assess the yield of screening for CAC. CAC prevalence was compared across FRS strata using chi-square tests. RESULTS: CAC levels of more than 0, of 100 or more, and of 300 or more were present in 46.4%, 20.6%, and 10.1% of participants, respectively. The prevalence and amount of CAC increased with higher FRS. A CAC level of 300 or more was observed in 1.7% and 4.4% of those with FRS of 0% to 2.5% and of 2.6% to 5%, respectively (number needed to screen, 59.7 and 22.7, respectively). Likewise, a CAC level of 300 or more was observed in 24% and 30% of those with FRS of 15.1% to 20% and more than 20%, respectively (number needed to screen, 4.2 and 3.3, respectively). Trends were similar when stratified by age, sex, and race or 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% to 20%).

Cardiovascular imaging for assessing cardiovascular risk in asymptomatic men versus women: the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD. METHODS AND RESULTS: The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62±10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05). CONCLUSIONS: There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.

Coronary artery calcium score and risk classification for coronary heart disease prediction.

CONTEXT: The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear. OBJECTIVE: To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk. DESIGN, SETTING, AND PARTICIPANTS: CACS was measured by computed tomography in 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident CHD were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement and compared the distribution of risk using model 2 vs model 1. MAIN OUTCOME MEASURES: Incident CHD events. RESULTS: During a median of 5.8 years of follow-up among a final cohort of 5878, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34; P < .001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2. CONCLUSION: In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.

The impact of obesity on the left ventricle: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVES: The purpose of this study was to evaluate the relationship of left ventricular (LV) remodeling assessed by cardiac magnetic resonance to various measures of obesity in a large population-based study. BACKGROUND: Obesity is a well-known risk factor for cardiovascular disease, yet its relationship with LV size and function is poorly understood. METHODS: A total of 5,098 participants (age 45 to 84 years; 48% men) in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cardiovascular disease underwent cardiac magnetic resonance to assess LV size and function as well as measures of obesity, including body mass index, waist-to-hip ratio and waist circumference, and cardiovascular risk factors. Fat mass (FM) was estimated based on height-weight models derived from bioelectrical impedance studies. The associations of obesity measures with LV size and function were evaluated using linear spline regression models for body mass index and multivariable regression models for other measures of obesity; they were displayed graphically using generalized additive models. RESULTS: LV mass and end-diastolic volume were positively associated with measures of obesity in both sexes after adjustment for risk factors (e.g., 5.7-g and 6.9-g increase in LV mass per 10-kg increase in FM in women and men, respectively [p < 0.001]). LV mass-to-volume ratio was positively associated with increased body mass index, waist-to-hip ratio, waist circumference, and estimated FM (e.g., 0.02-g/ml and 0.06-g/ml increase in mass-to-volume ratio per 10-kg increase in FM in women and men, respectively [p < 0.001]). The increased mass-to-volume ratio was due to a greater increase in LV mass relative to LV end-diastolic volume. All associations were stronger for men than for women. Ejection fraction showed no significant association with measures of obesity. CONCLUSIONS: Obesity was associated with concentric LV remodeling without change in ejection fraction in a large, multiethnic cohort study.

The association between A1C and subclinical cardiovascular disease: the multi-ethnic study of atherosclerosis.

OBJECTIVE: To test the hypothesis that A1C is associated with subclinical cardiovascular disease (CVD) in a population without evident diabetes, after adjusting for traditional CVD risk factors and BMI. RESEARCH DESIGN AND METHODS: This was a cross-sectional study of 5,121 participants without clinically evident CVD or diabetes (fasting glucose > or =7.0 mmol/l or use of diabetes medication), aged 47-86 years, enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Measurements included carotid intimal-medial wall thickness (CIMT) and coronary artery calcification (CAC). Results were adjusted for age, sex, ethnicity, smoking, systolic blood pressure, LDL cholesterol, HDL cholesterol, antihypertensive medication use, lipid-lowering medication use, and BMI. RESULTS: Compared with those in the lowest quartile for A1C ([mean +/- SD] 5.0 +/- 0.2%), participants in the highest quartile (6.0 +/- 0.3%) had higher adjusted mean values for common CIMT (0.85 vs. 0.87 mm, P = 0.003) and internal CIMT (1.01 vs. 1.08 mm, P = 0.003). A1C quartile was not associated with prevalence of CAC in the entire cohort (P = 0.27); however, the association was statistically significant in women (adjusted prevalence of CAC in lowest and highest A1C quartiles 37.5 vs. 43.0%, P = 0.01). Among those with some CAC, higher A1C quartile tended to be associated with higher CAC score, but the results were not statistically significant (adjusted P = 0.11). CONCLUSIONS: In this multiethnic cohort, there were small, positive associations between A1C, common CIMT, and internal CIMT in the absence of clinically evident diabetes. An association between higher A1C and CAC prevalence was evident only in women.

Prevention of atrial fibrillation: report from a national heart, lung, and blood institute workshop.

The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.

Alcohol and coronary artery calcium prevalence, incidence, and progression: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Alcohol use has been consistently found to have a J-shaped association with coronary heart disease, with moderate drinkers exhibiting a decreased risk compared with both heavy drinkers and nondrinkers. However, results of studies of the association between alcohol use and subclinical coronary artery disease are conflicting. OBJECTIVE: The objective was to determine whether alcohol is associated with the presence, amount, or progression of coronary calcium over a 2- to 4-y period. DESIGN: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective community-based cohort study of subclinical cardiovascular disease in a multi-ethnic cohort. In 2000-2002, 6814 participants free of clinical cardiovascular disease were enrolled at 6 participating centers. RESULTS: The subjects consisted of 3766 (55.5%) current drinkers, 1635 (24.1%) former drinkers, and 1390 (20.5%) never drinkers. Although light-to-moderate alcohol consumption was associated with lower coronary heart disease risk, we found no evidence of a protective or J-shaped association of alcohol and coronary artery calcium (CAC). In fact, there was evidence that heavy consumption of hard liquor was associated with greater CAC accumulation. Other alcoholic beverages were not associated with CAC prevalence, incidence, or progression. CONCLUSIONS: This was the first large study to evaluate the association of alcohol with CAC in 4 racial-ethnic groups and to evaluate the progression of calcification. These results suggest that the cardiovascular benefits that may be derived from light-to-moderate alcohol consumption are not mediated through reduced CAC accumulation.

Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Coronary artery calcium (CAC) and carotid intima-media thickness (IMT) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease (CVD) occurrence. Our objective was to assess whether maximum carotid IMT or CAC (Agatston score) is the better predictor of incident CVD. METHODS: A prospective cohort study of subjects aged 45 to 84 years in 4 ethnic groups, who were initially free of CVD (n = 6698) was performed, with standardized carotid IMT and CAC measures at baseline, in 6 field centers of the Multi-Ethnic Study of Atherosclerosis (MESA). The main outcome measure was the risk of incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up. RESULTS: There were 222 CVD events during follow-up. Coronary artery calcium was associated more strongly than carotid IMT with the risk of incident CVD. After adjustment for each other (CAC score and IMT) and age, race, and sex [corrected], the hazard ratio of CVD increased 2.1-fold (95% confidence interval [CI], 1.8-2.5) for each 1-standard deviation (SD) increment of log-transformed CAC score, vs 1.3-fold (95% CI, 1.1-1.4) for each 1-SD increment of the maximum IMT. For coronary heart disease, the hazard ratios per 1-SD increment increased 2.5-fold (95% CI, 2.1-3.1) for CAC score and 1.2-fold (95% CI, 1.0-1.4) for IMT. A receiver operating characteristic curve analysis also suggested that CAC score was a better predictor of incident CVD than was IMT, with areas under the curve of 0.81 vs 0.78, respectively. CONCLUSION: Although whether and how to clinically use bioimaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC score is a better predictor of subsequent CVD events than carotid IMT.