Multi-Ethnic Study Of Atherosclerosis Cohort Research Articles

A National Prediction Model for PM2.5Component Exposures and Measurement Error–Corrected Health Effect Inference

Background: Studies estimating health effects of long-term air pollution exposure often use a two-stage approach: building exposure models to assign individual-level exposures, which are then used in regression analyses. This requires accurate exposure modeling and careful treatment of exposure measurement error.Objective: To illustrate the importance of accounting for exposure model characteristics in two-stage air pollution studies, we considered a case study based on data from the Multi-Ethnic Study of Atherosclerosis (MESA).Methods: We built national spatial exposure models that used partial least squares and universal kriging to estimate annual average concentrations of four PM2.5 components: elemental carbon (EC), organic carbon (OC), silicon (Si), and sulfur (S). We predicted PM2.5 component exposures for the MESA cohort and estimated cross-sectional associations with carotid intima-media thickness (CIMT), adjusting for subject-specific covariates. We corrected for measurement error using recently developed methods that account for the spatial structure of predicted exposures.Results: Our models performed well, with cross-validated R2 values ranging from 0.62 to 0.95. Naïve analyses that did not account for measurement error indicated statistically significant associations between CIMT and exposure to OC, Si, and S. EC and OC exhibited little spatial correlation, and the corrected inference was unchanged from the naïve analysis. The Si and S exposure surfaces displayed notable spatial correlation, resulting in corrected confidence intervals (CIs) that were 50% wider than the naïve CIs, but that were still statistically significant.Conclusion: The impact of correcting for measurement error on health effect inference is concordant with the degree of spatial correlation in the exposure surfaces. Exposure model characteristics must be considered when performing two-stage air pollution epidemiologic analyses because naïve health effect inference may be inappropriate.Citation: Bergen S, Sheppard L, Sampson PD, Kim SY, Richards M, Vedal S, Kaufman JD, Szpiro AA. 2013. A national prediction model for PM2.5 component exposures and measurement error–corrected health effect inference. Environ Health Perspect 121:1017–1025; http://dx.doi.org/10.1289/ehp.1206010

Associations between aspirin and other non-steroidal anti-inflammatory drugs and aortic valve or coronary artery calcification: The Multi-Ethnic Study of Atherosclerosis and the Heinz Nixdorf Recall Study

BackgroundThe association between non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence of valvular and arterial calcification is not well established despite known associations between these drugs and cardiovascular events. ObjectiveTo compare the association between the baseline use of aspirin with other NSAID class medications with the incidence and prevalence of aortic valve calcification (AVC) and coronary artery calcification (CAC). MethodsThe relationship of NSAID use to AVC and CAC detected by computed tomography was assessed in 6814 participants within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling. Results were adjusted for age, sex, ethnicity, study site, anti-hypertensive medication use, education, income, health insurance status, diabetes, smoking, exercise, body mass index, blood pressure, serum lipids, inflammatory markers, fasting glucose, statin medication use, and a simple diet score. Medication use was assessed by medication inventory at baseline which includes the use of non-prescription NSAIDs. MESA collects information on both incident and prevalent calcification. The 4814 participants of the Heinz Nixdorf Recall (HNR) Study, a German prospective cohort study with similar measures of calcification, were included in this analysis to enable replication. ResultsMean age of the MESA participants was 62 years (51% female). After adjustment for possible confounding factors, a possible association between aspirin use and incident AVC (Relative Risk(RR): 1.60; 95%Confidence Interval (CI): 1.19–2.15) did not replicate in the HNR cohort (RR: 1.06; 95%CI: 0.87–1.28). There was no significant association between aspirin use and incident CAC in the MESA cohort (RR 1.08; 95%CI: 0.91–1.29) or in the HNR cohort (RR 1.24; 95%CI: 0.87–1.77). Non-aspirin NSAID use was not associated with either AVC or CAC in either cohort. There were no associations between regular cardiac dose aspirin and incident calcification in either cohort. ConclusionBaseline NSAID use, as assessed by medication inventory, appears to have no protective effect regarding the onset of calcification in either coronary arteries or aortic valves.

Association of Obesity and Kidney Function Decline among Non-Diabetic Adults with eGFR > 60 ml/min/1.73m2: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).

Obesity is associated with higher end-stage renal disease incidence, but associations with earlier forms of kidney disease remain incompletely characterized. We studied the association of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with rapid kidney function decline and incident chronic kidney disease in 4573 non-diabetic adults with eGFR ≥ 60 ml/min/1.73m2 at baseline from longitudinal Multi-Ethnic Study of Atherosclerosis cohort. Kidney function was estimated by creatinine and cystatin C. Multivariate analysis was adjusted for age, race, baseline eGFR, and hypertension. Mean age was 60 years old, BMI 28 kg/m2, baseline eGFRCr 82 and eGFRCys 95 ml/min/1.73m2. Over 5 years of follow up, 25% experienced rapid decline in renal function by eGFRCr and 22% by eGFRCys. Incident chronic kidney disease (CKD) developed in 3.3% by eGFRCys, 11% by eGFRCr, and 2.4% by both makers. Compared to persons with BMI < 25, overweight (BMI 25 - 30) persons had the lowest risk of rapid decline by eGFRCr (0.84, 0.71 - 0.99). In contrast, higher BMI categories were associated with stepwise higher odds of rapid decline by eGFRCys, but remained significant only when BMI ≥ 35 kg/m2 (1.87, 1.41 - 2.48). Associations of BMI with incident CKD were insignificant after adjustment. Large WC and WHR were associated with increased risk of rapid decline only by eGFRCys, and of incident CKD only when defined by both filtration markers. Obesity may be a risk factor for kidney function decline, but associations vary by filtration marker used.

Abstract 9718: Risk Factors for the Development and Progression of Thoracic Aorta Calcification: The Multi-Ethnic Study of Atherosclerosis (MESA)

Objective: To evaluate risk factors for the incidence and progression of thoracic aorta calcification (TAC) Introduction : Vascular calcification independently predicts cardiovascular disease (CVD) and computed tomography (CT) is a useful tool to evaluate and quantify TAC. Previous TAC progression reports were limited to dialysis and renal transplant patients, This is the first study to evaluate TAC progression in a large multi-ethnic cohort without clinically evident CVD at entry Methods: Non-contrast enhanced cardiac CT (EBCT or MSCT) were obtained in 5886 of the 6814 MESA participants (mean age 62 yrs; 48% male; 40% white, 27% African American (AA), 21% Hispanic, 12% Chinese. Baseline (BL) and follow up (FU) TAC scores were derived Results: 4308 (73%) subjects had no detectable BL TAC. Mean FU duration was 2.4±0.8 yrs, during which 12% developed TAC. The overall incidence rate was 4.8%/yr and was greater with age across gender and ethnic groups,TAC incidence was significantly lower in AA than whites. Regression analyses showed FU time, age, systolic BP, antihypertensives, and smoking were predictors of incident TAC. 1578 (27%) subjects had prevalent TAC at BL scan with a positive association between the averaged annual TAC change and BL age. While the overall median (25 th , 75 th %tiles) change was 32.9 (-1.4,112.2) Agatston units, 38% of study population showed an annual Agatston score progression change of 10-99 and AA showed the lowest median across all ethnic groups; 22.7 (-3,86.8). Regression analyses showed MSCT use, FU time, age, systolic BP, lipid-lowering medication, DM and current smoking were predictors of TAC progression (Tab1) Conclusion: In the MESA cohort, both TAC incidence and progression were significantly associated with traditional CV risk factors. AA had the lowest incidence and median change across ethnic groups, consistent with previous findings for coronary calcification. Further studies are needed to correlate progression with outcome data

Associations of LV Hypertrophy With Prevalent and Incident Valve Calcification: Multi-Ethnic Study of Atherosclerosis

The aim of this study was to evaluate the relationship between percentage of predicted left ventricular mass (%PredLVM) and valve calcification in the MESA (Multi-Ethnic Study of Atherosclerosis) study. Cardiac valve calcification has been associated with left ventricular hypertrophy (LVH), which portends cardiovascular events. However, this relationship and its mediators are poorly understood. The MESA study is a longitudinal cohort study of men and women 45 to 84 years of age without clinical cardiovascular disease in whom serial cardiac magnetic resonance and computed tomography imaging were performed. The relationships between baseline %PredLVM and the prevalence, severity, and incidence of aortic valve (AVC) and mitral annulus calcification (MAC) were determined by regression modeling. Prevalent AVC was observed in 630, and MAC was observed in 442 of 5,042 subjects (median 55.9 and 71.1 Agatston units, respectively). After adjustment for age, sex, body mass index (BMI), ethnicity, socioeconomic status, physical activity, diabetes, cholesterol levels, blood pressure, smoking, kidney function, serum lipids, and antihypertensive and statin medications, %PredLVM was associated with prevalent AVC (odds ratio [OR]: 1.18/SD increase in %PredLVM [95% confidence interval (CI): 1.08 to 1.30]; p = 0.0004) and MAC (OR: 1.18 [95% CI: 1.06 to 1.32]; p = 0.002). Similarly, %PredLVM was associated with increased severity of prevalent AVC (risk difference = 0.26 [95% CI: 0.15 to 0.38]; p < 0.0001) and MAC (risk difference = 0.20 [95% CI: 0.03 to 0.37]; p = 0.02). During follow-up (mean 2.4 ± 0.9 years), 153 subjects (4%) developed AVC, and 198 (5%) developed MAC. The %PredLVM was associated with incident AVC (OR: 1.24 [95% CI: 1.04 to 1.47]; p = 0.02) and MAC (OR: 1.18 [95% CI: 1.01 to 1.40]; p = 0.04). Further adjustment for inflammatory markers and coronary artery calcification did not attenuate these associations. Specifically, concentric LVH most strongly predicted incident valve calcification. Within the MESA cohort, LVH was associated with prevalence, severity, and incidence of valve calcification independent of hypertension and other identified confounders.

Intraindividual variability of C-reactive protein: The Multi-Ethnic Study of Atherosclerosis

BackgroundThe intraindividual variability of C-reactive protein (CRP) remains uncertain. Although guidelines suggest stability of serial CRP values comparable to that of cholesterol measures, several studies indicate greater fluctuations of CRP. We sought to compare the intraindividual variability of CRP with that of cholesterol measures using the multi-ethnic study of atherosclerosis (MESA). MethodsCRP measurements were available in 760 MESA participants after exclusion of those with comorbidities or medications known to affect CRP or CRP≥10 mg/L. Serial values were available for 255 participants. The intraclass correlation coefficient (ICC) was quantified for CRP, total cholesterol (TC), and non-HDL-cholesterol (non-HDL-C) as the ratio of between-subject variance to the sum of between-subject and within-subject variance. Fluctuation between baseline and follow-up categories was calculated by cross-classifying participants according to baseline tertiles. ResultsThe multivariable-adjusted ICC of CRP was 0.62 (95% CI, 0.55–0.68), significantly lower than that of TC (0.75; 95% CI, 0.70–0.81; p = 0.001 vs CRP) and non-HDL-C (0.76; 95% CI, 0.71–0.81; p = 0.001 vs CRP). 51% of participants in the highest baseline CRP tertile had discordant values on follow-up, while 54% and 27% were discordant in the middle and lowest baseline CRP tertiles. Among participants with baseline CRP levels exceeding 3 mg/L, a clinical threshold for higher risk, 69% had subsequent measurements falling within a lower risk category. ConclusionsIn the MESA cohort, intraindividual variation of CRP was significantly greater than that for cholesterol measures. Our results suggest that further evaluation of CRP variability is needed in large prospective studies using shorter intervals between measurements.

Normal Left Ventricular Myocardial Thickness for Middle-Aged and Older Subjects With Steady-State Free Precession Cardiac Magnetic Resonance

Background— Increased left ventricular myocardial thickness (LVMT) is a feature of several cardiac diseases. The purpose of this study was to establish standard reference values of normal LVMT with cardiac magnetic resonance and to assess variation with image acquisition plane, demographics, and left ventricular function. Methods and Results— End-diastolic LVMT was measured on cardiac magnetic resonance steady-state free precession cine long and short axis images in 300 consecutive participants free of cardiac disease (169 women; 65.6±8.5 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Mean LVMT on short axis images at the mid-cavity level was 5.3±0.9 mm and 6.3±1.1 mm for women and men, respectively. The average of the maximum LVMT at the mid-cavity for women/men was 7/9 mm (long axis) and 7/8 mm (short axis). Mean LVMT was positively associated with weight (0.02 mm/kg; P =0.01) and body surface area (1.1 mm/m 2 ; P &lt;0.001). No relationship was found between mean LVMT and age or height. Greater mean LVMT was associated with lower left ventricular end-diastolic volume (0.01 mm/mL; P &lt;0.01), a lower left ventricular end-systolic volume (−0.01 mm/mL; P =0.01), and lower left ventricular stroke volume (−0.01 mm/mL; P &lt;0.05). LVMT measured on long axis images at the basal and mid-cavity level were slightly greater (by 6% and 10%, respectively) than measurements obtained on short axis images; apical LVMT values on long axis images were 20% less than those on short axis images. Conclusions— Normal values for wall thickness are provided for middle-aged and older subjects. Normal LVMT is lower for women than men. Observed values vary depending on the imaging plane for measurement.

Aortic Valve Calcium Independently Predicts Coronary and Cardiovascular Events in a Primary Prevention Population

This study sought to test whether aortic valve calcium (AVC) is independently associated with coronary and cardiovascular events in a primary-prevention population. Aortic sclerosis is associated with increased cardiovascular morbidity and mortality among the elderly, but the mechanisms underlying this association remain controversial. Also, it is unknown whether this association extends to younger individuals. We performed a prospective analysis of 6,685 participants in MESA (Multi-Ethnic Study of Atherosclerosis). All subjects, ages 45 to 84 years and free of clinical cardiovascular disease at baseline, underwent computed tomography for AVC and coronary artery calcium scoring. The primary, pre-specified combined endpoint of cardiovascular events included myocardial infarctions, fatal and nonfatal strokes, resuscitated cardiac arrest, and cardiovascular death, whereas a secondary combined endpoint of coronary events excluded strokes. The association between AVC and clinical events was assessed using Cox proportional hazards regression with incremental adjustments for demographics, cardiovascular risk factors, inflammatory biomarkers, and subclinical coronary atherosclerosis. Over a median follow-up of 5.8 years (interquartile range: 5.6 to 5.9 years), adjusting for demographics and cardiovascular risk factors, subjects with AVC (n = 894, 13.4%) had higher risks of cardiovascular (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.10 to 2.03) and coronary (HR: 1.72; 95% CI: 1.19 to 2.49) events compared with those without AVC. Adjustments for inflammatory biomarkers did not alter these associations, but adjustment for coronary artery calcium substantially attenuated both cardiovascular (HR: 1.32; 95% CI: 0.98 to 1.78) and coronary (HR: 1.41; 95% CI: 0.98 to 2.02) event risk. AVC remained predictive of cardiovascular mortality even after full adjustment (HR: 2.51; 95% CI: 1.22 to 5.21). In this MESA cohort, free of clinical cardiovascular disease, AVC predicts cardiovascular and coronary event risk independent of traditional risk factors and inflammatory biomarkers, likely due to the strong correlation between AVC and subclinical atherosclerosis. The association of AVC with excess cardiovascular mortality beyond coronary atherosclerosis risk merits further investigation. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Association of SCARB1 Variants With Subclinical Atherosclerosis and Incident Cardiovascular Disease

We previously reported a statistically significant association of SCARB1 intronic single nucleotide polymorphism (SNP) rs10846744 with common carotid intimal-medial artery thickness in each of the 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups (white, Chinese, black, and Hispanic). Using an expanded sample of 7936 Multi-Ethnic Study of Atherosclerosis participants, phenotyped for measures of subclinical atherosclerosis, incident myocardial infarction, and cardiovascular disease, and genotyped through the SNP Health Association Resource project, we have now examined the genetic association of these phenotypes with 126 genotyped and imputed SCARB1 SNPs. We also performed stratified analyses to examine whether SCARB1 SNP effects differed by sex. Our analysis of the full Multi-Ethnic Study of Atherosclerosis cohort provides strong evidence for the association of rs10846744 with common carotid intimal-medial thickness (P=1.04E-4 in combined analysis of all 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups). In sex-stratified analysis, we observed statistically significant association of rs10846744 with incident cardiovascular disease events in males (P=0.01). Examining analytical results from the Myocardial Infarction Genetics Consortium for replication, we observed further support for the association of rs10846744 with myocardial infarction. The SCARB1 SNP, rs10846744, exerts a major effect on subclinical atherosclerosis and incident cardiovascular disease in humans.

Trabeculated (Noncompacted) and Compact Myocardium in Adults

Background— A high degree of noncompacted (trabeculated) myocardium in relationship to compact myocardium (trabeculated to compact myocardium [T/M] ratio &gt;2.3) has been associated with a diagnosis of left ventricular noncompaction (LVNC). The purpose of this study was to determine the normal range of the T/M ratio in a large population-based study and to examine the relationship to demographic and clinical parameters. Methods and Results— The thickness of trabeculation and the compact myocardium were measured in 8 left ventricular regions on long axis cardiac MR steady-state free precession cine images in 1000 participants (551 women; 68.1±8.9 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Of 323 participants without cardiac disease or hypertension and with all regions evaluable, 140 (43%) had a T/M ratio &gt;2.3 in at least 1 region; in 20 of 323 (6%), T/M &gt;2.3 was present in &gt;2 regions. A multivariable linear regression model revealed no association of age, sex, ethnicity, height, and weight with maximum T/M ratio in participants without cardiac disease or hypertension ( P &gt;0.05). In the entire cohort (n=1000), left ventricular ejection fraction (β=−0.02/%; P =0.015), left ventricular end-diastolic volume (β=0.01/mL; P &lt;0.0001), and left ventricular end-systolic volume (β=0.01/mL; P &lt;0.001) were associated with maximum T/M ratio in adjusted models, whereas there was no association with hypertension or myocardial infarction ( P &gt;0.05). At the apical level, T/M ratios were significantly lower when obtained on short- compared with long-axis images ( P =0.017). Conclusions— A ratio of T/M of &gt;2.3 is common in a large population-based cohort. These results suggest re-evaluation of the current cardiac MR criteria for left ventricular noncompaction may be necessary.

Cis-vaccenic acid and the Framingham risk score predict chronic kidney disease: The multi-ethnic study of atherosclerosis (MESA)

IntroductionData on the associations of fatty acids with chronic kidney disease (CKD) are sparse. Materials and methodsWe performed a cross-sectional study of 2792 men and women from the MESA cohort of African–American, Caucasian, Chinese and Hispanic adults without known cardiovascular disease. Plasma phospholipid fatty acid proportions were associated with estimated glomerular filtration rate (eGFR) and the albumin/creatinine ratio. ResultsCis-vaccenic acid (18:1n−7), adjusted for other fatty acids using multivariate logistic regression (CI: 1.0–1.4), and step-wise logistic regression (CI: 1.02–1.42), was positively associated with reduced eGFR. The Framingham Risk Score, when adjusting for fatty acid proportions and demographic factors, was positively associated with CKD as measured by the eGFR and the albumin/creatinine ratio. Discussion and conclusionsPlasma phospholipid proportions of the 18 carbon monounsaturated cis-vaccenic acid {18:1n−7}) and the Framingham Risk Score are associated with kidney function. The potential role of 18:1n−7 in the development of CKD warrants further investigation.

Aortic size, distensibility, and pulse wave velocity changes with aging: longitudinal analysis from Multi-Ethnic Study of Atherosclerosis (MESA)

Arterial stiffening is related to an intricate interplay between aging and other cardiovascular risk factors. The aortic arch accounts for most of the vascular buffering function and is primarily involved in arterial stiffening. MRI has been used to noninvasively measure strain, distensibility, and pulse wave velocity of the ascending aorta. We report aortic size and stiffness changes over mid to late adulthood in longitudinal comparisons with MRI over a 10-year period in the MESA cohort.

Metabolic Syndrome Derived from Principal Component Analysis and Incident Cardiovascular Events: The Multi Ethnic Study of Atherosclerosis (MESA) and Health, Aging, and Body Composition (Health ABC)

Background. The NCEP metabolic syndrome (MetS) is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA) of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC) study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP) in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA) cohort. We selected the first principal component as a continuous MetS score (MetS-PC). Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n = 377) adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37%) in the MESA cohort. Hazard ratio (HR) for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI) for CVD events for 1-SD (standard deviation) of MetS-PC was 1.71 (1.54–1.90) (P < 0.0001) overall after adjusting for potential confounders, and for each ethnicity, HRs were: Caucasian, 1.64 (1.39–1.94), Chinese, 1.39 (1.06–1.83), African, 1.67 (1.37–2.02), and Hispanic, 2.10 (1.66-2.65). Finally, when binary definitions were compared, HR for CVD events was 2.34 (1.91–2.87) for MetS-PC versus 1.79 (1.46–2.20) for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetS-PC per 1-SD (Health ABC) remained associated with CVD events (HR = 1.21, 95%CI 1.12–1.32) overall, and for each ethnicity, Caucasian (HR = 1.24, 95%CI 1.12–1.39) and African Americans (HR = 1.16, 95%CI 1.01–1.32). Finally, when using a binary definition of MetS-PC (cut point 0.505) designed to match the NCEP definition in terms of prevalence in the Health ABC cohort (35%), the fully adjusted HR for CVD events was 1.39, 95%CI 1.17–1.64 compared with 1.46, 95%CI 1.23–1.72 using the NCEP definition. Conclusion. MetS-PC is a continuous measure of metabolic syndrome and was a better predictor of CVD events overall and in individual ethnicities. Additionally, a binary MetS-PC definition was better than the NCEP MetS definition in predicting incident CVD events in the MESA cohort, but this superiority was not evident in the Health ABC cohort.

Preradiotherapy Calcium Scores of the Coronary Arteries in a Cohort of Women With Early-Stage Breast Cancer: A Comparison With a Cohort of Healthy Women

Breast cancer radiotherapy has been associated with an increased risk of cardiac toxicity. However, no data are available on the probability of developing coronary artery disease (CAD) in breast cancer patients when compared with healthy women. Therefore, baseline coronary artery calcium (CAC) scores, as an accepted tool to predict CAD, were determined and compared with the CAC scores of a healthy, asymptomatic cohort, the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Eighty consecutive patients with ductal carcinoma in situ or infiltrative breast cancer referred for radiotherapy after breast-conserving surgery were included in our study. Their cardiovascular risk profile was registered, and a 64 multislice CT scan was performed. The CAC scores of an unselected (Caucasian only) Radiotherapy Centre West (RCWEST) cohort, as well as of those of a selected (comorbidity and race adjusted) RCWEST cohort, were determined. The scores of both cohorts were compared with those of the female (Caucasian only) MESA cohort. For the unselected RCWEST cohort (n = 62) we found significant (p < .01) higher scores for women in the 55-64 age category compared with those of the MESA cohort. In the selected cohort (n = 55) the CAC scores of the women in the age category 55-64 were significantly (p = .02) higher compared with the MESA cohort. No significant differences were noted in the other age categories. Both cohorts revealed that CAC scores in the 55-64 age category were significantly higher than the CAC scores in the asymptomatic (female) MESA population. These data suggest that breast cancer patients bear a higher risk of developing coronary heart disease before the start of radiotherapy. Therefore, measures to decrease cardiac dose further in breast cancer radiotherapy are even more important.

Prevalence and Characteristics of Choroidal Nevi: The Multi-Ethnic Study of Atherosclerosis

To describe the prevalence of choroidal nevi in 4 racial or ethnic groups (white, black, Hispanic, and Chinese) in the United States. Cross-sectional study. Participants of the second examination of the Multi-Ethnic Study of Atherosclerosis (MESA), involving 6176 persons 44 to 84 years of age without clinical cardiovascular disease at baseline selected from 6 United States communities. Fundus images were taken using a 45° digital camera through dark-adapted pupils and were graded for choroidal nevi using the modified Wisconsin Age-Related Maculopathy Grading System and the Blue Mountains Eye Study protocol. Choroidal nevi. The overall prevalence of choroidal nevi in the whole cohort was 2.1%, with prevalences higher in whites (4.1%) than blacks (0.7%), Hispanics (1.2%), and Chinese (0.4%; P<0.001 for any differences among groups). The lowest prevalence of choroidal nevi occurred in those 75 to 84 years of age. The nevi were subfoveal in 4% of eyes with nevi and were not associated with a decrease in visual acuity. Characteristics of the nevi (size, shape, location, color, drusen on surface) did not differ among racial or ethnic groups. With the exception of associations with higher C-reactive protein levels (odds ratio [OR] per mg/dl on the logarithmic scale, 1.23; 95% confidence interval [CI], 1.06-1.43; P = 0.01) and lower systolic blood pressure (OR per 10 mmHg, 0.90; 95% CI, 0.82-0.99; P = 0.04), choroidal nevi were not associated with other potential risk factors (e.g., gender, smoking status, alcohol consumption, lipid levels, coagulation factors, or kidney disease). Low prevalences of choroidal nevi were found in the 4 groups participating in the MESA cohort, with whites having higher prevalence than the other racial or ethnic groups. The higher prevalence in whites than in other groups was not explained by any of the factors studied. When choroidal nevi were present, their characteristics did not differ among racial or ethnic groups. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Homocysteine and Reclassification of Cardiovascular Disease Risk

The purpose of this study was to examine whether adding homocysteine (Hcy) to a model based on traditional cardiovascular disease (CVD) risk factors improves risk classification. Data on using Hcy to reclassify individuals in various risk categories beyond traditional approaches have not been adequately scrutinized. We performed a post hoc analysis of the MESA (Multi-Ethnic Study of Atherosclerosis) and NHANES III (National Health and Nutrition Examination Survey III) datasets. Hcy was used to predict composite CVD and hard coronary heart disease (CHD) events in the MESA study and CVD and CHD mortality in the NHANES III survey using adjusted Cox-proportional hazard analysis. Reclassification of CHD events was performed using a net reclassification improvement (NRI) index with a Framingham risk score (FRS) model with and without Hcy. Hcy level (>15 μmol/l) significantly predicted CVD (adjusted hazard ratio [aHR]: 1.79, 95% confidence intervals [CI]: 1.19 to 1.95; p = 0.006) and CHD events (aHR: 2.22, 95% CI: 1.20 to 4.09; p = 0.01) in the MESA trial and CVD (aHR: 2.72, 95% CI: 2.01 to 3.68; p < 0.001) and CHD mortality (aHR: 2.61, 95% CI: 1.83 to 3.73; p < 0.001) in the NHANES III, after adjustments for traditional risk factors and C-reactive protein. The level of Hcy, when added to FRS, significantly reclassified 12.9% and 18.3% of the overall and 21.2% and 19.2% of the intermediate-risk population from the MESA and NHANES cohorts, respectively. The categoryless NRI also showed significant reclassification in both MESA (NRI: 0.35, 95% CI: 0.17 to 0.53; p < 0.001) and NHANES III (NRI: 0.57, 95% CI: 0.43 to 0.71; p < 0.001) datasets. From these 2 disparate population cohorts, we found that addition of Hcy level to FRS significantly improved risk prediction, especially in individuals at intermediate risk for CHD events.

The Association of Chronic Kidney Disease and Metabolic Syndrome with Incident Cardiovascular Events: Multiethnic Study of Atherosclerosis

Background. There is an association between chronic kidney disease (CKD) and metabolic syndrome (MetS). We examined the joint association of CKD and MetS with incident cardiovascular (CVD) events in the Multiethnic Study of Atherosclerosis (MESA) cohort. Methods. We analyzed 2,283 Caucasians, 363 Chinese, 1,449 African-Americans, and 1,068 Hispanics in the MESA cohort. CKD was defined by cystatin C estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2 and MetS was defined by NCEP criteria. Cox proportional regression adjusting for age, ethnicity, gender, study site, education, income, smoking, alcohol use, physical activity, and total and LDL cholesterol was performed to assess the joint association of CKD and MetS with incident CVD events. Participants were divided into four groups by presence of CKD and/or MetS and compared to the group without CKD and MetS (CKD−/MetS−). Tests for additive and multiplicative interactions between CKD and MetS and prediction of incident CVD were performed. Results. During follow-up period of 5.5 years, 283 participants developed CVD. Multivariate Cox regression analysis demonstrated that CKD and MetS were independent predictors of CVD (hazard ratio, 2.02 for CKD, and 2.55 for MetS). When participants were compared to the CKD−/MetS− group, adjusted HR for the CKD+/MetS+ group was 5.56 (95% CI 3.72–8.12). There was no multiplicative interaction between CKD and MetS (P = 0.2); however, there was presence of additive interaction. The relative excess risk for additive interaction (RERI) was 2.73, P = 0.2, and the attributable portion (AP) was 0.49 (0.24–0.74). Conclusion. Our findings illustrate that the combination of CKD and MetS is a strong predictor of incident clinical cardiovascular events due to presence of additive interaction between CKD and MetS.

Gene expression variation between African Americans and whites is associated with coronary artery calcification: the multiethnic study of atherosclerosis

Coronary artery calcium (CAC) is a strong indicator of total atherosclerosis burden. Epidemiological data have shown substantial differences in CAC prevalence and severity between African Americans and whites. However, little is known about the molecular mechanisms underlying initiation and progression of CAC. Microarray gene expression profiling of peripheral blood leucocytes was performed from 119 healthy women aged 50 yr or above in the Multi-Ethnic Study of Atherosclerosis cohort; 48 women had CAC score >100 and carotid intima-media thickness (IMT) >1 mm, while 71 had CAC <10 and IMT <0.65 mm. When 17 African Americans were compared with 41 whites in the low-CAC group, 409 differentially expressed genes (false discovery rate <5%) were identified. In addition, 316 differentially expressed genes were identified between the high- and low-CAC groups. A substantial overlap between these two gene lists was observed (148 genes, P < 10(-6)). Furthermore, genes expressed lower in African Americans also tend to express lower in individuals with low CAC (correlation 0.69, P = 0.002). Ontology analysis of the 409 race-associated genes revealed significant enrichment in mobilization of calcium and immune/inflammatory response (P < 10(-9)). Of note, 25 of 30 calcium mobilization genes were involved in immune/inflammatory response (P < 10(-10)). Our data suggest a connection between immune response and vascular calcification and the result provides a potential mechanistic explanation for the lower prevalence and severity of CAC in African Americans compared with whites.

230 Prevalence and risk factors of lower extremity artery disease in subjects without traditional modifiable cardiovascular risk factors. The multi-ethnic study of atherosclerosis

Lower-extremity peripheral artery disease (PAD) is associated with traditional cardiovascular disease risk factors (smoking, hypertension, dyslipidemia, diabetes). Among participants in the Multi-Ethnic Study of Atherosclerosis (MESA), we sought to assess the prevalence of PAD in a population without these risk factors. We hypothesized that this prevalence is not negligible, and that in this situation, PAD would still remain associated with other measures of subclinical atherosclerosis. In the MESA cohort, we selected those (n = 1932) meeting the following criteria: no smoking over the last 10 years, no history of hypertension, dyslipidemia or diabetes, and normal blood pressure (140/90), fasting blood glucose 1.26 g/l, and a total-/HDL-cholesterol ratio <5. Participants were classified according to their ankle-brachial index (ABI) into 3 groups: low (<1.00), normal (1.00–1.30) and high (>1.30) ABI. Measures of subclinical atherosclerosis included any coronary artery calcification (CAC) or carotid plaque. Overall, the mean estimated Framingham risk score for coronary heart disease was 0.61%/year. Low- and high ABI were found in 176 (9%) and 149 (7.8%) participants, respectively. In multivariable models including age, gender and ethnicity, lower glomerular filtration rates (OR: 0.88/10 units, p = 0.04) and higher interleukin-6 levels (OR:1.42/natural-log unit, p = 0.02) were associated with low ABI. Higher body-mass index (OR:1.07/unit, p<0.001) was associated with high ABI. In a fully-adjusted model, low-ABI, not high-ABI, was significantly associated with CAC prevalence (OR:1.22, p<0.03). No significant association was found with carotid plaque. In subjects without traditional risk factors, PAD is common. Such persons remain at higher risk for coronary artery disease.

Is Cystatin C the Answer to Detecting Progression in CKD?

Although increasing interest is given to early detection of chronic kidney disease (CKD), there is controversy over whether all patients need our attention. It has been argued, for example, that many patients with stage 3 or 4 CKD, especially the elderly, are not at increased risk for mortality and