The MESA cohort was initiated to investigate the prevalence, correlates, and progression of subclinical CVD. (i.e. disease detected by non-invasive means before it has manifested in clinical signs and symptoms). Details about the study design have previously been published.18
Briefly, between July 2000 and August 2002, 6814 men and women aged 45 to 84 years old, self-identified as white, black, Hispanic, or Chinese and free of clinically apparent CVD were recruited from portions of 6 US communities: Baltimore City and Baltimore County, Maryland; Chicago, Ill; Forsyth County, North Carolina; Los Angeles County, California; Northern Manhattan and the Bronx, New York; and St. Paul, Minn. Each field site recruited from locally available sources, which included lists of residents, lists of dwellings, and telephone exchanges. The institutional review boards at all participating centers approved the study, and all participants gave informed consent.
Participants underwent an extensive baseline evaluation, including an initial standardized questionnaire. Measurements of height, weight, body mass index, anthropometric data, and blood pressure were measured as well. Total and high-density lipoprotein cholesterol, triglycerides, and glucose levels were measured from blood samples obtained after a 12-hour fast. Low-density lipoprotein cholesterol was calculated with the Friedewald equation.19
Diabetes was defined as fasting glucose 126 mg/dL or use of hypoglycemic medication.
For electrocardiography, three 12-lead recordings are obtained using a Marquette MAC-PC instrument (Marquette Electronics, Milwaukee, Wisconsin) and read using both Minnesota Code (MC)20
and Novacode criteria (NC)21
. Readings are performed centrally at the EPICARE reading center, Wake Forest University. Major ECG abnormalities were defined by the presence of 1 or more of the following findings: ventricular conduction defect (NC 3.1, 3.2 or 3.3), major Q wave (NC 5.1, 5.2, or 5.3), minor Q, QS waves with ST-T abnormalities (NC 5.4), isolated ST-T wave abnormalities (NC 5.5 or 5.6), left ventricular hypertrophy (NC 6.1.1), atrial fibrillation (NC 1.5.1, 1.5.2, or 1.5.3) or first degree atrio-ventricular block (NC 2.1). Minor ECG abnormalities were defined by the presence of 1 or more of the following findings: Minor Q, QS waves (NC 5.7), high R waves(NC 6.1.0), minor isolated ST-T abnormalities(NC 5.8), ST elevation (MC 9-2), incomplete right bundle branch block (NC 3.4.1), long QT Interval (qti1 >=110, where qti1 = qtdur1* (hr + 100) / 656), short PR segment (< 120 ms), left axis deviation (>= −90, <= −30), or right axis deviation(>=120, <=210). Isolated minor STTA (NC 5.8) were included, a priori
, in a separate analysis as they represented a large percentage of the minor ECG abnormalities. Participants with major ECG abnormalities were excluded from the analyses examining minor ECG abnormalities and isolated minor STTA.
CAC was measured with either electron-beam computed tomography or multidetector computed tomography at 3 field centers and these scans were read independently at a centralized reading center. The amount of calcium was quantified with the Agatston scoring method.22
Interobserver agreement and intraobserver agreement were found to be very high (kappa =0.93 and 0.90, respectively). Coronary artery calcification was defined as being present (CAC+) if the calcium score was >0.23
Trained technicians in each field center performed B-mode ultrasonography of the right and left near and far walls of the internal carotid and common carotid arteries. An ultrasound reading center (Department of Radiology, Tufts–New England Medical Center, Boston, Massachusetts) measured maximal IMT of the common carotid artery defined as the mean of the maximal IMT of the near and far wall on both the left and right sides, and it was measured at mm proximal to the common carotid bulb.18
Internal Carotid IMT was not included in the present analysis due missing data.
All analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC). Baseline characteristics were compared, after stratification by sex, between participants using chi-square tests for categorical variables and t-tests or Wilcoxon rank-sum tests for continuous variables, as appropriate. To determine the cross-sectional association of ECG abnormalities with CAC+ (defined as CAC > 0), logistic regression models were fitted with the presence of CAC as the dependent variable and the presence of ECG abnormalities as the independent variable. To analyze the presence and extent of CAC, and given the large number of zero values and highly skewed distribution, we used mixed models to analyze CAC presence and ln (CAC + 1). For the association of ECG abnormalities with common carotid IMT, we used linear regression models with mean maximal CC-IMT as the dependent variable and ECG abnormalities as the independent variables. All regression models were adjusted for age, sex, and race initially; further adjustment for demographic and clinical covariates (age, smoking status, systolic blood pressure, blood pressure med, total cholesterol, high-density lipoprotein, cholesterol med, diabetes, body mass index was performed. To test for interaction of abnormal ECGs and age, we examined both age-stratified (< 65 years vs. > 65 years) models, as well as multiplicative interaction terms in the same models. In secondary analyses we also examined sex/race-specific analyses to determine whether the pattern of associations was consistent across all sex/race groups. A p-value <0.05 was considered statistically significant.