Population

MESA is an observational cohort study that includes a population of 6,814 men and women aged 45 to 84 years with no histories of clinical cardiovascular disease, enrolled between July 2000 and August 2002. The MESA cohort includes white, African American, Hispanic American, and Chinese participants (race and ethnicity were determined by questionnaire). Participants were excluded if they had physician-diagnosed heart attacks, strokes, transient ischemic attacks, heart failure, angina, atrial fibrillation, or histories of any cardiovascular procedures. Participants weighing > 300 lb, those who were pregnant, and those with any medical conditions that would prevent long-term participation were excluded. MESA protocols and all studies described herein have been approved by the institutional review boards of all collaborating institutions, and all participants gave informed consent.

We restricted our analyses to a subset of the MESA cohort of white ethnicity aged 45 to 54 years. We selected this younger subset of the MESA population because they are likely to have a lower burden of atherosclerosis than older participants, and the prevalence of plaques in this participants is likely to be the lowest. We sampled only one race to maintain homogeneity of our results given financial limitations.

Risk Factors and Anthropomorphic Variables

Age, gender, race or ethnicity, and medical history were self-reported. Use of antihypertensive medications was also recorded. Current smoking was defined as self-report of smoking one or more cigarettes in the past 30 days. Resting systolic and diastolic blood pressures were measured in a seated position using a Dinamap Pro 100 automated oscillometric sphygmomanometer (Critikon, Tampa, FL).

Lipids were measured after a 12-hour fast. Diabetes mellitus was determined using the 2003 American Diabetes Association fasting criteria algorithm. Total cholesterol was measured using a cholesterol oxidase method (Roche Diagnostics GmbH, Mannheim, Germany), as was high-density lipoprotein after precipitation of non-high-density lipoprotein cholesterol with magnesium/dextran.

Carotid Artery Measures

The patients were imaged in the supine position with the head rotated 45° toward the side opposite to the side being imaged. The CCA was then imaged at 45° from the vertical, with the beginning of the bulb shown on the image (to the left). A matrix-array probe (M12L; GE Medical Systems, Milwaukee, WI) was used, with the frequency set at 13 MHz and two focal zones at a frame rate of 32 frames/sec.

All carotid artery measurements were blinded and made at the ultrasound reading center in Boston. Far wall CCA IMT measurements were made on both sides of the neck at end-diastole (smallest carotid artery diameter). A continuous tracing was made of the far wall intima-media and lumen-intima interfaces. An algorithm was then used to calculate the mean distance between both interfaces as well as the maximum value. The mean of the mean right and left IMT values and the mean of the maximum right and left IMT values were averaged. Measurements were made at two CCA locations over a distance of 1 cm. The first set of measurements was made near the bulb, from where the lumen of the CCA starts to dilate ( Figure 1 A). The second set of measurements was made below the bulb, starting at the point at which the outer wall (adventitia) of the artery begins to diverge ( Figure 1 B). Every attempt was made to measure the segments over a distance of 1 cm starting from these two fiduciary points. As such, there was partial overlap of the measurements.

Location of IMT measurements. The location of the IMT measurements near to the bulb (A) on the far wall of the artery is outlined by the white box on this composite image of a carotid bifurcation. The measurement zone extends 1 cm toward the body ( right of the image ), starting where the lumen starts to diverge from parallel. The location of the IMT measurement below the bulb is shown (B) . The measurement zone also extends 1 cm towards the body ( right of the image ) but starts where the outer walls start to diverge. The zone of overlap is the length of the carotid artery between the divergence of the outer wall of the artery (adventitia) and the divergence of the lumen (intima). Cases in which the lumen-intima and media-adventitia interfaces remained parallel to each other ( arrows ) near to the bulb (C) were not included in the analyses.

We studied a random selection of 339 participants from the 723 white participants in this age range seen at baseline. Of these 339 participants, 60 participants with ultrasound studies in which the dilation of the carotid bulb was not visible, in which the luminal interfaces were parallel to the media-adventitia interfaces ( Figure 1 C), or with incomplete risk factor data were excluded.

We evaluated the consistency of our results by measuring images from second studies acquired at different visits in the 279 participants. The correlation coefficient between the two visits for mean of the mean IMT starting next to the bulb was 0.83 and for mean of the mean IMT starting below the bulb was 0.85. The correlation coefficients between visits for mean of the maximum IMT were 0.51 for near to the bulb and 0.61 for below the bulb.

Events

Events were identified during follow-up examinations and by telephone interviews conducted every 9 to 12 months to inquire about all interim hospital admissions, cardiovascular outpatient diagnoses, and deaths. Copies were obtained of all death certificates and of all medical records for hospitalizations and outpatient cardiovascular diagnoses. Two physicians from the MESA study events committee independently reviewed all medical records for end point classification and assignment of incidence dates. The review process included all generated International Classification of Diseases definitions, but the final adjudication of MESA end points was based on specific criteria applied to data obtained from medical records by two committee members or by the whole study events committee in case of disagreement. Coronary heart disease (CHD) events included myocardial infarction, resuscitated cardiac arrest, definite or probable angina followed by coronary revascularization, and definite angina not followed by coronary revascularization. Patients with coronary artery revascularization who did not have concurrent diagnoses of angina were not included.

Statistical Analyses

The means and standard deviations of continuous variables and the distribution of dichotomous variables as percentages in each group are shown.

Four multivariate linear regression models were generated with IMT as the outcome: (1) mean of the maximum IMT near the bulb, (2) mean of the mean IMT near the bulb, (3) mean of the maximum IMT below the bulb, and (4) mean of the mean IMT below the bulb. Traditional Framingham risk factors were used in the models, including lipid-lowering and blood pressure–lowering medications. The partial coefficients of determination between individual risk factors and IMT are reported, as well as the global association of individual IMT measurements and risk factors.

We evaluated potential associations between CHD events and IMT measurements using unadjusted Cox proportional-hazards models and forming minimally adjusted models for variables that were significantly associated with CHD, as well as forcing age and sex into the models. We verified our findings using forward selection in separate multivariate Cox proportional-hazards models for all candidate variables and the respective IMT measurement. We used a cut point of P < .05 for inclusion.

Kaplan-Meier curves are displayed for the respective IMT measurements using the respective median values as cut points.

Statistical analyses were performed using Stata version 11.2 (StataCorp LP, College Station, TX). The level of statistical significance was set at P ≤ .05 (two sided).

Kaplan-Meier curves showing the likelihood of not developing CHD events during follow-up. Values greater than the median of the mean far wall IMT measured farther away from the bulb (A) are associated with a greater likelihood of incident CHD ( P = .032, log-rank = 4.63), whereas mean of the maximum IMT measured in the same location (B) does not show a significant association ( P = .13, log-rank = 2.35). Values greater than the median of the far wall IMT nearer to the bulb (C) are also associated with CHD events ( P = .033, log-rank = 4.53), whereas mean of the maximum IMT measured at the same location (D) is not ( P = .77, log-rank = 0.09).