Multi-Ethnic Study of Atherosclerosis (MESA) Cohort

MESA
The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. MESA researchers study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Thirty-eight percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent.

Participants were recruited from six field centers across the United States: Wake Forest University, Columbia University, Johns Hopkins University, University of Minnesota, Northwestern University and University of California - Los Angeles. Each participant received an extensive physical exam and determination of coronary calcification, ventricular mass and function, flow-mediated endothelial vasodilation, carotid intimal-medial wall thickness and presence of echogenic lucencies in the carotid artery, lower extremity vascular insufficiency, arterial wave forms, electrocardiographic (ECG) measures, standard coronary risk factors, sociodemographic factors, lifestyle factors, and psychosocial factors. Selected repetition of subclinical disease measures and risk factors at follow-up visits allows study of the progression of disease. Blood samples have been assayed for putative biochemical risk factors and stored for case-control studies. DNA has been extracted and lymphocytes cryopreserved (for possible immortalization) for study of candidate genes and possibly, genome-wide scanning, expression, and other genetic techniques. Participants are being followed for identification and characterization of cardiovascular disease events, including acute myocardial infarction and other forms of coronary heart disease (CHD), stroke, and congestive heart failure; for cardiovascular disease interventions; and for mortality.

In addition to the six Field Centers, MESA involves a Coordinating Center, a Central Laboratory, and Central Reading Centers for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Ultrasound, and Electrocardiography (ECG). Protocol development, staff training, and pilot testing were performed in the first 18 months of the study. The first examination took place over two years, from July 2000 - July 2002. It was followed by four examination periods that were 17-20 months in length. Participants have been contacted every 9 to 12 months throughout the study to assess clinical morbidity and mortality.

MESA Family
The general goal of the MESA Family Study, an ancillary study to MESA funded by a grant from NHLBI, is to apply modern genetic analysis and genotyping methodologies to delineate the genetic determinants of early atherosclerosis. This is being accomplished by utilizing all the current organizational structures of the Multi-Ethnic Study of Atherosclerosis (MESA) and Genetic Centers at Cedars-Sinai Medical Center and University of Virginia.

In the MESA Family Study, the goal is to locate and identify genes contributing to the genetic risk for cardiovascular disease (CVD), by looking at the early changes of atherosclerosis within families (mainly siblings). 2128 individuals from 594 families, yielding 3,026 sibpairs divided between African Americans and Hispanic-Americans, were recruited by utilizing the existing framework of MESA. MESA Family studied siblings of index subjects from the MESA study and from new sibpair families (with the same demographic characteristics) and is determining the extent of genetic contribution to the variation in coronary calcium (obtained via CT Scan) and carotid artery wall thickness (B-mode ultrasound) in the two largest non-majority U.S. populations. In a small proportion of subjects, parents of MESA index subjects participating in MESA Family were studied but only to have blood drawn for genotyping.

The MESA Family cohort was recruited from the six MESA Field Centers. MESA Family participants underwent the same examination as MESA participants during May 2004 - May 2007. DNA was extracted and lymphocytes immortalized for study of candidate genes, genome-wide linkage scanning, and analyzed for linkage with these subclinical cardiovascular traits. While linkage analysis is the primary approach being used, an additional aspect of the MESA Family Study takes advantage of the existing MESA study population for testing a variety of candidate genes for association with the same subclinical traits. Genotyping and data analysis will occur throughout the study.

MESA Air
The general goal of the Multi-Ethnic Study of Atherosclerosis and Air Pollution ('MESA Air') is to prospectively examine the relation between an individual level assessment of long-term ambient air pollution exposures (including PM_2.5 and the progression of subclinical cardiovascular disease in a multi-city, multi-ethnic cohort. MESA Air will also prospectively examine the relationship between an individual level assessment of long-term ambient air pollution exposures and the incidence of cardiovascular disease, including myocardial infarction and cardiovascular death. MESA AIR is funded by a grant from the United States Environmental Protection Agency to the University of Washington and subcontracts from the UW to other participating institutions.

MESA Air will assess if ambient air pollution is associated with changes over time in subclinical measures of atherosclerosis and plasma markers of inflammation, oxidative damage, and endothelial activation in a longitudinal data model, adjusting for age, race/ethnicity, socioeconomic status, and specific cardiovascular risk factors (such as diabetes, hypertension, smoking, and diet). The study will similarly assess if the incidence of cardiovascular events is associated with long-term exposure to ambient air pollution, using a proportional hazards model. The study includes refinement of statistical tools, and explores joint/independent effects of acute and long-term pollutant exposure in the occurrence of cardiovascular disease.

The MESA Air study is built on the foundation of the ongoing MESA study. The parent MESA Study cohort is located in six geographic areas ('Field Centers') that capture tremendous exposure heterogeneity, comparable to or greater than the variability in locations of prior U.S. cohort studies. In addition to the six Field Centers, the study involves a Coordinating Center, a Central Laboratory, and Reading Centers for Computed Tomography (CT), ultrasound and air pollution data.

The cohort for the MESA Air study currently includes 6226 subjects: 5479 enrolled in the parent MESA study; 257 recruited specifically for this study, and 490 recruited from the MESA Family study. The entire MESA Air cohort will be followed over a 10-year project period for the occurrence of cardiovascular disease events.

On two occasions over the ten-year study period, 3600 subjects from the MESA Air cohort, residing in nine locales, will undergo computed tomography scanning to assess presence and extent of coronary artery calcification (CAC), and ultrasound of the carotid artery to determine intima-media thickness (IMT). We will also repeatedly assess plasma markers of inflammation, oxidative damage, and endothelial function in 720 subjects.

MESA Air adds state-of-the-art air pollution exposure assessment information to the MESA cohort study, and introduces new subjects and outcome measures to achieve our aims. The study will assess long-term individual-level exposure to ambient air pollutants for each subject using community-scale monitoring, outdoor spatial variation, subject proximity to pollution sources, pollutants' infiltration efficiency, and personal time-activity information. The exposure models will be validated using detailed monitoring in a subset of subjects.

The MESA Cohort is utilized in the following dbGaP substudies. To view genotypes, analysis, expression data, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" section of this top-level study page phs000209 MESA Cohort.

• phs000420 MESA SHARe
• phs000283 MESA CARe
• phs000403 MESA ESP Heart-GO

• Study Weblinks:
  • MESA
  • MESA Air
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Longitudinal
  • Family
• Subject Sample Telemetry Report (SSTR)

MESA
Eligible MESA participants were defined as persons living within the defined geographic boundaries for each Field Center between the ages of 45 and 84 at enumeration, who are African-American, Chinese-American, Caucasian, or Hispanic, and who do not meet any of the exclusion criteria (see below). Target race/ethnic groups for each field center were chosen to maximize efficiency to detect race/ethnic differences and to allow the separation of the effect of race/ethnicity from that of study site.

MESA's primary hypotheses are concerned with the determinants and natural history of subclinical cardiovascular disease. Therefore, participants with known clinical disease were not recruited. Most other exclusion criteria related to the long-term nature of the study or to incompatibility with certain components of the MESA exam. Eligibility (or ineligibility) status was determined from self-reported information and no attempt was made to validate the participant's response. MESA's exclusion criteria are below:

• Age younger than 45 or older than 84 years
• Physician-diagnosed heart attack
• Physician-diagnosed angina or taking nitroglycerin
• Physician-diagnosed stroke or TIA
• Physician-diagnosed heart failure
• Current atrial fibrillation
• Having undergone procedures related to cardiovascular disease (CABG, angioplasty, valve replacement, pacemaker or defibrillator implantation, any surgery on the heart or arteries)
• Active treatment for cancer
• Pregnancy
• Any serious medical condition which would prevent long-term participation
• Weight >300 pounds
• Cognitive inability as judged by the interviewer
• Living in a nursing home or on the waiting list for a nursing home
• Plans to leave the community within five years
• Language barrier (speaks other than English, Spanish, Cantonese or Mandarin)
• Chest CT scan in the past year

MESA Family
MESA Family participants are defined as siblings of index subjects from the MESA study. Unlike the main MESA cohort, participants with clinical cardiovascular disease were not excluded. When available, parents of MESA index subjects participating in MESA Family are studied but only had blood drawn for genotyping.

MESA Air
Criteria for MESA and MESA Family Participants
All existing MESA participants are eligible for inclusion into MESA Air if they live in an area that can be reasonably included in the MESA Air pollution exposure modeling. MESA Family participants with no known clinical cardiovascular disease are also recruited.

MESA Air New Recruit Inclusion Criteria
Eligible new MESA Air participants are defined as persons living within the defined geographic boundaries for each community without plans to move within eight years, between the ages of 50 and 90, (four years older than at MESA inception-to match the concurrent age of MESA cohort), of African-American, Chinese-American, Caucasian, or Hispanic ancestry, and who do not meet any of the exclusion criteria used in MESA.

• Primary Phenotype: Cardiovascular Diseases
• Atherosclerosis

• BioProject
• PubMed
• Sequence Read Archive
• BioSample
• MeSH
• PMC

• MESA Principal Investigators
  • Richard Kronmal, PhD. Coordinating Center, University of Washington, WA, USA.
  • Robyn McClelland, PhD. Coordinating Center, University of Washington, WA, USA.
  • Steven Shea, MD. Field Center, Columbia University, New York, NY, USA.
  • Wendy Post, MD, MS. Field Center, Johns Hopkins University, Baltimore, MD, USA.
  • Kiang Liu, PhD. Field Center, Northwestern University, Evanston, IL, USA.
  • Aaron Folsom, MD, MPH. Field Center, University of Minnesota, Minneapolis, MN, USA.
  • Karol Watson, MD, PhD. Field Center, University of California at Los Angeles, Los Angeles, CA, USA.
  • Gregory Burke, MD, MS. Field Center, Wake Forest University, Winston-Salem, NC, USA.
  • Russell Tracy, PhD. Central Laboratory, University of Vermont, Burlington, VT, USA.
  • Matthew J. Budoff, MD. CT Reading Center, University of California at Los Angeles, Torrance, CA, USA.
  • João A. Lima, MD. MRI Reading Center, Johns Hopkins University, Baltimore, MD, USA.
  • Daniel H. O'Leary, MD. Ultrasound Reading Center, New England Medical Center, Boston, MA, USA.
  • Elsayed Z. Soliman, MD, MSc. ECG Reading Center, Wake Forest University, Winston-Salem, NC, USA.
  • Jerome I. Rotter, MD. Genetics Center, Cedars-Sinai, Los Angeles, CA, USA.
  • Stephen Rich, PhD. Genetic Analysis Center, University of Virginia, Charlottesville, VA, USA.
  • Michael Tsai, PhD. Central Lipid Lab, University of Minnesota, Minneapolis, MN, USA.
• MESA Project Officer
  • Jean Olson, MD, MPH. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Deputy Project Officer
  • Lorraine Silsbee, MHS. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - Coordinating Center
  • N01 HC95159. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
  • HHSN268201500003I. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - UCLA Field Center
  • N01-HC-95160. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - Columbia University Field Center
  • N01-HC-95161. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - Columbia GCRC
  • RR-024156. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - Johns Hopkins University Field Center
  • N01-HC-95162. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - University of Minnesota Field Center
  • N01-HC-95163. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - Northwestern University Field Center
  • N01-HC-95164. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - Wake Forest University Field Center
  • N01-HC-95165. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - Central Laboratory
  • N01-HC-95166. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - Ultrasound Reading Center
  • N01-HC-95167. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - MRI Reading Center
  • N01-HC-95168. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Funding Source - CT Reading Center
  • N01-HC-95169. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Family Principal Investigators
  • Richard Kronmal, PhD. Coordinating Center, University of Washington, WA, Seattle.
  • Steven Shea, MD. Field Center, Columbia University, New York, NY, USA.
  • Wendy Post, MD, MS. Field Center, Johns Hopkins University, Baltimore, MD, USA.
  • Kiang Liu, PhD. Field Center, Northwestern University, Evanston, IL, USA.
  • James Pankow, PhD, MPH. Field Center, University of Minnesota, Minneapolis, MN, USA.
  • Karol Watson, MD, PhD. Field Center, University of California at Los Angeles, Los Angeles, CA, USA.
  • Gregory Burke, MD, MS. Field Center, Wake Forest University, Winston-Salem, NC, USA.
  • Russell Tracy, PhD. Central Laboratory, University of Vermont, Burlington, VT, USA.
  • Mary Frances Cotch, PhD. Retinal Reading Center, National Eye Institute, NIH, Bethesda, MD, USA.
  • Daniel H. O'Leary, MD. Ultrasound Reading Center, New England Medical Center, Boston, MA, USA.
  • Walter Palmas, MD. Field Center, Columbia University, New York, NY, USA.
  • Jerome I. Rotter, MD. Genetics Center, Cedars-Sinai, Los Angeles, CA, USA.
  • Stephen Rich, PhD. Genetic Analysis Center, University of Virginia, Charlottesville, VA, USA.
• MESA Family Project Officer
  • Jean Olson, MD PhD. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Family Funding Source - University of California at Los Angeles Field Center
  • R01HL071051. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Family Funding Source - Cedars-Sinai Medical Center Field Center
  • R01HL071205. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Family Funding Source - Northwestern University Field Center
  • R01HL071250. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Family Funding Source - University of Minnesota Field Center
  • R01HL071251. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Family Funding Source - Columbia University Field Center
  • R01HL071252. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Family Funding Source - Wake Forest University Field Center
  • R01HL071258. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Family Funding Source - Johns Hopkins University Field Center
  • R01HL071259. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Air Principal Investigators
  • Joel Kaufman, MD. Exposure Center, University of Washington, Seattle, WA, USA.
  • Richard Kronmal, PhD. Coordinating Center, University of Washington, WA, USA.
  • R. Graham Barr, MD DrPH. Field Center, Columbia University, New York, NY, USA.
  • Brad Astor, PhD, MPH. Field Center, Johns Hopkins University, Baltimore, MD, USA.
  • Martha Daviglus, MD, PhD. Field Center, Northwestern University, Evanston, IL, USA.
  • David Jacobs Jr, PhD. Field Center, University of Minnesota, Minneapolis, MN, USA.
  • Karol Watson, MD, PhD. Field Center, University of California at Los Angeles, Los Angeles, CA, USA.
  • Ed Avol, MS. Field Center, University of Southern California, Los Angeles, CA, USA.
  • Gregory Burke, MD, MS. Field Center, Wake Forest University, Winston-Salem, NC, USA.
  • Russell Tracy, PhD. Central Laboratory, University of Vermont, Burlington, VT, USA.
  • Matthew J. Budoff, MD. CT Reading Center, Los Angeles Biomedical Research Institute, Torrance, CA, USA.
  • Daniel H. O'Leary, MD. Ultrasound Reading Center, New England Medical Center, Boston, MA, USA.
• MESA Air Project Officer
  • Vito Ilacqua, PhD. National Center for Environmental Research, USEPA, Washington DC, USA.
  • Hanyu Ni, PhD, MPH. National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
• MESA Air Funding Source
  • RD83169701. United States Environmental Protection Agency, Washington DC, USA.