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Study Description

The Framingham Heart Study Original Cohort was enrolled in 1948. The offspring and spouses of the original cohort's offspring were enrolled into the Offspring study in 1971.

From June 2002 to April 2005, 3529 participants (2111 Third Generation, 1418 Offspring participants) underwent MDCT assessment of aortic and coronary calcium. Study inclusion was weighted towards participants who resided in the Greater New England area and from larger Framingham Heart Study families. All participants had to weigh less than 350 pounds, men had to be at least 35 years of age, and women at least 40 years of age and non-pregnant. As part of an ancillary study, 433 of the participants (222 Offspring and 211 Third Generation) were imaged using an identical imaging protocol from the National Heart, Lung, and Blood's Family Heart Study.

The study protocol was approved by the institutional review boards of the Boston University Medical Center and Massachusetts General Hospital. All subjects provided written informed consent.

MDCT scan protocol

Participants underwent radiographic assessment in a supine position utilizing 8-slice MDCT (LightSpeed Ultra, General Electric, Milwaukee, WI). An average of forty-eight contiguous 2.5 mm slices of the heart were taken using a prospectively ECG triggered CT scanning protocol with the image acquisition initiated at 70% of the cardiac cycle to obtain nearly motion free images of the coronary arteries (120 kVp, 400 mA, temporal resolution 330 ms). Participants underwent a second thoracic scan after being briefly repositioned on the table.

Intra-thoracic and Pericardial Fat Volumes Data Analysis

Pericardial and intra-thoracic fat tissue volumes (cm3) were measured using an offline workstation (Aquarius 3D Workstation, TeraRecon Inc., San Mateo, CA). A predefined image display setting was used to determine the intra-thoracic and pericardial fat tissue volumes (window width -195 to -45 HU; window center -120 HU) was used to identify pixels that correspond with adipose tissue. Intra-thoracic and pericardial fat were measured across total available imaging volume and was measured in cm3 using the above display settings. The reader manually traced the pericardium. Pericardial fat volume was defined as any adipose tissue located within the pericardial sac; intra-thoracic fat volume was defined as any adipose tissue within the pericardium and within the thorax from the level of the right pulmonary artery to the diaphragm and the chest wall to the descending aorta. Intra-reader reproducibility was excellent for intra-thoracic fat (intra-class correlation [ICC] 0.99) and for pericardial fat (ICC 0.97) on a sample of 100 participants. Inter-reader reproducibility was also excellent (intra-thoracic fat ICC 0.98; pericardial fat 0.95).

In 1948, researchers recruited men and women from the town of Framingham, Massachusetts, beginning the first round of extensive physical examinations and lifestyle interviews that would later be analyzed for common patterns related to CVD development.

Initially, the Framingham Heart Study enrolled 5,209 men and women from the Framingham area who were between the ages of 28 and 62 years. Beginning in 1971, the Framingham Heart Study enrolled 5,124 men and women, who were either offspring of the original cohort or spouses of those offspring. In 2002, 4,095 third generation participants (men and women) were enrolled.

During each clinic exam cycle, the participants undergo a detailed examination including physical examination, medical history, laboratory testing, and electrocardiogram. Over the years, other tests (that may not be performed at every exam cycle) have included pulmonary function, lifestyle, physical function, cognitive function questionnaires, and various noninvasive cardiovascular tests including echocardiograms. The content of each exam cycle differs for Original, Offspring and Generation 3 cohorts and can be found in the Exam Cycle Protocol Manuals.

Authorized Access
Publicly Available Data
Study Inclusion/Exclusion Criteria

From June 2002 to April 2005, 3529 participants (2111 Third Generation, 1418 Offspring participants) underwent MDCT assessment of aortic and coronary calcium. Study inclusion was weighted towards participants who resided in the Greater New England area and from larger Framingham Heart Study families. All participants had to weigh less than 350 pounds, men had to be at least 35 years of age, and women at least 40 years of age and non-pregnant. As part of an ancillary study, 433 of the participants (222 Offspring and 211 Third Generation) were imaged using an identical imaging protocol from the National Heart, Lung, and Blood's Family Heart Study.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina HumanHap550v1.1 555352 38431
Whole Genome Genotyping Affymetrix Mapping250K_Nsp 262264 33767 Affymetrix 500K Set comprises Mapping250K_Nsp and Mapping250K_Sty Arrays
Whole Genome Genotyping Affymetrix Mapping250K_Sty 238304 33766 Affymetrix 500K Set comprises Mapping250K_Nsp and Mapping250K_Sty Arrays
Whole Genome Genotyping Perlegen PERLEGEN-600K 599171 38687
Study History

The Original cohort began Exam 1 in 1948 (9/1948 - 4/1953) and has continued with biennial examinations to the present. Exam 29 was performed from 4/2006 - 12/2007.

The Offspring cohort began Exam 1 in 1971 (8/1971 - 9/1975) and has on average been examined every 3 to 4 years since enrollment. However, there was an eight year window between Exam 1 and Exam 2. Exam 8 was performed from 3/2005 - 1/25/2008.

The Generation 3 cohort Exam 1 was performed 4/2002 - 7/2005.

Examination of all three cohorts is ongoing.

Selected Publications
Diseases/Traits Related to Study (MeSH terms)
Authorized Data Access Requests
Study Attribution
  • Principal Investigator
    • Caroline S. Fox, MD, MPH. National Institutes of Health, Bethesda, MD, USA.
  • Institute
    • National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Funding Source
    • N01-HC-25195. National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, MD, USA.