Framingham SHARe Offspring and Third Generation Vitamin D

Moderate to severe vitamin D deficiency is widely prevalent, affecting as many as half of middle-aged to elderly adults. While vitamin D deficiency is well known to disrupt calcium homeostasis and musculoskeletal health, there is now ample evidence suggesting it also has adverse cardiovascular sequelae. Recent studies have demonstrated that low vitamin D levels are independently associated with numerous cardiometabolic risk factors as well as with prevalent and incident cardiovascular disease. Although variability in vitamin D levels is at least partially heritable, the genetic variants that contribute to this heritability is unknown. Genetic variants that influence concentrations of vitamin D could potentially alter susceptibility to bone health and cardiovascular disease.

Offspring Vitamin D Dataset
Vitamin D was obtained by a blood draw at the time of the Offspring Clinic Exam 7.

Third Generation Vitamin D Dataset
Vitamin D status, represented by serum 25-hydroxyvitamin D levels (the storage form of vitamin D), was assessed on specimens obtained from Framingham Study Third Generation participants attending their 1st examination.

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.

• Study Weblinks:
  • The Framingham Heart Study
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Longitudinal
• Total number of consented subjects: 6001
• Subject Sample Telemetry Report (SSTR)

Offspring cohort

Third Generation cohort; 1st examination

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.

• Primary Phenotype: Cardiovascular System
• Vitamin D Deficiency
• Cardiovascular Diseases
• Osteoporosis

• Principal Investigator
  • Thomas J. Wang, MD. Massachusetts General Hospital, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
• Co-Investigators
  • Vasan S. Ramachandran, MD. Boston University, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
  • Martin G. Larson, SD. Boston University, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
  • Caroline S. Fox, MD, MPH. Brigham and Women's Hospital, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
  • Christopher O'Donnell, MD, MPH. Massachusetts General Hospital, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
  • Gary Mitchell, MD. Cardiovascular Engineering, Inc, Waltham, MA, USA and Framingham Heart Study, Framingham, MA, USA.
  • Emelia J. Benjamin, MD, ScM. Boston University, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
  • Sarah Booth, PhD. Tufts Universisty, Boston, MA, USA.
  • Paul Jacques, PhD. Tufts University, Boston, MA, USA.
  • Jose Flores, MD, PhD. Massachusetts General Hospital, Boston, MA, USA and Broad Institute, Cambridge, MA, USA.
  • Douglas P. Kiel, MD, MPH. Boston University School of Medicine, Boston, MA, USA.
  • Joseph Massaro, PhD. Boston University, Boston, MA, USA.
  • Susan Cheng, MD. Massachusetts General Hospital, Boston, MA, USA.
  • Myles Wolf, MD. University of Miami, Miami, FL, USA.
• Funding Source
  • NO1-HC-25195. National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Grant-in-Aid. American Heart Association.