Early Repolarization in the Framingham Heart Study (ER-FHS)

Electrocardiograms were obtained using GE Mac 5000 electrocardiographs on Framingham Heart Study Generation 3 participants who attended the first examination. We visually inspected paper ECGs from generation 3 to identify individuals who had the early repolarization pattern. Recent reports have suggested that the early repolarization pattern may be a risk factor for sudden cardiac death. We sought to describe the clinical correlates of the pattern in the Framingham Heart Study and assess the heritability and genetic underpinnings of the pattern.

J-point elevation (presence and amplitude of ER). ER was defined as at least 0.1mV elevation of the J-point compared with baseline (the T-P segment). The J-point was defined as the earliest point of QRS offset (using a transparent ruler on paper ECG tracings, comparing all leads simultaneously). The J-point was measured in each lead separately. J-point elevation was coded as (1) absent, (2) ER pattern present (ER > 0 mV, but < 0.1 mV), (3) ER present (ER ≥ 0.1 mV, but < 0.2 mV), or (4) marked ER (ER ≥ 0.2 mV).

The morphology of the J point was coded as (1) notched, (2) slurred, (3) discrete notched (ER after signal return to baseline with a notch), or (4) discrete non-notched (ER after signal return to baseline without a notch). The ST-segment morphology was coded as (1) ascending (ST-amplitude ≥0.05 mV 100ms after J point), (2) horizontal, or (3) descending.

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
  • Cohort
• Total number of consented subjects: 4025
• Subject Sample Telemetry Report (SSTR)

Inclusion:

1. All individuals with ECG

Exclusion:

1. Very poor ECG quality or missing data
2. QRS-duration ≥ 120 msec
3. Arrhythmias (atrial fibrillation/flutter on ECG)
4. WPW syndrome
5. Pacemaker implanted prior to ECG aquisition
6. Upper age limit of 80 years old, lower age limit > 18 years old

The Generation 1 (or Original) cohort Exam 1 took place between 1948 and 1953. Biennial exams have continued to the present. Exam 29 took place between 2006 and 2007. Exam 30 began in 2008.

The Generation 2 (or Offspring) cohort Exam 1 took place between 1971 and 1975. This cohort on average has been examined every three to four years. However, there was an eight year gap between Exam 1 and Exam 2 and a seven year gap between Exam 7 and Exam 8. Exam 8 took place between 2005 and 2008.

The Generation 3 cohort Exam 1 took place between 2002 and 2005. Exam 2 began in 2008.

The New Offspring Spouse cohort Exam 1 took place between 2003 and 2005. Exam 2 began in 2008.

• Primary Phenotype: Cardiovascular System

• Principal Investigator
  • Christopher Newton-Cheh, MD, MPH. Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
• Co-Investigators
  • Peter A. Noseworthy, MD. Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Christopher J. O'Donnell, MD, MPH. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA and Framingham Heart Study, MA, USA.
• Funding Source
  • Burroughs Wellcome Fund, Research Triangle Park, NC, USA.