Cuarta Etapa: Consolidación de la información

At the FHS, participants are considered to have developed cardiovascular disease (CVD) if upon review by a panel of three investigators from the Framingham Endpoint Review Committee (FERC) there is agreement that there was a definite manifestation of coronary

heart disease, intermittent claudication, congestive heart failure, stroke or transient ischemic attack in absence of a previous manifestation of any of these diseases. Our investigation of the effect of different censoring methods was conducted on the Framingham second generation cohort with stroke, congestive heart failure, and myocardial infarction as end points (events) of interest. For each of these events, examination cycle 6 (1995-1998) was chosen as the entry time; attendees of the exam who were free of the event of interest were followed prospectively (for up to 14 years or through 2009). A person having more than one cardiovascular manifestation within the follow-up period is counted as an incident case only at the time of the first event.

Cardiovascular outcomes

Stroke: The diagnosis of stroke is based on the occurrence of a clinically evident stroke documented by clinical records reviewed by two neurologists. Stroke is defined as the sudden or rapid onset of a focal neurologic deficit persisting for greater than 24 hours. (Wolf et al, 1991, 1992)

Congestive heart failure (CHF): A definite diagnosis of CHF requires that a minimum of two major or one major and two minor criteria be present concurrently (Kannel et al, 1987). The presence of other conditions capable of producing the symptoms and signs are considered by physicians in evaluating the findings.

Major Criteria:

i. Paroxysmal nocturnal dyspnea or orthopnea

iii. Rales

iv. Increasing heart size by x-ray

v. Acute pulmonary edema on chest x-ray vi. Ventricular S (3) gallop

vii. Increased venous pressure > 16 cm H20 viii. Hepatojugular reflux

ix. Pulmonary edema, visceral congestion, cardiomegaly shown on autopsy x. Weight loss on CHF Rx: 10 lbs. /5days

Minor criteria:

i. Bilateral ankle edema ii. Night cough

iii. Dyspnea on ordinary exertion iv. Hepatomegaly

v. Pleural effusion by x-ray

vi. Decrease in vital capacity by one-third from maximum record vii. Tachycardia (120 beats per minute or more)

viii. Pulmonary vascular engorgement on chest x-ray

Myocardial Infarction (MI): Recent or acute MI is designated when there were at least two of three findings:

i. Symptoms indicative of ischemia

iii. Serial changes in the electrocardiograms indicating the evolution of an infraction including the loss of initial QRS potentials (that is, development of “pathologic” Q-waves of 0.04 second duration or greater) (Kannel et al, 1987).

Risk Factors

For each of these events we considered age, sex, hypertension, current smoking status, diabetes mellitus, atrial fibrillation, and C - reactive protein as risk factors of interest, defined as follows.

Hypertension: Stage I + hypertension is defined as a systolic blood pressure greater than or equal to 140 mmHg or diastolic blood pressure greater than or equal to 90 mmHg or under treatment for hypertension (JNC VII, 2003).

Smoking: Current smoking status is identified with participants self-reporting at the specific clinic exams.

Diabetes Mellitus (DM): DM is defined as random blood glucose greater than or equal to 200 mg/dL or fasting blood glucose greater than or equal to 126 mg/dL or currently under treatment for diabetes.

Atrial Fibrillation (AF): AF is an irregularity in the heartbeat or heart rhythm caused by atria, the two upper chambers of the heart, fibrillating and not beating effectively. Blood can pool in the atria and clots may occur. If a clot leaves the atria and stuck in an artery of the brain then stroke occurs. (Benjamin, Wolf et al, 1998)

C - reactive protein (CRP): CRP is one of the ‘acute-phase’ proteins synthesized in the liver and is normally present as a trace constituent of serum or plasma. Levels of CRP rise during general, nonspecific response to infectious and non-infectious inflammatory processes. (Koenig et al, 1999)

Follow-up Status

For each participant, follow-up status can be assessed based on whether during the observation (follow-up) period, he/she had an event, or was censored (these censored participants includes those who died event free or if he/she was alive and event free at the end of the observation). Follow-up time for a participant is the time from entry (date of examination cycle 6) to the survival date; the latter date depends on the event status of the participant. The survival date for a participant with an incident event is the date of that event. For those who died during follow-up, before experiencing the event of interest, the FERC reviews all evidence including death certificate and other records supplied by hospitals, attending physician, pathologists, medical examiner or family to confirm the cause of death – and the absence of the event of interest. The survival date for those is the date of death.

The survival date for the remaining participants is the last known date they are still at risk for the event of interest. This includes participants who are censored event free at the end of the observation period as well as those censored at some date before the end of the

observation period. The observation periods chosen for this study are from exam 6 through each of exam 7 (1998-2001), 2002, 2004, 2006, exam8 (2005-2008) and 2009.