The Framingham Heart Study is a community-based prospective observational study that began in 1948, enrolling 5209 men and women in an original study cohort.18
Original cohort members attended clinic examinations approximately every two years. In 1971, 5124 men and women enrolled into the Framingham Heart Study offspring cohort, which included the children and spouses of the children of the original cohort. Participant examinations for the offspring cohort occurred approximately every four to eight years; the design and methodology have been described elsewhere.19
This investigation included original and offspring cohort members.
We considered all original and offspring cohort members aged 40–89 years and free of AMI (recognized and unrecognized) at their first Framingham clinic examination in each decade of study (1960s, 1970s, 1980s, 1990s). Our final sample size consisted of 9,824 individuals. Each individual could enter the sample multiple times based on eligibility for time period and age group. For example, a participant aged 35 years in 1960 would not contribute follow-up time to the first time period until they turned 40 in 1965 thereafter contributing 5 years. That participant would contribute 5 years to 2nd time period and so on until the patient died or developed AMI. Similarly, a patient 75 years old in 1960 contributed at most 5 years to the last period. Participants provided written informed consent and the study protocol was approved by the Boston University Medical Center Institutional Review Board.
Risk Factor Assessment
At each routine clinic visit, participants underwent physical examination, 12-lead ECG, anthropometry, and laboratory assessment of vascular risk factors. Details regarding the ascertainment of risk factors have been previously described.19
Participants with systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥ 90 mm Hg (mean reading of two readings taken by an examining physician) or receiving medication for treatment of hypertension were defined as having hypertension. Plasma glucose and total cholesterol were measured. Diabetes was defined (throughout the study period) as fasting plasma glucose ≥126 mg/dL, a non-fasting glucose of ≥ 200 mg/dL, or treatment with either insulin or hypoglycemic agents. Participants were considered to be current smokers if they smoked on average at least one cigarette per day during the year prior to examination.
Serum biomarkers of myocardial infarction
Several serum biomarkers were used for AMI diagnosis during the study time period. Specific diagnostic biomarkers and the decades during which they were used for AMI diagnosis in the Framingham Heart Study included: SGOT (beginning in the mid-1950s), LDH (1960s), CPK (1970s), CPK-MB and LDH isoenzyme (1980s), and troponin (in the late 1990s). We did not use pre-specified cut-points to determine biomarker elevation since there was variability in assays used in the various hospitals from which medical records were collected. Thus, we considered a biomarker elevated if it exceeded the reference limit provided by the hospital laboratory report at the time of AMI hospitalization, according to the available medical record/chart.
Ascertainment of AMI and AMI Case-fatality
Framingham Heart Study participants are under continuous surveillance for CVD events and death. The surveillance process included the following: 1. A physician-administered questions about cardiovascular events during each routine follow-up Framingham Heart Study clinic visit and 2. A mailed health history update questionnaire (which prior to the late 1990’s consisted of a brief questionnaire for those who had not attending examinations and after the late 1990’s included detailed sections about interim cardiac events and hospitalizations). If a participant reported a possible interim event, all pertinent medical records were collected and reviewed by an events adjudication committee, consisting of three physicians who reviewed all available hospitalization records, physician office visit notes, and pathology reports.20
AMIs were diagnosed on the basis of 1) ischemic chest discomfort with diagnostic ECG changes (based on chart review) with or without diagnostic biomarker changes
(AMI-ECG) or 2) ischemic chest discomfort with diagnostic serum biomarkers of infarction but without diagnostic ECG changes
(AMI-marker). ECG criteria for AMI included development of pathologic Q-waves of ≥ 0.04 seconds, often accompanied by ST-elevation and followed by serial changes indicating a reversion of these ECG changes toward normal. We chose to exclude persons with unrecognized/silent AMI as it is impossible to determine the exact date of occurrence, which is assigned a midpoint between the last ECG without an abnormality and the first one manifesting Q-wave changes .
Case-fatality was assessed within 30-days, 1-year and 5-years. For 1-year and 5-year mortality, deaths occurring within the first 30-days were excluded from analysis. We did this in order to get a truer sense of how many “later” case fatalities occurred following AMI (since a large proportion of post- AMI deaths occur within 30 days of the index event as opposed to later). Furthermore, pathophysiologically “early” death from AMI is likely different from “later” deaths.
Prevalence rates and mean values (± standard deviations) of CVD risk factors were calculated for the study sample at the first examination cycle in each decade of study. We employed Poisson regression to calculate annual incidence rates of first AMI over four time periods (1960–69, 1970–79, 1980–89 and 1990–99), and compared rates of AMI-ECG with rates of AMI-marker. We tested for sex*age group, sex*time period, age group*time period, age group*AMI type, and time period*AMI type interactions for incidence rate trends; given multiple statistically significant p-values for these interactions, we present age- and sex-specific AMI incidence rates for each time period. Additionally, with small numbers of events for the oldest and youngest age groups, we provide trends in (log-transformed) event rates across the four time periods for age groups 50–59, 60–69 and 70–79 years, for men and women separately. We calculated tests of trend for overall AMI, AMI-ECG, and AMI-marker across time periods, with the 1960s serving as the referent decade (using a model accounting for the interactions listed above). We employed Cox proportional hazards models to calculate age- and sex-adjusted case-fatality curves and 30-day, 1-year and 5-year case-fatality rates following all AMI, AMI-ECG, and AMI-marker for each of the four time periods (1960–1969 serving as the as referent period). The follow-up period for case-fatality was until the end of 2006. The assumption of proportionality of hazards was satisfied over the 5-year follow-up period following AMI (p-value for time to death*period interaction >0.32 for overall AMI, AMI-ECG, and AMI-marker). A two-sided P value of less than 0.05 was considered to indicate statistical significance. All statistical analyses were performed with the use of the SAS statistical software (version 9.0).
Statement of Responsibility
The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.