October 3, 2013

Framingham Heart Study’s landmark impact examined

While the Framingham Heart Study is often referenced throughout the halls of academia, few know its origin or can fully appreciate the contribution it has made to the understanding and prevention of cardiovascular disease.

William Kannel, M.D., left, who helped pioneer the Framingham Heart Study since its inception in 1949, and X-ray technician John William Claffey record heart size measurements in 1964.

While the Framingham Heart Study is often referenced throughout the halls of academia, few know its origin or can fully appreciate the contribution it has made to the understanding and prevention of cardiovascular disease.

In the October issue of The Lancet, Vanderbilt’s Thomas J. Wang, M.D., and colleagues provide an insightful historical perspective on the study to coincide with the 65th anniversary of the examination of the first volunteer in 1948.

Thomas J. Wang, M.D.

Wang, chief of the Division of Cardiovascular Medicine, and co-authors searched the archives of the Framingham Heart Study at the National Heart, Lung, and Blood Institute, as well as Harvard University’s Widener Library collection of President Franklin D. Roosevelt’s Office Files, among other sources.

Among their findings is the role that Roosevelt’s premature death in 1945 at the age of 63 played in the origin of the Framingham Heart Study. Roosevelt died of a cerebral hemorrhage, with a blood pressure of 300/190 mm Hg.

His long illness started with uncontrolled hypertension and progressed to heart failure and stroke. “Like countless other Americans, he had succumbed to the national epidemic of cardiovascular disease,” the article states.

In 1948, President Harry Truman, who had been Roosevelt’s vice president, signed into law the National Heart Act, allocating a $500,000 seed grant for a 20-year epidemiological study of heart disease and also established the National Heart Institute, which is known today as the National Heart, Lung and Blood Institute.

Framingham, Mass., was selected as the site of the epidemiologic study because of the enthusiastic response of physicians in the area, its geographical proximity to the many cardiologists at Harvard and because the town had already participated in the Framingham Tuberculosis Demonstration.

The first long-term study of its kind, it examined its first participant on Oct. 11, 1948. The original cohort was recruited between 1948 and 1952 and consisted of 5,209 residents ages 28-62 years.

The first major findings of the study were reported in 1957 and documented the association between hypertension and coronary heart disease.

The investigators noted a near four-times increase in the incidence of coronary heart disease for study participants with a blood pressure of 160/95 mm Hg or higher.

In 1966, the initial 20-year funding commitment neared an end, and researchers sought private funds to keep it going. President Richard Nixon intervened in 1971 and provided support for the study through a federal contract. The study then began to recruit offspring of the original cohort to provide insight into the familial clustering of heart disease.

“The creation of a family-based cohort was far-sighted, in view of the emergence of new technologies for genotyping and sequencing a few decades later,” the authors write.

The study contributed to a shift in emphasis in the second half of the 20th century, from sole treatment of those with established cardiovascular disease to the prevention of disease in those at risk, and popularized the term “cardiovascular risk factor” in the medical lexicon in 1961.

The Framingham investigators proposed a prediction algorithm that is still in use today (the “Framingham Risk Score”) and included the following risk factors: age, gender, total cholesterol, HDL cholesterol, diabetes, smoking and systolic blood pressure.

By the end of the eighth examination cycle of the study, in 1966, investigators noted a rising prevalence of heart failure in the cohort. Investigators defined criteria that were used to show that hypertension was the leading risk factor for heart failure.

Toward the end of the 20th century, Framingham investigators recruited the third generation cohort (children of offspring cohort members), expanded to include minority residents, and performed genome-wide genotyping across all Framingham cohorts.

“The founders of Framingham and similar studies were obviously making an investment for the future. They had a fundamental understanding that collecting clinical observations in people over time would be extremely valuable for biomedical research,” Wang said.