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STILL STRONG AFTER ALL THESE YEARS:
Sixty and counting // Three generations of participants // More than 2,000 published papers // Untold numbers of lives saved // And now the famous Framingham Heart Study is entering a new chapter.

One Town’s Treasure

By Anita Slomski // Winter 2008
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Framingham Heart Study

Courtesy Framingham Heart Clinic

A small-town home for a world-changing study, Kingman House was the first of several old-house headquarters, preceding a move to an abandoned convent. The Framingham Heart Study now resides in a wing of a construction firm’s headquarters.

In 1965, when lipidologist William Castelli was recruited to run the laboratories of the Framingham Heart Study, then in its seventeenth year, a colleague advised, “I’d steer clear of Framingham. Every fifth guy in that town has a heart attack by age 60.” The warning was of no small concern. Everyone in Castelli’s immediate family had heart disease or had died from it, and his own cholesterol level would reach 260 mg/dL (milligrams per deciliter), exceeding that of many study participants who were succumbing to heart attacks.

But Framingham, Mass., was no anomalous industrial town killing off residents with mysterious toxins. On the contrary, Framingham epitomized Anytown, U.S.A.; the nation was facing an epidemic of heart disease. “Physicians then considered average to be normal, but the last person in the world you’d ever want to emulate was the average American,” Castelli says. “Doctors thought nothing of telling patients that any total cholesterol level below 300 mg/dL was normal. That was devastating advice; 90% of Framingham study participants whose total cholesterol even approached 300 had heart attacks.”

Extrapolating from such observations, the Framingham Heart Study (FHS) has played the role of America’s medical nag for 60 years now, challenging the lifestyles that contribute to chronic diseases as well as physicians’ misperceptions about diagnosing and treating those diseases. Arguably the world’s longest-running and best-known epidemiological study, Framingham can claim such landmark discoveries as linking cigarette smoking to heart disease; dispelling the myth of benign hypertension; showing that hormone-replacement therapy increases rather than decreases the risk of heart disease (long before the Women’s Health Initiative came to the same conclusion); and finding that exercise reduces heart disease instead of causing it.

All part of conventional medical wisdom today, such findings were almost always greeted with skepticism, if not outright scorn. “Every time we asserted something, it was said to be bunk,” says William Kannel, who joined FHS in 1951, became its second director and, at age 84, still does research for it.

Now, though, after publishing 2,000-plus peer-reviewed papers based on the examinations of study participants (there have been almost 15,000), the Framingham Heart Study is recognized as a singular modern medical achievement—and is firmly focused on what could become its twenty-first-century legacy. As the study’s participants have aged and developed myriad diseases, and as new diagnostic tools have entered the scene, Framingham researchers have gathered ever more data, broadening the study to include observations on such disorders as Alzheimer’s disease, osteoporosis, arthritis and cancer.

“While the ‘classic’ Framingham study was all about finding traditional risk factors related to disease, the modern Framingham is about discovering the genetic variations and other biomarkers that underlie blood pressure, lipids, obesity, coronary heart disease, stroke, blood disorders, bone density, dementia—and I can keep going,” says Christopher O’Donnell, Framingham’s associate director and the scientific director of its genomewide association study. Although there are dozens of research studies around the world looking for disease-causing genes, only a few are large-scale population studies. Having the DNA of thousands of people spanning three generations puts Framingham in a unique position to contribute to the next biomedical frontier—uncovering the molecular basis of disease.

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Milestones in Framingham

Heart attack is increased by cigarette smoking

The milestones of the Framingham Heart Study, which broke ground in heart disease research, just keep coming.

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1. A Change of Heart: Unraveling the Mysteries of Cardiovascular Disease, by Daniel Levy and Susan Brink (Vintage Books, 2005). A behind-the-scenes history of the people, science, politics and culture that created one of the longest-running epidemiology studies.

2. “You Changed America’s Heart: A 50th Anniversary Tribute to the Participants in the Framingham Heart Study.” A report that both enumerates the medical accomplishments of the study and offers the human side with anecdotes from participants.

3. “The Hidden Epidemic: Heart Disease in America,” PBS, February 2007. In a far-reaching and candid interview with Larry King, William Kannel, a former FHS director, discusses the early days of the Framingham study, how its findings influenced medical practices over the years and why heart disease remains a major problem in America.

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