William B. Kannel, MD, Pioneer in Cardiovascular Epidemiology, 19232011
William B. Kannel, MD, Director of the Framingham Heart Study, 1966-1979
William B. Kannel, MD, died Aug. 20, 2011. He is survived by his wife, four children, 12 grandchildren and 23 great-grandchildren.
Dr. Kannel was born in 1923 in New York, where he attended high school, and then graduated from the Medical College of Georgia in Augusta in 1949. He was trained in internal medicine in the US Public Health Service at Staten Island, New York, and was a fellow of the American Heart Association, the American College of Cardiology, the American Epidemiology Society, the American College of Epidemiology and the American College of Preventive Medicine. Dr. Kannel was Emeritus Professor of Medicine and Public Health at the Boston University School of Medicine (BUSM). He was a past Chairman of the Council of Epidemiology of the American Heart Association and a past Chief of the Section of Preventive Medicine and Epidemiology in the Department of Medicine at BUSM. He was a recipient of numerous national and international awards and honorary degrees, notable among which were the AHA Distinguished Scientist award (2006), the Lifetime Achievement award from the New York Academy of Medicine (2006), and the Joseph Stokes Award from the Board of the American Society for Preventive Cardiology (2011). Other important awards received by him include the Dana Award in Preventive Medicine (1972), the Dutch Einthoven Award (1973), the Canadian Gairdner Award (1976), the CIBA Award for Hypertension Research (1981), the James D. Bruce Memorial Award of the American College of Physicians (1982), and the Charles A. Dana Award for Pioneering Achievement in Health (1986). He served on the editorial board of numerous scientific journals, including Hypertension, the American Journal of Cardiology, and the American Heart Journal.
Dr. Kannel has been active in the field of cardiovascular epidemiology for more than 60 years and led the way for the world famous Framingham Heart Study to become the leader in cardiovascular epidemiologic research that it is today. He joined the Heart Study in 1950 and in 1966, he became the NIH Director of the Heart Study, replacing Dr. Thomas R. Dawber, the original architect of the study, serving in this capacity until 1979. Between 1979 and 1987, as Professor of Medicine and Chair of the Preventive Medicine Section at Boston University School of Medicine, he served as the Principal Investigator of the Framingham Study he succeeded Dr. Thomas R. Dawber the founder of the Framingham Study in this post.. Subsequently, he continued work as the senior-most investigator at the Heart Study until his recent illness curtailed those efforts.
The Framingham Study has been acknowledged among the top ten medical advances in the last century in several reports, in no small measure attributable to Dr. Kannel's scientific contributions. He published over 600 medical articles, numerous editorials and book chapters in premier texts. His work at the Framingham Study established the utility of population-based research for seeking out correctable predisposing conditions for cardiovascular disease (CVD), putting prevention at the forefront of cardiology. Dr. Kannel coined the medical term 'risk factor' in 1961 in a landmark publication in the Annals of Internal Medicine, and promoted the concept that CVD is multifactorial in origin, that is, that there is no single cause that is essential or sufficient by itself for CVD occurrence. He promoted the notion of combining information about multiple risk factors mathematically to estimate risk of CVD (the Framingham risk score). His research established the importance of distinguishing between usual (average in the population) and optimal risk factor levels. He described the risk factors for both heart attacks and brain attacks (stroke), and identified the importance of irregular heart beat (atrial fibrillation) as a precursor of stroke and high blood sugar (diabetes) as a risk factor for CVD.
In several seminal papers he dispelled the concept of "benign essential hypertension" and showed the systolic component of the blood pressure to be no less important than the diastolic level. Pioneering work conducted by him also identified risk factors for the individual components of CVD, including sudden death, heart failure, and peripheral artery disease. Data collected by Dr. Kannel and his colleagues at the Heart Study in the late 1950s and early 1960s determined CVD population incidence at a time when only mortality statistics were available. In 1971 (approximately three decades before the completion of the human genome project), Dr. Kannel began the second generation study called the Framingham Offspring Study that quantified the hazard of a family history of CVD based on observations on parents and their offspring. His research on the two generations of Study participants provided path-breaking insights on mechanisms of atherogenesis (build up of cholesterol plaques in the blood vessels), including: LDL and HDL dyslipidemia, obesity-induced clustering of CVD risk factors, importance of physical activity in CVD prevention, and smoking as a trigger for heart and brain attacks. His research stimulated national campaigns against smoking, high cholesterol, high blood pressure, and obesity.
There are few areas in cardiovascular disease epidemiology Dr. Kannel did not explore. His research highlighted the lethal nature of congestive heart failure and a thick left ventricular wall, the frequent occurrence of clinically silent myocardial infarction and the factors predisposing to sudden death, which until then had been under-appreciated. His research warned in 1985 of the lack of efficacy and danger of estrogen replacement for preventing CVD. In 2008, along with his colleagues he formulated the 'Framingham General CVD risk score', a profile that enables primary care physicians to pull together risk factor information to assess the global risk of heart attacks, failure, strokes, and peripheral artery disease.
By his example, Dr. Kannel influenced several generations of cardiologists and physicians and was one of a handful of "founding fathers" of preventive cardiology utilizing prospective observations to draw conclusions usually readily applicable to clinical practice. He also trained scores of postdoctoral research fellows at the Heart Study who are following in his footsteps inspired by the depth and breadth of his research.
A William B. Kannel Legacy Fund has been established at Boston University to support the Framingham Heart Study. Alternatively, contributions may be made in Dr. Kannel's memory to the Friends of the Framingham Heart Study, 73 Mt. Wayte Ave., Suite 2, Framingham, MA 01702.
Presentation by Framingham Heart Study at Adams Middle School
On April 13, 2011, Esta Shindler and Dr. Michael Chuang of the Framingham Heart Study made a presentation to some 200 students of the sixth grade at Adams Middle School in Holliston at the request of the sixth grade science teacher, Kathryn Buckley. Ms. Buckley created a teaching unit based on the Framingham Heart Study to teach the students how the digestive, circulatory and respiratory systems work together. She achieved national recognition at a conference in San Francisco for including in her unit the interactive calculator from the Heart Study's website into which users may enter variables to determine a person's approximate risk of heart disease,. Ms. Shindler presented the history of the Heart Study, followed by Research Fellow Dr. Chuang who explained the anatomy and functioning of the heart through various MRI images, as shown in the photo.
Photo by Allan Jung, Courtesy of MetroWest Daily News
Recognition by American Stroke Association of article from Framingham Heart Study showing that first definitive evidence of occurrence of stroke by age 65 years in a parent increased the risk of stroke in offspring by 3-fold
The American Stroke Association, a division of the American Heart Association, publishes annually in their journal Stroke an article entitled "Advances in Genetics". That article for 2010 cited a recent study from the Framingham Heart Study led by Dr. Sudha Seshadri showing the first definitive evidence that occurrence of stroke by age 65 years in a parent increased the risk of stroke in offspring by 3-fold. The study description from "Advances in Genetics" follows below:
"A recent Framingham study greatly added to understanding the relationship between parental history of stroke and risk of stroke in offspring. Parental occurrence of stroke by age 65 years increased the risk of stroke in offspring by 3-fold. This elevated risk persisted after adjusting for conventional risk factors. People with a parental history of stroke had higher risk than people without a parental history of stroke across all 5 quintiles of baseline risk estimated using the Framingham Stroke Risk Profile. The greatest effect of parental history of stroke occurred at the highest quintile of risk. Arguments can be made for and against targeted versus mass screening for preventing illness (the so-called Rose dilemma). In some settings, targeted screening appears to be more cost-effective for cardiovascular primary prevention. Screening for a parental history of stroke may be one way to screen for high-risk populations for targeted stroke prevention. As a screening tool, emerging genomic techniques may not prove superior."
Your Risk of Heart Disease
How to Turn Back the Clock When Your Blood Vessels Grow Old Before You Do
By Ron Winslow
"A man is as old as his arteries."
Thomas Sydenham, English physician, 1624-1689
This comment, made nearly four centuries ago, raises a provocative modern-day question: Do you know how old your arteries are?
It is a question gaining increasing attention as researchers look for more effective ways to communicate risk of cardiovascular disease to patients and to motivate them to make changes in their lives that can help prevent heart attacks, strokes and other serious heart-related problems later in life.
Several tools are available that enable doctors and patients to calculate vascular age. These suggest there can be a substantial difference between how old you are and how old your blood vessels are. For instance, the vascular age of a 35-year-old man who smokes and has diabetes, high blood pressure and abnormal cholesterol could be as high as 76 years oldmore than double his chronological age, according to a recent study. The arteries of a 30-year-old woman with similar risk factors could be equivalent to those of an average woman who is more than 80 years old.
Such a calculation "gives a sense that your risk-factor burden is making you age faster than you think you are," says Donald Lloyd-Jones, a preventive cardiologist at Northwestern University, Chicago, who co-authored the recent study, which appeared in the journal Circulation last August. "The more you can make it concrete, the better you can impart information about risk."
The good news, doctors say, is that by taking steps to reduce risk factors and the damage they inflict on arteries, it is possible to turn back the clock on vascular age.
With optimal cholesterol and blood pressure and no diabetes, the vascular age of a 74-year-old non-smoking man could be as low as 60, according to the report by Dr. Lloyd-Jones. A similarly healthy 74-year-old woman could have arteries as young as 53, or 21 years less than her chronological age.
The concept of vascular age underscores the crucial role blood vessels play in maintaining heart health. A single layer of cells called the endothelium lines the walls of every blood vessel in the body. Along with a layer of elastic tissue, the endothelium comprises what is called the intima.
Bryan Donohue, chief of cardiology at University of Pittsburgh Medical Center Shadyside, calls the intima "the governing intelligence" of vascular health. Knowledge it contains and communicates with the blood enables blood to course through the body without clotting, he says. It also helps to keep arteries flexible or compliant.
Over time, however, the effects of high blood pressure, cholesterol, blood sugar and tobacco smoke provide a toxic milieu that injures the endothelium. That causes an inflammatory response intended to heal the artery wall, but that in the face of continuous injury only makes things worse.
The progressive result is an accumulation of fatty deposits called plaque that can rupture or have their caps shear off, causing clots that lead to heart attacks. In addition, artery walls can stiffen, transforming compliant arteries into conduits like "Styrofoam tubes," Dr. Donohue says, that increase both blood pressure and the workload on the heart.
All of this explains in part why heart experts are concerned that the nation's obesity epidemic and the surge in diabetes rates threaten to unravel decades of progress against heart disease. Both high body mass, particularly belly fat that accounts for a person's bulging waist line, and diabetes have a pernicious effect on the health of adult blood vessels. In addition, recent research among children and adolescents at Cincinnati Children's Hospital and elsewhere has documented arterial stiffness and other heart-related structural abnormalities once thought to occur only in aging adults.
Even if your weight is under control, high cholesterol, high blood pressure, smoking, sedentary living and stress all are culprits that can accelerate vascular age. Over time, the steady beating of your heart70 times a minute, or more than 100,000 heartbeats a dayexacts wear and tear on your vessels as well.
Dr. Lloyd-Jones's analysis of vascular age is based on an updated version of the Framingham Risk Score, a widely used instrument that uses a formula based on gender, age, cholesterol and blood pressure levels and smoking status to estimate a person's 10-year risk of a heart attack or heart-related death. The new version, published in Circulation in 2008, added stroke, heart failure and disease in the leg arteries to broaden the scope of the tool, as well as a point system that linked a relative 10-year risk to vascular age.
"People may have a low 10-year risk, but their 40-year risk is going to be large," says Ralph D'Agostino, a Framingham Heart Study investigator and mathematician at Boston University. Looking at vascular age can "let them know where they might be heading if they don't start paying attention."
Similar warnings can come from deriving vascular age from a CT scan that detects accumulation of calcium in the coronary arteries, or on an ultrasound test known as CIMT (for carotid intima media thickness) that measures the thickness of the inner lining of the carotid arteries in the neck.
Typically, results of these tests are expressed in percentiles and risk probabilities, which "human beings don't understand at all," says Dr. Lloyd-Jones. For instance, a Framingham score may indicate someone has a 7% chance, or low risk, of having a heart attack in the next 10 years. "If I say you are 45, but you have the risk of an otherwise healthy 67-year-old,' that somehow gets in our brain better" than a percentage risk, he says.
Dr. Lloyd-Jones cautions that there isn't evidence linking a calculation of artery age directly to what's actually going on inside a patients' vessels. But, he says, "We hope this is another way to get patients to pay attention to their lifestyle and adhere to medicines if they need them."
Peter Tripoli is a case in point. A few weeks ago, the 50-year-old vice president of a software firm experienced shortness of breath and chest pain. Several tests didn't find any evidence of obstruction, but he went to Dr. Donohue's clinic in Washington, Pa., for a checkup with Linda Gordon, a nurse practitioner.
Mr. Tripoli, thick around the waist, acknowledged he had gained 40 pounds in the past three years. During the same time, his total cholesterol jumped to 249 from 192.
Mrs. Gordon took his blood pressure, which was 98/70, consistent with prior readings, he said, and well within healthy recommended levels of below 120/80. "If I don't get this blubber off me, it won't stay that way," he said. He said he just needed a little motivation.
Mrs. Gordon punched Mr. Tripoli's risk-factor numbers and other data into a software program she developed called Intimal Health. Based on evidence from clinical studies, it prints out recommendations customized to each patient as a guide to healthy habits that can help rejuvenate their arteries. She asked him to come back in six weeks for a progress report, when adding a cholesterol-lowering statin would be considered.
"Everything we dodiet, exercise, the medicationsthey are geared toward improving the environment that the artery lives in," Mrs. Gordon told him.
Using the traditional Framingham Risk Score, Mr. Tripoli's 10-year risk of a heart attackbolstered by his favorable blood pressure readingwas a low 6%. While keeping vessels young is a focus of the clinic, Mrs. Gordon doesn't usually calculate a patient's vascular age. But in this case, she ran Mr. Tripoli's age, cholesterol numbers and blood pressure through the updated Framingham Heart risk score.
The result: His arteries were equivalent to those of a 64-year-old man.
"That's striking," Mr. Tripoli said, indicating he was prepared to get it lower. "I'm one of those people who has a chance to avert a catastrophe."
Dr. Francis S. Collins, Director of NIH, Cites Framingham Heart Study as Major Contributor to Gains in Cardiovascular Disease
Department of Health and Human Services National Institutes of Health Fiscal Year 2011 Budget Request, Witness appearing before the House Subcommittee on Labor HHS Education Appropriations, Francis S.Collins, M.D., Ph.D. Director, National Institutes of Health
" U.S. life expectancy has increased dramatically over the past century and still continues to improve, gaining about one year of longevity every six years since 1990. A baby born today can look forward to an average life span of 77.7 years, almost three decades longer than a baby born in 1900. Not only are people living longer, they are staying active longer. From 1982 through 2005, the proportion of older people with chronic disabilities dropped by almost a third, from 27% to 19%.
Some of the most impressive gains have been made in the area of cardiovascular disease. In the mid-20th century, cardiovascular disease caused half of U.S. deaths, claiming the lives of many people still in their 50s or 60s. Today, the death rate for coronary heart disease is more than 60% lower -- and the death rate for stroke, 70% lower than in the World War II era.
What fueled these improvements? One major contributor has been the insights from the NIH-funded Framingham Heart Study, which began in the late 1940s and is still going strong. This population-based study, which changed the course of public health by defining the concept of disease risk factors, continues to break new ground with its recent move to add a genetic component to its analyses. "
Obama Recognizes Framingham Heart Study in Speech to NIH
President Obama visited the National Institutes of Health recently and announced an additional five billion dollars in research funding. In the same speech, he highlighted the work of the Framingham Heart Study:
"Through these investments in research, we will also have the opportunity to make strides in the treatment and prevention of heart disease, the leading cause of death in the United States. Since 1948, for example, researchers have been following generations of residents in the town of Framingham, Massachusetts, to better understand the cause of cardiovascular illness. Now, we have a chance to study the DNA of these participants and connect what we know after decades of observation to what we'll soon know about their genetic makeup. And perhaps we can identify those who are likely to get high blood pressure or high cholesterol and find ways to intervene before heart disease even develops."
On November 29, 2007, The Honorable Michael O. Leavitt, United States Secretary of Health and Human Services (HHS), came to the Sheraton Hotel in Framingham to express the nation's appreciation to participants of the Framingham Heart Study (FHS).
This event also celebrated the upcoming 60th anniversary of the Framingham Heart Study and included as guests Dr. Elias Zerhouni, Director of the National Institutes of Health. Dr. Elizabeth Nabel, Director of the National Heart, Lung and Blood Institute, Dr. Robert Brown, President of Boston University, Dr. Karen Antman, Dean of Boston University School of Medicine, Dr. Daniel Levy, Director of the Framingham Heart Study, and Dr. Philip Wolf, Principal Investigator of the Framingham Heart Study, as well as several local and state public officials. Each participant of the Heart Study received an invitation to attend this event along with family and guests. Below are excerpts of the remarks by the the Honorable Michael Leavitt.
" I asked Dr. Zerhouni and Dr. Nabel for this opportunity to come and talk with you because there are so many things to acknowledge and be thankful for here, as this Study begins its 60th year. The first thing to be thankful for is the Study itself. This is the Study that first pointed us toward the risk factors for cardiovascular disease that are so familiar to us all today.
These factors are part of the way I think about my own health and the choices I make about what to eat and how to exercise. And that holds true for people all across the country and around the world. When it comes to getting across a message, you've had quite a success! the Framingham Study has given us the knowledge and with it the power to make healthier choices, and to prevent disease, and to treat disease more effectively. That power was made possible by the willingness of 14,000 study participants in the Framingham area to share their health information. Framingham is a very special case: 60 years and three generations of sharing your health information. This is long-term, conscientious commitment. Maybe after all these years, it may seem no big deal to you. But it's a rare gift you've given, and that you're continuing to give.
For a health care researcher, the Framingham data looks like 24-carat gold. The reliability and the depth that researchers see in this data come from your consistency and openness over more than half a century. All of us at HHS, all those who work in the health care field, and indeed all Americans owe a debt of gratitude to patient volunteers. We owe an expression of thanks - and yet that thanks is rarely articulated.
Here today in Framingham - I am honored to have the opportunity today to say "thank you" to all those who take part in medical research everywhere. This is the silent gift of all patient volunteers. Every so often we should break that silence and say "Thank you". I'm honored to have that opportunity here today.
There's another reason to recognize the participants in the Framingham Heart Study at this point in time - and that's your willingness to take a new leap into the future. If the Framingham Study hasn't already given enough, I believe you're on the cusp of giving much more. I'm talking about Project SHARe. This new phase for the Framingham Study is so important. It's part of a new generation of research. And if this new research succeeds as we expect it to, it will help us achieve a new level of effectiveness in medical care. I call the goal "Personalized Health Care," and it means making health care much more individualized and precise for every patient. Personalized Health Care depends on learning much more about the genetic basis of our health. By understanding the connection between genes and specific health conditions, we'll be able to target health care much more precisely.
Today, our medical knowledge is tied to our anatomy. We talk about lung cancer and heart disease. But in the future, we'll be talking about diseases at a much different level. We'll be talking about molecular-based diseases. That will give us all kinds of new treatments that are effective for very specific conditions in individual patients. Personalized Health Care can help us know our individual vulnerabilities. It can make health care more preventive. It can help us spot the onset of disease at a much earlier stage. And it can help us prescribe new therapies that are much more targeted and more effective.
Now there's no way around the fact that we have a long way to go to achieve the promise of Personalized Health Care. We have years, and even decades of work ahead of us, in many different fields. But we also have a head start, in the form of studies like Framingham. One of the most fundamental building blocks for achieving Personalized Health Care is the kind of information that can be gathered from existing studies, just as is being done through Proejct SHARe.
In all of this, Framingham is a leader. And in the future, when health information technology is widely adopted, I believe we'll be turning again to this Study. We'll need new analytical tools and new structures to understand the large amount of patient data that will become available. And once again, Framingham will be ahead of the curve. This Study will have new lessons to teach us about aggregating and analyzing large amounts of patient data, getting sound results, and doing it securely.
That's why we're here today - to recognize the leadership of this Study and the generosity of its participants, in the past 60 years and in a future of Personalized Health Care."
Memorable Comments from the Event
"Framingham is a leader" in the field of health information technology
The Honorable Secretary of Health and Human Services, Mike Leavitt
"The [Framingham] Study has moved medicine from a paradigm of diagnosis and treatment to prediction and prevention "
Dr. Karen Antman, Dean of Boston University School of Medicine
"And through Framingham, the National Institutes of Health recognized the irreplaceable role that public participation must have in any successful biomedical research program I thank you for making NIH what it is today "
Dr. Elias Zerhouni, Director, National Institutes of Health
" Thus evolved a wonderful symbiotic relationship [between staff and participants] We have always trusted that, whatever we are asked to do, our best interests were always considered first and foremost "
Dr. David Anghinetti, Offspring Cohort Participant, Framingham Heart Study
" They [clinic staff] treated me great they showed me all the attention I was so grateful for all they did for me I am going to be 91 and I still can spell 'world' backwards."
Helen Vaughn, Original Cohort Participant, Framingham Heart Study
"On this occasion of the celebration of the 60th year of the Framingham Heart Study as well as the celebration of entering into a new phase, the SHARe project, I would want you to know that I am honored to 'Stand and Be Seen' I am happy to be seen as a participant of the OMNI Cohort of the Framingham Heart Study. Thank you for the inclusion of myself as well as the hundreds of other [minorities] from Framingham who have not only benefited from the Study by enabling them to be proactive in their own health care management, but also by giving them an opportunity to contribute to the furtherance of research in the field "
Rev. Dr. J. Anthony Lloyd, OMNI Participant, Framingham Heart Study
Genes & Populations
READ ARTICLE >>
After decades of research, scientists have identified all of the genetic "letters" that spell out the "words" of our genes. This library of genescalled the human genetic code, or the human genomeis the complete set of instructions for creating you or me. But scientists' ability to read the human genetic code is only a beginning. It will be many more years before researchers figure out what all of our genes do. This information holds tremendous promise for treating, curing, and preventing diseases. By participating in genetics research, you can help scientists understand how our genes influence the diseases we develop.
Reporting Genetic Results in Research Studies:
Summary and Recommendations of an NHLBI Working Group
READ ARTICLE >>
Prospective epidemiologic studies aid in identifying genetic variants associated with diseases, health risks, and physiologic traits. These genetic variants may eventually be measured clinically for purposes of diagnosis, prognosis, and treatment. As evidence of the potential clinical value of such information accrues, research studies face growing pressure to report these results to study participants or their physicians, even before sufficient evidence is available to support widespread screening of asymptomatic persons. There is thus a need to begin to develop consensus on whether and when genetic findings should be reported to participants in research studies. The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group on Reporting Genetic Results in Research Studies to discuss if, when, and how genetic information should be reported to study participants. The Working Group concluded that genetic test results should be reported to study participants when the associated risk for the disease is significant; the disease has important health implications such as premature death or substantial morbidity or has significant reproductive implications; and proven therapeutic or preventive interventions are available. Finally, the Working Group recommended procedures for reporting genetic research results and encouraged increased efforts to create uniform guidelines for this activity.