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History of Medicine

Framingham Contribution to

Rachel Hajar, M.D. Department of Cardiology, Hospital, Hamad Medical Corporation, Doha, Qatar

round 17.5 million people die each year from and is now on its third generation of participants. Much cardiovascular diseases (CVDs), an estimated of our appreciation of the pathophysiology of heart 31% of all deaths worldwide. This statistic is disease came from the results of studies from the FHS. A [1] expected to grow to more than 23.6 million by 2030. It established the traditional risk factors, such as high Of these deaths (17.5 million), estimated 7.4 million blood pressure, diabetes, and cigarette for are due to coronary heart disease and 6.7 million are coronary heart disease. Framingham also spearheaded due to stroke.[1] Epidemiologic studies have played an the study of chronic noninfectious diseases in the USA important role in elucidating the factors that predispose and introduced preventive medicine. to CVD and highlighting opportunities for prevention. Most CVDs can be prevented by addressing behavioral ORIGINS OF THE FRAMINGHAM HEART risk factors such as tobacco use, unhealthy diet and STUDY , physical inactivity, and harmful use of alcohol. CVDs are a group of disorders of the heart and In 2013, the FHS celebrated 65 years since its creation. blood vessels, and they include coronary heart disease, The investigation has provided substantial insight cerebrovascular disease, peripheral arterial disease; and into the epidemiology of CVD and its risk factors. The rheumatic heart disease, congenital heart disease, deep origin of the study is closely linked to the premature vein thrombosis, and pulmonary embolism. Heart attacks and strokes are usually acute events and are mainly death of the US President Franklin D. Roosevelt from caused by involving heart or brain. Strokes hypertensive heart disease and stroke in 1945. can also be caused by bleeding from a blood vessel in On March 27, 1944, President Roosevelt was admitted the brain or from blood clots. The cause of heart attacks to Bethesda Naval Hospital for dyspnea on exertion, and strokes is usually the presence of a combination of diaphoresis, and abdominal distension. He was described risk factors, such as tobacco use, unhealthy diet and by his cardiologist as “slightly cyanotic,” with “BP of 186/108 obesity, physical inactivity and harmful use of alcohol, mmHg” and a chest X‑ray (CXR) showing an “increase in , diabetes, and hyperlipidemia. size of the cardiac shadow.” The cardiologist, Dr. Howard Bruenn, diagnosed the President with “hypertension, [3] THE FRAMINGHAM HEART STUDY hypertensive heart disease, and cardiac failure.” However, Dr. Bruenn had few therapeutic options to provide, suggesting digitalis and salt intake reduction. After at first rejecting the Our understanding of the above key facts about heart cardiologist’s advice, the President eventually started digitalis disease was due mainly to research known as the with some symptom reliefs, and follow‑up CXR 2 weeks later Framingham Heart Study (FHS), the most influential showed reduced cardiomegaly. investigation in the history of modern medicine. It is a President Roosevelt suffered from due to long‑term, ongoing cardiovascular study on residents of untreated hypertension. His personal physician at the time the town of Framingham, , USA. The study was not a cardiologist, but a specialist in EENT (eye, ear, began in 1948 with 5209 adult subjects from Framingham nose, throat) who insisted that the President was healthy and Address for correspondence: Dr. Rachel Hajar, his blood pressure was “no more than normal for a man of Sr. Consultant Cardiologist, Director HH Publications and Executive Coordinator his age.”[3] A month after his hospital admission, Roosevelt’s for Research, Director Non‑invasive Cardiology 1981‑2014, Heart Hospital, Hamad Medical Corporation, blood pressure had risen to 240/130 mmHg. The President [3] Doha, Qatar. died of a massive cerebral hemorrhage on April 12, 1945. E‑mail: [email protected]

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DOI: How to cite this article: Hajar R. Framingham contribution to cardiovascular disease. Heart Views 2016;17:78-81. 10.4103/1995-705X.185130 © Gulf Heart Association 2016.

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Hajar: Framingham Contribution to Cardiovascular Disease

The death of President Roosevelt illustrates the under the direction of the National Heart, Lung, and deplorable state of our knowledge and understanding of Blood Institute (NHLBI) was established and became th CVD in the mid‑20 century. In the 1940s, CVDs were a joint project of the NHLBI and . The the number one cause of mortality among Americans, objective of the FHS was to identify the common factors accounting for 1 in 2 deaths. Prevention and treatment or characteristics that contribute to CVD by following were so poorly understood that “most Americans accepted early death from heart disease as unavoidable.”[4] its development over a long period in a large group of On June 16, 1948, President Harry Truman signed participants who had not yet developed overt symptoms into law the “National Heart Act.”[3] Thus, the FHS of CVD or suffered a heart attack or stroke.[5] FRAMINGHAM HEART STUDY RESEARCH MILESTONES[2]

1960 Cigarette smoking found to increase the risk of heart disease. 1961 level, blood pressure, and electrocardiogram abnormalities found to increase the risk of heart disease. 1967 Physical activity found to reduce the risk of heart disease and obesity to increase the risk of heart disease. 1970 High blood pressure found to increase the risk of stroke. 1970 increases stroke risk 5-fold. 1976 Menopause found to increase the risk of heart disease. 1978 Psychosocial factors found to affect heart disease. 1988 High levels of HDL cholesterol found to reduce risk of death. 1994 Enlarged left ventricle had shown to increase the risk of stroke. 1996 Progression from hypertension to heart failure described. 1998 Framingham Heart Study researchers identify that atrial fibrillation is associated with an increased risk of all-cause mortality. 1998 Development of simple coronary disease prediction algorithm involving risk factor categories to allow physicians to predict multivariate coronary heart disease risk in patients without overt CHD. 1999 Lifetime risk at age 40 years of developing coronary heart disease is one in two for men and one in three for women. 2001 High-normal blood pressure is associated with an increased risk of cardiovascular disease, emphasizing the need to determine whether lowering high-normal blood pressure can reduce the risk of cardiovascular disease. 2002 Lifetime risk of developing high blood pressure in middle-aged adults is 9 in 10. 2002 Obesity is a risk factor for heart failure. 2004 Serum aldosterone levels predict future risk of hypertension in nonhypertensive individuals. 2005 Lifetime risk of becoming exceeds 70%, that for obesity approximates 1 in 2. 2006 The National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health announces a new genome-wide association study at the Framingham Heart Study in collaboration with Boston University School of Medicine to be known as the SHARe project (SNP Health Association Resource). 2007 Based on evaluation of a densely interconnected of 12,067 people assessed as part of the Framingham Heart Study, network phenomena appear to be relevant to the biologic and behavioral trait of obesity, and obesity appears to spread through social ties. 2008 Based on analysis of a social network of 12,067 people participating in the Framingham Heart Study, researchers discover that social networks exert key influences on decision to quit smoking. 2008 Discovery by Framingham Heart Study and publication of four risk factors that raise probability of developing precursor of heart failure; new 30-year risk estimates developed for serious cardiac events.

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Hajar: Framingham Contribution to Cardiovascular Disease

2009 Framingham Heart Study cited by the American Heart Association among the top 10 cardiovascular research achievements of 2009, “Genome-wide Association Study of Blood Pressure and Hypertension: Genome-wide association study identifies eight loci associated with blood pressure”. 2009 A new genetic variant associated with increased susceptibility for atrial fibrillation, a prominent risk factor for stroke and heart failure, is reported in two studies based on data from the Framingham Heart Study 2009 Framingham Heart Study researchers find parental may lead to poor memory in middle-aged adults 2009 Framingham Heart Study researchers find high leptin levels may protect against Alzheimer’s disease and dementia 2010 tied to increased risk of stroke. 2010 Framingham Heart Study researchers identify additional genes that may play a role in Alzheimer’s disease. 2010 Framingham Heart Study finds around the abdomen associated with smaller, older brains in middle- aged adults. 2010 Framingham Heart Study finds genes link puberty timing and body fat in women. 2010 Having first-degree relative with atrial fibrillation associated with increased risk for this disorder. 2009-2010 Framingham Heart Study researchers contribute to discovering hundreds of new genes underlying major heart disease risk factors – body mass index, blood cholesterol, cigarette smoking, blood pressure, and glucose/diabetes. 2010 First definitive evidence that occurrence of stroke by age 65 years in a parent increased risk of stroke in offspring by 3-fold.

CARDIOVASCULAR DISEASE INSIGHTS on the effects of related factors, such as blood triglyceride FROM THE FRAMINGHAM HEART STUDY and high‑density lipoprotein cholesterol levels, age, gender, and psychosocial issues.[5] Momentous and revolutionary breakthroughs in the The study has produced approximately 1200 articles development of our knowledge in CVDs are because in leading medical journals. The concept of CVD risk of insights derived from the FHS. The researchers factors has become an integral part of the modern medical recruited 5209 men and women between the ages curriculum and has led to the development of effective of 30 and 62 years from the town of Framingham, treatment and preventive strategies in clinical practice.[5] Massachusetts, USA.[5] These subjects underwent The FHS continues to make important scientific extensive medical, physical examinations and lifestyle contributions. New diagnostic technologies, such as interviews which were later analyzed for common echocardiography, carotid artery ultrasound, magnetic patterns related to CVD development. resonance imaging of the heart and brain, and CT Since 1948, the subjects have continued to return scans of the heart and its vessels, have been integrated to the study every 2 years for a detailed medical history, into the past and ongoing protocols. The role of genes , and laboratory tests. In 1971, the in heart disease is currently being investigated by study enrolled a second generation – 5124 of the original Framingham researchers.[5] participants’ adult children and their spouses – to participate in similar examinations. In 1994, the need LEGACY OF THE FRAMINGHAM HEART to establish a new study reflecting a more diverse community of Framingham was recognized, and the STUDY first Omni cohort of the FHS was enrolled. In April 2002, the study entered a new phase, the enrollment of the The FHS (1) corrected clinical misconceptions; (2) third generation of participants, the grandchildren of revealed the impact of overt and subclinical CVD; (3) the Original Cohort. In 2003, the second group of Omni established the importance of the principle of participants was enrolled.[5] multivariable risk factor influences on CVD, with no Over the years, careful monitoring of the Framingham single essential and sufficient cause; (4) enhanced study population has led to the identification of the major mortality statistics with population‑based incidence CVD risk factors – high blood pressure, high blood of nonfatal cardiovascular events; (5) developed cholesterol, smoking, obesity, diabetes, and physical useful multivariable cardiovascular risk assessment inactivity – as well as a great deal of valuable information profiles (i.e., the ) to minimize

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Hajar: Framingham Contribution to Cardiovascular Disease

possibilities of falsely reassuring or needlessly alarming Financial support and sponsorship many potential CVD candidates;[6] and (6) introduced the Nil. concept of preventive cardiology to physicians. The three generations of Framingham participants Conflicts of interest make this study unique. Undoubtedly, the legacy of There are no conflicts of interest. the FHS continues with state‑of‑the‑art research into the epidemiology and genomic etiologies of CVD, new REFERENCES biomarkers and imaging tools, and identifying and managing risk factors. 1. Available from: https://www.heart.org/idc/groups/ahamahpublic/@ wcm/@sop/@smd/documents/downloadable/ucm_470704.pdf. THE FUTURE OF HEART DISEASE [Last access on 2016 Jun 13]. 2. Available from: https://www.framinghamheartstudy.org/about‑fhs/ Today, we know more about how to treat coronary research‑milestones.php. [Last access on 2016 Jun 13]. artery disease to lengthen and improve quality of life. 3. Mahmood SS, Levy D, Vasan RS, Wang TJ. The Framingham heart We also know more about how to reduce our risk of study and the epidemiology of cardiovascular disease: A historical heart disease. Future research efforts will determine perspective. Lancet 2014;383:999‑1008. 4. Bruenn HG. Clinical notes on the illness and death of President the screening and intervention strategies for heart Franklin D. Roosevelt. Ann Intern Med 1970;72:579‑91. disease prevention. However, we do not yet know all. 5. Available from: https://www.framinghamheartstudy.org/about‑fhs/ We need more models of research such as the FHS. history.php. [Last access on 2016 Jun 13]. We are still a long way from eliminating heart disease 6. Wong ND, Levy D. Legacy of the Framingham heart study: Rationale, from human history. design, initial findings, and implications. Glob Heart 2013;8:3‑9.

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