Around 17.5 million people die each year from cardiovascular diseases (CVDs), an estimated 31% of all deaths worldwide. This statistic is expected to grow to more than 23.6 million by 2030.[1] Of these deaths (17.5 million), estimated 7.4 million are due to coronary heart disease and 6.7 million are due to stroke.[1] Epidemiologic studies have played an important role in elucidating the factors that predispose to CVD and highlighting opportunities for prevention. Most CVDs can be prevented by addressing behavioral risk factors such as tobacco use, unhealthy diet and obesity, physical inactivity, and harmful use of alcohol.
CVDs are a group of disorders of the heart and blood vessels, and they include coronary heart disease, cerebrovascular disease, peripheral arterial disease; and rheumatic heart disease, congenital heart disease, deep vein thrombosis, and pulmonary embolism. Heart attacks and strokes are usually acute events and are mainly caused by arteriosclerosis involving heart or brain. Strokes can also be caused by bleeding from a blood vessel in the brain or from blood clots. The cause of heart attacks and strokes is usually the presence of a combination of risk factors, such as tobacco use, unhealthy diet and obesity, physical inactivity and harmful use of alcohol, hypertension, diabetes, and hyperlipidemia.
THE FRAMINGHAM HEART STUDY
Our understanding of the above key facts about heart disease was due mainly to research known as the Framingham Heart Study (FHS), the most influential investigation in the history of modern medicine. It is a long-term, ongoing cardiovascular study on residents of the town of Framingham, Massachusetts, USA. The study began in 1948 with 5209 adult subjects from Framingham and is now on its third generation of participants. Much of our appreciation of the pathophysiology of heart disease came from the results of studies from the FHS. It established the traditional risk factors, such as high blood pressure, diabetes, and cigarette smoking for coronary heart disease. Framingham also spearheaded the study of chronic noninfectious diseases in the USA and introduced preventive medicine.
ORIGINS OF THE FRAMINGHAM HEART STUDY
In 2013, the FHS celebrated 65 years since its creation. The investigation has provided substantial insight into the epidemiology of CVD and its risk factors. The origin of the study is closely linked to the premature death of the US President Franklin D. Roosevelt from hypertensive heart disease and stroke in 1945.
On March 27, 1944, President Roosevelt was admitted to Bethesda Naval Hospital for dyspnea on exertion, diaphoresis, and abdominal distension. He was described by his cardiologist as “slightly cyanotic,” with “BP of 186/108 mmHg” and a chest X-ray (CXR) showing an “increase in size of the cardiac shadow.” The cardiologist, Dr. Howard Bruenn, diagnosed the President with “hypertension, hypertensive heart disease, and cardiac failure.”[3] However, Dr. Bruenn had few therapeutic options to provide, suggesting digitalis and salt intake reduction. After at first rejecting the cardiologist's advice, the President eventually started digitalis with some symptom reliefs, and follow-up CXR 2 weeks later showed reduced cardiomegaly.
President Roosevelt suffered from heart failure due to untreated hypertension. His personal physician at the time was not a cardiologist, but a specialist in EENT (eye, ear, nose, throat) who insisted that the President was healthy and his blood pressure was “no more than normal for a man of his age.”[3] A month after his hospital admission, Roosevelt's blood pressure had risen to 240/130 mmHg. The President died of a massive cerebral hemorrhage on April 12, 1945.[3]
The death of President Roosevelt illustrates the deplorable state of our knowledge and understanding of CVD in the mid-20th century. In the 1940s, CVDs were the number one cause of mortality among Americans, accounting for 1 in 2 deaths. Prevention and treatment were so poorly understood that “most Americans accepted early death from heart disease as unavoidable.”[4]
On June 16, 1948, President Harry Truman signed into law the “National Heart Act.”[3] Thus, the FHS under the direction of the National Heart, Lung, and Blood Institute (NHLBI) was established and became a joint project of the NHLBI and Boston University. The objective of the FHS was to identify the common factors or characteristics that contribute to CVD by following its development over a long period in a large group of participants who had not yet developed overt symptoms 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 Cholesterol 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 Atrial fibrillation 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 overweight 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 social network 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.
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 dementia 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 Sleep apnea 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 fat 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 FROM THE FRAMINGHAM HEART STUDY
Momentous and revolutionary breakthroughs in the development of our knowledge in CVDs are because of insights derived from the FHS. The researchers recruited 5209 men and women between the ages of 30 and 62 years from the town of Framingham, Massachusetts, USA.[5] These subjects underwent extensive medical, physical examinations and lifestyle interviews which were later analyzed for common patterns related to CVD development.
Since 1948, the subjects have continued to return to the study every 2 years for a detailed medical history, physical examination, and laboratory tests. In 1971, the study enrolled a second generation – 5124 of the original participants' adult children and their spouses – to participate in similar examinations. In 1994, the need to establish a new study reflecting a more diverse community of Framingham was recognized, and the first Omni cohort of the FHS was enrolled. In April 2002, the study entered a new phase, the enrollment of the third generation of participants, the grandchildren of the Original Cohort. In 2003, the second group of Omni participants was enrolled.[5]
Over the years, careful monitoring of the Framingham study population has led to the identification of the major CVD risk factors – high blood pressure, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity – as well as a great deal of valuable information on the effects of related factors, such as blood triglyceride and high-density lipoprotein cholesterol levels, age, gender, and psychosocial issues.[5]
The study has produced approximately 1200 articles in leading medical journals. The concept of CVD risk factors has become an integral part of the modern medical curriculum and has led to the development of effective treatment and preventive strategies in clinical practice.[5]
The FHS continues to make important scientific contributions. New diagnostic technologies, such as echocardiography, carotid artery ultrasound, magnetic resonance imaging of the heart and brain, and CT scans of the heart and its vessels, have been integrated into the past and ongoing protocols. The role of genes in heart disease is currently being investigated by Framingham researchers.[5]
LEGACY OF THE FRAMINGHAM HEART STUDY
The FHS (1) corrected clinical misconceptions; (2) revealed the impact of overt and subclinical CVD; (3) established the importance of the principle of multivariable risk factor influences on CVD, with no single essential and sufficient cause; (4) enhanced mortality statistics with population-based incidence of nonfatal cardiovascular events; (5) developed useful multivariable cardiovascular risk assessment profiles (i.e., the Framingham risk score) to minimize possibilities of falsely reassuring or needlessly alarming many potential CVD candidates;[6] and (6) introduced the concept of preventive cardiology to physicians.
The three generations of Framingham participants make this study unique. Undoubtedly, the legacy of the FHS continues with state-of-the-art research into the epidemiology and genomic etiologies of CVD, new biomarkers and imaging tools, and identifying and managing risk factors.
THE FUTURE OF HEART DISEASE
Today, we know more about how to treat coronary artery disease to lengthen and improve quality of life. We also know more about how to reduce our risk of heart disease. Future research efforts will determine the screening and intervention strategies for heart disease prevention. However, we do not yet know all. We need more models of research such as the FHS. We are still a long way from eliminating heart disease from human history.
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Conflicts of interest
There are no conflicts of interest.
REFERENCES
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