question:从调查设计研究内容的角度对这篇文章进行评价。The Framingham Heart Study is a long-term, ongoing cardiovascular study on residents of the town of Framingham, Massachusetts. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of participants.[1] Prior to it almost nothing was known about the “epidemiology of hypertensive or arteriosclerotic cardiovascular disease”.[2] Much of the now-common knowledge concerning heart disease, such as the effects of diet, exercise, and common medications such as aspirin, is based on this longitudinal study. It is a project of the National Heart, Lung, and Blood Institute, in collaboration with (since 1971) Boston University. [1] Various health professionals from the hospitals and universities of Greater Boston staff the project. History Thomas Royle Dawber was Director of the study from 1949 to 1966. He was appointed as chief epidemiologist shortly after the start of the project, when it was not progressing well.[3] The study had been intended to last 20 years, but at that time Dawber moved to Boston and became chairman of preventive medicine, raising funds to continue the project and taking it with him. By 1968, a fight was underway to keep the Framingham Study going in an era marked by protests, assassinations, the struggle for civil rights, and controversy surrounding America’s military involvement with the Vietnam War. A committee gathered and considered that, after 20 years of research, the Framingham study should come to an end, since their hypothesis had been tested and extensive information concerning heart diseases had been gathered. Despite this conclusion, the study continued, and in 1971, it enrolled a second generation of participants.[1] In 1994, a more diverse sampling of Framingham residents was enrolled as the “Omni cohort.” In April 2002, a third generation was enrolled in the core study, and a second generation of Omni participants was enrolled in the following year. 2 Strong and weak points Over 1000 medical papers have been published related to the Framingham Heart Study. It is generally accepted that the work is outstanding in its scope and duration, and overall is considered very useful. The initial population was 5,209 healthy men and women aged 30 to 62, not the whole of the town population, as is sometimes assumed. It was rightly assumed from the start of the Framingham Heart Study that cardiac health can be influenced by lifestyle and environmental factors, and by inheritance. The Framingham Heart Study is the origin of the term risk factor. Before the Framingham Heart Study, doctors had little sense of prevention. In the 1950s, it was believed that clogging of arteries and narrowing of arteries (atherosclerosis, arteriosclerosis) was a normal part of aging and occurred universally as people became older. High blood pressure (hypertension) and elevated serum cholesterol (hypercholesterolemia) were also seen as normal consequences of aging in the 1950s, and no treatment was initiated. These and further risk factors, e.g., homocysteine, were gradually discovered over the years.[4][5][6][7][8] The Framingham Heart Study, along with other important large studies, e.g., the Seven Countries Study, Nurses’ Health Study, Women’s Health Initiative, also showed the importance of healthy diet, not being overweight or obese, and regular exercise in maintaining good health, and that there are differences in cardiovascular risk between men and women.[9][10] It also confirmed that cigarette smoking is a highly significant factor in the development of heart disease, leading to angina pectoris, myocardial infarction (MI), and coronary death, along with other important studies about smoking, e.g., the British Doctors Study. Recently the Framingham studies have become regarded as overestimating risk, particularly in the lower risk groups, e.g., for UK populations.[13] One question in evidence-based medicine is how closely the people in a study resemble the patient with which the healthcare professional is dealing.[14] There has been discussion of the study in this regard. Researchers recently used contact information given by subjects over the last 30 years to map the social network of friends and family in the study.[15] 3 Framingham Risk Score The 10-year cardiovascular risk of an individual can be estimated with the easy to use Framingham Risk Score, including individuals without known cardiovascular disease. The Framingham Risk Score is based on findings of the Framingham Heart Study.4 Major findings Major findings from the Framingham Heart Study, according to the researchers themselves:[16] 1960s Cigarette smoking increases risk of heart disease. Increased cholesterol and elevated blood pressure increase risk of heart disease. Exercise decreases risk of heart disease, and obesity increases it. 1970s Elevated blood pressure increases risk of stroke. In women who are postmenopausal, risk of heart disease is increased, compared with women who are premenopausal. Psychosocial factors affect risk of heart disease. 1980s High levels of HDL cholesterol reduce risk of heart disease. 1990s Having an enlarged left ventricle of the heart (left ventricular hypertrophy) increases risk of stroke. Elevated blood pressure can progress to heart failure. Framingham Risk Score is published, and correctly predicts 10-year risk of future coronary heart disease (CHD) events. At 40 years of age, the lifetime risk for CHD is 50% for men and 33% for women. 2000s So called “high normal blood pressure” increases risk of cardiovascular disease (high normal blood pressure is called prehypertension in medicine; it is defined as a systolic pressure of 120–139 mm Hg and/or a diastolic pressure of 80–89 mm Hg). Lifetime risk of developing elevated blood pressure is 90%. Obesity is a risk factor for heart failure. Serum aldosterone levels predict risk of elevated blood pressure. Lifetime risk for obesity is approximately 50%. The “SHARe” project is announced, a genome wide association study within the Framingham Heart Study. Social contacts of individuals are relevant to whether a person is obese, and whether cigarette smokers decide to quit smoking. Four risk factors for a precursor of heart failure are discovered. 30-year risk for serious cardiac events can be calculated. American Heart Association considers certain genomic findings of the Framingham Heart Study one of the top research achievements in cardiology. Some genes increase risk of atrial fibrillation. Risk of poor memory is increased in middle aged men and women if the parents had suffered from dementia. 5 To what the study participants consented The Framingham Heart Study participants, and their children and grandchildren, voluntarily consented to undergo a detailed medical history, physical examination, and medical tests every two years,[17] creating a wealth of data about physical and mental health, especially about cardiovascular disease. 6 Genetic research In recent years, scientists have been carrying out genetic research within the Framingham Heart Study. Inheritance patterns in families,[18] heritability and genetic correlations,[19] molecular markers,[20] and associations have been studied. The association studies include traditional genetic association studies, i.e., looking for associations of cardiovascular risk with gene polymorphisms (single-nucleotide polymorphisms, SNPs) in candidate genes, and genome wide association studies (GWAS).[8] For example, one genome wide study, called the 100 K Study, included almost 1400 participants of the Framingham Heart Study (from the original cohort, and the offspring cohort), and revealed a genetic variant associated with obesity. The researchers were able to replicate this particular result in four other populations.[21] Further, the SHARe Study (SNP Health Association Resource Study) uncovered new candidate genes, and confirmed already known candidate genes (for homocysteine and vitamin B12 levels) in participants of the Framingham Heart Study.[22] Because of these exciting genomic results, the Framingham Heart Study has been described as “on its way to becoming the gold standard for cardiovascular genetic epidemiology”. However, clinically, despite these (and other) efforts, the aggregate effect of genes on cardiovascular disease risk beyond that of traditional cardiovascular risk factors has not been established until now

question:FOR MANY YEARS atherosclerosis and diseases related to it were considered the inevitable result of the "aging process." Those seeking to discover possible causes of atherosclerotic disease were considered members of Mencken's "Cult of Hope," striving to find solutions to insoluble problems. In spite of the pessimism surrounding atherosclerotic disease, an increasing number of intensive investigations involving clinical, laboratory, and epidemiological research have greatly advanced our understanding of the nature of this disease and its determinants. Through epidemiological studies in particular, much has been learned concerning the circumstances under which coronary heart disease arises and flourishes. Such studies have also provided a basis for the development of preventive programs in coronary heart disease, the major adult health problem in the United States. The Heart Disease Epidemiology Study of the National Heart Institute in Framingham, Massachusetts, was one of the first to undertake successfully a detailed epidemiological study of this disease. An abortive attempt to undertake a population study of heart disease had been previously made by Sir James MacKenzie in 1920, but because of the limited resources available it was abandoned.1 International epidemiological studies, necessarily limited to gross observations, provided Clrculation, Volume XXXIV, October 1966 indirect evidence that certain host and environmental characteristics were related to the reported death rates from coronary heart disease in different geographic areas. The findings of these studies provided a stimulus for more definitive investigation of a number of factors in relation to the development of this disease.2 Armed with a number of hypotheses derived from such studies, combined with observations from clinical medicine, the Public Health Service through its National Heart Institute established a center for the prospective investigation of factors possibly related to the development of coronary heart disease and hypertension. This study was established in Framingham, Massachusetts, in 1949 and has continued its surveillance of the Framingham population up to the present time. The rationale for the study, its organization, and the methods employed were reported in detail early in the study.3 In brief, an adult population was selected by random sampling methods. This study population was examined and various characteristics were described. The population was then classified on the basis of pertinent characteristics and the rates of development of disease determined in the different subgroups. From this approach the incidence of the disease could be determined and the importance of various personal habits and traits in the development of coronaryheart disease assessed. It was also anticipated that a more complete picture of the natural history of this disease would eventually emerge. The initial expectations of this study have been largely fulfilled. Although, to date, not much light has been shed on the epidemiology of "hypertension," many important associations between the development of coronary heart disease and host and environmental factors have been clearly established. The first conclusions, based on very small numbers of subjects developing the disease, were available after 4 years of follow-up.4 Further surveillance of the population sample has supported the original observations and has at regular intervals added further information by assessing additional factors, new hypotheses, and the details of the relationships already established.5 Credible data on the incidence of coronary heart disease, including asymptomatic as well as overt manifestations, are obtainable only from epidemiological studies of general populations. The Framingham study has been one of the few sources for accurate data on the incidence of the various manifestations of coronary heart disease. The major objective of an epidemiological investigation is to determine the characteristics of those persons who are especially susceptible to the disease under investigation. The Framingham study has clearly demonstrated that certain attributes are strongly related to the development of coronary heart diesase. Included are elevated lipid levels, elevated blood pressure, excess body weight, lack of physical activity, the cigarette smoking habit, low vital capacity, gout, and diabetes. When more than one of these "risk factors" were present, a marked increase in susceptibility was found. In addition to establishing the importance of various risk factors, it has been possible to demonstrate their independent contribution and interrelationships and to make some inferences regarding their mode of action. For persons otherwise predisposed to coronary heart disease because of hypertension, elevated lipid levels, or diabetes, who showed evidence of certain electrocardiographic abnormalities not currently considered diagnostic of coronary heart disease, the risk of developing overt disease was extremely high. These electrocardiographic abnormalities may represent myocardial involvement due to ischemia. From observations in the Framingham study it has become clear that by using ordinary office procedures the physician can readily identify coronary-prone individuals as well as those with asymptomatic disease. The nature of the risk factors identified suggests that appropriate, safe, and reasonable preventive measures may be applied which may delay the onset of overt disease. Knowledge of the natural history of coronary heart disease obtained from the Framingham study has served to emphasize the need for a preventive approach. The high rate of sudden death and the frequency of unrecognized myocardial infarction, which has proved far from innocuous, indicate that a therapeutic approach alone is insufficient. In addition to identifying factors which relate to the development of initial attacks of coronary heart disease, it has been possible to explore circumstances possibly precipitating attacks in predisposed individuals and those affecting survival once an attack occurs. Factors precipitating heart attacks and those adversely affecting survival were not necessarily those related to the development of the underlying process, although the more severe the coronary artery atherosclerosis, the more likely was the attack to be fatal. The relative success of the Framingham study in meeting its objective served to spark a whole series of prospective studies designed to investigate chronic disease in general and cardiovascular disease in particular. Many studies in dissimilar populations have served to confirm and extend the Framingham observations, emphasizing the fundamental biological nature of the relationships established.6 8 In 1962, in conjunction with the Albany heart study, it was possible to examine jointly the relationship of cigarette smoking to risk of coronary heart disease in great detail, adding much to the understanding of therelationship of this habit to development of the disease.9 Similar efforts to pool and combine the results of prospective epidemiological studies are underway. As is generally the case, investigations in Framingham have raised almost as many questions as have been answered. The details of the relationships established are now being explored in an effort to establish the independent contribution of these multiple interrelated factors to development of disease and the mechanism involved. At present, the etiology of the disease appears to be multifactorial with no single essential factor yet identified. Periodically new hypotheses have been developed and the additional observations necessary have been recorded. Additional follow-up will be required to assess the relation of factors recently introduced (for example, pre-beta lipoprotein, triglyceride, emotional stress, physical fitness, and clotting factors among others) to development of the disease. As time has passed, the population has aged sufficiently that strokes and peripheral vascular disease are developing in increasing numbers. Factors predisposing to these manifestations of atherosclerosis are already being identified.10 The investigation of the several major manifestations of atherosclerosis is being actively pursued. The Framingham study has demonstrated that the prospective epidemiological approach in chronic disease is of value. This intensive, careful study of a relatively small population group should continue to provide useful information concerning the nature of atherosclerotic and hypertensive disease for many years to come. 从调查设计研究内容的角度对这篇文章进行评价。

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