William B. Kannel's research while affiliated with National Heart, Lung, and Blood Institute and other places

Publications (719)

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The Framingham Heart Study (FHS) was started in 1948 as a prospective investigation of cardiovascular disease in a cohort of adult men and women. Continuous surveillance of this sample of 5209 subjects has been maintained through biennial physical examinations. In 1971 examinations were begun on the children of the FHS cohort. This study, called th...
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AimsReduced physical activity is associated with increased risk of heart failure (HF) in middle-aged individuals. We hypothesized that physical inactivity is also associated with greater HF risk in older individuals, and examined if the association was consistent for HF with preserved ejection fraction (HFPEF) vs. HF with a reduced ejection fractio...
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Background: About one half of patients with heart failure (HF) have preserved ejection fraction (HFPEF) rather than reduced ejection fraction (HFREF). The differences in risk factors predisposing to the 2 subtypes of HF are poorly understood. We sought to identify clinical predictors of new-onset HF and to explore differences in HFPEF versus HFREF...
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Heart failure (HF) is a major public health burden worldwide. Of patients presenting with HF, 30-55% have a preserved ejection fraction (HFPEF) rather than a reduced ejection fraction (HFREF). Our objective was to examine discriminating clinical features in new-onset HFPEF vs. HFREF. Of 712 participants in the Framingham Heart Study (FHS) hospitali...
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Salt sensitivity, a trait characterized by a pressor blood pressure response to increased dietary salt intake, has been associated with higher rates of cardiovascular target organ damage and cardiovascular disease events. Recent experimental studies have highlighted the potential role of the natriuretic peptides and aldosterone in mediating salt se...
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Featured Article: Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham study. JAMA 1979;241:2035–8.3 This diabetes report extended prior Framingham study findings with more-robust 20-year data for estimating the relative risk of specified atherosclerotic cardiovascular events from prior diabetes. It prospectively compared the c...
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Cardiovascular disease (CVD) and its predisposing risk factors are major lifestyle and behavioral determinants of longevity. Dietary lifestyle choices such as a heart healthy diet, regular exercise, a lean weight, moderate alcohol consumption, and smoking cessation have been shown to substantially reduce CVD and increase longevity. Recent research...
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We sought to validate a recently published risk algorithm for incident atrial fibrillation (AF) in independent cohorts and other racial groups. We evaluated the performance of a Framingham Heart Study (FHS)-derived risk algorithm modified for 5-year incidence of AF in the FHS (n = 4764 participants) and 2 geographically and racially diverse cohorts...
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The high mortality rate in patients with heart failure (HF) is influenced by presence of multiple comorbidities. Data are limited on the relative contributions of cardiovascular versus noncardiovascular diseases to death in individuals with HF in the community. We examined the incidence and predictors of cardiovascular versus noncardiovascular deat...
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To evaluate the association of serum phosphorus with cardiac structure/function and incident heart failure. We related serum phosphorus to echocardiographic left ventricular (LV) measurements cross-sectionally, and to incident heart failure prospectively in 3300 participants (mean age 44 years, 51% women) free of heart failure, myocardial infarctio...
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Occurrence of all clinical manifestations of atherosclerosis increases with age. Aging is also associated with the acquisition of and increments in major modifiable risk factors that contribute to development of cardiovascular disease (CVD). This cluster of CVD risk factors accompanying advancing age could account for much of the rise in CVD incide...
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The relations of lipid concentrations to heart failure (HF) risk have not been elucidated comprehensively. In 6860 Framingham Heart Study participants (mean age, 44 years; 54% women) free of baseline coronary heart disease, we related high-density lipoprotein cholesterol (HDL-C) and non-HDL-C to HF incidence during long-term follow-up, adjusting fo...
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Targeting triglycerides as a vascular risk factor is justified because of the role of triglyceride-rich lipoproteins in atherogenesis. This review examines recent evidence connecting triglycerides with cardiovascular disease (CVD) in the context of advances in insights concerning the pathophysiology, population burden and prognostic impact of fasti...
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Framingham Heart Study cardiovascular disease prospective population epidemiologic research has played an important role in the evolution of modern cohort study design and the advancement of preventive cardiology. To date no single essential factor has been identified; multiple interrelated factors are promoting increased risk for development of CH...
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One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohort...
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It is often claimed that only 50% of the incidence of coronary artery disease in the population can be attributed to the standard major risk factors. A careful review of published research demonstrates that 75% to 90% of coronary artery disease incidence in a variety of populations is explained by the standard modifiable risk factors. In conclusion...
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Atrial fibrillation (AF), an escalating dysrhythmia, is accountable for extensive population morbidity and mortality. In the United States, approximately 2.3 million people are presently diagnosed with AF and it is estimated that this prevalence may increase to 5.6 million by 2050. Foremost predisposing risk factors for this dysrhythmia include adv...
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Atrial fibrillation contributes to substantial increases in morbidity and mortality. We aimed to develop a risk score to predict individuals' absolute risk of developing the condition, and to provide a framework for researchers to assess new risk markers. We assessed 4764 participants in the Framingham Heart Study from 8044 examinations (55% women,...
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Control of hypertension whether labile or fixed, systolic or diastolic, and at any age or in either sex, appears to be central to the prevention of atherothrombotic brain infarction (ABI). Prospectively, hypertension proved to be the most common and potent precursor of ABIs. Its contribution was direct and could not be attributed to factors related...
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Recent cross-sectional studies have suggested that higher serum sodium levels may be a marker of elevated blood pressure. It is unclear whether serum sodium levels are related to the risk of developing hypertension in the community. We investigated the association of serum sodium with longitudinal blood pressure tracking and incidence of hypertensi...
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Although mortality after myocardial infarction (MI) has declined in the United States in recent decades, there have been few community-based investigations of the long-term trends in the incidence of heart failure after MI, and their results appear to be conflicting. We evaluated 676 Framingham Heart Study participants between 45 and 85 years of ag...
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Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals. We evalua...
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Atrial fibrillation (AF) contributes to increased morbidity and mortality. An easily applicable AF risk score for incidence of AF in the community is unavailable. We examined 8044 person-exams among subjects who were 46 –95 years of age and attended routine Framingham Heart Study (FHS) exams (n=4764 individuals; mean age 61 years, 55% women). Multi...
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Dyslipidemia, hypertension, and diabetes mellitus have been appropriately highlighted as established predictors of cardiovascular disease. These risk factors have become preeminent targets for influencing cardiovascular risk; their assessment, treatment, and monitoring are major emphases of clinical care, research investigation, treatment guideline...
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Long-term blood pressure (BP) progression and its importance as a predictor of clinical outcome have not been well characterized across different periods. We evaluated period trends for 3 BP variables (long-term slope and mean BP during a baseline period of 16 years, and last baseline value) in an earlier period (1953-1971; n = 1644, mean participa...
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To compare implications of Angina Pectoris (AP) and Intermittent Claudication (IC) as indicators of clinical atherosclerosis in other vascular territories. Prospective cohort study of cardiovascular disease (CVD) in 5,209 men and women of Framingham, MA, aged 28-62 years at enrollment in 1948-1951, who received biennial examinations during the firs...
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Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of...
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There has been little attention to vascular calcium testing for generalized assessment of cardiovascular disease (CVD) outcomes, such as intermittent claudication (IC) and ischemic stroke (IS). We hypothesize that aortic calcium is an important predictor of CVD outcomes. Lumbar x-rays were obtained in 848 men and 1,301 women (mean ages 59.7 and 60....
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Atrial fibrillation (AF), an increasingly common dysrhythmia, is responsible for substantial morbidity and mortality. Currently in the United States, approximately 2.3 million people are diagnosed with AF and, based on the census, this number may rise to 5.6 million by 2050. Risk factors for AF include advancing age and cardiovascular disease and i...
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This chapter provides an introduction to the Framingham Heart Study and the genetic research related to cardiovascular diseases conducted in this unique population. It briefly describes the origins of the study, the risk factors that contribute to heart disease, and the approaches taken to discover the genetic basis of some of these risk factors. T...
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Increased triglycerides (TG) and decreased high-density lipoprotein (HDL) cholesterol are key metabolic abnormalities in patients with insulin resistance (IR) states, including diabetes mellitus. The TG/HDL cholesterol ratio was advocated as a simple clinical indicator of IR, but studies yielded inconsistent results. The total cholesterol/HDL chole...
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Studies suggest that targeting high-risk, nonhypertensive individuals for treatment may delay hypertension onset, thereby possibly mitigating vascular complications. Risk stratification may facilitate cost-effective approaches to management. To develop a simple risk score for predicting hypertension incidence by using measures readily obtained in t...
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In addition, persons har-boring these infarcts and a large burden of white-matterhyperintensities are predisposed to develop clinically appar-ent cerebral infarctions. Further, the presence of elevatedlevels of stroke risk factors exerts a measurable effect onbrain structure and function, which results in reduced totalcerebral volume and an increas...
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Previous studies relating plasma renin to cardiovascular disease (CVD) and mortality yielded conflicting results. We related plasma renin to incidence of CVD and mortality in 3408 individuals (mean age 59; 53% women) and in a hypertensive subset (n = 1413). On follow-up (mean 7.1 years), 176 participants (122 hypertensives) developed CVD and 215 in...
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Higher blood pressure and body mass index (BMI) are risk factors for heart failure. It is unknown whether the presence of these risk factors in midadulthood affect the future development of heart failure. In the community-based Framingham Heart Study, we examined the associations of antecedent blood pressure and BMI with heart failure incidence in...
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Low diastolic blood pressure is alleged to impose excess cardiovascular disease (CVD) risk in patients with treated hypertension, impeding aggressive reduction of blood pressure. Most investigations that assessed the potential J-shaped relations of diastolic blood pressure and adverse outcomes have not adequately considered systolic or pulse pressu...
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Atrial fibrillation (AF) is responsible for considerable morbidity and mortality, making identification of modifiable risk factors a priority. Increased pulse pressure, a reflection of aortic stiffness, increases cardiac load and may increase AF risk. To examine relations between pulse pressure and incident AF. Prospective, community-based observat...
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Context: Cardiovascular disease (CVD) is the leading cause of death among the largest and fastest growing ethnic minority in the United States, Latinos/Hispanics. CVD risk factors such as metabolic syndrome, obesity, and diabetes are prevalent in Latinos/Hispanics at alarming rates. It is therefore imperative to understand this population's risk o...
Chapter
– Epidemiologic studies have identified hundreds of risk factors and risk markers for development of cardiovascular disease (CVD) and coronary heart disease (CHD). – The established risk factors for CVD include dyslipidemia, hypertension, cigarette smoking, obesity, diabetes and impaired fasting glucose, and family history of premature CVD. –...
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To determine the scope, impact, and health care limitations relative to cardiovascular disease (CVD) in the Latino-Hispanic population. We reviewed MEDLINE and PubMed for studies published from January 1995 to June 2005 using a combination of search terms (epidemiology, Hispanic, CVD) and chose articles for review on the basis of direct information...
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Major risk factors for clinical atherosclerosis include dyslipidemia, hypertension, glucose intolerance, adiposity, cigarette smoking, hemostatic factors, inflammatory markers, and sedentary lifestyle. Sets of some of these and evidence of vascular damage such as left ventricular hypertrophy and atrial fibrillation are used to formulate multivariab...
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In replyThere is indeed growing evidence that sleep apnea is associated with impaired glucose tolerance and insulin resistance. There is also some evidence linking sleep apnea to stroke, although prospective population data demonstrating this are not yet available. One recently published prospective study followed subjects referred to the Yale Cent...
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Prolonged electrocardiographic QRS duration is frequently observed in congestive heart failure (CHF) patients. We hypothesized that CHF risk increases with longer QRS interval in individuals free of CHF. We evaluated 1759 Framingham Study participants (mean age, 69 years; 63% women) without prior myocardial infarction or CHF who attended a routine...
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Recent guidelines have targeted low-density lipoprotein (LDL) cholesterol for treatment of dyslipidemia. A lack of clear demarcation of potential coronary heart disease (CHD) cases solely on the basis of LDL cholesterol indicates the need to consider the dyslipidemic risk in the context of a lipid and risk factor profile. We prospectively examined...
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The lifetime risk (LTR) of stroke has not been reported for the United States population; such data would assist public education and health planning. Framingham Original cohort participants (n=4897) who were stroke- and dementia-free at 55 years of age were followed biennially for up to 51 years (115 146 person years). We estimated the sex-specifi...
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Metabolic syndrome (MetS) has been recognized as a prediabetic constellation of symptoms and an independent risk factor for cardiovascular disease. To evaluate the age-adjusted risk of stroke and population-attributable risk associated with MetS and compare with those of overt type 2 diabetes mellitus (hereinafter, "diabetes"), we determined the pr...
Chapter
A preventive approach to management of atherosclerotic cardiovascular disease (CVD) is needed because once CVD becomes manifest, it is often immediately lethal and those fortunate enough to survive seldom can be restored to full function. Prevention of the major atherosclerotic CVD events is now feasible because several modifiable predisposing risk...
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Hemostatic factors associated with the development of cardiovascular disease (CVD) include fibrinogen, von Willebrand factor, tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1), and factor VII. Each SD increment of these increases the association by 24-30%. Most hemostatic factors are intercorrelated with inflamma...
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death. With an average number of deaths of 15 annually, it has been estimated that on a basis of six cases to a death, there should be in Framingham ~90 active cases. It is interesting to note that among the 4500 individuals examined in the special drives in Framingham, there were 91 cases discovered, giving a morbidity rate of 2%. This rate applie...
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Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. Relevant studies were identified by computer-assisted searches, hand searches of reference lists...
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Declines in coronary disease and stroke mortality have occurred, but it remains unclear whether intermittent claudication (IC) incidence and mortality rates have changed. The authors sought to examine long-term trends for IC in the community. Cases of IC among Framingham Study participants aged ≥40 years were classified according to date of onset f...
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The number of deaths due to out-of-hospital coronary heart disease as determined by death certificates was compared with the number physician-adjudicated sudden cardiac deaths in the Framingham Heart Study from 1950 to 1999. Out-of-hospital coronary heart disease deaths overestimated sudden cardiac death by 47%, suggesting that out-of-hospital coro...
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Clinical trials indicate that a sizable proportion of adults have multiple borderline coronary risk factors and may benefit from treatment. To estimate the relative and absolute contributions of borderline and elevated risk factors to the population burden of coronary heart disease (CHD) events. A prospective cohort study and a national cross-secti...
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Serum uric acid (UA) has been implicated in the pathogenesis of hypertension. We investigated the relationship of serum UA to hypertension incidence and blood pressure (BP) progression in 3329 Framingham Study participants (mean age 48.7 years; 55.6% women) free of hypertension, myocardial infarction, heart failure, renal failure, or gout. At follo...
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CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches...
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Indications, choices of therapy, and goals of treatment for hypertension should be closely linked to the multivariate risk of cardiovascular events and ingredients of the vascular risk profile of patients with hypertension. Hypertension commonly occurs in combination with other cardiovascular disease risk factors, and the burden of the associated r...
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This report reviews current data pertaining to the development of dyslipidemia during treatment with protease inhibitors and the associated risk for cardiovascular disease in patients who have the human immunodeficiency virus. Most protease inhibitors used to manage the human immunodeficiency virus and the acquired immunodeficiency syndrome are ass...
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This article describes five decades of epidemiologic research that has contributed to an explosive expansion of knowledge about the causes and evolution of cardiovascular disease. Cardiovascular epidemiology has become a basic science of preventive cardiology and has provided vital information about predisposing but modifiable risk factors to publi...
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To develop a model for estimating the global risk of disease progression in patients with ocular hypertension and to calculate the "number-needed-to-treat" (NNT) to prevent progression to blindness as an aid to practitioners in clinical decision making. Development of a mathematical model for estimating risk of glaucoma progression. Population-base...
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To determine whether multivariable risk factor assessment can be as successful in developing disease prevention strategies in patients with ocular hypertension as it has been in patients at risk for coronary heart disease (CHD). From a literature review of the evolution of the global risk assessment model for CHD, parallels are drawn to the evoluti...
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Throughout the past 50 years, heart disease has been the leading cause of death in the United States. Although declines in coronary heart disease (CHD) mortality have been noted, there is still uncertainty about the magnitude of the decline and whether the trend is similar for sudden cardiac death (SCD). We examined temporal trends in SCD and nonsu...
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We prospectively tested in the combined original and offspring Framingham cohorts the hypothesis that the increase in cardiovascular disease (CVD) incidence at low diastolic blood pressure (BP) is largely confined to subjects with increased systolic BP and hence an increased pulse pressure. The 10-year risk of 951 nonfatal CVD events and 204 CVD de...