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Biomedical subjects

William B Kannel

Publications and source records attributed to William B Kannel.

At least 19 recordsLinked to original sources
PubMed2006

Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years.

CONTEXT: Prior estimates of long-term trends in the incidence and severity of stroke have varied; trends in lifetime risk have not been reported. OBJECTIVE: To determine long-term trends in the incidence, lifetime risk, severity, and 30-day mortality of clinical stroke. DESIGN, SETTING, AND PARTICIPANTS: Prospective evaluation of the community-based Framingham Study original and offspring cohorts. Participants were 9152 men and women free of prevalent stroke and undergoing follow-up for up to 50 years over 3 consecutive periods (1950-1977, 1978-1989, and 1990-2004), with biennial ascertainment of stroke risk factor data and active surveillance for incident clinical stroke and cause-specific mortality. MAIN OUTCOME MEASURES: Incidence (age-adjusted, sex-specific), severity, 30-day mortality, and mortality-adjusted 10-year and lifetime risk of stroke in each of the specified periods. RESULTS: There were 1030 incident clinical strokes (450 [44%] in men, 629 atherothrombotic brain infarctions [61%]) in 9152 persons 55 years or older over 174,917 person-years of follow-up. The age-adjusted incidence of first stroke per 1000 person-years in each of the 3 periods was 7.6, 6.2, and 5.3, respectively, in men (P = .02 for trend) and 6.2, 5.8, and 5.1 in women (P = .01 for trend). The lifetime risk at age 65 years decreased from 19.5% to 14.5% in men (P = .11) and from 18.0% to 16.1% in women (P = .61). Age-adjusted stroke severity did not vary across periods; however, 30-day mortality decreased significantly in men (from 23% to 14%; P = .01) but not significantly in women (from 21% to 20%; P = .32). CONCLUSIONS: In this cohort of men and women free of prevalent clinical stroke at initial examination, incidence of stroke has decreased over the past 50 years but the lifetime risk has not declined to the same degree, perhaps due to improved life expectancy. The results of this study suggest that improved control of risk factors has lowered stroke incidence but emphasize the need for continued primary prevention efforts.

Adult↗
PubMed2006

Electrocardiographic QRS duration and the risk of congestive heart failure: the Framingham Heart Study.

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 examination. QRS duration was analyzed as a continuous (log-transformed) and a categorical variable [referent, <100 ms; incomplete bundle branch block (BBB), 100 to 119 ms; complete BBB, > or =120 ms]. During follow-up (mean, 12.7 years), 324 participants (205 women) developed CHF. CHF incidence increased across the 3 baseline QRS duration categories in both sexes. Each SD increment in log-QRS duration was associated with a multivariable-adjusted 23% increase in CHF risk [95% confidence interval [CI] 8% to 38%; P<0.001]. In time- dependent models with QRS category and risk factors updated every 2 years, incomplete BBB was associated with a 1.4-fold (95% CI, 1.05 to 1.96; P=0.03) and complete BBB with a 1.7-fold (95% CI, 1.28 to 2.35; P<0.001) risk of CHF. These associations were maintained on adjustment for baseline left ventricular mass. In our community-based sample, longer electrocardiographic QRS was associated with increased CHF risk, consistent with the hypothesis that depolarization delay may increase CHF risk.

Aged↗
PubMed2006

Search for an optimal atherogenic lipid risk profile: from the Framingham Study.

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 the influence of individual lipids and their ratios on 20-year CHD development in 2,439 men and 2,812 women participating in the Framingham Offspring Study. The influence of the total/high-density (HDL) cholesterol ratio on CHD risk was examined in tertiles of LDL cholesterol and total cholesterol levels. During the 20-year period, 566 CHD events occurred in men and 327 events in women. The CHD risk increased stepwise two- to threefold in men and women from the first to third tertile of total/HDL cholesterol ratio, irrespective of the level of total or LDL cholesterol level. In men, the LDL cholesterol level reflected the lowest risk factor adjusted quintile 5 to quintile 1 relative risk (1.85), and the total/HDL cholesterol ratio predicted the greatest risk (relative risk 2.9). In women, LDL cholesterol imparted the highest risk of the individual lipids (relative risk 3.9), and this was not exceeded by the lipid ratio (relative risk 3.8). In conclusion, the levels of components of the total/HDL cholesterol ratio have little influence on its prediction of CHD. In men, elevated LDL need not be treated aggressively if the total/HDL cholesterol ratio is low. Conversely, modest elevations of LDL may warrant more aggressive treatment if the ratio is high. In women, the ratio is also a good CHD predictor, but a combination of a high ratio accompanied by high LDL cholesterol may warrant more aggressive therapy.

Adult↗
PubMed2006

Metabolic syndrome compared with type 2 diabetes mellitus as a risk factor for stroke: the Framingham Offspring Study.

BACKGROUND: Metabolic syndrome (MetS) has been recognized as a prediabetic constellation of symptoms and an independent risk factor for cardiovascular disease. METHODS: 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 prevalence of MetS alone, diabetes alone, and both in 2097 subjects in the Framingham Offspring Study, aged 50 to 81 years and free of stroke. Age-adjusted risk ratios, 10-year incidence, and population-attributable risks of stroke were estimated for men and women with MetS alone, diabetes alone, and both. RESULTS: Criteria for MetS were met in 30.3% of men and 24.7% of women. Twenty-four percent of men had MetS alone; 7% had diabetes alone; and 6% had both. Twenty percent of women had MetS alone; 3% had diabetes alone; and 5% had both. Over 14 years of follow-up, 75 men and 55 women developed a first stroke; all but 4 events were ischemic. Relative risk (RR) of stroke in persons with both diabetes and MetS (RR, 3.28; confidence interval [CI], 1.82-5.92) was higher than that for either condition alone (MetS alone: RR, 2.10; CI, 1.37-3.22; diabetes alone: RR, 2.47; CI, 1.31-4.65). The population-attributable risk, owing to its greater prevalence, was greater for MetS alone than for diabetes alone (19% vs 7%), particularly in women (27% vs 5%). CONCLUSIONS: Metabolic syndrome is more prevalent than diabetes and a significant independent risk factor for stroke in people without diabetes. Prevention and control of MetS and its components are likely to reduce stroke incidence.

Age Distribution↗
PubMed2006

The lifetime risk of stroke: estimates from the Framingham Study.

BACKGROUND AND PURPOSE: The lifetime risk (LTR) of stroke has not been reported for the United States population; such data would assist public education and health planning. METHODS: 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-specific 10-, 20-, and 30-year risks and LTR of developing a stroke by baseline age and blood pressure (BP) and compared it with the risk of developing Alzheimer disease (AD). RESULTS: A total of 875 participants (522 women) developed a first-ever stroke; 749 (448 women) had an ischemic stroke. LTR of stroke was high and remained similar at ages 55, 65, and 75 years, approximating 1 in 5 for women and 1 in 6 for men. Participants with a normal BP (<120/80 mm Hg) had approximately half the LTR of stroke compared with those with high BP (> or =140/90 mm Hg). The LTR of AD at age 65 (292 participants; 211 women) approximated 1 in 5 for women and 1 in 10 for men. The LTR of developing either stroke or dementia approximated 1 in 3 in both sexes. CONCLUSIONS: The LTR of stroke in middle-aged adults is 1 in 6 or more, which is equal to or greater than the LTR of AD. Women had a higher risk because of longer life expectancy. BP is a significant determinant of the LTR of stroke, and promotion of normal BP levels in the community might be expected to substantially reduce this risk.

Age Factors↗
PubMed2006

Peripheral and cerebral atherothrombosis and cardiovascular events in different vascular territories: insights from the Framingham Study.

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 multivariable risk profiles for peripheral artery disease and stroke. These global risk formulations facilitate office estimation of the risk of these disabling diseases, which often indicate diffuse systemic atherosclerosis. Because predisposing risk factors usually cluster, and the risk each imposes varies widely, global risk assessment is a necessity, especially now that average risk factor levels are recommended for treatment. Novel risk factors deserve attention, but the standard cardiovascular risk factors account for as much as 85% of the cardiovascular disease arising within the population. Further improvement in detection, evaluation, and control of the major risk factors by implementation of guidelines for primary and secondary prevention of stroke and peripheral artery disease is needed, particularly in the high-risk segment of the population.

Atherosclerosis↗
PubMed2005

Temporal trends in the incidence of intermittent claudication from 1950 to 1999.

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 >or=40 years were classified according to date of onset from the 1950s to the 1990s. IC was defined as the presence of exertional calf discomfort that was relieved with rest. Age- and sex-adjusted incidence rate ratios were estimated using log-linear Poisson regression, and 10-year survival was calculated using the Kaplan-Meier method. IC occurred in 668 participants (286 women). The age- and sex-adjusted incidence rate of IC fell from 282 per 100,000 person-years during the period 1950-1969 to 225 per 100,000 person-years in the 1990s. The decline in IC incidence across time periods was significant (p for trend=0.01), with an initial increase in the 1970s being followed by declines of 16% in the 1980s and 18% in the 1990s. Approximately 40% of persons with IC died within 10 years of diagnosis, with no significant change occurring during the study period. IC incidence has declined since 1950, but mortality has remained high and unchanged. Factors contributing to the declining incidence of IC need clarification.

Adult↗
PubMed2005

A comparison of death certificate out-of-hospital coronary heart disease death with physician-adjudicated sudden cardiac death.

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 coronary heart disease death rates derived from death certificates should be interpreted with caution.

Aged↗
PubMed2005

Relative importance of borderline and elevated levels of coronary heart disease risk factors.

BACKGROUND: Clinical trials indicate that a sizable proportion of adults have multiple borderline coronary risk factors and may benefit from treatment. OBJECTIVE: To estimate the relative and absolute contributions of borderline and elevated risk factors to the population burden of coronary heart disease (CHD) events. DESIGN: A prospective cohort study and a national cross-sectional survey. SETTING: The Framingham Study and the Third National Health and Nutrition Examination Survey (NHANES III). PARTICIPANTS: White non-Hispanic persons in the Framingham Study and in NHANES III who were between 35 to 74 years of age and had no CHD. MEASUREMENTS: Occurrence of first CHD events according to 5 major CHD risk factors: blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol levels, glucose intolerance, and smoking. Three categories-optimal, borderline, and elevated-were defined for each risk factor per national guidelines. Sex-specific 10-year CHD event rates from the Framingham Study were applied to numbers of at-risk individuals estimated from NHANES III and the 2000 U.S. Census. RESULTS: Twenty-six percent of men and 41% of women had at least 1 borderline risk factor in NHANES III. According to estimates, more than 90% of CHD events will occur in individuals with at least 1 elevated risk factor, and approximately 8% will occur in people with only borderline levels of multiple risk factors. Absolute 10-year CHD risk exceeded 10% in men older than age 45 years who had 1 elevated risk factor and 4 or more borderline risk factors and in those who had at least 2 elevated risk factors. In women, absolute CHD risk exceeded 10% only in those older than age 55 years who had at least 3 elevated risk factors. LIMITATIONS: The generalizability of the findings to persons of other ethnic backgrounds is unknown. CONCLUSIONS: Borderline CHD risk factors alone account for a small proportion of CHD events.

Adult↗
PubMed2005

Overview of hemostatic factors involved in atherosclerotic cardiovascular disease.

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 inflammatory markers [e.g., C-reactive protein (CRP)] and LDL cholesterol. Fibrinogen seems the most fundamental hemostatic risk factor for CVD. The Framingham Study reaffirms the significant linear risk factor trends across fibrinogen tertiles (P< 0.001) for age, body mass index, smoking, diabetes mellitus, total cholesterol, HDL cholesterol, and TG in both sexes. Fibrinogen may also directly increase CVD risk because of its role in platelet aggregation, plasma viscosity, and fibrin formation. Fibrinogen is also an acute-phase reactant that is elevated in inflammatory states. Fibrinogen mediates the thrombogenic effect of other risk factors. Fibrinogen levels increase with the number of cigarettes smoked and quickly fall after smoking cessation. This rapid fibrinogen decline may be a mechanism for CVD risk reduction after smoking cessation. Weight loss is accompanied by reduced fibrinogen. The correlation between fibrinogen and LDL cholesterol suggests that lipid-imposed CVD risk is mediated partly through fibrinogen. Hyperreactive platelets of diabetics may result in part from their increased fibrinogen. Elevated fibrinogen and CRP of unstable angina suggest an acute-phase reaction. Prevalence, case-control, angiographic, and echocardiogram investigations incriminate hemostatic and inflammatory markers as strong independent risk factors for initial and recurrent CVD. Framingham Study data indicate that each SD increase in fibrinogen imposes a 20% independent increment in risk. It may be concluded that fibrinogen and CRP determination may be useful screening tools to identify individuals at added risk for thrombotic complications of CVD.

Atherosclerosis↗
PubMed2004

Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence.

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 follow-up 4 years from baseline, 458 persons (13.8%) had developed hypertension, and 1201 persons (36.1%) had experienced progression to a higher BP stage. Age- and sex-adjusted rates of hypertension incidence increased progressively from 9.8% for the lowest quartile to 15.6% for the top quartile of serum UA; BP progression rates increased from 32.8% (lowest quartile) to 39.6% (top quartile). In multivariable analyses adjusting for age, sex, body mass index, diabetes, smoking, alcohol intake, serum creatinine, proteinuria, glomerular filtration rate, baseline BP, and interim weight change, a 1 SD higher serum UA was associated with an odds ratio (OR) of 1.17 (95% confidence interval [CI], 1.02 to 1.33) for developing hypertension, and an OR of 1.11 (95% CI, 1.01 to 1.23) for BP progression. In analyses of a subsample of 3157 individuals not on antihypertensive treatment at the follow-up examination, serum UA was positively associated with changes in systolic (P=0.02) and diastolic pressure 4 years later (P=0.04). In summary, serum UA level was an independent predictor of hypertension incidence and longitudinal BP progression at short-term follow-up in our community-based sample.

Adult↗
PubMed2004

Long-term cardiovascular risk with protease inhibitors and management of the dyslipidemia.

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 associated with prompt, marked, and sustained increases in serum lipid levels that are consistent with an increased 10-year risk for coronary heart disease as determined in the Framingham Heart Study. Management of lipid elevations in patients who use protease inhibitors is discussed. Novel protease inhibitors, which have minimal effects on lipid profiles, may have a role in the long-term management of the human immunodeficiency virus.

Cardiovascular Diseases↗
PubMed2004

A likely explanation for the J-curve of blood pressure cardiovascular risk.

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 deaths was estimated at diastolic pressures of <80, 80 to 90, and > or =90 mm Hg, according to concomitant systolic BP. An increasing tendency for a J-curve relation of CVD incidence to diastolic BP was observed with successive increments in accompanying systolic BP. In both genders, a statistically significant excess of CVD events was observed at a diastolic BP of <80 mm Hg only when accompanied by a systolic BP of >140 mm Hg that persisted after adjustment for age and associated CVD risk factors. Patients with this condition of isolated systolic hypertension have been shown to benefit from antihypertensive treatment.

Adult↗
PubMed2004

Temporal trends in coronary heart disease mortality and sudden cardiac death from 1950 to 1999: the Framingham Heart Study.

BACKGROUND: 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). METHODS AND RESULTS: We examined temporal trends in SCD and nonsudden CHD death in the Framingham Heart Study original and offspring cohorts from 1950 to 1999. SCD was defined as a death attributed to CHD with preceding symptoms that lasted less than 1 hour; all deaths were adjudicated by a physician panel. Log-linear Poisson regression was used to estimate CHD mortality and SCD risk ratios (RRs); RRs were adjusted for age and gender. There were 811 CHD deaths: 453 nonsudden and 358 SCDs. Ninety-one (20%) of nonsudden CHD deaths and 173 (48%) of SCDs were in subjects free of antecedent CHD. From 1950-1969 to 1990-1999, overall CHD death rates decreased by 59% (95% CI 47% to 68%, P(trend)<0.001). Nonsudden CHD death decreased by 64% (95% CI 50% to 74%, P(trend)<0.001), and SCD rates decreased by 49% (95% CI 28% to 64%, P(trend)<0.001). These trends were seen in men and women, in subjects with and without a prior history of CHD, and in smokers and nonsmokers. CONCLUSIONS: The risks of SCD and nonsudden CHD mortality have decreased by 49% to 64% over the past 50 years. These trends were evident in subjects with and without heart disease, which suggests important contributions of primary and secondary prevention to the decreasing risk of CHD death and SCD.

Adult↗
PubMed2004

Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study.

CONTEXT: The Framingham Heart Study helped to establish tools to assess coronary heart disease (CHD) risk, but the homogeneous nature of the Framingham population prevents simple extrapolation to other populations. Recalibration of Framingham functions could permit various regions of the world to adapt Framingham tools to local populations. OBJECTIVE: To evaluate the performance of the Framingham CHD risk functions, directly and after recalibration, in a large Chinese population, compared with the performance of the functions derived from the Chinese Multi-provincial Cohort Study (CMCS). DESIGN, SETTING, AND PARTICIPANTS: The CMCS cohort included 30 121 Chinese adults aged 35 to 64 years at baseline. Participants were recruited from 11 provinces and were followed up for new CHD events from 1992 to 2002. Participants in the Framingham Heart Study were 5251 white US residents of Framingham, Mass, who were 30 to 74 years old at baseline in 1971 to 1974 and followed up for 12 years. MAIN OUTCOME MEASURES: "Hard" CHD (coronary death and myocardial infarction) was used as the end point in comparisons of risk factors (age, blood pressure, smoking, diabetes, total cholesterol, and high-density lipoprotein cholesterol [HDL-C]) as evaluated by the CMCS functions, original Framingham functions, and recalibrated Framingham functions. RESULTS: The CMCS cohort had 191 hard CHD events and 625 total deaths vs 273 CHD events and 293 deaths, respectively, for Framingham. For most risk factor categories, the relative risks for CHD were similar for Chinese and Framingham participants, with a few exceptions (ie, age, total cholesterol of 200-239 mg/dL [5.18-6.19 mmol/L], and HDL-C less than 35 mg/dL [0.91 mmol/L] in men; smoking in women). The discrimination using the Framingham functions in the CMCS cohort was similar to the CMCS functions: the area under the receiver operating characteristic curve was 0.705 for men and 0.742 for women using the Framingham functions vs 0.736 for men and 0.759 for women using the CMCS functions. However, the original Framingham functions systematically overestimated the absolute CHD risk in the CMCS cohort. For example, in the 10th risk decile in men, the predicted rate of CHD death was 20% vs an actual rate of 3%. Recalibration of the Framingham functions using the mean values of risk factors and mean CHD incidence rates of the CMCS cohort substantially improved the performance of the Framingham functions in the CMCS cohort. CONCLUSIONS: The original Framingham functions overestimated the risk of CHD for CMCS participants. Recalibration of the Framingham functions improved the estimates and demonstrated that the Framingham model is useful in the Chinese population. For regions that have no established cohort, recalibration using CHD rates and risk factors may be an effective method to develop CHD risk prediction algorithms suited for local practice.

Adult↗