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Biomedical subjects

W B Kannel

Publications and source records attributed to W B Kannel.

At least 37 records · Page 2Linked to original sources

Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study.

BACKGROUND: Hyperuricemia is associated with risk for cardiovascular disease and death. However, the role of uric acid independent of established risk factors is uncertain. OBJECTIVE: To examine the relation of serum uric acid level to incident coronary heart disease, death from cardiovascular disease, and death from all causes. DESIGN: Community-based, prospective observational study. SETTING: Framingham, Massachusetts. PATIENTS: 6763 Framingham Heart Study participants (mean age, 47 years). MEASUREMENTS: Serum uricacid level at baseline (1971 to 1976); event rates per 1000 person-years by sex-specific uric acid quintile. RESULTS: During 117,376 person-years of follow-up, 617 coronary heart disease events, 429 cardiovascular disease deaths, and 1460 deaths from all causes occurred. In men, after adjustment for age, elevated serum uric acid level was not associated with increased risk for an adverse outcome. In women, after adjustment for age, uric acid level was predictive of coronary heart disease (P = 0.002), death from cardiovascular disease (P = 0.009), and death from all causes (P = 0.03). After additional adjustment for cardiovascular disease risk factors, uric acid level was no longer associated with coronary heart disease, death from cardiovascular disease, or death from all causes. In a stepwise Cox model, diuretic use was identified as the covariate responsible for rendering serum uric acid a statistically nonsignificant predictor of outcomes. CONCLUSIONS: These findings indicate that uric acid does not have a causal role in the development of coronary heart disease, death from cardiovascular disease, or death from all causes. Any apparent association with these outcomes is probably due to the association of uric acid level with other risk factors.

Age Distribution↗

Profile for estimating risk of heart failure.

CONTEXT: We devised a risk appraisal function to assess the hazard of heart failure in persons who are predisposed by coronary disease, hypertension, or valvular heart disease. OBJECTIVE: To provide general practitioners and internists with a cost-effective method to select people at high risk who are likely to have impaired left ventricular systolic function and may therefore require further evaluation and aggressive preventive measures. METHODS: The routinely measured risk factors used in constructing the heart failure profile include age, electrocardiographic left ventricular hypertrophy, cardiomegaly on chest x-ray film, heart rate, systolic blood pressure, vital capacity, diabetes mellitus, evidence of myocardial infarction, and valvular disease or hypertension. Based on 486 heart failure cases during 38 years of follow-up, 4-year probabilities of failure were computed using the pooled logistic regression model for each sex; a simple point score system was employed. A multivariate profile was also produced without the vital capacity or chest x-ray film because these may not be readily available in some clinical settings. RESULTS: Using the risk factors that make up the multivariate risk formulation-derived from ordinary office procedures-the probability of developing heart failure can be estimated and compared with the average risk for persons of the same age and sex. Using this risk profile, 60% of events in men and 73% in women occurred in subjects in the top quintile of multivariate risk. CONCLUSIONS: Using this multivariate risk formulation, it is possible to identify high-risk candidates for heart failure who are likely to have a substantial yield of positive findings when tested for objective evidence of presymptomatic left ventricular dysfunction. The risk profile may also identify candidates who are at high risk for heart failure because of multiple, marginal risk factor abnormalities that might otherwise be overlooked.

Aged↗

Clustering of metabolic factors and coronary heart disease.

BACKGROUND: The degree of clustering for common metabolic coronary disease risk factors is not well known, the antecedents of clustering are not well studied, and the impact of such clusters on coronary risk has not been assessed systematically. METHODS: Prospective community sample of 2406 men and 2569 women aged 18 to 74 years at baseline. The 6 metabolically linked risk factors considered were the lowest sex-specific quintile of high-density lipoprotein cholesterol and the highest quintiles of body mass index, systolic blood pressure, triglycerides, glucose, and serum total cholesterol. RESULTS: At baseline the risk factor sum, represented as integer values, ranged from 0 to 6, and clusters of 3 or more risk factors occurred at twice the rate predicted by chance. After adjustment for age and obesity level, a 2.25-kg (5-lb) weight increase over 16 years was associated with an increased risk factor sum in men (+20%; P=.002) and women (+37%; P<.001), and a 2.25-kg weight loss was associated with a decreased risk factor sum in men (-48%; P<.001) and women (-40%; P<.001). Clusters of 3 or more risk factors were associated with a 2.39 (95% confidence interval, 1.56-3.36) and 5.90 (95% confidence interval, 2.54-13.73) times greater risk of coronary heart disease in men and women, respectively (both P<.001). CONCLUSIONS: Atherogenic risk factor clustering is common in both sexes, worsens with weight gain, and is associated with greatly increased risk of coronary disease risk in both sexes.

Adult↗

Trends in the prevalence of hypertension, antihypertensive therapy, and left ventricular hypertrophy from 1950 to 1989.

BACKGROUND: Men and women with hypertension are at increased risk for cardiovascular disease, especially when left ventricular hypertrophy is present. We examined temporal trends in the use of antihypertensive medications and studied the relation between their use, the prevalence of high blood pressure, and the presence of electrocardiographic evidence of left ventricular hypertrophy. METHODS: A total of 10,333 participants in the Framingham Heart Study who were 45 to 74 years of age underwent a total of 51,756 examinations from 1950 to 1989. Data were obtained on blood pressure and the use of antihypertensive medications, and electrocardiograms were assessed for left ventricular hypertrophy. The generalized-estimating-equation method was used to test for trends over time. RESULTS: From 1950 to 1989, the rate of use of antihypertensive medications increased from 2.3 percent to 24.6 percent among men and from 5.7 percent to 27.7 percent among women. The age-adjusted prevalence of systolic blood pressure of at least 160 mm Hg or diastolic blood pressure of at least 100 mm Hg declined from 18.5 percent to 9.2 percent among men and from 28.0 percent to 7.7 percent among women. This decline was accompanied by age-adjusted reductions in the prevalence of electrocardiographic evidence of left ventricular hypertrophy, from 4.5 percent to 2.5 percent among men and from 3.6 percent to 1.1 percent among women. CONCLUSIONS: Our findings support the notion that the increasing use of antihypertensive medication has resulted in a reduced prevalence of high blood pressure and a concomitant decline in left ventricular hypertrophy in the general population. Our observations may in part explain the considerable decline in mortality from cardiovascular disease observed since the late 1960s.

Age Factors↗

Current status of the epidemiology of heart failure.

Epidemiologic investigation of the evolution of heart failure in the general population has provided clues to its pathogenesis, predisposing conditions, predictive modifiable risk factors, and indicators of deteriorating ventricular function. It is a major and growing problem because of the increased size of aging populations and the prolongation of the lives of cardiac patients by modern therapy. Susceptible persons must be detected early so that preventive measures can be started because the mortality rate once overt heart failure appears is unacceptably high despite recent innovations in treatment.

Age Distribution↗

Comparison of past versus recent physical activity in the prevention of premature death and coronary artery disease.

BACKGROUND: People who are physically active live longer, but it is unclear whether this is because of physical activity in the distant or more recent past. METHODS: We assessed activity levels in 5209 men and women in the Framingham Heart Study from 1956 to 1958 and again from 1969 to 1973. We included individuals who were alive and without cardiovascular disease in the period 1969 to 1973. The primary outcome was death from all causes during the 16 years after the 1969 to 1973 assessment. Secondary outcomes were incidence and mortality rate of cardiovascular disease. We used Cox proportional hazards regression to calculate the relative risk of being sedentary, both unadjusted and controlling for smoking, weight, systolic blood pressure, cholesterol, glucose intolerance, left ventricular hypertrophy, chronic obstructive pulmonary disease, and cancer. RESULTS: The overall 16-year mortality rate was 37% for men and 27% for women. When both distant and recent activity levels were included along with major cardiovascular disease risk factors, for recent activity the most active tertile had lower overall mortality rate than the least active tertile for men (risk ratio 0.58, 95% confidence interval, 0.43-0.79) and women (risk ratio 0.61, 95% confidence interval, 0.45-0.82). For distant activity there was no difference in overall mortality rate between the most and least active tertiles either for men or for women. Adjusting for major cardiovascular disease risk factors had little effect on the results. CONCLUSIONS: The reduction in overall mortality rates is more associated with recent activity than distant activity. These results suggest that for sedentary patients, it may never be too late to begin exercising.

Adult↗

Historic perspectives on the relative contributions of diastolic and systolic blood pressure elevation to cardiovascular risk profile.

The aim of this review was to examine the relative contributions of systolic and diastolic blood pressures to the risk of cardiovascular disease on the basis of epidemiologic evidence from the Framingham Heart Study and the change in attitudes toward systolic blood pressure that occurred during the course of the study. Historic texts were evaluated in comparison with data from the Framingham Heart Study, a prospective longitudinal analysis of the relation between blood pressure and occurrence of subsequent cardiovascular morbidity and mortality rates in a fixed cohort. Historically, systolic hypertension has been considered an innocent accompaniment to arterial stiffening, occurring as a compensatory phenomenon in the elderly. Epidemiologic data show that the development of hypertension is neither inevitable nor beneficial. The data also provide evidence that systolic pressure is more important than diastolic pressure as a determinant of cardiovascular sequelae. Mild or moderate elevations of systolic blood pressure, even when unaccompanied by diastolic pressure elevations, are associated with an increased risk of cardiovascular disease. Risk is increased further by the added presence of related metabolic disturbances such as dyslipidemia, glucose intolerance, insulin resistance, cardiac hypertrophy, and obesity. Over-reliance on diastolic blood pressure in assessing the risk of hypertension can be misleading. Systolic pressure constitutes a powerful predictor of cardiovascular disease and a valuable tool when incorporated within multivariate risk formulas for estimating the conditional probability of coronary and stroke events.

Blood Pressure↗

Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates.

Atrial fibrillation (AF) is the most common of the serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality in the general population. Its prevalence doubles with each advancing decade of age, from 0.5% at age 50-59 years to almost 9% at age 80-89 years. It is also becoming more prevalent, increasing in men aged 65-84 years from 3.2% in 1968-1970 to 9.1% in 1987-1989. This statistically significant increase in men was not explained by an increase in age, valve disease, or myocardial infarctions in the cohort. The incidence of new onset of AF also doubled with each decade of age, independent of the increasing prevalence of known predisposing conditions. Based on 38-year follow-up data from the Framingham Study, men had a 1.5-fold greater risk of developing AF than women after adjustment for age and predisposing conditions. Of the cardiovascular risk factors, only hypertension and diabetes were significant independent predictors of AF, adjusting for age and other predisposing conditions. Cigarette smoking was a significant risk factor in women adjusting only for age (OR = 1.4), but was just short of significance on adjustment for other risk factors. Neither obesity nor alcohol intake was associated with AF incidence in either sex. For men and women, respectively, diabetes conferred a 1.4- and 1.6-fold risk, and hypertension a 1.5- and 1.4-fold risk, after adjusting for other associated conditions. Because of its high prevalence in the population, hypertension was responsible for more AF in the population (14%) than any other risk factor. Intrinsic overt cardiac conditions imposed a substantially higher risk. Adjusting for other relevant conditions, heart failure was associated with a 4.5- and 5.9-fold risk, and valvular heart disease a 1.8- and 3.4-fold risk for AF in men and women, respectively. Myocardial infarction significantly increased the risk factor-adjusted likelihood of AF by 40% in men only. Echocardiographic predictors of nonrheumatic AF include left atrial enlargement (39%/ increase in risk per 5-mm increment), left ventricular fractional shortening (34% per 5% decrement), and left ventricular wall thickness (28% per 4-mm increment). These echocardiographic features offer prognostic information for AF beyond the traditional clinical risk factors. Electrocardiographic left ventricular hypertrophy increased risk of AF 3-4-fold after adjusting only for age, but this risk ratio is decreased to 1.4 after adjustment for the other associated conditions. The chief hazard of AF is stroke, the risk of which is increased 4-5-fold. Because of its high prevalence in advanced age, AF assumes great importance as a risk factor for stroke and by the ninth decade becomes a dominant factor. The attributable risk for stroke associated with AF increases steeply from 1.5% at age 50-59 years to 23.5% at age 80-89 years. AF is associated with a doubling of mortality in both sexes, which is decreased to 1.5-1.9-fold after adjusting for associated cardiovascular conditions. Decreased survival associated with AF occurs across a wide range of ages.

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Impact of atrial fibrillation on the risk of death: the Framingham Heart Study.

BACKGROUND: Atrial fibrillation (AF) causes substantial morbidity. It is uncertain whether AF is associated with excess mortality independent of associated cardiac conditions and risk factors. METHODS AND RESULTS: We examined the mortality of subjects 55 to 94 years of age who developed AF during 40 years of follow-up of the original Framingham Heart Study cohort. Of the original 5209 subjects, 296 men and 325 women (mean ages, 74 and 76 years, respectively) developed AF and met eligibility criteria. By pooled logistic regression, after adjustment for age, hypertension, smoking, diabetes, left ventricular hypertrophy, myocardial infarction, congestive heart failure, valvular heart disease, and stroke or transient ischemic attack, AF was associated with an OR for death of 1.5 (95% CI, 1.2 to 1.8) in men and 1.9 (95% CI, 1.5 to 2.2) in women. The risk of mortality conferred by AF did not significantly vary by age. However, there was a significant AF-sex interaction: AF diminished the female advantage in survival. In secondary multivariate analyses, in subjects free of valvular heart disease and preexisting cardiovascular disease, AF remained significantly associated with excess mortality, with about a doubling of mortality in both sexes. CONCLUSIONS: In subjects from the original cohort of the Framingham Heart Study, AF was associated with a 1.5- to 1.9-fold mortality risk after adjustment for the preexisting cardiovascular conditions with which AF was related. The decreased survival seen with AF was present in men and women and across a wide range of ages.

Adult↗

G-estimation of causal effects: isolated systolic hypertension and cardiovascular death in the Framingham Heart Study.

Time-dependent covariates are often both confounders and intermediate variables. In the presence of such covariates, standard approaches for adjustment for confounding are biased. The method of G-estimation allows for appropriate adjustment. Previous studies applying the G-estimation method have addressed effects on all-cause mortality rather than on specific causes of death. In the present study, a method to adjust for censoring by competing risks is presented. The authors used the approach to estimate the causal effect of isolated systolic hypertension on cardiovascular mortality in the Framingham Heart Study, with a 10-year follow-up using data from 1956 to 1970. Arterial rigidity is a major determinant of isolated systolic hypertension and may be a confounder of the relation between isolated systolic hypertension and cardiovascular death. Conversely, isolated systolic hypertension may by itself contribute to stiffening of the vessel wall, and arterial rigidity may therefore also be an intermediate variable in the causal pathway from isolated systolic hypertension to cardiovascular death. While controlling for arterial rigidity and other baseline and time-dependent covariates, isolated systolic hypertension decreased the time to cardiovascular death by 45% (95% confidence interval 3-69).

Adult↗

Prediction of coronary heart disease using risk factor categories.

BACKGROUND: The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions. METHODS AND RESULTS: This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P<.001). Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol and LDL cholesterol categories. The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used. After adjustment for other factors, approximately 28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal (> or =130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol (> or =200 mg/dL) was 27% in men and 34% in women. CONCLUSIONS: Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD.

Adult↗

The worth of controlling plasma lipids.

The worth of controlling plasma lipids is well established; clearly, it is better to prevent atherosclerosis than wait to treat it after it has reached an advanced stage.

Coronary Artery Disease↗

Impact of atrial fibrillation on mortality, stroke, and medical costs.

BACKGROUND: The impact of atrial fibrillation (AF) on mortality, stroke, and medical costs is unknown. METHODS: We conducted a prospective cohort study of hospitalized Medicare patients with AF and 1 other cardiovascular diagnosis (CVD) compared with a matched group without AF (n = 26,753), randomly selected in 6 age-sex strata from 1989 MedPAR files of more than 1 million patients diagnosed as having AF. Stroke rates were also determined in another cohort free of CVD (n = 14,267). Total medical costs after hospitalization were available from a 1991 cohort. Cumulative mortality, stroke rates, and costs following index admission were adjusted by multivariate and proportional hazard regression analyses. RESULTS: Mortality rates were high in individuals with CVD, ranging from 19.0% to 52.1% in 1 year. Adjusted relative mortality risk was approximately 20% higher in patients with AF in all age-sex strata during each of the 3 years studied (P < .05). Incidence of stroke was high in individuals with CVD, 6.2% to 15.4% in 1 year, with and without AF, and was at least 5-fold higher than in individuals without CVD. In those with CVD, stroke rates were approximately 25% higher in women with AF (P < .05) but only 10% higher in men. Adjusted total Medicare spending in 1 year was 8.6- to 22.6-fold greater in men, and 9.8- to 11.2-fold greater in women with AF (P < .05). Second- and third-year costs were increased as well. CONCLUSION: Prevention of AF and treatment of patients with AF and associated CVD may yield benefits in reduced mortality and stroke as well as reducing health care costs.

Age Distribution↗

Glucose intolerance, physical signs of peripheral artery disease, and risk of cardiovascular events: the Framingham Study.

BACKGROUND: Diabetes and peripheral artery disease (PAD) are acknowledged hallmarks of development of atherosclerotic cardiovascular disease (CVD). The prognostic implications of physical indicators of PAD, compared with and in conjunction with glucose intolerance based on population based data, are not well documented. METHODS AND RESULTS: The influence of carotid and femoral bruits and nonpalpable pedal pulses, with and without glucose intolerance, on development of coronary disease (CHD), congestive heart failure (CHF), and stroke (CVA) was investigated in a cohort of 1672 men and 2264 women ages 47 to 99 years participating in the Framingham Study. Cross-sectional pooling yielded 29,063 2-year person-examination units based on the sample of whom 440 men and 484 women had glucose intolerance develop. Over the 26 years of follow-up, 210 men and 199 women had 1 or more of the specified CVD events. Logistic regression analysis was used to estimate age-adjusted odds ratios comparing incidence of CVD events in subjects with glucose intolerance, signs of PAD, or both conditions with those with neither condition. Glucose intolerance was associated with a 2-fold excess occurrence of physical signs of PAD (P< .01 ). Femoral and carotid bruits were generally associated with greater increased risk of CHD, CHF, and CVA than was glucose intolerance alone. Particularly in women, the concomitant presence of bruits augmented the CVD risk of glucose intolerance. Nonpalpable pedal pulses were a stronger risk factor for CVD end points than glucose intolerance; particularly in men and in both sexes, those with both conditions were at substantially greater risk of CVD events than those with either alone. CONCLUSIONS: Physical findings of PAD appear to signify a compromised arterial circulation to the heart and brain as well as the limbs in persons with glucose intolerance. Persons with the combination are candidates at high risk for CHD, CHF, and CVA.

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Overview of atherosclerosis.

Cardiovascular disease is a serious threat to both life and health, accounting for 44% of the nation's mortality and much of its morbidity. Moreover, atherosclerotic cardiovascular disease is a growing problem because of the aging population. Coronary heart disease is the most common cause of lethal atherosclerotic disease, accounting for two thirds of all deaths resulting from heart disease and 70% of all deaths in those older than 75. A 1997 estimate put the economic cost of atherosclerotic cardiovascular disease at a staggering $259 billion. Indications are that atherosclerotic cardiovascular disease is a generalized process that involves the heart, brain, and peripheral arteries. Clinical manifestations tend to coexist, and the presence of one manifestation increases the likelihood of developing others, because major risk factors tend to affect all arterial territories. Also, clinical atherosclerosis in one area may directly predispose the patient to occurrence of atherosclerosis in another vascular territory. Therefore, measures taken to prevent one clinical manifestation of atherosclerosis should prevent the others as well. Multivariate risk profiles can identify persons at risk for atherosclerotic cardiovascular disease and target them for preventive treatment. Primary preventive measures also appear to be applicable to secondary prevention. Meta-analyses of randomized trials of the efficacy of low-dose aspirin and other antiplatelet agents in persons with overt cardiovascular disease have shown reductions of approximately 25% in the incidences of subsequent myocardial infarctions, strokes, and cardiovascular mortality. Comparison of the risk profiles for atherosclerotic cardiovascular disease indicates that correction of any particular set of risk factors or prevention of any cardiovascular disease outcome prevents other atherosclerotic disease outcomes as well. The challenge for all health care professionals is to implement comprehensive preventive measures for those at high risk for initial atherosclerotic events and even more vigorous measures for those who already have the disease.

Adult↗

Sudden coronary death in women.

OBJECTIVES: The objective of this study was to examine prospectively the incidence, predisposing cardiovascular conditions, and risk factors for sudden death in women compared with men. METHODS AND RESULT: The study design was a prospective general population examination of a cohort of 2873 women for development of sudden coronary death in relation to antecedent overt coronary heart disease (CHD), cardiac failure, and risk factors for coronary heart disease. Participants were women aged 30 to 62 years participating in the Framingham Study, receiving routine biennial examinations for risk factors and cardiovascular conditions. Among women monitored over a period of 38 years, there were 750 initial coronary events, of which 94 (12%) were sudden cardiac deaths. Of the 292 CHD fatalities in women, 32% were sudden cardiac deaths and 37% of the women had a history of prior CHD. Sudden death incidence in women logged behind that in men by >10 years. However, above age 75 years, 17% of all CHD events in women were sudden deaths. Sudden death risk in women with CHD was half as high as in men if they had CHD. In both sexes, a myocardial infarction conferred twice the risk of angina. Cardiac failure escalated sudden death risk of women 5-fold but was only one fourth that of men with failure or CHD. Ventricular ectopy increased sudden death risk only in women without prior overt CHD. Except for diabetes, CHD risk factors imposed a lower sudden death risk in women than men. However, even in women, sudden death risk increased over a 17-fold range in relation to their burden of CHD risk factors. CONCLUSIONS: Sudden death is a prominent feature of CHD in women as well as men, particularly in advanced age. A higher fraction of sudden deaths in women than men is unexpected occurring in the absence of prior overt CHD. It is subject to the same risk factors and as predictable in women as in men. However, at any level of multivariate risk, women are less vulnerable to sudden death than men.

Adult↗