Showing papers by "Ralph B. D'Agostino published in 1993"
TL;DR: Blood pressure levels and chronicity of hypertension were inversely related to the composite score and measures of attention and memory, and Hypertension-associated pathogenic processes may cause mild cognitive impairment.
Abstract: It was hypothesized that blood pressure would be inversely related to cognitive functioning, if unconfounded with antihypertensive medication and measured over many occasions prior to neuropsychological testing. For stroke-free Framingham Study participants aged 55-88 years (n = 1,702), blood pressure levels were averaged over five biennial examinations (1956-1964) when few hypertensives were being treated, and examined in relation to neuropsychological tests administered between 1976 and 1978. With age, education, occupation, cigarette smoking, alcohol consumption, and gender controlled, blood pressure levels and chronicity of hypertension were inversely related to the composite score and measures of attention and memory. This was true for the full sample, for a subsample untreated during blood pressure measurement (n = 1,485), and for a subsample untreated throughout the entire study period (n = 1,038). For example, decline per 10 mmHg increment in blood pressure ranged from -0.04 to -0.07 standard score units (z) for the composite score. A negative finding previously was most likely due to blood pressure measurement concurrently with neuropsychological testing, or too few measurements. Hypertension-associated pathogenic processes may cause mild cognitive impairment, but other mechanisms need to be considered.
647 citations
TL;DR: Exclusion of outcomes in the first 2 or 4 years after measurement of heart rate did not materially change the results, which suggests that rapid heart is not merely an indicator of preexisting illness and may be an independent risk factor for cardiovascular death in persons with hypertension.
616 citations
TL;DR: In a general population sample, incidence of dementia and of probable AD did not level off with age and was not different in men and women.
Abstract: objective: To determine the incidence of dementia and Alzheimer9s disease (AD) in a general population sample. Background: Utilizing subjects in the Framingham Study cohort determined to be free of dementia in 1976 to 1978, or on biennial examination 17 in 1982, all new cases of dementia arising in this cohort over a maximum of 10 years of follow-up were ascertained. Methods: On biennial examination 14/15, a screening neuropsychologic examination was administered to 2,117 subjects, and cases of probable prevalent dementia were identified. Beginning on examination 17 and on all successive biennial examinations, a Mini-Mental State Examination was administered. Subjects previously free of dementia and falling below age-education levels were evaluated by a neurologist and neuropsychologist to determine if dementia was present and to ascertain the dementia type using standard criteria. Results: Five-year incidence of dementia increased with age, doubling in successive 5-year age groups. Dementia incidence rose from 7.0 per 1,000 at ages 65 to 69 to 118.0 per 1,000 at ages 85 to 89 for men and women combined. Incidence of probable AD also doubled with successive quinquennia from 3.5 at ages 65 to 69 to 72.8 per 1,000 at ages 85 to 89 years. Incidence of dementia and of probable AD did not level off with age and was not different in men and women. Conclusions: In a general population sample, we determined incidence of dementia and of probable AD and will use these incident cases for study of precursors and natural history in this elderly cohort, which has been under close surveillance for over 40 years.
482 citations
TL;DR: The rate of missed acute myocardial infarction in the emergency department was only 1.9%, but death or potentially lethal complications occurred in 25% of missed AMI patients, and another 25% might have been prevented had patients who were recognized to have ischemic heart disease by the physician in the ED been admitted.
459 citations
TL;DR: Low-frequency hearing was related to cardiovascular disease events in both genders but more in the women, and five groups of risk factors were studied: hypertension and blood pressure; diabetes, glucose intolerance, and blood glucose level; smoking status and number of pack-years of cigarettes; relative weight; and serum lipid levels.
Abstract: • Hearing loss with age (presbycusis) is a substantial problem for the elderly. To investigate the possible relation of presbycusis to cardiovascular disease (CVD), the hearing status of a cohort of 1662 elderly men and women was determined and compared with their 30-year prevalence of cardiovascular disease. Age-adjusted multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) to describe the relation of hearing to cardiovascular disease events, cardiovascular disease risk factors, and both events and risk factors separately for the 676 men and for the 996 women. Cardiovascular disease events were the sum of coronary heart disease, stroke, and intermittent claudication. Five groups of risk factors were studied: hypertension and blood pressure; diabetes, glucose intolerance, and blood glucose level; smoking status and number of pack-years of cigarettes; relative weight; and serum lipid levels, including cholesterol, triglycerides, and lipoprotein fractions. Low-frequency hearing (low pure-tone average, 0.25 to 1.0 kHz) was related to cardiovascular disease events in both genders but more in the women. For women, the OR of having any cardiovascular disease event for a low pure-tone average of 40 dB hearing level was 3.06 (95% CI, 1.84 to 5.10); for a high pure-tone average (average of 4 to 8 kHz) of 40-dB hearing level, the OR for any cardiovascular disease event was 1.75 (95% CI, 1.28 to 2.40). In men with a low pure tone average of 40-dB hearing level, the OR for stroke was 3.46 (95% CI, 1.60 to 7.45) and for coronary heart disease the OR was 1.68 (95% CI, 1.10 to 2.57). In the women, a low pure-tone average of 40 dB hearing level was associated with an OR for coronary heart disease of 2.14 (95% CI, 1.21 to 3.79) and for intermittent claudication the OR was 4.39 (95% CI, 2.02 to 9.55). Adding cardiovascular disease risk factors to the logistic regression analyses did not affect the relationships. Of the suprathreshold tests, the synthetic sentence identification test showed a relation to heart attack or strokes in women. Of the risk factors, hypertension and systolic blood pressure were related to hearing thresholds in both men and women, and blood glucose level was related to low pure-tone average in the women. High-density lipoprotein levels were inversely related to low-frequency hearing thresholds only in the women. There is a small but statistically significant association of cardiovascular disease and hearing status in the elderly that is greater for women than men and more in the low than the high frequencies. Low-frequency presbycusis is classically associated with microvascular disease leading to atrophy of the stria vascularis. Further studies of the relation of vascular disease and hearing loss in the elderly are warranted to clarify the pathophysiologic mechanisms. (Arch Otolaryngol Head Neck Surg. 1993;119:156-161)
457 citations
TL;DR: Having six or more pregnancies was associated with a small but consistent increase in the risk of coronary heart disease and cardiovascular disease, and some other unmeasured factor accounts for the increase in risk requires further investigation.
Abstract: Background Whether increasing parity or gravidity is a risk factor for coronary heart disease has been debated, but the question remains unresolved. Methods We tested the association between the number of pregnancies and a variety of cardiovascular end points in two groups of women who had completed childbearing. One group comprised 2357 women who were followed for 28 years through the Framingham Heart Study, and the other 2533 women followed for at least 12 years through the first National Health and Nutrition Examination Survey National Epidemiologic Follow-up Study (NHEFS). Results The rates of coronary heart disease were higher among multigravid women than among women who had never been pregnant, in both the Framingham Heart Study and the NHEFS, but in both studies, the higher rates were statistically significant only in women with six or more pregnancies. For the women in the Framingham Study, the rate ratio adjusted for age and educational level in the group with six or more pregnancies (as compared...
289 citations
TL;DR: Among middle-aged men, but not women, anxiety levels are predictive of later incidence of hypertension, according to the results of the Framingham Heart Study.
Abstract: Objective. —To test the hypothesis that heightened anxiety, heightened anger intensity, and suppressed expression of anger increase the risk of hypertension, using the Framingham Heart Study. Design. —A cohort of men and women without evidence of hypertension at baseline were followed up for 18 to 20 years. Baseline measures of anxiety (tension), anger symptoms, and expression of anger (anger-in and anger-out) were taken, along with biological and behavioral predictors of hypertension (initial systolic blood pressure, heart rate, relative weight, age, hematocrit, alcohol intake, smoking, education, and glucose intolerance). Participants. —A total of 1123 initially normotensive persons (497 men, 626 women) were included. Analyses were stratified by age (45 to 59 or ≥60 years) and gender. Main Outcome Measures. —Hypertension was defined as either taking medication for hypertension or blood pressures higher than 160/95 mm Hg at a biennial examination. Results. —In univariate analyses, middle-aged men who went on to develop hypertension had greater baseline anxiety levels than men who remained normotensive ( P =.04). Older hypertensive men had fewer anger symptoms at baseline ( P =.04) and were less likely to hold their anger in ( P =.01) than normotensives. In multivariate Cox regression analysis including biological predictors, anxiety remained an independent predictor of hypertension in middle-aged men ( P =.02). Among older men, anger symptoms and anger-in did not remain significant predictors in the multivariate analysis. Further analysis showed that only middle-aged men with very high levels of anxiety were at increased risk (relative risk, 2.19; 95% confidence interval, 1.22 to 3.94). No psychological variable predicted hypertension in middle-aged or older women in either univariate or multivariate analyses. Conclusions. —The results indicate that among middle-aged men, but not women, anxiety levels are predictive of later incidence of hypertension. ( JAMA . 1993;270:2439-2443)
247 citations
TL;DR: The data confirm and extend the evidence of the detrimental influence of cigarette smoking on health, which was observed that cigarette smoking was the prime determinant of chronic cough, and reduced both forced vital capacity and the 1-second forced expiratory volume.
189 citations
TL;DR: This paper compares the performance of logistic regression to decision-tree induction in classifying patients as having acute cardiac ischemia using the database of 5773 patients originally used to develop the logistic-regression tool and test it prospectively.
145 citations
TL;DR: This report defined cardiovascular disease as coronary heart disease, stroke, intermittent claudication, and congestive heart failure as well as other clinically diagnosed diseases including mitral or aortic valve disease, arthritis, urinary disease, neurologic disease, and other vascular disease.
Abstract: Objective: To identify the benefits and adverse effects of weight loss. Design: Longitudinal, epidemiologic study in a defined population. Participants: Men and women (n=2500) who were between 35 and 54 years old at baseline, followed for 20 years in FraminBham, Massachusetts. Measurements: Height, weight, lipid levels, blood pressure, smoking status, diet, physical activity, prevalent and incident cardlovascular disease, diabetes, other diseases, and mortality rate were assessed. Results: Compared with those whose body mass index (BMI) or weight changed least, men and women who lost weight during a 10-year period were older, heavier, and had higher blood pressures and cholesterol levels initially but had the smallest gains in blood pressure and cholesterol levels
144 citations
TL;DR: Heart rate was a major determinant of all 5 Doppler indexes of diastolic filling; heart rate was inversely associated with peak velocity E, E, and time velocity integral E/A, and was directly associated withpeak velocity A and atrial filling fraction.
Abstract: The relations of heart rate and PR interval to Doppler-derived diastolic indexes were examined in 260 men (mean age 75 years) and 462 women (mean age 76 years) from the Framingham Heart Study. Subjects receiving any antihypertensive or cardiac medications were excluded from eligibility; those with mitral stenosis or prosthesis, pacemaker, atrial fibrillation, arrhythmia, left bundle branch block, congestive heart failure, previous myocardial infarction, and technically inadequate Doppler study were also excluded. Peak velocity of early (E) and late (A) diastolic left ventricular (LV) filling, ratio of peak velocities E/A, ratio of time velocity integrals E/A, and atrial filling fraction were studied by multivariable analyses adjusting for age, sex, blood pressure, heart rate and PR interval. Heart rate was a major determinant of all 5 Doppler indexes of diastolic filling; heart rate was inversely associated with peak velocity E, E/A, and time velocity integral E/A, and was directly associated with peak velocity A and atrial filling fraction. PR interval was inversely associated with time velocity integral E/A (p < 0.01) and directly associated with atrial filling fraction. The results were largely unaltered after further adjustment for LV wall thickness, LV end-diastolic diameter and left atrial diameter (in addition to age, sex and blood pressure). Heart rate and PR interval are independent contributors to Doppler-assessed LV diastolic filling in the elderly. The atrial contribution to LV filling depends on its timing in the cardiac cycle and on heart rate. Failure to account for heart rate and PR interval may lead to inappropriate assessment of Doppler diastolic filling.
TL;DR: There was a significant decline in stroke severity, but incidence of infarction fell only in women, and the decline in total case-fatality rate occurred only in men, resulting largely from an increased incidence of isolated TIAs.
TL;DR: Lovastatin was generally effective in improving the serum lipids of hypercholesterolemic hypertensive patients regardless of the type of antihypertensive medications received (including diuretics and beta blockers).
Abstract: A previously published study reported on an open-label, multicenter study of the efficacy and tolerability of lovastatin in the management of nonfamilial primary hypercholesterolemia. In the present report the results from the 213 hypercholesterolemic patients with systemic hypertension are presented. At baseline mean ± SD of total serum cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, and the ratio of total serum cholesterol to HDL cholesterol were 268 ± 24, 189 ± 22 and 43 ± 10 mg/dl and 6.6 ± 1.6, respectively. Of the 213 hypertensive patients only 24 were not receiving antihypertensive or related cardiac medication. Baseline mean systolic and diastolic blood pressures were 140 ± 20 and 84 ± 9 mm Hg, respectively. Within 1 month of lovastatin therapy the observed significant reductions in total serum cholesterol, low-density lipoprotein cholesterol and the ratio of total to HDL cholesterol were 19, 27 and 24%, respectively. HDL cholesterol was increased by 6%. Diastolic blood pressure did not change significantly during this 1-month period. The 1-month lipid results were maintained over the full 6 months of the study. The dosage of lovastatin was 20 mg/day for the first month of therapy and could subsequently be adjusted to response, up to a maximum of 80 mg/day. Again, without changes in diastolic blood pressure, lovastatin was generally effective in improving the serum lipids of hypercholesterolemic hypertensive patients regardless of the type of antihypertensive medications received (including diuretics and β blockers). Lovastatin was generally well tolerated.
TL;DR: The average level of risk for cardiovascular disease in the elderly is associated with Medicare claims costs that are 19% higher than those for persons with no elevated risk, equivalent to an average of $371 per elderly beneficiary or $9.3 billion per year in Medicare expenditures.
TL;DR: There was little evidence for a relationship between total serum cholesterol and dietary fat intake; whereas a marginally significant direct association was found with total fat in post menopausal women, total and plant fat and cholesterol were inversely associated, and only cholesterol was significant in premenopausal women.
TL;DR: This paper reviews briefly the various multiple comparison techniques available and discusses strategies for aiding investigators in applying these in settings typical in clinical trials (eg, confirmatory studies with placebo or positive controls or both).
Abstract: In many clinical trials there are multiple treatments under consideration which require multiple comparisons. Investigators are faced with the problems of Type I error control (experimentwise, familywise, or comparisonwise), maintenance of reasonable power for the study, and the selection of appropriate multiple comparison techniques to achieve these. This paper reviews briefly the various multiple comparison techniques available and discusses strategies for aiding investigators in applying these in settings typical in clinical trials (eg, confirmatory studies with placebo or positive controls or both). In a confirmatory setting, the treatment comparisons can often be divided into sets or families. Appropriate multiple comparison techniques, possibly differing across families, can then be applied within and across these. Study objectives can be better achieved by employing the strategies suggested.
TL;DR: The age and education association with the MMSE is able to be confirmed and two acknowledged limitations of the study are addressed.
Abstract: To the Editor. —Crum et al 1 report age- and education-specific norms on the Mini-Mental State Examination (MMSE) 2 based on a large community sample. Similar data are also available from the Framingham Study that provide further insight into the usefulness of the MMSE. Since 1982 the cohort participating in the Framingham Study has been screened for dementia with the MMSE as part of every biennial medical examination. Individuals suspected of being cognitively impaired have been further evaluated by a neurologist and neuropsychologist. A panel of two neurologists and a neuropsychologist made a final determination about the presence and subtype of dementia. We are able to confirm the age and education association with the MMSE and also address two acknowledged limitations of the study by Crum et al. Since a clinical diagnosis of dementia was made, our data allow us to comment on the performance of individuals with dementia and
TL;DR: This work proposes a technique for reducing a set of longitudinal data into four common summary statistics together with time, and derives them mathematically, thus justifying their use, which simplifies the subsequent analyses, and improves the interpretation of the results.
Abstract: Many studies collect longitudinal data but do not use them efficiently. We propose a technique for reducing a set of longitudinal data into four common summary statistics together with time. These statistics can be used in place of the raw data in further analyses, for example in a regression analysis. Instead of arbitrarily choosing the summary statistics, we derive them mathematically, thus justifying their use. This simplifies the subsequent analyses, and also improves the interpretation of the results. An example from the Framingham Heart Study illustrates the procedure.
TL;DR: Use of the stroke risk function enables the treating physician to determine the conditional probability of stroke in the individual patient and has been shown to be useful in predicting stroke recurrence and death.
Abstract: Identification of precursors of stroke is the first step in instituting a program for disease prevention. These precursors include risk factors: hypertension, diabetes, cigarette smoking, left ventricular hypertrophy by ECG, as well as predisposing diseases: coronary heart disease, cardiac failure and atrial fibrillation. Two preventive approaches may be taken: one is a public health approach whereby the entire population is informed of the dangers of certain highly prevalent risk factors for disease: antismoking and hypertension awareness campaigns and the current United States National Cholesterol Education Program are examples of this approach; the other is more focused and requires treatment by physicians of individuals found to be at increased risk of stroke. For the public health approach to be feasible, the risk factor under attack needs to be prevalent in the population and potent as a disease promotor. For precursors occurring infrequently in the population but with a high relative risk, or where the multiple borderline levels of risk factors are present, treatment of high risk individuals is in order. Use of the stroke risk function enables the treating physician to determine the conditional probability of stroke in the individual patient. The individual''s risk of stroke can be compared to that of an average person of the same age and sex and has been shown to be useful in predicting stroke recurrence and death.
TL;DR: In this article, the authors present a review of Mathematical Statistics for Clinical Trial Planning under Proportional Hazards: Putting It All Together, where the authors use the Logrank Test when Survival is Exponential.
Abstract: HOW TO USE THE SAMPLE SIZE PROGRAM. Identification of Parameters. DESIGN AND ANALYSIS OF RANDOMIZED CLINICAL TRIALS. Formulation of the Therapeutic Question. One-Sided vs. Two-Sided Question. Design of the Clinical Trial. Statistical Considerations. Conduct of the Trial. Analysis and Reporting of the Trial. Critical Elements. Binomial Comparison. Kaplan-Meier Comparison (Large Sample). Logrank Test. DERIVATION OF THE STATISTICAL RESULTS. Derivation of the Large Sample Distribution of the Logrank Statistic. Derivation of the Large Sample Distribution of the Kaplan-Meier Statistic. Difference between Kaplan-Meier Curves. Exponential Survival. Applications of the Logrank Test When Survival is Exponential. Exponential Survival with a Poisson Accrual Process. Extension to the Two-Sample Problem. Exponential Survival with \"Up-Front\" Accrual. Proportional Hazard Models and the Exponential Distribution. Consideration in Planning a Trial Under Proportional Hazards: Putting It All Together. Losses to Follow-Up and Sample Size Adjustment. Interpretation of the Program. Multi-Treatment Trials. Stratified Logrank Test. Intuitive Justification Why the Logrank Test and Kaplan-Meier Estimation for Actual Accrual Process Behave in the Limit in the Same Way as the Fixed Binomial Assumption. Alternate Standard Error for the Kaplan-Meier Estimator. Connection between Kaplan-Meier and Binomial. FIGURES. APPENDIX I: A Review of Mathematical Statistics. Expected Value of a Function of a Random Vector. Special Distributions.