Showing papers by "Ralph B. D'Agostino published in 1998"
TL;DR: A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD.
Abstract: 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, ’28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal ($130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ($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. (Circulation. 1998;97:1837-1847.)
9,227 citations
TL;DR: The propensity score, defined as the conditional probability of being treated given the covariates, can be used to balance the variance of covariates in the two groups, and therefore reduce bias as mentioned in this paper.
Abstract: In observational studies, investigators have no control over the treatment assignment. The treated and non-treated (that is, control) groups may have large differences on their observed covariates, and these differences can lead to biased estimates of treatment effects. Even traditional covariance analysis adjustments may be inadequate to eliminate this bias. The propensity score, defined as the conditional probability of being treated given the covariates, can be used to balance the covariates in the two groups, and therefore reduce this bias. In order to estimate the propensity score, one must model the distribution of the treatment indicator variable given the observed covariates. Once estimated the propensity score can be used to reduce bias through matching, stratification (subclassification), regression adjustment, or some combination of all three. In this tutorial we discuss the uses of propensity score methods for bias reduction, give references to the literature and illustrate the uses through applied examples.
4,948 citations
TL;DR: There was a significant AF-sex interaction: AF diminished the female advantage in survival and AF remained significantly associated with excess mortality, with about a doubling of mortality in both sexes in subjects free of valvular heart disease and preexisting cardiovascular disease.
Abstract: 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 survi...
4,390 citations
TL;DR: 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.
Abstract: 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=26753), 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=14267). 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 P P 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.
699 citations
TL;DR: Increased participation in nonvigorous as well as overall and vigorous physical activity was associated with significantly higher insulin sensitivity, and these findings lend further support to current public health recommendations for increased moderate-intensity physical activity on most days.
Abstract: Context.—Exercise training is associated with improved insulin sensitivity (SI), but the potential impact of habitual, nonvigorous activity is uncertain.Objective.—To determine whether habitual, nonvigorous physical activity, as well
as vigorous and overall activity, is associated with better SI.Design.—A multicultural epidemiologic study.Setting.—The Insulin Resistance Atherosclerosis Study, conducted in Oakland,
Calif; Los Angeles, Calif; the San Luis Valley, Colo; and San Antonio, Tex.Participants.—A total of 1467 men and women of African American, Hispanic, and non-Hispanic
white ethnicity, aged 40 to 69 years, with glucose tolerance ranging from
normal to mild non–insulin-dependent diabetes mellitus.Main Outcome Measure.—Insulin sensitivity as measured by an intravenous glucose tolerance
test.Results.—The mean SI for individuals who participated in vigorous
activity 5 or more times per week was 1.59 min−1·µU−1·mL−1·10−4 (95%
confidence interval [CI], 1.39-1.79) compared with 0.90 (95% CI, 0.83-0.97)
for those who rarely or never participated in vigorous activity, after adjusting
for potential confounders (P<.001). When habitual
physical activity (estimated energy expenditure [EEE]) was assessed by 1-year
recall of activities, the correlation coefficient between SI and
total EEE was 0.14 (P<.001). After adjustment
for confounders, vigorous and nonvigorous levels of EEE (metabolic equivalent
levels ≥6.0 and <6.0, respectively) were each positively and independently
associated with SI (P≤.01 for each).
The association was attenuated after adjustment for the potential mediators,
body mass index (a measure of weight in kilograms divided by the square of
the height in meters), and waist-to-hip ratio. Results were similar for subgroups
of sex, ethnicity, and diabetes.Conclusions.—Increased participation in nonvigorous as well as overall and vigorous
physical activity was associated with significantly higher SI.
These findings lend further support to current public health recommendations
for increased moderate-intensity physical activity on most days.
647 citations
01 Jan 1998
TL;DR: This tutorial discusses the uses of propensity score methods for bias reduction, gives references to the literature and illustrates the uses through applied examples.
Abstract: SUMMARY In observational studies, investigators have no control over the treatment assignment. The treated and non-treated (that is, control) groups may have large di⁄erences on their observed covariates, and these di⁄erences can lead to biased estimates of treatment e⁄ects. Even traditional covariance analysis adjustments may be inadequate to eliminate this bias. The propensity score, defined as the conditional probability of being treated given the covariates, can be used to balance the covariates in the two groups, and therefore reduce this bias. In order to estimate the propensity score, one must model the distribution of the treatment indicator variable given the observed covariates. Once estimated the propensity score can be used to reduce bias through matching, stratification (subclassification), regression adjustment, or some combination of all three. In this tutorial we discuss the uses of propensity score methods for bias reduction, give references to the literature and illustrate the uses through applied examples. ( 1998 John Wiley & Sons, Ltd.
500 citations
TL;DR: Sudden death is a prominent feature of CHD in women as well as men, particularly in advanced age, and at any level of multivariate risk, women are less vulnerable to sudden death than men.
392 citations
TL;DR: Stroke is followed by a significant decline in cognitive performance when prestroke and poststroke measurements are compared, and intellectual decline appears to be independent from the presence of depression.
Abstract: Background and Purpose —The causes and characteristics of cognitive decline after stroke are poorly defined, because most studies have relied on the diagnosis of dementia after stroke, without measurement of prestroke cognitive function.
Methods —The Mini-Mental State Examination (MMSE) was used to assess the cognitive performance of 74 subjects from the Framingham Study cohort who had suffered a stroke during a 13-year period. We compared their poststroke cognitive performance with the prestroke MMSE scores collected during their biennial examinations, and their prestroke/poststroke changes in MMSE score were then compared with those of 74 control subjects matched for age and sex. Cases and controls underwent testing for symptoms of depression using the Center for Epidemiologic Studies of Depression (CES-D) scale, and these findings were correlated with their cognitive performance. Changes in cognitive performance in the cases were correlated with the CT-documented characteristics of the stroke.
Results —The cases had a significantly lower mean±SE MMSE score at prestroke baseline (27.28±0.34) than did the control subjects (28.08±0.21), a difference that became more pronounced (23.57±0.92 versus 28.31±0.25; P <.001) after stroke. The poststroke decline in cognitive function in the cases was correlated only with a large, left-sided stroke on CT. The CES-D scores were significantly higher in the cases, but nondepressed cases had significantly lower MMSE scores than nondepressed controls.
Conclusions —Stroke is followed by a significant decline in cognitive performance when prestroke and poststroke measurements are compared. Although depression is more frequent in the stroke patients, their intellectual decline appears to be independent from the presence of depression.
158 citations
TL;DR: The increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes, and the relationship between glucose tolerance category and IMT was similar in men and women.
Abstract: OBJECTIVE: To assess whether people with impaired glucose tolerance (IGT) exhibit an increased risk of atherosclerosis as measured by the thickness of the carotid artery. RESEARCH DESIGN AND METHODS: We examined the relationship between glucose tolerance status and subclinical atherosclerosis in the Insulin Resistance Atherosclerosis Study (IRAS). The IRAS is an epidemiological study of 1,625 Hispanic, African-American, and white men and women, with approximately equal numbers of subjects with normal glucose tolerance (NGT), IGT, and type 2 diabetes as assessed by an oral glucose tolerance test. Half of those with diabetes were previously unaware of their condition and were defined as having new diabetes. Persons using insulin were excluded. The intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA) was measured as an index of subclinical atherosclerosis using B-mode ultrasonography. RESULTS: Adjusted for demographics and smoking, CCA-IMT increased most notably at the level of established diabetes (802, 822, 831, and 896 microm for NGT, IGT, new diabetes, and established diabetes, respectively). Adjustment for coronary heart disease (CHD) risk factors, which tended to worsen across glucose tolerance category, further minimized the slightly graded relationship. The relationship with the ICA-IMT was steeper and again suggested that the increased wall thickness is associated with diabetes, not with IGT. The relationship between glucose tolerance category and IMT was similar in men and women. CONCLUSIONS: We observed considerably greater IMT among persons with established diabetes but no significant increase in persons with IGT. These data suggest that the increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes.
151 citations
TL;DR: Abdominal decompression in patients with increased intra-abdominal pressure improves preload, pulmonary function, and visceral perfusion, which makes the PAOP an unreliable index of preload in these patients.
Abstract: ObjectiveIncreased intra-abdominal pressure (IAP) compromises cardiopulmonary function and visceral perfusion. Our goal was to characterize acute changes in these subsystems associated with operative abdominal decompression.Patient PopulationA series of 11 consecutive injured patients monitored with
113 citations
TL;DR: The association between proinsulin and IMT, while weak, appears to be stronger than the association between insulin andIMT, and studies of the insulin resistance syndrome and atherosclerosis that use insulin as a surrogate for insulin resistance should consider the use of specific insulin assays.
Abstract: Background and Purpose—Insulin resistance and hyperinsulinemia have been associated with atherosclerosis. Recent attention has focused on the possible role of proinsulin because most radioimmunoassays for insulin cross-react with proinsulin. Therefore, it is not known which of the two, insulin per se or proinsulin, is more strongly related to atherosclerosis. Methods—We examined the relation between fasting proinsulin, fasting split proinsulin, fasting and 2-hour insulin (after oral glucose load), and intima-media wall thickness (IMT) in the common carotid artery (CCA) and internal carotid artery (ICA) in 985 nondiabetic subjects from the Insulin Resistance Atherosclerosis Study, a multiethnic study of insulin resistance and atherosclerosis. Results—In the overall population, a weak but significant relation between proinsulin and CCA IMT was observed (r=0.07, P=0.029). However, the relation between proinsulin and IMT was stronger in Hispanics and non-Hispanic whites than in African Americans. In non-Hispa...
TL;DR: It is suggested that BMI, a potentially modifiable characteristic, is associated with the development of cortical and posterior subcapsular lens opacities.
TL;DR: A method to adjust for censoring by competing risks is presented and isolated systolic hypertension decreased the time to cardiovascular death by 45% (95% confidence interval 3-69) while controlling for arterial rigidity and other baseline and time-dependent covariates.
Abstract: 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).
TL;DR: In the Framingham cohort, 20-plus-year stroke survivors showed greater mortality than age- and sex-matched control subjects; functionally, however, the groups were very similar and in general quite independent.
Abstract: Background and Purpose—We examined the 20-or-more-year survival and functional levels of 148 stroke survivors and 148 age- and sex-matched control subjects from the Framingham Study Cohort, whom we originally studied in 1972–1974 to ascertain the survival and disability status of stroke survivors compared with that of controls. Methods—This long-term evaluation was done with use of data from the 1993–1995 Framingham Study Cohort Examination 23 on the 10 stroke survivors and 20 control subjects still living to identify and compare the host characteristics and functional status of each group. The survival curves for both stroke survivors and controls were derived from the ongoing Framingham Study database. Results—Twenty-plus-year stroke survivors experienced a greater mortality than age- and sex-matched controls (92.5% and 81%, respectively). The slopes of the two survival curves were essentially the same. Functional status (eg, walking and independence in activities of daily living) of stroke survivors, h...
TL;DR: A model of the costs and consequences of lipid-regulating therapy and the introduction of atorvastatin improved the cost-effectiveness of HMG-CoA reductase inhibition in primary and secondary prevention of coronary heart disease.
Abstract: Currently, 6 hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are marketed in the United States (US). Given the wide variation in the prices and efficacy of statins, formal cost-effectiveness analysis may improve drug selection decisions. To assess the cost-effectiveness of statin therapy in primary and secondary prevention of coronary heart disease, we developed a model of the costs and consequences of lipid-regulating therapy and estimated the incremental cost-effectiveness of 5 statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) at usual starting doses versus no therapy. Drug effects on serum lipids were assessed using data approved by the US Food and Drug Administration for product labeling. Annual risks of coronary event occurrence were estimated using Framingham Heart Study coronary risk equations developed for use in this model. Current estimates of direct medical costs of coronary heart disease were used to assign costs to health states and acute coronary events. Main outcome measurements were net cost (statin therapy minus savings in coronary heart disease treatment), gain in life expectancy, and cost per life-year saved. The maximum gain in life expectancy was achieved with atorvastatin, which also had a lower net cost than lovastatin, pravastatin, and simvastatin. Compared with fluvastatin, atorvastatin’s greater effectiveness is attained at a lower cost per life-year saved. The cost-effectiveness of HMG-CoA reductase inhibition in primary and secondary prevention of coronary heart disease has been improved with the introduction of atorvastatin.
TL;DR: It is suggested that current and former use of HRT is associated with reduced atherosclerosis and that women with type 2 diabetes may receive the same benefit from HRI as women without diabetes.
Abstract: OBJECTIVE: Atherosclerosis is the major underlying cause of death for women with type 2 diabetes. We examined the relationship between use of postmenopausal hormone replacement therapy(HRT) and subclinical atherosclerosis among women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was conducted among 623 postmenopausal women in the Insulin Resistance Atherosclerosis Study (IRAS). Current users of HRT, n = 200, were compared with 104 former users and 319 never users. Intimal-medial wall thicknesses (IMTs) of the common carotid (CCA) and internal carotid (ICA) arteries were used as measures of atherosclerosis. RESULTS: Significant differences between HRT user groups were noted for certain demographic, socioeconomic, and lifestyle factors. After adjustment for these and other coronary heart disease risk factors, current users had a 69 microm thinner ICA IMT than never users (P = 0.06). Former users had a 96 pm thinner ICA IMT than never users (P = 0.03). No significant difference was observed for the CCA. Although women with type 2 diabetes had thicker carotid IMT than women without diabetes, the association between HRT use and thinner IMT was similar in both groups. The difference between current and never users was attenuated by adjustment for HDL and LDL cholesterol. Neither duration of HRT use nor HRT regimen was associated with IMT in either artery. CONCLUSIONS: This analysis suggests that current and former use of HRT is associated with reduced atherosclerosis and that women with type 2 diabetes may receive the same benefit from HRI as women without diabetes.
TL;DR: The results of this investigation show that there is a strong association between atherosclerosis and hypertensive ESRD in older white patients and that a primary renal microvascular disorder may lead to both hypertension and progressive renal insufficiency.
TL;DR: It is necessary to select patients suitable for vaginal or laparoscopic mesh placement for intranasal administration based on prior history and once they provide informed consent for surgery.
Abstract: Clinical Pharmacology & Therapeutics (1998) 64, 579–596; doi:
01 Jan 1998
TL;DR: The population prevalence of risk factor clustering in the presence of hypertension has not been determined and how often coronary events result from hypertension occurring in conjunction with such risk factor clusters is not estimated.
Abstract: A tendency for hypertension to cluster with other risk factors has long been noted in the Framingham Heart Study and elsewhere [1,2]. A metabolic or physiologic basis for this clustering has been postulated [3–5]. Many of the risk factors that tend to cluster with elevated blood pressure also predict its occurrence and greatly influence its impact on the occurrence of atherosclerotic cardiovascular sequelae [1,2]. The population prevalence of risk factor clustering in the presence of hypertension has not been determined. Nor has it been estimated how often coronary events result from hypertension occurring in conjunction with such risk factor clusters.