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R B D'Agostino

Publications and source records attributed to R B D'Agostino.

At least 19 recordsLinked to original sources
PubMed2005

Abdominal obesity predicts declining insulin sensitivity in non-obese normoglycaemics: the Insulin Resistance Atherosclerosis Study (IRAS).

AIM: Cross-sectional studies have demonstrated a relationship between obesity and insulin sensitivity (S(I)); however, there is a lack of evidence from longitudinal studies. METHODS: The Insulin Resistance Atherosclerosis Study (IRAS) estimated S(I) (x10(-4)/min.microU/ml) directly using a frequently sampled intravenous glucose tolerance test with minimal model analysis in 504 normoglycaemic subjects. Partial correlation coefficients (r) were calculated to compare the relationship of change in S(I) from baseline to 5 years later (DeltaS(I)) with baseline waist circumference (waist) as a measure of abdominal obesity and body mass index (BMI) as a measure of overall obesity. Mean DeltaS(I) was -1.06 (SD = 1.85). RESULTS: Higher baseline waist (r = -0.16; p = 0.0005), but not BMI (r = -0.005; p = 0.91), was associated with (-) DeltaS(I) in models including sex, ethnicity, clinical centre and baseline S(I), BMI, waist, age and physical activity. The waist-DeltaS(I) relationship differed across the levels of baseline BMI, being significant only in normal weight (r = -0.21) and overweight subjects (r = -0.16), but not in obese subjects. DeltaS(I) was correlated with a 5-year change in either obesity measure (Deltawaist: r = -0.22 and DeltaBMI: r = -0.20; p = 0.0001). CONCLUSIONS: Among non-diabetics, waist circumference was a strong predictor of declining S(I) among lean subjects, a modest predictor among overweight subjects, but was not predictive among obese individuals. Waist circumference should be considered, in addition to BMI, when identifying individuals at high risk of diabetes or the insulin resistance syndrome.

Abdomen↗
PubMed2004

Stroke risk profile, brain volume, and cognitive function: the Framingham Offspring Study.

BACKGROUND: Mid-life stroke risk factors have been related to late-life cognitive impairment. This association may result not only from clinical strokes but also from subclinical brain injury, such as a global atrophy demonstrable on quantitative brain MRI. METHODS: The authors evaluated the community-based cohort of Framingham Offspring Study participants. A total of 1,841 subjects (mean age, 62 years; 857 men, 984 women) who underwent quantitative MRI and cognitive testing between 1999 and 2001 and were free of clinical stroke and dementia constituted our study sample. The authors used age- and sex-adjusted linear regression models to relate previous (1991 to 1995) and recent (1998 to 2001) Framingham Stroke Risk Profile (FSRP) scores to the total cerebral brain volume ratio (TCBVr) on follow-up MRI, and further to relate the TCBVr with education-adjusted scores on neuropsychological tests administered at the time of imaging. RESULTS: There was an inverse association between FSRP scores and TCBVr. The TCBVr also showed a significant positive association with performance on tests of attention (Trails A), executive function (Trails B), and visuospatial function (visual reproduction, Hooper visual organization), but not with performance on tests of verbal memory or naming. CONCLUSIONS: The Framingham Stroke Risk Profile may identify subjects with smaller brains and poorer cognitive function among stroke- and dementia-free subjects, reinforcing the importance of managing stroke risk factors.

Adult↗
PubMed2004

New developments in medical clinical trials.

This paper reviews several new developments and long-standing good practices for conducting clinical trials. Discussion starts with the need for clear statements of study objectives, proceeds to clarify target and sample population, and elaborates on primary vs. secondary variables with the need for alpha adjustment in the presence of multiple outcomes. Here we also review the issue of surrogate endpoints. Study design issues--including blinding, randomization, and multicenter studies--come next. Then we discuss the current trend of the replacement of placebo-controlled trials by active controlled non-inferiority trials, the increasing use of Independent Data Monitoring Committees, the prominence of analysis on Intention-to-Treat samples, and the importance of imputation of missing data. We close with a brief discussion of the unit of analysis, the role of newer statistical analysis methods, safety issues, subset analysis, and, most importantly, clinical significance.

Clinical Trials Data Monitoring Committees↗
PubMed2003

Robustness and power of analysis of covariance applied to ordinal scaled data as arising in randomized controlled trials.

In clinical trials comparing two treatments, ordinal scales of three, four or five points are often used to assess severity, both prior to and after treatment. Analysis of covariance is an attractive technique, however, the data clearly violate the normality assumption and in the presence of small samples, and large sample theory may not apply. The robustness and power of various versions of parametric analysis of covariance applied to small samples of ordinal scaled data are investigated through computer simulation. Subjects are randomized to one of two competing treatments and the pre-treatment, or baseline, assessment is used as the covariate. We compare two parametric analysis of covariance tests that vary according to the treatment of the homogeneity of regressions slopes and the two independent samples t-test on difference scores. Under the null hypothesis of no difference in adjusted treatment means, we estimated actual significance levels by comparing observed test statistics to appropriate critical values from the F- and t-distributions for nominal significance levels of 0.10, 0.05, 0.02 and 0.01. We estimated power by similar comparisons under various alternative hypotheses. The model which assumes homogeneous slopes and the t-test on difference scores were robust in the presence of three, four and five point ordinal scales. The hierarchical approach which first tests for homogeneity of regression slopes and then fits separate slopes if there is significant non-homogeneity produced significance levels that exceeded the nominal levels especially when the sample sizes were small. The model which assumes homogeneous regression slopes produced the highest power among competing tests for all of the configurations investigated. The t-test on difference scores also produced good power in the presence of small samples.

Analysis of Variance↗
PubMed2003

Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study.

OBJECTIVE: To determine the independent effects of obesity and hypertension on cognitive functioning. METHODS: Using a prospective design, male (n=551) and female (n=872) participants of the Framingham Heart Study were classified by presence or absence of obesity and hypertension based on data collected over an 18-y surveillance period. All subjects were free from dementia, stroke, and clinically diagnosed cardiovascular disease up to the time of cognitive testing. Statistical models were adjusted for age, education, occupation, cigarette smoking, alcohol consumption, total cholesterol, and a diagnosis of type II diabetes. Body mass index status (nonobese or obese) and blood pressure status (normotensive or hypertensive) were then related to cognitive performance (learning, memory, executive functioning, and abstract reasoning) on tests administered 4-6 y later. RESULTS: Adverse effects of obesity and hypertension on cognitive performance were observed for men only. Obese and hypertensive men performed more poorly than men classified as either obese or hypertensive, and the best performance was observed in nonobese, normotensive men. CONCLUSIONS: The adverse effects of obesity and hypertension in men are independent and cumulative with respect to cognitive deficit.

Aged↗
PubMed2002

The internal validity of a dietary pattern analysis. The Framingham Nutrition Studies.

STUDY OBJECTIVES: To examine the internal validity of a dietary pattern analysis and its ability to discriminate clusters of people with similar dietary patterns using independently assessed nutrient intakes and heart disease risk factors. DESIGN AND PARTICIPANTS: Population based study characterising dietary patterns using cluster analysis applied to data from the semiquantitative Framingham food frequency questionnaire collected from 1942 women ages 18-76 years, between 1984-88. SETTING: Framingham, Massachusetts. MAIN RESULTS: Of 1942 women included in the cluster analysis, 1828 (94%) were assigned to one of the five dietary pattern clusters: Heart Healthy, Light Eating, Wine and Moderate Eating, High Fat, and Empty Calorie. Dietary patterns differed substantially in terms of individual nutrient intakes, overall dietary risk, heart disease risk factors, and predicted heart disease risk. Women in the Heart Healthy cluster had the most nutrient dense eating pattern, the lowest level of dietary risk, more favourable risk factor levels, and the lowest probability of developing heart disease. Those in the Empty Calorie cluster had a less nutritious dietary pattern, the greatest level of dietary risk, a heavier burden of heart disease risk factors, and a relatively higher probability of developing heart disease. Cluster reproducibility using discriminant analysis showed that 80% of the sample was correctly classified. The cluster technique was highly sensitive and specific (75% to 100%). CONCLUSIONS: These findings support the internal validity of a dietary pattern analysis for characterising dietary exposures in epidemiological research. The authors encourage other researchers to explore this technique when investigating relations between nutrition, health, and disease.

Adolescent↗
PubMed2001

Predicting mortality in nursing home residents with lower respiratory tract infection: The Missouri LRI Study.

CONTEXT: Lower respiratory tract infection (LRI) is a leading cause of mortality and hospitalization in nursing home residents. Treatment decisions may be aided by a clinical prediction rule that identifies residents at low and high risk of mortality. OBJECTIVE: To identify patient characteristics predictive of 30-day mortality in nursing home residents with an LRI. DESIGN, SETTING, AND PATIENTS: Prospective cohort study of 1406 episodes of LRI in 1044 residents of 36 nursing homes in central Missouri and the St Louis, Mo, area between August 15, 1995, and September 30, 1998. MAIN OUTCOME MEASURE: Thirty-day all-cause mortality. RESULTS: Thirty-day mortality was 14.7% (n = 207). In a logistic analysis, using generalized estimating equations to adjust for clustering, we developed an 8-variable model to predict 30-day mortality, including serum urea nitrogen, white blood cell count, body mass index, pulse rate, activities of daily living status, absolute lymphocyte count of less than 800/microL (0.8 x 10(9)/L), male sex, and deterioration in mood over 90 days. In validation testing, the model exhibited reasonable discrimination (c =.76) and calibration (nonsignificant Hosmer-Lemeshow goodness-of-fit statistic, P =.54). A point score based on this model's variables fit to the entire data set closely matched observed mortality. Fifty-two percent of residents had low (score of 0-4) or relatively low (score of 5-6) predicted 30-day mortality, with 2.2% and 6.2% actual mortality, respectively. CONCLUSIONS: Our model distinguishes nursing home residents at relatively low risk for mortality due to LRI. If independently validated, our findings could help physicians identify nursing home residents in need of different therapeutic approaches for LRI.

Aged↗
PubMed2001

Elevated midlife blood pressure increases stroke risk in elderly persons: the Framingham Study.

BACKGROUND: Stroke risk predictions are traditionally based on current blood pressure (BP). The potential impact of a subject's past BP experience (antecedent BP) is unknown. We assessed the incremental impact of antecedent BP on the risk of ischemic stroke. METHODS: A total of 5197 stroke-free subjects (2330 men) in the community-based Framingham Study cohort were enrolled from September 29, 1948, to April 25, 1953, and followed up to December 31, 1998. We determined the 10-year risk of completed initial ischemic stroke for 60-, 70-, and 80-year-old subjects as a function of their current BP (at baseline), recent antecedent BP (average of readings at biennial examinations 1-9 years before baseline), and remote antecedent BP (average at biennial examinations 10-19 years earlier), with adjustment for smoking and diabetes mellitus. Models incorporating antecedent BP were also adjusted for baseline BP. The effect of each BP component (systolic BP, diastolic BP, and pulse pressure) was assessed separately. RESULTS: Four hundred ninety-one ischemic strokes (209 in men) were observed in eligible subjects. The antecedent BP influenced the 10-year stroke risk at the age of 60 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.68 [95% confidence interval, 1.25-2.25]; and men, 1.92 [95% confidence interval, 1.39-2.66]) and at the age of 70 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.66 [95% confidence interval, 1.28-2.14]; and men, 1.30 [95% confidence interval, 0.97-1.75]). This effect was evident for recent and remote antecedent BP, consistent in hypertensive and nonhypertensive subjects, and demonstrable for all BP components. CONCLUSIONS: Antecedent BP contributes to the future risk of ischemic stroke. Optimal prevention of late-life stroke will likely require control of midlife BP.

Adult↗
PubMed2001

Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort.

BACKGROUND: Moderate alcohol consumers have lower rates of cardiovascular disease than abstainers. One proposed mechanism is a beneficial effect on hemostatic parameters, but previous studies have provided conflicting results. METHODS AND RESULTS: We measured levels of fibrinogen, plasma viscosity, von Willebrand factor, factor VII, plasminogen activator inhibitor antigen-1, and tissue plasminogen activator antigen in a cross-sectional analysis of 3223 adults free of cardiovascular disease enrolled in the Framingham Offspring Study. We assessed their alcohol consumption with a standardized questionnaire. Light-to-moderate alcohol consumption was associated with lower levels of fibrinogen, plasma viscosity, von Willebrand factor, and factor VII. This association was most pronounced for consumers of 3 to 7 drinks weekly for viscosity and 7 to 21 drinks weekly for the other hemostatic measures. Alcohol intake of 7 to 21 drinks weekly or more was associated with impaired fibrinolytic potential, reflected by higher levels of plasminogen activator inhibitor antigen-1 and tissue plasminogen activator antigen. Wine drinkers had lower plasminogen activator inhibitor antigen-1 levels than other drinkers, particularly at 3 to 21 drinks weekly, but beverage type did not otherwise consistently affect the results. CONCLUSIONS: Light-to-moderate alcohol consumption is associated with lower levels of coagulatory factors, but higher intake is associated with impaired fibrinolytic potential. These findings are consistent with the hypothesis that a balance between hemostatic and fibrinolytic activity may contribute to the complex relation of alcohol use with coronary heart disease.

Alcohol Drinking↗
PubMed2001

Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation.

CONTEXT: The Framingham Heart Study produced sex-specific coronary heart disease (CHD) prediction functions for assessing risk of developing incident CHD in a white middle-class population. Concern exists regarding whether these functions can be generalized to other populations. OBJECTIVE: To test the validity and transportability of the Framingham CHD prediction functions per a National Heart, Lung, and Blood Institute workshop organized for this purpose. DESIGN, SETTING, AND SUBJECTS: Sex-specific CHD functions were derived from Framingham data for prediction of coronary death and myocardial infarction. These functions were applied to 6 prospectively studied, ethnically diverse cohorts (n = 23 424), including whites, blacks, Native Americans, Japanese American men, and Hispanic men: the Atherosclerosis Risk in Communities Study (1987-1988), Physicians' Health Study (1982), Honolulu Heart Program (1980-1982), Puerto Rico Heart Health Program (1965-1968), Strong Heart Study (1989-1991), and Cardiovascular Health Study (1989-1990). MAIN OUTCOME MEASURES: The performance, or ability to accurately predict CHD risk, of the Framingham functions compared with the performance of risk functions developed specifically from the individual cohorts' data. Comparisons included evaluation of the equality of relative risks for standard CHD risk factors, discrimination, and calibration. RESULTS: For white men and women and for black men and women the Framingham functions performed reasonably well for prediction of CHD events within 5 years of follow-up. Among Japanese American and Hispanic men and Native American women, the Framingham functions systematically overestimated the risk of 5-year CHD events. After recalibration, taking into account different prevalences of risk factors and underlying rates of developing CHD, the Framingham functions worked well in these populations. CONCLUSIONS: The sex-specific Framingham CHD prediction functions perform well among whites and blacks in different settings and can be applied to other ethnic groups after recalibration for differing prevalences of risk factors and underlying rates of CHD events.

Black or African American↗
PubMed2001

Platelet glycoprotein IIIa Pl(a) polymorphism, fibrinogen, and platelet aggregability: The Framingham Heart Study.

BACKGROUND: Recent data suggest that the Pl(A2) allele of the platelet glycoprotein IIIa receptor may be a genetic risk factor for cardiovascular disease. We previously reported that the Pl(A2) allele was associated with increased platelet aggregability, as indicated by lower epinephrine threshold concentrations. Paradoxically, however, it has been reported that Pl(A2)-positive platelets have reduced fibrinogen binding. Because fibrinogen mediates platelet aggregability, we hypothesized that plasma fibrinogen levels may interact with Pl(A) genotype in modulating platelet aggregability. Methods and Results-- Glycoprotein IIIa Pl(A) genotype, fibrinogen level, and platelet aggregability were ascertained in 1340 subjects enrolled into the Framingham Offspring Study. Platelet aggregability was evaluated by the Born method. Higher fibrinogen levels were associated with increased epinephrine-induced aggregation (P=0.002) and a trend for ADP-induced aggregation (P=0.07). The fibrinogen effect was genotype specific, however, in that the increase in platelet aggregability with higher fibrinogen was present for the Pl(A1/A1) genotype (P=0.0005 and P=0.03 for epinephrine- and ADP-induced aggregation, respectively) but not for the Pl(A2)-positive genotype (P>0.90). CONCLUSION: Higher fibrinogen levels were associated with increased platelet aggregability. However, the association between fibrinogen and platelet aggregability was genotype specific. This interaction may be responsible for the conflicting findings regarding Pl(A) genotype and platelet aggregability. Further study of this gene-environment interaction may provide insight into cardiovascular disease risk.

Adenosine Diphosphate↗
PubMed2001

Postmenopausal estrogen use, type of menopause, and lens opacities: the Framingham studies.

BACKGROUND: Previous studies of estrogen replacement therapy and lens opacities have not reported consistent findings. OBJECTIVE: To investigate whether postmenopausal estrogen use is associated with the occurrence of age-related lens opacities (nuclear, cortical, and posterior subcapsular). METHODS: Surviving members of the original cohort of the Framingham Heart Study who also participated in the Framingham Eye Study (1986-1989) were examined for the absence or presence of lens opacities. Data from the Framingham Heart Study, including information on menopausal status (collected biennially from approximately 1948) and use of estrogen replacement therapy (collected biennially from approximately 1960) were used to examine associations between lens opacities and duration of postmenopausal estrogen use, type of menopause, and age at menopause. Five hundred twenty-nine women, aged 66 to 93 years, were included. Multivariable-adjusted odds ratios of specific types of lens opacities were calculated for (1) duration of estrogen use (never and 1-2, 3-9, and >/=10 years), (2) surgical vs natural menopause, and (3) age at menopause. RESULTS: Longer duration of postmenopausal estrogen therapy was inversely associated with the presence of nuclear lens opacities in an adjusted model. Women who had taken estrogen for 10 years or longer had a 60% reduction in risk compared with nonusers (odds ratio, 0.4; 95% confidence interval, 0.2-1.01). Longer duration of estrogen use was associated with fewer posterior subcapsular opacities at a borderline level of significance. No association was noted for cortical opacities. The risk of posterior subcapsular opacities was significantly increased for women who had undergone surgical menopause compared with women with natural menopause (odds ratio, 2.2; 95% confidence interval, 1.1-4.3). No association was noted for lens opacities and age at menopause. CONCLUSION: Data from our study and other studies suggest that a reduction in the risk of lens opacities may be an additional benefit of postmenopausal estrogen use.

Aged↗
PubMed2001

Applicability of cholesterol-lowering primary prevention trials to a general population: the framingham heart study.

BACKGROUND: Four large trials have shown cholesterol-reduction therapy to be effective for primary prevention of coronary heart disease (CHD). METHODS: To determine the generalizability of these trials to a community-based sample, we compared the total cholesterol and high-density lipoprotein cholesterol (HDL-C) distributions of patients in the 4 trials with those of Framingham Heart Study subjects. Lipid profiles that have not been studied were identified. Twelve-year rates of incident CHD were compared between subjects who met eligibility criteria and those who did not. RESULTS: The Framingham sample included 2498 men and 2870 women aged 30 to 74 years. Among Framingham men, 23.4% to 42.0% met eligibility criteria for each of the 4 trials based on their lipid levels; 60.2% met eligibility criteria for at least 1 trial. For the 1 trial that included women, 20.2% of Framingham women met eligibility criteria. In general, subjects with desirable total cholesterol levels and lower HDL-C levels and subjects with average total cholesterol levels and average to higher HDL-C levels have not been included in these trials. Among subjects who developed incident CHD during follow-up, 25.1% of men and 66.2% of women would not have been eligible for any trial. Most ineligible subjects who developed CHD had isolated hypertriglyceridemia (>2.25 mmol/L [>200 mg/dL]). CONCLUSIONS: In our sample, 40% of men and 80% of women had lipid profiles that have not been studied in large trials to date. We observed a large number of CHD events in "ineligible" subjects in whom hypertriglyceridemia was common. Further studies are needed to define the role of lipid-lowering therapy vs other strategies for primary prevention in the general population.

Adult↗
PubMed2001

Hemostatic state and atrial fibrillation (the Framingham Offspring Study).

Atrial fibrillation (AF) is strongly associated with thromboembolic complications, although the mechanism for the increased risk has not been fully explained. To determine whether AF might be associated with a hypercoagulable state, we studied hemostatic factors in subjects with or without AF in the Framingham Heart Study. In 3,577 subjects, we measured fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (tPA) antigen, and plasminogen activator inhibitor-1 antigen. Forty-seven subjects had AF at the index clinic examination and 15 had AF on a prior examination, but not on the current examination. Before matching, the 47 subjects with prevalent AF had higher levels of fibrinogen, von Willebrand factor, and tPA antigen than those without AF, all p < or =0.03. Compared with 167 referent subjects matched for age, sex, and other risk factors, those with AF had higher tPA antigen levels than those without AF, 1 1.8 +/- 4.0 ng/ml versus 10.5 +/- 3.9 ng/ml (p = 0.04). However, when further stratified according to their cardiovascular disease status, the differences in hemostatic factors were no longer significant. We conclude that the prothrombotic profile associated with AF was explained by the risk factors of the subjects and the presence of cardiovascular disease. Nonetheless, the hemostatic changes may contribute toward the propensity for thromboembolic complications in AF. Further prospective studies are needed to evaluate whether measurement of these and other hemostatic factors will identify patients with AF who are at increased risk for thromboembolic complications, and who may therefore benefit from more intensive therapy.

Aged↗
PubMed2001

Quantitative analysis from CT is prognostic for local control of supraglottic carcinoma.

BACKGROUND: The purpose of this study was to determine whether pretreatment imaging with CT was prognostic for control of the primary site in patients with squamous cell carcinoma of the supraglottic larynx. METHODS: Pretreatment CT studies were obtained on 28 patients treated definitively with radiation therapy for supraglottic larynx cancer between 1991 and 1997. Follow-up ranged from 20-58 months. RESULTS: Local control was achieved in 61% of patients. Tumor volumes ranged from 0-68.6 cm(3), with a median of 3.1 cm(3). Local control rates for tumors with volumes greater than or less than 8 cm(3) were 20% and 70%, respectively (p =.0077). Mean tumor volumes for patients with and without recurrences were 10 cm(3) and 3.4 cm(3), respectively. CONCLUSIONS: This study demonstrates that quantitative analysis from CT imaging is prognostic for control of the primary site when radiation therapy is given for treatment of supraglottic cancer.

Carcinoma, Squamous Cell↗
PubMed2001

Serial positron emission tomography scans following radiation therapy of patients with head and neck cancer.

BACKGROUND: A single institution study was undertaken to evaluate the role of positron emission tomography (PET) scans with fluorodeoxyglucose (FDG) prior to radiation and following radiation. METHODS: Forty-five patients with head and neck cancers were evaluated with FDG-PET scans as well as either CT or MRI prior to treatment with definitive radiation (RT). These same scans were obtained following completion of RT at 1 month (36 patients), 4 months (28 patients), 12 months (19 patients), and 24 months (15 patients). Standard uptake values (SUV) normalized for blood glucose and lean body mass were calculated on the initial and 1-month post-treatment PET scans. RESULTS: Fifteen patients are alive without evidence of disease at 24 to 52 months following RT. Initial SUVs were calculated on the primary tumor site and ranged from 2.5 to 28.5. These values did not have any correlation with local control when examined for the entire group, primary site, or T stage. One-month post-RT SUV ranged from 1.8 to 6.24. Of the 36 1-month post-RT PET scans, six were interpreted as positive for residual disease and were confirmed by biopsy. Four of the five scans, which were interpreted as equivocal, were positive on biopsy. Seven of the 25 scans, which were interpreted as negative for tumor, were positive on biopsy. Four-month scans were more accurate for disease with disease noted in 0 of 18 negative scans, 6 of 7 positive scans, and 2 of 3 equivocal scans. CONCLUSIONS: PET is useful for initial imaging of head and neck cancers. SUV does not appear to be useful for predicting outcome following treatment with RT. One-month post-RT scans were inaccurate for predicting the presence of cancer. Four-month post-RT scans were a better predictor for the presence of cancer.

Fluorodeoxyglucose F18↗