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Ralph B D'Agostino

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

At least 19 recordsLinked to original sources
PubMed2007

Choice of time scale and its effect on significance of predictors in longitudinal studies.

Time-to-event regression is a frequent tool in biomedical research. In clinical trials this time is usually measured from the beginning of the study. The same approach is often adopted in the analysis of longitudinal observational studies. However, in recent years there has appeared literature making a case for the use of the date of birth as a starting point, and thus utilize age as the time-to-event. In this paper, we explore different types of age-scale models and compare them with time-on-study models in terms of the estimated regression coefficients they produce. We consider six proportional hazards regression models that differ in the choice of time scale and in the method of adjusting for the years before the study. By considering the estimating equations of these models as well as numerical simulations we conclude that correct adjustment for the age at entry is crucial in reducing bias of the estimated coefficients. The unadjusted age-scale model is inferior to any of the five other models considered, regardless of their choice of time scale. Additionally, if adjustment for age at entry is made, our analyses show very little to suggest that there exists any practically meaningful difference in the estimated regression coefficients depending on the choice of time scale. These findings are supported by four practical examples from the Framingham Heart Study.

Age Factors↗
PubMed2007

Elevated levels of the mismatch repair protein PMS2 are associated with prostate cancer.

BACKGROUND: Defects in mismatch repair (MMR) proteins have been identified in various types of cancer. However, an association with prostate cancer has been controversial. Defective MMR results in genome instability with detrimental consequences that significantly contribute to tumorigenesis. This study determined alterations in key MMR protein levels in prostate cancer with the goal to identify prognostic markers. METHODS: Prostatectomy samples were immunohistochemically stained and the relative presence or absence of key proteins MSH2, MLH1, and PMS2 determined. Cancer tissue of distinct grades was compared with the normal surrounding tissue. Microsatellite instability (MSI) in altered tissues was determined according to NCI guidelines. RESULTS: In contrast to reports that associate a lack of individual MMR proteins with tumorigenesis, a significant increase in PMS2 levels was identified in PIN lesions and prostate cancer tissue. This elevation in PMS2 was independent of changes in levels in its heterodimeric partner, MLH1. Prostate tumors with elevated levels of PMS2 were genetically unstable, which was corrected by MLH1 co-elevation. CONCLUSIONS: This is the first documentation of detrimental consequences associated with the increase in a MMR protein in human cancer. This study recognizes PMS2 elevation as a prognostic marker in pre-neoplastic and prostate cancer lesions. This result has significant implications for future diagnostic and treatment measures.

Adaptor Proteins, Signal Transducing↗
PubMed2007

Left ventricular mass, blood pressure, and lowered cognitive performance in the Framingham offspring.

The purpose of this study was to determine whether echocardiographic left ventricular mass is related to cognitive performance beyond casual blood pressure adjusting for the influence of other vascular risk factors. We used multivariable regression analyses to relate left ventricular mass assessed at a routine examination (1995-1998) to measures of cognitive ability obtained routinely (1998-2001) in 1673 Framingham Offspring Study participants (56% women; mean age: 57 years) free from stroke, transient ischemic attack, and dementia. We adjusted for the following covariates hierarchically: (1) age, education, sex, body weight, height, interval between left ventricular mass measurement and neuropsychological testing (basic model); (2) basic model+blood pressure+treatment for hypertension; and (3) basic model+blood pressure+treatment for hypertension+vascular risk factors and prevalent cardiovascular disease. For the basic model, left ventricular mass was inversely associated with abstract reasoning (similarities), visual-spatial memory and organization, and verbal memory. For the basic model+blood pressure+treatment for hypertension, left ventricular mass was inversely associated with similarities and visual-spatial memory and organization. For the basic+blood pressure+treatment for hypertension+risk factors+cardiovascular disease model, no significant associations were observed. Echocardiographic left ventricular mass is associated with cognitive performance beyond casual and time-averaged systolic blood pressure, but this association is attenuated and rendered nonsignificant with additional adjustment for cardiovascular risk factors and cardiovascular disease, thus suggesting that these variables play an important role in mediating the association between left ventricular mass and cognition.

Blood Pressure↗
PubMed2007

Validity of an adaptation of the Framingham cardiovascular risk function: the VERIFICA Study.

BACKGROUND: To assess the reliability and accuracy of the Framingham coronary heart disease (CHD) risk function adapted by the Registre Gironí del Cor (REGICOR) investigators in Spain. METHODS: A 5-year follow-up study was completed in 5732 participants aged 35-74 years. The adaptation consisted of using in the function the average population risk factor prevalence and the cumulative incidence observed in Spain instead of those from Framingham in a Cox proportional hazards model. Reliability and accuracy in estimating the observed cumulative incidence were tested with the area under the curve comparison and goodness-of-fit test, respectively. RESULTS: The Kaplan-Meier CHD cumulative incidence during the follow-up was 4.0% in men and 1.7% in women. The original Framingham function and the REGICOR adapted estimates were 10.4% and 4.8%, and 3.6% and 2.0%, respectively. The REGICOR-adapted function's estimate did not differ from the observed cumulated incidence (goodness of fit in men, p = 0.078, in women, p = 0.256), whereas all the original Framingham function estimates differed significantly (p<0.001). Reliabilities of the original Framingham function and of the best Cox model fit with the study data were similar in men (area under the receiver operator characteristic curve 0.68 and 0.69, respectively, p = 0.273), whereas the best Cox model fitted better in women (0.73 and 0.81, respectively, p<0.001). CONCLUSION: The Framingham function adapted to local population characteristics accurately and reliably predicted the 5-year CHD risk for patients aged 35-74 years, in contrast with the original function, which consistently overestimated the actual risk.

Adult↗
PubMed2006

Multiple biomarkers for the prediction of first major cardiovascular events and death.

BACKGROUND: Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events. METHODS: We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio. RESULTS: During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker" scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic. CONCLUSIONS: For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.

Biomarkers↗
PubMed2006

Carbohydrate nutrition, glycaemic load, and plasma lipids: the Insulin Resistance Atherosclerosis Study.

AIMS: We evaluated the relationship of carbohydrate nutrition and selected food groups with lipids using data from the Insulin Resistance Atherosclerosis Study (IRAS Exam I, 1992-1994). METHODS AND RESULTS: A total of 1026 middle-aged adults with normal or impaired glucose tolerance had complete data on fasting lipids and usual dietary intake from an interviewer-administered, validated food frequency questionnaire. Published glycaemic index (GI) values were assigned to food items and average dietary GI and glycaemic load (GL) were calculated per participant. Intake of carbohydrates differed by gender, men consuming more absolute digestible carbohydrates with higher GI and GL than women. In multivariate models adjusting for energy intake, in men, GL and carbohydrates were associated positively with total and LDL cholesterol, and inversely with HDL. In women, associations were limited to triglycerides. We estimated that a 100 g higher intake in GL or carbohydrates was associated with a 7-8 mg/dL higher total or LDL cholesterol level in men, and a 13-17 mg/dL higher triglyceride level in women. In the combined sample, GL and carbohydrates were consistently associated with all lipid levels and GI was inversely associated with HDL cholesterol. CONCLUSION: Our findings underscore the importance of carbohydrate nutrition for plasma lipids.

Adult↗
PubMed2006

Estimating lifetime risk of developing high serum total cholesterol: adjustment for baseline prevalence and single-occasion measurements.

The lifetime risk statistic is a powerful tool in epidemiology. It has been successfully applied to estimate and highlight the risks of numerous diseases, including breast cancer, Alzheimer's disease, stroke, and coronary heart disease and some of its risk factors. Application of this method to health-related conditions that may have an onset early in young adulthood or to measurements that can fluctuate over time introduces problems of under- or overestimation of risk. To correctly quantify the long-term risk of developing high serum total cholesterol (> or =240 mg/dl or use of lipid-lowering medication), the authors propose a key modification of the lifetime risk statistic: adjustment for baseline prevalence. It accounts for the fact that many people already have the condition at a young age (an age often chosen as baseline). The authors derive point estimators and confidence intervals and supply a SAS macro (SAS Institute, Inc., Cary, North Carolina). For assessment of the risk inflation due to single-occasion measurement, the authors suggest two diagnostic tools, one requiring the condition to be present on two consecutive occasions and the other taking into account intrasubject variability. As an illustration, the authors calculate risk estimates for US Caucasians based on hypercholesterolemia incidence (1971-early 2001) from the Framingham Heart Study and prevalence data from the 1999-2000 National Health and Nutrition Examination Survey.

Adult↗
PubMed2006

Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial.

CONTEXT: Carotid artery intima-media thickness (CIMT) is a marker of coronary atherosclerosis and independently predicts cardiovascular events, which are increased in type 2 diabetes mellitus (DM). While studies of relatively short duration have suggested that thiazolidinediones such as pioglitazone might reduce progression of CIMT in persons with diabetes, the results of longer studies have been less clear. OBJECTIVE: To evaluate the effect of pioglitazone vs glimepiride on changes in CIMT of the common carotid artery in patients with type 2 DM. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, comparator-controlled, multicenter trial in patients with type 2 DM conducted at 28 clinical sites in the multiracial/ethnic Chicago metropolitan area between October 2003 and May 2006. The treatment period was 72 weeks (1-week follow-up). CIMT images were captured by a single ultrasonographer at 1 center and read by a single treatment-blinded reader using automated edge-detection technology. Participants were 462 adults (mean age, 60 [SD, 8.1] years; mean body mass index, 32 [SD, 5.1]) with type 2 DM (mean duration, 7.7 [SD, 7.2] years; mean glycosylated hemoglobin [HbA1c] value, 7.4% [SD, 1.0%]), either newly diagnosed or currently treated with diet and exercise, sulfonylurea, metformin, insulin, or a combination thereof. INTERVENTIONS: Pioglitazone hydrochloride (15-45 mg/d) or glimepiride (1-4 mg/d) as an active comparator. MAIN OUTCOME MEASURE: Absolute change from baseline to final visit in mean posterior-wall CIMT of the left and right common carotid arteries. RESULTS: Mean change in CIMT was less with pioglitazone vs glimepiride at all time points (weeks 24, 48, 72). At week 72, the primary end point of progression of mean CIMT was less with pioglitazone vs glimepiride (-0.001 mm vs +0.012 mm, respectively; difference, -0.013 mm; 95% confidence interval, -0.024 to -0.002; P = .02). Pioglitazone also slowed progression of maximum CIMT compared with glimepiride (0.002 mm vs 0.026 mm, respectively, at 72 weeks; difference, -0.024 mm; 95% confidence interval, -0.042 to -0.006; P = .008). The beneficial effect of pioglitazone on mean CIMT was similar across prespecified subgroups based on age, sex, systolic blood pressure, duration of DM, body mass index, HbA(1c) value, and statin use. CONCLUSION: Over an 18-month treatment period in patients with type 2 DM, pioglitazone slowed progression of CIMT compared with glimepiride. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00225264

Adult↗
PubMed2006

Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study.

OBJECTIVE: To determine whether serum gamma-glutamyl transferase (GGT) predicts cardiovascular disease (CVD) morbidity and mortality, accounting for temporal changes in known CVD risk factors and C-reactive protein (CRP). METHODS AND RESULTS: In 3451 Framingham Study participants (mean age 44 years, 52% women) we examined the relations of GGT with CVD risk factors, and prospectively determined the risk of new-onset metabolic syndrome, incident CVD, and death. GGT was positively associated with body mass index, blood pressure, LDL cholesterol, triglycerides, and blood glucose in cross-sectional analysis (P<0.005). On follow-up (mean 19 years), 968 participants developed metabolic syndrome, 535 developed incident CVD, and 362 died. The risk of metabolic syndrome increased with higher GGT (multivariable-adjusted hazard ratio [HR] per SD increment log-GGT, 1.26 [95%CI; 1.18 to 1.35]). Adjusting for established CVD risk factors (as time-dependent covariates updated quadriennially) and baseline CRP, a 1-SD increase in log-GGT conferred a 13% increase in CVD risk (P=0.007) and 26% increased risk of death (P<0.001). Individuals in the highest GGT quartile experienced a 67% increase in CVD incidence (multivariable-adjusted HR 1.67, 95%CI; 1.25 to 2.22). CONCLUSIONS: An increase in serum GGT predicts onset of metabolic syndrome, incident CVD, and death suggesting that GGT is a marker of metabolic and cardiovascular risk.

Adult↗
PubMed2006

Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension.

OBJECTIVE: To test the validity and generalizability of the Ocular Hypertension Treatment Study (OHTS) prediction model for the development of primary open-angle glaucoma (POAG) in a large independent sample of untreated ocular hypertensive individuals and to develop a quantitative calculator to estimate the 5-year risk that an individual with ocular hypertension will develop POAG. DESIGN: A prediction model was developed from the observation group of the OHTS and then tested on the placebo group of the European Glaucoma Prevention Study (EGPS) using a z statistic to compare hazard ratios, a c statistic for discrimination, and a calibration chi2 for systematic overestimation/underestimation of predicted risk. The 2 study samples were pooled to increase precision and generalizability of a 5-year predictive model for developing POAG. PARTICIPANTS: The OHTS observation group (n = 819; 6.6 years' median follow-up) and EGPS placebo group (n = 500; 4.8 years' median follow-up). TESTING: Data were collected on demographic characteristics, medical history, ocular examination visual fields (VFs), and optic disc photographs. MAIN OUTCOME MEASURE: Development of reproducible VF abnormality or optic disc progression as determined by masked readers and attributed to POAG by a masked end point committee. RESULTS: The same predictors for the development of POAG were identified independently in both the OHTS observation group and the EGPS placebo group-baseline age, intraocular pressure, central corneal thickness, vertical cup-to-disc ratio, and Humphrey VF pattern standard deviation. The pooled multivariate model for the development of POAG had good discrimination (c statistic, 0.74) and accurate estimation of POAG risk (calibration chi2, 7.05). CONCLUSIONS: The OHTS prediction model was validated in the EGPS placebo group. A calculator to estimate the 5-year risk of developing POAG, based on the pooled OHTS-EGPS predictive model, has high precision and will be useful for clinicians and patients in deciding the frequency of tests and examinations during follow-up and advisability of initiating preventive treatment.

Cornea↗
PubMed2006

Heritability of the ankle-brachial index: the Framingham Offspring study.

The ankle-brachial blood pressure index (ABI) is a widely utilized measure for detecting peripheral arterial disease. Genetic contributions to variation in ABI are largely unknown. The authors sought to estimate ABI heritability in a community-based sample. From 1995 to 1998, ABI was measured in 1,097 men and 1,189 women (mean age = 57 years; range, 29-85 years) from 999 families in the Framingham Offspring cohort. Correlation coefficients for sibling pairs were calculated using the family correlations (FCOR) procedure in S.A.G.E. (Case Western Reserve University, Cleveland, Ohio). The heritability of ABI was estimated using variance-components methods in SOLAR (Southwest Foundation for Biomedical Research, San Antonio, Texas). Analyses were performed on normalized crude ABI and on normalized residuals from multiple linear regression analyses in SAS (SAS Institute, Inc., Cary, North Carolina) that adjusted for age, sex, smoking, diabetes, hypertension, ratio of total cholesterol to high density lipoprotein cholesterol, log triglyceride level, and body mass index. The mean ABI was 1.1 (range, 0.4-1.4). The age- and sex-adjusted and multivariable-adjusted sibling-pair correlation coefficients for normalized ABI were 0.15 and 0.11, respectively, resulting in heritability estimates of 0.30 and 0.22. Crude, age- and sex-adjusted, and multivariable-adjusted heritabilities for normalized ABI estimated using variance-components analysis were 0.27 (standard error, 0.06), 0.30 (standard error, 0.06), and 0.21 (standard error, 0.06), respectively (all p values < 0.0001). A modest proportion of the variability in ABI is explained by genetic factors.

Adult↗
PubMed2006

Implications of C-reactive protein or coronary artery calcium score as an adjunct to global risk assessment for primary prevention of CHD.

BACKGROUND: C-reactive protein (CRP) or coronary artery calcium (CAC) score have been suggested to identify a higher risk subset of intermediate-risk individuals, who potentially could be considered for more aggressive therapy. In the Multi-Ethnic Study of Atherosclerosis (MESA), we estimated the proportion of intermediate-risk participants whose risk status might change based on additional testing using CRP and/or CAC score. METHODS: Framingham 10-year CHD risk scores (FRS) were calculated and cross tabulations were used to determine the percent of individuals at intermediate-risk by FRS with a CRP >3mg/L and/or CAC score >100 AU. Similar analyses were performed using the gender-specific 75th percentile for CRP and CAC. RESULTS: Of the 30% of participants (N=1450) classified as intermediate-risk by FRS, 30% had a CRP >3mg/L and 33% had a CAC score >100 AU. Among intermediate-risk women, 49% had a CRP >3mg/L compared to 27% of intermediate-risk men (p<0.0001) while the same percent of intermediate-risk women and men (33%) had a CAC score >100 AU. Eleven percent or less of men or women had both a high CRP and CAC score whether conventional or gender-specific cut points were used. When the percent of intermediate-risk individuals with an elevated CRP and/or CAC score in MESA were applied to NHANES III data, over a million intermediate-risk individuals would move to high risk status if CRP or CAC screening directed treatment strategies were uniformly adopted in the U.S. CONCLUSION: There were differences in the number of intermediate-risk individuals reclassified as high risk depending on the screening test used, the cut points selected, and the demographics of the individuals being screened. These data highlight current limitations of broadly using risk markers such as CRP and CAC score in an intermediate-risk population.

Aged↗
PubMed2006

Endogenous sex hormones and cardiovascular disease incidence in men.

BACKGROUND: Data suggest that endogenous sex hormones (testosterone, dehydroepiandrosterone sulfate [DHEA-S], and estradiol) influence cardiovascular disease (CVD) risk factors and vascular function. Yet, prospective studies relating sex hormones to CVD incidence in men have yielded inconsistent results. OBJECTIVE: To examine the association of circulating sex hormone levels and CVD risk in men. DESIGN: Prospective cohort study. SETTING: Community-based study in Framingham, Massachusetts. PARTICIPANTS: 2084 middle-aged white men without CVD at baseline. MEASUREMENTS: The authors used multivariable Cox regression to relate baseline levels of testosterone, DHEA-S, and estradiol to the incidence of CVD (coronary, cerebrovascular, or peripheral vascular disease or heart failure) during 10 years of follow-up. RESULTS: During follow-up, 386 men (18.5%) experienced a first CVD event. After adjustment for baseline standard CVD risk factors, higher estradiol level was associated with lower risk for CVD (hazard ratio per SD increment in log estradiol, 0.90 [95% CI, 0.82 to 0.99]; P = 0.035). The authors observed effect modification by age: Higher estradiol levels were associated with lower CVD risk in older (median age >56 years) men (hazard ratio per SD increment, 0.86 [CI, 0.78 to 0.96]; P = 0.005) but not in younger (median age < or =56 years) men (hazard ratio per SD increment, 1.11 [CI, 0.89 to 1.38]; P = 0.36). The association of higher estradiol level with lower CVD incidence remained robust in time-dependent Cox models (updating standard CVD risk factors during follow-up). Serum testosterone and DHEA-S levels were not statistically significantly associated with incident CVD. LIMITATIONS: Sex hormone levels were measured only at baseline, and the findings may not be generalizable to women and nonwhite people. CONCLUSIONS: In the community-based sample, a higher serum estradiol level was associated with lower risk for CVD events in older men. The findings are consistent with the hypothesis that endogenous estrogen has vasculoprotective influences in men.

Cardiovascular Diseases↗
PubMed2006

Association of parental heart failure with risk of heart failure in offspring.

BACKGROUND: The association between heart failure in parents and the prevalence of left ventricular systolic dysfunction and the risk of heart failure in their offspring has not been investigated in a community-based setting. METHODS: We examined the cross-sectional association of heart failure in parents with the prevalence of left ventricular systolic dysfunction, as well as left ventricular mass, internal dimensions, and wall thickness, in 1497 participants of the Framingham Offspring Study (mean age, 57 years; 819 women) who underwent routine echocardiography. We also investigated prospectively whether heart failure in parents increased the risk of heart failure in 2214 offspring (mean age, 44 years; 1150 women). RESULTS: As compared with the 1039 participants whose parents did not have heart failure, the 458 participants in the cross-sectional cohort who had at least one parent with heart failure were more likely to have increased left ventricular mass (17.0 percent vs. 26.9 percent), left ventricular internal dimensions (18.6 percent vs. 23.4 percent), and left ventricular systolic dysfunction (3.1 percent vs. 5.7 percent); the multivariable-adjusted odds ratios were 1.35 (95 percent confidence interval, 0.99 to 1.84), 1.29 (95 percent confidence interval, 0.96 to 1.72), and 2.37 (95 percent confidence interval, 1.22 to 4.61), respectively. In the longitudinal cohort, heart failure developed in 90 offspring during follow-up (mean length of follow-up, 20 years). The age- and sex-adjusted 10-year incidence rates of heart failure were 2.72 percent among offspring with a parent with heart failure, as compared with 1.62 percent among those without a parent with heart failure. This increase in risk persisted after multivariable adjustment (hazard ratio, 1.70; 95 percent confidence interval, 1.11 to 2.60). CONCLUSIONS: Heart failure in parents is associated with an increased prevalence of left ventricular systolic dysfunction cross-sectionally and an elevated risk of heart failure longitudinally. Our data emphasize the contribution of familial factors to the heart-failure burden in the community.

Adult Children↗
PubMed2006

Trends in the incidence of type 2 diabetes mellitus from the 1970s to the 1990s: the Framingham Heart Study.

BACKGROUND: Recent studies indicate that the prevalence of type 2 diabetes mellitus is increasing in the United States; less is known about trends in the incidence of type 2 diabetes mellitus. METHODS AND RESULTS: Participants free of diabetes mellitus (n=3104; mean age 47 years; 1587 women) from the Framingham Offspring Study who attended a routine examination in the 1970s, 1980s, or 1990s were followed up for the 8-year incidence of diabetes mellitus. Diabetes was defined as a fasting plasma glucose > or = 7.0 mmol/L or treatment with either insulin or a hypoglycemic agent. Pooled logistic regression was used to compare diabetes incidence across decades for participants between 40 and 55 years of age in each decade. The age-adjusted 8-year incidence rate of diabetes was 2.0%, 3.0%, and 3.7% among women and 2.7%, 3.6%, and 5.8% among men in the 1970s, 1980s, and 1990s, respectively. Compared with the 1970s, the age- and sex-adjusted odds ratio (OR) for diabetes was 1.40 (95% confidence interval [CI], 0.89 to 2.22) in the 1980s and 2.05 (95% CI, 1.33 to 3.14) in the 1990s (P for trend=0.0006). Among women, the OR was 1.50 (95% CI, 0.75 to 2.98) in the 1980s and 1.84 (95% CI, 0.95 to 3.55) in the 1990s (P for trend=0.07) compared with the 1970s, whereas among men, the OR was 1.33 (95% CI, 0.72 to 2.47) in the 1980s and 2.21 (95% CI, 1.25 to 3.90) in the 1990s (P for trend=0.003). Most of the increase in absolute incidence of diabetes occurred in individuals with body mass index > or = 30 kg/m2 (P for trend=0.03). CONCLUSIONS: In the present community-based sample of middle-aged adults, we observed a doubling in the incidence of type 2 diabetes over the last 30 years. Careful surveillance of changes in diabetes incidence may be necessary if current trends of excess adiposity continue.

Adult↗
PubMed2006

Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease.

CONTEXT: Metabolic risk conferred by adiposity may be due to associated risk factor clustering. OBJECTIVE: The objective of this study was to assess risk for diabetes or cardiovascular disease (CVD) stratified by body mass index (BMI) and the presence or absence of metabolic syndrome (MetS) or insulin resistance (IR). DESIGN, SETTING, AND PARTICIPANTS: This was a community-based, longitudinal study of 2902 people (55% women, mean age 53 yr) without diabetes or CVD in 1989-1992 followed for up to 11 yr. We categorized subjects by normal weight (BMI < 25 kg/m(2)), overweight (25-29.9 kg/m(2)), or obese (>30 kg/m(2)) and by the National Cholesterol Education Program's Adult Treatment Panel MetS or the top quartile of homeostasis model IR. We used proportional hazard models to estimate risk relative to normal weight and no MetS or IR. MAIN OUTCOME MEASURE: Incident type 2 diabetes (treatment or fasting glucose > or = 7 mmol/liter, 141 events) or CVD (myocardial infarction, stroke, or claudication, 252 events) were measured. RESULTS: Among 1056 normal-weight subjects, 7% had MetS and a risk factor-adjusted relative risk for diabetes of 3.97 (95% confidence interval, 1.35-11.6) and for CVD of 3.01 (1.68-5.41). Among 638 obese subjects, 37% did not have MetS or significantly increased risk. Obese subjects with MetS had an adjusted relative risk for diabetes of 10.3 (5.44-19.5) and for CVD of 2.13 (1.43-3.18). Results were similar in analyses of BMI-IR categories. CONCLUSIONS: People with normal weight and MetS or IR or with obesity but no MetS or IR were not uncommon in our sample. Risk factor clustering or IR appear to confer much of the risk for diabetes or CVD commonly associated with elevated BMI.

Blood Glucose↗
PubMed2006

Predictors of mortality for lower respiratory infections in nursing home residents with dementia were validated transnationally.

BACKGROUND AND OBJECTIVE: Generalizability of clinical predictors for mortality from lower respiratory infection (LRI) in nursing home residents has not been assessed for residents with dementia. STUDY DESIGN AND SETTING: In prospective cohort studies of LRI in 61 nursing homes in the Netherlands (n = 541) and 36 nursing homes in Missouri, USA (n = 564), we examined 14-day and 1- and 3-month mortality in residents with dementia who were treated with antibiotics. RESULTS: A logistic model predicting 14-day mortality derived from Dutch data included eating dependency, elevated pulse, decreased alertness, respiratory difficulty, insufficient fluid intake, high respiratory rate, male gender, and pressure sores. After adjusting coefficients with the heuristic shrinkage factor, the 14-day model showed good discrimination and calibration in both datasets. The apparent c-statistic for the original Dutch model was 0.80 (after correction for optimism, it was 0.75); the c-statistic was 0.74 in the U.S. validation population. The models predicting 1- and 3-month mortality showed moderate performance. A scoring system for estimating 14-day mortality performed equally well as the original model. CONCLUSION: We identified a set of credible clinical predictors that are easily assessed and demonstrated validity in identifying residents at low risk of dying from LRI across different nursing home populations. This tool should inform decision-making for families and doctors.

Aged↗