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The progression of cardiometabolic disease: validation of a new cardiometabolic disease staging system applicable to obesity.

ABSTRACT: OBJECTIVE:To validate a Cardiometabolic Disease Staging (CMDS) system for assigning risk level for diabetes, and all-cause and cardiovascular disease (CVD) mortality. DESIGN AND METHODS:Two large national cohorts, CARDIA and NHANES III, were used to validate CMDS. CMDS: Stage 0: metabolically healthy; Stage 1: one or two metabolic syndrome risk factors [other than impaired fasting glucose (IFG)]; Stage 2: IFG or impaired glucose tolerance (IGT) or metabolic syndrome (without IFG); Stage 3: two of three (IFG, IGT, and/or metabolic syndrome); and Stage 4: type 2 diabetes mellitus/CVD. RESULTS:In the CARDIA study, compared with Stage 0 metabolically healthy subjects, adjusted risk for diabetes exponentially increased from Stage 1 [hazard ratio (HR) 2.83, 95% confidence interval (CI): 1.76-4.55], to Stage 2 (HR 8.06, 95% CI 4.91-13.2), to Stage 3 (HR 23.5, 95% CI 13.7-40.1) (P for trend <0.001). In NHANES III, both cumulative incidence and multivariable adjusted HRs markedly increased for both all-cause and CVD mortality with advancement of the risk stage from Stages 0 to 4. Adjustment for body mass index (BMI) minimally affected the risks for diabetes and all-cause/CVD mortality using CMDS. CONCLUSION:CMDS can discriminate a wide range of risk for diabetes, CVD mortality, and all-cause mortality independent of BMI, and should be studied as a risk assessment tool to guide interventions that prevent and treat cardiometabolic disease.

SUBMITTER: Guo F

PROVIDER: S-EPMC3866217 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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The progression of cardiometabolic disease: validation of a new cardiometabolic disease staging system applicable to obesity.

Guo Fangjian F Moellering Douglas R DR Garvey W Timothy WT

Obesity (Silver Spring, Md.) 20130905 1

<h4>Objective</h4>To validate a Cardiometabolic Disease Staging (CMDS) system for assigning risk level for diabetes, and all-cause and cardiovascular disease (CVD) mortality.<h4>Design and methods</h4>Two large national cohorts, CARDIA and NHANES III, were used to validate CMDS. CMDS: Stage 0: metabolically healthy; Stage 1: one or two metabolic syndrome risk factors [other than impaired fasting glucose (IFG)]; Stage 2: IFG or impaired glucose tolerance (IGT) or metabolic syndrome (without IFG); ...[more]

PMID: 23894121

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Project description:OBJECTIVES:The visceral adiposity index (VAI), an indirect marker of visceral adipose tissue, serves as a model associated with cardiometabolic risk, but has limitations regarding the Asian population. We sought to develop a new VAI (NVAI) for the Korean population and compare it to VAI for prediction of atherosclerotic cardiovascular disease (ASCVD) risk and development of major cardiovascular diseases (CVD) and stroke. METHODS:Patients (969) who underwent visceral fat area measurement were analyzed. After exclusion, 539 patients (142 men, 397 women) were randomly divided into internal (n = 374) and external validation (n = 165) data set. The NVAI was developed using univariate and multivariate logistic regression with backward selection of predictors. Receiver operating characteristic (ROC) curve analysis and comparison of the area under the curve (AUC) verified the better predictor of ASCVD risk score. Additionally, nationwide population-based cross-sectional survey data (Korean National Health and Nutrition Examination Survey [KNHANES] 2008-2010, n = 29,235) was used to validate the NVAI's ability to predict ASCVD risk and major CVD and stroke. RESULTS:The NVAI better reflected visceral fat area in internal and external data sets, with AUCs of 0.911 (95% confidence interval [CI]: 0.882-0.940) and 0.879 (95% CI: 0.828-0.931), respectively. NVAI better discriminated for ASCVD risk (AUC = 0.892, 95% CI: 0.846-0.938) compared to VAI (0.559, 95% CI: 0.439-0.679). The NVAI also better predicted MI or angina, and stroke with AUCs of 0.771 (95% CI: 0.752-0.789), and 0.812 (95% CI: 0.794-0.830), respectively, compared with waist circumference (WC), body mass index (BMI), TG to HDL ratio, and VAI via KNHANES, in a statistically significant manner. CONCLUSIONS:The NVAI has advantages as a predictor of visceral obesity and is significantly associated with ASCVD risks and development of major CVD and stroke in the Korean population. The NVAI could be a screening tool for improved risk estimation related to visceral obesity.

Project description:ImportanceTo our knowledge, there are no validation studies to date of the prognostic value of the AJCC Cancer Staging Manual, eighth edition (AJCC 8), criteria for eyelid and periocular squamous cell carcinoma.ObjectiveTo determine the association of tumor (T) category in AJCC 8 with local recurrence, nodal metastasis, distant metastasis, and disease-specific survival (DSS) for eyelid and periocular squamous cell carcinoma.Design, setting, and participantsIn this retrospective, single-center cohort study, 109 consecutive patients with eyelid and periocular squamous cell carcinoma treated from January 1999 to April 2018 were included. Patients with secondary involvement of the periocular region were excluded.Main outcomes and measuresLocal recurrence, nodal metastasis, distance metastasis, and DSS.ResultsOf the 109 included patients, 81 (74.3%) were male, and the median (range) age was 66 (40-91) years. At presentation, 43 patients (39.4%) had recurrent tumor, 4 (3.7%) had nodal metastasis, and 1 (0.9%) had distant metastasis. The median (range) follow-up was 23 (1-161) months. During follow-up, 11 patients (10.1%) developed local recurrence, 7 (6.4%) developed nodal metastasis, 2 (1.8%) developed distant metastasis, and 9 (8.3%) died of disease. The 5-year DSS rate was 87.7% (95% CI, 79.5-96.9). Chronic immunosuppression (hazard ratio, 47.24; 95% CI, 7.33-304.30; P < .001) and presentation with recurrent squamous cell carcinoma (hazard ratio, 5.22; 95% CI, 1.12-24.31; P = .04) were associated with local recurrence during follow-up. Of the 11 patients with local recurrence during follow-up, 7 (64%) had perineural invasion. T category was associated with nodal metastasis; clinical stage of T2c or worse at presentation was associated with higher risk of nodal metastasis and death of disease but not with a higher risk of local recurrence. Distant metastasis was associated with nodal metastasis at presentation (hazard ratio, 32.50; 95% CI, 1.97-536.40; P = .02) and during follow-up. A total of 33 patients (30.3%) had different T categories depending on whether disease was staged according to the seventh or eighth edition of the AJCC Cancer Staging Manual. Compared with AJCC 7, AJCC 8 showed a better predictive value in terms of local recurrence (T3, 17% vs 14%; T4, 11% vs 16%) and DSS.Conclusions and relevanceThese findings suggest that T category in AJCC 8 is associated with nodal metastasis and DSS. Immunosuppression and presentation with recurrent disease are associated with increased risk of future local recurrence. Patients with tumors of clinical stage T2c or worse at presentation are at increased risk of nodal metastasis and worse DSS and should undergo surveillance for nodal metastasis. Future studies, ideally prospective in design, could provide greater confidence in these findings.

Project description:ObjectiveIdentify and characterize circulating metabolite profiles associated with adiposity to inform precision medicine.MethodsUntargeted plasma metabolomic profiles in the Insulin Resistance Atherosclerosis Family Study (IRASFS) Mexican American cohort (n = 1108) were analyzed for association with anthropometric (body mass index, BMI; waist circumference, WC; waist-to-hip ratio, WHR) and computed tomography measures (visceral adipose tissue, VAT; subcutaneous adipose tissue, SAT; visceral-to-subcutaneous ratio, VSR) of adiposity. Genetic data, inclusive of genome-wide array-based genotyping, whole exome sequencing (WES) and whole genome sequencing (WGS), were evaluated to identify the genetic contributors. Phenotypic and genetic association signals were replicated across ancestries. Transcriptomic data were analyzed to explore the relationship between genetic and metabolomic data.ResultsA partially characterized metabolite, tentatively named metabolonic lactone sulfate (X-12063), was consistently associated with BMI, WC, WHR, VAT, and SAT in IRASFS Mexican Americans (PMA <2.02 × 10-27). Trait associations were replicated in IRASFS African Americans (PAA < 1.12 × 10-07). Expanded analyses revealed associations with multiple phenotypic measures of cardiometabolic health, e.g. insulin sensitivity (SI), triglycerides (TG), diastolic blood pressure (DBP) and plasminogen activator inhibitor-1 (PAI-1) in both ancestries. Metabolonic lactone sulfate levels were heritable (h2 > 0.47), and a significant genetic signal at the ZSCAN25/CYP3A5 locus (PMA = 9.00 × 10-41, PAA = 2.31 × 10-10) was observed, highlighting a putative functional variant (rs776746, CYP3A5∗3). Transcriptomic analysis in the African American Genetics of Metabolism and Expression (AAGMEx) cohort supported the association of CYP3A5 with metabolonic lactone sulfate levels (PFDR = 6.64 × 10-07).ConclusionsVariant rs776746 is associated with a decrease in the transcript levels of CYP3A5, which in turn is associated with increased metabolonic lactone sulfate levels and poor cardiometabolic health.

Project description:BackgroundAnthropometric-based classification schemes for excess adiposity do not include direct assessment of obesity-related comorbidity and functional status and thus have limited clinical utility. We examined the ability of the Edmonton obesity staging system, a 5-point ordinal classification system that considers comorbidity and functional status, in predicting mortality in a nationally representative US sample.MethodsWe analyzed data from the National Health and Human Nutrition Examination Surveys (NHANES) III (1988-1994) and the NHANES 1999-2004, with mortality follow-up through to the end of 2006. Adults (age ≥ 20 yr) with overweight or obesity who had been randomized to the morning session at the mobile examination centre were scored according to the Edmonton obesity staging system. We examined the relationship between staging system scores and mortality, and Cox proportional hazards models were adjusted for the presence of the metabolic syndrome or hypertriglyceridemic waist.ResultsOver 75% of the cohort with overweight or obesity were given scores of 1 or 2. Scores of 4 could not be reliably assigned because specific data elements were lacking. Survival curves clearly diverged when stratified by scores of 0-3, but not when stratified by obesity class alone. Within the data from the NHANES 1988-1994, scores of 2 (hazard ratio [HR] 1.57; 95% confidence interval [CI] 1.16 to 2.13) and 3 (HR 2.69; 95% CI 1.98 to 3.67) were associated with increased mortality compared with scores of 0 or 1, even after adjustment for body mass index and the metabolic syndrome. We found similar results after adjusting for hypertriglyceridemic waist (i.e., waist circumference ≥ 90 cm and a triglyceride level ≥ 2 mmol/L for men; the corresponding values for women were ≥ 85 cm and ≥ 1.5 mmol/L), as well as in a cohort eligible for bariatric surgery.InterpretationThe Edmonton obesity staging system independently predicted increased mortality even after adjustment for contemporary methods of classifying adiposity. The Edmonton obesity staging system may offer improved clinical utility in assessing obesity-related risk and prioritizing treatment.

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The progression of cardiometabolic disease: validation of a new cardiometabolic disease staging system applicable to obesity.

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The progression of cardiometabolic disease: validation of a new cardiometabolic disease staging system applicable to obesity.

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