National Health And Nutrition Examination Survey Cohort Research Articles

Prevalence of subclinical hypothyroidism and longitudinal thyroid stimulating hormone changes in youth with metabolic dysfunction-associated steatotic liver disease: an observational study.

Studies on adults have shown an association between overt or subclinical hypothyroidism (SH) and metabolic dysfunction-associated steatotic liver disease (MASLD). The goal of this study was to assess the relationship between thyroid-stimulating hormone (TSH) levels and the histological characteristics of MASLD in youth. This observational study used prospectively collected liver biopsy and clinical data from youth enrolled in two pediatric clinical trials in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Thyroid assays were compared between youth with MASLD and population-based controls aged ≤18 years from the National Health and Nutrition Examination Survey (NHANES). Individuals with overt hypothyroidism, abnormal anti-thyroid antibody, or thyroid-related medications were excluded. SH was defined as TSH between 4.5-10.0uIU/L. Multinomial logistic regression was used to test the association between TSH and MASLD histological changes at baseline, adjusting for age, sex, race/ethnicity, and body mass index. Mixed-effect models, including treatment and time, were used for the longitudinal analysis. Mean TSH, total thyroxine (T4), total triiodothyronine (T3), and free T4 levels were higher (p<0.001) in the NASH CRN cohort (n=218; 421 observations) than in the NHANES cohort (n=2,198). TSH levels were positively associated with increased steatosis over time (p=0.03). SH was associated with borderline or definite metabolic-associated steatohepatitis on histology at baseline (p=0.03) and with changes in fibrosis over time (p=0.01). The association between TSH and steatosis severity in individuals with normal thyroid hormone concentrations suggests an independent role of TSH in MASLD.

Building a predictive model for depression risk in fracture patients: insights from cross-sectional NHANES 2005–2020 data and an external hospital-based dataset

BackgroundDepression represents a frequent mental health challenge in individuals with fractures, negatively impacting their recuperation and overall well-being. The purpose of this research was to formulate and corroborate a prognostic framework for pinpointing depression risk among fracture sufferers by utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2020 and a separate hospital-based group.MethodsWe analyzed records from 1,748 individuals with fractures documented in the NHANES database spanning 2005 to 2020, of which 362 were diagnosed with depression, as indicated by a Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher. An additional validation group comprised 360 fracture patients sourced from a medical center. Considered variables for prediction encompassed demographic details, lifestyle habits, past medical conditions, and laboratory results. The method of least absolute shrinkage and selection operator (LASSO) regression facilitated the narrowing down of variables, while multivariate logistic regression was employed to pinpoint significant predictors. To assist in prediction, a nomogram was designed and subsequently validated.ResultsFive independent predictors were identified: drinking, insomnia, poverty-to-income ratio, education level, and white blood cell count. The nomogram showed good discrimination in the NHANES cohorts (training area under the curve (AUC) 0.734, validation AUC 0.740) and hospital-based external validation (AUC 0.711). Calibration curves and decision analysis supported its predictive accuracy and clinical value.ConclusionThe constructed nomogram offers a precise and clinically relevant instrument for forecasting depression risk in patients with fractures, facilitating the early detection of individuals at high risk and enabling prompt intervention.

Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults

Use of herbal and dietary supplements (HDSs) accounts for an increasing proportion of drug hepatotoxicity cases. Turmeric or curcumin, green tea extract, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha are the most frequently reported hepatoxic botanicals, but their prevalence and reasons for use in the general population are unknown. To assess the prevalence and clinical characteristics of adult consumers of 6 potentially hepatoxic botanicals. This survey study analyzed nationally representative data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative, cross-sectional survey of the general US population. Prescription drug and HDS exposure data in the past 30 days were analyzed, and 2020 US Census data were used for population estimates. Data were analyzed July 1, 2023, to February 1, 2024. Adult NHANES participants enrolled between January 2017 and March 2020. Baseline weighted characteristics of HDS users and users of 6 potentially hepatotoxic botanical products were compared with non-HDS users. Multivariable analysis was undertaken to identify factors associated with HDS use or at-risk botanical use. Among 9685 adults enrolled in this NHANES cohort, the mean (SE) age was 47.5 (0.5) years, and 51.8% (95% CI, 50.2%-53.4%) were female. The overall prevalence of HDS product use was 57.6% (95% CI, 55.9%-59.4%), while the prevalence of using the 6 botanicals of interest was 4.7% (95% CI, 3.9%-5.7%). Turmeric-containing botanicals were most commonly used (n = 236), followed by products containing green tea (n = 92), ashwagandha (n = 28), Garcinia cambogia (n = 20), red yeast rice (n = 20), and black cohosh (n = 19). Consumers of these 6 botanicals were significantly older (adjusted odds ratio [AOR], 2.36 [95% CI, 1.06-5.25]; P = .04 for 40-59 years of age and AOR, 3.96 [95% CI, 1.93-8.11]; P = .001 for ≥60 years of age), had a higher educational level (AOR, 4.78 [95% CI, 2.62-8.75]; P < .001), and were more likely to have arthritis (AOR, 2.27 [95% CI, 1.62-3.29]; P < .001) compared with non-HDS users. An estimated 15 584 599 (95% CI, 13 047 571-18 648 801) US adults used at least 1 of the 6 botanical products within the past 30 days, which was similar to the estimated number of patients prescribed potentially hepatotoxic drugs, including simvastatin (14 036 024 [95% CI, 11 202 460-17 594 452]) and nonsteroidal anti-inflammatory drugs (14 793 837 [95% CI, 13 014 623-16 671 897]). The most common reason for consuming turmeric and green tea was to improve or maintain health. In this survey study, an estimated 15.6 million US adults consumed at least 1 botanical product with liver liability within the past 30 days, comparable with the number of people who consumed nonsteroidal anti-inflammatory drugs and a commonly prescribed hypolipidemic drug. Given a lack of regulatory oversight on the manufacturing and testing of botanical products, clinicians should be aware of possible adverse events from consumption of these largely unregulated products.

Impact of non-alcoholic fatty liver disease and fibrosis on mortality and kidney outcomes in patients with type 2 diabetes and chronic kidney disease: A multi-cohort longitudinal study.

To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events. In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events. In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.

Estimating lead-attributable mortality burden by socioeconomic status in the USA.

This study aimed to estimate population-level and state-level lead-attributable mortality burdens stratified by socioeconomic status (SES) class in the USA. Based on the National Health and Nutrition Examination Survey (NHANES), we constructed individual-level SES scores from income, employment, education and insurance data. We assessed the association between the blood lead levels (BLL) and all-cause mortality by Cox regression in the NHANES cohort (n = 31 311, 4467 deaths). With estimated hazard ratios (HR) and prevalences of medium (2-5 μg/dL) and high (≥ 5 μg/dL) BLL, we computed SES-stratified population-attributable fractions (PAFs) of all-cause mortality from lead exposure across 1999-2019. We additionally conducted a systematic review to estimate the lead-attributable mortality burden at state-level. The HR for every 2-fold increase in the BLL decreased from 1.23 (1.10-1.38) for the lowest SES class to 1.05 (0.90-1.23) for the highest SES class. Across all SES quintiles, medium BLL exhibited a greater mortality burden. Individuals with lower SES had higher lead-attributable burdens, and such disparities haver persisted over the past two decades. In 2017-19, annually 67 000 (32 000-112 000) deaths in the USA were attributable to lead exposure, with 18 000 (2000-41 000) of these deaths occurring in the lowest SES class. Substantial disparities in the state-level mortality burden attributable to lead exposure were also highlighted. These findings suggested that disparities in lead-attributable mortality burden persisted within US adults, due to heterogeneities in the effect sizes of lead exposure as well as in the BLL among different SES classes.

The steatosis-associated fibrosis estimator (SAFE) outperformed the FIB-4 score in screening the population for liver disease

Introduction and ObjectivesAssessing fibrosis risk noninvasively is essential. The steatosis-associated fibrosis estimator (SAFE) score shows promise but needs validation. Patients and MethodsThis was a three-part study. In part 1, we compared the SAFE score with the Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) in the National Health and Nutrition Examination Survey (NHANES) cohort (2017–2020), using transient elastography (TE) as screening reference. In part 2, we examined patients who underwent liver biopsies at an Asian center between 2018 and 2020 to assess these models in various liver diseases. In part 3, the SAFE score was applied to adults in the NHANES cohort (1999–2016) to assess the correlation with mortality. ResultsIn part 1, we studied 6,677 patients, comprising 595 screening positive (TE ≥8 kPa). SAFE (cutoff 100) displayed a lower proportion of false positives (10.4 %) than FIB-4 (cutoff 1.3) and NFS (cutoff -1.455) (22.1 % and 43.6 %) while retaining a low proportion of false negatives (5.5 %). In part 2, SAFE outperformed FIB-4 (P = 0.04) and NFS (P = 0.04) in staging significant fibrosis (≥S2) in NAFLD and had similar accuracies in other etiologies. In part 3, the FIB-4, NFS, and SAFE score were associated with all-cause mortality in the general population, with c-statistics of 0.738, 0.736, and 0.759, respectively. ConclusionsThe SAFE score reduced futile referrals more effectively than FIB-4 without raising the missed TE ≥ 8 kPa rate. It correlated with all-cause mortality in the general population and excelled in staging significant fibrosis in NAFLD.

#1672 High level of HDL-C is associated with a higher risk of ESRD and all-cause mortality in patients with DM and CKD

Abstract Background and Aims Previous studies have regarded high-density lipoprotein cholesterol (HDL-C) as ‘good cholesterol’; however, recent research has unveiled a higher incidence of adverse events among individuals with extremely elevated HDL-C levels. Method Two cohorts of subjects were analyzed in this study. In the first cohort, a total of 375 participants with DKD who underwent renal-biopsy between January 2008 and September 2020, from West China Hospital T2DM-DKD cohort, were enrolled for the longitudinal observational study. Additionally, 3,262 participants with DM and chronic kidney disease (CKD) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the association between HDL-C concentration and the incidence of end-stage renal disease (ESRD) as well as all-cause mortality. Results Patients were divided into three groups based on HDL-C levels. After a median follow-up of 36 months, 44% of the patients developed ESRD in T2DM-DKD cohort. Patients in Group 3 (HDL-C ≥1.55 mmol/L) exhibited a higher risk of ESRD compared to Group 1 (HDL-C &amp;lt;1.03 mmol/L). After adjusting for confounders, Group 3 patients still had a significantly higher risk of ESRD (adjusted HR: 1.68, 95% CI: 1.03, 2.71). Analysis of HDL subfractions revealed that a higher HDL3/HDL2 ratio was associated with a lower risk of ESRD. Furthermore, in the NHANES cohort, higher HDL-C levels were linked to a higher risk of all-cause mortality during a median follow-up of 75 months as the result of the weighted Kaplan-Meier curves (p = 0.02). Notably, in patients with CKD stages 1-2, Group 3 participants had a significantly higher hazard ratio (HR: 1.61, 95% CI: 1.19, 2.19) after adjusting for confounders. Conclusion This study challenges the notion of HDL-C as ‘good cholesterol’ in patients with DKD, as higher HDL-C levels were associated with increased risks of ESRD and all-cause mortality. Additionally, the study highlights the potential protective effect of a higher HDL3/HDL2 ratio against ESRD. These findings contribute to reevaluating the role of HDL-C and its subfractions in DKD patients.

Association between dietary quality and accelerated aging: a cross-sectional study of two cohorts.

Background: Diet quality significantly influences aging processes and age-related health outcomes. This study aims to explore the association between dietary quality and accelerated aging in two large cohorts. Methods: This study collected data from the Kailuan and National Health and Nutrition Examination Survey (NHANES) cohorts; participants' dietary quality was evaluated using the American Heart Association (AHA) dietary score and Healthy Eating Index-2015 (HEI-2015), respectively. Accelerated aging in participants was determined by calculating the difference between phenotypic age and chronological age. Logistic regression models were used to explore the association between dietary quality scores and accelerated aging. Additionally, variations in this association across different subgroups were investigated. To minimize the influence of excessive aging, individuals aged 75 and above were excluded in sensitivity analyses. Results: In this study, we included 33 701 participants (27.3% female, mean age 57.29 ± 11.88) from the Kailuan study and 9285 participants (50.6% female, mean age 49.83 ± 17.62) from NHANES. In the Kailuan cohort, individuals with dietary scores ranging from 3 to 5 exhibited a 22% lower risk of accelerated aging compared to those scoring between 0 and 2 (OR = 0.78, 95% CI = 0.72-0.85). Similarly, in the NHANES cohort, participants in the highest quartile of HEI-2015 experienced a 34% reduction in the risk of accelerated aging compared to those in the lowest quartile (OR = 0.66, 95% CI = 0.52-0.84). Subgroup analyses underscored a more pronounced association between dietary quality and accelerated aging among males and individuals with unhealthy lifestyles. Sensitivity analyses confirmed the robustness of the association between dietary quality and accelerated aging. Conclusion: In summary, our study found a significant association between dietary quality and accelerated aging. Better dietary quality was associated with a reduced risk of accelerated aging, particularly among males, smokers, and participants with unhealthy lifestyles.

Development of a New Model of Insulin Sensitivity in Patients With Type 2 Diabetes and Association With Mortality.

Despite being one of the major drivers of diabetes incidence, the degree of insulin resistance in patients with type 2 diabetes (T2D) is not usually evaluated in clinical practice or in large epidemiologic studies. To identify a model of insulin sensitivity using widely available clinical and laboratory parameters in patients with T2D and evaluate its association with all-cause and cardiovascular mortality. One hundred forty patients with T2D underwent a euglycemic hyperinsulinemic clamp to measure total body glucose disposal rate (mg kg-1 minute-1). We used demographic, clinical, and common laboratory parameters to estimate insulin sensitivity (IS) via stepwise linear regression on 85 patients (training cohort) and validated it in the remaining 55 (validation cohort). The identified equation was then applied to 3553 patients with T2D from the 1999-2010 cycles of the National Health and Nutrition Examination Survey (NHANES) to evaluate its association with all-cause and cardiovascular mortality up to December 2015. The best model included triglycerides, gamma glutamyl transpeptidase, albumin excretion rate, and body mass index. The identified IS score correlated well with the clamp-derived glucose disposal rate in both the training (r = 0.77, P < .001) and the validation (r = 0.74, P < .001) cohorts. In the NHANES cohort, after a median follow-up of 8.3 years, 1054 patients died, 265 of cardiovascular causes. In a multivariable Cox proportional hazard model adjusted for age, sex, race-ethnicity, education, cigarette smoke, total cholesterol, chronic kidney disease, blood pressure, prevalent cardiovascular disease, and alcohol consumption, a higher estimated IS was associated with a lower risk of both all-cause and cardiovascular mortality. We propose a new model of IS in patients with T2D based on readily available clinical and laboratory data. Its potential applications are in both diagnosis as well as prognostication.

Comparison of the diagnostic performance of twelve noninvasive scores of metabolic dysfunction-associated fatty liver disease

BackgroundThe absence of distinct symptoms in the majority of individuals with metabolic dysfunction-associated fatty liver disease (MAFLD) poses challenges in identifying those at high risk, so we need simple, efficient and cost-effective noninvasive scores to aid healthcare professionals in patient identification. While most noninvasive scores were developed for the diagnosis of nonalcoholic fatty liver disease (NAFLD), consequently, the objective of this study was to systematically assess the diagnostic ability of 12 noninvasive scores (METS-IR/TyG/TyG-WC/TyG-BMI/TyG-WtHR/VAI/HSI/FLI/ZJU/FSI/K-NAFLD) for MAFLD.MethodsThe study recruited eligible participants from two sources: the National Health and Nutrition Examination Survey (NHANES) 2017-2020.3 cycle and the database of the West China Hospital Health Management Center. The performance of the model was assessed using various metrics, including area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), integrated discrimination improvement (IDI), decision curve analysis (DCA), and subgroup analysis.ResultsA total of 7398 participants from the NHANES cohort and 4880 patients from the Western China cohort were included. TyG-WC had the best predictive power for MAFLD risk in the NHANES cohort (AUC 0.863, 95% CI 0.855–0.871), while TyG-BMI had the best predictive ability in the Western China cohort (AUC 0.903, 95% CI 0.895–0.911), outperforming other models, and in terms of IDI, NRI, DCA, and subgroup analysis combined, TyG-WC remained superior in the NAHANES cohort and TyG-BMI in the Western China cohort.ConclusionsTyG-BMI demonstrated satisfactory diagnostic efficacy in identifying individuals at a heightened risk of MAFLD in Western China. Conversely, TyG-WC exhibited the best diagnostic performance for MAFLD risk recognition in the United States population. These findings suggest the necessity of selecting the most suitable predictive models based on regional and ethnic variations.

Greater Blood Heavy Metal Levels in the Participants of National ALS Biorepository Compared to the Participants of National Health And Nutrition Examination Survey (P2-5.024)

<h3>Objective:</h3> To determine the demographic and environmental exposure characteristics of participants in the National ALS Biorepository (Biorepository) and compare the blood levels of cadmium (Cd), lead (Pb), selenium (Se), manganese (Mn), and total mercury (tHg) to National Health and Nutrition Examination Survey (NHANES) participants. <h3>Background:</h3> Amyotrophic lateral sclerosis (ALS) is a rare and fatal disease of the upper and lower motor neurons. While 10% of ALS cases is hereditary, a gene-environment interaction is believed to be the main contributor in many sporadic cases. Elevated heavy metals in blood have been implicated in the pathology of several neurodegenerative diseases. We hypothesize the ALS cohort to have greater levels of blood heavy metals than NHANES participants. <h3>Design/Methods:</h3> Blood samples from Biorepository participants (n=549) collected in 2013–2015 and 2017 were analyzed following the same protocol used to analyze the subset of NHANES cohort (n=10,809) during 2013–2018. We report descriptive summary in demographic (age/sex/race/education/military history) and comparison of blood metal level means using t-test. Further, self-reported occupational- and non-occupational environmental exposures to pesticides, chemicals, and metals were described for Biorepository participants with available environmental risk factor data. NHANES analyses used survey weights and accounted for the complex design to generate nationally representative estimates. <h3>Results:</h3> ALS Biorepository participants had higher geometric means of blood level Cd, Pb, Se, and tHg compared to NHANES cohort. Among the Biorepository participants, exposure to pesticides (90.3%), chemicals (80.7%) and metals (85.8%) from non-occupational settings were self-reported in higher frequency than occupational exposure to these substances. <h3>Conclusions:</h3> Blood metal levels were elevated in ALS Biorepository participants compared to NHANES. Self-reported non-occupational exposures to pesticides, chemicals, and metals were more common than occupational exposures. Determining a potential association between blood metals and exposure history in our cohort can help further understand the role of environmental exposure in the etiology of ALS. <b>Disclosure:</b> Dr. Han has nothing to disclose. Theodore Larson has nothing to disclose. Maureen Orr has nothing to disclose. Jaime Raymond MPH has nothing to disclose. Laurie Wagner has nothing to disclose. Dr. Kaye has received personal compensation for serving as an employee of McKing Consulting Corporation. Dr. Kaye has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Association for the Protection of Human Research Participants. Paul Mehta has nothing to disclose. D. Kevin Horton has nothing to disclose.

Cardiometabolic risk in young adults with Down syndrome.

Studies regarding cardiometabolic risk (CMR) for individuals with Down syndrome (DS) conflict. Our previous research in youth with DS, aged 10-20 years, found increased prevalence of dyslipidemia and prediabetes compared to matched peers without DS. Herein, we compare CMR in young adults with DS, aged 18-35 years, to a similar population-based sample from the 2001-2018 National Health and Nutrition Examination Survey (NHANES). The group with DS had higher NonHDL-C (mean DS 131.9 mg/dL; NHANES 126.1 p < 0.001), lower HDL-C (DS 47.5 mg/dL; NHANES 52.2 p < 0.001), higher LDL-C (DS 109.3 mg/dL; NHANES 105.4 p < 0.001), higher triglycerides (DS 102.9 mg/dL; NHANES 86.9 p < 0.001), but lower fasting glucose (DS 85.8 mg/dL; NHANES 95.2 p < 0.0001), lower HOMA-IR (DS 2.17; NHANES 2.24 p = 0.0006), lower systolic (DS 109.7 mmHg; NHANES 114.6 p < 0.0001) and lower diastolic (DS 60.9 mmHg; NHANES 67.8 p < 0.0001) blood pressures. There was relationship of higher HDL-C, triglycerides, glucose, systolic, and diastolic blood pressure with increasing BMI in the NHANES cohort which was dampened in the group with DS. These results indicate that more information is needed to guide clinicians in screening for CMR in individuals with DS.

The Association Between Insulin Use and Asthma: An Epidemiological Observational Analysis and Mendelian Randomization Study.

Asthma is a common respiratory disease caused by genetic and environmental factors, but the contribution of insulin use to the risk of asthma remains unclear. This study aimed to investigate the association between insulin use and asthma in a large population-based cohort, and further explore their causal relationship by Mendelian randomization (MR) analysis. An epidemiological study including 85,887 participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018 was performed to evaluate the association between insulin use and asthma. Based on the inverse-variance weighted approach, MR analysis were conducted to estimate the causal effect of insulin use on asthma from the UKB and FinnGen datasets, respectively. In the NHANES cohort, we found that insulin use was associated with an increased risk of asthma [odd ratio (OR) 1.38; 95% CI 1.16-1.64; p < 0.001]. For the MR analysis, we found a causal relationship between insulin use and a higher risk of asthma in both Finn (OR 1.10; p < 0.001) and UK Biobank cohorts (OR 1.18; p < 0.001). Meanwhile, there was no causal association between diabetes and asthma. After multivariable adjustment for diabetes in UKB cohort, the insulin use remained significantly associated with an increased risk of asthma (OR 1.17, p < 0.001). An association between insulin use and an increased risk of asthma was found via the real-world data from the NHANES. In addition, the current study identified a causal effect and provided a genetic evidence of insulin use and asthma. More studies are needed to elucidate the mechanisms underlying the association between insulin use and asthma.

Lifetime Cardiovascular Disease Risk by Coronary Artery Calcium Score in Individuals With and Without Diabetes: An Analysis From the Multi-Ethnic Study of Atherosclerosis.

To assess lifetime cardiovascular disease (CVD) risk by coronary artery calcium (CAC) score in individuals with diabetes from the Multi-Ethnic Study of Atherosclerosis (MESA) and compare risk with that in individuals without diabetes. We developed a microsimulation model with well, diabetes, post-CVD, and death health states using multivariable time-dependent Cox regression with age as time scale. We initially used 10-year follow-up data of 6,769 MESA participants, including coronary heart disease (CHD) (n = 272), heart failure (n = 201), stroke (n = 186), and competing death (n = 619) and assessed predictive validity at 15 years. We externally validated the model in matched National Health and Nutrition Examination Survey (NHANES) participants. Subsequently, we predicted CVD risk until age 100 years by diabetes, 10-year pooled cohort equations risk, and CAC score category (0, 1-100, or 100+). The model showed good calibration and discriminative performance at 15 years, with discrimination indices 0.71-0.78 across outcomes. In the NHANES cohort, predicted 15-year mortality risk corresponded well with Kaplan-Meier risk, especially for those with diabetes: 29.6% (95% CI 24.9-34.8) vs. 32.4% (95% CI 27.2-37.2), respectively. Diabetes increased lifetime CVD risk, similar to shifting one CAC category upward (from 0 to 1-100 or from 1-100 to 100+). Patients with diabetes and CAC score of 0 had a lifetime CVD risk that overlapped with that of individuals without diabetes who were at low 10-year pooled cohort equations risk (<7.5%). Patients with diabetes carry a spectrum of CVD risk. CAC scoring may improve decisions for preventive interventions for patients with diabetes by better delineating lifetime CVD risk.

Differences in estimates for 10-year risk of cardiovascular disease in Black versus White individuals with identical risk factor profiles using pooled cohort equations: an in silico cohort study

SummaryBackgroundSex-specific and race-specific pooled cohort equations (PCEs) are recommended for estimating the 10-year risk of cardiovascular disease, with an absolute risk of more than 7·5% indicating a clinical decision threshold. We compared differences between Black and White individuals in PCE-estimated absolute cardiovascular disease risk across various plausible risk factor combinations with the aim of evaluating if using the PCE might result in different clinical decisions in Black versus White individuals with identical risk profiles.MethodsWe generated in silico patient risk profiles by combining numerical risk factors (age [5-year intervals], total cholesterol [20-mg/dl intervals], HDL cholesterol [5-mg/dl intervals], systolic blood pressure [10-mm Hg intervals]) and binary risk factors (smoking, diabetes, and antihypertensive treatment). We compared PCE-estimated 10-year cardiovascular disease risk in Black versus White individuals with identical risk profiles. We did similar comparisons using eligible participants in the Framingham Heart Study (FHS) third generation cohort and the National Health and Nutrition Examination Survey (NHANES) 2017–18.FindingsFor our in silico analysis, we evaluated 29 515 risk factor combinations for women and 30 565 for men, after excluding profiles that generated 10-year cardiovascular disease risk estimates below 1% or above 30%. There were 6357 risk profiles associated with 10-year cardiovascular disease risk above 7·5% for Black men but not for White men (median risk difference [RD] 6·25%, range 0·15–22·8; median relative risk [RR] 2·40, range 1·02–12·6). There were 391 profiles with 10-year cardiovascular disease risk above 7·5% for White men but not Black men (median RD 2·68%, range 0·07–16·9%; median RR 1·42, range 1·01–3·57). There were 6543 risk profiles associated with 10-year estimated cardiovascular disease risk above 7·5% for Black women but not for White women (median RD 6·14%, range 0·35–26·8%; median RR 2·29, range 1·05–12·6). There were 318 profiles with 10-year cardiovascular disease risk above 7·5% for White women but not Black women (median RD 3·71%, range 0·22–20·1%; median RR 1·66, range 1·03–5·46). For the population-based samples, we calculated the PCE-based 10-year cardiovascular disease risk for 1272 eligible participants (378 women; median age 48 years [IQR 44–52]; 100% White) in the FHS third generation cohort and 550 participants (223 women [36·8% Black] and 327 men [40·4% Black]; median age 61 years [IQR 52–67]) in the NHANES cohort. The population-based samples showed similar risk differences to that of the in silico analyses.InterpretationThe PCE might generate substantially divergent cardiovascular disease risk estimates for Black versus White individuals with identical risk profiles, which could introduce race-related variations in clinical recommendations for cardiovascular disease prevention.FundingUS National Institutes of Health.

The risk of diabetes after giving birth to a macrosomic infant: data from the NHANES cohort

AimsGestational diabetes (GDM) increases the risk of developing type 2 diabetes and thus warrants earlier and more frequent screening. Women who give birth to a macrosomic infant, as defined as a birthweight greater than 9 lbs. (or approximately 4000 g), are encouraged to also get early type 2 diabetes screening, as macrosomia may be a surrogate marker for GDM. This study investigates whether a macrosomic infant, as defined as 9lbs, apart from GDM, increases the risk for diabetes later in life.MethodsData on parous women from the National Health and Nutrition Examination Survey (NHANES) 2007–2016 were utilized. Rates of diabetes were compared in those with and without macrosomic infants in Rao-Scott’s chi-square test. Multiple logistic regression was used to test the independent effect of macrosomia on type 2 diabetes controlling for the confounding covariates and adjusting for the complex sampling design. To investigate how onset time affects diabetes, we implemented Cox proportional hazard regressions on time to have diabetes.ResultsAmong 10,089 parous women, macrosomia significantly increased the risk of maternal diabetes later in life in the chi-square test and logistic regression. Independent of GDM, women who deliver a macrosomic infant have a 20% higher chance of developing diabetes compared to women who did not. The expected hazards of having type 2 diabetes is 1.66 times higher in a woman with macrosomic infant compared to counterparts.ConclusionsWomen who gave birth to a macrosomic infant in the absence of GDM should be offered earlier and more frequent screening for type 2 diabetes.

Benign ethnic neutropenia in a South African population, and its association with HIV acquisition and adverse event reporting in an HIV vaccine clinical trial.

Benign ethnic neutropenia (BEN) is defined as a neutrophil count of <1.5×109 cells/L in healthy individuals and is more common in populations of certain ethnicities, e.g. African or Middle Eastern ethnicity. Neutrophil values are commonly included in eligibility criteria for research participation, but little is known about the relationship between BEN, HIV acquisition, and the occurrence of adverse events during clinical trials. We investigated these relationships using data from an HIV vaccine efficacy trial of healthy adults from 5 South African sites. We analysed data from the double-blind, placebo-controlled, randomized trial HVTN 503, and its follow-on study HVTN 503-S to assess the prevalence of BEN, its association with HIV infection, and adverse event reporting. These data were then compared with a time- and age-matched, non-pregnant cohort from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007–2008 in the United States (US). The 739 South African participants had a median age of 22.0 years (interquartile range = 20–26) and 56% (n = 412) were male. Amongst the US cohort of 845 participants, the median age was 26 (IQR: 21–30) and the majority (54%, 457/745) were also male. BEN was present at enrolment in 7.0% (n = 52) of South African participants (6% in the placebo group versus 8% in the vaccine group); 81% (n = 42) of those with BEN were male. Pretoria North had the highest prevalence of BEN (11.6%, 5/43), while Cape Town had the lowest (0.7%, 1/152). Participants with BEN had a lower median neutrophil count (1.3 vs. 3.2x109 cells/L; p<0.001) and BMI (20.8 vs. 22.3 kg/m2; p<0.001) when compared to those without BEN. A greater proportion of Black South Africans had neutrophil counts <1.5×109 cells/L compared to US non-Hispanic Whites from the NHANES cohort (7% [52/739] vs. 0.6% [3/540]; p<0.001). BEN did not increase the odds for HIV infection (adjusted odds ratio [aOR]: 1.364, 95% confidence interval [95% CI]: 0.625–2.976; p = 0.4351). However, female gender (aOR: 1.947, 95% CI: 1.265–2.996; p = 0.0025) and cannabis use (aOR: 2.192, 95% CI: 1.126–4.266; p = 0.0209) increased the odds of HIV acquisition. The incidence rates of adverse events were similar between participants in the placebo group with BEN, and those without: 12.1 (95% CI: 7.3–20.1) vs. 16.5 (95% CI: 14.6–18.7; p = 0.06) events per 100 person-years (py) were noted in the infections and infestations system organ class, respectively. The vaccine group had an event incidence rate of 19.7 (95% CI: 13.3–29.2) vs. 14.8 (95% CI: 13.0–16.8; p = 0.07) events per 100py in the group with, and without BEN, respectively. BEN is more prevalent in Black South Africans compared to US Non-Hispanic Whites. Our data do not support excluding populations from HIV vaccine trials because of BEN. BEN was not associated with increased risk for HIV infection or Adverse events on a vaccine trial. Predictors of HIV infection risk were females and cannabis use, underlying the continued importance of prevention programmes in focusing on these populations.

Clinical characterization of data-driven diabetes subgroups in Mexicans using a reproducible machine learning approach

IntroductionPrevious reports in European populations demonstrated the existence of five data-driven adult-onset diabetes subgroups. Here, we use self-normalizing neural networks (SNNN) to improve reproducibility of these data-driven diabetes subgroups in...

Electronic cigarettes and insulin resistance in animals and humans: Results of a controlled animal study and the National Health and Nutrition Examination Survey (NHANES 2013-2016).

BackgroundThe popularity of electronic cigarettes (E-cigarettes) has risen considerably. Several studies have suggested that nicotine may affect insulin resistance, however, the impact of E-cigarette exposure on insulin resistance, an early measure of cardiometabolic risk, is not known.Methods and resultsUsing experimental animals and human data obtained from 3,989 participants of the United States National Health and Nutrition Examination Survey (NHANES), respectively, we assessed the association between E-cigarette and conventional cigarette exposures and insulin resistance, as modelled using the homeostatic model assessment of insulin resistance (HOMA-IR) and glucose tolerance tests (GTT). C57BL6/J mice (on standard chow diet) exposed to E-cigarette aerosol or mainstream cigarette smoke (MCS) for 12 weeks showed HOMA-IR and GTT levels comparable with filtered air-exposed controls. In the NHANES cohort, there was no significant association between defined tobacco product use categories (non-users; sole E-cigarette users; cigarette smokers and dual users) and insulin resistance. Compared with non-users of e-cigarettes/conventional cigarettes, sole E-cigarette users showed no significant difference in HOMA-IR or GTT levels following adjustment for age, sex, race, physical activity, alcohol use and BMI.ConclusionE-cigarettes do not appear to be linked with insulin resistance. Our findings may inform future studies assessing potential cardiometabolic harms associated with E-cigarette use.

Age-Specific Predictive Models of the Upper Quintile of Periodontal Attachment Loss

A practical method to identify people who are most affected by periodontitis in their age group is currently unavailable. We focused on individuals with mean clinical attachment loss (CAL) above the 80th percentile within each of 10 age groups (5-y intervals between 30 and 74 y as well as ≥75 y). We developed predictive models using combined data from 2 cohorts (2009 to 2010 and 2011 to 2012) from the NHANES (National Health and Nutrition Examination Survey; development cohort [DC], n = 6,757), and we carried out external validation using data from a third NHANES cohort (2013 to 2014; validation cohort [VC], n = 3,447). We used 1) age-specific logistic regression models with stepwise selection to identify significant demographic variables, habits, medical conditions, and selected clinical periodontal parameters (proportion of teeth with probing depth ≥4 mm at incisors and molars and with visible [≥2 mm] recession) and to calculate propensity scores (PSs); 2) Youden’s J statistic to select optimum PS cutoffs to maximize diagnostic performance using receiver operating characteristic curves; and 3) bootstrap resampling with 1,000 replicates to validate the age-specific models and adjust the PS and optimal PS cutoffs for overfitting. The bootstrap-adjusted PSs were used as single predictors of mean CAL over the 80th percentile in the VC. The age-specific upper quintiles of mean CAL ranged between 1.63 and 3.24 mm in the DC and between 1.87 and 3.20 mm in the VC. The area under the curve of the models exceeded 0.85 in all age groups in the DC and 0.84 in the VC, indicating well-validated diagnostic performance. In the DC, sensitivity values ranged between 0.75 and 0.97 and exceeded 0.83 in 8 of 10 age groups. Corresponding values in the VC ranged between 0.56 and 0.89 and exceeded 0.68 in 8 of 10 age groups. We conclude that modeling that incorporates readily obtainable variables through a brief patient interview and an abbreviated periodontal examination accurately identifies individuals who are most affected by periodontitis in different ages.