Association Between High-Sensitivity C-Reactive Protein and Metabolic Syndrome Among Hispanic/Latino Participants of the Hispanic Community Health Study/Study of Latinos.

Purpose: To determine whether high-sensitivity C-reactive protein (hsCRP) is associated with incident Metabolic Syndrome (MetS) among U.S. Hispanic/Latino adults. Patients and Methods: The Hispanic Community Health Study/Study of Latinos is a longitudinal observational cohort assessing cardiovascular health among diverse U.S. Hispanic/Latino adults. hsCRP was measured at visit 1 (2008-2011) and classified as low, moderate, or high, based on the Centers for Disease Control and Prevention and American Heart Association (CDC/AHA) guidelines. All MetS components [abdominal obesity, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, and fasting glucose] were measured at visit 1 and visit 2 (2014-2017). MetS was defined as the presence of three or more components based on the 2005 definition from the modified Third Report of the National Cholesterol Education Program Adult Treatment Panel (modified NCEP ATP III). Participants free of MetS at visit 1 and with complete data on hsCRP and all MetS components were included (n = 6121 participants). We used Poisson regression analysis to determine whether hsCRP was associated with incident MetS after adjusting for demographic, behavioral, and clinical factors. All analyses accounted for the complex survey design of the study. Results: In fully adjusted models, moderate versus low hsCRP was associated with a 33% increased risk of MetS [incidence rate ratio (IRR): 1.33, 95% confidence interval (CI): 1.10-1.61], while high versus low hsCRP was associated with a 89% increased risk of MetS (IRR: 1.89, 95% CI: 1.58-2.25). Conclusions: Greater levels of hsCRP were associated with new onset of MetS in a diverse sample of U.S. Hispanic/Latino adults. Results suggest that hsCRP may be an independent risk factor for MetS.

Prevalence and Associations Between Metabolic Syndrome Components and Hyperuricemia by Race: Findings From US Population, 2011-2020.

OBJECTIVE: We explored the trend in prevalence of hyperuricemia and metabolic syndrome in US populations and investigated associations between components of metabolic syndrome and hyperuricemia by race. METHODS: We analyzed data from the four most recent National Health and Nutrition Examination Survey (NHANES) cycles (2011 to March 2020), comprising 10,175 participants. Hyperuricemia is defined as serum urate >7.0 mg/dL (men) or >5.7 mg/dL (women), following the NHANES-III guideline. The definition of metabolic syndrome follows the National Cholesterol Education Program's Adult Treatment Panel III guideline. We estimated the prevalence of metabolic syndrome and hyperuricemia in each cycle and performed subgroup analyses with logistic regression to investigate the patterns of associated components of metabolic syndrome with hyperuricemia. RESULTS: In the most recent cycle (2017 to March 2020), the prevalence of metabolic syndrome was 45.9% and that of hyperuricemia was 20.7%. Over the 2011 to 2020 period, a significant rise in metabolic syndrome prevalence was observed among Hispanic and Asian populations, and the prevalence of hyperuricemia has increased significantly only in the Hispanic population. After adjustment for confounding factors, patients with metabolic syndrome exhibited a higher hyperuricemia in women than in men. Elevated blood pressure was the strongest factor with hyperuricemia. The association was the weakest in the Asian population. Waist circumference was the only significant factor associated with hyperuricemia in the Asian population. CONCLUSION: The prevalence of metabolic syndrome has an increasing pattern, but there was no specific decadal trend in prevalence of hyperuricemia. There is an ethnicity-specific association of metabolic syndrome and hyperuricemia, especially among Asians.

Disparities in Metabolic Syndrome and Neurocognitive Function Among Older Hispanics/Latinos with Human Immunodeficiency Virus.

Neurocognitive impairment and metabolic syndrome (MetS) are prevalent in persons with HIV (PWH). We examined disparities in HIV-associated neurocognitive function between Hispanic and non-Hispanic White older PWH, and the role of MetS in explaining these disparities. Participants included 116 community-dwelling PWH aged 50-75 years enrolled in a cohort study in southern California [58 Hispanic (53% Spanish speaking) and 58 age-comparable non-Hispanic White; overall group: age: M = 57.9, standard deviation (SD) = 5.7; education (years): M = 13, SD = 3.4; 83% male, 58% AIDS, 94% on antiretroviral therapy]. Global neurocognition was derived from T-scores adjusted for demographics (age, education, sex, ethnicity, language) on a battery of 10 cognitive tests. MetS was ascertained via standard criteria that considered central obesity, and fasting elevated triglycerides, low high-density lipoprotein cholesterol and elevated glucose, or medical treatment for these conditions. Covariates examined included sociodemographic, psychiatric, substance use and HIV disease characteristics. Compared with non-Hispanic Whites, Hispanics showed worse global neurocognitive function (Cohen's d = 0.56, p < 0.05) and had higher rates of MetS (38% vs. 56%, p < 0.05). A stepwise regression model including ethnicity and significant covariates showed Hispanic ethnicity was the sole significant predictor of worse global neurocognition (B = -3.82, SE = 1.27, p < 0.01). A model also including MetS showed that both Hispanic ethnicity (B = -3.39, SE = 1.31, p = 0.01) and MetS (B = -2.73, SE = 1.31, p = 0.04) were independently associated with worse neurocognition. In conclusion, findings indicate that increased MetS is associated with worse neurocognitive function in both Hispanic and non-Hispanic White older PWH, but does not explain neurocognitive disparities. MetS remains an important target for intervention efforts to ameliorate neurocognitive dysfunction among diverse older PWH.

Ethnic differences in metabolic syndrome in high-income countries: A systematic review and meta-analysis.

This review aimed to systematically quantify the differences in Metabolic Syndrome (MetS) prevalence across various ethnic groups in high-income countries by sex, and to evaluate the overall prevalence trends from 1996 to 2022. We conducted a systematic literature review using MEDLINE, Web of Science Core Collection, CINAHL, and the Cochrane Library, focusing on studies about MetS prevalence among ethnic groups in high-income countries. We pooled 23 studies that used NCEP-ATP III criteria and included 147,756 healthy participants aged 18 and above. We calculated pooled prevalence estimates and 95% confidence intervals (CI) using both fixed-effect and random-effect intercept logistic regression models. Data were analysed for 3 periods: 1996-2005, 2006-2009, and 2010-2021. The pooled prevalence of MetS in high-income countries, based on the NCEP-ATP III criteria, was 27.4% over the studied period, showing an increase from 24.2% in 1996-2005 to 31.9% in 2010-2021, with men and women having similar rates. When stratified by ethnicity and sex, ethnic minority women experienced the highest prevalence at 31.7%, while ethnic majority women had the lowest at 22.7%. Notably, MetS was more prevalent in ethnic minority women than men. Among ethnic minorities, women had a higher prevalence of MetS than men, and the difference was highest in Asians (about 15 percentage points). Among women, the prevalence of MetS was highest in Asians (41.2%) and lowest in Blacks/Africans (26.7%). Among men, it was highest in indigenous minority groups (34.3%) and lowest among in Blacks/Africans (19.8%). MetS is increasing at an alarming rate in high-income countries, particularly among ethnic minority women. The burden of MetS could be effectively reduced by tailoring interventions according to ethnic variations and risk profiles.

Ethnic variations in metabolic syndrome components and their associations with the gut microbiota: the HELIUS study.

BACKGROUND: The occurrence of metabolic syndrome (MetS) and the gut microbiota composition are known to differ across ethnicities yet how these three factors are interwoven is unknown. Also, it is unknown what the relative contribution of the gut microbiota composition is to each MetS component and whether this differs between ethnicities. We therefore determined the occurrence of MetS and its components in the multi-ethnic HELIUS cohort and tested the overall and ethnic-specific associations with the gut microbiota composition. METHODS: We included 16,209 treatment naïve participants of the HELIUS study, which were of Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish, and Moroccan descent to analyze MetS and its components across ethnicities. In a subset (n = 3443), the gut microbiota composition (16S) was associated with MetS outcomes using linear and logistic regression models. RESULTS: A differential, often sex-dependent, prevalence of MetS components and their combinations were observed across ethnicities. Increased blood pressure was commonly seen especially in Ghanaians, while South-Asian Surinamese and Turkish had higher MetS rates in general and were characterized by worse lipid-related measures. Regarding the gut microbiota, when ethnic-independent associations were assumed, a higher α-diversity, higher abundance of several ASVs (mostly for waist and triglyceride-related outcomes) and a trophic network of ASVs of Ruminococcaceae, Christensenellaceae, and Methanobrevibacter (RCM) bacteria were associated with better MetS outcomes. Statistically significant ethnic-specific associations were however noticed for α-diversity and the RCM trophic network. Associations were significant in the Dutch but not always in all other ethnicities. In Ghanaians, a higher α-diversity and RCM network abundance showed an aberrant positive association with high blood pressure measures compared to the other ethnicities. Even though adjustment for socioeconomic status-, lifestyle-, and diet-related variables often attenuated the effect size and/or the statistical significance of the ethnic-specific associations, an overall similar pattern across outcomes and ethnicities remained. CONCLUSIONS: The occurrence of MetS characteristics among ethnicities is heterogeneous. Both ethnic-independent and ethnic-specific associations were identified between the gut microbiota and MetS outcomes. Across multiple ethnicities, a one-size-fits-all approach may thus be reconsidered in regard to both the definition and/or treatment of MetS and its relation to the gut microbiota.

Waist circumference and cardiometabolic parameters in people of African/Caribbean ancestry with HIV in South London (CKD-AFRICA study).

BACKGROUND: There are no validated waist circumference (WC) cut-offs to define metabolic syndrome in Black people with HIV. METHODS: Cross-sectional analyses within the CKD-AFRICA study. We used Pearson correlation coefficients and receiver operating characteristic (ROC) curves to describe the relationship between WC and cardiometabolic parameters including triglycerides, cholesterol, glucose, glycated haemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR), and to identify optimal WC cut-offs for each of these outcomes. RESULTS: We included 383 participants (55% female, median age 52 years) with generally well controlled HIV. Female and male participants had similar WC (median 98 vs. 97 cm, p = .16). Generally weak correlations (r2 < 0.2) between WC and other cardiometabolic parameters were observed, with low (<0.7) areas under the ROC curves. The optimal WC cut-offs for constituents of the metabolic syndrome, HbA1c and HOMA-IR ranged from 92 to 101 cm in women and 89-98 cm in men, respectively; these cut-offs had variable sensitivity (52%-100%) and generally poor specificity (28%-72%). CONCLUSIONS: In this cohort of Black people with HIV, WC cut-offs for cardiometabolic risk factors in male participants were in line with the recommended value of 94 cm while in female participants they vastly exceeded the recommended 80 cm for white women.

Understanding ethnic inequalities in the design and implementation of digital health interventions for cardiometabolic disease: a qualitative study.

BACKGROUND: The use of digital health interventions (DHIs), such as apps and wearable devices, for prevention and management of cardiometabolic disease, has been accelerated by the impact of COVID-19 on health-care services. Digital inequalities disproportionately affect those most at risk of wider health inequalities (e.g., older age, minority ethnicity, and lower household income) and might intersect with populations with higher cardiometabolic disease risk such as South Asians in the UK. We wanted to understand how those involved in DHI implementation perceive and address these inequalities, to help develop recommendations to reduce the risk of DHI implementation exacerbating existing health inequalities. METHODS: For this qualitative study we used a purposive sampling strategy, whereby focus groups and semi-structured interviews were done online between April 7 and Dec 8, 2022, with stakeholders, including health-care professionals (n=15); technology developers and digital experts (n=10); those in strategy, evaluation, or policy roles (n=15); and charities (n=4). Discussions covered barriers and facilitators to inclusive design and implementation of DHIs, with focus dependent on expertise. Findings from a qualitative study with South Asian patients have been reported separately. Audio recordings were transcribed and coded using reflexive thematic analysis. Participants provided written consent and the study received NHS Health Research Authority approval from London - Brent Research Ethics Committee (IRAS 261047). FINDINGS: Participants had a good understanding of barriers to DHI use for cardiometabolic disease faced by South Asians, highlighting the need to design for language, culture, and diet. Many emphasised the link between digital exclusion and socioeconomic deprivation, across all ethnic groups in the UK. The potential for DHIs in improving patient outcomes was recognised; however, equity concerns included unequal patient access, lack of data and resources to target support, and need for quality evidence to recommend and commission digital tools. A range of solutions for improving equity were suggested such as resourcing support for digital upskilling, community engagement, and the role of regulation in embedding improved design and evaluation of DHIs available through health-care services. INTERPRETATION: This study reflects the experiences of professionals interested in (digital) health inequalities. However, challenges to equitable digital health implementation and use are well described. Our findings present multi-sectoral responsibilities and opportunities for action. FUNDING: National Institute for Health and Care Research (NIHR).

Disparities in absolute cardiovascular risk, metabolic syndrome, hypertension, and other risk factors by income within racial/ethnic groups among middle-aged and older US people.

This cross-sectional study determined income disparities in age-adjusted prevalence and trends of 10-year high absolute cardiovascular disease (CVD) risk, metabolic syndrome, hypertension, diabetes, obesity, chronic kidney disease (CKD), leisure-time physical activity (LTPA), and current tobacco smoking within racial/ethnic groups in the US. National Health and Nutrition Examination Survey 2001-2016 data of 40-79-year-old people were analyzed. Survey periods were grouped as 2001-2006, 2007-2012, and 2013-2016. Race/ethnicity was grouped as non-Hispanic whites, non-Hispanic blacks, and other races/ethnicities. Three equal-sized strata (low-, middle-, and high income) were made from the family income-to-poverty ratio. Of the 25,777 participants (mean age: 55.6 years, 48% males), a majority of the studied prevalence was higher in most survey years among non-Hispanic blacks compared to non-Hispanic whites. Most studied prevalence was also higher among low-income people than middle-/high-income people. Within racial/ethnic groups, the prevalence also differed by income for high CVD risk, metabolic syndrome, hypertension, diabetes, obesity, CKD, LTPA, and tobacco smoking (P < 0.05) in most survey periods. After stratifying by race/ethnicity, the prevalence of many conditions remained disproportionately higher among low- and middle-income people, compared to those with high income during most survey periods in all racial/ethnic groups. These results reveal income in addition to race/ethnicity to be an important correlate of cardiovascular health and underscore the need to consider each when controlling for risk factors.

The impact of progredient vessel and tissue stiffening for the development of metabolic syndrome.

Established risk factors for the metabolic syndrome as diabetes and arterial hypertension are believed to be the cause of arteriosclerosis and subsequently following diseases like coronary heart disease, apoplexy, or chronic renal failure. Based on broad evidence from the already available experimental literature and clinical experience, an alternative hypothesis is presented that puts an increased vessel and organ stiffness to the beginning of the pathophysiological scenario. The stiffness itself is caused by a persistent activation of mechano-sensitive cation channels like the epithelial/endothelial sodium channel. A further enhancement takes place by proteins like JACD and RhoA coupled phospholipase C coupled G-protein receptors and integrins. A self-enhancing positive feedback loop by activation of YAP/TAZ signaling is a further central pillar of this theory. Further investigations are necessary to verify this hypothesis. If this hypothesis could be confirmed fundamental changes regarding the pharmacologic therapy of the diseases that are currently summarizes as metabolic syndrome would be the consequence.

Vitamin D status and prevalence of metabolic syndrome by race and Hispanic origin in US adults: findings from the 2007-2014 NHANES.

BACKGROUND: Vitamin D status has been found to be inversely associated with metabolic syndrome (MetS) in some studies. Vitamin D status varies by race and ethnicity, and the association of MetS with vitamin D status in US adults and by race and Hispanic origin has not been evaluated extensively. OBJECTIVES: We aimed to examine the associations between vitamin D status and MetS overall, and across race and Hispanic origin groups, in a nationally representative sample of US adults who participated in the NHANES from 2007 to 2014. METHODS: The total sample included 8639 adults, ≥20 y of age. Serum vitamin D was measured using a standardized LC-tandem MS method and was categorized using data-driven tertiles. MetS was defined using measured waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were fitted [accounting for sociodemographic and lifestyle factors, dietary supplement use, and BMI (in kg/m2)] to examine the associations of serum vitamin D with MetS among adults overall, and by race and Hispanic origin. RESULTS: Serum vitamin D in the lowest tertile (≤56 nmol/L) was significantly associated with increased odds of MetS compared with the highest tertile (>77.9 nmol/L) (fully adjusted model OR: 1.85; 95% CI: 1.51, 2.27). Inverse associations were noted for all race-Hispanic origin groups: non-Hispanic white (NHW) (OR: 2.24; 95% CI: 1.67, 3.01), non-Hispanic black (OR: 1.56; 95% CI: 1.06, 2.29), and Hispanic (OR: 1.48; 95% CI: 1.03, 2.14) adults. CONCLUSIONS: Lower vitamin D status was significantly associated with MetS among US adults after adjusting for sociodemographic and lifestyle factors, dietary supplement use, and BMI. This finding was noted across all race and Hispanic origin groups, although the strength of the association varied, being strongest for NHW adults.

Distinct racial and ethnic metabolic syndrome characteristics: A comparative assessment in low-income children 7-10 years of age.

BACKGROUND: Pediatric MetS prevalence varies due to lack of consensus on evaluative criteria and associated thresholds, with most not recommending a diagnosis <10 years. However, MetS risk components are becoming evident earlier in life and affect races and ethnicities disproportionately. OBJECTIVES: To compare the prevalence of MetS based on existing definitions and elucidate racial- and ethnic-specific characteristics associated with MetS prevalence. METHODS: The baseline and follow-up samples included 900 and 557 children 7-10 years, respectively. Waist circumference, BMI percentile, blood pressure, fasting plasma glucose (FPG), insulin, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were measured. Agreement between MetS definitions was quantified via kappa statistics. MetS and risk factor prevalence and the predictability of metabolic parameters on MetS eight months later was evaluated via logistic regression. McFadden pseudo-R2 was reported as a measure of predictive ability, and the Akaike information criterion evaluated fit of each model. RESULTS: The baseline sample was 55.0% male and 71.6% Hispanic, followed by non-Hispanic White (NHW) (17.3%) and non-Hispanic Black (NHB) (11.1%), with an average age of 9.2 years. MetS prevalence ranged from 7.6% to 21.4%, highest in Hispanic (9.0%-24.0%) and lowest in NHB children (4.0%-14.0%). Highest agreement was between Ford et al. and Cook et al. definitions (K = 0.88) and lowest agreements were consistently with the International Diabetes Federation criteria (K ≤ 0.57). Compared to NHW children, Hispanic children had higher odds for MetS (OR: 1.7; p = 0.03) and waist circumference, HDL-C, and FPG risk factors (p < 0.05), while NHB children had higher odds for the FPG risk factor (p ≤ 0.007) and lower odds for the plasma triglycerides risk factor (p = 0.002), across multiple MetS definitions. In longitudinal analyses, HDL-C was the strongest independent predictor of MetS in Hispanic and NHW children (p < 0.001 and p < 0.01, respectively), while plasma triglycerides was the strongest independent predictor of MetS in NHB children (p < 0.05). CONCLUSIONS: MetS prevalence was high in children ≤10 years, and proposed criteria are susceptible to racial and ethnic bias, diagnosing some populations more than other populations with high cardiovascular risk. Earlier preventative measures should be imposed in clinical settings, accounting for racial and ethnic differences, to mitigate disease onset.

Metabolic syndrome and prostate cancer in Afro-Caribbean men.

INTRODUCTION AND OBJECTIVES: Metabolic syndrome (MetS) is a group of risk factors that increases the likelihood of developing cardiovascular diseases. Although suggested, the relationship between MetS and prostate cancer (PCa) is still inconclusive. Very few studies have addressed this question in populations of African descent, which are disproportionately affected by PCa. This study aimed to assess the prevalence of MetS among incident cases of Afro-Caribbean PCa and estimate its association with adverse clinicopathological features and the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: We included 285 consecutive patients with incident cases of PCa attending the University Hospital of Guadeloupe (French West Indies). MetS was evaluated at the time of diagnosis by collecting information on blood pressure, glycaemic status, triglyceride and high-density lipoprotein cholesterol levels, and obesity through various surrogates, including two waist circumference indicators (≤94 cm, ≥102 cm), the waist-to-hip ratio (≥0.95), and body mass index (BMI; ≥30 kg/m2 ). We followed 245 patients who underwent RP as primary treatment of localized PCa. RESULTS: The prevalence of MetS varied greatly, from 31.6% to 16.4%, when a waist circumference ≥94 cm or BMI were used as obesity surrogates, respectively. No significant associations were found between MetS, regardless of the obesity criteria employed, and the risk of adverse pathological features or BCR. CONCLUSIONS: The high variability in MetS resulting from the diversity of obesity criteria used may explain the discordant associations reported in the literature. Further studies using strict and uniform criteria to define MetS on homogeneous ethnic groups are encouraged to clarify the association, if any, between MetS and PCa outcomes.

Metabolic syndrome is not associated to an increased risk of low bone mineral density in men at risk for osteoporosis.

PURPOSE: We have recently demonstrated a significant association between osteoporosis (Op) and metabolic syndrome (MetS) in Caucasian women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. This cross-sectional study was performed to evaluate the association between MetS and Op in Caucasian men enrolled in the same geographical area, with identical criteria and in the same time range. METHODS: Among subjects enrolled in the SIMON study, we selected the medical records of all free-living men who performed a contextual evaluation of both bone mineral density (BMD) by DXA and MetS constitutive elements (arterial blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose). All enrolled subjects refer to "COMEGEN" general practitioners' cooperative operating in Naples, Southern Italy. RESULTS: Overall, the medical records of 880 men were examined. No significant association between MetS and Op was observed. Among MetS constitutive elements, waist circumference was inversely related to Op risk. CONCLUSION: In Caucasian men examined by DXA for suspected Op, no significant association was observed between Op and MetS. The study results contrast to those observed in women enrolled in the same geographical area, with identical criteria and in the same time range and may be related to sexual dimorphism occurring in clinical expressiveness of both MetS and Op.

Specific Dietary Protein Sources Are Associated with Cardiometabolic Risk Factors in the Boston Puerto Rican Health Study.

BACKGROUND: Puerto Rican adults residing in the US mainland experience a high prevalence of metabolic syndrome (MetS). A diet containing healthy protein-rich sources may help control risk factors for MetS. OBJECTIVE: This study aimed to evaluate 2-year longitudinal associations between intake of various protein-rich foods and changes in the six MetS components. DESIGN: This is a secondary analysis of a longitudinal cohort study using data from the baseline (2004-2007) and 2-year follow-up visits (2006-2011) in the Boston Puerto Rican Health Study. PARTICIPANTS/SETTING: Participants were self-identified Puerto Ricans, aged 45 to 75 years, residing in Boston, Massachusetts, or the surrounding area (n = 1,126). MAIN OUTCOME MEASURES: MetS components were fasting glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic and diastolic blood pressures, and waist circumference. STATISTICAL ANALYSIS: Baseline intake of foods reported in a semiquantitative food frequency questionnaire were expressed as servings/day, and protein-rich foods were categorized as unprocessed white meat, unprocessed red meat, processed meat, milk and yogurt, cheese, fish and seafood, beans, nuts, and eggs. Associations between each continuous protein food group and continuous 2-year change in MetS components were assessed using linear mixed models adjusted for socioeconomic and behavioral factors, and other dietary sources. RESULTS: The top contributors to total protein intake were unprocessed red meat (13.3%) and unprocessed poultry (13.0%), and the lowest were eggs (2.92%) and nuts (0.91%). Higher intake of processed meats was associated with an increase in waist circumference over 2 years (ß = 1.28; standard error [SE] = 0.63), whereas higher intake of fish and seafood was associated with a decrease in waist circumference (ß = -3.47; SE = 1.39). Intake of unprocessed poultry was associated with a decrease in triglycerides (ß = -24.5; SE = 9.13). No other significant associations were observed between protein sources and 2-year changes in MetS components. CONCLUSIONS: Consuming less processed meat and more fish and seafood and unprocessed poultry was associated with decreases in waist circumference and triglycerides among US mainland Puerto Ricans. Other dietary protein sources were not related to cardiometabolic health.

A 6-CpG validated methylation risk score model for metabolic syndrome: The HyperGEN and GOLDN studies.

There has been great interest in genetic risk prediction using risk scores in recent years, however, the utility of scores developed in European populations and later applied to non-European populations has not been successful. The goal of this study was to create a methylation risk score (MRS) for metabolic syndrome (MetS), demonstrating the utility of MRS across race groups using cross-sectional data from the Hypertension Genetic Epidemiology Network (HyperGEN, N = 614 African Americans (AA)) and the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, N = 995 European Americans (EA)). To demonstrate this, we first selected cytosine-guanine dinucleotides (CpG) sites measured on Illumina Methyl450 arrays previously reported to be significantly associated with MetS and/or component conditions in more than one race/ethnic group (CPT1A cg00574958, PHOSPHO1 cg02650017, ABCG1 cg06500161, SREBF1 cg11024682, SOCS3 cg18181703, TXNIP cg19693031). Second, we calculated the parameter estimates for the 6 CpGs in the HyperGEN data (AA) and used the beta estimates as weights to construct a MRS in HyperGEN (AA), which was validated in GOLDN (EA). We performed association analyses using logistic mixed models to test the association between the MRS and MetS, adjusting for covariates. Results showed the MRS was significantly associated with MetS in both populations. In summary, a MRS for MetS was a strong predictor for the condition across two race groups, suggesting MRS may be useful to examine metabolic disease risk or related complications across race/ethnic groups.

Potential evidence for epigenetic biomarkers of metabolic syndrome in human whole blood in Latinos.

Metabolic syndrome (MetS) is highly prevalent worldwide. In the United States, estimates show that more than 30% of the adult population has MetS. MetS consists of multiple phenotypes, including obesity, dyslipidemia, and impaired glucose tolerance. Therefore, identifying the molecular mechanisms to explain this complex disease is critical for diagnosing and treating MetS. We previously showed 70 increased genes and 20 decreased genes in whole blood in MetS participants. The present study aimed to identify blood-based DNA methylation biomarkers in non-MetS versus MetS participants. The present study analyzed whole blood DNA samples from 184 adult participants of Latino descent from the Arizona Insulin Resistance (AIR) registry. We used the National Cholesterol Education Program Adult Treatment Panel III (NCEP: ATP III) criteria to identify non-MetS (n = 110) and MetS (n = 74) participants. We performed whole blood methylation analysis on select genes: ATP Synthase, H+ Transporting mitochondrial F1 Complex, Epsilon Subunit (ATP5E), Cytochrome C Oxidase Subunit VIc (COX6C), and Ribosomal Protein L9 (RPL9). The pyrosequencing analysis was a targeted approach focusing on the promoter region of each gene that specifically captured CpG methylation sites. In MetS participants, we showed decreased methylation in two CpG sites in COX6C and three CpG sites in RPL9, all p < 0.05 using the Mann-Whitney U test. There were no ATP5E CpG sites differently methylated in the MetS participants. Furthermore, while adjusting for age, gender, and smoking status, logistic regression analysis reaffirmed the associations between MetS and mean methylation within COX6C and RPL9 (both p < 0.05). In addition, Spearman's correlation revealed a significant inverse relationship between the previously published gene expression data and methylation data for RPL9 (p < 0.05). In summary, these results highlight potential blood DNA methylation biomarkers for the MetS phenotype. However, future validation studies are warranted to strengthen our findings.

Association of elevated serum aminotransferase levels with chronic kidney disease measures: hispanic community health study/study of latinos.

BACKGROUND: Previous studies have shown an association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), but it is unclear whether the association is independent of metabolic syndrome. METHODS: Data from 13,006 participants aged 18 to 74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) without viral hepatitis, excessive alcohol consumption, or high transferrin saturation levels were analyzed. Suspected NAFLD was defined as presence of sex-specific elevations in serum aminotransferase levels (aspartate aminotransferase (AST) > 37 U/L or alanine aminotransferase (ALT) > 40 U/L for men and AST or ALT > 31 U/L for women). Logistic regression was used to examine cross-sectional associations of elevated serum aminotransferase levels with low estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2 based on cystatin C), and with high urinary albumin-to-creatinine ratio (UACR) (> 17 mg/g in men and > 25 mg/ g in women) in separate models adjusting for demographic characteristics and metabolic syndrome. RESULTS: Mean (SD) age was 41 (0.27) years, and 45 % were male. Elevated serum aminotransferase levels were noted in 18.8 % of the population and were associated with greater odds of high UACR (OR = 1.31; 95 % CI = 1.10, 1.56) after adjusting for demographic characteristics; this association became non-significant after adjustment for metabolic syndrome (OR = 1.11, 95 % CI = 0.92, 1.33). In contrast, elevated serum aminotransferase levels were not associated with low eGFR (odds ratio (OR) = 0.73; 95 % confidence interval (CI) = 0.45, 1.18) after adjusting for covariates. CONCLUSIONS: In this sample of diverse U.S. Hispanic Latino adults, elevated serum aminotransferase levels were not independently associated with measures of CKD.

Metabolic syndrome in antipsychotic-naïve patients with first-episode psychosis: a systematic review and meta-analysis.

BACKGROUND: It is unclear what the prevalence of metabolic syndrome (MetS) in drug-naïve first-episode of psychosis (FEP) is, as previous meta-analyses were conducted in minimally exposed or drug-naïve FEP patients with psychotic disorder at any stage of the disease; thus, a meta-analysis examining MetS in naïve FEP compared with the general population is needed. METHODS: Studies on individuals with FEP defined as drug-naïve (0 days exposure to antipsychotics) were included to conduct a systematic review. A meta-analysis of proportions for the prevalence of MetS in antipsychotic-naïve patients was performed. Prevalence estimates and 95% CI were calculated using a random-effect model. Subgroup analyses and meta-regressions to identify sources and the amount of heterogeneity were also conducted. RESULTS: The search yielded 4143 articles. After the removal of duplicates, 2473 abstracts and titles were screened. At the full-text stage, 112 were screened, 18 articles were included in a systematic review and 13 articles in the main statistical analysis. The prevalence of MetS in naïve (0 days) FEP is 13.2% (95% CI 8.7-19.0). Ethnicity accounted for 3% of the heterogeneity between studies, and diagnostic criteria used for MetS accounted for 7%. When compared with controls matched by sex and age, the odds ratio is 2.52 (95% CI 1.29-5.07; p = 0.007). CONCLUSIONS: Our findings of increased rates of MetS in naïve FEP patients suggest that we are underestimating cardiovascular risk in this population, especially in those of non-Caucasian origin. Our findings support that altered metabolic parameters in FEPs are not exclusively due to antipsychotic treatments.

Hypertriglyceridemia as an Independent Predictor for Ten-Year Incidence of Diabetes in Thais.

BACKGROUND: Fasting hypertriglyceridemia commonly associates with insulin resistance and is frequently prevalent in type 2 diabetes mellitus (DM). However, hypertriglyceridemia has not been investigated as an independent predictor of incidence of DM, especially in Thais. METHODS: A 10-year hospital-based retrospective cohort study was conducted in a tertiary care setting in Thailand. Health check-up data in 2007 from healthy participants without underlying disease were extracted as baseline data. In 2017, 10 years following an initial examination, the diagnosis of DM and other laboratory data were identified. Hypertriglyceridemia was defined as fasting triglyceride level ≥ 150 mg/dL. A generalized additive model (GAM) was applied to demonstrate a relationship between fasting TG level and probability of incident DM in 10 years. An association between hypertriglyceridemia and 10-year incidence of DM was evaluated using univariable and multivariable logistic regression analysis. RESULTS: A total of 1342 non-diabetic adults with complete both baseline and 10-year follow-up data were included in the analysis. The incidence of DM in the study period was 10.3%. Baseline fasting triglyceride level is significantly higher in participants with incidence of DM, with a median difference of 45 mg/dL (P < 0.01). Univariable logistic regression showed that hypertriglyceridemia was associated with 10-year incidence of DM (odds ratio (OR) 3.03, 95% CI 2.12-4.35). After adjusting for potential confounders, hypertriglyceridemia remained significantly associated with incidence of DM (OR 2.33, 95% CI 1.61-3.39). CONCLUSION: Fasting triglyceride level is an independent risk factor for the development of new-onset DM. Testing for hypertriglyceridemia in people without diabetes may be an alternative screening tool to identify populations at risk of developing future DM, as well as providing triglyceride as a new target for DM risk reduction.

Cholesterol efflux capacity and its association with prevalent metabolic syndrome in a multi-ethnic population (Dallas Heart Study).

Metabolic syndrome (MetS) is characterized by adiposity and atherogenic dyslipidemia consisting of elevated triglyceride and decreased high density lipoprotein cholesterol (HDL-C) levels however, cholesterol concentration alone does not reflect HDL functionality. Cholesterol efflux capacity (CEC) captures a key anti-atherosclerotic function of HDL; studies linking CEC to MetS have yielded inconsistent findings and lacked racial/ethnic diversity. The aim of this study was to evaluate the association between CEC and MetS in a large multi-ethnic population utilizing two different CEC assays interrogating overlapping but distinct reverse cholesterol transport pathways. A cross-sectional study was performed using the Dallas Heart Study cohort and cholesterol efflux was measured with radiolabeled and fluorescent cholesterol assays. The relationship between CEC and MetS was assessed using multivariable regression analyses. A total of 2241 participants were included (mean age was 50 years; 38% men and 53% Blacks). CEC was independently and inversely associated with MetS irrespective of efflux assay (CEC-radiolabeled, adjusted OR 0·71 [95% CI 0·65-0·80]. CEC-fluorescent, adjusted OR 0·85 [95% CI 0·77-0·94]). Both CEC measures were inversely associated with waist circumference and directly associated with HDL-C but not with other MetS components. There was an interaction by sex but not by race such that the inverse associations between CEC and MetS were somewhat attenuated in men (OR 0·86, 95%CI 0·74-1·01). In this large multi-ethnic cohort, impaired CEC is linked to MetS irrespective of efflux assay and race/ethnicity but less so among men. Future studies are needed to assess whether CEC mediates the atherosclerotic cardiovascular disease risk of MetS.