Cardiometabolic Risk Research Articles (Page 1)

The prevalence and severity of Obstructive Sleep Apnea(OSA) vary by ethnicity, yet data comparing OSA and its anthropometric risk factors across global, population-based cohorts remain limited. We aimed to determine associations between morphological factors and OSA severity, as well as whether OSA-related cardiometabolic risks differ among Swiss, Beninese, and Indian adults. We analyzed pooled data from 4,663 adults enrolled in three population-based sleep cohorts: HypnoLaus(Switzerland), BeSAS(Benin), and BLESS(India). Associations between OSA severity (apnea-hypopnea index, AHI) and anthropometric measures [body mass index (BMI), neck circumference, and waist circumference] were examined using multivariable regression models adjusted for age and sex, with effect modification by cohort assessed. Associations between OSA (AHI ≥ 15) and major cardiometabolic comorbidities (hypertension, diabetes, and metabolic syndrome) were also evaluated. For each 1 Kg/m2 increase in BMI, AHI increased by 5.95%, 7.31%, and 8.06% in Beninese, Swiss, and Indians, respectively. OSA was consistently associated with increased odds of hypertension in all populations (OR: 1.30, 1.76, and 1.63 in Swiss, Indian, and Beninese populations, respectively). Moreover, OSA was associated with increased odds of metabolic syndrome [in Swiss (OR:1.64) and Indian (OR: 1.89)]. Associations between obesity-related anthropometric factors, OSA severity, and cardiometabolic comorbidities differ across populations, with the strongest relationships observed in the Indian and Swiss cohorts. These findings underscore the importance of population-specific risk stratification and highlight the need to consider local anthropometric and epidemiologic contexts in OSA management and prevention strategies.

Chronic kidney disease (CKD) is common and often coexists with cardiometabolic risk factors and cardiovascular disease (CVD). To evaluate CKD prevalence and awareness among US adults overall and in those with cardiometabolic risk factors or CVD. This serial cross-sectional study was conducted among US adults aged 20 years or older participating in the National Health and Nutrition Examination Survey between 2011 and March 2020. The primary outcomes were prevalence of CKD, defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2 or urine albumin to creatinine ratio of 30 mg/g or greater, and awareness, based on self-report of a "yes" response to the question "Ever told you had weak/failing kidneys?" among all US adults and those with cardiometabolic conditions (hypertension, diabetes, hyperlipidemia, obesity) or CVD. Survey-weighted logistic regression models were also fit to determine temporal changes in prevalence over the study period. This cross-sectional study included 24 646 adults (weighted mean age, 49 years; 48.4% female), including 20 224 adults with cardiometabolic risk factors or CVD. The overall prevalence of CKD among US adults was 14.6% (95% CI, 14.0%-15.3%), and only 12.3% (95% CI, 11.1%-13.5%) were aware of "weak/failing" kidneys. Among adults with cardiometabolic risk factors or CVD, CKD prevalence was 16.7% (95% CI, 16.0%-17.4%). Awareness of "weak/failing" kidneys was low in this population-only 13.2% (95% CI, 11.9%-14.4%) were aware of their diagnosis over the study period, and the largest awareness gaps occurred among those aged 20 to 64 years, women, and Hispanic adults. Although awareness among adults with CKD and cardiometabolic conditions increased modestly, from 11.5% (95% CI, 8.5%-14.5%) in 2011-2012 to 15.1% (95% CI, 13.1%-17.2%) in 2017 through March 2020 (P = .02), these gains were concentrated among older adults aged 65 years or older (10.8%; 95% CI, 6.9%-14.6% to 17.7%; 95% CI, 14.2%-21.3%), men (9.7%; 95% CI, 5.6%-13.8% to 18.4%; 95% CI, 15.5%-21.4%), and non-Hispanic White adults (10.8%; 95% CI, 6.1%-15.5% to 16.3%; 95% CI, 13.4%-19.2%). No significant improvements in awareness were observed among younger adults aged 20 to 64 years, women, or Black and Hispanic adults. In this nationally representative study, CKD affected 1 in 6 US adults with cardiometabolic conditions, and only a minority of respondents were aware of "weak/failing" kidneys. These findings underscore a significant opportunity to promote awareness and optimal management of CKD.

The uric acid (UA) to HDL-cholesterol ratio (UHR) has recently been proposed as a novel marker of cardiometabolic and inflammatory risk. This study aimed to investigate the association between UHR and infertility in U.S. women of reproductive age. We analyzed data from 2447 women aged 18 to 45 years in the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018 cycles. The primary outcome - infertility - was assessed based on self-reported responses from the reproductive health questionnaire of the National Health And Nutrition Examination Survey dataset, and was not clinically validated. UHR was calculated as the ratio of serum UA to HDL-C. Multivariable logistic regression models were constructed to evaluate the association between UHR and infertility risk. Women with infertility had significantly higher mean age, body mass index, UA levels, and log (UHR) values compared to non-infertile participants (all P <.01). In the fully adjusted model, each unit increase in log-transformed UHR was associated with a higher odd of infertility (OR = 2.04, 95% CI: 1.28-3.27, P = .01). Compared with the lowest quartile of UHR, the adjusted odds ratios for infertility were 1.72 (95% CI: 1.09-2.72) for Q2, 1.91 (95% CI: 1.17-3.12) for Q3, and 1.98 (95% CI: 1.15-3.41) for Q4 (P for trend = .017). Subgroup analyses revealed consistent associations across women aged ≥35 years, those living with a partner, never-smokers, women without diabetes mellitus or hypertension, and those with regular menstrual periods or a history of pelvic infection, although no significant interactions were observed. Elevated UHR is associated with an increased risk of infertility in reproductive-aged women, as observed in this cross-sectional analysis. However, due to the study's cross-sectional nature, causality cannot be inferred, and further prospective studies are needed to validate these findings.

Metabolic syndrome (MetS) is a clinical condition defined by abdominal obesity, insulin resistance, hypertension, and dyslipidaemia, associated with increased cardiovascular risk and type 2 diabetes (T2D). Emerging evidence suggests a role for iron metabolism and ferroptosis in the pathophysiology of MetS and its related complications. This study aimed to explore the association between serum iron levels and clinical, anthropometric, and biochemical parameters in a population with cardiometabolic risk factors. Weongoing treatment for such analysed data from 893 patients attending the Metabolic Disease Unit of the Interdisciplinary Medicine Department at the University of Bari "Aldo Moro". Patients with MetS, elevated BMI, hypertension, and T2D exhibited significantly lower serum iron levels compared to healthy controls. Serum iron showed a strong inverse correlation with age (r = -0.09, p = 0.0061), fasting plasma glucose (r = -0.10, p = = .002), and HbA1c (r = -0.18, p < 0.0001) in the overall population, while no correlations were found with Framingham Risk Score, triglycerides, waist circumference, and BMI. Conversely, when stratifying by sex, we observed that serum iron was inversely correlated with BMI (r = -0.12, p = 0.008) and waist circumference (r = -0.12, p = 0.008) in females only. Metabolic dysfunction is associated with reduced serum iron levels, with sex-specific patterns observed in relation to adiposity markers. Elucidating the interplay between iron metabolism, sex hormones, and adipose tissue biology may uncover new targets for personalized treatment strategies for metabolic diseases. Further research is warranted to clarify how modulation of iron homeostasis affects adipose tissue function, particularly in women with obesity and related metabolic disorders.

Mild autonomous cortisol secretion (MACS) is associated with increased cardiometabolic risk factors including hypertension, type 2 diabetes and dyslipidaemia. By using evening doses of metyrapone, a short-acting 11-β hydroxylase inhibitor, it has been shown that it is possible to reset the abnormal circadian cortisol rhythm in MACS. This study aimed to evaluate the tolerability and impact of this approach on cardiometabolic outcomes in patients with MACS. We conducted a single-centre retrospective, longitudinal review of patients with MACS who received evening metyrapone (250-500 mg at 6 PM and 250 mg at 10 PM) to evaluate adverse events, tolerability, and cardiometabolic outcomes (systolic and diastolic blood pressure, HbA1c, weight and non-HDL cholesterol) at 6 months, compared to controls. Age and sex-matched controls were identified from patients with adrenal incidentalomas and non-suppressed serum cortisol following 1 mg overnight dexamethasone suppression testing. Fifteen patients and 15 matched controls were identified. Over 6 months there were no adrenal crises. Metyrapone was stopped in 2/15 patients in view of side effects. In the metyrapone group compared to controls, there were significant decreases in systolic blood pressure (-17.7 (SE 5.8) vs. +8.7 (5.7)mmHg, p = 0.008, n = 9) and diastolic blood pressure (-9.9 (4.2) vs. +3.0 (3.6)mmHg, p = 0.024). The differences between groups for HbA1c, weight and non-HDL cholesterol were not statistically significant. Evening metyrapone was associated with significant reductions in systolic and diastolic blood pressure in patients with MACS, without causing adrenal insufficiency, indicating its potential safe clinical utility. A well-powered, controlled, prospective study is needed to validate these findings and comprehensively investigate the broader metabolic outcomes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and atrial fibrillation (AF) are two highly prevalent conditions that share overlapping cardiometabolic risk factors, including obesity, type 2 diabetes, hypertension, and dyslipidemia. Growing evidence suggests that these two disease entities are pathophysiologically linked through systemic inflammation, oxidative stress, and structural remodeling. Population-based studies and meta-analyses report an association between steatotic liver disease and both incident and recurrent AF. While several analyses observe persistence of this association after adjustment for cardiometabolic risk factors, residual confounding and limitations of observational designs preclude firm causal inference. Conversely, heart rhythm disturbances may exacerbate hepatic fibrosis and dysfunction. Lifestyle interventions—particularly sustained weight loss—have demonstrated significant benefits in both conditions. Emerging pharmacological options, including incretin mimetics, flozins, statins, and thiazolidinediones, show promise in addressing the liver–heart axis, while appropriate anticoagulation remains essential in AF management. This review summarizes current epidemiological data, mechanistic insights, diagnostic approaches, and therapeutic strategies related to the coexistence of MASLD and AF. Emphasis is placed on shared pathogenic pathways, non-invasive diagnostic tools, and integrated management options.

Insulin resistance (IR) drives early cardiometabolic risk in low-resource settings, yet gold-standard measures are impractical. We assessed routine lipids, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and the TG/HDL-C ratio, as predictors of IR in 781 adults aged 20–29 years from the Ellisras Longitudinal Study (Lephalale, Limpopo). IR was defined as HOMA-IR ≥2.5. Participants were 51.8% female and 39.1% diabetic. Diabetic participants showed higher fasting glucose, insulin, and HOMA-IR, and more adverse lipid profiles than non-diabetics (all p < 0.001). Receiver-operating-characteristic analysis showed the TG/HDL-C ratio discriminated IR best (AUC 0.88, 95% CI 0.85–0.91), outperforming TG (0.78, 0.74–0.82) and HDL-C (0.75, 0.71–0.79). A practical cut-off of ≥2.0 yielded 82.1% sensitivity and 85.0% specificity. In multivariable models adjusted for age and sex, TG ≥1.7 mmol/L (aOR 2.92, 95% CI 2.04–4.18), low HDL-C (AOR 2.47, 1.75–3.48), and TG/HDL-C ≥ 2.0 (aOR 4.85, 3.32–7.08) were independently associated with IR; each year of age increased odds (AOR 1.06), and sex was not significant. Performance was consistent across diabetes status (AUC 0.84 non-diabetic; 0.81 diabetic) and sex (0.86 males; 0.83 females). The TG/HDL-C ratio is a simple, low-cost screening tool for IR in semi-rural South Africa and merits integration into primary care.

People with Down syndrome represent a highly vulnerable population, frequently showing vitamin D deficiency together with an elevated risk of metabolic and neuromuscular dysfunction. This susceptibility derives from several factors, including muscular hypotonia, excess body weight, thyroid abnormalities, and immune dysregulation. The coexistence of these conditions compromises bone and muscle health, increases cardiometabolic risk, and reduces motor abilities and coordination, thereby predisposing individuals to falls, sarcopenia, sarcopenic obesity, and long-term disability. Vitamin D, traditionally known for its essential role in bone health, is now recognized as a pleiotropic hormone regulating immune responses, metabolic balance, and muscle performance. Its deficiency is increasingly linked to obesity, insulin resistance, diabetes mellitus, dyslipidemia, and metabolic syndrome. These adverse outcomes are mediated through mechanisms involving chronic inflammation, oxidative stress, mitochondrial impairment, and disrupted adipokine signaling. This review integrates current molecular, cellular, and clinical evidence on the multifaceted actions of vitamin D in Down syndrome. Particular emphasis is placed on its effects on insulin signaling, adipose tissue metabolism, inflammatory regulation, and muscle strength. Finally, vitamin D is discussed as a biomarker and therapeutic target to guide personalized interventions aimed at improving metabolic health, maintaining muscle function, and promoting long-term independence in this high-risk population.

Introduction: Metabolic dysregulation is posited to underlie observed links between chronic distress and higher cardiometabolic disease risk. We recently identified a plasma metabolite-based distress score (MDS) related to prevalent depression and associated with increased risk of incident diabetes and cardiovascular disease. This study leverages repeated metabolomics measures in an ongoing cohort of women to assess the longitudinal relationship between depression and MDS. Hypotheses: We hypothesized that (1) depression at baseline is associated with greater increase in MDS over follow-up and (2) more severe distress is associated longitudinally with higher MDS. Methods: This is a secondary analysis with participants drawn from a harmonized data source of nested case-control studies within the Nurses’ Health Study (N=1152). White women with metabolomics data, depression measured by the Mental Health Inventory (MHI-5), and covariate data at baseline (1990) and follow-up (2000) were included. Women who developed major health conditions within two years of blood draws were excluded. To test if baseline depression status (MHI-5 ≤ 52) was associated with changes in the MDS, we performed multiple linear regression analyses (H1). To assess if depression severity (continuous MHI-5 score) was associated with MDS levels longitudinally, we fitted linear mixed models with random individual intercepts (H2). Both analyses adjusted for potential confounders incrementally in nested models: (1) baseline MDS and matching factors, (2) medical covariates, and (3) biobehavioral covariates. Results: At baseline, the average age was 56 (sd = 7), 53 women (4.6%) had severe depression, and mean MDS (scaled to sd = 1) was -0.064, increasing to -0.026 at follow-up. After adjusting for all relevant covariates, severe depression at baseline was associated with larger increases in MDS (β=0.29, 95% CI [0.05, 0.53]). A one-point increase in MHI-5 (i.e., less severe depressive symptoms) was linked to lower MDS levels (-0.004, [-0.007, -0.0004]). Conclusions: We establish novel longitudinal explorations revealing that depression severity is associated with increased MDS. Depression earlier in life could potentially lead to adverse longitudinal changes of metabolic profiles linked to cardiometabolic health over the course of ten years, which may have important implications for screening and managing cardiometabolic health in individuals with psychological distress.

Family history of cardiovascular disease is a known risk factor for cardiometabolic conditions, yet few studies have examined how nativity shapes intergenerational cardiometabolic risk patterns among Black adults, despite the rising number of foreign-born Black people in the U.S. This study examined the associations between nativity status and both family history and individual cardiometabolic risk among Black adults. Method: Self-reported data from the All of Us Research Program was used with nativity status as the main predictor and family cardiometabolic risk scores (sum of binary indicators for relatives with documented history of hypertension, diabetes, high cholesterol, heart attack, heart failure, valve disease, coronary heart disease, and other heart conditions) and individual cardiometabolic risk scores (sum of participants' self-reported diagnoses of the same conditions) as the outcomes. Negative binomial regression was used to examine the association between nativity status and family risk, whereas Poisson regression was fitted to examine the relations between nativity and individual risk, both adjusting for age, gender, education, and ethnicity as covariates. Results: We included 49,055 Black adults ( M age, ±14.7 years, 72% female, and 6% foreign-born). Foreign-born participants were younger, more likely to be male, more educated, and more likely to identify as Hispanic compared to U.S.-born participants. Family risk scores ranged from 0-12 ( M =1.46). In the unadjusted analysis, U.S.-born individuals reported significantly higher family cardiometabolic risk scores ( M =1.49) compared to their foreign-born counterparts ( M =1.14); a 31% higher risk ( p &lt;0.001). In the multivariable negative binomial regression, after adjusting for covariates U.S.-born status remained significantly associated with higher family cardiometabolic risk (Incidence Rate Ratio (IRR) =1.32, 95% CI: 0.23-0.32). For individual cardiometabolic risk, U.S.-born participants had higher risk scores in the adjusted Poisson regression (β = 0.11, p &lt; 0.001). Increased reporting among U.S.-born participants may reflect greater awareness or access to family health history compared to foreign-born individuals. Conclusion: These findings highlight the importance of disaggregating health data within the Black population in the U.S. and underscore the critical role of family health history knowledge in understanding risk profiles and informing culturally appropriate preventive care strategies.

Physical activity (PA) is a key strategy in preventing and treating metabolic syndrome (MetS). The purpose is to investigate the associations of leisure-time PA (LTPA) trajectories across adulthood and current PA with MetS at age 61. Participants were 159 Finnish adults (52% women). LTPA frequency was assessed at ages 27, 42, 50, and 61 with a single question. Current PA at age 61 included self-reported vigorous, muscle-strengthening, commuting, and occupational PA. Cardiometabolic risk factors at age 61 included waist circumference, blood pressure, high-density lipoprotein (HDL) cholesterol, triglycerides, and glucose. MetS was defined based on the ATP III criteria. LTPA trajectories were conducted using k means for longitudinal data. Of the three LTPA trajectories found, consistently inactive (N=34) and increasingly active (N=58) had a higher risk of MetS compared to consistently active (N=67) (odds ratio [95% confidence interval]: 3.93 [1.55, 10.01] and 2.39 [1.14, 4.99], respectively). Only the difference between consistently inactive and consistently active remained statistically significant when the current PA indicators were included in the model. Considering the individual components of MetS, those who were consistently inactive and increasingly active had higher waist circumference, lower HDL, and higher triglyceride levels compared to consistently active. These differences did not remain statistically significant when current PA was included. Although consistently inactive and increasingly active individuals had higher cardiometabolic risk at age 61 compared to those who were consistently active across adulthood, current PA participation at the beginning of late adulthood attenuated these risks. These findings emphasize the importance of promoting and sustaining PA throughout life to reduce the burden of MetS in the aging population.

Introduction: Cardiometabolic risk factors remain the leading cause of cardiovascular disease (CVD) and death in the US. US women veterans (WV) are a growing, high-risk population with higher rates of chronic conditions and increasing engagement with veteran affair (VA) healthcare yet remain understudied. Objectives: This study aimed to investigate the potential ethnic/racial and age group differences in the life-long prevalence of traditional cardiometabolic risk factors among US WV from 2000-2019. Methods: The national VA electronic health records (her) were used to assess the prevalence of diabetes, hypertension, hyperlipidemia, smoking, and neuroendocrine disorders among US WV who visited a VA facility from 1/1/2000 to 12/31/2019. Diagnoses were based on international classification of disease (ICD)-9 and -10 codes. Participants were stratified by races/ethnicities (non-Hispanic White, Black, Asian, American Indian/Pacific Islander, and Hispanic/Latino) and age group (18-39, 40-59, 60+). Age-standardized lifelong prevalence of CVD risk factors was assessed overall, by races/ethnicities, and by age groups. Age-standardized lifelong prevalence represents the sum of raw age-specific risk factor rates multiplying the standard age-specific proportion in the 2000 U.S. census reference population Results: The WV cohort expanded from 80,707 in 2000 to 739,309 in 2019. Significant racial/ethnic disparities emerged. Blacks demonstrated the highest prevalence of diabetes (from 13.5% to 19.2%) and hypertension (38.2% to 43.9%). Notably, American Islanders showed the most rapid escalation in diabetes (1.9-fold increase). Whites maintained the highest prevalence of smoking, hyperlipidemia, and neuroendocrine disorders. Asians experienced a 9.6-fold surge in smoking (3.8% to 36.5%), while Black saw a 3.1-fold rise in hyperlipidemia (11.5% to 35.8%) and a 3.1-fold rise in neuroendocrine disorders. The remaining subgroups exhibited absolute prevalence increases of approximately 40% for smoking and 20% for hyperlipidemia. Marked age-related patterns also emerged. The 60+ age group had the highest prevalence of risk factors from 2000-2019, except smoking. This group also exhibited the greatest fold increases in every category except hypertension. Conclusion: The cardiometabolic risk burden among U.S. women veterans has reached critical levels, with pronounced racial/ethnic and age group disparities, necessitating immediate targeted public health interventions.

Backround: Hepatic steatosis and hepatic fibrosis are systemic conditions that increase cardiometabolic risk. However, nationally representative data evaluating these associations are limited. Research Question: Among adults in the United States, does the presence of hepatic steatosis, and within steatosis, the presence of hepatic fibrosis, increase the likelihood of having metabolic syndrome and higher levels of insulin resistance? Methods: We analyzed data from 9,086 adults aged ≥20 years from the 2017–2023 National Health and Nutrition Examination Survey. Hepatic steatosis was defined by a controlled attenuation parameter ≥290 dB/m (corresponding to S3 steatosis), and significant hepatic fibrosis by liver stiffness measurement ≥8.0 kPa (corresponding to F2 fibrosis). Modified metabolic syndrome was defined as meeting ≥3 of 5 criteria: central obesity, hypertension, dysglycemia, low high-density lipoprotein cholesterol, and elevated non-high-density lipoprotein cholesterol. Insulin resistance was assessed using the homeostasis model assessment. Analyses applied appropriate complex survey weights. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Group differences in insulin resistance were tested with weighted t-tests. Results: After adjusting for age and sex, hepatic steatosis was associated with a fivefold increase in odds of modified metabolic syndrome (OR 4.97; 95% CI, 4.44–5.57). The strongest contributing components were central obesity (OR 10.19; 95% CI, 8.57–12.11) and dysglycemia (OR 2.93; 95% CI, 2.63–3.25). Among individuals with hepatic steatosis, those with hepatic fibrosis had 76% higher odds of metabolic syndrome (OR 1.76; 95% CI, 1.35–2.28). Mean insulin resistance was significantly higher in those with hepatic steatosis compared to those without (6.57 ± 11.57 vs 2.90 ± 6.97; p &lt; 0.001), and was further elevated in those with hepatic fibrosis (10.53 ± 19.30 vs 5.55 ± 8.23; p &lt; 0.001). Conclusion: In a nationally representative sample of U.S. adults, hepatic steatosis was strongly associated with clustering of cardiometabolic risk factors and elevated insulin resistance. Hepatic fibrosis further intensified these associations. These findings support early metabolic screening and intensive risk-factor management in individuals with hepatic steatosis, particularly those with hepatic fibrosis.

Background: Cholesterol levels in early adulthood are a key determinant of lifetime cardiovascular risk, yet young adults are often overlooked in screening and prevention efforts. In recent years, the cardiometabolic risk profile of this population has shifted significantly, with increasing rates of obesity, diabetes, and other metabolic conditions emerging at younger ages. Evaluating changes in total cholesterol and low-density lipoprotein cholesterol (LDL-C) over the past two decades is essential to assess the adequacy of current prevention strategies and to detect early signs of worsening cardiometabolic risk in a population not routinely targeted by clinical guidelines. Aim: To evaluate trends in total cholesterol and LDL-C among young adults in the U.S. from 2005 to 2024. Methods: This retrospective serial cross-sectional study used data from Epic’s Cosmos, a large, nationally representative, deidentified electronic health record database. Adults aged 20 to 39 years with documented total cholesterol and LDL-C measurements between 2005 and 2024 were included. Pregnant individuals and those missing sex or race/ethnicity data were excluded. Age adjustment was performed using 2020 U.S. Census population weights across 5-year strata. Mean lipid values were reported with 95% confidence intervals, calculated using the normal approximation method. Results: The study cohort included 19,795,711 non-pregnant U.S. adults aged 20–39 years (57.5% female; 68.3% White, 16.7% Black, 8.2% Hispanic, 6.8% Asian). Between 2005 and 2018, both total cholesterol and LDL-C levels declined steadily across all sex (Panels A and B) and racial/ethnic groups (Panels C and D). This period of improvement was followed by a reversal beginning in 2019, with lipid levels suddenly rising and then plateauing through 2024. The trend was most pronounced among Asian and Hispanic individuals, whose LDL-C levels increased by ~6 mg/dL from their respective lows, approaching or exceeding levels observed at the start of the study period. Conclusion: While lipid levels improved through the late 2010s, emerging trends suggest a plateau—or even a reversal—of earlier progress. Given the cumulative nature of atherosclerotic burden and the lack of prevention guidelines specifically targeting this age group, a renewed focus on lipid surveillance and early intervention in young adulthood is essential to sustain long-term gains in population health.

Introduction: ZIP code is one of the strongest predictors of cardiometabolic health, often surpassing genetic and clinical factors. Regional disparities in areas such as environment and socioeconomic status manifest as compromised SDoH, increasing cardiometabolic risk. While prior studies have correlated ZIP-level deprivation with outcomes, few have gathered patient-reported SDoH and paired it with ICD-10-defined conditions. This study aimed to quantify SDoH infractions by ZIP and evaluate their association with cardiometabolic disease. Methods: In this dual-center study, patients completed a 13-item SDoH questionnaire adapted from the CMS Accountable Health Communities Health-Related Social Needs (AHC HRSN) tool through a hard copy or QR-linked digital form following informed consent. Domains included housing, food insecurity, transportation, safety, utilities, employment, education, finances, physical activity, substance use, mental health, disability, and social support. Utilizing ICD-10 documentation, an EMR review identified diagnoses of HTN, DM, HLD, ASCVD, overweight status, and obesity. Data analysis was stratified by ZIP and SDoH status, with the latter defined as ≥1 infraction. Results: Eighty-one patients completed the SDoH questionnaire across 56 unique ZIP codes, with 58.9% (n = 47) having ≥1 SDoH infraction. The most frequent domains were financial strain (25.9%), physical activity problems (24.7%), and mental health concerns (24.7%). SDoH burden varied, with the highest-burden ZIP reporting 14 infractions (Figure 1). HTN, DM, and obesity prevalence were 58.7%, 26.1%, and 37.0% among those with ≥1 SDoH infraction versus 40.4%, 10.6%, and 21.3% in those without. Odds ratios were 3.62 (p = 0.009), 3.88 (p = 0.033), and 3.00 (p = 0.038), respectively. HLD, ASCVD, or overweight status saw no significant differences (Figure 2). ZIPs with ≥1 SDoH infraction had significantly lower median incomes than those without ($62,964 vs. $93,443; p = 0.045, Cd = 0.79), supporting geographic clustering of social risk in lower-income areas (Figure 3). Conclusion: This study supports ZIP-based stratification of SDoH and cardiometabolic risk. Integrating SDoH screening may inform patient-centered care, equity efforts, and local planning. Mapping SDoH types may also serve as a needs assessment tool for policy development.

Background: Hepatic steatosis is closely linked to cardiometabolic risk factors (CMRF) in adults; however, less is known in childhood. In particular, data is lacking in younger children because of the challenges in the accurate measurement of liver fat. We investigated hepatic steatosis (HS) and cardiometabolic risks in pre-pubertal Hispanic/Latino children. Methods: This was a prospective cohort study including 130 Hispanic/Latino children aged 6–9 years old (NCT05292352). Eight binary cardiometabolic risk factors (CMRFs) were combined into one risk CMRFs score (range 0–8): waist-to-height ratio (WHR) ≥0.5, triglycerides ≥100 mg/dL, total cholesterol (TC) ≥170 mg/dL, HDL &lt;45 mg/dL, LDL &gt;110 mg/dL, fasting glucose ≥100 mg/dL, HbA1c ≥ 5.7% and insulin &gt;15 μU/mL. High-risk was classified as ≥3 CMRFs. HS was measured via MRI-proton density fat fraction (MRI-PDFF) and was defined as low (&lt;3%), subclinical (3-5%), and clinical (≥5%). Prevalences of individual CMRFs and high-risk classification were compared across HS categories using Fisher’s exact tests. Statistical analysis was performed using R v.4.3.2. Results: Mean (SD) age was 8.0 (1.1), 42.3% female, 56.2% had a BMI &gt;95 th percentile. The most prevalent CMRFs were increased WHR (73.1%), elevated TC (33.1%), and low HDL (32.3%). Prevalence of several individual CMRFs rose with increasing HS (p-trend &lt; 0.0003 for all). Among those with HS &lt;3%, 3-&lt;5%, and ≥5% respectively, prevalences were, 1) High triglycerides: 6.7%, 25.0%, and 54.3%, 2) Low HDL: 15%, 29.2%, 56.5%; 3) High WHR: 48.3%, 87.5%, and 97.8%, and 4) High insulin: 1.7%, 16.7%, 26.1%. There was no significant trend between elevated HS and prevalence of high LDL, TC, HbA1C, or fasting glucose. The prevalence of high-risk conditions (≥3 CMRFs) increased from 16.7% among those with low HS to 37.5% and 54.3% among those with subclinical and clinical HS, respectively. None of the patients had more than 6 CMRFs. Conclusion: Over one-third of children of Hispanic/Latino school-age with subclinical steatosis of 3 - &lt;5 % had ≥3 CMRFs. These findings support re-evaluating current pediatric guidelines, which recommend screening beginning at age 10 and intervention only for HS ≥5%.

Introduction: Diabetes affected 529 million people globally by 2021, largely due to rising obesity contributing to Type 2 diabetes (DM2). In the U.S., it is the seventh leading cause of death and closely linked to cardiovascular disease, the leading cause of mortality in this population. Effective, low-cost strategies to improve glycemic and cardiometabolic health are essential. Psyllium, a viscous soluble fiber, has been shown to lower LDL cholesterol and improve glycemic indices, whereas non-viscous fibers like wheat dextrin lack similar benefits. Emerging lipid markers such as ceramides are associated with cardiometabolic risk but have not been studied in response to fiber. The interaction between fiber and GLP-1 agonists is also unclear. Hypothesis: Psyllium supplementation will improve cardiometabolic markers more than wheat dextrin in people with DM2. Methods: In this randomized trial at Mayo Clinic, adults with DM2 (HbA1c 6.5–10%) were randomized to psyllium or wheat dextrin for 12 weeks. Participants were recruited via electronic health records. Key exclusions: GI disease, bariatric surgery, steroid use, and pregnancy. Follow-up visits occurred at weeks 4, 8, and 12. Primary endpoints were changes in HbA1c and fasting glucose; secondary endpoints included lipids, ceramides, hsCRP, and BMI. An ex post facto analysis evaluated GLP-1 use. Primary analysis was intention-to-treat. Adherence = ≥85% dose completion. Results: Ninety-eight participants enrolled (Psyllium n=50, Dextrin n=48) with similar baseline characteristics. At 12 weeks, psyllium significantly reduced HbA1c (-0.38 ± 0.69, p=0.002). Among adherent users, HbA1c dropped further (-0.41 ± 0.70, p=0.001) with reduced fasting glucose (-14.5 ± 38.2, p=0.013). Wheat dextrin showed no benefit. In subgroup analysis, GLP-1 users on psyllium saw greater HbA1c reductions than non-users (-0.45 vs. -0.23), while GLP-1 users on dextrin had no change (+0.06). No significant changes were found in ceramides, lipids, or BMI in any analysis. CRP trended lower in adherent psyllium users (p=0.055). Conclusion: Psyllium significantly reduced HbA1c over 12 weeks in DM2, especially in adherent and GLP-1–treated groups. Effects may be attributed to psyllium's ability to form a gel in the gastrointestinal tract, modulating nutrient absorption. No effects were seen on ceramides or lipids, likely due to low baseline levels in the latter. Psyllium appears to be a safe, accessible adjunct for glycemic control in DM2.

Prenatal exposure to pesticides has been linked to disrupted fetal growth, which contributes to cardiometabolic disease risk. The placenta, as the maternal–fetal interface, undergoes extensive DNA methylation remodeling that may record environmental exposures and mediate downstream metabolic effects, including those related to cardiometabolic risk in offspring. We hypothesized that placental DNA methylation patterns vary with maternal pesticide exposure, that exposure-associated CpG sites overlap with those predictive of neonatal anthropometry, and that genes with altered methylation may represent pathways relevant to cardiometabolic health. We analyzed 254 term placentas from the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) cohort using the Illumina EPIC v2.0 array. Robust linear regression models assessed associations between placental DNA methylation and infant head circumference, birth length, and birth weight z-scores. Each outcome was analyzed separately, adjusting for estimated proportions of eight placental cell types, infant sex, maternal age, BMI, and gestational age. Parallel analyses examined urinary organophosphate metabolites (OP), pyrethroid metabolites (PYR), and a composite exposure index (MIX). CpGs with Benjamini–Hochberg FDR &lt; 0.05 were considered significant. Significant CpGs were intersected across exposures and outcomes and mapped to genes for Gene Ontology and KEGG pathway enrichment (FDR &lt; 0.05). EWAS of growth traits identified 26, 1,626, and 1,729 CpGs associated with head circumference, birth length, and birthweight, respectively. CpGs associated with weight and length were enriched for pathways including insulin resistance and MAPK signaling. Exposure-related EWAS identified 46,519 significant CpGs for OP and 46,564 for MIX; none for PYR. MAPK signaling was the top enriched pathway for both OP and MIX. Intersection of OP and MIX signatures yielded 46,417 shared CpGs, with 102 and 135 overlapping length- and weight-associated sites, respectively. Nine genes were common to both exposure and growth signatures, with IRS1 identified as a central node linking insulin and MAPK pathways. Placental methylation patterns associated with prenatal pesticide exposure overlap with epigenetic signals linked to neonatal growth, particularly involving insulin resistance and MAPK signaling, highlighting mechanisms of fetal programming relevant to long-term cardiometabolic health.

Background: Androgen precursors such as 17α-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone (DHEA) play significant roles in endocrine and metabolic pathways, yet their relationships with cardiovascular outcomes remain underexplored. While androgens have been implicated in cardiometabolic risk, the impact of upstream precursors on heart failure (HF), coronary artery disease (CAD), or myocardial infarction (MI) is unclear. This study aimed to examine whether circulating levels of these androgen precursors are associated with incident cardiovascular events in a representative U.S. population sample. Methods: We conducted a cross-sectional analysis of 5,489 to 5,545 adults from the National Health and Nutrition Examination Survey (NHANES) with available serum levels of 17α-hydroxyprogesterone (ng/dL), androstenedione (ng/dL), and DHEA (µg/dL). Participants were stratified into quartiles (Q1–Q4) of hormone levels. Sex-specific and overall associations with cardiovascular events (HF, CAD, or MI) were evaluated using multivariate logistic regression models. Models were adjusted for age, sex, race, BMI, smoking status, diabetes mellitus, dyslipidemia, and hypertension. Results: There were no significant associations between 17α-hydroxyprogesterone levels and cardiovascular outcomes in either sex or the overall cohort. For androstenedione, a modest inverse association was observed in females at Q2 (OR 0.69; 95% CI: 0.48–1.00; P &lt; 0.05), but not in males. Notably, DHEA showed robust, dose-dependent inverse associations with cardiovascular events. In the overall population, higher quartiles of DHEA were associated with significantly lower odds of events: Q2 (OR 0.74; 95% CI: 0.58–0.95; P &lt; 0.05), Q3 (OR 0.57; 95% CI: 0.42–0.78; ** P &lt; 0.001), and Q4 (OR 0.32; 95% CI: 0.19–0.54; ** P &lt; 0.001). These associations remained significant in both males and females, with Q4 DHEA showing a strong protective effect in females (OR 0.20; 95% CI: 0.05–0.85; P &lt; 0.05). Conclusions: Among the androgen precursors analyzed, DHEA was independently and significantly associated with lower odds of HF, CAD, or MI across sexes, suggesting a potential cardioprotective role. In contrast, 17α-hydroxyprogesterone and androstenedione showed limited or sex-specific associations. These findings support further investigation into DHEA as a biomarker or therapeutic target for cardiovascular risk reduction.

Introduction: Vitamin E (α-tocopherol) is a lipid-soluble antioxidant with anti-inflammatory effects, studied for its role in managing metabolic syndrome (MetS). This is especially important for vulnerable groups such as Hispanics/Latinos, who have higher cardiometabolic risk and often insufficient vitamin E intake. Significant heterogeneity within these populations may impact health outcomes. This study investigates associations between vitamin E intake and nutritional status with cardiometabolic profiles and MetS among Brazilians and U.S. Hispanic/Latino individuals. Hypothesis: We hypothesize that the relationships between vitamin E (intake and plasma/serum levels) and cardiometabolic markers and MetS differ between these populations. Methods: This cross-sectional study used data from the 2015 Health Survey of São Paulo (ISA) and the 2017–2018 NHANES focusing on Hispanic/Latino participants. Dietary intake was measured by two 24-hour recalls. Plasma/serum vitamin E concentrations were normalized by blood lipids (vit E/lipid). Cardiometabolic profile included total cholesterol, HDL-c, LDL-c, non-HDL-c, triglycerides, glucose, blood pressure, BMI, and waist circumference. MetS was defined by International Diabetes Federation criteria. Associations were evaluated with generalized linear models (p &lt; 0.05). Results: In ISA and NHANES, adults composed 66.8% and 83.3% of participants; females were 47.2% and 50.3%. Median vit E/lipid was 2.74 mg/g (ISA) and 3.84 mg/g (NHANES), with inadequacy rates of 99.99% and 96.89%. MetS prevalence was 35.8% (ISA) and 65.5% (NHANES). In ISA, vit E/lipid was inversely associated with total cholesterol, LDL-c, non-HDL-c, and triglycerides. In NHANES, vit E/lipid was inversely associated with BMI, waist circumference, triglycerides, and directly with HDL-c. Vitamin E intake inversely related to triglycerides in both groups. MetS was inversely associated with vit E/lipid and intake in NHANES, and with vit E/lipid in ISA. Conclusions: Vitamin E intake and plasma concentrations are associated with cardiometabolic outcomes, showing different patterns by population. ISA data showed stronger links with plasma levels, while NHANES emphasized intake associations. These findings highlight the need for tailored strategies addressing vitamin E status and cardiometabolic health in diverse populations.