Cardiometabolic Comorbidities Research Articles

From the Sun to the Cell: Examining Obesity through the Lens of Vitamin D and Inflammation.

Obesity affects more than one billion people worldwide and often leads to cardiometabolic chronic comorbidities. It induces senescence-related alterations in adipose tissue, and senescence is closely linked to obesity. Fully elucidating the pathways through which vitamin D exerts anti-inflammatory effects may improve our understanding of local adipose tissue inflammation and the pathogenesis of metabolic disorders. In this narrative review, we compiled and analyzed the literature from diverse academic sources, focusing on recent developments to provide a comprehensive overview of the effect of vitamin D on inflammation associated with obesity and senescence. The article reveals that the activation of the NF-κB (nuclear factor kappa B subunit 1) and NLRP3 inflammasome (nucleotide-binding domain, leucine-rich-containing, pyrin domain-containing-3) pathways through the toll-like receptors, which increases oxidative stress and cytokine release, is a common mechanism underlying inflammation associated with obesity and senescence, and it discusses the potential beneficial effect of vitamin D in alleviating the development of subclinical inflammation. Investigating the main target cells and pathways of vitamin D action in adipose tissue could help uncover complex mechanisms of obesity and cellular senescence. This review summarizes significant findings related to opportunities for improving metabolic health.

1984. Effects of Semaglutide on Adipose Tissue in HIV-Associated Lipohypertrophy

Abstract Background Lipohypertrophy (central adipose tissue (AT) accumulation) is a common and significant problem in people with HIV (PWH). Pathogenesis remains elusive; yet, AT abnormalities are key drivers of cardiometabolic co-morbidities in HIV. We aimed to assess effects of semaglutide, a glucagon-like peptide-1 receptor agonist, on AT in PWH with lipohypertrophy. Methods We conducted a randomized, double-blinded, placebo-controlled trial of virologically-suppressed, non-diabetic PWH ≥ 18 years of age on stable antiretroviral therapy (ART) with body mass index (BMI) ≥ 25 kg/m2, increased waist circumference/waist-to-hip ratio, and subjective increased abdominal girth after ART initiation. Participants were randomized 1:1 to 32 weeks semaglutide (8-week titration + 24 weeks 1.0 mg weekly subcutaneous injection) or matching placebo. Computed tomography and whole-body dual-energy X-ray absorptiometry were used to measure area/density in abdominal AT [total (TAT), visceral (TAT), and subcutaneous (SAT)] and body composition [lean body mass (LBM), limb/trunk/total body fat (TBF)], resp. Semaglutide effects were estimated using generalized estimating equations or simultaneous quantile regressions on outcome variables. Results 108 participants were enrolled (N = 54 semaglutide: median age = 52 years, 70% male, 61% Black, 83% integrase inhibitor). Groups were well-matched at baseline. In unadjusted models, semaglutide group had greater reductions (P < 0.05) in BMI, homeostatic model of insulin resistance (HOMA-IR), trunk fat, TBF (at quantile ≥ 75th), TAT, and SAT with trends (P < 0.1) for limb fat and VAT (Fig 1/Table 1). Semaglutide effects remained significant for BMI, HOMA-IR, trunk fat, TAT, and VAT after adjusting for age, sex, CD4, and ART duration (Table 2); caloric intake was also significant at ≤ 50th quantile. No differences were seen in LBM, AT density, or VAT/TAT ratio. Semaglutide was well-tolerated; serious adverse events were rare. Conclusion Semaglutide significantly decreased central fat in PWH with lipohypertrophy, primarily driven by reductions in VAT. Semaglutide may offer an effective treatment to decrease visceral adiposity and reduce co-morbidity risk. Further investigation is needed to determine mechanisms by which reductions in visceral adiposity occur. Disclosures Grace A. McComsey, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support

Epidemiology and Management of Hypertension and Diabetes Mellitus in Patients with Mild Autonomous Cortisol Secretion: A Review.

Mild autonomous cortisol secretion (MACS) is associated with a higher cardiometabolic risk than that observed in patients with nonfunctioning adrenal adenomas and in the general population. In patients with MACS, the excess of glucocorticoids affects various metabolic pathways, leading to different manifestations of metabolic syndrome and other comorbidities. Hypertension and diabetes mellitus are two of the most common cardiometabolic comorbidities associated with MACS, reaching a prevalence of up to 80% and up to 40%, respectively. In addition, they are the comorbidities that experienced a greater improvement after adrenalectomy in patients with MACS. Hypertension pathogenesis is multifactorial, including the coexistence of comorbidities such as obesity or diabetes and the role of the different polymorphisms of the glucocorticoid receptor gene, among others. Glucocorticoid-induced diabetes mellitus is mainly related to the detrimental effects of glucocorticoids on insulin-dependent glucose uptake in peripheral tissues, gluconeogenesis and insulin secretion. There are no specific recommendations for hypertension and diabetes treatment in patients with MACS. Thus, considering the similar underlying pathogenesis of hypertension and diabetes mellitus in overt and mild hypercortisolism, our recommendation is to follow this general stepwise approach: surgically remove the adrenal culprit lesion to induce remission from hypercortisolism; control hypercortisolism with steroidogenesis inhibitors; and treat elevated blood pressure or high glucose levels using carefully selected anti-hypertensives and glucose-lowering medications if blood pressure and glucose levels remain uncontrolled, respectively. In this review, we summarize the epidemiology, physiopathology and management of diabetes mellitus and hypertension in patients with MACS.

Cardiometabolic comorbidities in Hispanic/Latino cancer survivors: prevalence and impact on health-related quality of life and supportive care needs.

The aim of this study was to characterize the prevalence of cardiometabolic comorbidities (i.e., diabetes, peripheral vascular disease, myocardial infarction, congestive heart failure, cerebrovascular disease) among Hispanic/Latino cancer survivors and examine the impact of cardiometabolic comorbidities on health-related quality of life (HRQoL), unmet supportive care needs, patient-provider communication self-efficacy, satisfaction with cancer care, and increases in healthy behaviors. Hispanics/Latinos diagnosed with breast, prostate, or colorectal cancer (N = 288) were assessed within 15months of primary treatment completion. One-quarter (24.7%) of survivors were diagnosed with diabetes and one-fifth (20.8%) were diagnosed with peripheral vascular disease. Survivors with at least one cardiometabolic comoribidity were older (t(278) = -.3.622, p < .001) and more likely to have a household income of less than $25,000 (X2 = 8.369, p = .004). When adjusting for sociodemographic and medical covariates, survivors with cardiometabolic comorbidities demonstrated worse overall HRQoL (B = -4.792, p = .050), emotional (B = -1.479, p = .018) and physical (B = -2.228, p = .005) wellbeing, a higher odds of unmet psychological (OR = 2.095, p = .027) and sexuality (OR = 2.898, p = .004) needs, and greater patient-provider communication self-efficacy (B = .179, p = .045). There were no differences in healthy behavior changes or satisfaction with cancer care. Cardiometabolic comorbidities may be highly prevalent among Hispanic/Latino cancer survivors and increase the risk of worse HRQoL and unmet supportive care needs. Targeted interventions are needed to optimize health among Hispanic/Latino cancer survivors with cardiometabolic comorbidities.

Psychiatric comorbidities in women with cardiometabolic conditions with and without ADHD: a population-based study

BackgroundLeveraging a large nationwide study of Icelandic women, we aimed to narrow the evidence gap around female attention-deficit/hyperactivity disorder (ADHD) and cardiometabolic comorbidities by determining the prevalence of obesity, hypertension, type 2 diabetes, and cardiovascular diseases among women with ADHD and examine the association between cardiometabolic conditions and co-occurring ADHD with anxiety and mood disorders, alcoholism/substance use disorder (SUD), self-harm, and suicide attempts.MethodsWe conducted a cross-sectional analysis of the nationwide, all-female, population-based SAGA Cohort Study (n = 26,668). To ascertain diagnoses and symptoms, we used self-reported history of ADHD diagnoses, selected cardiometabolic conditions and psychiatric disorders, and measured current depressive, anxiety, and PTSD symptoms through appropriate questionnaires (PHQ-9, GAD-7, and PCL-5). We calculated age-adjusted prevalences of cardiometabolic conditions by women’s ADHD status and estimated adjusted prevalence ratios (PR) and 95% confidence intervals (CI), using modified Poisson regression models. Similarly, we assessed the association of cardiometabolic conditions and co-occurring ADHD with current psychiatric symptoms and psychiatric disorders, using adjusted PRs and 95% CIs.ResultsWe identified 2299 (8.6%) women with a history of ADHD diagnosis. The age-adjusted prevalence of having at least one cardiometabolic condition was higher among women with ADHD (49.5%) than those without (41.7%), (PR = 1.19, 95% CI 1.14–1.25), with higher prevalence of all measured cardiometabolic conditions (myocardial infarctions (PR = 2.53, 95% CI 1.83-–3.49), type 2 diabetes (PR = 2.08, 95% CI 1.66–2.61), hypertension (PR = 1.23, 95% CI 1.12–1.34), and obesity (PR = 1.18, 95% CI 1.11–1.25)). Women with cardiometabolic conditions and co-occurring ADHD had, compared with those without ADHD, substantially increased prevalence of (a) all measured mood and anxiety disorders, e.g., depression (PR = 2.38, 95% CI 2.19–2.58), bipolar disorder (PR = 4.81, 95% CI 3.65–6.35), posttraumatic stress disorder (PR = 2.78, 95% CI 2.52–3.07), social phobia (PR = 2.96, 95% CI 2.64–3.32); (b) moderate/severe depressive, anxiety, and PTSD symptoms with PR = 1.76 (95% CI 1.67–1.85), PR = 1.97 (95% CI 1.82–2.12), and PR = 2.01 (95% CI 1.88–2.15), respectively; (c) alcoholism/SUD, PR = 4.79 (95% CI 3.90–5.89); and (d) self-harm, PR = 1.47 (95% CI 1.29–1.67) and suicide attempts, PR = 2.37 (95% CI 2.05–2.73).ConclusionsADHD is overrepresented among women with cardiometabolic conditions and contributes substantially to other psychiatric comorbidities among women with cardiometabolic conditions.

Cardiometabolic comorbidities in autosomal dominant polycystic kidney disease: a 16-year retrospective cohort study

BackgroundAutosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disease and the fourth leading cause of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Nevertheless, there is a paucity of epidemiological research examining the risk factors and survival on RRT for ADPKD. Thus, we aimed to investigate the cumulative effects of cardiometabolic comorbidities, including hypertension (HTN), type 2 diabetes mellitus (DM), and dyslipidemia (DLP) to clinical outcomes in ADPKD.MethodsWe identified 6,142 patients with ADPKD aged ≥ 20 years from 2000 to 2015 using a nationwide population-based database. HTN, DM, and DLP diagnoses before or at the time of ADPKD diagnosis and different combinations of the three diagnoses were used as the predictors for the outcomes. Survival analyses were used to estimate the adjusted mortality risk from cardiometabolic comorbidities and the risk for renal survival.ResultsPatients with ADPKD who developed ESRD had the higher all-cause mortality (HR, 5.14; [95% CI: 3.88–6.80]). Patients with all three of the diseases had a significantly higher risk of entering ESRD (HR:4.15, [95% CI:3.27–5.27]), followed by those with HTN and DM (HR:3.62, [95% CI:2.82–4.65]), HTN and DLP (HR:3.54, [95% CI:2.91–4.31]), and HTN alone (HR:3.10, [95% CI:2.62–3.66]) compared with those without any three cardiometabolic comorbidities.ConclusionsOur study discovered the cumulative effect of HTN, DM, and DLP on the risk of developing ESRD, which reinforces the urgency of proactive prevention of cardiometabolic comorbidities to improve renal outcomes and overall survival in ADPKD patients.

Abstract 12341: Cardiometabolic Comorbidity Burden and Risk of Hospitalization in Heart Failure Patients

Background: Cardiometabolic comorbidities, obesity, diabetes, and hypertension, are highly prevalent in heart failure (HF). However, the implications of comorbidity burden on all-cause hospitalization, overall and among HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are unknown. Hypothesis: Higher cardiometabolic burden is associated with increased hospitalization in individuals with HF. Methods: In a retrospective EHR-based cohort of adults 18 with HF, we categorized individuals based on the number of cardiometabolic comorbidities present prior to 10/1/2021. Specifically, we defined presence of hypertension and/or diabetes mellitus by diagnosis code, and obesity by BMI 30kg/m2. Cox regression models were used to assess the association between number of cardiometabolic comorbidities and time to all-cause hospitalization within 1 year, adjusting for age, sex, race, and insurance status. Separate analyses were also conducted for HFpEF and HFrEF subgroups. Results: There were 26,800 individuals with HF in the study population (mean age 75 13.7, 46% female, 69% White) who experienced 4,284 (16%) hospitalizations over a 1-year period. Compared to those with absent comorbidities (n=3,420), there was an increase in risk for all-cause hospitalization with increasing number of comorbidities, with adjusted hazard ratio (HR) 1.19 (95% CI 1.05-1.34) for 1 comorbidity (n=7,988), HR 1.25 (95% CI 1.11-1.41) for 2 comorbidities (n=9,553), and HR 1.43 (95% CI 1.26-1.62) for 3 comorbidities (n=5,839). ( Figure ) A similar association was also seen for the HFpEF subgroup, but not for the HFrEF subgroup. Conclusions: Greater number of cardiometabolic comorbidities (hypertension, diabetes, and obesity) was associated with increased risk of all-cause hospitalization in HF, especially among patients with HFpEF. This suggests a possible role for targeting cardiometabolic comorbidities to reduce HF morbidity in HFpEF.

Abstract 12547: Incidence of Pulmonary Hypertension in the Echocardiographic Referral Population

Background: Incident rates (IRs) for pulmonary hypertension (PH) using diagnostic data rather than diagnostic codes (DC) have not been reported. We examined PH IRs, risk factors, and mortality among patients (pts) referred for echocardiography (TTE) in a national healthcare system and a separate tertiary care center. Methods: Pulmonary artery systolic pressure (PASP) estimates were extracted from the Veterans Affairs (1999-2020) and Vanderbilt (1994-2020) systems. PH was defined as PASP &gt;35 mmHg. Individuals free of PH at baseline were followed through incident PH, death, or censored at end of study. Secondary outcome was mortality rate (MR) after incident PH. We used Poisson regression to estimate IRs and cox models for hazard ratios. Results: We identified 245,067 veterans (60 years [IQR 55-64], 94% male, 20% Black) and 117,526 VUMC pts (60 years [IQR 46-70], 46% male, 11% Black) free of PH at baseline. Only 22% of pts with TTE-based PH had a DC for PH. PH IRs and adjusted hazard were substantially higher in pts with HF or COPD and highest in pts with both ( Table 1 ). MR after incident PH was highest in pts with both HF and COPD and lowest in pts without either (Figure 1A ). MRs increased markedly at PASP values &gt;45mmHg ( Figure 1B ). Independent risk factors for incident PH included older age (HR 1.07; 95%CI 1.06-1.09), male sex (HR 1.24; 95%CI 1.17-1.30), black race (HR 1.10; 95%CI 1.07-1.13), and cardiometabolic comorbidities. Conclusions: PH IRs estimated by raw diagnostic data are higher than DC-based IRs and strongly associated with HF and COPD. PASP &gt;45mmHg at the time of incident PH is associated with high mortality.

Serum apelin-12 and obesity-related markers in Egyptian children with Down syndrome

Children with Down syndrome (DS) exhibit higher overweight/obesity rates than their typically developing peers. Apelin-12 is a bioactive adipokine that exerts vital roles in obesity-related cardiometabolic comorbidities. To date, apelin-12 has not been investigated in obese-DS. This study aimed to explore the possible association between serum apelin-12 and obesity-related markers and to evaluate the efficiency of apelin-12 in the prediction of metabolic syndrome (MetS) in obese-DS compared to BMI Z-score matched obese-control. The cross-sectional study included 150 prepubertal children classified into three groups; obese-DS (n = 50), obese-control (n = 50), and normal-weight-control (n = 50). Anthropometric parameters, body adiposity, fasting serum levels of blood glucose (FBG), insulin, lipid profile, and apelin-12 were evaluated. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from FBG and insulin. MetS was defined using Adult Treatment Panel III criteria modified for the pediatric age group. ROC curves were analyzed to evaluate the efficiency of apelin-12 in predicting MetS in obesity groups. Obese-DS exhibited higher body adiposity with marked central fat distribution, atherogenic lipid profile, and higher HOMA-IR compared to obese-control. Apelin-12 was significantly higher in obese-DS and obese-DS with MetS compared to obese-control and obese-control with MetS respectively (p < 0.001). The increase in apelin-12 with higher obesity grades was pronounced in obese-DS. Apelin-12 strongly correlated with body adiposity, several MetS risk factors, and HOMA-IR in obese-DS. Significantly higher AUC for apelin-12 in the diagnosis of MetS among obese-DS than obese-control (AUC = 0.948 vs. AUC = 0.807; p = 0.04).Conclusions: The current study supports the crucial role of apelin-12 in obesity-related clinical and biochemical markers and in MetS in obese-DS and obese-control. Serum apelin-12 is a potential diagnostic biomarker for MetS with greater performance in obese-DS than obese-control raising its potential for clinical and therapeutic applications.What is Known:• Obese-DS children displayed excess body adiposity, Pronounced central fat distribution, atherogenic lipid profile, higher HOMA-IR, and higher prevalence of MetS than obese-control.What is New:• Higher serum apelin-12 was observed in obese-DS and obese-DS with MetS than obese-control and obese-control with MetS respectively. The increase in apelin-12 level with increasing obesity grades was more pronounced in obese-DS.• Apelin-12 strongly correlated with obesity-related markers and MetS components in obese-DS. Apelin-12 performed better as a diagnostic biomarker for MetS in obese-DS than obese-control.

Decoding clinical and molecular pathways of liver dysfunction in Psoriatic Arthritis: Impact of cumulative methotrexate doses

BackgroundThe occurrence of liver abnormalities in Psoriatic Arthritis (PsA) has gained significant recognition. Identifying key factors at the clinical and molecular level can help to detect high-risk patients for non-alcoholic fatty liver disease in PsA. Objectivesto investigate the influence of PsA and cumulative doses of methotrexate on liver function through comprehensive in vivo and in vitro investigations. MethodsA cross-sectional study involving 387 subjects was conducted, 200 patients with PsA, 87 NAFLD-non-PsA patients, and 100 healthy donors (HDs), age and sex-matched. Additionally, a retrospective longitudinal study was carried out, including 83 PsA patients since initiation with methotrexate. Detailed clinical, and laboratory parameters along with liver disease risk were analyzed. In vitro, experiments with hepatocyte cell line (HEPG2) were conducted. ResultsPsA patients present increased liver disease risk associated with the presence of cardiometabolic comorbidities, inflammatory markers, onychopathy, and psoriasis. The treatment with PsA serum on hepatocytes encompassed inflammatory, fibrotic, cell stress, and apoptotic processes. At the molecular level, methotrexate impacts liver biology, although the cumulative doses did not affect those alterations, causing any potential damage to liver function at the clinical level. Finally, anti-PDE-4 or anti-JAK decreased the inflammatory profile induced by PsA serum on hepatocytes. Conclusion1)This study identifies the complex link between liver disease risk, comorbidities, and disease-specific features in PsA patients. 2)Methotrexate dose in PsA patients had no significant effect on liver parameters, confirmed by hepatocyte in vitro studies. 3)Anti-PDE-4 and anti-JAK therapies show promise in reducing PsA serum-induced hepatocyte activation, potentially aiding liver complication management.

Association between psoriasis and cardiometabolic comorbidities in a racially and ethnically diverse low-income primary care population.

Psoriasis is associated with cardiometabolic comorbidities, including obesity, diabetes, hyperlipidaemia and hypertension. Many studies that established these associations originated from primarily White and/or relatively affluent populations. To evaluate whether there is a differential risk for cardiometabolic comorbidities in racial/ethnic minorities, we performed a cross-sectional analysis comparing cardiometabolic comorbidities between those with and without psoriasis in a racially and ethnically diverse population of 56 987 low-income patients, stratified by race/ethnicity, and assessed whether race/ethnicity acts as an effect modifier for cardiometabolic comorbidities. We found that psoriasis was statistically significantly associated with obesity, diabetes, hyperlipidaemia and hypertension. The association of psoriasis with comorbidities did not differ significantly by race/ethnicity; thus, we did not find evidence of effect modification. However, our diverse, low-income population had an extremely high baseline prevalence of cardiometabolic comorbidities compared with previous populations studied. Our results suggest education and intervention regarding modifiable risk factors are particularly important among vulnerable populations.

Metabolic syndrome, soluble CD40L, and biomarkers of endothelial dysfunction in people living with HIV.

In the present study, we aimed to investigate the association between soluble CD40 ligand (sCD40L, a marker of platelet activation), soluble thrombomodulin, and syndecan-1 (both well-described markers of endothelial dysfunction) and metabolic syndrome in a large cohort of well-treated people with HIV (PWH) and to elucidate their association with HIV-specific variables. We included 862 PWH with undetectable viral replication. Our hypotheses were tested using uni- and multivariable logistic regression models a priori adjusted for well-known confounders. While no association of soluble thrombomodulin and syndecan-1 with MetS was found, high levels of sCD40L (aOR 1.54 [1.07-2.22]) were associated with excess risk of MetS. Given the previously described association between sCD40L, vascular inflammation and endothelial damage, the results presented in our study may suggest a potential role for sCD40L in the well-known association between cardiometabolic comorbidity and HIV infection.

New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium.

Obesity is a chronic disease that affects more than 650 million adults worldwide. Obesity not only is a significant health concern on its own, but predisposes to cardiometabolic comorbidities, including coronary heart disease, dyslipidemia, hypertension, type 2 diabetes, and some cancers. Lifestyle interventions effectively promote weight loss of 5% to 10%, and pharmacological and surgical interventions even more, with some novel approved drugs inducing up to an average of 25% weight loss. Yet, maintaining weight loss over the long-term remains extremely challenging, and subsequent weight gain is typical. The mechanisms underlying weight regain remain to be fully elucidated. The purpose of this Pennington Biomedical Scientific Symposium was to review and highlight the complex interplay between the physiological, behavioral, and environmental systems controlling energy intake and expenditure. Each of these contributions were further discussed in the context of weight-loss maintenance, and systems-level viewpoints were highlighted to interpret gaps in current approaches. The invited speakers built upon the science of obesity and weight loss to collectively propose future research directions that will aid in revealing the complicated mechanisms involved in the weight-reduced state.

Dapagliflozin and Apparent Treatment-Resistant Hypertension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The DELIVER Trial.

Apparent treatment-resistant hypertension (aTRH) is prevalent and associated with adverse outcomes in heart failure with mildly reduced or preserved ejection fraction. Less is known about the potential role of sodium-glucose co-transporter 2 inhibition in this high-risk population. In this post hoc analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), we evaluated clinical profiles and treatment effects of dapagliflozin among participants with aTRH. DELIVER participants were categorized on the basis of baseline blood pressure (BP), with aTRH defined as BP ≥140/90 mm Hg (≥130/80 mm Hg if diabetes) despite treatment with 3 antihypertensive drugs including a diuretic. Nonresistant hypertension was defined as BP above threshold but not meeting aTRH criteria. Controlled BP was defined as BP under threshold. Incidence of the primary outcome (cardiovascular death or worsening heart failure event), key secondary outcomes, and safety events was assessed by baseline BP category. Among 6263 DELIVER participants, 3766 (60.1%) had controlled BP, 1779 (28.4%) had nonresistant hypertension, and 718 (11.5%) had aTRH at baseline. Participants with aTRH had more cardiometabolic comorbidities and tended to have higher left ventricular ejection fraction and worse kidney function. Rates of the primary outcome were 8.7 per 100 patient-years in those with controlled BP, 8.5 per 100 patient-years in the nonresistant hypertension group, and 9.5 per 100 patient-years in the aTRH group. Relative treatment benefits of dapagliflozin versus placebo on the primary outcome were consistent across BP categories (Pinteraction=0.114). Participants with aTRH exhibited the greatest absolute reduction in the rate of primary events with dapagliflozin (4.1 per 100 patient-years) compared with nonresistant hypertension (2.7 per 100 patient-years) and controlled BP (0.8 per 100 patient-years). Irrespective of assigned treatment, participants with aTRH experienced a higher rate of reported vascular events, including myocardial infarction and stroke, over study follow-up. Dapagliflozin modestly reduced systolic BP (by ≈1 to 3 mm Hg) without increasing risk of hypotension, hypovolemia, or other serious adverse events, irrespective of BP category, but did not improve the proportion of participants with aTRH attaining goal BP over time. aTRH was identified in >1 in 10 patients with heart failure and left ventricular ejection fraction >40% in DELIVER. Dapagliflozin consistently improved clinical outcomes and was well-tolerated, including among those with aTRH. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03619213.

Associations between Normal-Weight Obesity and Disturbances in the Lipid Profile of Young Adults.

Normal-weight obesity (NWO) is characterized by normal body mass index (BMI) but high body fat percentage (%BF) that increases the risks of cardiometabolic comorbidities. Accurate assessment and interpretation of body composition data are necessary to reduce these risks. To compare the cardiometabolic profile of individuals with NWO and normal %BF and evaluate the associated risk factors. A cross-sectional study was conducted with 222 Brazilian adults from a university community, of whom 157 had NWO and 65 had normal BMI and %BF (non-NWO). All participants reported being asymptomatic and without underlying health conditions. Socioeconomic, lifestyle, food intake, anthropometry, body composition measures (using dual-energy radiological absorptiometry), and lipid and glycemic profiles were evaluated. A p < 0.05 was established as significant. The median age of the participants was 23 years (interquartile range: 21 to 25), and most were female (67.1%). No significant differences were found in blood pressure, age, or physical activity levels between the NWO and non-NWO groups. However, the frequency of lipid profile disturbances was higher in the NWO group (54%) compared to the non-NWO group (34%) (p < 0.006). Neck circumference, %BF, and lipid profile disturbances were positively associated with NWO. Individuals with NWO have a worse cardiometabolic profile than those without NWO, and this condition is associated with important biomarkers. Addressing these outcomes is important for preventing long-term cardiometabolic complications. Accurate assessment and interpretation of body composition data, regardless of BMI, are crucial in this scenario.

THU628 Causal Relationship Between The Menstrual Cycle Length And Basal Metabolic Rate: A Two-sample Mendelian Randomization Study

Abstract Disclosure: M. Kazemi: None. S.A. Parry: None. Long or irregular menstrual cycles, as a hallmark reproductive trait in polycystic ovary syndrome (PCOS), have been associated with aberrant energy expenditure, obesity, and cardiometabolic comorbidities. However, current observational studies addressing the contributions of energy expenditure to menstrual cyclicity have generated conflicting results and have not utilized the full extent of known single nucleotide polymorphisms associated with basal energy expenditure. Whether the relationship is causal is uncertain. We conducted a two-sample Mendelian Randomization study to interrogate the causal relationships between basal metabolic rate and length of menstrual cycles. The (MR) analyses were performed using publicly released genome-wide association studies (GWAS) statistics from 2 separate European cohorts using the UK Biobank database. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), to detect and correct the effect of horizontal pleiotropy. The result of the IVM method revealed that genetically determined basal metabolic rate has an inverse causal effect on the length of the menstrual cycle (β, -0.13, SE, 0.03; P=2.17 E-05). The results of MR-Egger regression, weighted median, and weighted mode methods were consistent with those of the IVW method. Sensitivity analyses revealed that horizontal pleiotropy was unlikely to distort the causal estimates. Collectively, our MR analysis revealed that basal metabolic rate appears to be causally affecting the length of menstrual cycles. Our findings reflect novel insights into the role of energy metabolism on menstrual disturbances. However, the molecular mechanisms should be investigated. Future MR analysis is warranted to confirm our findings by controlling for potentially relevant confounders, including obesity and age. Nevertheless, our findings have perturbations to elucidate causal pathways explaining obesity in relevant conditions, including PCOS. Presentation: Thursday, June 15, 2023

FRI405 PCOS Health-related Quality-of-life And Depressive Symptoms Across The Lifespan

Abstract Disclosure: P.J. Wright: None. C.F. Corbett: None. A.S. Tavakoli: None. Polycystic ovary syndrome (PCOS) is a complex, heterogenous collection of symptoms attributed to hormonal dysregulation. Of women diagnosed with PCOS, approximately 50% have obesity, 70% have dyslipidemia, and 80% have insulin resistance (1). These clinical features increase the risk for cardiovascular disease, diabetes, and reproductive cancers by ≥50% while negatively impacting health-related quality-of-life (HRQoL). To date, most PCOS studies have only examined the cardiometabolic disturbances and HRQoL among women of reproductive age. However, PCOS is a chronic condition that transcends the reproductive years and requires management across a woman’s lifespan. Older women with PCOS continue to cope with multiple risk factors due to persistent hormonal dysregulation and/or because they have developed ≥1 cardiometabolic comorbidities. As such, we hypothesize that HRQoL among peri-postmenopausal women with PCOS remains compromised and depressive symptoms remain common. The purpose of our cross-sectional study was to compare HRQoL and depressive symptoms among peri-postmenopausal women with PCOS aged ≥43 years relative to premenopausal women with PCOS aged 18-42 years. An online survey link comprising questionnaires about demographics, HRQoL, and depressive symptoms was posted on two PCOS-specific Facebook groups. Respondents (n = 1,044) were separated into two age cohorts: women with PCOS aged 18-42 years (n = 935) and women with PCOS aged ≥43 years (n = 109). Data from the online survey were analyzed using descriptive statistics, Pearson correlations, and multiple regression via SAS. Results were interpreted through the lens of life course theory. Life course theory describes a sequence of age-differentiated events and roles embedded in sociocultural context that people enact over time. Sociocultural contexts include stages of life (e.g., parenthood, menopause), social conditions (e.g., age-related norms), and relationships with other people (e.g., family, friends) during periods of human development (adolescence, adulthood, etc). Chronic health conditions impact human development and often alter the sociocultural context for women as they navigate the life course. Age, marital status, and children significantly differed between groups. HRQoL among older women with PCOS was significantly better as compared to those aged 18-42 years. Results indicated significant positive linear associations between the HRQoL psychosocial/emotional subscale and other HRQoL subscales and a significant negative association with age. Fertility and sexual function HRQoL subscales were not significantly associated with the psychosocial/emotional subscale among women aged ≥43 years. Women in both groups had moderate depressive symptoms. Study findings demonstrate the need to tailor PCOS management and PCOS-specific HRQoL assessment instruments to women’s life stage. This knowledge can inform future research about peri-postmenopausal women with PCOS and age appropriate and patient-centered healthcare, including requisite clinical screenings (e.g., depressive symptoms) and lifestyle counseling across the lifespan. Azziz, R. (2020). Epidemiology and pathogenesis of the polycystic ovary syndrome in adults. http://www.uptodate.com/contents/epidemiology-and-pathogenesis-of-the-polycysticovary-syndrome/ Presentation: Friday, June 16, 2023

THU635 Metabolic Characteristics Among Polycystic Ovary Syndrome-Phenotypes In A Sample Of Hispanic Patients

Abstract Disclosure: L.A. Gonzalez-Rodriguez: Research Investigator; Self; Eli Lilly &amp; Company. I.C. Arroyo: None. B. Diaz-Rios: None. L. González-Sepúlveda: None. C.M. Casas-Loyola: None. J. Bermúdez-Santos: None. C. Pérez-Cardona: None. J. Romaguera: None. R. Azziz, MD, MBA, MPH: Advisory Board Member; Self; Arora Forge. Consulting Fee; Self; Rani Therapeutics, Spruce Biosciences, Fortress Biotech, Core Access Surgical Technologies. Grant Recipient; Self; Ferring Pharmaceuticals. Stock Owner; Self; Martin Imaging. PURPOSE: Polycystic Ovary Syndrome (PCOS), a common endocrinopathy affecting women in their reproductive years, is associated with an increased risk for cardiometabolic comorbidities. Even though PCOS is a common condition, there is often a delay in diagnosis and treatment due to several proposed diagnostic criteria. Due to the complexity of this syndrome and different clinical manifestations, it has been recommended to identify their 4 phenotypes. This study aimed to compare the clinical and metabolic characteristics among PCOS-phenotypes in a sample of Hispanic patients. METHODS: This is a cross-sectional study of females between 21-45 years of age with confirmed PCOS using the Rotterdam criteria. Patients were classified according to phenotypes: A, hyperandrogenism (HA), oligoovulation/menstrual dysfunction (OA/MD), and polycystic ovarian morphology (PCOM); B, HA + OA/MD; C, HA + PCOM; D, OA/MD + PCOM. Metabolic Syndrome (MetS) was diagnosed using ATP III criteria. Metabolic characteristics were compared between groups. RESULTS: Sixty-three patients with PCOS were evaluated with phenotypes A (60%), B (21%), C (5%), and D (14%). Only 26 patients (41%) had a previous diagnosis of PCOS. The prevalence of MetS in this sample was 52.4%. Among the phenotypes, phenotype B had the higher prevalence of MetS (61.5%) followed by phenotype D (55.6%) and phenotype A (52.6%). Significant differences in obesity, waist, and hip circumference were found, with phenotype-C having lower parameters (p ≤ 0.05). A tendency for lower BMI, waist-to-hip-ratio, HOMA-IR, and hs-CRP levels was also observed in phenotype-C. CONCLUSION: Our study found a high prevalence of MetS in this sample of patients with PCOS; phenotypes affected by menstrual dysregulation having a higher prevalence. Less than half of patients with PCOS were previously diagnosed despite multiple medical evaluations for symptoms, which emphasizes the importance of an early diagnosis to avoid cardiometabolic complications. Presentation: Thursday, June 15, 2023

FRI147 A Direct-To-Patient Primary Aldosteronism Screening Program In The United States: Implementing Guidelines Nationwide

Abstract Disclosure: J.M. Brown: Consulting Fee; Self; Bayer, Inc. B. Bacare: None. Y.M. Niebuhr: None. L.C. Tsai: None. E.E. Abel: None. B. Honzel: None. A. Vaidya: Consulting Fee; Self; Corcept Therapeutics, HRA Pharmaceuticals, Mineralys. Context: Primary aldosteronism (PA) is a prevalent but grossly underrecognized contributor to the global burden of hypertension, excess cardiovascular and renal disease, and death. Though Endocrine Society guidelines recommend high risk populations who should be screened for PA, fewer than 2% of these at-risk patients are ever tested. Given the poor rates of routine screening within guideline-eligible populations, we designed and implemented a direct-to-patient virtual-based PA screening intervention. Methods: Participants with one or more guideline indications for PA screening were recruited using social media, online recruitment platforms, and online patient portals to participate in a video visit to review medical history and to arrange a local reference lab draw for plasma renin activity (PRA), aldosterone (via LC-MS/MS), and a basic metabolic panel, without adjustment of medications. Screening results were categorized as “Likely Confirmed PA”, “Possible PA”, or “Unlikely PA” based on established diagnostic frameworks. Test results, their interpretations, and possible next clinical steps (i.e., further testing, referral, empiric treatment) were communicated directly to patients and their primary care providers, with annual reminders and follow-up. Results: To date, 3220 participants from 12 states in the eastern USA had been contacted, with 2504 eligible. At the time of submission, 212 participants had completed laboratory assessment, with the remainder pending. 79 (37.3%) participants had resistant hypertension, 95 (44.8%) had hypertension with hypokalemia, 75 (35.4%) had hypertension with sleep apnea, 11 (5.2%) had hypertension with adrenal mass, and 90 (42.5%) had hypertension with a family history of early hypertension and/or stroke. Indicated PA screening had not previously been performed despite access to specialist care: 55% had an endocrinologist, cardiologist, and/or nephrologist. 27.4% of the participants had screening results consistent with either “likely confirmed PA” (7.1%) or “possible PA” (20.3%). Of those with both resistant hypertension and hypokalemia, 35.0% met criteria for “likely confirmed” or “possible” PA. A “likely confirmed” diagnosis of PA was associated with a median aldosterone-to-renin ratio of 33 ng/dL per ng/mL/h [IQR: 24, 76] and prevalent cardiometabolic comorbidities (33.3% had diabetes, 20.0% coronary artery disease, 13.3% heart failure). Conclusions: This ongoing, prospective, virtual-based, direct-to-patient PA screening program identified confirmed or possible PA in up to 27.4% of guideline-eligible participants. By reaching patients directly, rather than relying on routine clinical screening that is known to be dramatically underutilized, this study highlights the unrecognized prevalence of PA and demonstrates a novel approach to identifying this common, morbid, and treatable condition across the USA. Presentation: Friday, June 16, 2023

Associations between ultra-processed food consumption and kidney function in an older adult population with metabolic syndrome

Ultra-processed food (UPF) consumption has increased dramatically over the last decades worldwide. Although it has been linked to some cardiometabolic comorbidities, there is limited evidence regarding kidney function. This study aimed to cross-sectionally and longitudinally assess the association between UPF consumption and estimated-glomerular filtration rate (eGFR) based on Cystatin C (CysC). Older adults (mean age 65±5.0 years, 46% women) with overweight/obesity and metabolic syndrome (MetS) who had available data of CysC at baseline (n=1909), at one-year and at 3-years of follow-up (n=1700) were analyzed. Food consumption was assessed using a validated 143-item semi-quantitative food frequency questionnaire and UPF consumption (% of g/d) at baseline and changes after one-year of follow-up were estimated according to NOVA classification system. Multivariable-adjusted linear and logistic regression models were performed to evaluate the cross-sectional associations between UPF consumption with eGFR levels and decreased kidney function (eGFR <60ml/min/1.73m2) at baseline. Multivariable-adjusted mixed-effects linear regression models were fitted to investigate the associations between one-year changes in UPF and eGFR over 3-years of follow-up. Individuals with the highest baseline UPF consumption showed lower eGFR (β:-3.39ml/min/1.73m2; 95% CI:-5.59 to-1.20) and higher odds of decreased kidney function (OR: 1.64; 95% CI: 1.21 to 2.22) at baseline, compared to individuals in the lowest tertile. Participants in the highest tertile of one-year changes in UPF consumption presented a significant decrease in eGFR after one-year of follow-up (β:-1.45ml/min/1.73m2; 95% CI:-2.90 to-0.01) as well as after 3-years of follow-up (β:-2.18ml/min/1.73m2; 95% CI:-3.71 to-0.65) compared to those in the reference category. In a Mediterranean population of older adults with overweight/obesity and MetS, higher UPF consumption at baseline and one-year changes towards higher consumption of UPF were associated with worse kidney function at baseline and over 3-years of follow-up, respectively. ISRCTN89898870.