Citations

Objective: To compare 1-year changes in estimated 10-year and lifetime atherosclerotic cardiovascular disease (ASCVD) risk following metabolic and bariatric surgery (MBS) versus glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy among adults with obesity. Summary Background Data: Obesity is a major driver of ASCVD through adverse metabolic and inflammatory pathways. Metabolic and bariatric surgery and GLP-1 receptor agonists represent the most effective contemporary treatments for obesity and are increasingly used to mitigate cardiovascular risk. However, their comparative effects on integrated short-term and lifetime ASCVD risk in real-world clinical practice remain incompletely characterized. Methods: We conducted a retrospective cohort study of adults with obesity (body mass index ≥30 kg/m²) who underwent MBS or initiated GLP-1RA therapy between 2020 and 2023 within a large tertiary health care system in the United States. Participants were identified from electronic health records and followed for 12 months. Primary outcomes were 1-year changes in estimated 10-year and lifetime ASCVD risk. Secondary outcomes included percent total body weight loss, blood pressure, and lipid parameters. Multivariable linear regression models were used to adjust for baseline body mass index and baseline ASCVD risk. Results: The final cohort included 812 patients, of whom 579 underwent MBS and 233 initiated GLP-1RA therapy. At baseline, patients receiving GLP-1RAs were older and had higher estimated ASCVD risk. At 1 year, reductions in 10-year ASCVD risk were similar between groups (−0.8% vs. −1.1%; P =.36). In contrast, lifetime ASCVD risk decreased significantly more following MBS than GLP-1RA therapy (−8.6% vs. −1.7%; P <.001). MBS was associated with greater percent total body weight loss (−27.8% vs. −11.1%; P <.001) and more favorable lipid changes, including larger reductions in low-density lipoprotein cholesterol and greater increases in high-density lipoprotein cholesterol. After adjustment, MBS remained independently associated with a greater reduction in lifetime ASCVD risk compared with GLP-1RA therapy (β −6.92; 95% CI −9.22 to −4.62). Conclusions: In this real-world cohort, both MBS and GLP-1RA therapy were associated with improvements in estimated cardiovascular risk, but MBS conferred substantially greater reductions in lifetime ASCVD risk, accompanied by superior weight loss and lipid improvements. These findings highlight the complementary roles of surgical and pharmacologic therapies in obesity management and may inform strategies to optimize long-term cardiovascular risk reduction.

Background: Functional hypothalamic amenorrhea (FHA) is a common form of secondary amenorrhea caused partly by undernutrition relative to demand. Objective: To compare the dietary nutritional intake between women with FHA and eumenorrheic controls and evaluate micronutrient profiles. Methods: This cross-sectional study included 30 women with FHA and 29 eumenorrheic controls not on hormones. FHA was defined as ≥3 consecutive months of amenorrhea, estradiol of <50 pg/mL, and FSH and LH of <10 mIU/L, excluding other etiologies. A 3-day food diary was collected for dietary analysis, excluding dietary supplements using ESHA Research Food Processor. Results: The mean age of women with FHA and controls was 26.4 years ± 6.2 versus 30.3 years ± 3.7 ( p = 0.002), with no differences in BMI ( p = 0.16) or the waist-to-hip ratio ( p = 0.71). Women with FHA and controls consumed comparable median calorie intake (1784 kcal [1465, 2011] vs. 1732 kcal [1578, 1982], p = 0.62), with no differences in self-reported exercise patterns. Women with FHA consumed more dietary protein (84.2g [74, 112] vs. 74 g [59, 92], p = 0.001) and dietary fiber (30.1 g [22, 43] vs. 17.3 g [15, 23], p = 0.02) versus controls, respectively. When expressed as a percentage of estimated average requirements (% estimated average requirement), women with FHA had higher intakes of vitamin A (105% [45, 219] vs. 43% [21, 86], p = 0.005), vitamin C (201% [139, 351] vs. 107% [75, 190], p = 0.004), and iron (169% [146, 220] vs. 120% [99, 192], p = 0.027) compared with controls. Conclusions: Women with FHA had similar caloric intake to eumenorrheic controls but consumed more dietary protein, fiber, vitamin A, vitamin C, and iron. Future studies should examine the nutritional profiles of women with FHA in relation to long-term health consequences such as bone and vascular health.

Objective: Perimenopause is the time leading up to a woman’s last menstrual cycle and includes the 12 months afterward. Studies that systematically compare perimenopause symptoms across diverse cultural and geographic settings are lacking. This study, utilizing data from Flo, an international mobile health application, aimed to assess global knowledge and symptom experiences related to perimenopause. Methods: This cross-sectional survey was conducted via the Flo application, offered to users aged 18 years and above. The primary endpoints were knowledge of perimenopause symptoms from all survey participants, and self-reported perimenopause symptoms for survey participants aged 35 years and above. Secondary analyses compared knowledge scores and symptoms across geographic regions. Results: A total of 17,494 women from 158 countries were included. Commonly recognized perimenopause symptoms included hot flashes (71%), sleep problems (68%), and weight gain (65%). Of the participants, 12,681 were aged 35 years or above, with the most common self-reported symptoms being fatigue (83%), physical and mental exhaustion (83%), irritability (80%), depressive mood (77%), sleep problems (76%), digestive issues (76%), and anxiety (75%). This pattern of symptoms was similar among those who self-reported being in perimenopause, though higher than in those not in perimenopause. International variation in perimenopause symptom knowledge and symptoms experienced was noted ( P <0.001). Conclusions: This survey highlights a discordance between perimenopause knowledge and actual symptoms experienced across diverse global populations. While hot flashes were the most widely recognized symptom, respondents aged 35 years or above most commonly reported experiencing fatigue, physical and mental exhaustion, and irritability.

Background/Objectives: Individuals with type 2 diabetes (T2D) achieve less total body weight loss (TBWL) with obesity medications compared to those without T2D. The individualized metabolic surgery (IMS) score, originally developed to predict T2D remission after bariatric surgery, inversely correlates with TBWL response to semaglutide. IMS reflects T2D severity, incorporating HbA1c and T2D duration and medication use. This study aims to evaluate TBWL with tirzepatide across IMS severity categories and identify predictors of response in a real-world cohort. Methods: This retrospective analysis included 717 adults with T2D using tirzepatide for overweight or obesity within the Mayo Clinic Health System. Patients were stratified by IMS severity (mild, moderate, severe) and quartiles. Primary endpoint: TBWL% at 15 months. Secondary endpoints: categorical thresholds (≥5%, ≥10%, ≥15%, ≥20%) and predictors of TBWL%. Linear mixed-effects models and regression models were employed. Results: At 15 months, TBWL was greater in mild versus severe IMS groups (14.8% vs. 11.0%, p = 0.015), with similar trends across quartiles. The proportion achieving ≥ 20% TBWL was nearly two-fold higher in mild versus severe IMS (27% vs. 14%, p = 0.03). Female sex independently predicted greater TBWL, whereas insulin use, higher T2D medication burden (particularly weight-promoting agents), and HbA1c > 7% were associated with less TBWL. Conclusions: Tirzepatide produced clinically meaningful TBWL across all IMS categories, although TBWL declined with increasing IMS severity. Glycemic control and T2D medication use emerged as strong predictors of TBWL. The IMS score may serve as a practical tool to anticipate weight-loss trajectories, guide personalized treatment decisions, and inform patient counseling.

Background: Peripheral artery disease (PAD) is a global health challenge. Advances in artificial intelligence (AI), such as large language models (LLMs) and chain-of-thought (CoT) reasoning, offer novel approaches for clinical recommendations. This study compared the readability and guideline adherence of responses from physicians and AI for a standardized PAD case. Methods: This cross-sectional study gathered responses from 30 specialized physicians (11 cardiologists, 19 vascular surgeons) across seven Latin American countries and 13 LLM systems (10 standard, three CoT). Both groups addressed diagnosis, treatment, risks, and prognosis; LLMs responded as vascular specialists. Responses were blindly evaluated with five validated Spanish readability indices and compared to the 2024 ACC/AHA multisocietal PAD guideline. Three experts scored guideline adherence; nonparametric tests were applied. Results: Guideline adherence did not differ significantly between physicians (median 5.8 [3.4–7.6]) and LLMs (7.3 [4.7–9.7], p = 0.169), though CoT-LLMs achieved the highest scores (9.7 [8.5–11.0]). LLMs more often recommended supervised exercise (84.6% vs 30.0%, p = 0.002) and revascularization for quality of life (69.2% vs 20.0%, p = 0.004), whereas physicians favored cilostazol (60.0% vs 30.8%, p = 0.104). LLM responses had lower Readability μ values (46.9 vs 51.4, p = 0.012). Inter-rater reliability was highest for CoT-LLMs (intraclass correlation coefficient [ICC] = 0.98) versus physicians (ICC = 0.76). Conclusion: LLM showed comparable guideline adherence to physicians although CoT models achieved the highest scores. The difference in physician and AI treatment preferences suggest the potential of AI as adjunct clinical tools and warrants further study.

Abstract Disclosure: R. Castaneda: None. D. Bechenati: None. R.D. Rivera Gutierrez: None. M.A. Espinosa: None. J.L. Villamarin: None. E. Tama: None. J.L. Meek: None. P. Bennett: None. A. Acosta: Novo Nordisk, Gila Therapeutics, Amgen Inc, Regeneron Pharmaceuticals, Boehringer Ingelheim, Rhythm Pharmaceuticals, General Mills, Currax, Nestle, Phenomix Sciences, Busch Health, RareDiseases, National Institute of Health, Vivus Pharmaceuticals, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical. S. Faubion: Era Women’s Health Platform, PriMed, MedAll, AiCME, Medscape, Weight Watchers. C. Shufelt: Bayer Advisory Board. M.D. Hurtado: Novo Nordisk, National Institute of Health, Phenomix. Introduction: Tirzepatide, a dual GIP and GLP-1 receptor agonist, is an FDA-approved medication demonstrating the highest efficacy for weight loss among currently available treatments. However, the influence of sex and age on weight loss outcomes with tirzepatide remains unclear. Objective: To investigate the influence of sex and age on weight loss outcomes in patients treated with tirzepatide. Methods: This retrospective study evaluated weight loss outcomes associated with tirzepatide across sex and age groups. Patients with active malignancy, prior bariatric surgery, or concurrent anti-obesity medication were excluded. The primary endpoint was total body weight loss percentage (TBWL%) at 15 months by sex and age. The influence of age was analyzed as a categorical (≤45, 46-59, ≥60 years) and continuous variable. Secondary outcomes included TBWL% at 3, 6, 9, and 12 months by sex and age. Data were analyzed using independent t-tests, one-way ANOVA, and multivariate regression; results are reported as mean ± standard deviation. Results: The study included 1033 patients (57.1% female; mean age 56 ± 11 years; mean BMI, 37.7 ± 8 kg/m2). By age category, 18.8% (196) were ≤45 years (35.7% males, 64.3% females), 45.9% (473) were 46-59 years (42.7% males, 57.3% females), and 35.3% (364) were ≥60 years (54.7% males, 45.3% females). At all timepoints, TBWL was significantly greater in females compared to males at all timepoints. At 15 months females had a higher TBWL than males: 15.3% ± 10, n=340, vs. 10.2% ± 8, n=244, (p &lt; 0.001). Among females, premenopausal women achieved a higher TBWL than postmenopausal women: 16.9% ± 10 vs 14.4% ± 9, p = 0.04. Analysis by age groups revealed a trend toward higher TBWL in younger patients that did not reach statistical significance (p = 0.152): ≤45 years (14.7% ± 10%), 46-59 years (12.9% ± 10%), and ≥60 years (12.7% ± 9%). After adjusting for baseline age, BMI, and diabetes status, sex remained a strong predictor for weight loss outcomes (PE= 4.5, 95% CI [2.96, 5.97], p &lt; 0.001), following type 2 diabetes status (PE= 4.8, 95% CI [3.0, 6.7], p &lt; 0.001). Conclusion: Sex but not age was a strong predictor of weight loss with tirzepatide. Female sex was associated with greater weight loss than male sex. These results emphasize the importance of considering sex-specific factors in weight loss strategies and warrant further investigation into the underlying biological mechanisms. Differential weight loss by menopause, underscores the role of sex hormones. Presentation: Monday, July 14, 2025

Abstract Disclosure: R.D. Rivera Gutierrez: None. D. Bechenati: None. R. Castaneda: None. M.A. Espinosa: None. J.L. Villamarin: None. E. Tama: None. J.L. Meek: None. T.M. Taaffe: None. P.K. Bennett: None. A.J. Acosta: Novo Nordisk, Gila Therapeutics, Rhythm Pharmaceuticals, Amgen Inc, General Mills, Regeneron Pharmaceuticals, Boehringer Ingelheim, Currax, Nestle, Phenomix Sciences, Busch Health, RareDiseases, National Institute of Health, Vivus Pharmaceuticals, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical. S. Faubion: Era Women’s Health Platform, PriMed, AiCME, MedAll, Medscape, Weight Watchers. C. Shufelt: Bayer Advisory Board. M.D. Hurtado: Novo Nordisk, National Institute of Health, Phenomix Sciences. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular (CV) benefits. Tirzepatide (TZP), a dual GLP-1 and gastric inhibitory polypeptide (GIP) receptor agonist approved for weight management and glycemic control, currently lacks evidence on CV outcomes. This study evaluates TZP’s impact on cardiometabolic parameters and atherosclerotic cardiovascular disease (ASCVD) risk scores. Methods: We conducted a multicenter retrospective study of adults prescribed TZP from June 1, 2022, to November 1, 2024. Inclusion criteria included 12 months of TZP use and age &gt;18 years. Exclusion criteria were pregnancy, active malignancy, concurrent FDA-approved antiobesity medications, and prior bariatric surgery. Endpoints included changes in blood pressure, lipid profiles, liver enzymes, glucose control parameters, medication use (statins, aspirin, antihypertensives), and ASCVD risk scores from baseline to 12 months, stratified by sex. Data were obtained from electronic medical records. We present data as mean differences [95% CI]. We used T-tests and multivariate regression analyses for analyses. Results: Among 831 participants (59.4% female; 91.2% White; mean age: 58 ± 12 years), 12-month weight loss was -12% [-13, -11], p&lt;0.001. We observed significant improvement in systolic blood pressure (SBP) (-4 [-5, -3] mmHg, p&lt;0.001), triglycerides (TG) (-38 [-52, -23] mg/dL, p&lt;0.001), total cholesterol (TC) (-7 [-10, -4] mg/dL, p&lt;0.001), LDL cholesterol (LDL) (-6 [-9, -4] mg/dL, p&lt;0.001), fasting glucose (FG) (-39 [-48, -29] mg/dL, p&lt;0.001), ALT (-10 [-15, -5] U/L, p&lt;0.001), HbA1c (-1.3% [-1.5, -1.2], p&lt;0.001), and HDL cholesterol (HDL) (+4 [+3, +5] mg/dL, p&lt;0.001). The Lifetime and 10-year ASCVD scores did not significantly change after 12 months (p&gt;0.05), underscoring TZP’s potential in mitigating the aging-associated increase in CV risk. Considering sex, females had greater weight loss (-13% [-14, -12] vs. -10% [-11, -9], p&lt;0.001), and greater improvements in TC (-5% [-8, -2] vs -3% [-6, 0.1], p&lt;0.001) and LDL (-10% [-14, -6] vs -4% [-8, 1], p&lt;0.001). Males had a greater reduction in DBP (-2% [-4, -1] vs (-1% [-6, 3], p=0.006). Both males and females demonstrated similar improvements in FG and HbA1c. Conclusion: TZP significantly improved CV and metabolic parameters after 12 months, with greater benefits observed in females. These improvements effectively mitigated the age-related rise in ASCVD risk scores. Larger, prospective studies are warranted to confirm these findings and further investigate TZP’s long-term CV effects. Presentation: Monday, July 14, 2025