BACKGROUND:Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide. Echocardiographic assessment of left ventricular (LV) asynchrony may provide additional value for detecting ischemia or infarction. OBJECTIVES:To assess the systolic and diastolic mechanical dispersion (MD) by 3D-echocardiography and its correlation with left ventricular ejection fraction (LVEF) and ischemia or infarction by myocardial perfusion study (MPS) gated 99m-Tc Sestamibi-SPECT. METHODS:Cross-sectional study of patients with angina. Systolic and diastolic MD were defined as the standard deviation (SD) of the time to reach minimum ventricular volume, corrected for the R-R interval. Association with LVEF was assessed with correlation and linear regression. ROC curves identified ischemia or infarction and compared with E/A ratio, TRIVI, and E/e' ratio. RESULTS:205 patients were studied with median age 62 (IQR: 54-69) years. 51% (n = 104) presented ischemia or infarction. We observed a negative correlation with systolic (r = -0.343, 95% -0.459 to -0.215; p < 0.001) and diastolic (r = -0.184, 95% -0.314 to -0.047; p < 0.01) MD and MPS-LVEF, which contributes to 8.9% and 11.8% of variance, respectively. Both parameters displayed an area under the curve (AUC) of 0.634 (95% 0.559-0.709, p < 0.001) and 0.604 (95% CI 0.527-0.679, p < 0.001) are shown to detect ischemia/infarction. In patients with transmural infarction the AUC for systolic MD improved to 0.691 (95% 0.582-0.801, p < 0.05). CONCLUSIONS:Systolic and diastolic MD are useful and simple parameters for assessment of LV function and ischemia or infarction.

ABSTRACT Body mass index (BMI) alone may underestimate clinically relevant obesity because it does not capture central fat distribution. We compared obesity prevalence in Mexico using BMI-only criteria, adiposity-confirmed criteria, and the clinical obesity definition proposed by the Lancet Diabetes and Endocrinology Commission. We conducted a population-based, cross-sectional study of 13,160 adults aged 18 years or older who participated in the 2018-2019 Mexican National Health and Nutrition Survey (ENSANUT). Obesity prevalence was estimated through survey-weighted analyses that accounted for the complex sampling design. The weighted prevalence of obesity based on BMI was 34.5% (95% CI, 33.1-35.9), while 30.9% (95% CI, 29.6-32.2) met criteria for clinical obesity. One quarter of individuals with clinical obesity had a BMI under 30 kg/m 2 , a phenotype more common among older adults. Half of adults with a BMI under 30 kg/m 2 showed elevated central adiposity. BMI alone underestimates clinically relevant obesity in Mexican adults. Adding waist-based measurements could improve the identification of individuals with excess fat and metabolic risk, both in clinical settings and population monitoring.

BACKGROUND:Effective cardiovascular disease (CVD) risk management is essential for optimal diabetes care. Here, we estimated the prevalence and determinants of CVD risk factor control among individuals with diagnosed diabetes in Mexico. METHODS:We analyzed data from individuals ≥20 years with diagnosed diabetes from 2016 to 2023 Mexican National Health and Nutrition Surveys. We estimated the prevalence of glycemic, blood pressure, noncurrent smoking, low-density lipoprotein cholesterol, and combined CVD risk factor control. We estimated use of blood pressure-lowering, cholesterol-lowering, and glucose-lowering medication and explored determinants of control achievement using logistic regression. RESULTS:We analyzed data from 2916 participants, representing 43.2 million adults with diagnosed diabetes during 2016 to 2023. In 2023, glycemic control was 29% (95% CI, 21%-38%), blood pressure control 22.9% (95% CI, 14%-31%), and noncurrent smoking 89% (95% CI, 81%-96%). The prevalence of high or very-high CVD risk using Systematic Coronary Risk Evaluation 2-Diabetes increased from 59.8% (95% CI, 52.1%-67.0%) in 2016 to 68.4% (95% CI, 55.6%-78.9%) in 2023, representing ~5.1 million adults. Low-density lipoprotein cholesterol control increased from 2.8% (95% CI, 1.2%-4.4%) in 2016 to 6.6% (95% CI, 1.9%-11.2%) in 2023 and statin use from 5.5% in 2016 to 63% in 2023. Combined risk factor control achievement was low due to suboptimal low-density lipoprotein cholesterol control and was more likely achieved in women, younger individuals, and those with college education or living in states with higher socioeconomic position. CONCLUSIONS:Despite increasing CVD risk during this period, glycemic and CVD risk factor management for adults with diabetes in Mexico remains suboptimal. Our findings suggest a need for strategies to improve CVD risk management to reduce diabetes-related mortality and complications.

Type 2 diabetes (T2D) is a heterogeneous disease and a major public health concern in low- and middle-income countries (LMICs). To address this heterogeneity, several subgroup classification frameworks have been proposed. Among them, the most widely used is the data-driven classification proposed by Ahlqvist et al., which includes severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). However, reproducing this framework is limited by the need for specialized measurements of beta-cell function and insulin resistance, which are not routinely available in most clinical or epidemiological settings in LMICs. To overcome these barriers, we derived a classification algorithm to reproduce these diabetes subgroups. Here, we present a four-step roadmap in which this framework may help characterize T2D heterogeneity across Mexico, potentially guide pathophysiology-oriented treatment strategies, support public health monitoring, and enhance our understanding of T2D heterogeneity to improve diabetes care in our country.

Aims: The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) has emerged as a potential marker of cardiometabolic dysfunction. However, evidence regarding its association with prediabetes remains limited in Hispanic populations. We evaluated the association between UHR and prediabetes in Mexican-Mestizo adults from the Genetics of Atherosclerotic Disease (GEA) study. Methods: This retrospective cross-sectional analysis included 1395 adults without diabetes or coronary artery disease. Prediabetes was defined as fasting glucose levels between 100 and 125 mg/dL. Participants were stratified into sex-specific UHR tertiles. Logistic regression models adjusted for demographic, lifestyle, and cardiometabolic variables were used to evaluate the association between UHR and prediabetes. Results: Mean age was 53 ± 6 years, 51% were women, and 17% had prediabetes. Individuals in the highest UHR tertile exhibited higher adiposity indices, triglycerides, Apo-B, hsCRP, HOMA-IR, and lower HDL-C and adiponectin levels. Prediabetes prevalence increased progressively across UHR tertiles (11%, 15%, and 24%; p < 0.001). After multivariable adjustment, each 0.1-unit increase in UHR was associated with prediabetes (OR 1.65, 95% CI 1.26–2.17). Compared with the lowest tertile, individuals in the highest UHR tertile had more than two-fold higher odds of prediabetes (OR 2.03, 95% CI 1.36–3.05, p < 0.001). A significant interaction between UHR and sex was observed, with a stronger association in women than in men (OR 3.39, 95% CI 2.1–5.5 vs. 1.19, 95% CI 0.84–1.67). Conclusions: Higher UHR was independently associated with prediabetes and an adverse cardiometabolic profile in Mexican-Mestizo adults. UHR may serve as a simple complementary marker of glucose metabolic disturbances.

Background: Prediabetes is highly prevalent in older adults and is characterized by heterogeneous clinical trajectories, including regression to normoglycemia and progression to diabetes. While prediabetes has been associated with impaired physical function and frailty, the longitudinal impact of both a single diagnosis and dynamic glycemic transitions on functional outcomes remains unclear. We aimed to evaluate associations between baseline prediabetes and glycemic transitions over time with trajectories of functional capacity and frailty in older adults. Methods: We conducted a pooled analysis of harmonized data from five nationally representative longitudinal aging cohorts (MHAS, HRS, CHARLS, ELSA, CRELES) within the Gateway to Global Aging Data, including adults aged ≥50 years with ≥1 HbA1c measurements. Prediabetes was defined per ADA criteria (HbA1c 5.7-6.4%). Functional outcomes included activities of daily living (ADL), instrumental ADL (IADL), and frailty assessed using Fried phenotype, FRAIL scale, and a deficit-accumulation Frailty Index (FI). Mixed-effects Poisson models estimated incidence rate ratios (IRRs) for baseline prediabetes, while generalized estimating equations assessed time-varying glycemic status and transition trajectories. Models were adjusted for age, sex, cohort, and time-varying covariates, with sensitivity analyses including BMI, smoking, and alcohol intake. Findings: Among 18,571 participants (median follow-up 13.6 years), baseline prediabetes was associated with increased progression of functional deficits and frailty compared with normoglycemia, including higher FI values and accelerated FI progression. Prediabetes was associated with higher incidence of ADL, IADL, and multimorbidity deficits from early follow-up, although time-dependent changes in incidence rates were not significant. In time-varying analyses (n=7,840), both prediabetes and diabetes were associated with higher incidence of functional deficits compared with normoglycemia, with diabetes showing the strongest effects across all outcomes. Diabetes was associated with greater FI burden and accelerated progression, whereas prediabetes showed a smaller increase, with attenuation over time. Among individuals with baseline prediabetes, regression to normoglycemia occurred in 20.8% and was associated with increased incidence of ADL and frailty deficits. In contrast, progression to diabetes occurred in 24.3%, and was associated with lower risk of incident ADL and Fried frailty deficits compared to stable prediabetes. Interpretation: Prediabetes is associated with increased risk of functional decline, frailty, and deficit accumulation in older adults, independent of progression to diabetes. Regression to normoglycemia was associated with higher risk of functional deterioration. These findings suggest that prediabetes reflects a state of metabolic vulnerability linked to biological aging rather than solely a precursor to diabetes and highlights a need to reframe its clinical significance in older populations. Funding: This research was supported by Instituto Nacional de Geriatria in Mexico. Keywords: Prediabetes; Glycemic transitions; Frailty; Functional decline; Aging; Multimorbidity ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by Instituto Nacional de Geriatria in Mexico. The funding source had no role in study design, data collection, analysis, interpretation or writing of the report. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This secondary analysis used anonymised publicly available data, and was approved by the Research and Ethics committee at Instituto Nacional de Geriatría (DI-PI-005/2025). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All code and materials regarding implemented G2A studies are available for reproducibility of results http://github.com/oyaxbell/prediabetes_g2a/.

Summary: Background: Visceral adipose tissue (VAT) may causally contribute to cardiovascular disease (CVD); however, evidence in Latin America is limited. Here, we evaluated the association between estimated VAT (eVAT) and incident CVD among individuals without diabetes and estimated its population-attributable fraction (PAF) using data from the Cohorts Consortium of Latin America and the Caribbean (CC-LAC). Methods: We pooled data from 15 prospective cohorts across 7 countries (n = 23,097; 62% women [n = 14,383], median age 51 years). Baseline eVAT (in grams [g]) was estimated using the Metabolic Score for Visceral Fat (METS-VF) index, incorporating age, sex, an insulin resistance index, and waist-to-height ratio. The primary outcome was incident CVD events, including fatal and non-fatal outcomes. Cause-specific Cox proportional hazards models estimated adjusted hazard ratios (aHR). PAF estimates used scenario-based eVAT quartile reductions. Findings: Over a median follow-up of 4 years (113,622 person-years), 436 participants (1.9%) experienced an incident CVD event (174 fatal; 262 non-fatal). Uniformly age- and sex-standardized incidence rates were 3.8 (95% CI: 3.5–4.2) per 1000 person-years. Each 100 g increase in eVAT was associated with a 4% higher CVD hazard (aHR 1.04, 1.03–1.06). Compared with Q1 (<735 g), those in Q3 (1069–1441 g) and Q4 (≥1441 g) had a higher CVD hazard (Q3 aHR: 1.78 [1.28–2.49]; Q4 aHR: 2.03 [1.48–2.79]; p-for-trend <0.001). Associations were stronger for non-fatal events. In PAF estimates, shifting individuals from Q4 to lower quartiles could prevent 8.8% (2.8%–14.7%) of CVD events over 10 years. Interpretation: Higher eVAT was associated with increased CVD risk in Latin America, supporting the view that modest VAT reductions could decrease regional CVD burden. Funding: CC-LAC was funded by the Wellcome Trust.

Background:Cardiovascular disease (CVD) is the leading cause of mortality in Latin America, yet most CVD risk equations were developed in high-income countries with limited validations in these settings. Here, we externally validated CVD risk prediction models for fatal CVD, and recalibrated the Globorisk-fatal model in Mexican population. Methods:We analyzed 112,262 adults ≥40 years, 67% (75,320) female and 33% (36,942) males, mean age 54.6 ± 10.7 years without prior CVD from the Mexico City Prospective Study. The primary outcome was 10-year fatal CVD, including myocardial infarction (MI) and stroke. CVD risk was estimated using the laboratory- and office-based Framingham, Globorisk, Globorisk-LAC, WHO, and SCORE2 equations. Discrimination was assessed with Harrell's c-statistic and AUROCs, calibration with mean estimates, slopes, and calibration curves, and overall performance with Brier scores. Sex-specific recalibration of the Globorisk-fatal model was performed using observed risks of fatal CVD. Findings:During 10 years of follow-up, 2429 fatal CVD events were recorded (1667 MI, 762 stroke). All models showed good discrimination, with c-statistics ranging from 0.761 to 0.805 in males and 0.797-0.831 in females. The Globorisk-fatal model had the highest c-statistic in females (0.831, 95% CI 0.821-0.841), and the laboratory-based WHO-MI model in males (0.805, 95% CI 0.783-0.827). Despite this, all equations consistently overestimated CVD risk, particularly in females. Calibration analyses revealed systematic overprediction at higher risk levels. Recalibration of the Globorisk-fatal model improved agreement between predicted and observed risks. Interpretation:CVD risk models showed good discrimination but consistently overestimated risk in this Mexican cohort. The recalibrated Globorisk-fatal model improves risk estimation of fatal CVD in Mexican adults. Funding:This research was supported by Instituto Nacional de Geriatría in Mexico.

BACKGROUND:Visceral adipose tissue (VAT) has been associated with cardiovascular disease (CVD) mortality. However, the comparative performance of VAT-related clinical surrogates remains poorly characterised. OBJECTIVES:To evaluate the performance of seven VAT-related clinical surrogates for predicting cause-specific CVD mortality. METHODS:We analysed data from the Mexico City Prospective Cohort, a population-based prospective cohort study, with baseline recruitment between 1998 and 2004 and ongoing mortality follow-up. CVD mortality included deaths from cardiac, stroke-related and other vascular causes. Seven VAT-related surrogates (METS-VF, CVAI, EVA, DAAT, LAP, VAI and DAI) were estimated using clinical, biochemical and anthropometric data at baseline. Associations with outcomes were evaluated using Cox regression models to estimate adjusted hazard ratios (aHR). Discrimination was assessed with Harrell's C-statistic (Cs) and calibration with slope plots. RESULTS:In a subsample of 102 385 participants without diabetes (median age: 47 years; 67% female) followed through a median of 20.13 years, 4068 (3.97%) died from any CVD causes. An increase in 1-SD unit of METS-VF (Cs: 0.73; aHR: 1.23, 95% CI: 1.18-1.29), EVA (Cs: 0.73; aHR: 1.19, 1.15-1.24), CVAI (Cs: 0.71; aHR: 1.19, 1.15-1.23) and DAAT (Cs: 0.63; aHR: 1.18, 1.14-1.23) was associated with CVD mortality and showed the highest predictive capacity and good calibration among the surrogates. Adding METS-VF to the Globorisk score among individuals classified as intermediate risk slightly improved discrimination for CVD mortality. CONCLUSIONS:In this large cohort of Mexican adults, four VAT-related clinical surrogates, particularly METS-VF, showed good discriminatory performance for long-term CVD mortality. Our results could support future studies that could incorporate VAT estimation to improve CVD risk stratification.

Anthracyclines and HER2-targeted breast cancer treatments can cause cancer therapy–related cardiac dysfunction (CTRCD). The Heart Failure Association–International Cardio-Oncology Society (HFA-ICOS) risk tool assesses this risk, but its accuracy remains uncertain. We aimed to (1) determine CTRCD incidence using the 2021 CTRCD definition in breast-cancer patients receiving doxorubicin and/or trastuzumab; (2) evaluate the HFA-ICOS risk proformas, and (3) assess the individual risk factors incorporated in the proformas. In this prospective study, 186 women with early-stage breast cancer were enrolled to undergo baseline and serial cardiac evaluations over 12 months. After exclusions, 177 patients were included for risk stratification using the Heart Failure Association–International Cardio-Oncology Society (HFA-ICOS) score. Baseline risk distribution was 67

Background:Cardiovascular disease (CVD) is a leading cause of diabetes-related mortality in Mexico. Although diabetes subgroups capture underlying disease heterogeneity, their association and utility for risk prediction for fatal CVD in Mexican adults remain unclear. Here, we aimed to assess the risk of fatal CVD risk and their complementary role for fatal CVD risk prediction across diabetes subgroups in Mexican adults. Methods:We included adults with diabetes from the Mexico City Prospective Study (MCPS). Participants were classified into mild obesity-related (MOD), severe insulin-deficient (SIDD), severe insulin-resistant (SIRD), and mild age-related (MARD) diabetes using a self-normalizing neural network algorithm. Fatal CVD was defined as death from ischemic heart disease or stroke (ICD-10 I20-I25, I60-I69). SCORE2-Diabetes was internally recalibrated for fatal CVD outcomes only for use within MCPS, as this does not represent a formal validation of the original composite endpoint. Cause-specific Cox proportional hazards and Fine & Gray competing risk regression models were used to estimate subgroup-specific risk, and sequential models evaluated the incremental predictive value of diabetes subgroups combined with SCORE2-Diabetes and traditional risk factors. Findings:We analyzed data from 24,943 adults living with diabetes (mean age 58 ± 12, 67% female, no ethnicity data available). Over a median follow-up of 19.3 years (IQR 12.7-20.6), 2218 fatal CVD events (8.9%) were recorded. SIDD was the most prevalent subgroup (50.0%), followed by SIRD (14.1%), MARD (17.7%), and MOD (18.3%). SIDD and MARD showed the highest adjusted risk of fatal CVD (HR 1.58 [95% CI 1.38-1.81] and 1.35 [1.13-1.60]), whereas MOD and SIRD had lower risk, even when considering competing causes of non-CVD deaths. Recalibrated SCORE2-Diabetes demonstrated adequate discrimination overall (c-statistic 0.748, 95% CI 0.734-0.762) and for most diabetes subgroups but underperformed in MARD, with internal recalibration for fatal CVD outcomes improving risk assessment. The combination of diabetes subgroups and SCORE2-Diabetes modestly improved prediction for fatal CVD outcomes. Interpretation:Diabetes subgroups show heterogeneity in fatal CVD risk in Mexican adults. SIDD and MARD identify high-risk individuals and integration subgroup classification with SCORE2-Diabetes is complementary for fatal CVD risk prediction. Funding:This research was supported by a grant provided by the Bernard Lown Scholars in Cardiovascular Health Program grant number BLSCHP-2403.

BACKGROUND:Systemic arterial hypertension is a public health concern, and timely diagnosis and management are critical to mitigate long-term effects. Here, we evaluated prevalence trends and determinants of hypertension phenotypes in the Mexican population over 2 decades. METHODS:We analyzed cross-sectional Mexican Health and Nutrition Surveys (2000-2024), including 146 904 adults aged ≥20 years. Hypertension was defined as self-reported diagnosis or blood pressure ≥140/90 mm Hg; undiagnosed hypertension (UDH) as blood pressure ≥140/90 mm Hg without prior diagnosis; and untreated hypertension as a prior diagnosis without treatment. UDH was classified as isolated systolic, isolated diastolic, or systolic-diastolic hypertension. We assessed trends with Poisson models and determinants of UDH and untreated hypertension with logistic models. RESULTS:We observed an overall decrease in hypertension prevalence from 33.1% in 2000 to 26.0% in 2024, concurrently with increases in diagnosed (12.3%-19.3%) and decreases in undiagnosed (20.7%-6.7%) hypertension. Isolated diastolic hypertension and systolic-diastolic hypertension declined over time, while isolated systolic hypertension increased, particularly among older adults. Among diagnosed cases, treatment percentage increased (69%-80%) and blood pressure control improved (40.5%-81.1%). Despite these trends, by 2024, ≈5 million Mexican adults still had UDH (25.9% of all hypertension cases), 2.9 million remained untreated, and 2.7 million were uncontrolled. Lack of diagnosis and treatment were more likely among men, individuals with unhealthy lifestyles, and those with social disadvantage. CONCLUSIONS:Results highlight evolving trends in hypertension diagnosis, treatment, and control in Mexico, with persistent challenges in UDH and untreated hypertension. Strengthening screening, treatment access, and equity is crucial to reduce hypertension-related cardiovascular risk.

Biological age (BA) has been proposed as a complementary construct to chronological age (CA) for quantifying interindividual heterogeneity in aging trajectories. Biological aging clocks (BACs) integrate molecular, clinical and multi-omics biomarkers to estimate aging-related phenotypes beyond CA. This narrative review critically examines the biological foundations, statistical methodologies, interpretative challenges and translational applications of BACs. We discuss the mechanistic basis of BACs development within the frameworks of the hallmarks and domains of aging, emphasizing the roles of age-related methylome remodeling, immunosenescence, and chronic low-grade inflammation. BACs are classified into three major generations according to their training objectives: first-generation clocks optimized to predict CA, second-generation clocks designed to estimate morbidity and mortality risk, and third-generation clocks developed to quantify the pace of aging from longitudinal biomarker changes. We also review multi-omics and artificial intelligence-based approaches that aim to capture the multidimensional nature of aging. Important limitations remain regarding biological specificity, causal interpretation, reverse causation, confounding, generalizability and clinical applicability of BACs. Current evidence suggests that BACs represent distinct operationalizations of biological aging instead of interchangeable measures of a single construct. Future advances will require longitudinal, mechanistic and diverse population-based studies to improve interpretability, reproducibility, and translational utility.

Adipose tissue (AT) dysfunction can lead to increased visceral AT (VAT) and metabolic damage. The adiponectin/leptin ratio (ALR) has been proposed as a biomarker of AT functionality. However, its participation in VAT accumulation and the impact of sex on these associations have not been evaluated. In an analytical cross-sectional study, 54 adults (29 male, 25 postmenopausal females, aged 30-70 years, BMI 19-31 kg/m2) were analysed. Anthropometric data, fasting serum samples, and subcutaneous AT (SAT) biopsies were obtained. Morpho-functional AT characteristics included ALR, adipocyte size, macrophage content and AT insulin resistance (ADIPO-IR). Using multivariate and mediation models, we evaluated the associations of SAT characteristics with systemic IR (TyG index), systemic inflammation (C-reactive protein), and VAT area. In postmenopausal females, ALR was inversely associated with adipocyte size, macrophage number, TyG index, CRP, and VAT area. SAT inflammation and ADIPO-IR were independently associated with VAT, and a mediation model suggested ALR as a possible precursor of VAT. Among males, ADIPO-IR and ALR were independently associated with VAT. These findings emphasize the importance of considering sex differences in the prevention and treatment strategies for metabolic diseases among Mexican-Mestizo populations, although these results should be confirmed by prospective studies.

BACKGROUND:Breast cancer (BC) remains a leading cause of cancer-related deaths among women. Administration of anthracyclines and/or anti-human epidermal growth factor receptor-2 (HER2) antibodies has been associated with chemotherapy-induced cardiotoxicity. Cardio-oncology rehabilitation programs aim to mitigate these outcomes. However, their preventive role in cancer therapy-related cardiac dysfunction (CTRCD) remains uncertain. OBJECTIVES:To evaluate the effectiveness of a structured exercise program compared with only exercise recommendation in preventing CTRCD, defined by the 2022 European Society of Cardiology criteria, as a left ventricular ejection fraction above 50%, with a relative decrease in global longitudinal strain exceeding 15% from baseline and/or a newly detected elevation in cardiac troponin I or T or natriuretic peptides. Secondary outcomes include the impact on systolic and diastolic echocardiographic parameters, cardiometabolic biomarkers, quality of life, and exploring the role of traditional cardiovascular risk factors in CTRCD onset. METHODS:CARPTOX-BC is a randomized, open-label clinical trial with an active control group. Women aged 18-70 years with stage I-III BC scheduled for neoadjuvant or adjuvant therapy with anthracyclines and/or trastuzumab will be eligible. The intervention includes three supervised out of five weekly aerobic and resistance exercise. A total of 284 participants will be randomized 1:1 to intervention or control arms. RESULTS:Results will be disclosed at completion. CONCLUSIONS:We expect a structured exercise program may reduce the incidence of CTRCD associated with anthracycline and/or HER2 antibody and provide a potential non-pharmacological therapy that could also enhance cardiometabolic markers and quality of life among this population. TRIAL REGISTRATION:NCT06881940 (registered March 18th, 2025).

Introduction: Visceral adipose tissue (VAT) is a key contributor to adverse cardiometabolic outcomes. However, its direct measurement via imaging techniques is costly and impractical in primary care settings, particularly in low- and middle-income countries. The Metabolic Score for Visceral Fat (METS-VF), a previously validated index based on simple clinical and biochemical parameters, provides an accessible estimate of VAT (eVAT) in grams. Nevertheless, its association with incident fatal and non-fatal cardiovascular events remains understudied in Latin America. Research Question: Is higher eVAT associated with an increased risk of incident fatal and non-fatal cardiovascular events in Latin American adults? Methods: We analyzed data from adults without type 2 diabetes participating in the Cohorts Consortium of Latin America and the Caribbean (CC-LAC). eVAT was estimated using the following equation: METS-VF = 4.466 + 0.011(Ln(METS-IR))^3 + 3.239(Ln(WHtr))^3 + 0.319*(Sex) + 0.594*(Ln(Age))**, where METS-IR = (Ln((2*G0) + TG0) * BMI) / (Ln(HDL-C)). We applied Cox proportional hazards regression models to estimate adjusted hazard ratios (aHR) for fatal and non-fatal cardiovascular events per 100 g increase and by eVAT quartiles. Models were adjusted for age, sex, residence, smoking status, non-HDL cholesterol, systolic blood pressure, and prior diabetes diagnosis. Results: Among 23,097 adults (median age: 52) followed for a total of 113,622 person-years, 436 participants (1.9%) experienced an incident cardiovascular event (262 [1.1%] non-fatal; 174 [0.75%] fatal). Each 100 g increase in eVAT was associated with a 4% higher risk of any cardiovascular event (95% CI: 1.03–1.05). Compared to the lowest quartile (<726 g), participants in the third (1,058–1,426 g) and fourth (>1,426 g) quartiles had 68% (95% CI: 1.23–2.29) and 85% (95% CI: 1.37–2.50) higher risk, respectively. Stratified analyses showed consistent associations across subgroups, with a stronger effect observed among overweight individuals (p-for-interaction < 0.001). Conclusion: In this large, prospective cohort of Latin American adults without diabetes, higher eVAT was significantly associated with increased risk of cardiovascular events. These findings underscore the role of visceral adiposity in cardiovascular disease development and the need to incorporate its assessment in primary care risk stratification. METS-VF may serve as a practical tool to support this objective in resource-limited settings

Therapeutic Area ASCVD/CVD Risk Assessment Background Cardiovascular disease (CVD) is the leading cause of death in Mexico, and risk prediction models are crucial for CVD prevention. While several models are endorsed in international guidelines, most were developed for non-Latin American populations, highlighting the need for validation in Mexican populations. This study aims to assess the external validity of various office-based and laboratory-based CVD risk models in Mexico. Methods We conducted an external validation using data from a prospective study of 118,564 adults aged >40 years. We evaluated office-based and laboratory-based models for predicting fatal events (NFOB-F, NFLBF, FLB) and fatal plus non-fatal events (NFOB, NFLB) over 10 years of follow-up. Events were identified through death registries and self-reports in a resurvey. Model performance was assessed using discrimination (C-statistics, AUC), calibration (mean, weak and moderate calibration), and clinical utility (Decision Curve Analysis). Results We identified 6,758 (4.4%) total CVD events, including 6,314 (4.1%) fatal events and 461 (0.3%) non-fatal events in resurveyed participants (n=8,061). The highest AUROC values were observed for SCORE2 in the NFLB-F subset (0.821, 95%CI 0.794–0.829) and Globorisk in the FLB subset (0.818, 95%CI 0.800–0.836). In contrast, the Framingham model consistently performed worse across all subsets. Uno’s C-statistic did not significantly differ from the AUC, and Harrel’s C-statistic produced nearly identical results. Calibration assessments showed low mean calibration for most models, with WHO models performing better. Weak calibration was poorest for the Framingham model across subpopulations. Moderate calibration revealed that most models performed well for predicting risks up to 5% or 7.5%, but overpredicted higher-risk cases. Finally, clinical net benefit analyses indicated that the clinical utility of these models, when compared to chronological age, was small. Overall, the models showed variable predictive capacity, with some models demonstrating better performance in certain subsets. Conclusions The study validated CVD risk models in Mexico, finding variable performance, with some models showing better predictive capacity in specific subsets.

BACKGROUND:Prediabetes has been associated with increased all-cause and cardiovascular mortality. However, no large-scale studies have been conducted in Mexico or Latin America examining these associations. METHODS:We analyzed data from 114 062 adults without diabetes (diagnosed or undiagnosed) from the Mexico City Prospective Study. Participants were followed until January 1, 2021, for cause-specific mortality. We defined prediabetes according to the American Diabetes Association (ADA; HbA1c ≥ 5.7% to <6.5%) and the International Expert Committee (IEC; HbA1c ≥ 6.0 to <6.5%) definitions. Cox regression adjusted for confounders was used to estimate all-cause and cause-specific mortality rate ratios (RR) for deaths occurring at ages 35 to 74 years associated with prediabetes. RESULTS:After median 18.4 (IQR 17.6-19.7) years of follow-up, individuals with prediabetes had higher risk of all-cause mortality at ages 35 to 74 compared to those without prediabetes (RR 1.13 [1.07-1.20] for ADA-defined and 1.27 [1.17-1.38] for IEC-defined prediabetes), as well as higher risk of cardiovascular (RR 1.23 [1.11-1.37] and 1.44 [1.24-1.67], respectively), renal (RR 1.33 [1.06-1.66] and 1.62 [1.18-2.23], respectively), and acute diabetic deaths (RR 2.62 [1.75-3.93] and 3.42 [2.09-5.61], respectively). The absolute excess risk associated with ADA-defined prediabetes at ages 35 to 74 accounted for 7% of cardiovascular, 9% of renal, and 31% of acute diabetic deaths. IEC-defined prediabetes accounted for 4%, 5% and 14% of cardiovascular, renal, and acute diabetic deaths. Prediabetes-associated excess mortality risks were, at least in part, explained by adiposity. CONCLUSION:Prediabetes is a significant risk factor for all-cause, cardiovascular, renal, and acute diabetic deaths in Mexican adults. Early identification and timely management of prediabetes among individuals at risk of this condition could reduce premature mortality in this population.