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Abstract Background and Aims Clinical models incompletely capture the molecular pathways driving heart failure (HF) progression. This study evaluated whether molecular risk stratification provides incremental prognostic information beyond established clinical predictors in patients with HF. Methods A total of 2432 patients from the Global Congestive Heart Failure (G-CHF) registry with available genotyping, DNA methylation, and proteomic profiling were analysed. Three molecular scores were assessed: a composite cardiovascular polygenic risk score (PRS) from DNA sequence polymorphisms, a methylation risk score (MRS) derived from epigenome-wide associations, and a 23-protein-based score (ProteomicDeath23). Each score was tested individually and in combination with the clinical Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels for mortality prediction. Validation was performed in an HF subset of the UK Biobank (UKB). Results Over a median follow-up of 3.0 years in G-CHF, 523 patients died from any cause (7.64 per 100 person-years [PY]). In multivariable analyses, ProteomicDeath23 was the strongest independent predictor of all-cause mortality (hazard ratio [HR] per 1 standard deviation, 2.23), outperforming NT-proBNP (HR 2.00), MRSMortality (HR 1.66), PRSmetaCVD (HR 1.10), and the MAGGIC score (HR 1.70). A model combining ProteomicDeath23 with MAGGIC and NT-proBNP achieved the highest discrimination for mortality (C-index, 0.77). Addition of MRSMortality to this proteomic-clinical model resulted in only small improvements in discrimination (ΔC-index, +0.004, P = .0039), while the PRSmetaCVD provided no incremental benefit. Among patients with low NT-proBNP/MAGGIC score, mortality rates increased from 1.71 to 8.12 per 100 PY across ProteomicDeath23 tertiles. Consistent results were observed in the UKB-HF validation cohort. Conclusion A proteomic score was the strongest molecular predictor of mortality in HF. Integrating proteomic signatures with clinical risk factors significantly improved risk prediction.

Hypertension is the main risk factor for cardiovascular disease (CVD), affecting 20–40% of Latin American (LATAM) adults, and responsible for more than two million deaths annually due to CVD. The different ethnic, economic, geographic, and cultural characteristics of the LATAM population influence the high prevalence of all cardiovascular risk factors (CVRF), particularly metabolic disturbances such as type 2 diabetes (DM2), obesity and the metabolic syndrome. Their main determinants in LATAM includes environment, food quality, social inequity, low education, political aspects, contextual behaviour, and genetics. The prevalence of overweight and obesity in LATAM increased during the last four decades reaching figures of 10–20% in childhood, 30–40% in adolescence, and 60–70% in adults. Many studies in the region have reported the extremely low rates of awareness, treatment, and control of CVRF in the general population of LATAM, particularly in patients with metabolic disorders, and the consequent high cardiovascular morbidity and mortality. This 2026 LATAM consensus is developed by a large group of experts from different LATAM countries, the USA and Europe, representing areas of internal medicine, cardiology, nephrology, endocrinology, geriatrics, paediatrics, pharmacology, and epidemiology. A careful search for novel studies in LATAM, together with new evidence that has emerged since the 2019 LATAM consensus, support the statements and recommendations in the current report. This update aims to provide clear and useful recommendations for health professionals to improve awareness, treatment, and control of hypertension and associated CVRF in the region.

Background Patients with atrial fibrillation ( AF ) and hypertension are at high risk for stroke. Previous studies have shown elevated risk of stroke in patients with AF who have a history of hypertension (regardless of blood pressure [ BP ] control) and in patients with elevated BP . We assessed the association of hypertension and BP control on clinical outcomes. Methods and Results In ARISTOTLE (n=18 201), BP was evaluated as history of hypertension requiring treatment and elevated BP (systolic ≥140 and/or diastolic ≥90 mm Hg) at study entry and any point during the trial. Hazard ratios ( HR s) were derived from Cox proportional hazards models including BP as a time‐dependent covariate. A total of 15 916 (87.5%) patients had a history of hypertension requiring treatment. In patients with elevated BP measurement at any point during the trial, the rate of stroke or systemic embolism was significantly higher ( HR , 1.53; 95% confidence interval [ CI ], 1.25–1.86), as was hemorrhagic stroke ( HR 1.85; 95% CI , 1.26–2.72) and ischemic stroke ( HR , 1.50; 95% CI , 1.18–1.90). Rates of major bleeding were lower in patients with a history of hypertension ( HR , 0.80; 95% CI , 0.66–0.98) and nonsignificantly lower in patients with elevated BP at study entry ( HR , 0.89; 95% CI , 0.77–1.03). The benefit of apixaban versus warfarin on preventing stroke or systemic embolism was consistent among patients with and without a history of hypertension ( P interaction=0.27), BP control at baseline ( P interaction=0.43), and BP control during the trial ( P interaction=0.97). Conclusions High BP measurement at any point during the trial was independently associated with a substantially higher risk of stroke or systemic embolism. These results strongly support efforts to treat elevated BP as an important strategy to optimally lower risk of stroke in patients with AF . Clinical Trial Registration URL : https://ClinicalTrials.gov/ . Unique identifier: NCT 00412984.

Background— Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves. Methods and Results— We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51–0.97 and HR, 0.84; 95%, CI 0.67–1.04; interaction P =0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61–1.04 and HR, 0.65; 95% CI, 0.55–0.77; interaction P =0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84–1.22 and HR, 0.84; 95% CI, 0.73–0.96; interaction P =0.10). Conclusions— More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00412984.