Abstract Aims This study investigated the S2I2N0–3 score, a simple tool comprising stroke history, insulin‐treated diabetes, and N‐terminal pro‐brain natriuretic peptide, for forecasting mortality and morbidity in heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results Analysing 890 GUIDE‐IT HFrEF trial participants, we stratified them by baseline S2I2N0–3 risk score into three risk groups. We examined the score's association with five adverse outcomes over short (90 days) and extended periods (median follow‐up of 15 months) using Cox and competing risk models. Our analysis revealed significant positive associations between the S2I2N0–3 strata and adverse outcomes. When analysed as a continuous variable, each point increment of the S2I2N0–3 score was associated with a higher risk of short‐ and long‐term cardiovascular death [short term: hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.03–1.98; long term: HR 1.18, 95% CI 1.02–1.38], all‐cause death (HR 1.52, 95% CI 1.12–2.07; HR 1.18, 95% CI 1.03–1.36), HF hospitalization (HR 1.39, 95% CI 1.20–1.62; HR 1.18, 95% CI 1.06–1.31), any hospitalization (HR 1.19, 95% CI 1.06–1.34; HR 1.09, 95% CI 1.00–1.19), and the composite outcome of cardiovascular death and HF hospitalization (HR 1.39, 95% CI 1.21–1.60; HR 1.17, 95% CI 1.06–1.30). The S2I2N0–3 demonstrated reliable prognostic value, with C‐indices ranging from 0.619 to 0.753 across outcomes and time points. When compared with the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score using Z‐statistics, net reclassification index, and integrated discrimination improvement, the S2I2N0–3 showed comparable predictive power for all outcomes during both short‐ and long‐term follow‐ups. Conclusions The S2I2N0–3 risk score had modest predictive values for both short‐ and long‐term clinical outcomes in HFrEF patients, offering equivalent performance to the established MAGGIC score.

Cardiovascular diseases (CVDs) are often linked to structural and functional impairments, such as heart defects and circulatory dysfunction, leading to compromised peripheral perfusion and heightened morbidity risks. Metabolic remodeling, particularly in the context of cardiac fibrosis and inflammation, is increasingly recognized as a pivotal factor in the pathogenesis of CVDs. Metabolic syndromes further predispose individuals to these conditions, underscoring the need to elucidate the metabolic underpinnings of CVDs. Lactate, a byproduct of glycolysis, is now recognized as a key molecule that connects cellular metabolism with the regulation of cellular activity. The transport of lactate between different cells is essential for metabolic homeostasis and signal transduction. Disruptions to lactate dynamics are implicated in various CVDs. Furthermore, lactylation, a novel post-translational modification, has been identified in cardiac cells, where it influences protein function and gene expression, thereby playing a significant role in CVD pathogenesis. In this review, we summarized recent advancements in understanding the role of lactate and lactylation in CVDs, offering fresh insights that could guide future research directions and therapeutic interventions. The potential of lactate metabolism and lactylation as innovative therapeutic targets for CVD is a promising avenue for exploration.

Introduction: Whether the hypertension burden is associated with stroke incidence is inconclusive. In this study, we aimed to investigate the relationship between hypertension burden and stroke risk in patients with heart failure with preserved ejection fraction (HFpEF). Methods: HFpEF patients from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were divided into three groups (low, medium, and high risk) according to their hypertension burden values. Higher hypertension burden risk represented the longer duration of hypertension. We evaluated the association of hypertension burden with stroke risk using Fine and Gray's competing risk models. Results: A total of 3431 HFpEF patients (mean age: 68.5 +/- 9.58 years, 51.6% females) were enrolled. During a median follow-up of 3.3 years, per 10-point increase in hypertension burden was associated with any stroke (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.21), new-onset stroke (HR 1.14, 95% CI 1.07-1.21), and ischemic stroke (HR 1.10, 95% CI 1.02-1.17). When hypertension burden was analyzed as a categorical variable, any stroke risk was increased in the medium- (HR 1.59, 95% CI 1.01-2.40) and high-risk (HR 3.19, 95% CI 2.05-4.97) groups when compared with the low-risk group. For the outcomes of new-onset (HR 2.92, 95% CI 1.80-4.74) and ischemic stroke (HR 2.46, 95% CI 1.41-4.29), similar results were observed in patients with high-versus low-risk hypertension burden. Conclusions: Increasing hypertension burden was associated with an increased risk of stroke, suggesting that shortening hypertension duration might appropriately minimize the stroke incidence in HFpEF patients.

Introduction: Triglyceride-glucose index (TyG) is a reliable surrogate marker of insulin resistance, and insulin resistance has been implicated in Alzheimer's disease pathophysiology. However, the relationship between the TyG index and Alzheimer's disease remains unclear. This study aimed to evaluate the association of the TyG index with the risk of Alzheimer's disease.Methods: This prospective study included 2,170 participants free of Alzheimer's disease from the Framingham Heart Study Offspring Cohort Exam 7 (1998-2001), whose follow-up data were col-lected until 2018. The TyG index was calculated as Ln(fasting triglyceride [mg/dL] pound fasting glucose [mg/dL]/2). The association of the TyG index with Alzheimer's disease was evaluated by competing risk regression model. Statistical analyses were performed in 2023. Results: During a median follow-up of 13.8 years, 163 (7.5%) participants developed Alzheimer's disease. When compared with the reference (TyG index <= 8.28), a significantly elevated risk of Alz-heimer's disease was seen in the group with a triglyceride-glucose index of 8.68-9.09 (adjusted haz-ard ratio=1.69, 95% CI=1.02, 2.81). When the TyG index was considered as a continuous variable, each unit increment in the TyG index was not significantly associated with the risk of Alzheimer's disease (adjusted hazard ratio=1.32, 95% CI=0.98, 1.77).Conclusions: This study showed that moderately elevated TyG index was independently associated with a higher incidence of Alzheimer's disease. TheTyG index might be used to define a high-risk population of Alzheimer's disease. Am J Prev Med 2023;65(6):1042-1049.(c) 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

BACKGROUND:Transthyretin amyloid cardiomyopathy (ATTR-CM) is often found in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence regarding ATTR-CM and prognosis in HFpEF remains scarce. This study sought to determine whether the ATTR-CM burden was associated with clinical outcomes in HFpEF patients. METHODS:We evaluated the associations of baseline ATTR-CM score with adverse outcomes in HFpEF patients from the TOPCAT trial using the Cox proportional hazards model or the competing risk regression model. The discriminatory ability of the ATTR-CM score was assessed using the area under the time-dependent receiver operating characteristic curve (AUC). RESULTS:We included 870 HFpEF patients, 18.9% of which had an ATTR-CM score ≥6. Per 1 increment in the ATTR-CM score was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.12-1.27) with an AUC of 0.652 (0.594-0.711), whereas patients with ATTR-CM score ≥6 presented higher risks of the primary outcome (adjusted HR 2.20, 95% CI 1.65-2.95). Similar results were observed toward the secondary outcomes. CONCLUSIONS:The simple ATTR-CM score identified an 18.9% ATTR-CM burden in HFpEF patients, and a higher ATTR-CM burden might predict adverse outcomes with moderate discriminatory abilities in HFpEF.

Background Several published studies have examined the association of coffee consumption with atrial fibrillation (AF) risk, but their findings are still controversial. Therefore, we performed a systematic review and dose–response meta-analysis of prospective studies to determine the relationship between coffee consumption and the risk of incident AF. Methods We systematically retrieved the PubMed and Embase databases until October 2021 for pertinent studies that reported the association of coffee consumption (caffeinated or decaffeinated coffee) with AF risk. A cubic spline random-effects model was used to fit the potential dose–response curve. The effect estimates were expressed as adjusted risk ratios (RRs) and 95% CIs. Results A total of 10 prospective studies (11 cohorts) involving 30,169 AF events and 723,825 participants were included. In the dose–response analysis, there was a linear inverse association between coffee intake and risk of AF although not statistically significant (Pnon–linearity = 0.25). Compared with participants with no coffee consumption, the RRs (95% CI) of AF risk estimated directly from the dose–response curve were 1.01 (0.98–1.03), 1.00 (0.97–1.04), 0.99 (0.92–1.02), 0.95 (0.89–1.01), 0.94 (0.87–1.01), 0.89 (0.79–1.02), and 0.87 (0.76–1.02) for 1–7 cups of coffee per day, respectively. One cup per day increased in coffee consumption was associated with a 2% reduced risk of AF (RR = 0.98, 95% CI: 0.97–1.00, P = 0.02). Conclusions Our evidence from this meta-analysis suggested that coffee consumption had a trend toward reducing the risk of AF in a dose–response manner. Further studies could be conducted to reinforce our findings.

心力衰竭是各种心脏疾病的终末阶段,其高死亡率和再住院率一直是治疗的难点.经过多年的临床和基础研究,心力衰竭的诊疗进展迅速.现行的国家心力衰竭指南将心力衰竭分为多个类别,对每个类别都有具体的诊疗方法.文章根据中国、美国和欧洲的心力衰竭指南,从流行病学、病因与诱因以及各类心力衰竭的诊疗、并发症和预后管理等方面对心力衰竭进行全面介绍.简要分析并整理现有的基础研究和临床试验,以期使更多读者了解该疾病.

Although several meta‐analyses have examined the effects of off‐label underdosing of nonvitamin K antagonist oral anticoagulants (NOACs) compared with their recommended doses in patients with atrial fibrillation (AF), they combined different kinds of NOACs in their primary analyses. Herein, we first conducted a meta‐analysis to separately assess the effects of off‐label underdosing versus on‐label dosing of four individual NOACs on adverse outcomes in the AF population.