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Aims: Heart failure (HF) is a global health issue, with lipid metabolism and inflammation critically implicated in its progression. This study harnesses cutting‐edge, expanded genetic information for lipid and inflammatory protein profiles, employing Mendelian randomization (MR) to uncover genetic risk factors for HF. Methods: We assessed genetic susceptibility to HF across 179 lipidomes and 91 inflammatory proteins using instrumental variables (IVs) from recent genome‐wide association studies (GWASs) and proteome‐wide quantitative trait loci (pQTL) studies. GWASs involving 47 309 HF cases and 930 014 controls were obtained from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) Consortium. Data on 179 lipids from 7174 individuals in a Finnish cohort and 91 inflammatory proteins from a European pQTL study involving 14 824 individuals are available in the HGRI‐EBI catalogue. A two‐sample MR approach evaluated the associations, and a two‐step mediation analysis explored the mediation role of inflammatory proteins in the lipid–HF pathway. Sensitivity analyses, including MR‐RAPS (robust adjusted profile score) and MR‐Egger, ensured result robustness. Results: Genetic IVs for 162 lipids and 74 inflammatory proteins were successfully identified. MR analysis revealed a genetic association between HF and 31 lipids. Among them, 18 lipids, including sterol ester (27:1/18:0), cholesterol, 9 phosphatidylcholines, phosphatidylinositol (16:0_20:4) and 6 triacylglycerols, were identified as HF risk factors [odds ratio (OR) = 1.037–1.368]. Cholesterol exhibited the most significant association with elevated HF risk [OR = 1.368, 95% confidence interval (CI) = 1.044–1.794, P = 0.023]. In the inflammatory proteome, leukaemia inhibitory factor receptor (OR = 0.841, 95% CI = 0.789–0.897, P = 1.08E‐07), fibroblast growth factor 19 (OR = 0.905, 95% CI = 0.830–0.988, P = 0.025) and urokinase‐type plasminogen activator (OR = 0.938, 95% CI = 0.886–0.994, P = 0.030) were causally negatively correlated with HF, whereas interleukin‐20 receptor subunit alpha (OR = 1.333, 95% CI = 1.094–1.625, P = 0.004) was causally positively correlated with HF. Mediation analysis revealed leukaemia inhibitory factor receptor (mediation proportion: 23.5%–25.2%) and urokinase‐type plasminogen activator (mediation proportion: 9.5%–10.7%) as intermediaries in the lipid–inflammation–HF pathway. No evidence of directional horizontal pleiotropy was observed (P > 0.05). Conclusions: This study identifies a genetic connection between certain lipids, particularly cholesterol, and HF, highlighting inflammatory proteins that influence HF risk and mediate this relationship, suggesting new therapeutic targets and insights into genetic drivers in HF. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether changes in presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 levels predict mortality in septic patients in the intensive care unit. This study enrolled septic patients between November 2020 and December 2021. Levels of presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 were measured on the first (PSEP_0, PCT_0, hsCRP_0, IL-6_0) and third days (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional hazards regression analysis, ΔPSEP (= PSEP_3 – PSEP_0) > 211.49 pg/mL (hazard ratio, 2.70; 95% confidence interval, 1.17–6.22), ΔPCT (= PCT_3 – PCT_0) > –0.13 ng/mL (hazard ratio, 7.31; 95% confidence interval, 2.68–19.80), ΔhsCRP (= hsCRP_3 – hsCRP_0) > −19.29 mg/L (hazard ratio, 6.89; 95% confidence interval, 1.61–29.40), and ΔIL-6 (= IL-6_3 – IL-6_0) > 1.00 pg/mL (hazard ratio, 3.13; 95% confidence interval, 1.35–7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all 4 distinct biomarkers was highest (concordance index, 0.83; 95% confidence interval, 0.76–0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the Acute Physiology and Chronic Health Evaluation II and Sequential (sepsis-related) Organ Failure Assessment scores, the combination of the 4 biomarkers had a larger net benefit. Interestingly, interleukin 6 was predominantly produced by monocytes upon lipopolysaccharide stimulation in peripheral blood mononuclear cells. ΔPSEP, ΔPCT, ΔhsCRP, and ΔIL-6 are reliable biomarkers for predicting mortality in septic patients in the intensive care unit, and their combination has the best performance. [ABSTRACT FROM AUTHOR]

Heart failure (HF) represents a critical stage of cardiac disease, associated with high morbidity and mortality. Cardiac resynchronization therapy (CRT) has become a pivotal treatment for HF patients with prolonged QRS duration. This therapy employs a biventricular pacing system to correct cardiac electromechanical dyssynchrony, thereby improving cardiac function, symptoms, and prognosis. Numerous clinical trials have consistently highlighted the benefits of CRT in this subgroup, leading to its unanimous recommendation in clinical practice guidelines. However, a significant proportion of patients do not achieve an adequate therapeutic response, despite adherence to these guidelines. As CRT treats patients by correcting cardiac electromechanical dyssynchrony, assessing electrical and mechanical dyssynchrony is crucial in candidate selection. This review explores the evidence, recent clinical practice guidelines, and insight into electrical and mechanical dyssynchrony to optimize CRT candidate selection in HF patients with prolonged QRS duration. [ABSTRACT FROM AUTHOR]

Background: Aortic dissection (AD) is a lethal cardiovascular emergency involving high mortality and disability. However, its specific pathogenesis remains to be elucidated. Methods: A bibliometric analysis based on the Web of Science database, VOSviewer software and Citex platforms was conducted to have a knowledge of the development trends, frontiers and hot spots of AD. Subsequently, the top five AD‐related genes from the titles and abstracts of published literature were searched. Lastly, the roles of the top five genes and their encoded proteins in the onset of AD were reviewed. Results: The bibliometrics showed that most studies are exploring the molecular drivers related to AD, especially gene mutations. The top five AD‐related genes were transforming growth factor‐β (TGFB)‐related genes, elastin (ELN), fibrillin‐1 (FBN1), angiotensinogen (AGT) and matrix metalloproteinase 9 (MMP9). In particular, regulation of the structure of elastic fiber by TGFB‐related genes, ELN and FBN1, appears to be the principal mechanism contributing to AD onset. Activation of the renin‐angiotensin system is the principal mechanism by which AGT triggers AD. MMP9 promotes the formation and development of AD by degrading extracellular matrix components. Conclusion: TGFB, ELN, FBN1, AGT and MMP9 are the five top molecular drivers of AD, providing a comprehensive mechanistic insight into AD. [ABSTRACT FROM AUTHOR]

Objectives: Brain-derived neurotrophic factor (BDNF) as a biomarker of depressive symptoms manifests a novel role in the cardiovascular system. This study aims to indicate the association of BDNF levels between depressive symptoms and the cardiovascular prognosis in coronary heart disease (CHD) patients. Methods: Participants were recruited from hospitalized CHD patients between November 18, 2020 and November 26, 2021, in the First Affiliated Hospital of Shantou University Medical College. Serum BDNF levels were measured by the enzyme-linked immunosorbent assays. Depressive symptom was evaluated using Patient Health Questionnaire (PHQ-9). The cardiovascular events were the endpoint outcomes across the 12-month follow-up. Kaplan–Meier curves and Cox proportional hazards regression models were used to investigate the relationship of serum BDNF levels between depressive symptom and prognosis. Results: A total of 102 CHD patients (60.6 ± 10.4 year, 76% male) were enrolled. Based on the median serum BDNF levels, the participants were grouped into those "low BDNF (≤0.65 ng/mL)" versus "high BDNF (≥0.65 ng/mL)." CHD patients with low BDNF levels had a higher prevalence of depressive symptoms (PHQ–9 ≥10) compared with high BDNF levels. Within a median 540 days of follow-up, low serum BDNF increased the risk of cardiovascular events (adjusted hazard ratio = 3.26; 95% confidence interval = 1.18–9.02, P = 0.02) after adjustment for confounding factors. Conclusions: CHD patients with low serum BDNF levels were significantly associated with an increased risk of cardiovascular events, independently of depressive symptoms. [ABSTRACT FROM AUTHOR]