Unveiling IL-17's role: Therapeutic insights and cardiovascular implications.

Interleukin-17 (IL-17), a pivotal cytokine in immune regulation, has attracted significant attention in recent years due to its roles in various physiological and pathological processes. This review explores IL-17 in immunological context, emphasizing its structure, production, and signaling pathways. Specifically, we explore its involvement in inflammatory diseases and autoimmune diseases, with a notable focus on its emerging implications in cardiovascular system. Through an array of research insights, IL-17 displays multifaceted functions yet awaiting comprehensive discovery. Highlighting therapeutic avenues, we scrutinize the efficacy and clinical application of four marketed IL-17 mAbs along other targeted therapies, emphasizing their potential in immune-mediated disease management. Additionally, we discussed the novel IL-17D-CD93 axis, elucidating recent breakthroughs in their biological function and clinical implications, inviting prospects for transformative advancements in immunology and beyond.

Cholesterol 25-hydroxylase prevents type 2 diabetes mellitus induced cardiomyopathy by alleviating cardiac lipotoxicity.

OBJECTIVES: Diabetic cardiomyopathy (DCM) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients, with its underlying mechanisms still elusive. This study aims to investigate the role of cholesterol-25-monooxygenase (CH25H) in T2DM induced cardiomyopathy. METHODS: High fat diet combined with streptozotocin (HFD/STZ) were used to establish a T2DM model. CH25H and its product 25-hydroxycholesterol (25HC) were detected in the hearts of T2DM model. Gain- or loss-of-function of CH25H were performed by receiving AAV9-cTNT-CH25H or CH25H knockout (CH25H-/-) mice with HFD/STZ treatment. Cardiac function was evaluated using echocardiography, and cardiac tissues were collected for immunoblot analysis, histological assessment and quantitative polymerase chain reaction (qPCR). Mitochondrial morphology and function were evaluated using transmission electron microscopy (TEM) and Seahorse XF Cell Mito Stress Test Kit. RNA-sequence analysis was performed to determine the molecular changes associated with CH25H deletion. RESULTS: CH25H and 25HC were significantly decreased in the hearts of T2DM mice. CH25H-/- mice treated with HFD/STZ exhibited impaired mitochondrial function and structure, increased lipid accumulation, and aggregated cardiac dysfunction. Conversely, T2DM mice receiving AAV9-CH25H displayed cardioprotective effects. Mechanistically, RNA sequencing and qPCR analysis revealed that CH25H deficiency decreased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and its target gene expression. Additionally, administration of ZLN005, a potent PGC-1α activator, partially protected against high glucose and palmitic acid induced mitochondria dysfunction and lipid accumulation in vitro. CONCLUSION: Our study provides compelling evidence supporting the protective role of CH25H in T2DM-induced cardiomyopathy. Furthermore, the regulation of PGC-1α may be intricately involved in this cardioprotective process.

Association of IL-17 Inhibitors with Hypertension in Patients with Autoimmune Diseases: A Systematic Review and Meta-analysis on Randomized Controlled Trials.

The influence of IL-17 inhibition on blood pressure in autoimmune disease patients remains inconclusive. Our objective is to examine the risk of hypertension in patients with autoimmune diseases undergoing IL-17 inhibition therapies via meta-analysis of randomized, placebo-controlled trials (RCTs). We obtained integrated data from PubMed, Embase, and ClinicalTrials.gov. Incident hypertension rates were calculated, and hazard ratios (HRs) with 95% confidence intervals (CIs) were analyzed, along with Ι^2 statistics to assess heterogeneity. Sequential analysis ensured conclusion reliability. In 30 RCTs involving 9,909 patients with diverse autoimmune diseases treated with anti-IL-17 agents, our meta-analysis revealed a significant increase in hypertension risk (RR 1.69, CI 1.24-2.31, p=0.001), robustly supported by trial sequential analysis. Among the four agents (secukinumab, ixekizumab, bimekizumab, and brodalumab), only secukinumab exhibited a notable association with hypertension. Patients with various primary autoimmune diseases, particularly those with psoriatic arthritis, had a higher likelihood of developing hypertension; in rheumatic arthritis patient cohorts, anti-IL-17 agents did not elevate hypertension risk. Prolonged treatment duration correlated with an increased hypertension risk. Stratifying by gender, studies with a female predominance demonstrated a higher risk ratio for hypertension compared to male-predominant studies. This highlights that anti-IL-17 treatment escalates hypertension risk, emphasizing the need for extra caution when managing autoimmune disease patients. (Registered by PROSPERO, CRD42016053112).

B cell subsets contribute to myocardial protection by inducing neutrophil apoptosis after ischemia and reperfusion.

A robust, sterile inflammation underlies myocardial ischemia and reperfusion injury (MIRI). Several subsets of B cells possess the immunoregulatory capacity that limits tissue damage, yet the role of B cells in MIRI remains elusive. Here, we sought to elucidate the contribution of B cells to MIRI by transient ligation of the left anterior descending coronary artery in B cell-depleted or -deficient mice. Following ischemia and reperfusion (I/R), regulatory B cells are rapidly recruited to the heart. B cell-depleted or -deficient mice exhibited exacerbated tissue damage, adverse cardiac remodeling, and an augmented inflammatory response after I/R. Rescue and chimeric experiments indicated that the cardioprotective effect of B cells was not solely dependent on IL-10. Coculture experiments demonstrated that B cells induced neutrophil apoptosis through contact-dependent interactions, subsequently promoting reparative macrophage polarization by facilitating the phagocytosis of neutrophils by macrophages. The in vivo cardioprotective effect of B cells was undetectable in the absence of neutrophils after I/R. Mechanistically, ligand-receptor imputation identified FCER2A as a potential mediator of interactions between B cells and neutrophils. Blocking FCER2A on B cells resulted in a reduction in the percentage of apoptotic neutrophils, contributing to the deterioration of cardiac remodeling. Our findings unveil a potential cardioprotective role of B cells in MIRI through mechanisms involving FCER2A, neutrophils, and macrophages.

Association between low-density lipoprotein cholesterol level and all-cause mortality in idiopathic dilated cardiomyopathy patients: a single-institutional study.

AIMS: To determine the association between all-cause mortality and low-density lipoprotein cholesterol (LDL-C) in patients with idiopathic cardiomyopathy (iDCM). BACKGROUND: LDL-C had long been considered as a dangerous predictor of cardiovascular diseases; however, the correlation between them was not fully clarified. METHODS: A total of 1058 patients who met the World Health Organization criteria for iDCM in West China Hospital (2009-2016) were enrolled in this retrospective study. Baseline demographic characteristics and correlations between variables were calculated and analyzed, and potential predictors were explored using univariate and multivariate regressions. Cox proportional hazards models were used to determine correlation on a continuous scale. RESULTS: LDL-C is an independent prognostic factor and higher LDL-C levels are associated with better prognosis in iDCM patients according to cox regression analysis. Compared with individuals which LDL > 2.28 mmol/L (75th-100th percentile), the multivariable-adjusted hazard ratio for all-cause mortality was 1.52 (95%CI: 1.03-2.26) in patients with LDL-C < 1.78 mmol/L (0-25th percentile). In patients with New York Heart Association function III and IV, LDL-C levels have a hazard ratio of 0.83 (confidence interval 0.73-0.95). CONCLUSIONS: In patients with iDCM, lower LDL-C level was associated with an increased risk of all-cause mortality. The correlation between mortality and LDL-C level was stronger in patients with worse heart function. LDL-C levels have a potential predictive value in iDCM patients.

The influence of pressure injury risk on the association between left ventricular ejection fraction and all-cause mortality in patients with acute myocardial infarction 80 years or older.

BACKGROUND: We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction (LVEF) with all-cause death in patients with acute myocardial infarction (AMI) aged 80 years or older. METHODS: This retrospective cohort study included 677 patients with AMI aged 80 years or older from a tertiary-level hospital. Pressure injury risk was assessed using the Braden scale at admission, and three risk groups (low/minimal, intermediate, high) were defined according to the overall score of six different variables. LVEF was measured during the index hospitalization for AMI. All-cause death after hospital discharge was the primary outcome. RESULTS: Over a median follow-up period of 1,176 d (interquartile range [IQR], 722-1,900 d), 226 (33.4%) patients died. Multivariate Cox regression analysis showed that reduced LVEF was associated with an increased risk of all-cause death only in the high-risk group of pressure injury (adjusted hazard ratios [HR]=1.81, 95% confidence interval [CI]: 1.03-3.20; P=0.040), but not in the low/minimal- (adjusted HR=1.29, 95%CI: 0.80-2.11; P=0.299) or intermediate-risk groups (adjusted HR=1.14, 95%CI: 0.65-2.02; P=0.651). Significant interactions were detected between pressure injury risk and LVEF (adjusted P=0.003). The cubic spline with hazard ratio plot revealed a distinct shaped curve relation between LVEF and all-cause death among different pressure injury risk groups. CONCLUSIONS: In older patients with AMI, the risk of pressure injury mediated the association between LVEF and all-cause death. The classification of older patients for both therapy and prognosis assessment appears to be improved by the incorporation of pressure injury risk assessment into AMI care management.

The long noncoding RNA THBS1-AS1 promotes cardiac fibroblast activation in cardiac fibrosis by regulating TGFBR1.

Cardiac fibrosis is associated with an adverse prognosis in cardiovascular disease that results in a decreased cardiac compliance and, ultimately, heart failure. Recent studies have identified the role of long noncoding RNA (lncRNA) in cardiac fibrosis. However, the functions of many lncRNAs in cardiac fibrosis remain to be characterized. Through a whole-transcriptome sequencing and bioinformatics analysis on a mouse model of pressure overload-induced cardiac fibrosis, we screened a key lncRNA termed thrombospondin 1 antisense 1 (THBS1-AS1), which was positively associated with cardiac fibrosis. In vitro functional studies demonstrated that the silencing of THBS1-AS1 ameliorated TGF-ß1 effects on cardiac fibroblast (CF) activation, and the overexpression of THBS1-AS1 displayed the opposite effect. A mechanistic study revealed that THBS1-AS1 could sponge miR-221/222 to regulate the expression of TGFBR1. Moreover, under TGF-ß1 stimulation, the forced expression of miR-221/222 or the knockdown TGFBR1 significantly reversed the THBS1-AS1 overexpression induced by further CF activation. In vivo, specific knockdown of THBS1-AS1 in activated CFs significantly alleviated transverse aorta constriction-induced (TAC-induced) cardiac fibrosis in mice. Finally, we demonstrated that the human THBS1-AS1 can also affect the activation of CFs by regulating TGFBR1. In conclusion, this study reveals that lncRNA THBS1-AS1 is a potentially novel regulator of cardiac fibrosis and may serve as a target for the treatment of cardiac fibrosis.

Relationship of body fat and left ventricular hypertrophy with the risk of all-cause death in patients with coronary artery disease.

BACKGROUND: Left ventricular hypertrophy (LVH) is prevalent in obese individuals. Besides, both of LVH and obesity is associated with subclinical LV dysfunction. The study aims to investigate the interplay between body fat and LVH in relation to all-cause death in patients with coronary artery disease (CAD). METHODS: In this retrospective cohort study, a total of 2243 patients with angiographically proven CAD were included. Body fat and LV mass were calculated using established formulas. Patients were grouped according to body fat percentage and presence or absence of LVH. Cox-proportional hazard models were used to observe the interaction effect of body fat and LVH on all-cause death. RESULTS: Of 2243 patients enrolled, 560 (25%) had a higher body fat percentage, and 1045 (46.6%) had LVH. After a median follow-up of 2.2 years, the cumulative mortality rate was 8.2% in the group with higher body fat and LVH, 2.5% in those with lower body fat and no LVH, 5.4% in those with higher body fat and no LVH, and 7.8% in those with lower body fat and LVH (log-rank P < 0.001). There was a statistically significant interaction between body fat percentage and LVH ( P interaction was 0.003). After correcting for confounding factors, patients with higher body fat and LVH had the highest risk of all-cause death (HR = 3.49, 95% CI: 1.40-8.69, P = 0.007) compared with those with lower body fat and no LVH; in contrast, patients with higher body fat and no LVH had no statistically significant difference in risk of death compared with those with lower body fat and no LVH (HR = 2.03, 95% CI: 0.70-5.92, P = 0.195). CONCLUSION: A higher body fat percentage was associated with a different risk of all-cause death in patients with CAD, stratified by coexistence of LVH or not. Higher body fat was significantly associated with a greater risk of mortality among patients with LVH but not among those without LVH.

Patients With Bicuspid Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

Objective: We sought to conduct a systematic review and meta-analysis of clinical adverse events in patients undergoing transcatheter aortic valve replacement (TAVR) with bicuspid aortic valve (BAV) vs. tricuspid aortic valve (TAV) anatomy and the efficacy of balloon-expandable (BE) vs. self-expanding (SE) valves in the BAV population. Comparisons aforementioned will be made stratified into early- and new-generation devices. Differences of prosthetic geometry on CT between patients with BAV and TAV were presented. In addition, BAV morphological presentations in included studies were summarized. Method: Observational studies and a randomized controlled trial of patients with BAV undergoing TAVR were included according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Results: A total of 43 studies were included in the final analysis. In patients undergoing TAVR, type 1 BAV was the most common phenotype and type 2 BAV accounted for the least. Significant higher risks of conversion to surgical aortic valve replacement (SAVR), the need of a second valve, a moderate or severe paravalvular leakage (PVL), device failure, acute kidney injury (AKI), and stroke were observed in patients with BAV than in patients with TAV during hospitalization. BAV had a higher risk of new permanent pacemaker implantation (PPI) both at hospitalization and a 30-day follow-up. Risk of 1-year mortality was significantly lower in patients with BAV than that with TAV [odds ratio (OR) = 0.85, 95% CI 0.75-0.97, p = 0.01]. BE transcatheter heart valves (THVs) had higher risks of annular rupture but a lower risk of the need of a second valve and a new PPI than SE THVs. Moreover, BE THV was less expanded and more elliptical in BAV than in TAV. In general, the rates of clinical adverse events were lower in new-generation THVs than in early-generation THVs in both BAV and TAV. Conclusions: Despite higher risks of conversion to SAVR, the need of a second valve, moderate or severe PVL, device failure, AKI, stroke, and new PPI, TAVR seems to be a viable option for selected patients with severe bicuspid aortic stenosis (AS), which demonstrated a potential benefit of 1-year survival, especially among lower surgical risk population using new-generation devices. Larger randomized studies are needed to guide patient selection and verified the durable performance of THVs in the BAV population.

Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice.

BACKGROUND: After myocardial infarction, anti-inflammatory macrophages perform key homeostatic functions that facilitate cardiac recovery and remodeling. Several studies have shown that lactate may serve as a modifier that influences phenotype of macrophage. However, the therapeutic role of sodium lactate in myocardial infarction (MI) is unclear. METHODS: MI was established by permanent ligation of the left anterior descending coronary artery followed by injection of saline or sodium lactate. Cardiac function was assessed by echocardiography. The cardiac fibrosis area was assessed by Masson trichrome staining. Macrophage phenotype was detected via qPCR, flow cytometry, and immunofluorescence. Signaling proteins were measured by Western blotting. RESULTS: Sodium lactate treatment following MI improved cardiac performance, enhanced anti-inflammatory macrophage proportion, reduced cardiac myocytes apoptosis, and increased neovascularization. Flow-cytometric analysis results reported that sodium lactate repressed the number of the IL-6+, IL-12+, and TNF-α+ macrophages among LPS-stimulated bone marrow-derived macrophages (BMDMs) and increased the mRNA levels of Arg-1, YM1, TGF-ß, and IL-10. Mechanistic studies revealed that sodium lactate enhanced the expression of P-STAT3. Furthermore, a STAT3 inhibitor eliminated sodium lactate-mediated promotion macrophage polarization. CONCLUSION: Sodium lactate facilitates anti-inflammatory M2 macrophage polarization and protects against MI by regulating P-STAT3.

Variation of computed tomographic angiography-based fractional flow reserve after transcatheter aortic valve implantation.

OBJECTIVES: We sought to identify the impact of transcatheter aortic valve implantation (TAVI) on changes of fractional flow reserve computed tomography (FFRCT) values and the associated clinical impact. METHODS: A retrospective analysis was done with CT obtained pre-TAVI, prior to hospital discharge and at 1-year follow-up, which provided imaging sources for the calculation of FFRCT values based on an online platform. RESULTS: A total of 190 patients were enrolled. Patients with pre-procedural FFRCT value > 0.80 (i.e., negative) and ≤ 0.80 (i.e., positive) demonstrated a significantly opposite change in the value after TAVI (0.8798 vs. 0.8718, p < 0.001 and 0.7634 vs. 0.8222, p < 0.001, respectively). The history of coronary artery disease (CAD) was identified as an independent predictor for FFRCT changing from negative to positive after TAVI (odds ratio [OR] 2.927, 95% confidence interval [CI] 1.130-7.587, p = 0.027), with lesions more severely stenosed (OR 1.039, 95% CI 1.003-1.076, p = 0.034) and in left anterior descending coronary artery (LAD) (OR 3.939, 95% CI 1.060-14.637, p = 0.041) being prone to change. CONCLUSIONS: TAVI directly brings improvement in FFRCT values in patients with compromised coronary flow. Patients with a history of CAD, especially with lesions more severely stenosed and in LAD, were under risk of FFRCT changing from negative to positive after TAVI. KEY POINTS: •The effect of TAVI on coronary hemodynamics might be influenced by different ischemic severity and coronary territories reflected by FFRCT values. •As different FFRCT variations did not impact outcomes of TAVI patients, AS, but not coronary issues, may be the primary problem to affect, which needs further validation.

Activating transcription factor 4 regulates angiogenesis under lipid overload via methionine adenosyltransferase 2A-mediated endothelial epigenetic alteration.

Lipid overload is intimately connected with the change of endothelial epigenetic status which impacts cellular signaling activities and endothelial function. Activating transcription factor 4 (ATF4) is involved in the regulation of lipid metabolism and meanwhile an epigenetic modifier. However, the role of ATF4 in the angiogenesis under lipid overload is not well understood. Here, to induce lipid overload status, we employed high-fat diet (HFD)-induced obese mouse model in vivo and palmitic acid (PA) to stimulate endothelial cells in vitro. Compared with mice fed with normal chow diet (NCD), HFD-induced obese mice showed angiogenic defects evidenced by decline in (1) blood flow recovery after hind limb ischemia, (2) wound healing speed after skin injury, (3) capillary density in injured tissues and matrigel plugs, and (4) endothelial sprouts of aortic ring. ATF4 deficiency aggravated above angiogenic defects in mice while ATF4 overexpression improved the blunted angiogenic response. Mechanistically, lipid overload lowered the H3K4 methylation levels at the regulatory regions of NOS3 and ERK1 genes, leading to reduced angiogenic signaling activity. Methionine adenosyltransferase 2A (MAT2A) is identified as a target of ATF4 and formed complex with ATF4 to direct lysine methyltransferase 2A (MLL1) to the regulatory regions of both genes for the maintenance of the H3K4 methylation level and angiogenic signaling activity. Here, we uncovered a novel metabolic-epigenetic coupling orchestrated by the ATF4-MAT2A axis for angiogenesis. The ATF4-MAT2A axis links lipid overload milieu to altered epigenetic status of relevant angiogenic signaling in endothelial cells, suggesting a potential therapeutic target for angiogenesis impaired by lipid overload.

Clinical characteristics and in-hospital outcomes of patients receiving contemporary intensive cardiac care: retrospective study from a large centre in China.

BACKGROUND: Few studies from developed countries have quantitatively characterized the clinical characteristics and outcomes of patients receiving contemporary intensive cardiac care. We sought to investigate these data in patients admitted to a Chinese intensive cardiac care unit (ICCU). METHODS: We conducted a retrospective study using data from 2,337 consecutive admissions to the ICCU at a large centre in China from June 2016 to May 2017. Data were captured after systematic inspection of individual medical records regarding current demographics, primary diagnosis, comorbidities, illnesses severity, and in-hospital outcomes. RESULTS: The mean age was 65.6 ± 14.2 years, and females accounted for 32.0% of patients. The Charlson Comorbidity Index and Oxford Acute Severity of Illness Score were 2.4 ± 1.8 and 22.5 ± 10.4, respectively. The top reason for admission was ST-segment elevation myocardial infarction (32.0%), and nonischaemic heart diseases accounted for 31.2% of all primary diagnoses. Noncardiovascular diseases were prevalent in the ICCU population, including chronic illnesses and acute noncardiovascular critical illnesses (ANCIs); in particular, 21.7% of patients were marked by acute respiratory failure (14.6%), acute kidney injury (13.7%), sepsis (4.2%), or gastrointestinal bleeding (3.3%). The median length of stay in the ICCU and hospital were 1.1 days [interquartile range (IQR): 0.8-2.6 days] and 6.3 days (IQR: 3.8-10.9 days), respectively. The overall incidence of in-hospital death or discharge against medical advice under extremely critical conditions was 7.6% (n = 177). Multivariate logistic regression analysis showed that the complexity of chronic illnesses and incident ANCIs were strong independent determinants for in-hospital outcomes. CONCLUSIONS: Remarkable patient diversity and breadth of critical illnesses were observed in a Chinese ICCU population. Particularly, noncardiovascular diseases were prevalent and associated with adverse outcomes. Reformation of organization and staffing practices may be considered to adapt to the changed landscape.

MARCH5 restores endothelial cell function against ischaemic/hypoxia injury via Akt/eNOS pathway.

MARCH5 is a critical regulator of mitochondrial dynamics, apoptosis and mitophagy. However, its role in cardiovascular system remains poorly understood. This study aimed to investigate the role of MARCH5 in endothelial cell (ECs) injury and the involvement of the Akt/eNOS signalling pathway in this process. Rat models of myocardial infarction (MI) and human cardiac microvascular endothelial cells (HCMECs) exposed to hypoxia (1% O2 ) were used in this study. MARCH5 expression was significantly reduced in ECs of MI hearts and ECs exposed to hypoxia. Hypoxia inhibited the proliferation, migration and tube formation of ECs, and these effects were aggravated by knockdown of MARCH5 but antagonized by overexpressed MARCH5. Overexpression of MARCH5 increased nitric oxide (NO) content, p-eNOS and p-Akt, while MARCH5 knockdown exerted the opposite effects. The protective effects mediated by MARCH5 overexpression on ECs could be inhibited by eNOS inhibitor L-NAME and Akt inhibitor LY294002. In conclusion, these results indicated that MARCH5 acts as a protective factor in ischaemia/hypoxia-induced ECs injury partially through Akt/eNOS pathway.

Renal function as a predictor of outcomes in patients with hypertrophic cardiomyopathy: A cohort study of a hospitalized population.

BACKGROUND: The relationship between renal function and outcomes among patients with hypertrophic cardiomyopathy (HCM) remains undefined. We sought to investigate the prevalence of renal dysfunction and its prognostic value in HCM patients. METHODS: A total of 581 patients with HCM were consecutively recruited. The chronic kidney disease epidemiology equation was used to estimate the glomerular filtration rate (eGFR). Patients were divided into 2 eGFR categories: ≥60 or <60 ml/min/1.73 m2. The predictive value of renal function was assessed using Cox regression. RESULTS: The proportions of eGFR 60-90 ml/min/1.73 m2 and <60 ml/min/1.73 m2 were 41.8% and 15.3%, respectively. Estimated GFR independently predicted the risk of all-cause mortality [HR 0.98, 95% confidence interval (CI) 0.96-0.99, P < 0.001]. Compared to those with eGFR ≥ 60 ml/min/1.73 m2, patients with eGFR < 60 ml/min/1.73 m2 were independently associated with all-cause mortality (HR, 3.42 95% CI 1.86-6.28), cardiovascular mortality (HR 2.98, 95% CI 1.36-6.50) and combined adverse outcomes (HR 1.60, 95% CI 1.02-2.49). HRs for all-cause mortality with renal dysfunction were attenuated in patients with older ages (P for interaction = 0.034). CONCLUSIONS: Renal dysfunction is a common comorbidity in HCM. Renal function is an independent predictor of outcomes in patients with HCM. These findings highlight the clinical importance of renal dysfunction in HCM.

Hypertension is a risk factor for adverse outcomes in patients with coronavirus disease 2019: a cohort study.

BACKGROUND: Comorbidities are commonly seen in patients with coronavirus disease 2019 (COVID-19), but the clinical implication is not yet well-delineated. We aim to characterize the prevalence and clinical implications of comorbidities in patients with COVID-19. METHODS: This is a retrospective multi-centre study involving patients admitted between January 16th and March 10th 2020. The composite endpoint was defined as the presence of at least one of the following, intensive care unit (ICU) admission, or the need for mechanical ventilation, or death. RESULTS: A total of 472 consecutive cases admitted to 51 certified COVID-19 tertiary care hospitals were enrolled (median age was 43 [32-53.5] years and 53.0% were male). There were 101 (21.4%) patients presented with comorbidities, including hypertension (15.0%), diabetes mellitus (7.8%), coronary artery disease (2.6%), chronic obstructive pulmonary disease (1.3%) and cerebrovascular disease (1.9%). The composite endpoint occurred in 65 (13.8%) patients. Multivariate stepwise logistic regression analysis indicated that older age (odds ratio [OR] 1.39, 95% confidence interval (CI) 1.05-1.85, per 10-year increment), antecedent hypertension (OR 2.82, 95% CI 1.09-7.29), neutrophil counts (OR 1.33, 95% CI 1.14-1.56) and lactate dehydrogenase level (OR 1.01, 95% CI 1.00-1.01) were independently associated with the presence of composite endpoint. Hypertensive patients, compared with controls, had a greater chance of experiencing the composite endpoint (p < .001) and each individual endpoint, i.e. ICU admission (p < .001), mechanical ventilation (p < .001) and death (p = .012). In the stepwise regression analysis of anti-hypertensive medications, none of the therapy predicted the composite endpoint. CONCLUSIONS: Hypertension is a common comorbidity in patients with COVID-19 and associated with adverse outcomes. KEY MESSAGES Hypertension was identified as the comorbidity associated with the prognosis of COVID-19 in this retrospective cohort. Patients with hypertension could experience an increased risk of the composite endpoint. Anti-hypertensive therapy did not affect patient outcomes.

Influence of Gender on Clinical Characteristics and Outcomes in Chinese Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Gender plays a crucial role in the prevalence, clinical presentation, management and outcomes of various cardiovascular diseases. The aim of this study was to evaluate the impact of gender on clinical manifestations and outcomes in the Chinese patients with hypertrophic cardiomyopathy (HCM). METHODS: We evaluated 576 Chinese patients (316 males) who were diagnosed with HCM at West China Hospital from 2008 to 2016 and followed over 3.2 ± 2.3 years. RESULTS: Compared to male patients, female patients were older (57.2 ± 16.7 years vs. 53.0 ± 15.7 years, P = 0.002) and more symptomatic [New York Heart Association class III-IV symptoms 46.9% vs. 30.7%, P < 0.001] at the time of diagnosis, and had higher left ventricular outflow tract gradient at rest [33 (12-58) mmHg vs. 24 (8-42) mmHg, P = 0.007]. During the follow-up period, survival analysis showed no significant differences in the incidences of all-cause mortality (P = 0.657) and cardiovascular mortality (P = 0.214) but the rate of rehospitalization due to heart failure was higher in females than in males (P = 0.015). Multivariable Cox analysis showed that left ventricular ejection fraction (hazard ratio [HR], 0.96 [95% confidence interval [CI], 0.94-0.99]; P = 0.003) and New York Heart Association class III-IV (HR, 2.86 [95% CI, 1.38-5.94]; P = 0.005) were independently associated with cardiovascular mortality. CONCLUSIONS: Compared to males, females were older and more symptomatic at presentation, and had higher risk of progression to heart failure in Chinese HCM patients but there were no differences in cardiovascular mortality.

Acute myocardial injury is common in patients with COVID-19 and impairs their prognosis.

OBJECTIVE: We sought to explore the prevalence and immediate clinical implications of acute myocardial injury in a cohort of patients with COVID-19 in a region of China where medical resources are less stressed than in Wuhan (the epicentre of the pandemic). METHODS: We prospectively assessed the medical records, laboratory results, chest CT images and use of medication in a cohort of patients presenting to two designated covid-19 treatment centres in Sichuan, China. Outcomes of interest included death, admission to an intensive care unit (ICU), need for mechanical ventilation, treatment with vasoactive agents and classification of disease severity. Acute myocardial injury was defined by a value of high-sensitivity troponin T (hs-TnT) greater than the normal upper limit. RESULTS: A total of 101 cases were enrolled from January to 10 March 2020 (average age 49 years, IQR 34-62 years). Acute myocardial injury was present in 15.8% of patients, nearly half of whom had a hs-TnT value fivefold greater than the normal upper limit. Patients with acute myocardial injury were older, with a higher prevalence of pre-existing cardiovascular disease and more likely to require ICU admission (62.5% vs 24.7%, p=0.003), mechanical ventilation (43.5% vs 4.7%, p<0.001) and treatment with vasoactive agents (31.2% vs 0%, p<0.001). Log hs-TnT was associated with disease severity (OR 6.63, 95% CI 2.24 to 19.65), and all of the three deaths occurred in patients with acute myocardial injury. CONCLUSION: Acute myocardial injury is common in patients with COVID-19 and is associated with adverse prognosis.

Association of fine particulate matter exposure with acute noncardiovascular critical illnesses and in-hospital outcomes in patients receiving intensive cardiac care.

BACKGROUND: The effect of short-term exposure to fine particulate matter (PM2.5) on the incidence of acute noncardiovascular critical illnesses (ANCIs) and clinical outcomes is unknown in patients with acute cardiovascular diseases. METHODS: We conducted a retrospective study in 2337 admissions to an intensive cardiac care unit (ICCU) from June 2016 to May 2017. We used the 2-day average PM2.5 concentration before ICCU admission to estimate the individual exposure level, and patients were divided into 3 groups according to the concentration tertiles. Major ANCI was defined as the composite of acute respiratory failure, acute kidney injury, gastrointestinal hemorrhage, or sepsis. The primary endpoint was all-cause death or discharge against medical advice in extremely critical condition. RESULTS: During the 12-month study period, the annual median concentration of PM2.5 in Chengdu, China was 48 µg/m3 (IQR, 33-77 µg/m3). More than 20% of admissions were complicated by major ANCI, and the primary endpoints occurred in 7.6% of patients during their hospitalization. The association of short-term PM2.5 exposure levels with the incidence of acute respiratory failure (adjusted OR [odds ratio] =1.31, 95% CI [confidence interval]1.12-1.54) and acute kidney injury (adjusted OR = 1.20, 95% CI 1.02-1.41) showed a significant trend. Additionally, there were numerically more cases of sepsis (adjusted OR = 1.21, 95% CI 0.92-1.60) and gastrointestinal hemorrhage (adjusted OR = 1.29, 95% CI 0.94-1.77) in patients with higher exposure levels. After further multivariable adjustment, short-term PM2.5 exposure levels were still significantly associated with incident major ANCI (adjusted OR = 1.32, 95% CI 1.12-1.56), as well as a higher incidence of the primary endpoint (adjusted OR = 1.52, 95% CI 1.09-2.12). CONCLUSION: Short-term PM2.5 exposure before ICCU admission was associated with an increased risk of incident major ANCI and worse in-hospital outcomes in patients receiving intensive cardiac care.