Cumulative non-high-density lipoprotein cholesterol burden and risk of atherosclerotic cardiovascular disease: a prospective community-based study.

Background: The relationship between cumulative non-high-density lipoprotein cholesterol (non-HDL-C) burden and atherosclerotic cardiovascular disease (ASCVD) remains unclear. Objective: To prospectively examine the association between cumulative non-HDL-C burden and ASCVD risk in the Kailuan cohort of China. Methods: A total of 49,679 subjects who were free of ASCVD participated in three consecutive examinations in 2006, 2008 and 2010 were enrolled. Duration and concentration of cumulative exposure to non-HDL-C (cumNon-HDL-C) were respectively used to estimate the extent of cumulative non-HDL-C burden. The participants were divided into four groups according to durations of cumNon-HDL-C (0, 2, 4 and 6 years) and five groups according to the quintiles of cumNon-HDL-C concentration (<10.93, 10.93-12.68, 12.69-14.32, 14.33-16.72 and ≥16.73 mmol/L). Cox regression models were used to analyze the influence of cumulative non-HDL-C burden on ASCVD risk. Results: We identified 1,134 incident ASCVD cases during a mean of 4.89 years of follow-up. Multivariable adjusted analysis revealed that compared with no exposure, cumNon-HDL-C duration 2, 4 and 6 years increased ASCVD risk by 26% (HR: 1.26, 95% CI: 1.07-1.47), 56% (HR: 1.56, 95% CI: 1.31-1.86) and 91% (HR: 1.91, 95% CI: 1.59-2.31) respectively; The hazard ratios (HRs) for the fourth and fifth versus lowest quintile of cumNon-HDL-C concentration were 1.25 and 1.72 for ASCVD. Each standard deviation increment in cumNon-HDL-C concentration was associated with a 10% increased risk of ASCVD. Conclusion: Long-term and higher cumNon-HDL-C were all significantly associated with an increased risk of ASCVD independent of single non-HDL-C level.

Short QRS Duration After His-Purkinje Conduction System Pacing Predicts Left Ventricular Complete Reverse Remodeling in Patients With True Left Bundle Branch Block and Heart Failure.

Objective: This study aimed to explore the outcomes of His-Purkinje conduction system pacing (HPCSP) and to screen the predictors of left ventricular (LV) complete reverse remodeling in patients with true left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF). Methods: Patients who underwent HPCSP for true LBBB and HFrEF from April 2018 to August 2020 were consecutively enrolled. All participants were followed up for at least 1 year. Thrombosis, infection, lead dislodgement, perforation, and other complications were observed after HPCSP. Clinical data, including echocardiographic parameters, electrocardiogram measurements, and cardiac function, were assessed before and after the procedure. Results: A total of 46 patients were enrolled. HPCSP was successfully deployed in 42 cases (91.30%), which included 37 cases with His bundle pacing (HBP) and 5 cases with left bundle branch pacing (LBBP). The QRS duration decreased significantly (169.88 ± 19.17 ms vs. 113.67 ± 20.68 ms, P < 0.001). Left ventricular end-systolic volume (LVESV) (167.67 ± 73.20 ml vs. 85.97 ± 62.24 ml, P < 0.001), left ventricular end-diastolic diameter (LVEDD) (63.57 ± 8.19 mm vs. 55.46 ± 9.63 mm, P = 0.003) and left ventricular ejection fraction (LVEF) (26.52 ± 5.60% vs. 41.86 ± 11.56%, P < 0.001) improved dramatically. Complete reverse remodeling of the LV with normalized LVEF and LVEDD was found in nearly half of the patients (45.24%). A short QRS duration after HPCSP was a strong predictor of normalized LVEF and LVEDD (P < 0.001). The thresholds increased markedly in two patients approximately 6 months after HBP. No patients died during the total follow-up period of 20.07 ± 6.45 months. Conclusion: Complete reverse remodeling of the LV could be found in nearly half of the patients with HFrEF and true LBBB after HPCSP, and the short QRS duration after HPCSP was a strong predictor.

Risks of Ischemic Stroke/Transient Ischemic Attack Based on CHA2DS2-VASc Scores in Non-Atrial Fibrillation Chinese Patients with Sinus Rhythm.

This study aims to evaluate the incidence of ischemic stroke or transient ischemic attack (TIA) based on CHA2DS2-VASc scores in non-AF Chinese patients with sinus rhythm.We used health check-up data of 101,510 participants from the Kailuan Cohort Study. Participants' risk levels were defined by their CHA2DS2-VASc scores (range 0-3): Men with scores of 0, 1, or ≥ 2 and women with scores of 1, 2, or ≥ 3 were considered at low, intermediate, or high risk, respectively. Cox proportional hazards model was used to assess the association between the CHA2DS2-VASc-determined risk and the incidence of ischemic stroke/TIA.The mean 7.5 year follow-up examination revealed 2968 ischemic strokes/TIA events. The incidence rates for ischemic stroke/TIA events in men and women were 3.8% and 1.5%, respectively. The incidence of ischemic stroke/TIA increased with elevated predicted risks based on CHA2DS2-VASc scores in men: 2.2% for low-risk, 4.1% for intermediate-risk, and 7.8% for high-risk groups (P < 0.001 for trend). The incidences of ischemic stroke/TIA also increased with elevated predicted risks in women: 0.8% for low-risk, 2.1% for intermediate-risk, and 5.0% for high-risk groups (P < 0.001 for trend). Compared with low-risk group, the crude hazard ratio (95% confidence interval) of ischemic stroke/TIA for men in moderate- and high-risk groups were 1.96 (1.79-2.14; P < 0.001) and 4.18 (3.81-4.57; P < 0.001). Similar findings were observed in women.Risks of ischemic stroke/TIA events was high, particularly among those with high CHA2DS2-VASc scores.

E/E' Is a New Independent Predictor of Recovered Ejection Fraction in Patients With Systolic Heart Failure Undergoing Ablation for Atrial Fibrillation.

Aims: Catheter ablation should be considered in patients with atrial fibrillation (AF) and with heart failure (HF) with reduced ejection fraction (EF; HFrEF) to improve survival and reduce heart failure hospitalization. Careful patient selection for AF ablation is key to achieving similar outcome benefits. However, limited data exist regarding predictors of recovered ejection fraction. We aimed to evaluate the predictors of recovered ejection fraction in consecutive patients with HF undergoing AF ablation. Methods and Results: A total of 156 patients [67.3% men, median age 63 (11)] with AF and HF underwent initial catheter ablation between September 2017 and October 2019 in the First Affiliated Hospital of Dalian Medical University. Overall, the percentage of recovered ejection fractions was 72.3%. Recovered EFs were associated with a 39% reduction in all-cause hospitalization compared to non-recovered EFs at the 1-year follow-up [23.8 vs. 62.8 (odds ratio) OR 2.09 (1.40-3.12), P < 0.001]. Univariate analysis for recovered EFs showed that diabetes (P = 0.083), prevalent HF (P = 0.014), prevalent AF (P = 0.051), LVEF (P = 0.022), and E/E' (P = 0.001) were associated with EF improvement. Multivariate analysis showed that the only independent predictor of EF recovery was E/E' [OR 1.13 (1.03-1.24); P = 0.011]. A receiver operating characteristic analysis determined that the suitable cut-off value for E/E' was 15 (sensitivity 38.7%, specificity 89.2%, the area under curve 0.704). Conclusions: Ejection fraction (EF) recovery occurred in 72.3% of patients, associated with a 39% reduction in all-cause hospitalization compared to the non-recovered EFs in our cohort. The only independent predictor of recovered EF was E/E' < 15 in our series.

Correction to: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes improves myocardial function and reverses ventricular remodeling in infarcted rat hearts.

The original article omits an affiliation for authors, He Zhang and Dongjin Wang. The omitted affiliation can be viewed in this Correction article.

Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has produced a significant health burden worldwide, especially in patients with cardiovascular comorbidities. The aim of this systematic review and meta-analysis was to assess the impact of underlying cardiovascular comorbidities and acute cardiac injury on in-hospital mortality risk. METHODS: PubMed, Embase and Web of Science were searched for publications that reported the relationship of underlying cardiovascular disease (CVD), hypertension and myocardial injury with in-hospital fatal outcomes in patients with COVID-19. The ORs were extracted and pooled. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity. RESULTS: A total of 10 studies were enrolled in this meta-analysis, including eight studies for CVD, seven for hypertension and eight for acute cardiac injury. The presence of CVD and hypertension was associated with higher odds of in-hospital mortality (unadjusted OR 4.85, 95% CI 3.07 to 7.70; I2=29%; unadjusted OR 3.67, 95% CI 2.31 to 5.83; I2=57%, respectively). Acute cardiac injury was also associated with a higher unadjusted odds of 21.15 (95% CI 10.19 to 43.94; I2=71%). CONCLUSION: COVID-19 patients with underlying cardiovascular comorbidities, including CVD and hypertension, may face a greater risk of fatal outcomes. Acute cardiac injury may act as a marker of mortality risk. Given the unadjusted results of our meta-analysis, future research are warranted.

Transplantation of human induced pluripotent stem cell-derived cardiomyocytes improves myocardial function and reverses ventricular remodeling in infarcted rat hearts.

BACKGROUND: Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have shed great light on cardiac regenerative medicine and specifically myocardial repair in heart failure patients. However, the treatment efficacy and the survival of iPSC-CMs in vivo after transplantation have yielded inconsistent results. OBJECTIVES: The objective of this study was to evaluate the ability of human iPSC-CMs to improve myocardial function in a rat postinfarction heart failure model. METHODS: Eight-week-old male Sprague-Dawley rats were randomly selected to receive an intramyocardial injection of 5% albumin solution with or without 1 × 107 human iPSC-CMs 10 days after undergoing left anterior descending (LAD) coronary artery ligation. Cyclosporine A and methylprednisolone were administered before iPSC-CM injection and until the rats were killed to prevent graft rejection. Cardiac function was evaluated by echocardiography. The survival of grafted cardiomyocytes was confirmed by observing the fluorescent cell tracer Vybrant™ CM-DiI or expression of the enhanced green fluorescent protein (eGFP) in transplanted cells, or survival was demonstrated by polymerase chain reaction (PCR)-based detection of human mitochondrial DNA. Sirius red stain was used to evaluate the fibrosis ratio. Hematoxylin-eosin staining was used to observe the formation of teratomas. RESULTS: Four weeks after intramyocardial injection of iPSC-CMs, animals undergoing iPSC-CM transplantation had lower mortality than the control group. Animals injected with cell-free solution (control group) demonstrated significant left ventricular (LV) functional deterioration, whereas grafting of iPSC-CMs attenuated this remodeling process. In the control group, the ejection fraction deteriorated by 10.11% (from 46.36 to 41.67%), and fractional shortening deteriorated by 9.23% (from 24.37 to 22.12%) by 4 weeks. In the iPSC-CM injection group, the ejection fraction improved by 18.86% (from 44.09 to 52.41%), and fractional shortening improved by 23.69% (from 23.08 to 28.54%). Cell labeling, tracking, and molecular biology techniques indicated that the grafted cardiomyocytes survived in the rat heart 1 month after iPSC-CM transplantation. Myocardial fibrosis was also attenuated in the iPSC-CM treatment group. CONCLUSIONS: Human iPSC-CM grafts survived in infarcted rat hearts and restored myocardial function 4 weeks after transplantation. Cell replacement therapy also reversed ventricular remodeling, indicating the potential of iPSC-CMs for cardiac repair strategies.

Data for short and long-term prothrombotic biomarkers after cryoballoon and radiofrequency ablation.

Data presented in this article are supplementary analyzed tables and individual raw data to our research article entitled "Short and long-term changes in platelet and inflammatory biomarkers after cryoballoon and radiofrequency ablation (Bin Waleed K et al., 2019) [1]". These supplementary analyzed tables and individual raw data included platelet activation biomarkers [P-selectin (CD62P), CD40 ligand (CD40L), platelet factor-4 (PF-4), mean platelet volume (MPV), platelet-leukocyte ratio (P-LCR), and platelet distribution width (PDW)]; and inflammatory biomarkers [high sensitivity CRP (hs-CRP) and interleukin-6 (IL-6)] after cryoballoon (CB) and radiofrequency (RF) ablation. The provided raw data are intended to show the difference at short and long-term in platelet and inflammatory biomarkers values between CB and RF ablation.

Short and long-term changes in platelet and inflammatory biomarkers after cryoballoon and radiofrequency ablation.

BACKGROUND: Cryoballoon (CB) versus radiofrequency (RF) ablation response on prothrombotic biomarkers obtained different results at short-term, while long-term is still unknown in atrial fibrillation (AF) treatment. We evaluated short and long-term changes in platelet and inflammatory biomarkers after CB and RF ablation. METHODS: Fifty-eight paroxysmal AF patients were randomized for pulmonary vein (PV) isolation using either CB (n = 29) or RF (n = 29) ablation. Biomarkers of platelet activation [P-selectin (CD62P), CD40 ligand (CD40L), platelet factor-4 (PF-4), mean platelet volume (MPV), platelet-leukocyte ratio (P-LCR), and platelet distribution width (PDW)]; and inflammatory [high sensitivity CRP (hs-CRP) and interleukin-6 (IL-6)] were measured at baseline, 18-24 h and 6-Months postablation. RESULTS: Twenty-four (86.2%) and twenty-six (89.7%) patients remained in sinus rhythm at 6-Months in CB and RF group respectively (p = 0.500). After 18-24 h postablation, CD62P, CD40L, PF-4, hs-CRP, and IL-6 levels were significantly activated in both groups (p < 0.001). However, CD62P was significantly lower in CB than RF (p = 0.017). At 6-Month postablation in CB group, all platelet biomarkers CD62P (p = 0.021), CD40L (p < 0.001), PF-4 (p < 0.001), MPV (p = 0.010), PDW (p = 0.004), and P-LCR (p = 0.033) were significantly decreased compared to baseline levels. However in RF group, CD40L and PF-4 (p < 0.001) significant decreased, CD62P (p = 0.022) increased, and no change in MPV and P-LCR (p > 0.05) compared to baseline levels. hs-CRP and IL-6 levels were comparable between baseline and 6-Months in both groups (p > 0.05). CONCLUSIONS: CB ablation might influence the risk of thromboembolism due to less platelet activation after PV isolation and decreased platelet activation at long-term in maintained sinus rhythm patients compared to RF.

Atrial fibrillation is related to lower incidence of deep venous thrombosis in patients with pulmonary embolism.

BACKGROUND: Atrial fibrillation (AF) is an established risk factor of left atrial thrombosis and systemic embolism. Traditionally pulmonary embolism (PE) is a recognized complication of deep vein thrombosis (DVT). However, whether AF is responsible for right atrial thrombosis and leads to PE has not been examined. METHODS: We retrospectively analyzed medical records of patients with confirmed diagnosis of PE with AF (study group) from 2002-2015. Patients with PE without AF, matched by age and sex, served as controls (control group). The CHA2DS2-VASc and CHADS2 scores were classified into two categories, low-intermediate (<2 points) and high-risk (≥2 points). RESULTS: A total of 330 patients (110 in study group and 220 in control group). The study group had significantly lower incidence of newly diagnosed DVT (21% vs. 44%, P<0.001), previous history of DVT (6% vs. 17%, P=0.006) and recent surgery or trauma (10% vs. 23%, P=0.004) compared to the control group. When stratified by the CHADS2 score, 49 patients (44.5%) were considered low-intermediate risk. This proportion significantly differed when stratified using CHA2DS2-VASc, in which 13 patients (13.6%) were considered low-intermediate risk, P<0.001. CONCLUSIONS: The incidence of DVT was much lower in the study group, suggesting the possibility of clots originated from the right heart that may increase the risk of PE. The CHA2DS2-VASc scoring system might be more sensitive for prediction and stratification of the PE in AF patients than the CHADS2 score.

CXCL1-CXCR2 axis mediates angiotensin II-induced cardiac hypertrophy and remodelling through regulation of monocyte infiltration.

Aims: Chemokine-mediated monocyte infiltration into the damaged heart represents an initial step in inflammation during cardiac remodelling. Our recent study demonstrates a central role for chemokine receptor CXCR2 in monocyte recruitment and hypertension; however, the role of chemokine CXCL1 and its receptor CXCR2 in angiotensin II (Ang II)-induced cardiac remodelling remain unknown. Methods and results: Angiotensin II (1000 ng kg-1 min-1) was administrated to wild-type (WT) mice treated with CXCL1 neutralizing antibody or CXCR2 inhibitor SB265610, knockout (CXCR2 KO) or bone marrow (BM) reconstituted chimeric mice for 14 days. Microarray revealed that CXCL1 was the most highly upregulated chemokine in the WT heart at Day 1 after Ang II infusion. The CXCR2 expression and the CXCR2+ immune cells were time-dependently increased in Ang II-infused hearts. Moreover, administration of CXCL1 neutralizing antibody markedly prevented Ang II-induced hypertension, cardiac dysfunction, hypertrophy, fibrosis, and macrophage accumulation compared with Immunoglobulin G (IgG) control. Furthermore, Ang II-induced cardiac remodelling and inflammatory response were also significantly attenuated in CXCR2 KO mice and in WT mice treated with SB265610 or transplanted with CXCR2-deficienct BM cells. Co-culture experiments in vitro further confirmed that CXCR2 deficiency inhibited macrophage migration and activation, and attenuated Ang II-induced cardiomyocyte hypertrophy and fibroblast differentiation through multiple signalling pathways. Notably, circulating CXCL1 level and CXCR2+ monocytes were higher in patients with heart failure compared with normotensive individuals. Conclusions: Angiotensin II-induced infiltration of monocytes in the heart is largely mediated by CXCL1-CXCR2 signalling which initiates and aggravates cardiac remodelling. Inhibition of CXCL1 and/or CXCR2 may represent new therapeutic targets for treating hypertensive heart diseases.

Lipid profile and incidence of atrial fibrillation: A prospective cohort study in China.

BACKGROUND: The association between dyslipidemia, a major risk factor for cardiovascular diseases, and atrial fibrillation (AF) is not clear because of limited evidence. HYPOTHESIS: Dyslipidemia may be associated with increased risk of AF in a Chinese population. METHODS: A total of 88 785 participants free from AF at baseline (2006-2007) were identified from the Kailuan Study. Fasting levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured at baseline using standard procedures. The study population was stratified based on quartiles of lipid profile. Incident AF was ascertained from electrocardiograms at biennial follow-up visits (2008-2015). The associations between incident AF and the different lipid parameters (TC, LDL-C, HDL-C, and TG) were assessed by Cox proportional hazards regression analysis. RESULTS: Over a mean follow-up period of 7.12 years, 328 subjects developed AF. Higher TC (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43-0.84) and LDL-C (HR: 0.60, 95% CI: 0.43-0.83) levels were inversely associated with incident AF after multivariable adjustment. HDL-C and TG levels showed no association with newly developed AF. The results remained consistent after exclusion of individuals with myocardial infarction or cerebral infarction, or those on lipid-lowering therapy. Both TC/HDL-C and LDL-C/HDL-C ratios were inversely associated with risk of AF (per unit increment, HR: 0.88, 95% CI: 0.79-0.98 and HR: 0.77, 95% CI: 0.66-0.91, respectively). CONCLUSIONS: TC and LDL-C levels were inversely associated with incident AF, whereas no significant association of AF with HDL-C or TG levels was observed.

Higher High-Sensitivity C Reactive Protein is Associated with Future Premature Ventricular Contraction: a Community Based Prospective Cohort Study.

We aimed to determine whether hs-CRP is a predictor of future premature ventricular contraction (PVC) events in a community based population. A total of 101,510 participants were recruited at baseline (2006-2007). The follow-up visits were conducted every two years. Participants who were free from PVC at baseline and achieved the fourth visit, or diagnosed of PVC during the subsequent visits were included for analyses. Diagnosis of PVC was based on standard supine resting, 10-s 12-lead ECG. Cox regression was applied to evaluate the association between quartiles of hs-CRP and the incidence of PVCs. 60710 participants (male: 79.9%, mean age 49.4 years) were included for analyses. During a mean follow-up of 74.9 ± 7.4 months, 908 (1.5%) participants were diagnosed with PVC. Participants of the highest quartile of hs-CRP had significantly increased risk of PVC events as compared with the lowest quartile (HR 1.36; 95% CI 1.12-1.66); and stratified analyses showed similar result in males (HR 1.45; 95% CI 1.16-1.80), but not in females (HR 1.12; 95% CI 0.71-1.79). Moreover, elevated serum hs-CRP was associated with future PVC in participants without history of myocardial infarction or stroke (HR 1.34; 95% CI 1.09-1.65). Elevated hs-CRP was an independent predictor of PVC in Chinese population, especially in men.

Association of total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol with atherosclerotic cardiovascular disease and cancer in a Chinese male population.

This prospective study included 68,759 Chinese male adults from Kailuan cohort of China who had a standardized medical examination between 2006 and 2007 and were followed up for approximately 8 years until occurrence of ASCVD, cancer or death or until December 31, 2014. Subjects were divided into four categories based on the quartiles of TC, LDL-C and non-HDL-C. Cox regression models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs). During follow-up, 2,916 males developed ASCVD and 1,884 developed cancer. Compared with the lowest quartile, the upper-most quartiles of TC, LDL-C and non-HDL-C were all associated with increased ASCVD risk (HR 1.53; HR 1.16; HR 1.55); however, the upper-most quartiles of TC, LDL-C and non-HDL-C were all negatively associated with cancer (HR0.84; HR 0.82; HR 0.80) and these associations were present after exclusion of incident cancers during the first 4 years of follow-up. In a word, we report that high TC, LDL-C and non-HDL-C concentrations increased ASCVD incidence in a male population and that these lipid profiles were inversely associated with total cancer and several individual cancers.

Protection against doxorubicin-induced myocardial dysfunction in mice by cardiac-specific expression of carboxyl terminus of hsp70-interacting protein.

Carboxyl terminus of Hsp70-interacting protein (CHIP) is a critical ubiquitin ligase/cochaperone to reduce cardiac oxidative stress, inflammation, cardiomyocyte apoptosis and autophage etc. However, it is unclear whether overexpression of CHIP in the heart would exert protective effects against DOX-induced cardiomyopathy. Cardiac-specific CHIP transgenic (CHIP-TG) mice and the wild-type (WT) littermates were treated with DOX or saline. DOX-induced cardiac atrophy, dysfunction, inflammation, oxidative stress and cardiomyocyte apoptosis were significantly attenuated in CHIP-TG mice. CHIP-TG mice also showed higher survival rate than that of WT mice (40% versus 10%) after 10-day administration of DOX. In contrast, knockdown of CHIP by siRNA in vitro further enhanced DOX-induced cardiotoxic effects. Global gene microarray assay revealed that after DOX-treatment, differentially expressed genes between WT and CHIP-TG mice were mainly involved in apoptosis, atrophy, immune/inflammation and oxidative stress. Mechanistically, CHIP directly promotes ubiquitin-mediated degradation of p53 and SHP-1, which results in activation of ERK1/2 and STAT3 pathways thereby ameliorating DOX-induced cardiac toxicity.