Targeting Macrophage Phenotypes and Metabolism as Novel Therapeutic Approaches in Atherosclerosis and Related Cardiovascular Diseases.

PURPOSE OF THE REVIEW: Macrophage accumulation and activation function as hallmarks of atherosclerosis and have complex and intricate dynamics throughout all components and stages of atherosclerotic plaques. In this review, we focus on the regulatory roles and underlying mechanisms of macrophage phenotypes and metabolism in atherosclerosis. We highlight the diverse range of macrophage phenotypes present in atherosclerosis and their potential roles in progression and regression of atherosclerotic plaque. Furthermore, we discuss the challenges and opportunities in developing therapeutic strategies for preventing and treating atherosclerotic cardiovascular disease. RECENT FINDINGS: Dysregulation of macrophage polarization between the proinflammatory M1 and anti-inflammatory M2 phenotypealters the immuno-inflammatory response during atherosclerosis progression, leading to plaque initiation, growth, and ultimately rupture. Altered metabolism of macrophage is a key feature for their function and the subsequent progression of atherosclerotic cardiovascular disease. The immunometabolism of macrophage has been implicated to macrophage activation and metabolic rewiring of macrophages within atherosclerotic lesions, thereby shifting altered macrophage immune-effector and tissue-reparative function. Targeting macrophage phenotypes and metabolism are potential therapeutic strategies in the prevention and treatment of atherosclerosis and atherosclerotic cardiovascular diseases. Understanding the precise function and metabolism of specific macrophage subsets and their contributions to the composition and growth of atherosclerotic plaques could reveal novel strategies to delay or halt development of atherosclerotic cardiovascular diseases and their associated pathophysiological consequences. Identifying biological stimuli capable of modulating macrophage phenotypes and metabolism may lead to the development of innovative therapeutic approaches for treating patients with atherosclerosis and coronary artery diseases.

Non-Traditional Risk Factors as Contributors to Cardiovascular Disease.

Cardiovascular disease (CVD) remains one of the primary causes of morbidity and mortality worldwide. Classic cardiovascular risk factors, such as hypertension, diabetes mellitus (DM), hyperlipidemia, and smoking, have been well identified and given increased attention in clinical practice. However, the incidence and prevalence of CVD remains high, especially in developing countries. Therefore, there has been more attention to non-traditional CVD risk factors such as gut microbiota, sleep disorders, dietary structure, and psychosocial factors in their important roles in the development of CVD. In this review we summarize the association of non-traditional risk factors with CVD with the aim of further reducing the risk of CVD.

Discordance of Circulating Non-HDL Cholesterol with LDL Cholesterol Concerning Long-Term Prognosis in Statin-Treated Individuals with Acute Coronary Syndrome and Previous Coronary Artery Bypass Grafting Undergoing Percutaneous Coronary Intervention.

Background: Some individuals who maintain desirable low-density lipoprotein cholesterol (LDL-C) levels still experience the progression of atherosclerosis, which may eventually lead to cardiovascular events. Non-high-density lipoprotein cholesterol (non-HDL-C) levels are quantified to assess residual risk in statin-treated patients with coronary heart disease. The study aimed to estimate the predictive performance of discordance between non-HDL-C and LDL-C on clinical prognosis in statin-treated patients with previous coronary artery bypass grafting (CABG). Methods: 468 statin-treated patients with previous CABG undergoing percutaneous coronary intervention (PCI) as a secondary coronary treatment due to acute coronary syndrome (ACS) were retrospectively enrolled in this study. The definition of major adverse cardiovascular events (MACEs) was a composite endpoint of cardiovascular death, recurring myocardial infarction, and a need for repeat revascularization. Cox proportional hazards modeling, restricted cubic splines regression, and discordance analysis were conducted to the association between all lipid parameters and the occurrence of MACEs. Discordant values were defined as LDL-C concentrations ≤ 1.8 mmol/L accompanied by non-HDL-C > 2.6 mmol/L. Results: MACEs occurred in 95 patients over a median follow-up period of 744.5 days. Cox models demonstrated that increased concentrations of non-HDL-C and LDL-C levels were independent risk indicators of MACEs (p < 0.001). The restricted cubic spline analysis revealed a linear relationship between non-HDL-C concentrations and MACEs (p-nonlinear: 0.26), whereas a nonlinear relationship was observed between LDL-C concentrations and MACEs (p < 0.01). In the subgroup analysis, the spline curves revealed that the odds of the individuals with desirable LDL-C levels suffering MACEs emerged when non-HDL-C levels were above 2.07 mmol/L. Individuals who exhibited discordance involving high non-HDL-C/low LDL-C levels had an elevated risk of experiencing MACEs compared to those with concordantly low LDL-C and low non-HDL-C levels [hazard ratios (HRs) = 2.44, 95% confidence interval (CI) = 1.14-5.22, p = 0.02]. Conclusions: Non-HDL-C levels could predict the residual risk of MACEs in ACS patients with previous CABG and statin therapy that underwent percutaneous coronary intervention. A discordance between non-HDL-C and LDL-C in individuals with desirable LDL-C levels could be useful in identifying those with a residual risk of cardiovascular complications.

Adeno-associated virus-mediated in vivo suppression of expression of EPHX2 gene modulates the activity of paraventricular nucleus neurons in spontaneously hypertensive rats.

BACKGROUND: Hypertension can be attributed to increased sympathetic activities. Presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus are capable of modulating sympathetic outflow, thus contributing to the pathogenesis of neurogenic hypertension. Epoxyeicosatrienoic acids (EETs) were reported to have anti-hypertensive effects, which could be degraded by soluble epoxide hydrolase (sEH), encoded by EPHX2. However, the potential effect of EETs on PVN neuron activity and the underlying molecular mechanism are largely unknown. METHODS: Knockdown of EPHX2 in spontaneously hypertensive rats (SHRs) was achieved by tail-intravenous injection of AAV plasmid containing shRNA targeting EPHX2. Whole-cell patch clamp was used to record action potentials of PVN neurons. An LC-MS/MS System was employed to determine 14,15-EET levels in rat cerebrospinal fluid. qPCR and western blotting were applied to examine the expression level of EPHX2 in various tissues. ELISA and immunofluorescence staining were applied to examine the levels of ATP, D-serine and glial fibrillary acidic protein (GFAP) in isolated astrocytes. RESULTS: The expression level of EPHX2 was higher, while the level of 14,15-EET was lower in SHRs than normotensive Wistar-Kyoto rats (WKY) rats. The spike firing frequency of PNV neurons in SHRs was higher than in WKY rats at a given stimulus current, which could be reduced by either EPHX2 downregulation or 14,15-EET administration. In isolated hypothalamic astrocytes, the elevated intracellular ATP or D-serine induced by Angiotensin II (Ang II) treatment could be rescued by 14,15-EET addition or 14,15-EET combing serine racemase (SR) downregulation by siRNA, respectively. Furthermore, 14,15-EET treatment reduced the Ang II-induced elevation of GFAP immunofluorescence. CONCLUSIONS: The elevation of EET levels by EPHX2 downregulation reduced presympathetic neuronal activity in the PVN of SHRs, leading to a reduced sympathetic outflow in hypertension rats. The ATP/SR/D-serine pathway of astrocytes is involved in EET-mediated neuroprotection.

Nomogram for Risk Prediction of Mortality for Patients with Critical Cardiovascular Disease Treated by Continuous Renal Replacement Therapy in Coronary Care Unit.

Aims: To establish a nomogram-scoring model for evaluating the risk of death in patients with critical cardiovascular disease after continuous renal replacement therapy (CRRT) in a coronary care unit (CCU). Methods: This retrospective cohort study included data collected on 172 patients, in whom CRRT was initiated in the CCU between January 2017 and June 2021. Predictors of mortality were selected using an adaptive least absolute shrinkage and selection operator logistic model and used to construct a nomogram. The nomogram was evaluated using the concordance index (C-index) and Hosmer-Lemeshow test. Results: The number of patients who died in-hospital after CRRT was 91 (52.9%). The results of the multivariate logistic regression analyses clarified that age, history of hypertension and/or coronary artery bypass grafting, a diagnosis of unstable angina pectoris or acute myocardial infarction, ejection fraction, systolic blood pressure, creatinine, neutrophil, and platelet counts before CRRT initiation were significant predictors of early mortality in patients treated with CRRT. The nomogram constructed on these predictors demonstrated significant discriminative power with an unadjusted C-index of 0.902 (95% CI: 0.858-0.945) and a bootstrap-corrected C-index of 0.875. Visual inspection showed a good agreement between actual and predicted probabilities (Hosmer-Lemeshow χ 2 = 5.032, p-value = 0.754). Conclusions: Our nomogram based on nine readily available predictors is a reliable and convenient tool for identifying critical patients undergoing CRRT at risk of mortality in the CCU.

First post-discharge heart rate and long-term prognosis in patients with acute myocardial infarction.

BACKGROUND: Elevated heart rate (HR) is associated with cardiovascular mortality and other events associated with acute myocardial infarction (AMI). The heart rate after discharge is likely superior to reflect the deteriorating heart function, which negatively responds to normal physical activity. This study aimed to explore the effect of HR at the first outpatient visit on clinical outcomes. METHODS: We retrospectively identified 605 patients with AMI. HRs at admission, discharge, and first outpatient visits were measured. The primary endpoint was defined as major adverse cardiovascular events (MACEs), including cardiovascular (CV) death, readmission for worsening heart failure, recurrent nonfatal myocardial infarction (MI), repeated coronary revascularization, and ischemic stroke. RESULTS: During the follow-up period, 145 cases of MACE occurred, including 34 CV deaths, 31 recurrent MI, 89 revascularizations, 41 heart failures, and 4 strokes. The event group displayed an elevated HR at the first outpatient visit compared to the event-free group (p < 0.001). After adjustment for confounding risk factors, Cox models showed that the outpatient HR had the best correlation with MACE [Hazard ratio (HR) = 1.33, 95% confidence interval (CI) = 10.8-59.3, p < 0.01 for increments of 1 standard deviation (SD) in the outpatient HR) and CV mortality (HR = 1.18, 95% CI = 1.052-1.325, p < 0.01) compared with the other two HRs. The restricted spline model indicated that HR at the first post-discharge above 71 bpm was associated with CV mortality. CONCLUSIONS: Elevated HR at the first outpatient visit over a period of 2-4 weeks is related to the adverse outcomes of AMI and may identify AMI patients at higher risk of CV mortality.

Prediction of SYNTAX score II improvement by adding temporal heart rate changes between discharge and first outpatient visit in patients with acute myocardial infarction.

BACKGROUND: The prognostic ability of the temporal changes in resting heart rate (ΔHR) in patients with acute myocardial infarction (AMI) for cardiovascular (CV) mortality and clinical outcomes is rarely examined. This study investigated the predictive value of ΔHR using models with SYNTAX score II (SxS-II) for the long-term prognosis of patients with AMI. METHODS: Six hundred five AMI patients with vital signs recorded at the first outpatient visit (2-4 weeks after discharge) were retrospectively recruited into this study. The changes between discharge and outpatient resting heart rate (D-O ΔHR) were calculated by subtracting the HR at the first post-discharge visit from the value recorded at discharge. The major adverse cardiovascular and cerebrovascular events (MACCE) include cardiovascular death, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predictive values and reclassification ability of the different models were assessed using a likelihood ratio test, Akaike's information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: During the follow-up period, a drop-in resting heart rate (RHR) from discharge to first outpatient visit was independently associated with less risk of CV mortality [D-O ΔHR: hazards ratio (HR) = 0.97, 95% CI = 0.96-0.99, P < 0.001] and MACCE (HR = 0.98, 95% CI = 0.97-0.99, p = 0.001). The likelihood test indicated that the combined model of SxS-II and D-O ΔHR yielded the lowest AIC for CV mortality and MACCE (P < 0.001). Moreover, D-O ΔHR alone significantly improved the net reclassification and integrated discrimination of the models containing SxS-II for CV mortality and MACCE (CV mortality: NRI = 0.5600, P = 0.001 and IDI = 0.0759, P = 0.03; MACCE: NRI = 0.2231, P < 0.05 and IDI = 0.0107, P < 0.05). CONCLUSIONS: The change in D-O ΔHR was an independent predictor of long-term CV mortality and MACCE. The D-O ΔHR combined with SxS-II could significantly improve its predictive probability.

One-Stop Hybrid Coronary Revascularization Versus Off-Pump Coronary Artery Bypass Grafting.

One-stop hybrid coronary revascularization (HCR) is a promising revascularization strategy for treating multivessel coronary artery disease (MVCAD). However, its safety and feasibility remain controversial. Therefore, we introduced our experience with midterm follow-up of HCR in patients with MVCAD and compared it with conventional off-pump coronary artery bypass grafting (CABG).Patients with MVCAD undergoing one-stop HCR at Beijing Chaoyang Hospital between March 2018 and December 2020 were retrospectively enrolled. These patients were matched in a 1:2 ratio to patients treated with off-pump CABG at the same period via a propensity score analysis with the nearest neighbor matching algorithm.In the adjusted analysis, no significant difference was found in the rate of perioperative myocardial infarction, stroke, death, prolonged ventilation, reoperation for bleeding, and renal failure between the HCR group and the CABG group. No in-hospital repeated revascularization occurred in either group. HCR was associated with lower blood transfusion rate (HCR 11.0% versus CABG 22.8%; P = 0.006) and shorter postoperative length of stay (> 10 days: 31.5% versus 81.0%; P < 0.001) compared with CABG. After the median 21-month follow-up, no significant difference was found in the major adverse cardiac and cerebrovascular events (MACCE), death, myocardial infarction, repeated revascularization, and stroke rate. Besides, the freedom-from MACCE survival rate was similar between the two groups.One-stop HCR seemed to be a safe and feasible revascularization strategy in patients with MVCAD, with faster recovery and similar outcomes when compared with off-pump CABG.

Altered synthesis of genes associated with short-chain fatty acids in the gut of patients with atrial fibrillation.

BACKGROUND: The gut microbiota provides health benefits in humans by producing short-chain fatty acids (SCFAs), whose deficiency causes multiple disorders and inflammatory diseases. However, gut bacteria producing SCFAs in patients with atrial fibrillation (AF), an arrhythmia with increasing prevalence, have not been reported. To investigate major gut microbial organisms related to SCFA synthesis, SCFAs-associated KEGG orthologues (KOs), enzymatic genes, and potential producers were examined according to metagenomic data-mining in a northern Chinese cohort comprising 50 non-AF control and 50 AF patients. RESULTS: Compared with non-AF controls, individuals with AF had marked differences in microbial genes involved in SCFA-related synthesis, including 125 KOs and 5 SCFAs-related enzymatic genes. Furthermore, there were 10 species that harbored SCFA-synthesis related enzymatic genes, and were markedly decreased in the gut of AF patients. Notably, discriminative features about SCFA-synthesis related function, including 8 KOs (K01752, K01738, K00175, K03737, K01006, K01653, K01647 and K15023), 4 genes (menI, tesB, yciA and CO dehydrogenase acetyl-CoA synthase complex) and 2 species (Coprococcus catus and Firmicutes bacterium CAG:103), were selected as key factors based on LASSO analysis. Furthermore, PLS-SEM analysis showed that 72.8 and 91.14 % of the overall effects on gut microbiota diversity and key species on AF, respectively, were mediated by the key KOs. Meanwhile, 46.31 % of the total effects of SCFA-synthesis related function on left atrial enlargement was mediated by hsCRP. Upon incorporation of clinical properties in AF, the KO score was still significantly associated with AF incidence (OR = 0.004, P = 0.001). CONCLUSIONS: The current study revealed that dysbiotic gut microbiota in AF is coupled with disrupted SCFA-synthesis related genes, characterized by decreased abundances of KEGG orthologues, synthesis enzymatic genes and harboring species.

Predictive value of ACEF II score in patients with multi-vessel coronary artery disease undergoing one-stop hybrid coronary revascularization.

BACKGROUND: We aimed to investigate the predictive value of recently updated ACEF II score on major adverse cardiac and cerebrovascular events (MACCE) in patients with multi-vessel coronary artery disease (MVCAD) undergoing one-stop hybrid coronary revascularization (HCR). METHODS: Patients with MVCAD undergoing one-stop HCR were retrospectively recruited from March 2018 to September 2020. Several prediction risk models, including ACEF II score, were calculated for each patient. Kaplan-Meier curve was used to evaluate freedom from cardiac death and MACCE survival rates. Differences of prediction performance among risk scores for predicting MACCE were compared by receiver operating characteristic (ROC) curve. RESULTS: According to the ACEF II score, a total of 120 patients undergoing one-stop HCR were assigned to low-score group (80 cases) and high-score group (40 cases). During the median follow-up time of 18 months, the incidence of MACCE in the low-score group and high-score group were 8.8 % and 37.5 %, respectively (p < 0.001); and the cardiac death rate of the two were 2.5% and 12.5%, respectively (p < 0.05). Moreover, the cumulative freedom from cardiac death (97.5% vs. 86.8, p < 0.05) and MACCE (75.2% vs. 52.8%, p < 0.001) survival rates in the high-score group were significantly lower than in the low-score group. According to the Cox proportional hazards regression, the ACEF II score was an independent prognostic indicator for MACCE with hazards ratio (HR) 2.24, p = 0.003. The ROC curve analysis indicated that the areas under the curve (AUC) of MACCE from the ACEF II score was 0.740 (p < 0.001), while the AUC of MACCE from the SYNTAX score II CABG was 0.621 (p = 0.070) and the AUC from the EuroSCORE II was 0.703 (p < 0.001). Thus, the accurate predictive value of ACEF II score was similar to the EuroSCORE II but much higher than the SYNTAX score II CABG. CONCLUSIONS: The updated ACEF II score is a more convenient and validated prediction tool for MACCE in patients with MVCAD undergoing one-stop HCR comparing to other risk models.

The long-term impact of a chronic total occlusion in a non-infarct-related artery on acute ST-segment elevation myocardial infarction after primary coronary intervention.

OBJECTIVES: To investigate the long-term outcome of patients with acute ST-segment elevation myocardial infarction (STEMI) and a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) and the risk factors for mortality. METHODS: The enrolled cohort comprised 323 patients with STEMI and multivessel diseases (MVD) that received a primary percutaneous coronary intervention between January 2008 and November 2013. The patients were divided into two groups: the CTO group (n = 97) and the non-CTO group (n = 236). The long-term major adverse cardiovascular and cerebrovascular events (MACCE) experienced by each group were compared. RESULTS: The rates of all-cause mortality and MACCE were significantly higher in the CTO group than they were in the non-CTO group. Cox regression analysis showed that an age ≥ 65 years (OR = 3.94, 95% CI: 1.47-10.56, P = 0.01), a CTO in a non-IRA(OR = 5.09, 95% CI: 1.79 ~ 14.54, P < 0.01), an in-hospital Killip class ≥ 3 (OR = 4.32, 95% CI: 1.71 ~ 10.95, P < 0.01), and the presence of renal insufficiency (OR = 5.32, 95% CI: 1.49 ~ 19.01, P = 0.01), stress ulcer with gastraintestinal bleeding (SUB) (OR = 6.36, 95% CI: (1.45 ~ 28.01, P = 0.01) were significantly related the 10-year mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 (OR = 2.97,95% CI:1.46 ~ 6.03, P < 0.01) and the presence of renal insufficiency (OR = 5.61, 95% CI: 1.19 ~ 26.39, P = 0.03) were significantly related to the 10-year mortality of patients with STEMI and a CTO. CONCLUSIONS: The presence of a CTO in a non-IRA, an age ≥ 65 years, an in-hospital Killip class ≥ 3, and the presence of renal insufficiency, and SUB were independent risk predictors for the long-term mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 and renal insufficiency were independent risk predictors for the long-term mortality of patients with STEMI and a CTO.

Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation.

Alternations of gut microbiota (GM) in atrial fibrillation (AF) with elevated diversity, perturbed composition and function have been described previously. The current work aimed to assess the association of GM composition with AF recurrence (RAF) after ablation based on metagenomic sequencing and metabolomic analyses and to construct a GM-based predictive model for RAF. Compared with non-AF controls (50 individuals), GM composition and metabolomic profile were significantly altered between patients with recurrent AF (17 individuals) and non-RAF group (23 individuals). Notably, discriminative taxa between the non-RAF and RAF groups, including the families Nitrosomonadaceae and Lentisphaeraceae, the genera Marinitoga and Rufibacter and the species Faecalibacterium spCAG:82, Bacillus gobiensis and Desulfobacterales bacterium PC51MH44, were selected to construct a taxonomic scoring system based on LASSO analysis. After incorporating the clinical factors of RAF, taxonomic score retained a significant association with RAF incidence (HR = 2.647, P = .041). An elevated AUC (0.954) and positive NRI (1.5601) for predicting RAF compared with traditional clinical scoring (AUC = 0.6918) were obtained. The GM-based taxonomic scoring system theoretically improves the model performance, and the nomogram and decision curve analysis validated the clinical value of the predicting model. These data provide novel possibility that incorporating the GM factor into future recurrent risk stratification.

Myofibroblast-Derived Exosomes Contribute to Development of a Susceptible Substrate for Atrial Fibrillation.

OBJECTIVE: Atrial fibrosis plays a critical role in atrial fibrillation (AF). A key event in the pathogenesis of fibrosis is the activation of fibroblasts (FBs) into myofibroblasts (MFBs). Paracrine factors released from MFBs lead to ion channel expression changes in cardiomyocytes (CMs). Downregulation of L-type calcium channel Cav1.2 expression is a hallmark of AF-associated ionic remodeling. However, whether exosome (Exo)-mediated crosstalk between MFBs and CMs regulates Cav1.2 expression remains unknown. METHODS: Atrial FBs and CMs were isolated and cultured from neonatal rats by enzymatic digestion. The activation of FBs into MFBs was induced by angiotensin II. Co-culture assay and in vitro Exo treatment were used to determine the effect of MFB-derived Exos on Cav1.2 expression. Confocal Ca2+ imaging was performed to examine the adrenergic stimulation-elicited Ca2+ influx signals. The levels of potential Cav1.2-inhibitory microRNAs (miRNAs) were measured by qRT-PCR. RESULTS: Untreated FBs expressed limited amounts of alpha smooth muscle actin (α-SMA), while angiotensin II induced a significant upregulation of α-SMA-expressing MFBs. Co-cultures of MFBs and CMs resulted in downregulation of Cav1.2 expression in CMs, which was largely abolished by pretreatment of MFBs with exosomal inhibitor GW4869. More importantly, treatment with MFB-derived Exos caused repression of Cav1.2 expression in CMs. Additionally, the adrenergic receptor agonist-elicited Ca2+ influx signals in CMs were remarkably attenuated by pretreatment with MFB-derived Exos, corresponding to the paralleled change in Cav1.2 expression. Finally, miR-21-3p, a potential Cav1.2-inhibitory miRNA, was enriched in MFB-derived Exos and upregulated in CMs in response to MFB-derived Exos. CONCLUSION: We uncover an Exo-mediated crosstalk between MFBs and CMs, contributing to increased vulnerability to AF by reducing the expression of Cav1.2 in CMs.

Blood group A: a risk factor for heart rupture after acute myocardial infarction.

INTRODUCTION: Studies have been performed to identify the association between ABO blood groups and coronary artery disease. However, data is scarce about the impact of ABO blood groups on heart rupture (HR) after acute myocardial infarction (AMI). METHODS: We conducted a retrospective case-control study that included 61 consecutive patients with HR after AMI during a period from 1 January 2012 to 1 December 2019. The controls included 600 patients who were selected randomly from 8143 AMI patients without HR in a ratio of 1:10. Univariate and multivariate logistic regression analysis were used to identify the association between ABO blood groups and HR. RESULTS: Patients with blood group A had a greater risk of HR after AMI than those with non-A blood groups (12.35% vs 7.42%, P < 0.001). After adjusting for age, gender, heart rate at admission, body mass index (BMI), and systolic blood pressure (SBP), blood group A was independently related to the increased risk of HR after AMI (OR = 2.781, 95% CI 1.174-7.198, P = 0.035), and remained as an independent risk factor of HR after AMI in different multivariate regression models. CONCLUSION: Blood group A is significantly associated with increased HR risk after AMI.

Prognostic values of the SYNTAX score II and the erythrocyte sedimentation rate on long-term clinical outcomes in STEMI patients with multivessel disease: a retrospective cohort study.

BACKGROUND: There is a paucity of evidence on the combination of the SYNTAX score II (SSII) and erythrocyte sedimentation rate (ESR) in assessing the long-term prognosis of patients with ST-elevated myocardial infarction (STEMI) and multivessel disease. The objective of this study was to investigate whether the ESR could enhance the predictive value of SSII on the long-term prognosis of STEMI patients. METHODS: A retrospective cohort study involving 483 STEMI and multivessel disease subjects receiving primary percutaneous coronary intervention was conducted. Major adverse cardiovascular events (MACE) included cardiovascular death, acute heart failure, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predicted values of different models were estimated by a likelihood ratio test, Akaike's information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: During the follow-up period of up to 52 months, both the SSII and ESR were independently associated with MACE (hazard ratio [HR] = 1.032, p < 0.001; and HR = 1.021, p < 0.001, respectively). The likelihood test indicated that ESR could improve the prognostic model containing SSII (p < 0.001), while the combined model of SSII and ESR attained a lower AIC (p < 0.001). The area under the ROC curve of the combined model containing SSII and ESR increased by 0.05 (p = 0.04) compared to that of the model with SSII alone. The net reclassification and integrated discrimination of the SSII alone model improved significantly with ESR (NRI = 0.0319, p < 0.001; IDI = 0.0334, p < 0.001). CONCLUSIONS: The prognostic model containing SSII, which is an independent risk factor of MACE, had a significantly enhanced predictive probability with the addition of ESR.

Study on the relationship between telomere length changes and recurrence of atrial fibrillation after radiofrequency catheter ablation.

INTRODUCTION: Advanced age is the foremost risk factor for atrial fibrillation (AF). Telomere length is a surrogate for biological aging, but the association between shortened leukocyte telomere length (LTL) and recurrence of AF (RAF) after ablation remains inconclusive. METHODS: In this prospective analysis, 282 patients underwent an initial catheter ablation for paroxysmal or persistent AF. The association between RAF and LTL was analyzed by univariate and multivariate Cox regression, as well as time-dependent receiver operating characteristic (ROC) analysis and Kaplan-Meier analysis. RESULTS: After a mean follow-up of 14.20 ± 5.04 months, RAF was documented in 78 of the 277 patients who completed the study (28.16%). In Cox proportional hazards models, LTL, age, diagnosis to ablation time (DTAT), N-terminal pronatriuretic peptide, and CHA2DS2-VASc score were significantly associated with RAF. After multivariable adjustment, LTL and DTAT were predicted as independent risk factors for RAF with hazard ratio (HR) of 3.17 (95% confidence interval [CI]: 1.23-8.15, P = 0.017) and 1.43 (95% CI: 1.10-1.86, P = 0.007), respectively. In addition, ROC analysis indicated the potential diagnostic value of LTL with an area under the curve of 0.64 (P < 0.001; sensitivity = 60.3%, specificity = 57.8%), and an optimum cut-off value of 1.040. LTL less than or equal to 1.040 was defined as shortened LTL, while LTL greater than 1.040 nonshortened LTL. Kaplan-Meier analysis showed RAF rate curve was separated significantly between two groups (21.2% vs 35.9%, log-rank test result P = 0.007). Patients with shortened LTL might have a higher risk for RAF with HR = 1.84 (P = 0.008). CONCLUSIONS: Shortened LTL is an independent risk factor for AF recurrence. Shortened LTL could be a potential biomarker in predicting RAF after ablation.

The combined presence of hypertension and vitamin D deficiency increased the probability of the occurrence of small vessel disease in China.

BACKGROUND: The exact relationship between 25-hydroxyvitamin D [25(OH) D] levels and small vessel disease (SVD) are not clear in China. The aim of this study was to determine such the association between 25(OH) D and SVD in China. METHODS: We retrospectively enrolled 106 patients with SVD and 115 controls between Jan 2017 and Dec 2017. All the subjects were categorized into three subgroups according to the level of 25 (OH) D: vitamin D deficiency (< 12 ng/ml), insufficiency (12-20 ng/ml) and sufficiency (> 20 ng/ml). RESULTS: Among 106 SVD patients, 80 (75.5%) were men and the mean age was 61.6 ± 13.2 years. The deficiency of 25(OH) D was observed in 76 (71.7%) of SVD patients and 47 (40.9%) of controls (P = 0.001). Compared with controls, patients with SVD were more likely to be male, a stroke history, smokers, with hyperlipidemia, higher systolic and diastolic blood pressure and low-density lipoprotein, and lower of 25(OH)D level (P < 0.05). Logistic regression analysis revealed the level of 25 (OH) D as an independent predictor of SVD (OR 0.772, 95% CI 0.691-0.862, P = 0.001). Compared with the sufficient 25 (OH) D group, the ORs of SVD in deficient and insufficient 25(OH)D group were 5.609 (95% CI 2.006-15.683) and 1.077 (95% CI: 0.338-3.428) after adjusting for potential confounders, respectively. In hypertensives with vitamin D deficient and insufficient group compared with sufficient group, the ORs of SVD increased to 9.738 (95% CI 2.398-39.540) and 1.108 (95% CI 0.232-5.280), respectively (Pinteraction = 0.001). CONCLUSION: We found significant associations between SVD and 25(OH)D deficiency. The combined presence of hypertension and vitamin D deficiency increased the probability of developing SVD. Our findings will warrant further prospective studies in the future.

Effect modification of hypertension on the association of vitamin D deficiency with severity of coronary stenosis.

AIMS: There may exist an effect modification of hypertension on the relation of vitamin D deficiency with cardiovascular disease. The aim of this study was to investigate this interaction on coronary heart disease. METHODS: We investigated 348 consecutive patients (mean age 62.4 ± 10.5 years; 56.3% male) who underwent coronary angiography because of chest discomfort at our heart center. Serum 25-OH vitamin D was also detected by ELISA method in these patients. Multivariable logistic regression models were used to estimate odd ratios (ORs) of CHD across vitamin D levels in hypertensives and normotensives, respectively. RESULTS: We found the multivariable-adjusted ORs of CHD in the bottom(≤8.5 ng/ml) and middle tertiles (8.5-13 ng/ml) of 25-OH vitamin D were 2.86 (95% confidence interval [CI]: 1.38, 5.92) and 1.63 (0.83, 3.20), respectively, compared with those in top tertiles (>13ng/ml) among hypertensives (Ptrend=0.005). In contrast, the corresponding ORs of the above two groups were 0.88 (0.28, 2.74) and 1.23 (0.42, 4.00), respectively, in the normotensives (Ptrend = 0.800; Peffect modification = 0.020). The multivariable-adjusted OR of CHD in patients with severe hypovitaminosis D (<10 ng/ml) versus those with higher vitamin D (≧10 ng/ml) was also greater in hypertensives (2.76; 95% CI: 1.51, 5.04) than that in normotensives (0.92; 95% CI: 0.37, 2.33; Peffect modification=0.013). Similar results were observed when Gensini Score was treated as a dependent variable. CONCLUSION: Our finding suggests the presence of hypertension may modify the association of vitamin D deficiency with severity of coronary stenosis.

Interaction Between Vitamin D and Lipoprotein (a) on the Presence and Extent of Coronary Heart Disease.

BACKGROUND: Given both lipoprotein (Lp)(a) and vitamin D have been found to be associated with coronary heart disease (CHD) risk and a biochemical link between vitamin D and cholesterol on atherosclerosis has been proposed, we hypothesised there could exist an interaction between Lp(a) and vitamin D on the severity of CHD. METHODS: Lp(a) and 25-OH vitamin D were measured in the plasma of 348 consecutive patients (mean age 62.4±10.5 years; 56.3% male) undergoing coronary angiography at our Heart Center. A multivariate logistic regression model was used to estimate the odds ratios (ORs) of CHD. RESULTS: Of these patients, CHD was identified in 212 (60.9%). A multivariable logistic regression model showed multivariable-adjusted ORs (95% CI) of CHD for patients with Lp(a)≧30mg/dl and vitamin D <10 ng/ml, Lp(a) <30mg/dl and vitamin D <10 ng/ml, and Lp(a)≧30mg/dl and vitamin D ≧10 ng/ml were 4.62 (2.04-10.46), 1.79 (1.00-3.17), and 1.70 (0.88-3.31), respectively, compared with those with Lp(a) <30mg/dl and vitamin D ≧10 ng/ml; the multivariable-adjusted ORs of a higher Gensini Score for the above three corresponding groups were 3.48 (1.84-6.60), 1.59 (0.96-2.65), and 1.55 (0.86-2.79), respectively. The interaction term between Lp(a) and vitamin D in each of the above two models was significant (p=0.004 and p=0.005, respectively). CONCLUSIONS: Among patients undergoing coronary angiography, there existed an interaction between Lp(a) and vitamin D on the severity of CHD. Future cohort studies are warranted to confirm this finding.

Body Mass Index and the Risk of Cardiovascular and All-Cause Mortality Among Patients With Hypertension: A Population-Based Prospective Cohort Study Among Adults in Beijing, China.

BACKGROUND: Studies on the association between body mass index (BMI) and death risk among patients with hypertension are limited, and the results are inconsistent. We investigated the association between BMI and cardiovascular disease (CVD) and all-cause mortality among hypertensive patients in a population of Beijing, China. METHODS: We conducted a prospective cohort study of 2535 patients with hypertension aged 40 to 91 years from Beijing, China. Participants with a history of CVD at baseline were excluded from analysis. Cox proportional hazards regression models were used to estimate the association of different levels of BMI stratification with CVD and all-cause mortality. RESULTS: During a mean follow-up of 8.1 years, 486 deaths were identified, including 233 cases of CVD death. The multivariable-adjusted hazards ratios for all-cause mortality associated with BMI levels (<20, 20-22, 22-24, 24-26 [reference group], 26-28, 28-30, and ≥30 kg/m2) were 2.03 (95% confidence interval [CI], 1.48-2.78), 1.61 (95% CI, 1.18-2.20), 1.30 (95% CI, 0.95-1.78), 1.00 (reference), 1.12 (95% CI, 0.77-1.64), 1.33 (95% CI, 0.90-1.95), and 1.66 (95% CI, 1.10-2.49), respectively. When stratified by age, sex, or smoking status, the U-shaped association was still present in each subgroup (P > 0.05 for all interactions). Regarding the association of BMI with CVD mortality, a U-shaped trend was also observed. CONCLUSIONS: The present study showed a U-shaped association of BMI with CVD and all-cause mortality among patients with hypertension. A lowest risk of all-cause mortality was found among hypertensive patients with BMI between 24 and 26 kg/m2.