The cardiovascular effects of SGLT2 inhibitors, RAS inhibitors, and ARN inhibitors in heart failure.

AIMS: No studies have comprehensively compared the efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitors, renin-angiotensin system (RAS) inhibitors, and angiotensin receptor neprilysin (ARN) inhibitors based on different type of heart failure, including heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The aim of this network meta-analysis was to evaluate the relative efficacy of SGLT2 inhibitor (SGLT2i), RAS inhibitor (RASi) and ARN inhibitor (ARNI) in different types of heart failure. METHODS: A systemic literature search was performed from inception to 19 November 2022 for randomized control trials assessing the risk of cardiovascular (CV) death or hospitalization for heart failure (HHF) of these drugs in HF. A network meta-analysis was performed. Risk ratio (RR) with 95% confidence intervals (CI) were synthesized. RESULTS: Seventeen studies were selected with a total of 61 489 patients. In patients with HFrEF, ARNI led to a reduced risk of a composite outcome of CV death or HHF when compared with placebo (RR = 0.83, 95% CI 0.77-0.89). Similar trends were observed when focusing on the outcome of CV death or HHF alone. In patients with HFpEF, SGLT2i showed the beneficial effects on the CV death or HHF events when compared with placebo and RASi (RR = 0.82, 95% CI 0.74-0.92; RR = 1.16, 95% CI 1.02-1.31). For CV death, all these three drugs could not show beneficial effects in HFpEF. For the incidence of HHF in HFpEF, both SGLT2i and ARNI demonstrated the beneficial effects but SGLT2i was superior to ARNI. There were no differences in the events of discontinuation under these drugs when compared with placebo or each other in either HFrEF or HFpEF patients. SGLT2i showed the least renal injury among these interventions in HFrEF and there were no differences in the incidence of renal injury of these interventions in HFpEF. CONCLUSIONS: Among these drugs, ARNI showed the greatest ability to lower the incidence of CV death or HHF and SGLT2i exerted the least renal injury in patients with HFrEF. In patients with HFpEF, SGLT2i was associated with a reduction in the risk of CV death or HHF. There were no differences in the incidence of renal injury of these interventions in HFpEF. The intolerance of these drugs were comparable in both HFrEF and HFpEF.

Circulating FAM19A5 level is associated with the presence and severity of coronary artery disease.

BACKGROUND: Family with sequence similarity 19 member A5 (FAM19A5) has been identified as a novel adipokine that plays an important role in inhibiting inflammation and vascular smooth muscle cell proliferation. However, the clinical associations between FAM19A5 levels and the presence and severity of coronary artery disease (CAD) remains uncertain. METHODS: We measured serum FAM19A5 levels in 186 CAD patients and 58 non-CAD patients who underwent coronary arteriography (CAG) recruited in Shanxi Medical University Affiliated Second Hospital. The severity of coronary artery stenosis was represented in the Gensini score. Logistic and linear regression analyses were used to analyze the relationship between serum FAM19A5 and CAD. RESULTS: Serum FAM19A5 levels in CAD group were significantly lower than those in the non-CAD group [1.53 (1.13-2.27) ng/mL vs 2.33 (1.69-3.51) ng/mL; P = 0.013]. Logistic regression analysis showed that decreased serum FAM19A5 level was a risk factor for CAD (OR: 0.563, 95% CI: 0.409-0.776, P < 0.001). Circulating FAM19A5 levels were negatively associated with the Gensini score. FAM19A5 had 87.9% sensitivity and 52.7% specificity for identifying CAD. CONCLUSIONS: Serum FAM19A5 levels were negatively associated with the presence and severity of CAD and may represent a novel biomarker for diagnosing and indication the severity of CAD.

Selenium Supplementation Protects Against Lipopolysaccharide-Induced Heart Injury via Sting Pathway in Mice.

Sepsis-induced myocardial dysfunctions are associated with high morbidity and mortality. Selenium, an essential trace element, has been reported to exert anti-inflammation, anti-oxidative stress, and anti-apoptosis. However, the protective effects of selenium on LPS-induced heart injury are still poorly illustrated. Therefore, in the present study, we sought to explore the effects of selenium pretreatment on LPS-induced myocardial injury in mice. We firstly found that selenium pretreatment significantly improved markers of myocardial injury and alleviated LPS-induced myocardial dysfunctions. Moreover, selenium supplementation reduced pro-inflammatory cytokines expression, decreased oxidative stress, and inhibited myocardial apoptosis. In addition, selenium supplementation inactivated the Sting pathway. In conclusion, our study suggests that selenium exerts protective effects on LPS-induced myocardial injury, and the underlying molecular mechanism may be related to the inactivation of Sting pathway, implying a potential therapy for sepsis-induced myocardial dysfunctions.

Diallyl Trisulfide Suppresses Angiotensin II-Induced Vascular Remodeling Via Inhibition of Mitochondrial Fission.

OBJECTIVE: We have shown previously that diallyl trisulfide (DATS) ameliorates mitochondrial fission and oxidative stress in a hyperglycemia-induced endothelial apoptosis and diabetic mouse model. The aim of this study was to investigate whether DATS mitigates Ang II-induced vascular smooth muscle cell (VSMC) phenotypic switching and vascular remodeling, and if so, to determine the underlying molecular events. METHODS: Male C57BL/6 mice were used to establish a vascular remodeling model by continuous 2-week Ang II infusion using a subcutaneous osmotic pump. Animals were intraperitoneally injected with DATS or vehicle. Physiological parameters, vascular morphology, and molecular markers were assessed. For in vitro studies, VSMCs were pretreated with or without DATS for 1 h, then were stimulated with Ang II, and mitochondrial morphology and phenotypic switching of VSMCs were also measured. RESULTS: In primary mouse VSMCs, we found that Drp1-dependent mitochondrial fission regulated mitochondrial reactive oxygen species (mtROS) generation, which eventually promoted Ang II-induced VSMC proliferation, migration, and phenotypic switching. Moreover, Ang II was found to up-regulate the Rho-associated coiled coil-containing protein kinase 1 (ROCK1), which regulated mitochondrial fission and VSMC phenotypic switching by phosphorylating Drp1. However, the biological effect of Ang II was abrogated by DATS. Consistent with the effects in VSMCs, we found that DATS markedly alleviated mitochondrial fission, VSMC differentiation, and vessel wall thickening in an animal model of Ang II-induced vascular remodeling, which was regulated by the ROCK1/Drp1 signal. CONCLUSIONS: Our findings showed that DATS mitigated Ang II-induced vascular remodeling by suppressing Drp1-mediated mitochondrial fission in an ROCK1-dependent manner.

Triptolide reduces ischemia/reperfusion injury in rats and H9C2 cells via inhibition of NF­κB, ROS and the ERK1/2 pathway.

Myocardial ischemia/reperfusion (I/R) induces cardiac cell injury; however, the mechanism underlying cardiac damage remains unclear. A previous study demonstrated that triptolide (TP) exerts protective effects against I/R in cerebral cells. The present study aimed to evaluate the protective effects of TP on cardiac cells, and investigated the potential mechanisms involved in I/R­induced damage. Rats and cardiac H9C2 cells undergoing I/R were pretreated with TP, and cell damage was assessed in vivo and in vitro. Hematoxylin and eosin and terminal deoxynucleotidyl­transferase­mediated dUTP nick end labeling staining were employed to evaluate I/R injury in rat cardiac tissue. Inflammatory factors, including tumor necrosis factor­α, interleukin (IL)­1ß and IL­6, were detected by ELISA. Biochemical analyses were performed to evaluate the bioactivity of superoxide dismutase, malondialdehyde and catalase. In addition, viability of H9C2 cells was measured using the Cell Counting kit 8 assay. Flow cytometry was used to evaluate cell apoptosis and reactive oxygen species (ROS) generation. Furthermore, the expression levels of proteins associated with apoptosis, peroxide and inflammation were measured using western blot analysis. H9C2 cells were also treated with N­acetylcysteine and pyrrolidine dithiocarbamate, and cell injury was assessed after peroxidation or I/R. The results demonstrated that TP exerted a significant protective effect on cardiac cells in vivo and in vitro. TP reduced the inflammatory response, as determined by nuclear factor­κB inhibition. In addition, TP decreased ROS­mediated lipid peroxidation, and reduced ROS generation. TP also inhibited cell apoptosis by activating the extracellular signal­regulated kinase 1/2 pathway. In conclusion, TP may protect cardiac cells from I/R injury; the potential protective mechanisms of TP against I/R include anti­inflammatory action, antioxidation and apoptotic resistance.

Metabolic syndrome and coronary artery calcification: a community-based natural population study.

BACKGROUND: Little is known about the influence of metabolic syndrome (MetS) on coronary artery calcification (CAC) in China. In this article, we aimed to explore the distribution of CAC in populations with and without MetS, and estimate the influence of MetS and its components on CAC in a community-based population of Beijing. METHODS: A total of 1647 local residents of Beijing, age 40-77 years, were recruited for a cardiovascular risk factors survey and were determined fasting plasma glucose (FPG), blood lipids, and 64 multi-detector computed tomography (64-MDCT) coronary artery calcium score (CACS) measurement (Agatston scoring). The distribution of CAC was described, and the influence of MetS components on CAC was evaluated. RESULTS: In this population, the prevalence and extent of CAC increased with increasing age and both were higher in MetS subjects compared to nonMetS subjects (all P < 0.05), with the exception of those older than 65 years old. The risk of CAC increased with increasing numbers of MetS components, and the odds ratios for predicting positive CAC in subjects with 1, 2, 3, and = 4 MetS components were 1.60, 1.84, 2.12, and 3.12, respectively (all P < 0.05). Elevated blood pressure, elevated FPG, elevated triglycerides, and overweight increased the risk of CAC, yielding odds ratios of 2.64, 1.67, 1.32, and 1.37, respectively (all P < 0.05). CONCLUSIONS: In the Beijing community-based population, MetS increases the risk of CAC. The risk of CAC increases with increasing numbers of MetS components. Not only the number, but also the variety of risk factors for MetS is correlated with the risk of CAC. Elevated blood pressure, hyperglycemia, hypertriglyceridemia and overweight increase the risk of CAC.

[Coronary atherosclerosis lesion features in coronary artery disease patients complicating with metabolic syndrome].

PURPOSE: To compare coronary plaque burden, composition, distribution and the degree of coronary artery stenosis in invasive coronary angiography (ICA) diagnosed coronary artery disease (CAD) patients with or without metabolic syndrome (MetS). METHODS: From January 2008 to June 2011, consecutive patients underwent both coronary computed tomography angiography (CCTA) and ICA within three months were enrolled. Patients with history of previous percutaneous coronary interventions (PCI) and coronary artery bypass grafting (CABG) were excluded. Plaque characteristics and maximal luminal diameter stenosis were analyzed on a 16-segment basis as suggested by the American Heart Association classification. RESULTS: The study population consisted of 872 patients [age (60.2 ± 10.0) years, 72.70% males] including 377 patients with MetS and 495 patients without MetS. The median coronary artery calcium score (CACS) was higher in MetS patients than in non-MetS patients [102 (10, 410) vs. 58 (0, 274) , P < 0.01]. Percentage of patients with no coronary artery calcium was significantly lower in MetS group than in non-MetS group [19.63% (74/377) vs. 30.71% (152/495) , P < 0.01], while percentage of patients with severe coronary calcium (CACS ≥ 1000) were significantly higher in MetS than non-MetS group [8.22% (31/377) vs. 4.65% (23/495) , P = 0.03]. The proportion of patients with 1-vessel disease was lower [23.61% (89/377) vs. 36.77% (182/495), P < 0.01], 2-vessel [29.71% (112/377) vs. 22.83% (113/495), P < 0.05] and 3-vessel disease [35.54% (134/377) vs. 24.44% (121/495) , P < 0.01] were higher in MetS group than in non-MetS group. Calcified plaque of LM and the middle and distal coronary artery were significantly higher in MetS group than in non-MetS group (all P < 0.05) . CONCLUSIONS: CAD patients with MetS are associated with severer coronary artery calcium deposition and higher percentage of calcified plaque in the middle and distal coronary arteries and severer obstructive coronary vessels.

Congenital anomalies of coronary arteries in complex congenital heart disease: diagnosis and analysis with dual-source CT.

BACKGROUND: Congenital heart diseases (CHDs) are sometimes associated with coronary artery anomalies (CAAs). Accurate preoperative evaluation of coronary artery anatomy is essential for successful surgical repair of complex CHD. OBJECTIVE: The aim of this study was to evaluate the incidence of congenital CAAs in patients with complex CHD at dual-source CT. METHODS: Four hundred seventeen consecutive patients with complex CHD underwent contrast-enhanced cardiac CT angiography. The results were retrospectively analyzed, including the types and incidences of CAAs in various forms of complex CHD. Each patient was analyzed independently by 2 experienced cardiovascular radiologists. Image quality of coronary arteries was assessed on a 5-point scale with 2 or less being nondiagnostic. RESULTS: Thirty-five of 417 studies were nondiagnostic (8.39%). Sixty-three cases of CAA (15.11%) were detected by anomalous ostia and coronary arteries. CAA was involved in 6 of 108 patients with tetralogy of Fallot (5.56%), 18 of 84 patients with double outlet right ventricle (21.43%), 11 of 97 patients with pulmonary artery atresia (11.34%), 7 of 36 patients with transposition of the great arteries (22.22%), 15 of 41 patients with single ventricle (36.59%), 4 of 12 patients with truncus arteriosus/aortopulmonary window (33.33%), and 2 of 39 patients with interruption of the aortic arch/coarctation of the aorta (5.13%). Twenty of these were accompanied with an anomalous coronary course (31.74%). CONCLUSION: Patients with complex CHD have a higher prevalence of CAAs, which should be considered before surgery. Dual-source CT is an effective technique to visualize and evaluate complex CHD.

[Relation between uric acid and coronary artery calcification:a community-based cross-sectional survey among Beijing natural population].

OBJECTIVE: To investigate the influence of uric acid on coronary artery calcification in the natural population in Beijing. METHODS: From April to July 2012, 903 subjects from the natural population(aged 37-76 years for men, aged 42-76 years for women)in Xishan community, Beijing, were selected to accept a survey on the risk factors of cardiovascular. Blood tests and CT coronary artery calcium scans were carried out. RESULTS: At the 1 Quartile(1 Q), 2 to 3 Quartile(2-3 Q)and 4 Quartile(4 Q)of uric acid levels, the prevalence rates of coronary artery calcium were 37.2% , 45.5% , 60.6% (P<0.001) and the coronary artery calcium scores were (109.7±333.1)AU, (133.9±356.9)AU, (200.8±459.4) AU (P < 0.001)respectively. Data from the univariate logistic regression analysis showed that with the increase of uric acid, the prevalence rates of coronary artery calcium also increased(OR2-3Q = 1.41, 95% CI:1.02-1.95, P = 0.040; OR4Q = 2.60, 95% CI:1.78-3.80, P < 0.001). However, the relationship between uric acid and coronary artery calcium disappeared when using the multivariate logistic regression analysis(OR2-3Q = 0.92, 95% CI: 0.60-1.43, P = 0.713;OR4Q = 1.38, 95% CI:0.80-2.39, P = 0.247). CONCLUSION: Uric acid did not seem to be an independent risk factor for coronary artery calcium, although the prevalence and extent of coronary artery calcium increased along with the increasing trend of uric acid.

Matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) levels in patients with nonobstructive coronary artery disease detected by coronary computed tomographic angiography.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate whether matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) are elevated in patients with nonobstructive coronary artery disease. MATERIALS AND METHODS: Eighty-four patients with nonobstructive coronary artery disease (group A) and 90 patients with no coronary plaques (group B) were enrolled. MMP-9 and MPO levels were compared between the two groups. The relationships between these biomarkers and Framingham risk score were analyzed. Receiver-operating characteristic curves were used to evaluate the ability of these biomarkers to predict the presence of coronary artery plaques. RESULTS: The MMP-9 and MPO values in group A were significantly higher than in group B (P < .001). The levels of MMP-9 and MPO showed significant correlations with Framingham risk score (r = 0.796, P < .001, and r = 0.409, P < .001, respectively). The areas under the receiver-operating characteristic curves for MMP-9 and MPO were 0.80 (95% confidence interval, 0.74-0.87) and 0.74 (95% confidence interval, 0.66-0.81), respectively. CONCLUSIONS: Levels of MMP-9 and MPO are positively correlated with Framingham risk score. Additionally, in patients with nonobstructive coronary artery disease, elevated levels of MMP-9 and MPO may identify patients at risk for future myocardial infarction or sudden cardiac death.

Coronary artery atherosclerosis and risk stratification in young adults with an intermediate pretest likelihood detected by multidetector computed tomography.

RATIONALE AND OBJECTIVES: To document the prevalence of coronary artery disease (CAD) and major adverse cardiac events (MACE) in patients younger than 45 years of age with intermediate pretest likelihood of CAD, and to determine whether coronary computed tomography angiography (cCTA) is useful for risk stratification of this cohort. MATERIALS AND METHODS: We followed 452 intermediate pretest likelihood (according to Diamond and Forrester) outpatients who were suspected of CAD and underwent cCTA. They were all younger than 45 years old. The endpoint was MACE, defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization. RESULTS: Follow-up was completed in 427 patients (94.5%) with a median follow-up period of 1081 days. No plaque was noted in 357 (83.6%) patients. Nonsignificant CAD was noted in 33 (7.7%) individuals and 37 (8.7%) patients with significant CAD. At the end of the follow-up period, 12 (2.8%) patients experienced MACE. The annualized event rate was 0.2% in patients with no plaque, 2.0% in patients with nonsignificant CAD, and 7.3% in patients with significant CAD. Hypertension, smoking, and significant CAD in cCTA were significant predictors of MACE in univariate analysis. Moreover, cCTA remained a predictor (P < .001) of events after multivariate correction (hazard ratio: 8.345, 95% CI: 3.438-17.823, P < .001). CONCLUSION: The prevalence of CAD and MACE in young adults with an intermediate pretest likelihood of CAD was considerable. cCTA is effective in restratifying patients into either a low or high posttest risk group. These results further emphasize the usefulness of cCTA in this cohort.

[Studies on use and residue levels of pesticides in fruit and vegetable in Tianjin Area and its control measures].

OBJECTIVE: To investigate pesticide abuse on fruits and vegetables in Tianjin Area, to detect pesticide residues in fruits and vegetables, to study the methods for reducing pesticide residues in fruits and vegetables. METHODS: (1) A questionnaire on the pesticide application during growing fruit and vegetable was administered to 185 farmers in Tianjin Area. (2) According to the information from the questionnaire survey, fruit and vegetable samples were collected in four seasons around the year and measured for organophosphorus pesticide residues by gas chromatography. (3) Fruit and vegetable samples contained pesticide residue were treated by scald, immersion in 0.15% and 0.30% detergent solution, immersion in pure water, peeling and cutting root and pesticide residues were measured before and after the treatment. RESULTS: The percentage of pesticide abuse in growing fruit and vegetable was 65.00% in Tianjin area, and 31.60% of the fruits and vegetable samples collected in summer were positive for high toxic organophosphorus pesticides. Significant decrease of pesticide residue in fruit and vegetable was found by scald, immersion in 0.15% and 0.30% detergent solution, as well as peeling and cutting root, and over 80.00% pesticide residue in the samples could be reduced by scald. CONCLUSIONS: It is necessary to strengthen pesticide abuse control and market surveillance and inspection, in order to reduce the harmful effects of pesticide residue in fruit and vegetables to human health.