Danger-associated metabolites trigger metaflammation: A crowbar in cardiometabolic diseases.

Cardiometabolic diseases (CMDs) are characterized by a series of metabolic disorders and chronic low-grade inflammation. CMDs contribute to a high burden of mortality and morbidity worldwide. Host-microbial metabolic regulation that triggers metaflammation is an emerging field of study that promotes a new perspective for perceiving cardiovascular risks. The term metaflammation denotes the entire cascade of immune responses activated by a new class of metabolites known as "danger-associated metabolites" (DAMs). It is being proposed by the present review for the first time. We summarize current studies covering bench to bedside aspects of DAMs to better understand CMDs in the context of DAMs. We have focused on the involvement of DAMs in the pathophysiological development of CMDs, including the disruption of immune homeostasis and chronic inflammation-triggered damage leading to CMD-related adverse events, as well as emerging therapeutic approaches for targeting DAM metabolism in CMDs.

Remnant cholesterol associates with hypertension beyond low-density lipoprotein cholesterol among the general US adult population.

Background: Previous findings have indicated that elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are associated with hypertension. We aim to explore whether higher RC levels may be associated with hypertension beyond LDL-C in the general US adult population. Methods: This study included 10,842 adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Weighted multivariable logistic regression models were used to estimate the odds ratios (ORs) of hypertension for LDL-C and RC. We also performed analyses examining the association between hypertension and LDL-C vs. RC concordant/discordant groups. Results: A total of 4,963 (41.54%, weighted) individuals had hypertension. The weighted median levels were LDL-C: 118mg/dL, RC: 20mg/dL. At lower LDL-C clinical cut-point, the proportion of discordantly high RC dramatically increased. After multivariable adjustment, log RC was associated with higher prevalence of hypertension [OR 2.54, 95% confidence interval (CI) 2.17-2.99]. Participants with the highest tertile of RC were more likely to have hypertension (OR 2.18; 95% CI 1.89-2.52) compared with those with the lowest tertile of RC. This association remained marked after including body mass index (BMI), LDL-C, high-density lipoprotein cholesterol (HDL-C) or triglycerides. The association between LDL-C and hypertension was absent after adjusting for BMI, RC or triglycerides. Compared with low LDL-C/low RC group, the discordant low LDL-C/high RC group was associated with hypertension (OR 2.04; 95% CI 1.72-2.42), whereas the high LDL-C/low RC group was not, regardless of BMI, HDL-C or triglycerides. Similar results were observed when examining discordance among different clinical cut-points, except for the cut-point of LDL-C 70 mg/dL and RC 13 mg/dL. To better understand the association, we performed an additional analysis, which showed that among participants with apolipoprotein B < median (92mg/dL), those with discordant RC ≥ median (20mg/dL) had significantly higher odds of having hypertension (OR 1.73; 95% CI 1.38-2.17). Conclusion: RC was associated with hypertension beyond LDL-C in the general US adult population. This association went beyond increased triglycerides levels, and lipoproteins other than apoB may be involved.

Causal associations of remnant cholesterol with cardiometabolic diseases and risk factors: a mendelian randomization analysis.

BACKGROUND: Emerging evidence suggests that remnant cholesterol (RC) is strongly associated with an increased incidence of cardiometabolic diseases (CMD). However, the causality have not been confirmed. We aimed to evaluate the causal associations of RC with CMD and the relative risk factors using two-sample Mendelian randomization (MR) methods. METHODS: Summary-level statistics of RC, CMD, and cardiometabolic risk factors were obtained from the published data from individuals with a predominantly European ancestry mainly from the UK Biobank and the FinnGen biobank. Univariable and multivariable MR analyses were used to evaluate the causal relationships between RC and CMD. A bidirectional MR analysis was performed to estimate the causality between RC and cardiometabolic risk factors. The main MR method was conducted using the inverse-variance weighted method. RESULTS: Univariable MR analyses showed that genetically predicted RC was causally associated with higher risk of ischemic heart disease, myocardial infarction, atrial fibrillation and flutter, peripheral artery disease, and non-rheumatic valve diseases (all P < 0.05). Multivariable MR analyses provided compelling evidence of the harmful effects of RC on the risk of ischemic heart disease (P < 0.05). Bidirectional MR analysis demonstrated that RC was bidirectionally causally linked to total cholesterol, triglycerides, low-density lipoprotein cholesterol, hypercholesterolemia (all P < 0.05). However, no genetic association was found between RC and metabolic disorders or the other cardiometabolic risk factors. CONCLUSIONS: This MR study demonstrates that genetically driven RC increases the risk of several CMD and cardiometabolic risk factors, suggesting that targeted RC-lowering therapies may be effective for the primary prevention of CMD.

Potential benefits of spicy food consumption on cardiovascular outcomes in patients with diabetes: A cohort study of the China Kadoorie Biobank.

OBJECTIVES: Dietary capsaicin from spicy foods has potential benefits for those with cardiometabolic diseases (CMDs). However, to our knowledge there is no evidence linking spicy food consumption with cardiovascular outcomes in individuals with diabetes. The aim of this study was to explore the association between spicy food consumption and the incidence of major adverse cardiovascular events (MACEs) in individuals with diabetes from the CKB (China Kadoorie Biobank) study and to provide evidence-based dietary recommendations for those with CMDs. METHODS: This prospective study enrolled 26 163 patients from the CKB study who had diabetes without coronary heart disease, stroke, or cancer to our knowledge. Of the 26 163 patients enrolled, 17 326 never or rarely ate spicy food (non-spicy group), and 8837 ate spicy food ≥1 d/wk (spicy group). The primary outcomes were MACEs, including cardiac death, non-fatal myocardial infarction, and stroke. Cox proportional hazards models were used to estimate the hazard ratio (HR) of MACEs and their associated 95% confidence intervals (CIs). RESULTS: During a median follow-up of 8.5 y, MACEs occurred in 5465 participants (20.9%), with 3820 (22%) and 1645 (18.6%) cases occurring in the non-spicy and spicy groups, respectively. Spicy food consumption was independently associated with a decreased tendency for MACEs, with an adjusted HR of 0.94 (95% CI, 0.89-1.00; P = 0.041). Subgroup analysis showed consistency in the results that the regular spicy eating groups were associated with significantly lower incidence of MACEs than the non-spicy group. There was no statistical difference in the incidence of MACEs among the three different spicy eating frequency groups. CONCLUSION: This cohort study revealed that the consumption of spicy food was independently associated with a reduced incidence of adverse cardiovascular events in Chinese adults with diabetes, suggesting a beneficial effect on cardiovascular health. Further studies are needed to confirm the association between the consumption of different doses of spicy food and cardiovascular outcomes and the exact mechanism of action.

Whole genome methylation combined with RNA-seq reveals the protective effects of Gualou-Xiebai herb pair in foam cells through DNA methylation mediated PI3K-AKT signaling pathway.

DNA methylation, including aberrant hypomethylation and hypermethylation, plays a significant role in atherosclerosis (AS); therefore, targeting the unbalanced methylation in AS is a potential treatment strategy. Gualou-xiebai herb pair (GXHP), a classic herb combination, have been used for the treatment of atherosclerotic-associated diseases in traditional Chinese medicine. However, the effects and underlying mechanism of GXHP on AS remain nebulous. In this study, the CCK-8 method was applied to determine the non-toxic treatment concentrations for GXHP. The formation of foam cells played a critical role in AS, so the foam cells model was established after RAW264.7 cells were treated with ox-LDL. The contents of total cholesterol (TC) and free cholesterol (FC) were determined by Gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was used to check the expressions of inflammatory factors including IL-1ß, TNF-α, and VCAM-1. Methyl-capture sequencing (MC-seq) and RNA-seq were applied to observe the changes in genome-wide DNA methylation and gene expression, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyze differentially methylated genes (DMGs) and differentially expressed genes (DEGs). The targeted signaling pathway was selected and verified using western blotting (WB). The results showed that the lipids and inflammatory factors in foam cells significantly increased. GXHP significantly reduced the expression of TC, FC, and inflammatory factors. MC-seq and RNA-seq showed that GXHP not only corrected the aberrant DNA hypermethylation, but also DNA hypomethylation, thus restored the aberrant DEGs in foam cells induced by ox-LDL. GXHP treatment may target the PI3K-Akt signaling pathway. GXHP reduced the protein levels of phosphorylated(p)-PI3K and p-AKT in foam cells. Our data suggest that treatment with GXHP showed protective effects against AS through the inhibition of DNA methylation mediated PI3K-AKT signaling pathway, suggesting GXHP as a novel methylation-based agent.

Potential Benefits of Selenium Supplementation in Reducing Insulin Resistance in Patients with Cardiometabolic Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Selenium is a trace element that has been reported to be effective in regulating glucose and lipid metabolism. However, there is conflicting evidence from different clinical trials of selenium supplementation in treating cardiometabolic diseases (CMDs). OBJECTIVE: This meta-analysis aimed to identify the effects of selenium supplementation on insulin resistance, glucose homeostasis, and lipid profiles in patients with CMDs. METHODS: Randomized controlled trials (RCTs) of selenium supplementation for treating CMDs were screened in five electronic databases. Insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), and glycosylated hemoglobin A1C (HbA1c) were defined as the primary outcome markers, and lipid profiles were considered the secondary outcome markers. RESULTS: Ten studies involving 526 participants were included in the meta-analysis. The results suggested that selenium supplementation significantly reduced serum insulin levels (standardized men difference [SMD]: -0.53; 95% confidence interval [CI] [-0.84, -0.21], p = 0.001, I2 = 68%) and HOMA-IR (SMD: -0.50, 95% CI [-0.86, -0.14], p = 0.006, I2 = 75%) and increased high-density lipoprotein cholesterol (HDL-C) levels (SMD: 0.97; 95% CI [0.26, 1.68], p = 0.007, I2 = 92%), but had no significant effect on FPG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C). CONCLUSION: Current evidence supports the beneficial effects of selenium supplementation on reducing insulin levels, HOMA-IR, and increasing HDL-C levels. Selenium supplementation may be an effective strategy for reducing insulin resistance in patients with CMDs. However, more high-quality clinical studies are needed to improve the certainty of our estimates.

Qing-Xin-Jie-Yu Granule alleviates atherosclerosis by reshaping gut microbiota and metabolic homeostasis of ApoE-/- mice.

BACKGROUND: Atherosclerosis (AS) is a key pathological factor in cardiovascular disease (CVD) and is characterized by high mortality and morbidity worldwide. Metabolic disorders, including pathoglycemia and dyslipidemia that lead to chronic inflammation, represent the prominent pathological characteristics of atherosclerotic CVD, Qing-Xin-Jie-Yu Granule (QXJYG) is a Chinese traditional decoction that has been clinically proven to be effective for patients with CVD. However, the underlying mechanisms have not been completely elucidated. PURPOSE: To investigate the protective effects of QXJYG against AS and its potential mechanisms. METHODS: QXJYG was orally administered at doses of 1.664 and 4.992 g·kg-1·d-1 in a high-fat diet (HFD)-induced AS model using ApoE-/- mice. Histopathological and immunohistochemical analyses, ELISA, untargeted and targeted metabolomics analysis, 16S rRNA analysis, and RT-qPCR were performed to identify the therapeutic effects and mechanisms of QXJYG in treating HFD-induced AS. RESULTS: QXJYG retarded HFD-induced weight gain and reduced the increased serum levels of total cholesterol, triglycerides, and low-density lipoprotein-cholesterol, whereas high-dose QXJYG increased the serum level of high-density lipoprotein-cholesterol in HFD-fed ApoE-/- mice. Meanwhile, QXJYG reduced the serum levels, as well as aortas mRNA levels of the inflammatory cytokines, IL-1ß and IL-6, which indicates that QXJYG is effective against metaflammation. Mechanistically, QXJYG reshaped the gut microbiota and its associated bile acids (BAs) metabolomic phenotype, partly by increasing the levels of BA synthesis enzymes, hepatic CYP7A1, and CYP27A1, while decreasing ileal FGF15 and ß-Klotho mRNA expression, favoring facilitated de novo BAs synthesis and thereby driving cholesterol catabolic excretion. CONCLUSION: Our findings indicate that QXJYG is effective against HFD-triggered chronic inflammation, and contributes to the alleviation of AS development, and the antiatherogenic properties of QXJYG may be partly due to the remodeling of the gut microbiota and BA metabolism. Although the results are encouraging, further clinical studies of anti-AS herbal medicines are required to elucidate the full potential of the gut microbiota and BA metabolism.

Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases.

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.

Efficacy and safety of drug-coated balloon in the treatment of acute myocardial infarction: a meta-analysis of randomized controlled trials.

Acute myocardial infarction (AMI) is one of the main causes of death in the world, and the incidence of AMI is increasing in the young population. Drug-coated balloon (DCB) has become an effective concept for the treatment of in-stent restenosis, small vessel disease, bifurcation lesions, high blood risk conditions, and even de novo large vessel disease. To ensure whether DCB can play an alternative role in AMI, we conducted a comprehensive meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of DCB in the treatment of AMI. Electronic databases were searched for RCTs that compared DCB with stent for AMI. The primary outcome was major adverse cardiac events (MACEs), the secondary outcome was late lumen loss (LLL). RevMan 5.3 software and RStudio software were used for data analysis. Five RCTs involving 528 patients with 6-12 months of follow-up were included. There was no significant difference in the incidence of MACEs between DCB group and stent group (RR, 0.85; 95% CI 0.42 to 1.74; P = 0.66). Lower LLL was shown in DCB group (WMD, - 0.29; 95% CI - 0.46 to - 0.12; P < 0.001). This meta-analysis of RCT showed that DCB might provide a promising way on AMI compared with stents. Rigorous patients' selection and adequate predilation of culprit lesions are necessary to optimize results and prevent bailout stent implantation.PROSPERO registration number: CRD42020214333.

The Effect of Ticagrelor on Endothelial Function Compared to Prasugrel, Clopidogrel, and Placebo: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVE: Endothelial dysfunction is associated with the long-term outcomes in patients with coronary artery disease (CAD). Recent evidence suggests that ticagrelor, a potent antiplatelet agent, improves endothelial function. However, several studies demonstrated contrasting results. The objective of this meta-analysis was to determine the efficacy of ticagrelor treatment on endothelial function. MATERIALS AND METHODS: A systematic literature study was conducted on databases including PubMed, Web of Science, EMBASE, Scopus, and the Cochrane Library. A historical search was performed for a reference list of the selected studies as of August 2021. The randomized controlled trials (RCTs) were assessed using the Cochrane tool. The weighted mean difference (WMD) 95% CI was treated as the overall effect size, and data were pooled using the fixed-effect model or random-effect model according to the heterogeneity. Subgroup and sensitivity analyses were performed to measure the effects of potential confounders. RESULTS: A total of 21 studies were included. The meta-analysis indicated that ticagrelor resulted in a significant increase of flow-mediated dilation (FMD) (WMD: 1.48; 95% CI: 0.36, 2.60), reactive hyperemia index (RHI) (WMD: 0.06; 95% CI: 0.00, 0.13), and circulating progenitor endothelial cells (CEPCs) (WMD: 13.84; 95% CI: 5.70, 21.98), and a reduction in the index of microvascular resistance (IMR) (WMD: -15.39; 95% CI: -25.11, -5.68). CONCLUSION: Ticagrelor has a significant effect on some markers of endothelial function in patients with CAD. However, the results should be interpreted with caution due to the heterogeneity and limited studies.

Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan, China.

IMPORTANCE: An ongoing outbreak of COVID-19 has exhibited significant threats around the world. We found a significant decrease of T lymphocyte subsets and an increase of inflammatory cytokines of hospitalized patients with COVID-19 in clinical practice. METHODS: We conducted a retrospective, single-center observational study of in-hospital adult patients with confirmed COVID-19 in Hubei Provincial Hospital of traditional Chinese and Western medicine (Wuhan, China) by Mar 1, 2020. Demographic, clinical, laboratory information, especially T lymphocyte subsets and inflammatory cytokines were reported. For patients who died or discharge from hospital, the associations of T lymphocyte subsets on admission were evaluated by univariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs), warning values to predict in-hospital death were assessed by Receiver Operator Characteristic (ROC) curves. RESULTS: A total of 187 patients were enrolled in our study from Dec 26, 2019 to Mar 1, 2020, of whom 145 were survivors (discharge = 117) or non-survivors (in-hospital death ==28). All patients exhibited a significant drop of T lymphocyte subsets counts with remarkably increasing concentrations of SAA, CRP, IL-6, and IL-10 compared to normal values. The median concentrations of SAA and CRP in critically-ill patients were nearly 4- and 10-fold than those of mild-ill patients, respectively. As the severity of COVID-19 getting worse, the counts of T lymphocyte drop lower.28 patients died in hospital, the median lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell and B-cell were significantly lower than other patients. Lower counts (/uL) of T lymphocyte subsets lymphocyte (<500), CD3+T-cell (<200), CD4+ T-cell (<100), CD8+ T-cell (<100) and B-cell (<50) were associated with higher risks of in-hospital death of CIVID-19. The warning values to predict in-hospital death of lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and B-cell were 559, 235, 104, 85 and 82, respectively. CONCLUSION: We find a significant decrease of T lymphocyte subset is positively correlated with in-hospital death and severity of illness. The decreased levels of T lymphocyte subsets reported in our study were similar with SARS but not common among other virus infection, which may be possible biomarkers for early diagnosis of COVID-19. Our findings may shed light on early warning of high risks of mortality and help early intervention and treatment of COVID-19.

Adjuvant Effects of Health Education of Chinese Medicine for Chronic Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the adjuvant effects of health education of Chinese medicine (HECM) for patients with three types of common noncommunicable diseases (NCD-hypertension, diabetes, and coronary heart disease (CHD)). METHODS: The protocol of this review was registered in the PROSPERO website (CRD42017058325). Six databases were searched till Sep. 30, 2019. Randomized controlled trials (RCTs) comparing HECM plus conventional therapy with conventional therapy were retrieved. Participants were diagnosed as one of the 3 above NCDs. HECM is regarded as lectures and classes about diet therapy, exercise therapy, emotion balance, and other knowledge according to Chinese medicine theory. The control rate of the disease was defined as a primary outcome in this review. Outcomes were synthesized using meta-analyses where reporting was sufficiently homogeneous or alternatively synthesized in a systematic review. RESULTS: In total, 12 trials with 1142 patients were included in this review. Since all the trials may have unclear or high risk of bias, only low quality evidence could be found for supporting the adjunctive effect of HECM in treating hypertension, diabetes, and CHD, to reduce the control rate (risk ratio -1.58), the blood pressure level (mean difference -9.38 mmHg), the fasting plasma glucose level (mean difference -1.26 mmol/L), and the symptoms of angina. CONCLUSION: The adjunctive effect of HECM on increasing the control rate of hypertension, improving the symptoms of diabetes and CHD, was only supported by low-quality evidence in this review. More rigorous trials with larger sample sizes and higher quality are warranted to provide a high quality of evidence.

Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal Pathway.

Background: Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA's anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in ApoE-deficient (ApoE-/-) mice. Methods: Male ApoE-/- mice (6 weeks) were fed with a high-fat diet for 13 weeks and then randomized to the model group (MOD) or Tan IIA groups [high dose: 90 mg/kg/day (HT), moderate dose: 30 mg/kg/day (MT), low dose: 10 mg/kg/day (LT)] or the atorvastatin group (5 mg/kg/day, ATO) for 13 weeks. Male C57BL/6 mice (6 weeks) were fed with ordinary rodent chow as control. The plaque stability was evaluated according to the morphology and composition of aortic atherosclerotic (AS) plaque in H&E staining and Movat staining sections by calculating the area of extracellular lipid, collagenous fiber, and foam cells to the plaque. The expression of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear factor-kappa B (NF-κB) signal pathway in aorta fractions was determined by immunohistochemistry. Serum levels of blood lipid were measured by turbidimetric inhibition immunoassay. The concentrations of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by cytometric bead array. Results: Tan IIA stabilized aortic plaque with a striking reduction in the area of extracellular lipid (ATO: 13.15 ± 1.2%, HT: 12.2 ± 1.64%, MT: 13.93 ± 1.59%, MOD: 18.84 ± 1.46%, P < 0.05) or foam cells (ATO: 16.05 ± 1.26%, HT: 14.88 ± 1.79%, MT: 16.61 ± 1.47%, MOD: 22.08 ± 1.69%, P < 0.05) to the plaque, and an evident increase in content of collagenous fiber (ATO: 16.22 ± 1.91%, HT: 17.58 ± 1.33%, MT: 15.71 ± 2.26%, LT:14.92 ± 1.65%, MOD: 9.61 ± 0.7%, P < 0.05) to the plaque than that in the model group, concomitant with down-regulation of the protein expression of TLR4, MyD88, and NF-κB p65, and serum level of MCP-1 and TNF-α in a dose-dependent manner. There were no differences in serum TC, LDL, HDL, or TG levels between ApoE-/- mice and those treated with atorvastatin. Conclusions: These results suggest that Tan IIA could stabilize vulnerable AS plaque in ApoE-/- mice, and this anti-inflammatory and immune-regulating effect may be achieved via the TLR4/MyD88/NF-κB signaling pathway.

Expecting the holistic regulation from Chinese medicine based on the "solar system" hypothesis of ischemic heart disease.

Stenosis of the coronary artery has been considered as an essential component of ischemic heart disease (IHD). Consequently, revascularization [e.g., percutaneous coronary intervention (PCI) and coronary artery bypass] has been the primary therapeutic approach to IHD. Such strategy has indeed revolutionized the management of IHD patients. However, not all patients with myocardial ischemia have visible coronary stenosis. Moreover, cardiovascular events occur in nearly 20% patients with stable coronary artery disease who have undergone PCI. The recently proposed "solar system" hypothesis of IHD postulates that coronary stenosis is only one (albeit important) of its features. Mechanistic contribution and clinical implication of multiple pathophysiological processes beyond coronary stenosis are highlighted in this hypothesis. On the basis of a holistic regulation and individualized medicine, Chinese medicine (CM) has been used in the real-world setting to manage a variety of diseases, including IHD, for more than two thousands years. In this article, we summarize the evidence of CM that supports the "solar system" IHD hypothesis, and argue for a comprehensive approach to IHD. At the theoretical level, the central features of this approach include a holistic view of disease and human subjects, as well as individualized medicine. At the practical level, this approach emphasizes anoxia-tolerance and self-healing.

Systematic review on randomized controlled trials of coronary heart disease complicated with depression treated with Chinese herbal medicines.

OBJECTIVES: This systemic review evaluated the efficacy and safety of Chinese herbal medicines (CHMs) in patients with coronary heart disease (CHD) complicated with depression. METHODS: All databases were retrieved till September 30, 2014. Randomized controlled trials (RCTs) comparing CHMs with placebo or conventional Western medicine were retrieved. Data extraction, analyses and quality assessment were performed according to the Cochrane standards. RevMan 5.3 was used to synthesize the results. RESULTS: Thirteen RCTs enrolling 1,095 patients were included. Subgroup analysis was used to assess data. In reducing the degree of depression, CHMs showed no statistic difference in the 4th week [mean difference (MD)=-1.06; 95% confidence interval (CI)-2.38 to 0.26; n=501; I(2)=73%], but it was associated with a statistically significant difference in the 8th week (MD=-1.00; 95% CI-1.64 to-0.36; n=436; I(2)=48%). Meanwhile, the combination therapy (CHMs together with antidepressants) showed significant statistic differences both in the 4th week (MD=-1.99; 95% CI-3.80 to-0.18; n=90) and in the 8th week (MD=-5.61; 95% CI-6.26 to-4.97; n=242; I(2)=87%). In CHD-related clinical evaluation, 3 trials reported the intervention group was superior to the control group. Four trials showed adverse events in the intervention group was less than that in the control group. CONCLUSIONS: CHMs showed potentially benefits on patients with CHD complicated with depression. Moreover, the effect of CHMs may be similar to or better than antidepressant in certain fields but with less side effects. However, because of small sample size and potential bias of most trials, this result should be interpreted with caution. More rigorous trials with larger sample size and higher quality are warranted to give high quality of evidence to support the use of CHMs for CHD complicated with depression.

[Practical Diagnostic Criterion of Blood Stasis Syndrome: Introduction, Reliability, and Validity].

OBJECTIVE: To introduce practical diagnostic criterion of blood stasis syndrome (BSS), and to evaluate its reliability and validity. METHODS: By referring to three diagnostic criteria of BSS [practical diagnostic criterion of BSS (criterion A), diagnostic criterion of BSS in 1986 (criterion B), Consensus of Integrative Medicine on BSS Diagnosis in 2011 (criterion C)], 712 patients from different departments of Xiyuan Hospital were recruited. The reliability of criterion A and its consistency with the other two criteria were assessed using Kappa coefficient. A Bayesian approach was also employed to assess the sensitivity and specificity of criterion A. RESULTS: According to the consistency check, criterion A presented good consistency when used by different researchers (the diagnostic accordance rate was 91. 96%, Kappa =0. 82, P <0.001). Meanwhile, there was an acceptable diagnostic consistency among the three diagnostic criteria. Bayesian estimation suggested that criterion A had higher sensitivity but similar specificity, as compared with criterion B or criterion C. Compared with criterion B [the median of sensitivity and specificity were 0. 762 (95% Cl: 0. 731 -0. 790) and 0. 902 (95% Cl: 0. 858 -0. 936) respectively, the median of sensitivity and specificity of criterion A were 0. 911 (95% CI: 0. 888 - 0. 930) and 0. 875 (95% CI: 0. 826 - 0. 915) respectively. Estimating the difference between criterion A and B, the median of sensitivity and specificity were 0. 149 (95% CI: 0. 112 -0.184) and -0. 026 (95% CI:-0. 085 -0. 033) respectively. Compared with criterion C [the median of sensitivity and specificity were 0. 831 (95% Cl: 0. 804 -0. 857) and 0. 892 (95% CI: 0. 848 - 0. 926) respectively], the median of sensitivity and specificity of criterion A were 0. 912 (95% CI: 0. 889 -0. 932) and 0. 880 (95%CI: 0. 833 - 0.919) respectively. Estimating the difference between criterion A and C, the median of sensitivity and specificity were 0. 081 (95% CI: 0.047 - 0.114) and -0.011 (95%CI: -0.070 -0.046) respectively. CONCLUSION: Compared with criterion B and C, criterion A not only had better reliability, but also could significantly improve the sensitivity without obviously lowering the specificity.