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.

Short-term socioeconomic status shift and long-term cardiovascular outcomes in China: a population-based cohort study.

INTRODUCTION: Limited studies have discussed the effect of socioeconomic status (SES) shift on cardiovascular outcomes, especially in less developed regions and countries. We; therefore, explored the association between short-term SES shift and long-term cardiovascular outcomes in China. METHODS: In participants who had completed China Kadoorie Biobank study resurvey, 18 672 were included in the final analysis after excluding those who had cardiovascular diseases at baseline, and those who had a cardiovascular event before the resurvey. We used education, occupation, household income and healthcare cover as measurement of SES, and generated SES class for each individual at baseline and resurvey using latent class analysis. Outcomes of interest included cardiovascular death, major coronary event (MCE) and stroke. We used accelerated failure time model to obtain survival time ratio for each level of SES shift. RESULTS: During a mean time gap of 2.6 years, 10 273 (55%) individuals remained stable in SES, 7763 (41.6%) shifted towards higher SES and 636 (3.4%) shifted towards lower SES. Participants were followed up for a mean of 9.8 years. After adjusting for baseline factors, sharp but not moderate SES downshift was significantly associated with shortened event-free survival time before cardiovascular deaths (p=0.02) and MCEs (p<0.001) occurred. Contrarily, moderate and sharp SES upshift was significantly associated with prolonged event-free survival time before cardiovascular deaths (p=0.0027 and p<0.001) and MCEs (p=0.0079 and p=0.009) occurred. CONCLUSION: Short-term SES improvement is associated with better long-term cardiovascular outcome in China. High baseline SES might buffer out some unfavourable impact brought by moderate SES downshift. More comprehensive strategies should be considered in policy-making for socioeconomic development.

The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis.

Objective: The objective of this study was to measure the efficacy of various types and dosages of statins on C-reactive protein (CRP) levels in patients with dyslipidemia or coronary heart disease. Methods: Randomized controlled trials were searched from PubMed, Embase, Cochrane Library, OpenGray, and ClinicalTrials.gov. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for data extraction and synthesis. The pairwise meta-analysis compared statins and controls using a random-effects model, and a network meta-analysis compared the types and dosages of statins using the Bayesian random-effects model. The PROSPERO registration number is CRD42021242067. Results: The study included 37 randomized controlled trials with 17,410 participants and 20 interventions. According to the pairwise meta-analysis, statins significantly decreased CRP levels compared to controls (weighted mean difference [WMD] = -0.97, 95% confidence interval [CI] [-1.31, -0.64], P < 0.0001). In the network meta-analysis, simvastatin 40 mg/day appeared to be the best strategy for lowering CRP (Rank P = 0.18, WMD = -4.07, 95% CI = [-6.52, -1.77]). The same was true for the high-sensitivity CRP, non-acute coronary syndrome (ACS), <12 months duration, and clear measurement subgroups. In the CRP subgroup (rank P = 0.79, WMD = -1.23, 95% CI = [-2.48, -0.08]) and ≥12-month duration subgroup (Rank P = 0.40, WMD = -2.13, 95% CI = [-4.24, -0.13]), atorvastatin 80 mg/day was most likely to be the best. There were no significant differences in the dyslipidemia and ACS subgroups (P > 0.05). Node-splitting analysis showed no significant inconsistency (P > 0.05), except for the coronary heart disease subgroup. Conclusion: Statins reduced serum CRP levels in patients with dyslipidemia or coronary heart disease. Simvastatin 40 mg/day might be the most effective therapy, and atorvastatin 80 mg/day showed the best long-term effect. This study provides a reference for choosing statin therapy based on LDL-C and CRP levels.

A Bibliometric and Knowledge-Map Analysis of Macrophage Polarization in Atherosclerosis From 2001 to 2021.

In recent years, studies of macrophage polarization in atherosclerosis have become an intense area of research. However, there are few bibliometric analyses regarding this area. In this review, we used CiteSpace 5.8.R3 and VOSviewer 1.6.16 software to perform text mining and knowledge-map analysis. We explored the development process, knowledge structure, research hotspots, and potential trends using a bibliometric and knowledge-map analysis to provide researchers with a macroscopic view of this field. The studies concerning macrophage polarization in atherosclerosis were downloaded from the Web of Science Core Collection. A total of 781 studies were identified and published by 954 institutions from 51 countries/regions. The number of studies of macrophage polarization in atherosclerosis increased over time. Arteriosclerosis Thrombosis and Vascular Biology published the highest number of articles and was the top co-cited journal. De Winther was the most prolific researcher, and Moore had the most co-citations. The author co-occurrence map illustrated that there was active cooperation among researchers. The most productive countries were the United States and China. Amsterdam University, Harvard University, and Maastricht University were the top three productive institutions in the research field. Keyword Co-occurrence, Clusters, and Burst analysis showed that "inflammation," "monocyte," "NF kappa B," "mechanism," and "foam cell" appeared with the highest frequency in studies. "Oxidative stress," "coronary heart disease," and "prevention" were the strongest citation burst keywords from 2019 to 2021.

Knowledge Mapping of Necroptosis From 2012 to 2021: A Bibliometric Analysis.

Background: Necroptosis, a recently discovered programmed cell death, has been pathologically linked to various diseases and is thus a promising target for treating diseases. However, a comprehensive and objective report on the current status of entire necroptosis research is lacking. Therefore, this study aims to conduct a bibliometric analysis to quantify and identify the status quo and trending issues of necroptosis research in the last decade. Methods: Articles were acquired from the Web of Science Core Collection database. We used two bibliometric tools (CiteSpace and VOSviewer) to quantify and identify the individual impact and cooperation information by analyzing annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. Afterwards, we identified the trending research areas of necroptosis by analyzing the co-occurrence and burst of keywords and co-cited references. Results: From 2012 to 2021, a total of 3,111 research articles on necroptosis were published in 786 academic journals by 19,687 authors in 885 institutions from 82 countries/regions. The majority of publications were from China and the United States, of which the United States maintained the dominant position in necroptosis research; meanwhile, the Chinese Academy of Sciences and Ghent University were the most active institutions. Peter Vandenabeele published the most papers, while Alexei Degterev had the most co-citations. Cell Death & Disease published the most papers on necroptosis, while Cell was the top 1 co-cited journal, and the major area of these publications was molecular, biology, and immunology. High-frequency keywords mainly included those that are molecularly related (MLKL, TNF-alpha, NF-κB, RIPK3, RIPK1), pathological process related (cell-death, apoptosis, necroptosis, necrosis, inflammation), and disease related (cancer, ischemia/reperfusion injury, infection, carcinoma, Alzheimer's disease). Conclusion: Necroptosis research had a stable stepwise growth in the past decade. Current necroptosis studies focused on its cross-talk with other types of cell death, potential applications in disease treatment, and further mechanisms. Among them, the synergy with ferroptosis, further RIPK1/RIPK3/MLKL studies, its association with inflammation and oxidative stress and translational applications, and the therapeutic potential to treat cancer and neurodegenerative diseases are the trending research area. These might provide ideas for further research in the necroptosis field.

Association Between Lipoprotein(a) and Calcific Aortic Valve Disease: A Systematic Review and Meta-Analysis.

Background: Preliminary studies indicated that enhanced plasma levels of lipoprotein(a) [lp(a)] might link with the risk of calcific aortic valve disease (CAVD), but the clinical association between them remained inconclusive. This systematic review and meta-analysis were aimed to determine this association. Methods: We comprehensively searched PubMed, Embase, Web of Science, and Scopus databases for studies reporting the incidence of CAVD and their plasma lp(a) concentrations. Pooled risk ratio (RR) and 95% confidence interval (95% CI) were calculated to evaluate the effect of lp(a) on CAVD using the random-effects model. Subgroup analyses by study types, countries, and the level of adjustment were also conducted. Funnel plots, Egger's test and Begg's test were conducted to evaluate the publication bias. Results: Eight eligible studies with 52,931 participants were included in this systematic review and meta-analysis. Of these, four were cohort studies and four were case-control studies. Five studies were rated as high quality, three as moderate quality. The pooled results showed that plasma lp(a) levels ≥50 mg/dL were associated with a 1.76-fold increased risk of CAVD (RR, 1.76; 95% CI, 1.47-2.11), but lp(a) levels ≥30 mg/dL were not observed to be significantly related with CAVD (RR, 1.28; 95% CI, 0.98-1.68). We performed subgroup analyses by study type, the RRs of cohort studies revealed lp(a) levels ≥50 mg/dL and lp(a) levels ≥30 mg/dL have positive association with CAVD (RR, 1.70; 95% CI, 1.39-2.07; RR 1.38; 95% CI, 1.19-1.61). Conclusion: High plasma lp(a) levels (≥50 mg/dL) are significantly associated with increased risk of CAVD.

Association between dietary inflammatory index and atherosclerosis cardiovascular disease in U.S. adults.

Objective: To evaluate the association between dietary inflammatory index (DII) and Atherosclerotic cardiovascular disease (ASCVD) among U.S. adults. Methods: We collected data from National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. Adults who reported complete information to diagnose ASCVD and calculate DII were included. We used three models to differentially adjust the covariates, including age, sex, race or ethnicity, education level, smoking status, poverty, insurance, body mass index, hyperlipemia, hypertension, and diabetes. Logistic regression was used to estimate the Odds Ratio (OR) and 95% confidence interval (95% CI) for ASCVD grouped by DII deciles. We additionally conducted spline smoothing with the generalized additive model (GAM) and the log-likelihood ratio to examine the non-linear relationship between DII and ASCVD. If exists, the segmented linear regression will be used to detect the cutoff point. The subgroup analyses were stratified by various atherosclerotic cardiovascular diseases (i.e., CHD, angina, heart attack, and stroke) and sex. Results: A total of 48,733 participants (mean age, 47.13 ± 0.19 years) with 51.91% women were enrolled, of which 5,011 were diagnosed with ASCVD. In the crude model, participants in the five highest deciles (D6, 7, 8, 9, and 10) of DII score had a significantly higher risk of having ASCVD compared to those in the first decile. In the fully adjusted model, those in the tenth decile [OR = 1.47, 95% CI = (1.18,1.84)] of DII had a significantly increased risk of ASCVD compared to the first decile. Notably, when DII is above 3, the ASCVD risk increased by 41% for each one increase in DII [OR = 1.41, 95% CI = (1.15,1.73)]. This relationship was more pronounced in females. Conclusion: Our study revealed a positive and non-linearly association between DII and ASCVD in U.S. adults. This relationship was more pronounced in females. The findings provide a reference for future research and diet recommendations.

Chinese Herbal Medicines and Active Metabolites: Potential Antioxidant Treatments for Atherosclerosis.

Atherosclerosis is a complex chronic disease that occurs in the arterial wall. Oxidative stress plays a crucial role in the occurrence and progression of atherosclerotic plaques. The dominance of oxidative stress over antioxidative capacity generates excess reactive oxygen species, leading to dysfunctions of the endothelium and accelerating atherosclerotic plaque progression. Studies showed that Chinese herbal medicines and traditional Chinese medicine (TCM) might regulate oxidative stress; they have already been used to treat diseases related to atherosclerosis, including stroke and myocardial infarction. This review will summarize the mechanisms of oxidative stress in atherosclerosis and discuss studies of Chinese herbal medicines and TCM preparations treating atherosclerosis, aiming to increase understanding of TCM and stimulate research for new drugs to treat diseases associated with oxidative stress.

The Prognostic Value of Reticulated Platelets in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Reticulated platelets (RPs) represent the young population in the circulating platelet pool, indicating platelet turnover. Preliminary studies suggested circulating levels of RPs were associated with cardiovascular events (CVEs) in patients with coronary artery disease (CAD). Methods: This study systematically searched PubMed, Scopus, Embase, and Web of Science for eligible studies which reported RPs as a prognostic factor and the incidence of CVEs in patients with CAD. The risk estimates and 95% confidence intervals (95% CI) were analyzed for adjusted and unadjusted associations separately using random-effects model. Meta-regression and subgroup analysis were used to identify the source of heterogeneity. Funnel plots, Egger's test, and trim and fill methods were used to assess the publication bias. Results: A total of six cohort studies were included in this meta-analysis. Four studies were rated as high quality with the remaining rated as moderate quality. The funnel plot, Egger's test, and trim and fill method suggested the presence of publication bias. The pooled results indicated elevated RPs were associated with a higher risk of composite CVEs [risk ratio (RR), 2.26; 95% CI, 1.72-2.98, with little heterogeneity] and cardiovascular death (RR, 2.33; 95% CI, 1.66-3.28, with little heterogeneity). Based on results of separate meta-analysis, we found RPs might be a good predictor for revascularization but not for myocardial infarction or cerebrovascular events. After adjustment of conventional prognostic factors, the pooled result still suggested the prognostic value of RPs for composite CVEs (RR, 2.00; 95% CI, 1.30-3.08; p < 0.00001, with substantial heterogeneity). Subgroup analysis and meta-regression of adjusted risk estimates revealed that the number of adjustment factors might be the source heterogeneity. Conclusion: Circulating level of RPs might be a useful prognostic marker for CVEs in patients with CAD, even after adjustment of other prognostic factors.

Coronary Artery Calcification Under Statin Therapy and Its Effect on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Objective: To compare Agatston scores between patients without statin therapy and those under standard and intensive statin therapy and to systematically review the relationship between coronary artery calcification (CAC) progression under statin therapy and cardiovascular outcomes. Methods: Literature search was conducted across databases. Randomized controlled trials and observational studies that reported Agatston scores at baseline and follow-up from patients with and without statin therapy were included. A systematic review and meta-analysis was conducted. Results: Seven studies were subjected to qualitative and quantitative analyses. Agatston scores in all groups were increased at follow-up. Meta-analysis of data from the included studies revealed an insignificantly lower CAC score at follow-up in the experimental groups. Subgroup analysis showed that statins slowed down CAC progression mildly but with statistical significance in population with baseline CAC score >400 in the experimental groups (P = 0.009). Despite that calcification progressors had worse cardiovascular outcome than did non-progressors, it appeared that baseline CAC score had more decisive effects on cardiovascular outcomes. CAC progression under statin therapy did not increase cardiovascular risk, although more supportive data are needed. Conclusion: Statins do not reduce or enhance CAC as measured by Agatston score in asymptomatic populations at high risk of cardiovascular diseases, but seem to slow down CAC progression. Although our result was robust, it was restricted by small sample size and relatively short follow-up period. Further studies on the relationship between CAC progression under statin therapy and cardiovascular outcomes are needed.

[Network pharmacology-based study on mechanisms of Danhong Injection in treatment of aspirin resistance].

This paper aims to discuss the potential targets,pathways and possible mechanisms of Danhong Injection in treatment of aspirin resistance by using network pharmacology concept and network analysis technique. Active ingredients and potential targets of Danhong Injection were collected from TCMSP database and the ingredients were further screened based on their topological characteristics. The active ingredients with nodal degree of freedom≥9 were selected as the main active ingredients. Targets related to aspirin resistance were collected from Genecards database. Drug-active ingredient-target-disease network was constructed by using Cytoscape3. 7. 0,and Funrich 3. 1. 3 software was used for gene enrichment analysis. Sixty main active ingredients were screened out from 110 active ingredients of Danhong Injection,including 51 ingredients in Salviae Miltiorrhizae Radix et Rhizoma and 11 ingredients in Carthami Flos,2 of which were both in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. In addition,159 potential targets were collected. The results of gene enrichment analysis showed that Danhong Injection could improve aspirin resistance mainly through21 pathways involving coagulation process,inflammatory response and metabolism. This study revealed the effects of Danhong Injection for improving aspirin resistance in multi-component,multi-target and multi-pathway means mainly through regulation in coagulation process,inflammatory response and metabolism,providing more abundant information and basis for subsequent research and experimental work.