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.

Efficacy and Safety of Oral Anticoagulants in Older Adult Patients With Atrial Fibrillation: Pairwise and Network Meta-Analyses.

OBJECTIVE: To evaluate the efficacy and safety of oral anticoagulants for older adult patients with atrial fibrillation (AF). DESIGN: Pairwise and network meta-analyses. SETTING AND PARTICIPANTS: Patients with AF aged ≥75 years. METHODS: PubMed, Embase, and the Cochrane library were searched for published randomized controlled trials and adjusted observational studies evaluating the use of a non-vitamin K antagonist oral anticoagulants (NOACs), vitamin K antagonist, or antiplatelet drug for the prevention of stroke. The primary efficacy and safety outcomes were the composite of stroke and systemic embolism (SSE) and major bleedings. RESULTS: This study included 38 studies enrolling 1,022,908 older adult patients with AF. Results from pairwise meta-analyses showed that NOACs were superior to warfarin for all outcomes, except that dabigatran increased the risk of gastrointestinal (GI) bleedings. Aspirin was associated with a higher risk of SSE and ischemic stroke than warfarin or NOACs. Results of network meta-analyses indicated that apixaban significantly reduced the risk of SSE, major bleedings, and GI bleedings than warfarin, rivaroxaban, and dabigatran. Apixaban, edoxaban, rivaroxaban, and dabigatran reduced the risk of ischemic stroke and intracranial bleeding compared to warfarin. Dabigatran showed lower risk of all-cause mortality than warfarin and of intracranial bleeding than rivaroxaban. CONCLUSIONS AND IMPLICATIONS: NOACs are of at least equal efficacy, or even superior to warfarin. The safety profile of individual NOAC agents was significantly different, as apixaban performs better than the other oral anticoagulants in reducing major bleeding and GI bleeding, whereas dabigatran increased the risk of GI bleeding.

Plasma homocysteine levels and risk of congestive heart failure or cardiomyopathy: A Mendelian randomization study.

Background: Although observational studies have demonstrated associations between elevated plasma homocysteine levels and the risk of cardiovascular diseases, controversy remains. Objective: This study investigated the causal association of plasma homocysteine levels with congestive heart failure and cardiomyopathy risk. Methods: We performed a two-sample Mendelian randomization (MR) study of congestive heart failure (n = 218,792), cardiomyopathy (n = 159,811), and non-ischemic cardiomyopathy (n = 187,152). Genetic summary data on the association of single-nucleotide polymorphisms with homocysteine were extracted from the most extensive genome-wide association study of 44,147 individuals. MR analyses, including the random-effect inverse variance-weighted (IVW) meta-analysis, weighted median, simple median, maximum likelihood, penalized weighted median, MR-PRESSO, and MR-Egger regression, were used to estimate the associations between the selected single-nucleotide polymorphisms and congestive heart failure or cardiomyopathy. Results: The MR analyses revealed no causal role of higher genetically predicted plasma homocysteine levels with congestive heart failure risk (random-effect IVW, odds ratio [OR] per standard deviation (SD) increase in homocysteine levels = 1.753, 95% confidence interval [CI] = 0.674-4.562, P = 0.250), cardiomyopathy (random-effect IVW, OR per SD increase in homocysteine levels = 0.805, 95% CI = 0.583 to 1.020, P = 0.189), or non-ischemic cardiomyopathy (random-effect IVW, OR per SD increase in homocysteine levels = 1.064, 95% CI = 0.927-1.222, P = 0.379). The results were consistent with other analytical methods and sensitivity analyses. Conclusion: Genetically predicted homocysteine level was not associated with congestive heart failure or cardiomyopathy risk. It is unlikely that homocysteine-lowering therapy decreases the incidence or improves the outcomes of congestive heart failure and cardiomyopathy.

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.

Qing-Xin-Jie-Yu Granule inhibits ferroptosis and stabilizes atherosclerotic plaques by regulating the GPX4/xCT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qing-Xin-Jie-Yu Granule (QXJYG) is an integrated traditional Chinese medicine formula used to treat atherosclerotic (AS) cardiovascular diseases. A randomized controlled trial found that QXJYG reduced cardiovascular events and experiments also verified that QXJYG attenuated AS by remodeling the intestinal flora. AIM OF THE STUDY: To determine whether QXJYG would attenuate AS and plaque vulnerability by regulating ferroptosis in high-fat diet-induced atherosclerotic ApoE-/- mice and to investigate the effects of QXJYG on macrophage ferroptosis in RAS-selective lethal 3 (RSL3)-induced J744A.1 cells. METHODS: AS models in ApoE-/- mice and RSL3-induced ferroptosis in J744A.1 cells were established to measure the protective and anti-ferroptotic effects of QXJYG in vivo and in vitro. The glutathione peroxidase 4 (GPX4)/cystine glutamate reverse transporter (xCT) signal pathway was examined by immunohistochemistry and western blotting. RESULTS: QXJYG attenuated AS progression and plaque vulnerability. Characteristic morphological changes of ferroptosis in the QXJYG-treated animals were rare. Total iron was significantly lower in the QXJYG group than in the model group (P < 0.05); QXJYG suppressed the lipid peroxidation (LPO) levels (malondialdehyde), enhanced the antioxidant capacity (superoxide dismutase and glutathione), and reduced inflammatory factors (interleukin [IL]-6, IL-1ß, tumor necrosis factor-α) associated with ferroptosis. Expression of GPX4/xCT in aorta tissues was remarkably increased in the QXJYG group. QXJYG inhibited ferroptosis in J744A.1 macrophages disturbed using RSL3. The Fe2+, LPO, and reactive oxygen species levels were lower in the QXJYG group than in the RSL3 group (P < 0.05). The QXJYG group showed higher expression of the GPX4/xCT signal pathway. CONCLUSION: QXJYG inhibits ferroptosis in vulnerable AS plaques partially via the GPX4/xCT signaling pathway.

Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials.

Objectives: To explore the associations between different types and doses of statins and adverse events in secondary prevention of cardiovascular disease. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials that compared statins with non-statin controls or different types or doses of statins. The primary outcomes included muscle condition, transaminase elevations, renal insufficiency, gastrointestinal discomfort, cancer, new onset or exacerbation of diabetes, cognitive impairment, and eye condition. We also analyzed myocardial infarction (MI), stroke, death from cardiovascular diseases (CVD), and all-cause death as the secondary outcomes to compare the potential harms with the benefits of statins. We conducted pairwise meta-analyses to calculate the odds ratio (OR) and 95% confidence intervals (CIs) for each outcome. Network meta-analyses were performed to compare the adverse effects of different statins. An Emax model was used to examine the dose-response relationships of the adverse effects of each statin. Results: Forty-seven trials involving 107,752 participants were enrolled and followed up for 4.05 years. Compared with non-statin control, statins were associated with an increased risk of transaminase elevations [OR 1.62 (95% CI 1.20 to 2.18)]. Statins decreased the risk of MI [OR 0.66 (95% CI 0.61 to 0.71), P < 0.001], stroke [OR 0.78 (95% CI 0.72 to 0.84), P < 0.001], death from CVD [OR 0.77 (95% CI 0.72 to 0.83), P < 0.001] and all-cause death [OR 0.83 (95% CI 0.79 to 0.88), P < 0.001]. Atorvastatin showed a higher risk of transaminase elevations than non-statin control [OR 4.0 (95% CI 2.2 to 7.6)], pravastatin [OR 3.49 (95% CI 1.77 to 6.92)] and simvastatin [OR 2.77 (95% CI 1.31 to 5.09)], respectively. Compared with atorvastatin, simvastatin was associated with a lower risk of muscle problems [OR 0.70 (95% CI 0.55 to 0.90)], while rosuvastatin showed a higher risk [OR 1.75 (95% CI 1.17 to 2.61)]. An Emax dose-response relationship was identified for the effect of atorvastatin on transaminase elevations. Conclusion: Statins were associated with increased risks of transaminases elevations in secondary prevention. Our study provides the ranking probabilities of statins that can help clinicians make optimal decisions when there is not enough literature to refer to. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021285161].

Left atrial appendage flow velocity predicts recurrence of atrial fibrillation after catheter ablation: A systematic review and meta-analysis.

Purpose: There is increasing evidence that left atrial appendage flow velocity (LAAFV) is linked to the recurrence of atrial fibrillation (AF) after catheter ablation (CA), suggesting the potential predictable significance of LAAFV in this setting. We performed a systematic review and meta-analysis to assess whether LAAFV is association with AF recurrence after CA. Methods: Up to May 1, 2022, six databases (PubMed, EMBASE, Web of Science, Cochrane Library, Scopus, and CINAHL) were searched for literature reporting the association between LAAFV and AF recurrence after CA. All statistical analyses were carried out using STATA version 16 software. Heterogeneity was determined by the Cochrane's Q test and I2 statistics. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of each included study, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was adopted to evaluate the quality of evidence. Result: Sixteen studies with 5,006 AF patients after CA (1,479 patients with AF recurrence, 3,527 without AF recurrence) were included in the meta-analysis. The meta-analysis of 15 studies (16 data sets) showed that patients with recurrence exhibited lower LAAFV values than those without recurrence [standardized mean difference (SMD): -0.65, 95% CI: -0.88 to -0.42, P < 0.01]. Moreover, we evaluated the association of LAAFV and the risk of AF recurrence after CA. Nine studies (11 data sets) defined LAAFV as continuous variables, and the pooled analysis suggested that for every 1 cm/s rise in LAAFV values, the risk of AF recurrence after CA decreased by 3% [Odds Ratio (OR): 0.97, 95% CI: 0.95 to 0.99, P < 0.01]. Seven studies defined LAAFV as categorical variables, and the pooled analysis showed that lower LAAFV were associated with an increased risk of AF recurrence after CA [OR: 2.28, 95% CI: 1.46 to 3.57, P < 0.01]. The subgroup analyses showed that the association between LAAFV and AF recurrence after CA was not significantly affected by the AF type and ablation procedure. The NOS indicated that included studies were moderate to high quality, while the GRADE assessment suggested a low certainty of the evidence. Conclusion: Lower LAAFV may be associated with an increased risk of AF recurrence after CA. Further studies with well designed and randomized studies for LAAFV should be conducted. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022333627].

Global research trends in atherosclerosis: A bibliometric and visualized study.

Background: Increasing evidence has spurred a considerable evolution of concepts related to atherosclerosis, prompting the need to provide a comprehensive view of the growing literature. By retrieving publications in the Web of Science Core Collection (WoSCC) of Clarivate Analytics, we conducted a bibliometric analysis of the scientific literature on atherosclerosis to describe the research landscape. Methods: A search was conducted of the WoSCC for articles and reviews serving exclusively as a source of information on atherosclerosis published between 2012 and 2022. Microsoft Excel 2019 was used to chart the annual productivity of research relevant to atherosclerosis. Through CiteSpace and VOSviewer, the most prolific countries or regions, authors, journals, and resource-, intellectual-, and knowledge-sharing in atherosclerosis research, as well as co-citation analysis of references and keywords, were analyzed. Results: A total of 20,014 publications were retrieved. In terms of publications, the United States remains the most productive country (6,390, 31,93%). The most publications have been contributed by Johns Hopkins Univ (730, 3.65%). ALVARO ALONSO produced the most published works (171, 0.85%). With a betweenness centrality of 0.17, ERIN D MICHOS was the most influential author. The most prolific journal was identified as Atherosclerosis (893, 4.46%). Circulation received the most co-citations (14,939, 2.79%). Keywords with the ongoing strong citation bursts were "nucleotide-binding oligomerization (NOD), Leucine-rich repeat (LRR)-containing protein (NLRP3) inflammasome," "short-chain fatty acids (SCFAs)," "exosome," and "homeostasis," etc. Conclusion: The research on atherosclerosis is driven mostly by North America and Europe. Intensive research has focused on the link between inflammation and atherosclerosis, as well as its complications. Specifically, the NLRP3 inflammasome, interleukin-1ß, gut microbiota and SCFAs, exosome, long non-coding RNAs, autophagy, and cellular senescence were described to be hot issues in the field.

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.

Associations between calcium channel blocker therapy and mortality in heart failure with preserved ejection fraction.

AIMS: Treatment of heart failure with preserved ejection fraction (HFpEF) is urgently needed; however, effective treatments are lacking. Current evidence showed a possible association between the use of calcium channel blockers (CCBs) and improved outcomes in HFpEF patients. We aimed to investigate the impact of CCBs on mortality in patients with HFpEF. METHODS AND RESULTS: This was a post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular and noncardiovascular mortality. We analysed hazard ratios (HRs) in patients taking CCBs compared with those not taking CCBs using Cox proportional hazard models. We considered 3440 HFpEF patients. The mean follow-up period was 3.4 ± 1.7 years, and 530 patients died during the study period. All-cause mortality rates in patients taking and not taking CCB were 37.3 and 50.8 events per 1000 person-years, respectively. The adjusted HR for all-cause mortality was significantly lower in those taking CCBs than those not taking CCBs [HR: 0.72, 95% confidence interval (CI): 0.59-0.88, P = 0.001]. The risk of cardiovascular and noncardiovascular mortality was also significantly lower in patients taking CCBs than in those not taking CCBs (HR: 0.75, 95% CI: 0.59-0.96, P = 0.023 and HR: 0.68, 95% CI: 0.49-0.93, P = 0.018, respectively). CONCLUSION: The use of CCBs was associated with reduced risks of mortality in patients with HFpEF.

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.

Knowledge Domain and Emerging Trends in Ferroptosis Research: A Bibliometric and Knowledge-Map Analysis.

OBJECTIVES: To identify the cooperation and impact of authors, countries, institutions, and journals, evaluate the knowledge base, find the hotspot trends, and detect the emerging topics regarding ferroptosis research. METHODS: The articles and reviews related to ferroptosis were obtained from the Web of Science Core Collection on November 1, 2020. Two scientometric software (CiteSpace 5.7 and VOSviewer 1.6.15) were used to perform bibliometric and knowledge-map analysis. RESULTS: A total of 1,267 papers were included, in 466 academic journals by 6,867 authors in 438 institutions from 61 countries/regions. The ferroptosis-related publications were increasing rapidly. Cell Death & Disease published the most papers on ferroptosis, while Cell was the top co-cited journal, publication journals and co-cited journals were major in the molecular and biology fields. The United States and China were the most productive countries; meanwhile, the University of Pittsburgh, Columbia University and Guangzhou Medical University were the most active institutions. Brent R Stockwell published the most papers, while Scott J Dixon had the most co-citations; simultaneously, active cooperation existed in ferroptosis researchers. Ten references on reviews, mechanisms, and diseases were regarded as the knowledge base. Five main aspects of ferroptosis research included regulation mechanisms, nervous system injury, cancer, relationships with other types of cell death, and lipid peroxidation. The latest hotspots were nanoparticle, cancer therapy, iron metabolism, and in-depth mechanism. Notably Nrf2 might have turning significance. The emerging topics on ferroptosis research were the further molecular mechanism of ferroptosis and the wider application of ferroptosis-related disease with advanced technology. CONCLUSION: This study performed a full overview of the ferroptosis research using bibliometric and visual methods. The information would provide helpful references for scholars focusing on ferroptosis.

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.

Estimated Glomerular Filtration Rate Is Associated With an Increased Risk of Death in Heart Failure Patients With Preserved Ejection Fraction.

Background: Renal dysfunction is associated with adverse cardiovascular outcomes in patients with heart failure (HF), but its impact on patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. Methods: 3,392 subjects of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial were assigned to two groups by estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 or 30-59 ml/min/1.73 m2. The outcomes, including all-cause death, cardiovascular death and HF hospitalization, were examined by multivariable cox models. Results: Over a median follow-up of 3.4 ± 1.7 years, a total of 524 all-cause deaths, 334 cardiovascular deaths and 440 HF hospitalizations occurred. Compared with patients with eGFR ≥ 60 ml/min/1.73 m2, those with eGFR 30-59 ml/min/1.73 m2 were associated with an increased risk of the all-cause death [adjusted hazard ratio (HR), 1.47; 95% confidence interval (CI), 1.24-1.76; P < 0.001], cardiovascular death (adjusted HR, 1.53; 95% CI: 1.23-1.91; p < 0.001), and HF hospitalization (adjusted HR: 1.21; 95% CI: 1.00-1.47; p = 0.049) after multivariable adjustment for potential confounders. Conclusions: eGFR 30-59 ml/min/1.73 m2 was related to an increased risk of all-cause death, cardiovascular death and HF hospitalization in HFpEF patients.

Evaluation of Optimal Diastolic Blood Pressure Range Among Adults With Treated Systolic Blood Pressure Less Than 130 mm Hg.

Importance: Extremely low diastolic blood pressure has been reported to be associated with increased adverse cardiovascular events (ie, the diastolic J-shape phenomenon); however, current US guidelines recommend an intensive blood pressure target of less than 130/80 mm Hg without mentioning the lower limits of diastolic blood pressure. Objectives: To evaluate whether there is a diastolic J-shape phenomenon for patients with an treated systolic blood pressure of less than 130 mm Hg and to explore the safe and optimal diastolic blood pressure ranges for this patient population. Design, Setting, and Participants: This cohort study analyzed outcome data of patients at high cardiovascular risk who were randomized to intensive or standard blood pressure control and achieved treated systolic blood pressure of less than 130 mm Hg in the Systolic Blood Pressure Intervention Trial (SPRINT) and Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial. Data were collected from October 2010 to August 2015 (SPRINT) and from September 1999 to June 2009 (ACCORD-BP). Data were analyzed from January to May 2020. Exposure: Treated diastolic blood pressure, divided in intervals of less than 60, 60 to less than 70, 70 to less than 80, and 80 mm Hg and greater. Main Outcomes and Measures: The primary outcome was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. A composite cardiovascular outcome, including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, was among the key secondary outcomes. Results: A total of 7515 patients (mean [SD] age, 65.6 [8.7] years; 4553 [60.6%] men) were included in this analysis. The nominally lowest risk was observed at a diastolic blood pressure between 70 and 80 mm Hg for the primary outcome, the composite cardiovascular outcome, nonfatal myocardial infarction, and cardiovascular death. A mean diastolic blood pressure of less than 60 mm Hg was associated with significantly increased risk of the primary outcome (hazard ratio [HR], 1.46; 95% CI, 1.13-1.90; P = .004), the composite cardiovascular outcome (HR, 1.74; 95% CI, 1.26-2.41; P = .001), nonfatal myocardial infarction (HR, 1.73; 95% CI, 1.15-2.59; P = .008), and nonfatal stroke (HR, 2.67; 95% CI, 1.26-5.63; P = .01). Conclusions and Relevance: This cohort study found that lowering diastolic blood pressure to less than 60 mm Hg was associated with increased risk of cardiovascular events in patients with high cardiovascular risk and an treated systolic blood pressure less than 130 mm Hg. The finding that a diastolic blood pressure value between 70 and 80 mm Hg was an optimum target for this patient population merits further study.

Effect of different types and dosages of statins on plasma lipoprotein(a) levels: A network meta-analysis.

BACKGROUND AND AIM: Studies differ with respect to the effects of statins and their on lipoprotein(a)[Lp(a)] levels. The aim of the present study was to resolve these differences by determining the effect of various types and dosages of statins on Lp(a) levels. METHODS: We searched PubMed, Embase and the Cochrane library for randomized controlled trials (RCTs) investigating the efficacy of statins on plasma Lp(a) levels. Study selection, data extraction and risk of bias assessment were conducted independently by four authors. We conducted pairwise meta-analysis and network meta-analysis (NMA). Consistency models were applied to NMA and the ranking probabilities for each treatment's efficacy were calculated. Node-splitting analysis was used to test inconsistency. This study was registered with PROSPERO, number CRD42020167612. RESULTS: Twenty RCTs with 23,605 participants were included, involving 11 interventions. Most of the included studies presented some risks of bias, especially risks of performance and detection bias. In the pairwise meta-analysis, pooled results showed a small but statistically significant difference between high-intensity rosuvastatin and placebo on Lp(a) levels (MD = 1.81, 95 % CI [0.43, 3.19], P = 0.01). In the NMA, different types and dosages of statins showed no significant effect on the level of Lp(a), and there was no obvious difference between them. Subgroup analysis based on different populations and treatment durations did not provide any statistically significant findings about different statins on Lp(a) levels. Node-splitting analysis showed that no significant inconsistency existed (P > 0.05). CONCLUSIONS: Statins have no clinically significant effect on Lp(a) levels, and there is no significant difference in the effect on Lp(a) levels between different types and dosages of statins. Moderate-intensity pitavastatin tended to have the best effect on reducing Lp(a) levels; nevertheless, it was insignificant. Our findings highlight the necessity for further study of the effect of statins on Lp(a) levels in future studies.

Chaihu Longgu Muli decoction, a Chinese herbal formula, for the treatment of insomnia: A systematic review and meta-analysis.

PURPOSE: To review the literature on the efficacy and safety of Chaihu Longgu Muli decoction (CLMD) for insomnia. METHODS: A systematic literature search was performed for five databases up to May of 2019 to identify randomized control trials involving CLMD for patients with insomnia. The experimental group was CLMD monotherapy or CLMD plus conventional treatment. Comparators were placebo, no treatment, or conventional medicine. The main comparison was CLMD against conventional drugs. The primary outcome was sleep quality (assessed using the Pittsburgh Sleep Quality Index, PSQI). The secondary outcomes were clinical effectiveness rate, total sleep time, and adverse event rate. RevMan 5.3 software was used for meta-analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with 95% confidence interval (CI). RESULTS: A total of 22 studies involving 2029 patients were included. All the included studies presented some risk of bias, especially risks of performance, and detection bias. The main meta-analysis showed that CLMD alone was more effective than conventional medications by reducing PSQI (MD = -2.80, 95% CI [-5.48, -0.13], P = .04), improving the clinical effectiveness rate (RR = 1.23, 95% CI [1.16, 1.31], P < .00001), and prolonging total sleep time (MD = 1.01, 95% CI [0.19, 1.83], P = .002). The adverse event rate in the CLMD group was lower than that of the control group (RR = 0.22, 95% CI [0.09, 0.51], P = .0005). CLMD also improved sleep quality better than conventional medications as an adjunct therapy (P < .05). The funnel plot was symmetrical, representing a low risk of publication bias. CONCLUSION: CLMD presented better efficacy and safety than conventional medications and had the potential to become an alternative to conventional medications for the treatment of insomnia. However, as the included studies showed significant risks of bias, these results will need to be confirmed by future double-blind randomized controlled trials. PROSPERO REGISTRATION NUMBER: CRD42019133103.