Cholesterol Efflux Capacity and Its Association With Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis.
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ABSTRACT:
SUBMITTER: Lee JJ
PROVIDER: S-EPMC8710716 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:It is unclear whether high-density lipoprotein (HDL) cholesterol concentration plays a causal role in atherosclerosis. A more important factor may be HDL cholesterol efflux capacity, the ability of HDL to accept cholesterol from macrophages, which is a key step in reverse cholesterol transport. We investigated the epidemiology of cholesterol efflux capacity and its association with incident atherosclerotic cardiovascular disease outcomes in a large, multiethnic population cohort.We measured HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity at baseline in 2924 adults free from cardiovascular disease who were participants in the Dallas Heart Study, a probability-based population sample. The primary end point was atherosclerotic cardiovascular disease, defined as a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes. The median follow-up period was 9.4 years.In contrast to HDL cholesterol level, which was associated with multiple traditional risk factors and metabolic variables, cholesterol efflux capacity had minimal association with these factors. Baseline HDL cholesterol level was not associated with cardiovascular events in an adjusted analysis (hazard ratio, 1.08; 95% confidence interval [CI], 0.59 to 1.99). In a fully adjusted model that included traditional risk factors, HDL cholesterol level, and HDL particle concentration, there was a 67% reduction in cardiovascular risk in the highest quartile of cholesterol efflux capacity versus the lowest quartile (hazard ratio, 0.33; 95% CI, 0.19 to 0.55). Adding cholesterol efflux capacity to traditional risk factors was associated with improvement in discrimination and reclassification indexes.Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events in a population-based cohort. (Funded by the Donald W. Reynolds Foundation and others.).
| S-EPMC4308988 | biostudies-literature
Project description:A low plasma level of high-density lipoprotein (HDL) cholesterol (HDL-C) is associated with cardiovascular risk. A key cardioprotective property of HDL is cholesterol efflux capacity (CEC), the ability of HDL to accept cholesterol from macrophages. In this study, we aimed to identify the predictive value of CEC for cardiovascular risk.The relative risks (RRs) and 95% confidence intervals (CIs) were pooled to analyze the association between CEC and the incidence of cardiovascular events and all-cause mortality. The odds ratios (ORs) and 95% CIs were pooled to estimate the association of CEC and the prevalence of cardiovascular events.A total of 15 studies were included. Results showed that the highest CEC was significantly associated with a reduced risk of cardiovascular events incidents compared to the lowest CEC (RR, 0.56; 95% CI, 0.37 to 0.85; I 2, 89%); the pooled RR of cardiovascular risk for per unit SD increase was 0.87 (95% CI, 0.73 to 1.04; I 2, 67%). Dose-response curve indicated that cardiovascular risk decreased by 39% (RR, 0.61; 95% CI, 0.51 to 0.74) for per unit CEC increase. Similarly, an inverse association was observed between CEC and the prevalence of cardiovascular events (highest vs. lowest, OR, 0.30; 95% CI, 0.17 to 0.5; I 2 = 63%; per unit SD increase, OR, 0.94; 95% CI, 0.90 to 0.98; I 2 = 71%). However, based on the current data, CEC was not significantly associated with all-cause mortality.Findings from this meta-analysis suggest that HDL-mediated CEC is inversely associated with cardiovascular risk, which appears to be independent of HDL concentration. The growing understanding of CEC and its role in cardiovascular risk decrease may improve the accuracy of cardiovascular risk prediction and also open important avenues to develop novel therapeutic targeting HDL metabolism.
| S-EPMC5681808 | biostudies-other
Project description:ImportanceCardiovascular adverse events (CVAE) with carfilzomib in patients with multiple myeloma can be potentially life-threatening and remain incompletely characterized. We performed the first systematic review and meta-analysis of carfilzomib-associated CVAE.ObjectiveTo determine the incidence of carfilzomib-associated CVAE and to compare the rates of carfilzomib CVAE among different doses and companion therapies.Data sourcesPubMed, EMBASE, Web of Science, and clinicaltrials.gov were queried for the keywords "carfilzomib," "Kyprolis," and "PX-171" through January 1, 2017.Study selectionPhase 1 to 3 prospective clinical trials of carfilzomib in patients with multiple myeloma with evaluable toxic effects data were eligible for meta-analysis.Data extraction and synthesisData were independently extracted by 2 reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Pooled incidence rates and relative risks (for randomized trials) and 95% confidence intervals were calculated using a random effects model. Subgroup analyses were performed to assess study-level characteristics associated with CVAE.Main outcomes and measuresCardiovascular adverse events were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grades 3 or higher AEs and study characteristics were recorded.ResultsA total of 514 studies were assessed for eligibility. Of those, 24 studies were eligible, including a total of 2594 patients with multiple myeloma. All-grade and grades 3 and higher CVAE were seen in 617 (18.1%) and 274 (8.2%), respectively. Phase 2 or 3 studies and carfilzomib doses of 45 mg/m2 or higher were associated with high-grade CVAE. Median age older than 65 years, prior myeloma therapies, and concurrent myeloma therapies were not associated with CVAE. For the 3 randomized clinical trials, the summary relative risk of all-grade and grade 3 or higher CVAE for patients receiving carfilzomib compared with noncarfilzomib-receiving control patients were 1.8 and 2.2, respectively.Conclusions and relevanceCarfilzomib was associated with a significant incidence of CVAE, with higher rates seen with higher doses of carfilzomib. Phase 1 studies may be underdetecting CVAE. Future studies are needed to identify patients at high risk for CVAE, develop optimal monitoring strategies, and explore strategies to mitigate these risks.
| S-EPMC5885859 | biostudies-literature
Project description:BackgroundThe preventive effect of cholesterol efflux capacity (CEC) on the progression of atherosclerotic lesions has been confirmed in animal models, but findings in the population are inconsistent. Therefore, this meta-analysis aimed to systematically investigate the relationship of CEC with coronary artery disease (CAD) and cardiovascular mortality in a general population.MethodsFour electronic databases (PubMed, Embase database, Cochrane Library, Web of Science) were searched from inception to February 1st, 2022 for relevant studies, without any language restriction. For continuous variables, the mean and standard deviation (SD), maximum adjusted odds ratios (ORs), relative risks (RRs), or hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted. The random-effects model was adopted to calculate the pooled results, and dose-response analyses were conducted. All pooled results were expressed by standardized mean difference (SMD) and ORs.ResultsFinally, 18 observational studies were included. Compared with the non-CAD group, the CAD group (SMD -0.48, 95% CI - 0.66 to - 0.30; I2 88.9%) had significantly lower CEC. In the high-CEC population, the risks of CAD (OR 0.52, 95% CI 0.37 to 0.71; I2 81%) significantly decreased, and a linear negative dose-response was detected. However, an association between CEC and the risk of cardiovascular mortality was not found (OR 0.44, 95% CI 0.18 to 1.06; I2 83.2%).ConclusionsThis meta-analysis suggests that decreased CEC is strongly associated with the risk of CAD, independent of HDL-C level. However, a decreased CEC seems not to be related to cardiovascular mortality. Meanwhile, CEC is linearly negatively correlated with the risk of CAD.
| S-EPMC9148501 | biostudies-literature
Project description:BackgroundThis review aims to examine the association of Parkinson's disease (PD) with the increased risk of cardiovascular events.MethodsPubMed, Embase, CENTRAL, and Scopus databases were electronically searched for papers published up to 5 May 2023. Studies reporting the association between PD and the subsequent risks of stroke, myocardial infarction (MI), and cardiovascular mortality were included.ResultsSixteen studies were included in this review. The clinical data of 101,712 PD patients were compared with that of the control group of 204,901 patients without PD in the included studies. Meta-analysis showed that PD patients had an increased risk of stroke compared with patients without PD (odds ratio (OR): 1.49; 95% confidence interval (CI): 1.30, 1.72; I2 = 76%). The pooled analysis demonstrated no significant increase in the risk of MI (OR: 1.16; 95% CI: 0.85, 1.59; I2 = 82%) and cardiovascular mortality (OR: 1.20; 95% CI: 0.93, 1.54; I2 = 65%) in PD patients. However, data from cohort studies indicated a possibility of higher risk of MI (OR: 1.36; 95% CI: 1.01, 1.84; I2 = 80%) and cardiovascular mortality (OR: 1.22; 95% CI: 1.00, 1.60; I2 = 62%) in patients with PD.ConclusionPatients with PD may have an increased risk of stroke as compared with the age- and gender-matched general population. While our results show that PD does not increase the overall risk of MI and cardiovascular mortality, analysis of cohort studies alone demonstrated that these risks may be higher in patients with PD. The current evidence is of very low quality. Further prospective cohort studies from different countries that would account for important cardiovascular risk factors are needed to improve the current evidence.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42023421924).
| S-EPMC10748497 | biostudies-literature
Project description:Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to cardiovascular disease (CVD). The aim of this study is to assess whether and to what extent the excess risk of CVD is conferred by NAFLD in a meta-analysis. We systematically searched PubMed, EmBase, Web of Science, and Cochrane Library for reports published between 1965 and July 3, 2015. Studies that reported data on association between NAFLD and adverse cardiovascular events or mortality were included. Thirty-four studies (164,494 participants, 21 cross-sectional studies, and 13 cohort studies) were included. NAFLD was not associated with overall mortality (HR?=?1.14, 95% CI: 0.99-1.32) and CVD mortality (HR?=?1.10, 95% CI: 0.86-1.41). However, NAFLD was associated with an increased risk of prevalent (OR?=?1.81, 95% CI: 1.23-2.66) and incident (HR?=?1.37, 95% CI: 1.10-1.72) CVD. For some specific CVDs, NAFLD was associated with an increased risk of prevalent (OR?=?1.87, 95% CI: 1.47-2.37) and incident (HR?=?2.31, 95% CI: 1.46-3.65) coronary artery disease (CAD), prevalent (OR?=?1.24, 95% CI: 1.14-1.36) and incident (HR?=?1.16, 95% CI: 1.06-1.27) hypertension, and prevalent (OR?=?1.32, 95% CI: 1.07-1.62) atherosclerosis. In conclusion, the presence of NAFLD is associated with an increased risk of major adverse cardiovascular events, although it is not related to mortality from all causes or CVD.
| S-EPMC5026028 | biostudies-literature
Project description:ObjectiveTo examine the association between antihypertensive treatment and specific adverse events.DesignSystematic review and meta-analysis.Eligibility criteriaRandomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or higher blood pressure targets compared with lower targets. To avoid small early phase trials, studies were required to have at least 650 patient years of follow-up.Information sourcesSearches were conducted in Embase, Medline, CENTRAL, and the Science Citation Index databases from inception until 14 April 2020.Main outcome measuresThe primary outcome was falls during trial follow-up. Secondary outcomes were acute kidney injury, fractures, gout, hyperkalaemia, hypokalaemia, hypotension, and syncope. Additional outcomes related to death and major cardiovascular events were extracted. Risk of bias was assessed using the Cochrane risk of bias tool, and random effects meta-analysis was used to pool rate ratios, odds ratios, and hazard ratios across studies, allowing for between study heterogeneity (?2).ResultsOf 15?023 articles screened for inclusion, 58 randomised controlled trials were identified, including 280?638 participants followed up for a median of 3 (interquartile range 2-4) years. Most of the trials (n=40, 69%) had a low risk of bias. Among seven trials reporting data for falls, no evidence was found of an association with antihypertensive treatment (summary risk ratio 1.05, 95% confidence interval 0.89 to 1.24, ?2=0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, ?2=0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, ?2=0.122, n=26), hypotension (1.97, 1.67 to 2.32, ?2=0.132, n=35), and syncope (1.28, 1.03 to 1.59, ?2=0.050, n=16). The heterogeneity between studies assessing acute kidney injury and hyperkalaemia events was reduced when focusing on drugs that affect the renin angiotensin-aldosterone system. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial. Antihypertensive treatment was associated with a reduced risk of all cause mortality, cardiovascular death, and stroke, but not of myocardial infarction.ConclusionsThis meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function.RegistrationPROSPERO CRD42018116860.
| S-EPMC7873715 | biostudies-literature
Project description:IntroductionPercutanous coronary intervention (PCI) has been increasingly used for patients suffered from severe coronary artery disease. However, physical trauma and potential adverse events related to the procedure often result in detrimental psychological stress. Accumulating evidences have shown that depression is closely related to coronary artery disease. However, the association of depression following percutanous coronary intervention with adverse cardiovascular events is still unknown.ObjectiveThis review is designed to assess the prognostic association of depression following PCI with adverse cardiac events.Methods and analysisThe following databases will be searched, PubMed, the EMBASE, CINAHL and Web of Science of English-language publications from inception to 30 October 2018. Cross-referencing from retrieved studies will be conducted additionally, and observational studies were included. Two independent review authors will do the study selection on the basis of the study eligibility criteria. Extracted data will be used for quantitative and qualitative evidence synthesis as well as to assess methodological quality of studies using the Newcastle-Ottawa checklist. The primary objective of this review is adverse cardiac events, presented as a composition of myocardial infarction, repeat coronary revascularization, cardiac readmission, and cardiac death. The accumulated evidence is evaluated and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE).Results and conclusionsThis review will explain the association of depression following percutanous coronary intervention with adverse cardiovascular events, and provide physicians with scientific evidence for psychological intervention in patients after PCI.Prospero registration numberCRD42018112486.
| S-EPMC6336612 | biostudies-literature
Project description:BackgroundThere have been postmarketing reports of adverse cardiovascular events associated with the use of varenicline, a widely used smoking cessation drug. We conducted a systematic review and meta-analysis of randomized controlled trials to ascertain the serious adverse cardiovascular effects of varenicline compared with placebo among tobacco users.MethodsWe searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, websites of regulatory authorities and registries of clinical trials, with no date or language restrictions, through September 2010 (updated March 2011) for published and unpublished studies. We selected double-blind randomized controlled trials of at least one week's duration involving smokers or people who used smokeless tobacco that reported on cardiovascular events (ischemia, arrhythmia, congestive heart failure, sudden death or cardiovascular-related death) as serious adverse events asociated with the use of varenicline.ResultsWe analyzed data from 14 double-blind randomized controlled trials involving 8216 participants. The trials ranged in duration from 7 to 52 weeks. Varenicline was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo (1.06% [52/4908] in varenicline group v. 0.82% [27/3308] in placebo group; Peto odds ratio [OR] 1.72, 95% confidence interval [CI] 1.09-2.71; I(2) = 0%). The results of various sensitivity analyses were consistent with those of the main analysis, and a funnel plot showed no publication bias. There were too few deaths to allow meaningful comparisons of mortality.InterpretationOur meta-analysis raises safety concerns about the potential for an increased risk of serious adverse cardiovascular events associated with the use of varenicline among tobacco users.
| S-EPMC3168618 | biostudies-literature
Project description:ImportanceCardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized.ObjectiveTo determine the association of BRAF and MEK inhibitor treatment with CVAEs in patients with melanoma compared with BRAF inhibitor monotherapy.Data sourcesPubMed, Cochrane, and Web of Science were systematically searched for keywords vemurafenib, dabrafenib, encorafenib, trametinib, binimetinib, and cobinimetinib from database inception through November 30, 2018.Study selectionRandomized clinical trials reporting on CVAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected.Data extraction and synthesisData assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Pooled relative risks (RRs) and 95% CIs were determined using random-effects and fixed-effects analyses. Subgroup analyses were conducted to assess study-level characteristics associated with CVAEs.Main outcomes and measuresThe selected end points were pulmonary embolism, a decrease in left ventricular ejection fraction, arterial hypertension, myocardial infarction, atrial fibrillation, and QTc interval prolongation. All-grade and high-grade (≥3) CVAEs were recorded.ResultsOverall, 5 randomized clinical trials including 2317 patients with melanoma were selected. Treatment with BRAF and MEK inhibitors was associated with an increased risk of pulmonary embolism (RR, 4.36; 95% CI, 1.23-15.44; P = .02), a decrease in left ventricular ejection fraction (RR, 3.72; 95% CI, 1.74-7.94; P < .001), and arterial hypertension (RR, 1.49; 95% CI, 1.12-1.97; P = .005) compared with BRAF inhibitor monotherapy. The RRs for myocardial infarction, atrial fibrillation, and QTc prolongation were similar between the groups. These results were consistent when assessing high-grade CVAEs (left ventricular ejection fraction: RR, 2.79; 95% CI, 1.36-5.73; P = .005; I2 = 29%; high-grade arterial hypertension: RR, 1.54; 95% CI, 1.14-2.08; P = .005; I2 = 0%), but RRs for high-grade pulmonary embolism were similar between groups. A higher risk of a decrease in left ventricular ejection fraction was associated with patients with a mean age younger than 55 years (RR, 26.50; 95% CI, 3.58-196.10; P = .001), and the associated risk of pulmonary embolism was higher for patients with a mean follow-up time longer than 15 months (RR, 7.70; 95% CI, 1.40-42.12; P = .02).Conclusions and relevanceTherapy with BRAF and MEK inhibitors was associated with a higher risk of CVAEs compared with BRAF inhibitor monotherapy. The findings may help to balance between beneficial melanoma treatment and cardiovascular morbidity and mortality.
| S-EPMC6692687 | biostudies-literature