Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

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GW29-e0177 Increased risk of ischemic stroke associated with new-onset atrial fibrillation complicating acute coronary syndrome: a systematic review and meta-analysis

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2018.08.991 ◽

2018 ◽

Vol 72 (16) ◽

pp. C232

Author(s):

Jiachen Luo ◽

Hongqiang Li ◽

Xiaoming Qin ◽

Baoxin Liu ◽

Jinlong Zhao ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Acute Coronary Syndrome ◽

Ischemic Stroke ◽

Meta Analysis ◽

Coronary Syndrome ◽

Increased Risk ◽

Onset Atrial Fibrillation ◽

New Onset

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5132Effect of PCSK9 inhibitors treatment on acute coronary syndrome and stroke incidence: a metanalysis of currently available clinical trials

European Heart Journal ◽

10.1093/eurheartj/ehz746.0046 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Cordero ◽

L Facila ◽

M Rodriguez-Manero ◽

M Gomez-Martinez ◽

V Bertomeu-Gonzalez ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Cardiovascular Events ◽

Meta Analysis ◽

Density Lipoprotein ◽

Cochrane Collaboration ◽

Significant Heterogeneity ◽

Pcsk9 Inhibitors ◽

Stroke Incidence ◽

Coronary Syndrome ◽

Major Cardiovascular Events

Abstract Background Proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors have demonstrated to induce large reductions in low-density lipoprotein cholesterol (LDLc) and major cardiovascular events but none of the studies was statistically powered to demonstrate reductions in specific endpoints rather than a combined end-point of major cardiovascular events. Methods We performed an intention-to-treat meta-analysis in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement using currently available studies involving PCSK9 inhibitors. The endpoint assessed were acute coronary syndrome (ACS) and stroke. Results We included 81,544 patients, 41,147 treated with a PSCK9 inhibitors: 17,179 with evolocumab; 13,718 with bococizumab and 10,250 with alirocumab (table 1). A total of 1,316 ACS were registered in the treatment group vs. 1,608 in controls, resulting in 18.0% reduction associated with PCSK9 treatment (figure 1). This result was reproduced exactly in the EBCT althougt a non-significant heterogeneity was detected (p=0.052). Metaregression analyses did not demonstrate the implication of the study (p=0.45), study drugs (p=0.26), age (p=0.89), hypertension (p=0.81) or diabetes (p=0.81) on such result. Results on stroke incidence are presented in figure 2. PCSK9 inhibitors treatment resulted in a 24% reduction of stroke when all studies were analyzed together; heterogeneity was statistically significant (p=0.021) but it was not observed in the EBCT analysis where PCSK9 inhibitors were associated with 24% stroke incidence reduction. Conclusions The meta-analysis of currently available studies demonstrates that PCSK9 inhibitors treatment reduces the incidence of ACS by 18% and stroke by 24%.

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Anxiety and clinical outcomes of patients with acute coronary syndrome: a meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-034135 ◽

2020 ◽

Vol 10 (7) ◽

pp. e034135 ◽

Cited By ~ 1

Author(s):

Jie Li ◽

Feng Ji ◽

Junxian Song ◽

Xiangyang Gao ◽

Deguo Jiang ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Clinical Outcomes ◽

Mortality Risk ◽

Meta Analysis ◽

Secondary Outcome ◽

Coronary Syndrome ◽

Increased Risk ◽

Follow Up Studies ◽

Poor Outcomes

ObjectivesAnxiety has been suggested to be associated with poor outcomes in patients with acute coronary syndrome (ACS). However, results of previous follow-up studies were inconsistent. The aim of this meta-analysis was to evaluate the association between anxiety and clinical outcomes in patients with ACS, and to investigate the potential role of depression underlying the above association.DesignA meta-analysis of prospective follow-up studies.SettingHospitals.ParticipantsPatients with ACS.InterventionsWe included related prospective follow-up studies up through 20 July 2019 that were identified by searching PubMed and Embase databases. A random-effect model was used for the meta-analysis. Anxiety was evaluated by validated instruments at baseline.Primary and secondary outcome measuresWe determined the association between anxiety and risks of mortality and adverse cardiovascular events (MACEs) in patients with ACS.ResultsOur analysis included 17 studies involving 39 038 patients wqith ACS. Anxiety was independently associated with increased mortality risk (adjusted risk ratio (RR) 1.21, 95% CI 1.07 to 1.37, p=0.002) and MACEs (adjusted RR 1.47, 95% CI 1.24 to 1.74, p<0.001) in patients with ACS. Subgroup analyses showed that depression may at least partly confound the association between anxiety and poor outcomes in patients with ACS. Adjustment of depression significantly attenuated the association between anxiety and MACEs (adjusted RR 1.25, 95% CI 1.04 to 1.52, p=0.02). Moreover, anxiety was not significantly associated with mortality risk after adjusting for depression (adjusted RR 0.88, 95% CI 0.66 to 1.17, p=0.37).ConclusionsAnxiety is associated with increased risk of mortality and MACEs in patients with ACS. However, at least part of the association may be confounded by concurrent depressive symptoms in these patients.

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Fasting Blood Glucose to High-Density Lipoprotein Cholesterol Ratio in Relation to Short-Term Outcomes in Patients with Acute Coronary Syndrome

10.21203/rs.3.rs-1056228/v1 ◽

2021 ◽

Author(s):

Simin Deng ◽

Zhaojun Wang ◽

Yifeng Zhang ◽

Ying Xin ◽

Cheng Zeng ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Blood Glucose ◽

Regression Model ◽

Piecewise Linear ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Short Term ◽

Piecewise Linear Regression ◽

Coronary Syndrome ◽

Increased Risk

Abstract BackgroundBiochemical markers are crucial for determining risk in patients with coronary artery disease (CAD); however, the association between the fasting blood glucose to high-density lipoprotein cholesterol (FG/HDL-C) ratio and short-term outcomes in patients with acute coronary syndrome (ACS) remains unknown. We investigated the association between the FG/HDL-C ratio and 30-day major adverse cardiovascular events (MACEs) and cardiovascular (CV) death in patients with ACS.eMethodsWe performed a post-hoc analysis of data from the Acute Coronary Syndrome Quality Improvement in Kerala (ACS-QUIK) study. A total of 11,284 patients with ACS were subdivided into quartiles according to their FG/HDL-C ratios. We used a multivariate logistic regression model, generalized additive model (GAM), and two-piecewise linear regression model to determine the association of the FG/HDL-C ratio with MACEs (death, reinfarction, stroke, and major bleeding) and CV death. ResultsThe FG/HDL-C ratio was significantly associated with an increased risk of MACEs and CV death in patients with ACS in the highest quartile (MACEs, odds ratio [OR]: 1.49; 95% confidence interval [CI], [1.11, 1.99]; P<0.01; CV death, OR: 1.69; 95% CI, [1.01, 1.41]; P=0.04). The GAM and two-piecewise linear regression model demonstrated that the relationship between the FG/HDL-C ratio and MACEs and CV death was non-linear (non-linear P<0.05); the threshold values were 3.02 and 3.00 for MACEs and CV death, respectively.ConclusionsA higher FG/HDL-C ratio is associated with an increased risk of MACEs and CV death in patients with ACS.

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Association Between Metabolic Syndrome and All-Cause Mortality in Patients with Acute Coronary Syndrome: A Meta-Analysis

Hormone and Metabolic Research ◽

10.1055/a-1381-8245 ◽

2021 ◽

Author(s):

Yong Yang ◽

Haili Shen ◽

Zhigeng Jin ◽

Dongxing Ma ◽

Qing Zhao ◽

...

Keyword(s):

Metabolic Syndrome ◽

Acute Coronary Syndrome ◽

Hospital Mortality ◽

Meta Analysis ◽

Survival Outcome ◽

Coronary Syndrome ◽

Increased Risk ◽

All Cause Mortality

AbstractThe association between metabolic syndrome (MetS) and survival outcome after acute coronary syndrome (ACS) remains controversial. This meta-analysis sought to examine the association of MetS with all-cause mortality among patients with ACS. Two authors independently searched PubMed and Embase databases (from their inception to June 27, 2020) for studies that examined the association of MetS with all-cause mortality among patients with ACS. Outcome measures were in-hospital mortality and all-cause mortality during the follow-up. A total of 10 studies involving 49 896 ACS patients were identified. Meta-analysis indicated that presence of MetS was associated with an increased risk of long-term all-cause mortality [risk ratio (RR) 1.25; 95% CI 1.15–1.36; n=9 studies] and in-hospital mortality (RR 2.35; 95% CI 1.40–3.95; n=2 studies), respectively. Sensitivity and subgroup analysis demonstrated the credibility of the value of MetS in predicting long-term all-cause mortality. MetS is associated with an increased risk of long-term all-cause mortality among patients with ACS. However, additional studies are required to investigate the association of MetS with in-hospital mortality.

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The Association between Nutritional Status and In-Hospital Mortality among Patients with Acute Coronary Syndrome—A Result of the Retrospective Nutritional Status Heart Study (NSHS)

Nutrients ◽

10.3390/nu12103091 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3091

Author(s):

Michał Czapla ◽

Piotr Karniej ◽

Raúl Juárez-Vela ◽

Katarzyna Łokieć

Keyword(s):

Acute Coronary Syndrome ◽

Nutritional Status ◽

Hospital Mortality ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Nutrition Risk ◽

Risk Of Death ◽

Coronary Syndrome ◽

Heart Study ◽

Increased Risk

Background: Nutritional status is related to the prognosis and the length of hospitalization of individuals with myocardial infarction. This study aimed to assess the effects of nutritional status on in-hospital mortality in patients with acute coronary syndrome. Methods: We performed a retrospective study of 1623 medical records of patients admitted to the cardiology department of the University Clinical Hospital in Wroclaw (Poland) between 2017 and 2019. Results: It was found that, of those who died in the sample, 50% had a BMI within the normal range, 29% were in the overweight range and 18% were in the obese range. Patients who died had significantly more frequent occurrences of the following: Nutrition Risk Screening (NRS) ≥ 3 (20% vs. 6%; p < 0.001); heart failure (53% vs. 25%; p < 0.001); or a history of stroke (22% vs. 9%; p < 0.001), arterial hypertension (66% vs. 19%; p < 0001) or diabetes (41% vs. 19%; p < 0.001). Statistically significant differences were found when considering the type of infarction, diabetes or people with low-density lipoprotein greater than or equal to 70 mg/dL. Conclusions: This study shows that malnutrition correlates with an increased risk of death during hospitalization.

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The effectiveness of clopidogrel in the prevention of thrombotic complications in patients with acute coronary syndrome and genetic factors

Kazan medical journal ◽

10.17816/kmj2312 ◽

2012 ◽

Vol 93 (2) ◽

pp. 294-297

Author(s):

A S Galyavich ◽

D D Valeeva

Keyword(s):

Acute Coronary Syndrome ◽

Meta Analysis ◽

Prognostic Significance ◽

Antiplatelet Drug ◽

C3435t Polymorphism ◽

Risk Of Death ◽

Coronary Syndrome ◽

P Glycoprotein ◽

Cyp2c19 Polymorphism ◽

Increased Risk

This review article presents the current views on genotyping during administration of clopidogrel - an antiplatelet drug from the class of thienopyridines, for patients with acute coronary syndrome. Highlighted were the data on genetic disorders affecting the absorption and metabolism of clopidogrel. The gene ABCB1 (MDR1) encodes the intestinal transporter P-glycoprotein. The variability of this gene may affect the bioavailability of clopidogrel. However, data on the relationship between C3435T polymorphism of ABCB1 gene and the expression of P-glycoprotein still remain controversial. Differences in the effects of C3435T may reflect the differences in the frequency of ABCB1 polymorphism among ethnic groups and the complex of effects of different polymorphisms in the same gene within a haplotype, or confounding factors of the environment. The most important role in the metabolism of clopidogrel is played by cytochrome P-450 (iso-enzyme CYP2C19). Several large studies have confirmed the prognostic significance of CYP2C19 polymorphism in patients receiving clopidogrel. In a recent meta-analysis of nine pharmacogenetic studies of clopidogrel, which included 9685 patients with acute coronary syndrome, revealed was a significant association between the homozygous and heterozygous alleles with reduced CYP2C19 function and an increased risk of death due to cardiovascular disease, myocardial infarction or stroke. Two large randomized studies of CYP2C19 genotyping did not reveal any relationship between its variants and the occurrence of cardiovascular events in patients with acute coronary syndrome or atrial fibrillation. Thus, in genetic studies of the antiplatelet effectiveness of clopidogrel, there are many uncertainties; domestic data on this subject is extremely scarce.

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Weekend effect in acute coronary syndrome: A meta-analysis of observational studies

European Heart Journal Acute Cardiovascular Care ◽

10.1177/2048872618762634 ◽

2018 ◽

Vol 8 (5) ◽

pp. 432-442 ◽

Cited By ~ 4

Author(s):

Chun Shing Kwok ◽

Mohammed Al-Dokheal ◽

Sami Aldaham ◽

Claire Rushton ◽

Rob Butler ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Patient Outcomes ◽

Observational Studies ◽

Meta Analysis ◽

Early Mortality ◽

Weekend Effect ◽

Coronary Syndrome ◽

Increased Risk ◽

St Elevation ◽

Meta Regression

Background: The effect of a weekend compared with a weekday hospital admission on patient outcomes after an acute coronary syndrome is unclear. This study aims to determine whether collectively there is a weekend effect in acute coronary syndrome. Method: We conducted a systematic review and meta-analysis of cohort studies examining the association between weekend compared to weekday admission at any time of the day and early mortality (in-hospital or 30-day). A search was performed on Medline and Embase and relevant studies were pooled using random effects meta-analysis for risk of early mortality. Additional analyses were performed considering only more recent studies (conducted after 2005) and by patient group (ST-elevation myocardial infarction [STEMI] or non-STEMI [NSTEMI]), as well as meta-regression according to starting year and mean year of study. Results: A total of 18 studies were included with over 14 million participants incorporating 3 million weekend and over 11.5 million weekday admissions and the rates of mortality were 19.2% and 23.4%, respectively. The pooled results of all 18 studies suggest that weekend admission was associated with a small increased risk of early mortality (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03–1.09). The results for subgroups of STEMI and NSTEMI cohorts were not statistically significant and timing of admission after 2005 had minimal influence on the results (OR 1.06, 95% CI 0.95–1.17). Conclusions: There is a small weekend effect for admission with acute coronary syndrome that has persisted over time.

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