Abstract 3526: Medication Non-adherence Is Associated With A Broad Range Of Adverse Outcomes In Patients With Coronary Artery Disease

Background: Little is known about the effect of non-adherence among coronary artery disease (CAD) patients on a broad spectrum of outcomes including cardiovascular mortality, cardiovascular hospitalizations or revascularization procedures. Methods: This was a retrospective cohort study of 15,767 patients with CAD in a managed care organization. Medication adherence was calculated as proportion of days covered (PDC) for filled prescriptions of β-blockers, ACE-inhibitors, and statin medications. Multivariable Cox regression assessed the association between medication non-adherence as a time-varying covariate and mortality (all-cause and cardiovascular), adjusting for demographics and clinical characteristics. Median follow-up was 4.1 years. Results: Across the three classes of medications, non-adherent patients were more likely to be younger and have a diagnosis of COPD or depression. In unadjusted analysis, non-adherence to each individual class of medication was associated with higher all-cause and cardiovascular mortality. In multivariable analysis, non-adherence remained significantly associated with increased all-cause mortality risk for β-blockers (HR 1.50; 95% CI 1.33–1.71), ACE-inhibitors (HR 1.74; 95% CI 1.52–1.98), and statins (HR 1.85; 95% CI 1.63–2.09). In addition, non-adherence remained significantly associated with higher risk of cardiovascular mortality for β-blockers (HR 1.53; 95% CI 1.16 –2.01), ACE-inhibitors (HR 1.66; 95% CI 1.26 –2.20), and statins (HR 1.62; 95% CI 1.124 –2.13). The findings of increased risk associated with non-adherence were consistent for cardiovascular hospitalization and revascularization procedures. Conclusions: Non-adherence to cardioprotective medications is associated with a broad range of adverse outcomes. These findings support the importance of non-adherence in clinical practice and suggest that medication non-adherence should be a target for future interventions.

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Association between Serum Interleukin-6 Concentration and Mortality in Patients with Coronary Artery Disease

Mediators of Inflammation ◽

10.1155/2013/726178 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 32

Author(s):

Dongfang Su ◽

Zhongxia Li ◽

Xinrui Li ◽

Yuming Chen ◽

Yuan Zhang ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Mortality ◽

Interleukin 6 ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Increased Risk ◽

Artery Disease

Objectives. To evaluate whether serum interleukin-6 (IL-6) is associated with increased risk of mortality in coronary artery disease (CAD) patients.Methods. We performed a prospective cohort study of 718 CAD patients from the Guangzhou Cardiovascular Disease Cohort (GCDC) study. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 with all-cause and cardiovascular mortality.Results. During the 1663 person-years of followup, the cumulative all-cause mortality and cardiovascular mortality were 6.5% (n=47) and 3.3% (n=24), respectively. The mean length of followup was2.32±0.81years. In the multivariable analyses, a one-SD increment in log-transformed serum IL-6 was positively associated with an increased risk of all-cause and cardiovascular mortality, with hazard ratios (HR) of 2.93 (95% CI, 2.11–4.08) and 2.04 (95% CI, 1.34–3.68) within the patients combined and 2.98 (95% CI, 2.12–4.18) and 3.10 (95% CI, 1.98–4.85) within males, respectively. Patients in the highest serum IL-6 tertile versus the lowest tertile were at higher risk of all-cause and cardiovascular mortality, with HR of 17.12 (95% CI 3.11–71.76) and 8.68 (95% CI, 1.88–37.51), respectively.Conclusions. In hospitalized patients with CAD, serum IL-6 is significantly associated with all-cause and cardiovascular mortality.

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Asymmetrical Dimethylarginine Independently Predicts Total and Cardiovascular Mortality in Individuals with Angiographic Coronary Artery Disease (The Ludwigshafen Risk and Cardiovascular Health Study)

Clinical Chemistry ◽

10.1373/clinchem.2006.076711 ◽

2007 ◽

Vol 53 (2) ◽

pp. 273-283 ◽

Cited By ~ 160

Author(s):

Andreas Meinitzer ◽

Ursula Seelhorst ◽

Britta Wellnitz ◽

Gabriele Halwachs-Baumann ◽

Bernhard O Boehm ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Cardiovascular Risk ◽

Coronary Artery ◽

Cardiovascular Risk Factors ◽

Cardiovascular Mortality ◽

Asymmetrical Dimethylarginine ◽

Hazard Ratios ◽

Increased Risk ◽

Artery Disease

Abstract Background: Asymmetrical dimethylarginine (ADMA) is increased in conditions associated with increased risk of atherosclerosis. We investigated the use of ADMA to predict total and cardiovascular mortality in patients scheduled for coronary angiography. Methods: In 2543 persons with and 695 without coronary artery disease (CAD) identified by angiography we measured ADMA and recorded total and cardiovascular mortality during a median follow-up of 5.45 years. Results: ADMA was correlated positively to age, female sex, diabetes mellitus, former and current smoking, and C-reactive protein and inversely to HDL cholesterol and triglycerides. ADMA was not associated with body mass index, hypertension, LDL cholesterol, or the presence or absence of angiographic CAD. Glomerular filtration rate and homocysteine were the strongest predictors of ADMA. At the 2nd, 3rd and 4th quartile of ADMA, hazard ratios for all-cause mortality adjusted for age, sex, and cardiovascular risk factors were 1.12 [95% confidence interval (CI) 0.83–1.52], 1.35 (95% CI 1.01–1.81), and 1.87 (95% CI 1.43–2.44), respectively, compared with the 1st quartile. Hazard ratios for cardiovascular death were 1.13 (95% CI 0.78–1.63), 1.42 (95% CI 1.00–2.02), and 1.81 (95% CI 1.31–2.51). ADMA in the highest quartile remained predictive of mortality after accounting for medication at baseline. The predictive value of ADMA was similar to that in the entire cohort in persons with CAD, stable or unstable, but was not statistically significant in persons without angiographic CAD. Conclusions: ADMA concentration predicts all-cause and cardiovascular mortality in individuals with CAD independently of established and emerging cardiovascular risk factors.

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Comprehensive Metabolomics Identified the Prominent Role of Glycerophospholipid Metabolism in Coronary Artery Disease Progression

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.632950 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hui Chen ◽

Zixian Wang ◽

Min Qin ◽

Bin Zhang ◽

Lu Lin ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Adverse Outcomes ◽

Combined Model ◽

C Statistic ◽

Lipid Species ◽

Increased Risk ◽

Traditional Risk Factors ◽

Artery Disease

Background: Coronary stenosis severity determines ischemic symptoms and adverse outcomes. The metabolomic analysis of human fluids can provide an insight into the pathogenesis of complex disease. Thus, this study aims to investigate the metabolomic and lipidomic biomarkers of coronary artery disease (CAD) severity and to develop diagnostic models for distinguishing individuals at an increased risk of atherosclerotic burden and plaque instability.Methods: Widely targeted metabolomic and lipidomic analyses of plasma in 1,435 CAD patients from three independent centers were performed. These patients were classified as stable coronary artery disease (SCAD), unstable angina (UA), and myocardial infarction (MI). Associations between CAD stages and metabolic conditions were assessed by multivariable-adjusted logistic regression. Furthermore, the least absolute shrinkage and selection operator logistic-based classifiers were used to identify biomarkers and to develop prediagnostic models for discriminating the diverse CAD stages.Results: On the basis of weighted correlation network analysis, 10 co-clustering metabolite modules significantly (p < 0.05) changed at different CAD stages and showed apparent correlation with CAD severity indicators. Moreover, cross-comparisons within CAD patients characterized that a total of 72 and 88 metabolites/lipid species significantly associated with UA (vs. SCAD) and MI (vs. UA), respectively. The disturbed pathways included glycerophospholipid metabolism, and cysteine and methionine metabolism. Furthermore, models incorporating metabolic and lipidomic profiles with traditional risk factors were constructed. The combined model that incorporated 11 metabolites/lipid species and four traditional risk factors represented better discrimination of UA and MI (C-statistic = 0.823, 95% CI, 0.783–0.863) compared with the model involving risk factors alone (C-statistic = 0.758, 95% CI, 0.712–0.810). The combined model was successfully used in discriminating UA and MI patients (p < 0.001) in a three-center validation cohort.Conclusion: Differences in metabolic profiles of diverse CAD subtypes provided a new approach for the risk stratification of unstable plaque and the pathogenesis decipherment of CAD progression.

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Relative value of plasma nitrotyrosine for predicting mortality in patients with coronary artery diseases

Clinical & Investigative Medicine ◽

10.25011/cim.v30i4.2855 ◽

2007 ◽

Vol 30 (4) ◽

pp. 83

Author(s):

C L Heslop ◽

J J Frohlich ◽

J S Hill

Keyword(s):

Oxidative Stress ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Mortality ◽

Plaque Rupture ◽

Lipid Lowering ◽

Relative Value ◽

Increased Risk ◽

All Cause Mortality ◽

Artery Disease

Background: Reactive oxygen species (ROS) mediate the signalling of chief inflammatory pathways throughout all stages of atherosclerosis from endothelial dysfunction to plaque rupture. Activated leukocytes within the atherosclerotic lesion produce ROS, causing local and systemic oxidative injury; however, contributions of ROS production to the clinical features atherosclerosis have not yet been clearly established. Markers of oxidative stress include nitrotyrosine (N-tyr), a post-translational modification generated by reactive nitrogen species. N-tyr is enriched in atherosclerotic lesions, where it activates interstitial metalloproteases, which destabilize the lesion and induce plaque rupture. Recent findings associate circulating N-tyr levels with CAD pathogenesis: N-tyr levels are elevated in patients with established CAD, increased by risk factors associated with atherosclerosis, and reduced by statin therapy. The value circulating N-tyr may have for predicting outcome in CAD patients has not yet been determined. Study Design: We tested the hypothesis that elevated N-tyr predicts mortality in patients with coronary artery disease. Plasma levels of N-tyr were measured using an enzyme-linked immunoassay (Hycult) in a cohort of 619 patients with angiographic evidence of coronary artery disease. After a mean follow-up time of 8.5 years, cases of all-cause mortality (145 cases) and cardiovascular mortality (76 cases) were collected using BC Vital Statistics Agency. The relative value of plasma N-tyr for prediction of mortality was determined using Cox proportional hazards model with adjustment for the following covariates: age, sex, smoking status, hypertension, BMI, LDL-cholesterol, total:HDL-cholesterol, plasma c-reactive protein, personal or known family history of CAD, and reported use of lipid-lowering or antioxidant therapies. Interpretation: Patients whose plasma N-tyr levels were above the cohort median (71.75 nmol/L) had an increased risk of mortality, however this increased risk did not reach conventional statistical significance after covariate adjustment [HR(CI):1.39(0.96-2.01) p=0.07]. No significant association was observed between N-tyr levels and risk of cardiovascular mortality. While this investigation did not reveal a strong association between elevated N-tyr levels and cardiovascular mortality, the trend for increased risk of all-cause mortality indicates that this marker of oxidative stress could be used to identify patients for whom oxidative processes contribute significantly to disease pathogenesis. Further studies are warranted to establish the clinical value of N-tyr and other oxidative stress biomarkers, with the ultimate goal of improving patient risk assessment, and monitoring primary and secondary cardiovascular risk-reduction strategies.

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Population-specific and transethnic genome-wide analyses reveal distinct and shared genetic risks of coronary artery disease

10.1101/827550 ◽

2019 ◽

Author(s):

Satoshi Koyama ◽

Kaoru Ito ◽

Chikashi Terao ◽

Masato Akiyama ◽

Momoko Horikoshi ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Mortality ◽

Large Scale ◽

Meta Analysis ◽

Genotype Imputation ◽

Polygenic Risk Score ◽

Genome Wide ◽

Increased Risk ◽

Artery Disease

AbstractTo elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study (GWAS) of 168,228 Japanese (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,782 CAD cases and 3,148 controls. We detected 9 novel disease-susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a transethnic meta-analysis and discovered 37 additional novel loci. Using the result of the meta-analysis, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European GWAS. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improves clinical characterization of CAD genetics and suggests the utility of transethnic meta-analysis for PRS derivation in non-European populations.

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Women who have angina and report more physical symptoms are at increased risk for coronary artery disease

PsycEXTRA Dataset ◽

10.1037/e556942006-001 ◽

1999 ◽

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Physical Symptoms ◽

Increased Risk ◽

Artery Disease

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Molecular Evaluation of MicroRNA-146 Gene Variability (rs2910164 C> G) and its Association with Increased Susceptibility to Coronary Artery Disease

MicroRNA ◽

10.2174/2211536609666201209151130 ◽

2020 ◽

Vol 09 ◽

Author(s):

Rashid Mir ◽

Imadeldin Elfaki ◽

Chandan k Jha ◽

Jamsheed Javid ◽

Suriya Rehman ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Genetic Factors ◽

Mirna Gene ◽

Amplification Refractory Mutation System ◽

Coronary Artery Diseases ◽

Increased Risk ◽

Inheritance Model ◽

Artery Disease ◽

Increased Susceptibility

Aim: Apart from the modifiable risk factors, genetic factors are believed to also influence the outcome of the coronary artery diseases (CAD). Under the genetic factors, miRNA polymorphisms, namely Hsa-miR-146a-5p (rs2910164) have become an important tool to study the mechanism that underlies the pathogenesis of this disease. Therefore, we investigated the association of miR-146a gene variations with susceptibility of coronary artery diseases. Methodology: This study was conducted on 100 CAD patients and 117 matched healthy individuals. Genotyping of the Hsa-miR-146a-5p C>G gene variation was performed by using amplification refractory mutation system PCR method (ARMS-PCR). Results: The distribution of Hsa-miR-146a-5p rs2910164 C>G genotypes observed between patients and controls was significantly different (P=0.048). Moreover, the frequency of G allele (fG) was found to be significantly higher among patients than in controls (0.36 vs. 0.25). Our findings showed that the Hsa-miR-146a-5p C>G variant was associated with an increased risk of CAD in codominant inheritance model CC vs. CG genotype (OR = 1.84, 95 % CI, 1.02-3.31; p=0.040) and (OR = 3.18, 95 % CI, 1.02-9.9; p=0.045) for CC vs. GG genotype in dominant inheritance model. Whereas the G allele significantly increased the risk of coronary artery disease (OR =1,81, 95 % CI, 1.18-2.78; p=0.006) compared to C allele. Taken together, these results demonstrated that miR-146a/rs2910164 is associated with susceptibility to coronary artery disease, providing novel insights into the genetic etiology and underlying biology of coronary artery disease. Conclusion: Our findings indicated that Hsa-miR-146a-5p rs2910164 GG genotype and G allele are associated with an increased susceptibility to Coronary Artery Disease. A larger sample size can be the key to progress in establishing the genetic co-relation of miRNA gene polymorphisms and cardiovascular diseases.

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Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease

Clinical Research in Cardiology ◽

10.1007/s00392-021-01922-y ◽

2021 ◽

Author(s):

Rutao Wang ◽

Scot Garg ◽

Chao Gao ◽

Hideyuki Kawashima ◽

Masafumi Ono ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Coronary Revascularization ◽

Long Term Outcomes ◽

Vital Status ◽

Increased Risk ◽

Artery Disease ◽

The Impact

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

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Association between Pre-Existing Coronary Artery Disease and 5-Year Mortality in Stroke Patients with High-Grade Carotid Artery Stenosis

European Neurology ◽

10.1159/000512407 ◽

2020 ◽

pp. 1-7

Author(s):

Ching-I Wu ◽

Chia-Lun Wu ◽

Feng-Chieh Su ◽

Shun-Wen Lin ◽

Wen-Yi Huang

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Carotid Artery ◽

Carotid Artery Stenosis ◽

Significant Risk ◽

Cox Proportional Hazards Model ◽

Artery Stenosis ◽

High Grade ◽

Increased Risk ◽

Artery Disease

Background: The coincidence of coronary artery disease (CAD) and carotid artery stenosis (CAS) was observed. However, the association between pre-existing CAD and ischemic stroke (IS) outcome in patients with high-grade CAS remains unclear. We aimed to investigate the association between pre-existing CAD and outcomes of acute IS patients with high-grade CAS. Methods: From January 1, 2007, to April 30, 2012, we enrolled 372 acute IS patients with high-grade CAS and prospectively observed them for 5 years. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between patients with and without pre-existing CAD. Results: Among 372 individuals, 75 (20.2%) patients had pre-existing CAD and 297 (79.8%) patients did not have pre-existing CAD. The prevalence rates of hypertension, congestive heart failure, chronic kidney disease, and gout in patients with pre-existing CAD were significantly higher than in those without pre-existing CAD (p = 0.017, p < 0.001, p = 0.002, and p < 0.001, respectively). The multivariate Cox proportional hazards model revealed that pre-existing CAD was a significant risk factor for a 5-year all-cause mortality in acute IS patients with high-grade CAS (hazard ratio = 2.26; 95% confidence interval = 1.35–3.79; p = 0.002). Conclusion: Pre-existing CAD was associated with an increased risk of 5-year mortality in acute IS patients with high-grade CAS. Intensive treatment for the pre-existing CAD may reduce long-term mortality in acute IS patients with high-grade CAS.

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Prognostic value of serum soluble ST2 in stable coronary artery disease: a prospective observational study

Scientific Reports ◽

10.1038/s41598-021-94714-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hack-Lyoung Kim ◽

Jung Pyo Lee ◽

Nathan Wong ◽

Woo-Hyun Lim ◽

Jae-Bin Seo ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Stable Coronary Artery Disease ◽

Stable Condition ◽

Baseline Serum ◽

Soluble St2 ◽

Increased Risk ◽

Artery Disease ◽

Stable Cad

AbstractThe role of ST2 in stable coronary artery disease (CAD) has not yet been well defined. This study was performed to investigate baseline serum soluble ST2 (sST2) level can predict clinical outcomes in patients with stable CAD. A total of 388 consecutive patients with suspected CAD (65 years and 63.7% male) in stable condition referred for elective invasive coronary angiography (ICA) was prospectively recruited. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke during clinical follow-up was assessed. Most of the patients (88.0%) had significant CAD (stenosis ≥ 50%). During median follow-up of 834 days, there was 29 case of MACE (7.5%). The serum sST2 level was significantly higher in patients with MACE than those without (47.3 versus 30.6 ng/ml, P < 0.001). In multiple Cox regression model, higher sST2 level (≥ 26.8 ng/ml) was an independent predictor of MACE even after controlling potential confounders (hazard ratio, 13.7; 95% confidence interval 1.80–104.60; P = 0.011). The elevated level of baseline sST2 is associated with an increased risk of adverse clinical events in stable CAD patients. Studies with larger sample size are needed to confirm our findings.

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