Abstract 15496: Combined Effect of an Interleukin-6 Gene Variant and Smoking on Endothelial Function, Inflammatory and Thrombotic Processes and Prevalence of Coronary Artery Disease

Introduction: Smoking is a well known risk factor for coronary artery disease (CAD). Moreover, controversial data suggest that the -174 G/C polymorphism on Interleukin-6 (IL-6) gene promoter (rs1800795) may represent an early marker of inflammatory activation, closely related to the initiation and evolution of atherosclerosis. However, no data exist concerning a combined effect of smoking and this IL-6 genetic variant on several aspects of inflammation and thrombosis, endothelial function and the presence of CAD. Methods: 646 subjects (361 non smokers) were subjected to appropriate genotyping. Endothelial function was assessed by the flow mediated dilatation (FMD) of brachial artery. IL-6 (pg/ml), Tumor Necrosis Factor-a (TNF-a) (pg/ml), high sensitivity CRP (hsCRP) (mg/l) and D-dimers (μg/l) were measured with appropriate methods. Results: An increased incidence of CAD was found among the carriers of the allele C, compared to GG homozygotes, (OR:1.59, CI:1.26-2.93, p=0.032) in smokers, while a decreased incidence was observed in non smokers (OR:0.42, CI:0.26-0.68, p<0.001), after adjustment for all risk factors for CAD. The C allele carriers, compared to GG homozygotes, were associated with significantly higher serum levels of IL-6 (3.09±1.4 vs 1.3±0.7), TNF-a (5.3±2.4 vs 2.57±1.8), hsCRP (2.09±0.9 vs 1.05±0.69) in smokers as well as in non smokers (IL-6: 2.62±1.2 vs 1.64±0.89, TNF-a: 3.57±1.67 vs 4.43±2.1, hsCRP: 1.84±0.82 vs 1.62±0.77), p<0.01 for all. Importantly, the C allele, compared to GG homozygotes, enhanced the expression of fibrinogen (488.3±115.1 vs 318.5±61.1 p<0.001) and D-dimers (513±313.4 vs 355.1±218.4, p=0.025) in smokers, while it down-regulated the expression of fibrinogen in non-smokers (351.9±84.5 vs 479.4±126.4, p<0.001). Impressively, the C allele carriers were correlated with significantly impaired endothelial function in the smoking group (3.9±2.7 vs 5.2±3.3, p=0.003), while no effect was observed among non-smokers (4.8±2.9 vs 5.04±2.6, p=0.64). Conclusions: The C allele of rs1800795 exerts a synergistic effect on smoking resulting to a significantly increased risk for CAD. This action is mediated by inflammatory and thrombotic mechanisms as well as by the impairment of endothelial function.

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The effect of polymorphisms (174G> C and 572C> G) on the Interleukin-6 gene in coronary artery disease: a systematic review and meta-analysis

Genes and Environment ◽

10.1186/s41021-021-00172-8 ◽

2021 ◽

Vol 43 (1) ◽

Author(s):

Nader Salari ◽

Kamran Mansouri ◽

Amin Hosseinian-Far ◽

Hooman Ghasemi ◽

Masoud Mohammadi ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Interleukin 6 ◽

Odds Ratio ◽

Meta Analysis ◽

Serum Levels ◽

Protective Effects ◽

Increased Risk ◽

Artery Disease ◽

The Relationship

Abstract Background Coronary Artery Disease (CAD) is caused by the blockage of the coronary arteries. it is argued that there has an association between the Interleukin-6 gene and the occurrence of atherosclerosis, coronary artery disease, Due to the short half-life and high variability of Interleukin-6 (IL-6), limited studies have been performed on the association of serum levels of interleukin-6 with coronary artery disease. The aim of this study is to investigate the relationship between IL-6 gene polymorphisms and coronary artery disease. Methods This study was conducted as a meta-analysis of selected articles with no lower time limit and upto March 2020. Articles related to the subject were obtained by searching several data sources,such as the SID, IranDoc, Scopus, Embase, Web of Science (ISI), PubMed, Science Direct, and Google Scholar databases. The heterogeneity of the studies was assessed using the I2 index in the Comprehensive Meta-Analysis software. Results The GG genotype of the IL-6174 G> C polymorphism with a 0.8 odds ratio tended to reduce the risk of CAD by 20%. The odds ratio of CAD in CG and GG genotypes were found to be 1.16 and 1.48 times respectively, indicating the increasing effect of these two genotypes. In the IL-6-572 C>G polymorphism, CG and GG genotypes increased the risk of CAD by 1.21 and 1.27 times respectively, and the CC genotype tended to reduce the risk of CAD by 15%, considering the odds ratio of 0.85. Conclusion This study showed a relationship between IL-6174G> C and Interleukin-6 (IL-6) 572 C>G genes and coronary artery disease. Moreover, the protective effects of GG genotype in IL-6 gene 174 G> C and CC genotype in IL-6 gene 572 C>G gene were reported. The study also confirmed that the CG and CC genotypes of the G>C IL-6174 gene have an increasing effect on coronary artery disease. Moreover, CG and GG genotypes in the IL-6 gene 572 C>G increased the risk of developing CAD. It should be noted that the increased risk of developing CAD was limited to meta-analytic studies in reported literatures.

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RELATIONSHIP BETWEEN INTERLEUKIN-6 GENE POLYMORPHISM AND HEART FAILURE IN PATIENTS WITH CORONARY ARTERY DISEASE AND OBESITY

Wiadomości Lekarskie ◽

10.36740/wlek202008109 ◽

2020 ◽

Vol 73 (8) ◽

pp. 1637-1640

Author(s):

Pavlo G. Kravchun ◽

Olga I. Kadykova ◽

Natalia G. Ryndina ◽

Svitlana O. Krapivko ◽

Mykhailo I. Kozhyn ◽

...

Keyword(s):

Heart Failure ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Interleukin 6 ◽

Gene Promoter ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Increased Risk ◽

Normal Body Weight ◽

Artery Disease

The aim: To examine the association between polymorphisms of the IL-6 gene promoter and HF in patients with CAD and obesity. Material and methods: 222 patients with coronary artery disease and obesity were identified. Comparison group consisted of 115 patients with coronary artery disease with normal body weight. The groups were comparable in age and sex. The exclusion group consisted of patients with severe concomitant diseases of the respiratory and digestive organs, kidneys and people with cancer. One single nucleotide polymorphisms in the interleukin-6 promoter region was analyzed. Odds ratio (OR) and 95 % confident interval (95 % CI) were calculated. Results: The combined course of coronary artery disease and obesity was characterized by the detection of allele C in 62 patients (27.93 %), allele G – in 160 patients (72.07 %), and genotypes CC, CG and GG – at 24 (10.81 %), 67 (30.18 %) and 131 (59.01 %) patients respectively. The results showed that the −174G allele and GG genotype in patients with coronary artery disease and obesity were associated with heart failure (OR = 2.55, 95% CI = [1.72-3.79], χ2 = 22.8; p<0.05) and (OR = 11.95, 95% CI = [3.41-41.91], χ2 = 22.5; p<0.05), whereas allele C−174 was associated with a decrease in the risk of heart failure (OR = 0.39, 95% CI = [0.26-0.58 ], χ2 = 22.75, p<0.05). Conclusions: The obtained results testify that the −174G>C polymorphism in the interleukin-6 gene is significantly associated with increased risk of heart failure in patients with coronary artery disease and obesity.

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Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients

Current Vascular Pharmacology ◽

10.2174/1570161117666191022095246 ◽

2020 ◽

Vol 18 (5) ◽

pp. 523-530 ◽

Cited By ~ 2

Author(s):

Konstantinos Maniatis ◽

Gerasimos Siasos ◽

Evangelos Oikonomou ◽

Manolis Vavuranakis ◽

Marina Zaromytidou ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Vascular Function ◽

Serum Levels ◽

Atherosclerosis Progression ◽

Control Subjects ◽

Significant Difference ◽

Artery Disease ◽

Stable Cad

Background: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). Methods: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Results: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04]. Conclusion: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

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Association of Longitudinal Change in High-Sensitivity Troponin with All-Cause Mortality in Coronary Artery Disease: The Heart and Soul Study

Cardiology ◽

10.1159/000503954 ◽

2020 ◽

Vol 145 (2) ◽

pp. 63-70

Author(s):

Yaanik B. Desai ◽

Rakesh K. Mishra ◽

Qizhi Fang ◽

Mary A. Whooley ◽

Nelson B. Schiller

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

High Sensitivity ◽

Community Dwelling ◽

Longitudinal Change ◽

Clinical Variables ◽

Risk Of Death ◽

Increased Risk ◽

All Cause Mortality ◽

Artery Disease

Background: Serial increases in high-sensitivity cardiac troponin (hs-cTnT) have been associated with death in community-dwelling adults, but the association remains uninvestigated in those with coronary artery disease (CAD). Methods: We measured hs-cTnT at baseline and after 5 years in 635 ambulatory Heart and Soul Study patients with CAD. We also performed echocardiography at rest and after treadmill exercise at baseline and after 5 years. Participants were subsequently followed for the outcome of death. We used a multivariable-adjusted Cox proportional hazards model to evaluate the association between 5-year change in hs-cTnT and subsequent all-cause mortality. Results: Of the 635 subjects, there were 386 participants (61%) who had an increase in hs-cTnT levels between baseline and year 5 measurements (median increase 5.6 pg/mL, IQR 3.2–9.9 pg/mL). There were 182 deaths after a mean 4.2-year follow-up after the year 5 visit. After adjusting for clinical variables, a >50% increase in hs-cTnT between baseline and year 5 was associated with a nearly 2-fold increased risk of death from any cause (hazard ratio 1.7, 95% confidence interval 1.1–2.7). When addition of year 5 hs-cTnT was compared to a model including clinical variables and baseline hs-cTnT, there was a modest but statistically significant increase in C-statistic from 0.82 to 0.83 (p = 0.04). Conclusion: In ambulatory patients with CAD, serial increases in hs-cTnT over time are associated with an increased risk of death.

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P3645Prognosis in relation to high-sensitivity C-reactive protein levels in patients with non-obstructive coronary artery disease

European Heart Journal ◽

10.1093/eurheartj/ehz745.0502 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H W Zhang ◽

Y X Cao ◽

J L Jin ◽

Y L Guo ◽

Y Gao ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Obstructive Coronary Artery Disease ◽

High Sensitivity ◽

C Reactive Protein ◽

Development Fund ◽

Reactive Protein ◽

Increased Risk ◽

Hs Crp ◽

Artery Disease

Abstract Background It has been reported that coronary artery disease (CAD) is characterized by inflammation and non-obstructive CAD (NOCAD) increases the risk of cardiovascular events (CVEs) compared with ones with normal or near-normal coronary arteries (NNCA), even is similar to obstructive CAD (OCAD). We hypothesized that elevated high-sensitivity C-reactive protein (hs-CRP) may be linked to CVEs in those patients with NOCAD. Purpose To investigate the predictive role of hs-CRP in patients with NOCAD. Methods Of 7,746 consecutive patients with angina-like chest pain admissions, 4,662 eligible patients were enrolled who received coronary artery angiography (CAG) and followed up for the CVEs comprising all-cause mortality, myocardial infarction, stroke and late revascularization. According to the results of CAG, the patients were classified as NNCA group (<20% stenosis, n=698, 15.0%), NOCAD group (20–49% stenosis, n=639, 14.3%), and OCAD group (≥50% stenosis, n=3325, 70.7%). They were further subdivided into 3 groups according to baseline hs-CRP levels (<1, 1–3 and >3 mg/L). Proportional hazards models were used to assess the risk of CVEs in all patients enrolled. Results A total of 338 patients (7.3%) experienced CVEs during an average of 13403 person-years follow-up. Patients with NOCAD and OCAD had higher rates of CVEs compared to those with NNCA (p<0.05, respectively). In Cox's models after adjustment of confounders, the risk of CVEs elevated with the increasing degrees of CAD with hazard ratio of 2.01 [95% confidence interval (95% CI): 1.07–3.79, p=0.03] for patients with NOCAD and 2.81 (95% CI: 1.60–4.93, p<0.001) for patients with OCAD compared with the NNCA group. Moreover, elevated hs-CRP levels were associated with the severity of coronary lesions and an elevated increased risk of CVEs in patients with NOCAD and OCAD compared those with NNCA (p<0.05, respectively). Conclusions Patients with NOCAD had indeed worse outcomes and hs-CRP levels were positively in relation to the CVEs in those with NOCAD, which may help to the risk assessment in ones with NOCAD. Acknowledgement/Funding This study was partly supported by Capital Health Development Fund (201614035) and CAMS Innovation Fund for Medical Sciences (2016-I2M-1-011) awarded

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IMMUNOLOGICAL STUDY OF CORONARY ARTERY DISEASE ASSOCIATED WITH DIABETES MELLITUS TYPE II IN IRAQI PATIENTS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i12.27620 ◽

2018 ◽

Vol 11 (12) ◽

pp. 269

Author(s):

Mundher Jabbar Al-okhedi ◽

Mohammed Qais Al-ani ◽

Marrib N Rasheed

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Serum Levels ◽

Control Group ◽

Immunological Study ◽

Increased Risk ◽

Artery Disease

Objective: The objective of this study was to investigate the association between proinflammatory cytokines in special, the interleukin-6 (IL-6), and insulin-like growth factor (IGF-1) levels in coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM).Methods: This study was conducted from November 2017 to March 2018 in Anbar, Iraq. We studied a total of 90 individuals (46 men and 44 women) aged between 20 and 87 years. The samples were divided into four groups: CAD patients (n=23), T2DM patients (n=23), coronary artery disease and type 2 diabetes together in the same patient (n=23), and control group (n=21). The concentrations of IL-6 and IGF-1 were determined using a commercially available enzyme-linked immune sorbent assay.Results: The results of the present study showed that there were elevated serum levels of IL-6 and low levels of IGF-1 in all the tested groups, compared with the control. The difference was statistically significant at p<0.05. The results showed a positively correlated between IL-6 and IGF-1 in the CAD group and T2DM group, while it was a negative correlation between serum levels of IL-6 and IGF-1 in the T2DM+CAD group.Conclusion: Elevated levels serum of IL-6 predicts the development of CAD and T2DM. These data support a possible role for inflammation in diabetogenesis and complication of the cardiovascular disease. There is an inverse relationship between the levels serum of IGF-1 and increased risk of CAD and development of T2DM.

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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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Interleukin-6 concentration predicts coronary artery disease better than high-sensitivity C-reactive protein

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(02)81474-7 ◽

2002 ◽

Vol 39 ◽

pp. 328

Author(s):

Brent P. Davis ◽

Joseph B. Muhlestein ◽

John F. Carlquist ◽

Jason M. Lappe' ◽

Benjamin D. Home ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Interleukin 6 ◽

High Sensitivity ◽

C Reactive Protein ◽

Reactive Protein ◽

Artery Disease ◽

Better Than

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Association of Interleukin-6 Gene Promoter Polymorphism with Coronary Artery Disease in Pakistani Families

The Scientific World JOURNAL ◽

10.1155/2013/538365 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 21

Author(s):

Humayoon Shafiq Satti ◽

Sabir Hussain ◽

Qamar Javed

Keyword(s):

Gene Expression ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Gene Polymorphism ◽

Interleukin 6 ◽

Promoter Polymorphism ◽

Binary Logistic Regression Model ◽

Increased Risk ◽

Hs Crp ◽

Artery Disease

Interleukin-6 (IL-6) is a well-known inflammatory cytokine and suggested to be involved in the development of coronary artery disease (CAD). IL-6 gene expression has been investigated with controversy in CAD patients. This study investigates the association of the IL-6 gene expression with CAD, the molecular basis for the regulation of interleukin-6 expression in a Pakistani population. Our data show that the serum IL-6 levels were increased in patients with CAD compared with healthy controls and that the IL-6 gene polymorphism at -174 was more prevalent in CAD cases. There was a statistically significant association between the IL-6 gene polymorphism and CAD, which may be associated with an increased risk for the disease. Moreover, circulating IL-6 and hs-CRP levels were significantly higher in patients with CC genotype (P<0.0001andP<0.0001, resp.). In a binary logistic-regression model, an independent association was found between CAD and increased serum IL-6 and hs-CRP levels and -174G>C polymorphism. This is the first report on the IL-6 expression and the IL-6 gene polymorphism in patients with CAD from Pakistan, and hence it highlights a novel risk factor for the disease.

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