CYP3A4 *1B Gene Polymorphism in Coronary Artery Disease Patients with Obesity Undergoing Statin Treatment

2021 ◽  
Vol 18 ◽  
Author(s):  
Elifcan Gezer ◽  
Mehtap Cevik ◽  
Cansu Selcan Akdeniz ◽  
Ismail Polat Canbolat ◽  
Selen Yurdakul ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Statin Therapy ◽  
Plasma Lipid ◽  
Blood Cholesterol ◽  
Study Group ◽  
Genotype Distribution ◽  
Obese Patients ◽  
Artery Disease

Objective: Coronary artery disease (CAD) is the one of the leading cause of morbidity and mortality worldwide and statins are frequently prescribed in the treatment of CAD to help lower blood cholesterol levels. Since the main enzyme involved in the metabolism of statins is CYP3A4, we aimed to investigate the effect of CYP3A4 * 1B genotypes on plasma lipid profile in Turkish cardiovascular disease subject with and without obesity taking statin. Materials and Methods: The study group consisted of 85 cardiovascular disease patients who were prescribed statins and had routine biochemical analysis data. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) assay were performed for genotyping of CYP3A4 *1B (rs2740574) polymorphism. Results: Genotype distribution of CYP3A4 *1B polymorphism was found for homozygous wild (AA) and homozygous polymorphic (GG) genotypes as 94.1% and 5.9% respectively. We did not detect patients with heterozygous genotype in our study group. We found that the mean LDL-c, TG and TC levels were higher in patients with CYP3A4 *1B GG compared to AA genotype. The frequency of CYP3A4 *1B GG genotype frequency (9.5%) was detected higher in the obese patients compared to the non-obese patients (7.7%) (χ2=0.037, p=0.85). Conclusions: Our results demonstrate that CYP3A4 *1B homozygous polymorphic genotype distribution tend to be higher in obese patients compared to non- obese patients with cardiovascular disease which may point *1B allele to have a slight effect on serum lipids during statin therapy. Additional studies with higher samples are needed for evaluating the role of CYP3A4 *1B on lipids in patients under statin therapy.

Atherosclerotic Cardiovascular Risk in Adult Patients with Hemophilia: What We Can Do to Reduce Risk of Cardiovascular Events? Implementation of 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol in Patients with Hemophilia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4687-4687
Author(s):  
Kamila Izabela Cisak ◽  
Jianmin Pan ◽  
Shesh Nath Rai ◽  
Patricia Ashby ◽  
Vivek R. Sharma
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Blood Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Artery Disease

Abstract Introduction Hemophilia A and B are genetic disorders characterized by deficiency of clotting factors resulting in delayed bleeding. Despite hypocoagulable state, patients with hemophilia are prone to developing coronary artery disease or its equivalents. It is known that proper treatment of dyslipidemia has relevant impact of atherosclerotic cardiovascular events reduction. The goal of our study was to determine implementation of newest 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol in our patients with hemophilia and assess how many more patients currently may require lipid-lowering therapy. Methods We performed retrospective chart review of patients followed at single hemophilia treatment center in United States. We included 30 patients with factor VIII or IX deficiency, age 30 and older, followed in clinic between 2005 and 2014 with available lipid profile results. Patients with acquired hemophilia were excluded from study. We used stepwise approach proposed by above guidelines and divided patients into four groups. Results 4 patients among 30 were already on lipid lowering therapy. 1 (3.3%) additional patient [95% CI 0.001-0.17] required lipid lowering therapy due to presence of clinical atherosclerotic cardiovascular disease (group 1), 0 patients had LDL-C at least 190 mg/dl (group 2), 2 (6.7%) additional patients [95% CI 0.008-0.21] required therapy due to presence of diabetes mellitus and 40 to 75 year of age and LDL-C levels of 70 to 189 mg/dl (group 3); 9 (30%) additional patients [95% CI 0.17-0.51] should receive therapy due to age 40 to 75 and estimated 10-year ASCVD risk above 7.5%. We had total 12 (40%) additional patients among 30 with known lipid profile who were not on lipid lowering therapy but who require such therapy based on the latest 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol. Conclusion Aggressive cardiovascular risk factor modifications play a significant role in prevention of coronary artery disease, stroke and peripheral vascular disease. This may be even more relevant in patients with hemophilia who have an increased baseline risk of bleeding and may therefore be at greater risk of complications from anti-thrombotic therapies used for treating cardiovascular disease. Above results suggest that according to actual 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol, a significant number of patients with hemophilia may require lipid lowering therapy. It is important for hemophilia treatment centers to screen their patients with regard to this since many of them may either not have primary care physicians or may not be perceived as having high risk for cardiovascular disease due to their bleeding disorder. Disclosures No relevant conflicts of interest to declare.

scholarly journals Angiographic Comparison of Coronary Artery Disease between Diabetic Men and Women

2013 ◽  
Vol 6 (1) ◽  
pp. 3-9
Author(s):  
Md. Sk. Mamun ◽  
AAS Majumder ◽  
M Ullah ◽  
S Alam
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Angiography ◽  
Diabetic Patients ◽  
Study Group ◽  
Coronary Artery Lesions ◽  
Group I ◽  
Group Ii ◽  
Artery Disease

Background: Cardiovascular diseases are the leading cause of death and morbidity in diabetic patients and this group is two to four times as likely to develop cardiovascular disease than the nondiabetic group, women being specially involved in this situation. In women , diabetes appear to be a stronger risk factor for the development of coronary heart disease than in men regardless of age ,menopausal status and whether or not the patient is insulin or non-insulin dependent. Objective of this study was to compare the angiographic extent of coronary artery disease between diabetic men and diabetic women. Method: This observational study was undertaken on 100 diabetic patients ( 50 women and 50 men) admitted inNational Institute of Cardiovascular disease (NICVD) during the period of July, 2006 to April ,2007.Diabetic women with coronary artery disease constitute the study group-I and diabetic men with coronary artery disease matched for age (±5 years) and risk factors , the study group-II . Coronary angiography was done in all patients & findings were analyzed. Segmental distribution method for coronary artery lesions was used to describe the distribution of atherosclerotis in coronary artery. Results: The mean age of group I was 51.02 ±8.93 years and that of the group II was 50.99± 9.83 years. In this study it was found that Diabetic women with coronary artery disease (CAD) had a higher coronary artery score, CAS (11.02±5.034) as compared to the diabetic men with CAD ( 8.04±4.866) (p<0.001). Diabetic women had also higher number of diseased vessels ( 78.67% vs 67.34%; p<0.01) and higher number of vessel score 3 ( 58% vs 34%; p<0.001). As compared to the diabetic men, diabetic women had a higher total number of coronary artery lesions (183 vs 136; p<0.001), a higher number of lesions per patient (3.66/ patients vs 2.72/patients; p<0.001) and a higher number of diffuse vessels (13.56% vs 8.91%;p<0.05). Conclusion: Diabetic women with coronary artery disease have more severe disease on coronary angiography as compared to diabetic men with coronary artery disease. The diffuse coronary artery involvement was also significantly higher in diabetic women than men. Cardiovascular Journal Volume 6, No. 1, 2013, Page 3-9 DOI: http://dx.doi.org/10.3329/cardio.v6i1.16108

Genetic predictors for symptoms recurrenсe in coronary artery disease after percutaneous coronary intervention

2017 ◽  
pp. 81-86
Author(s):  
Г.А. Березовская ◽  
Е.С. Клокова ◽  
Н.Н. Петрищев
Keyword(s):  
Coronary Artery Disease ◽  
Percutaneous Coronary Intervention ◽  
Coronary Artery ◽  
Coronary Intervention ◽  
Folate Metabolism ◽  
Genotype Distribution ◽  
Polymorphic Markers ◽  
Percutaneous Coronary ◽  
Artery Disease

Гены тромбообразования и фолатного обмена играют важную роль в развитии и прогрессии ишемической болезни сердца (ИБС). Однако о возможной роли полиморфных маркеров в рецидиве ИБС после чрескожного коронарного вмешательства (ЧКВ) известно недостаточно. Цель исследования: Оценить роль генетических факторов системы тромбообразования и фолатного обмена (полиморфных маркеров генов F5, F2, F13A1, PAI1, HPA1, MTHFR, FGB ), в возобновление клиники ИБС после ЧКВ. Методика: Исследование проводили с использованием выборки из 90 больных ИБС в возрасте от 40 до 75 лет: 75 пациентов после планового ЧКВ (60 мужчин и 15 женщин) и 15 лиц после экстренного ЧКВ (12 мужчин и 3 женщины). Молекулярно-генетическое исследование было выполнено с помощью комплекта реагентов «Сердечно-сосудистые заболевания СтрипМетод»® (ViennaLab Diagnostics GmbH, Австрия), выявляющие следующие варианты: F5, F2, F13A1, PAI1, HPA1, MTHFR, FGB . Результаты: В результате исследования была показана ассоциация полиморфного маркера G103T ( Val34Leu ) гена F13A1 (фактор свертываемости крови 13, субъединица A1) с развитием рецидивирующего состояния ИБС после ЧКВ. Выявлены статистически значимые различия в распределении частот генотипов полиморфного маркера Val34Leu гена F13A1 . Показано, что частота генотипа Val/Val у пациентов с осложнениями была выше, чем у пациентов без таковых: 0,700 и 0,400 соответственно (c = 7,78; p = 0,020), при этом генотип Val/Val проявил себя как фактор риска развития осложнений: ОШ = 3,50 (95%ДИ 1,37-8,93). При сравнении аллелей выявили, что частота аллеля L у больных с осложнениями была ниже, чем у лиц без таковых: 0,167 и 0,375 соответственно (p = 0,004), и носительство аллеля L уменьшало вероятность развития осложнений: ОШ = 0,33 (95%ДИ 0,15-0,72). Заключение: Носительство варианта 34V гена F13A1 , кодирующего A-субъединицу фактора свёртывания 13, предрасполагает к возобновлению клинических проявлений ИБС после ЧКВ. Genes of thrombosis and folate metabolism play an important role in development and progression of coronary artery disease (CAD). However, a possible role of polymorphic markers in CAD relapse following percutaneous coronary intervention (PCI) is not sufficiently understood. Background. Reports have indicated an association of genetic factors generally related with thrombophilia and recurrence of symptoms for coronary artery disease (CAD) following a percutaneous coronary intervention (PCI) due to restenosis and in-stent thrombosis. However, the relapse can also be caused by progression of atherosclerosis and endothelial dysfunction in unoperated blood vessels. Aim: To assess the role of genetic risk factors involved in thrombosis and folate metabolism (polymorphic markers of F5, F2, F13A1, PAI1, HPA1, MTHFR, and FGB genes) in recurrence of CAD symptoms after PCI. Methods: The study included 90 patients with CAD aged 40-75; 75 of these patients had undergone elective PCI (60 men and 15 women) and 15 patients - emergency PCI (12 men and 3 women). Molecular genetic tests were performed using a CVD StripAssays® reagent kit (ViennaLab Diagnostics GmbH, Austria) to identify the following genetic variations: F5, F2, F13A1, PAI1, HPA1, MTHFR, and FGB . Results: The study results showed a significant association of the G103T ( Val34Leu ) polymorphism in the F13A1 gene with relapses of IHD after PCI. Significant differences were found in genotype distribution frequencies of the Val34Leu polymorphism in the F13A1 gene. The frequency of Val / Val genotype was higher in patients with complications than without complications, 0.700 and 0.400, respectively (c = 7.78, p = 0.020). Furthermore, the Val/Val genotype can be classified as a risk factor for complications (OR = 3.50; 95% CI, 1.37-8.93). The L allele frequency was lower in patients with complications than in those without complications (0.167 and 0.375, respectively, p = 0.004), and carriage of the L allele reduced the likelihood of complications (OR = 0.33; 95% CI 0.15-0.72). Conclusion: Carriage of the 34V variant in the F13A1 gene that encodes the coagulation factor XIII A subunit predisposes to a relapse of CAD symptoms after PCI.

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

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

Eicosapentaenoic Acid Combined with Optimal Statin Therapy Improves Endothelial Dysfunction in Patients with Coronary Artery Disease

2013 ◽  
Vol 28 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Kentaro Toyama ◽  
Toshihiko Nishioka ◽  
Ami Isshiki ◽  
Toshiyuki Ando ◽  
Yoshiro Inoue ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Eicosapentaenoic Acid ◽  
Statin Therapy ◽  
Artery Disease

scholarly journals Epicardial Adipose Tissue as a Source of Nuclear Factor-κB and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease

2009 ◽  
Vol 94 (1) ◽  
pp. 261-267 ◽  
Author(s):  
A. R. Baker ◽  
A. L. Harte ◽  
N. Howell ◽  
D. C. Pritlove ◽  
A. M. Ranasinghe ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Inflammatory Profile ◽  
Artery Disease ◽  
And Control

Abstract Context: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated. Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-κB (NFκB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects. Design: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies. Results: Western blotting showed epicardial AT had significantly higher NFκB, inhibitory-κB kinase (IKK)-γ, IKKβ, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-α. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 ± 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 ± 0.57 EU/ml; P&lt;0.05]. Conclusion: Epicardial AT from patients with CAD shows increased NFκB, IKKβ, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFκB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.

scholarly journals Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1644
Author(s):  
Bowen Liu ◽  
Amy M. Mason ◽  
Luanluan Sun ◽  
Emanuele Di Angelantonio ◽  
Dipender Gill ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
General Population ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Disease Outcomes ◽  
Artery Disease ◽  
Diagnosed Diabetes

(1) Aim: To investigate the causal effects of T2DM liability and glycated haemoglobin (HbA1c) levels on various cardiovascular disease outcomes, both in the general population and in non-diabetic individuals specifically. (2) Methods: We selected 243 variants as genetic instruments for T2DM liability and 536 variants for HbA1c. Linear Mendelian randomization analyses were performed to estimate the associations of genetically-predicted T2DM liability and HbA1c with 12 cardiovascular disease outcomes in 367,703 unrelated UK Biobank participants of European ancestries. We performed secondary analyses in participants without diabetes (HbA1c < 6.5% with no diagnosed diabetes), and in participants without diabetes or pre-diabetes (HbA1c < 5.7% with no diagnosed diabetes). (3) Results: Genetically-predicted T2DM liability was positively associated (p < 0.004, 0.05/12) with peripheral vascular disease, aortic valve stenosis, coronary artery disease, heart failure, ischaemic stroke, and any stroke. Genetically-predicted HbA1c was positively associated with coronary artery disease and any stroke. Mendelian randomization estimates generally shifted towards the null when excluding diabetic and pre-diabetic participants from analyses. (4) Conclusions: This genetic evidence supports causal effects of T2DM liability and HbA1c on a range of cardiovascular diseases, suggesting that improving glycaemic control could reduce cardiovascular risk in a general population, with greatest benefit in individuals with diabetes.

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