scholarly journals The influence of metabolic activity of platelets on sensitivity to Acetylsalicylic acid in patients with coronary heart disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Kosinova ◽  
Y Grinshtein ◽  
A Savchenko ◽  
M Goncharov

Abstract Background Acetylsalicylic acid (ASA) is used to reduce the risk of shunt occlusion after coronary artery bypass grafting (CABG). From 5% to 60% of CHD patients do not respond to ASA. This phenomenon was defined as ASA resistance. The functional activity of platelets is largely determined by the state of their metabolism. Methods The venous blood samples were acquired from 66 patients with CHD before CABG, on the first day after surgery, and on the 8–10th day after surgery. The aggregometry was carried out for all participants by an optical aggregometer with 1 mM of arachidonic acid (AA) and 5 mM Adenosinediphosphate (ADP). Resistance to ASA was determined at the level of platelet aggregation with AA over 20% on ASA therapy or over 20% after platelet incubation with ASA in vitro before CABG. Patients were divided into ASA sensitive (sASA) and ASA resistant (rASA) groups. The level of synthesis of primary and secondary reactive oxygen species (ROS) by platelets was determined using chemiluminescent analysis. We investigated the overall level of radical synthesis from the values of Imax and S (area under the chemiluminescence curve), which, respectively, characterizes the maximum synthesis per unit time and the total amount of radical. The kinetics of ROS synthesis was characterized by Tmax (time to reach the maximum for the chemiluminescent curve). The activity of NAD- and NADP-dependent dehydrogenases in platelets was determined by the bioluminescent method. Results It was found that the aggregation activity of platelets depended on the sensitivity of CHD patients to ASA and decreased during postoperative ASA therapy. The most pronounced differences in metabolic parameters of platelets in sASA and rASA patients were detected by Nox2 activity. Platelet aggregation activity was correlated with platelet Nox2 activity only in sASA patients and only before CABG. The level of AA-induced platelet aggregation with the addition of ASA in sASA patients before CABG was negatively correlated with the Imax of ADP-induced lucigenin-enhanced (r=−0.27, p=0.046) and S of spontaneous luminol-enhanced (r=−0.31, p=0.022) platelet chemiluminescence. Patients with rASA before CABG had positive correlations of AA-induced aggregation with S of spontaneous (r=0.63, p=0.029) as well as Imax (r=0.85, p<0.001) and S (r=0.87, p<0.001) of ADP-induced luminol-enhanced chemiluminescence of platelets. Therefore, the absence of correlations between platelet aggregation activity and Nox2 activity was determined by ASA resistance and postoperative ASA therapy. The synthesis of secondary ROS (Table) by platelets of CHD patients did not depend on the sensitivity of patients to ASA but increased during postoperative treatment with ASA. The activity of NAD(P)-dependent dehydrogenases in platelets did not differ in sASA and rASA patients with CHD. Conclusions Metabolic Activity of Platelets could influence on resistance to ASA in Patients with CHD. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The reported study was funded by Russian Foundation for Basic Research, Government of Krasno-yarsk Territory, Krasnoyarsk Regional Fund of Science to the research project: “Antiplatelet therapy personification in patients with coronary heart disease (CHD) depending on the level of P-selectin gene expression, the intensity of intercellular interaction and inflammation”

2020 ◽  
Vol 13 (8) ◽  
pp. 178
Author(s):  
Yuriy I. Grinshtein ◽  
Andrei A. Savchenko ◽  
Aleksandra A. Kosinova ◽  
Maxim D. Goncharov

Sensitivity to acetylsalicylic acid (ASA) is important in the treatment of patients with coronary heart disease (CHD) after coronary artery bypass grafting (CABG). Patients were divided into ASA sensitive (sASA) and ASA resistant (rASA) by the activity of platelet aggregation induced arachidonic acid (ARA) together with ASA. Induced platelet aggregation activity was studied in sASA and rASA patients with CHD before and after CABG. The level of synthesis of primary and secondary reactive oxygen species (ROS) by platelets was determined using chemiluminescent analysis. The activity of NAD- and NADP-dependent dehydrogenases in platelets was determined by the bioluminescent method. It was found that the aggregation activity of platelets depended on the sensitivity of CHD patients to ASA and decreased during postoperative ASA therapy. The most pronounced differences in metabolic parameters of platelets in sASA and rASA patients were detected by Nox2 activity. The synthesis of secondary ROS by platelets of CHD patients did not depend on the sensitivity of patients to ASA but increased during postoperative treatment with ASA. The activity of NAD(P)-dependent dehydrogenases in platelets did not differ in sASA and rASA patients with CHD.


1992 ◽  
Vol 1 (1) ◽  
pp. 59-68
Author(s):  
Poppy S Roebiono ◽  
Dede Kusmana ◽  
Aulia Sani ◽  
Faisal Baraas ◽  
Andang Yusuf ◽  
...  

[no abstract available]


2020 ◽  
pp. 5-10
Author(s):  
O. M. Korzh

Among the cardiovascular diseases associated with atherosclerosis, chronic coronary heart disease, including angina, is the most common form. It is the myocardium lesion that develops as a result of an imbalance between the coronary circulation and metabolic needs of heart muscle. The presence of angina symptoms often indicates a pronounced narrowing of one or more coronary arteries, but also occurs in non−obstructive arterial impairment and even in normal coronary arteries. Factors of functional damage to the coronary arteries are spasm, temporary platelet aggregation and intravascular thrombosis. Today there are opportunities not only to use the therapy with proven effectiveness, aimed at reducing the risk of complications, including fatal, but also to treat angina (ischemia), which improves the patient's life quality. The drug protocol includes the ones with a proven positive effect on this disease prognosis, which are mandatory if there are no direct contraindications to use, as well as a large group of antianginal or anti−ischemic drugs. The choice of a particular drug or its combinations with other drugs is carried out in accordance with generally accepted recommendations: taking into account the individual approach, the severity of angina, hemodynamic parameters (heart rate and blood pressure, presence of comorbid conditions). If drug therapy is ineffective, the option of coronary myocardial revascularization (percutaneous coronary angioplasty or coronary artery bypass grafting) is considered. Due to the high mortality and morbidity rates of coronary heart disease worldwide, one of the priorities of practical health care is the prevention of diseases caused by atherosclerosis. Key words: coronary heart disease, angina, family physician, prognosis, drug therapy.


2017 ◽  
Author(s):  
Abhiram S. Rao ◽  
Daniel Lindholm ◽  
Manuel A. Rivas ◽  
Joshua W. Knowles ◽  
Stephen B. Montgomery ◽  
...  

AbstractPCSK9 inhibitors are a potent new therapy for hypercholesterolemia and have been shown to decrease risk of coronary heart disease. Although short-term clinical trial results have not demonstrated major adverse effects, long-term data will not be available for some time. Genetic studies in large well-phenotyped biobanks offer a unique opportunity to predict drug effects and provide context for the evaluation of future clinical trial outcomes. We tested association of the PCSK9 loss-of-function variant rsll591147 (R46L) in a hypothesis-driven 11 phenotype set and a hypothesis-generating 278 phenotype set in 337,536 individuals of British ancestry in the United Kingdom Biobank (UKB), with independent discovery (n = 225K) and replication (n = 112K). In addition to the known association with lipid levels (OR 0.63) and coronary heart disease (OR 0.73), the T allele of rs11591147 showed a protective effect on ischemic stroke (OR 0.61, p = 0.002) but not hemorrhagic stroke in the hypothesis-driven screen. We did not observe an association with type 2 diabetes, cataracts, heart failure, atrial fibrillation, and cognitive dysfunction. In the phenome-wide screen, the variant was associated with a reduction in metabolic disorders, ischemic heart disease, coronary artery bypass graft operations, percutaneous coronary interventions and history of angina. A single variant analysis of UKB data using TreeWAS, a Bayesian analysis framework to study genetic associations leveraging phenotype correlations, also showed evidence of association with cerebral infarction and vascular occlusion. This result represents the first genetic evidence in a large cohort for the protective effect of PCSK9 inhibition on ischemic stroke, and corroborates exploratory evidence from clinical trials. PCSK9 inhibition was not associated with variables other than those related to low density lipoprotein cholesterol and atherosclerosis, suggesting that other effects are either small or absent.


2007 ◽  
Vol 13 (3) ◽  
pp. 308-312 ◽  
Author(s):  
Ilknur I. Bütün ◽  
Hakan Ekmekçi ◽  
Hüseyin Sönmez ◽  
Çiğdem Gürel ◽  
Özlem Çiftçi ◽  
...  

2019 ◽  
Vol 6 (4) ◽  
pp. 41
Author(s):  
Umme Rumana ◽  
Richard Kones ◽  
Montather O. Taheer ◽  
Mohamed Elsayed ◽  
Craig W. Johnson

In diabetes patients with chronic ≥3 vessel disease, coronary artery bypass grafting (CABG) holds a class I recommendation in the American College of Cardiology and American Heart Association (ACC/AHA) 2011 guidelines, and this classification has not changed to date. Much of the literature has focused upon whether CABG or percutaneous coronary intervention (PCI) produces better outcomes; there is a paucity of data comparing the odds of receiving these procedures. A secondary analysis was conducted in a de-identified database comprised of 30,482 patients satisfying the entry criteria. Odds of occurrence (CABG, PCI) were determined as the binary dependent variable in period 1, (17 October 2009 through 31 December 2011), and period 2 (1 January 2013 through 16 March 2015), before and after the 2011 guidelines, while controlling for gender, ethnicity/race, and ischemic heart disease as covariates. The odds of performing CABG rather than PCI in period 2 were not statistically significantly different than in period 1 (p = 0.400). The logistic regression model chi-square statistic was statistically significant, with χ2 (7) = 308.850, p < 0.0001. The Wald statistic showed that ethnicity/race (African American, Caucasian, Hispanic and Other), gender, and heart disease contributed significantly to the prediction model with p < 0.05, but ethnicity ‘Unknown’ did not. The odds of CABG versus PCI in period 2 were 0.98 times those in period 1 95% confidence interval (CI) = (0.925, 1.032), statistically controlling for covariates. There was no significant rise in the odds of undergoing a CABG among this dataset of high-risk patients with diabetes and multivessel coronary heart disease. Modern practice has evolved regarding patient choice and additional variables that impact the final revascularization method employed. The degree to which odds of occurrence of procedures are a reliable surrogate for provider compliance with guidelines remains uncertain.


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