Association of platelet reactivity and endothelial function and anti-inflammatory effects in patients with stable coronary artery disease

Coronary artery disease is the leading cause of morbidity and mortality worldwide. The most common pathophysiologic substrate is atherosclerosis which is an inflammatory procedure that starts at childhood and develops throughout life. Endothelial dysfunction is associated with the initiation and progression of atherosclerosis and is characterized by the impaired production of nitric oxide. In general, endothelial dysfunction is linked to poor cardiovascular prognosis and different methods, both invasive and non-invasive, have been developed for its evaluation. Ultrasound evaluation of flow mediated dilatation of the branchial artery is the most commonly used method to assessed endothelial function while intracoronary administration of vasoactive agents may be also be used to test directly endothelial properties of the coronary vasculature. Endothelial dysfunction has also been the subject of therapeutic interventions. This review article summarizes the knowledge about evaluation of endothelial function in acute coronary syndromes and stable coronary artery disease and demonstrates the current therapeutic approaches against endothelial dysfunction.

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Effects of Monotherapy with Clopidogrel vs. Aspirin on Vascular Function and Hemostatic Measurements in Patients with Coronary Artery Disease: The Prospective, Crossover I-LOVE-MONO Trial

Journal of Clinical Medicine ◽

10.3390/jcm10122720 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2720

Author(s):

Hyun-Woong Park ◽

Min-Gyu Kang ◽

Jong-Hwa Ahn ◽

Jae-Seok Bae ◽

Udaya S. Tantry ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Vascular Function ◽

Platelet Reactivity ◽

Reactive Hyperemia ◽

Open Label ◽

Peripheral Arterial Tonometry ◽

Coagulation Activity ◽

Artery Disease

To evaluate the effect of clopidogrel vs. aspirin monotherapy on vascular function and hemostatic measurement. Background: Monotherapy with P2Y12 receptor inhibitor vs. aspirin can be a useful alterative to optimize clinical efficacy and safety in high-risk patients with coronary artery disease (CAD). Methods: We performed a randomized, open-label, two-period crossover study in stented patients receiving at least 6-month of dual antiplatelet therapy (DAPT). Thirty CAD patients with moderate-to-high ischemic risk were randomly assigned to receive either 75 mg of clopidogrel or 100 mg of aspirin daily for 4 weeks, and were crossed over to the other strategy for 4 weeks. Vascular function was evaluated with reactive hyperemia-peripheral arterial tonometry (RH-PAT) and brachial-ankle pulse wave velocity (baPWV). Hemostatic profiles were measured with VerifyNow and thromboelastography (TEG). The primary endpoint was the reactive hyperemia index (RHI) during clopidogrel or aspirin monotherapy. Results: Clopidogrel vs. aspirin monotherapy was associated with better endothelial function (RHI: 2.11 ± 0.77% vs. 1.87 ± 0.72%, p = 0.045), lower platelet reactivity (130 ± 64 vs. 214 ± 50 P2Y12 reaction unit [PRU], p < 0.001) and prolonged reaction time (TEG R: 5.5 ± 1.2 vs. 5.1 ± 1.1 min, p = 0.037). In multivariate analysis, normal endothelial function (RHI ≥ 2.1) was significantly associated with clot kinetics (TEG angle ≤ 68 degree) and ‘PRU ≤ 132’. ‘PRU ≤ 132’ was achieved in 46.2% vs. 3.8% during clopidogrel administration vs. aspirin monotherapy (odds ratio 21.4, 95% confidence interval 2.7 to 170.1, p < 0.001). Conclusions: In CAD patients, clopidogrel vs. aspirin monotherapy was associated with better endothelial function, greater platelet inhibition and lower coagulation activity, suggesting pleiotropic effects of clopidogrel on endothelial function and hemostatic profiles.

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Abstract 2872: Interleukin-18/interleukin-10 Ratio is an Independent Predictor of Cardiovascular Events in Patients with Stable Coronary Artery Disease

Circulation ◽

10.1161/circ.116.suppl_16.ii_639-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Paulo V Camargo ◽

Raquel M Roman ◽

Ana Paula W Rossini ◽

Anderson Dedonelli ◽

Steffan F Stella ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Inflammatory Cytokine ◽

Stable Coronary Artery Disease ◽

Vascular Event ◽

Coronary Syndrome ◽

Anti Inflammatory ◽

Hs Crp ◽

Artery Disease ◽

Stable Cad

Background: The balance between pro-inflammatory cytokine IL-18 and anti-inflammatory cytokine IL-10 has been suggested to play a role in atherogenesis and in the prognosis of acute coronary syndrome (ACS). We hypothesized that stable coronary artery disease (CAD) patients have a pro-inflammatory profile prior to an acute event. Methods : A case-control study nested in a cohort of stable CAD patients was performed. Patients were consecutively included and blood samples collected at 3-months intervals. Cases were patients who presented any vascular event (death, ACS, ischemic stroke, peripheral arterial occlusion and revascularization) and controls were retrieved from a sequential list, in a 1:2 ratio, after 22 ± 9 months of follow-up. Serum hs-CRP, interleukin (IL)-10, IL-18 were measured in two serial samples, collected before the events. Results : Among 176 CAD patients, 42 developed a vascular event (cases) and 76 were selected to the control group. Serum levels of IL-18 were significantly higher among cases (411 ± 185 vs. 340 ± 133pg/ml; p = 0.037). Hs-CRP levels (5.4 vs. 5.1mg/l), IL-10 (7.4 vs. 7.2pg/ml), and IL-18/IL-10 ratio (66 vs. 61) were not different between cases and controls in both samples. Cox regression analysis showed that IL-18 levels (HR 1.75 (0.89 –3.5;p = 0.11) and IL-18/IL-10 ratio (HR 1.97; 1.0 –3.8) were predictors of worse prognosis (Figure ). Conclusion: In this study, IL-18 and IL-18/IL-10 ratio were associated with clinical outcomes and support the hypothesis that the balance between pro-inflammatory and anti-inflammatory cytokines may be an important determinant of vascular events in stable CAD patients.

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Increased Platelet Reactivity and Circulating Monocyte-Platelet Aggregates in Patients With Stable Coronary Artery Disease

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)00510-x ◽

1998 ◽

Vol 31 (2) ◽

pp. 352-358 ◽

Cited By ~ 337

Author(s):

Mark I Furman ◽

Stephen E Benoit ◽

Marc R Barnard ◽

C.Robert Valeri ◽

Marie L Borbone ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Platelet Reactivity ◽

Stable Coronary Artery Disease ◽

Platelet Aggregates ◽

Artery Disease

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LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 LEVELS ARE ASSOCIATED WITH ENDOTHELIAL FUNCTION AND ARTERIAL STIFFNESS IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(16)32336-1 ◽

2016 ◽

Vol 67 (13) ◽

pp. 2335

Author(s):

Gerasimos Siasos ◽

Evangelos Oikonomou ◽

Marina Zaromitidou ◽

Sotirios Tsalamandris ◽

Konstantinos Mourouzis ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Arterial Stiffness ◽

Endothelial Function ◽

Phospholipase A2 ◽

Stable Coronary Artery Disease ◽

Artery Disease

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Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease

Thrombosis and Haemostasis ◽

10.1160/th16-12-0973 ◽

2017 ◽

Vol 117 (06) ◽

pp. 1208-1216 ◽

Cited By ~ 26

Author(s):

Gianluca Campo ◽

Francesco Vieceli Dalla Sega ◽

Rita Pavasini ◽

Giorgio Aquila ◽

Francesco Gallo ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Pulmonary Disease ◽

Primary Endpoint ◽

Stable Coronary Artery Disease ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Artery Disease

SummaryPatients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR). The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD). Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin. The following parameters were assessed at baseline and after 1 month: i) rate of apoptosis and ii) nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs), iii) levels of reactive oxygen species (ROS) in peripheral blood mononuclear cell, iv) 29 cytokines/chemokines, v) on-treatment PR. The primary endpoint of the study was the 1-month rate of HUVECs apoptosis. The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor (7.4 ± 1.3% vs 9.3 ± 1.5%, p<0.001), satisfying the pre-specified primary endpoint. In the ticagrelor arm, levels of NO were higher (10.1 ± 2.2 AU vs 8.5 ± 2.6 AU, p=0.03) while those of ROS (4 ± 1.8 AU vs 5.7 ± 2.8 AU, p=0.02) and P2Y12 reactivity units (52 ± 70 PRU vs 155 ± 62 PRU, p<0.001) were lower. There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups. In patients with SCAD and COPD undergoing PCI, ticagrelor, as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR (ClinicalTrials.gov, NCT02519608).Supplementary Material to this article is available online at www.thrombosis-online.com.

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