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

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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INCREMENTAL SIGNIFICANCE OF ENDOTHELIAL FUNCTION ASSESSED BY REACTIVE HYPEREMIA PERIPHERAL ARTERIAL TONOMETRY FOR PREDICTING CARDIOVASCULAR EVENTS IN STABLE PATIENTS WITH CORONARY ARTERY DISEASE

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(12)61494-6 ◽

2012 ◽

Vol 59 (13) ◽

pp. E1493

Author(s):

Yasushi Matsuzawa ◽

Seigo Sugiyama ◽

Eiichi Akiyama ◽

Satoshi Umemura ◽

Kazuo Kimura ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Cardiovascular Events ◽

Reactive Hyperemia ◽

Peripheral Arterial Tonometry ◽

Arterial Tonometry ◽

Artery Disease ◽

Peripheral Arterial

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Predicting Severity of Coronary Artery Disease in Patients With Diabetes Using Endothelial Function Measured With Peripheral Arterial Tonometry: PROCEED Study

Angiology ◽

10.1177/0003319719833265 ◽

2019 ◽

Vol 70 (7) ◽

pp. 613-620 ◽

Cited By ~ 2

Author(s):

Shreenidhi Venuraju ◽

Anand Jeevarethinam ◽

Vishal Shahil Mehta ◽

Sherezade Ruano ◽

Alain Dumo ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Reactive Hyperemia ◽

Peripheral Arterial Tonometry ◽

Arterial Tonometry ◽

Artery Disease ◽

Peripheral Arterial

Endothelial dysfunction is common in patients with type 2 diabetes mellitus (T2DM) and is associated with atherosclerotic disease. This study aimed to determine prognostic factors for endothelial dysfunction and identify relationships between reactive hyperemia index (RHI) score, clinically relevant coronary artery disease (>50% stenosis), and major adverse cardiovascular events (MACEs) in patients with T2DM. Endothelial function was assessed using peripheral arterial tonometry and correlated with patient characteristics and cardiovascular outcomes during a median follow-up of 22.8 months. Among 235 patients with a median duration of T2DM of 13 years, mean (standard deviation) RHI score was 2.00 (0.76). Serum low- and high-density lipoprotein cholesterol levels positively ( P = .004) and negatively ( P = .02) predicted RHI score, respectively. Median coronary artery calcium (CAC) score was 109 Agatston units, but no correlation between CAC and RHI scores was observed. The RHI score did not predict the number or severity of coronary plaques identified using computed tomography coronary angiography. Additionally, there was no association between RHI score and the risk of an MACE during follow-up. Overall, endothelial function was not predictive of CAC score, extent, and severity of coronary plaque or MACEs and did not demonstrate utility in cardiovascular risk stratifying patients with T2DM.

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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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A new peripheral endothelial function measurement improves prediction of symptomatic coronary artery disease

Journal of International Medical Research ◽

10.1177/0300060520932818 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052093281

Author(s):

Beibei Du ◽

Daoyuan Si ◽

Dong Zhao ◽

Yanan Zhao ◽

Kenji Wagatsuma ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Endothelial Function ◽

Reactive Hyperemia ◽

Multivariate Logistic Regression Analysis ◽

Area Under The Curve ◽

Pairwise Comparison ◽

Function Measurement ◽

Framingham Risk ◽

Artery Disease

Objective This study aimed to determine whether a peripheral artery volume (PAV) test can improve the predictive value of the age-adjusted Framingham risk score (AFRS) for coronary artery disease (CAD) in symptomatic patients. Methods A total of 317 consecutive patients who were referred for coronary angiography were prospectively enrolled. Before cardiac catheterization, a PAV test was performed to measure changes in pulsatile blood flow volume following reactive hyperemia. Results PAV was significantly lower in patients with CAD than in those without CAD (1.21 ± 0.32 vs. 1.50 ± 0.45). Multivariate logistic regression analysis showed that PAV and the AFRS were independent predictors of CAD. Pairwise comparison of receiver operating characteristic curves showed that the predictive power for CAD increased when PAV was incorporated into the AFRS (area under the curve: from 0.76 to 0.80). The net reclassification index was also improved when PAV was added to the AFRS (0.65, 95% confidence interval: 0.44–0.85). Conclusions Digital endothelial function measurement is an independent predictor of CAD. PAV is potentially useful for identifying patients at high risk for CAD.

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