Influence Of Exercise Based Cardic Rehabilitation On Platelet Function In Patients With Coronaryartery Diseases

Back grand:Cardiac rehabilitation（CR）have favorable effects in reducing cardiac mobility and morbidity in patients with coronary heart diseases（CHD）,however,may also increase the risk of acute cardiac events during or shortly after exercise training.Platelet may plays an role in exercise related acute cardiac events.Objectives:To investigate the platelet function changes in patients with CHD who attend the cardiac rehabilitation program.Methods:This registered clinical trial was carried out in Beijing First Hospital of Integrated Chinese and Western Medicine（registry number:Chi CTR-INR-17010717）,from March 1^st,2017 to October 17,2017.A total of 30 patients with stable CHD were enrolled in this study.Symptom-limited CPET with a cycle ergometer was performed on all the patients.Before and after CPET,platelet function was evaluated using light transmission aggregometry and whole blood flow cytometry.Statistical analyses were performed using SPSS version 23.0（IBM,Chicago,USA）.Results:The average age of the selected population was 55±8 years,among which 86.7%were males.All patients completed the CPET without provoked cardiac events,and the mean value of peak oxygen uptake（VO₂max）was 19.3±3ml/（kg·min）.The ADP-induced platelet aggregation was increased from 55.3%to 63%（p<0.001）after the first cardiopulmonary exercise test.Multivariate regression analysis showed that platelet aggregation was affected by dual-antiplatelet therapy（DAPT）.Subgroup analysis was performed according to the difference of anti-platelet regimens（Aspirin or DAPT）.Prior to CPET,platelet aggregation was significantly suppressed in DAPT group compared to Aspirin group（43.0±21.5 vs.72.9±7.5%,p<0.001）.CPET promoted platelet aggregation in Aspirin group（72.9±7.5 vs.80.9±7.6%,p=0.005）and DAPT group（43.0±21.5 vs.50.1±20.9%,p=0.010）,and platelet count was increased in Aspirin(210.9±54.6 vs.227.5±58.1×10¹²/L,p=0.001)and DAPT group(217.5±63.8 vs.229.7±63.7×10¹²/L,p=0.001).At rest,the expression levels of CD62p and PAC-1 on platelet membrane remained unchanged,and ADP was able to induce the expression of CD62p and PAC-1 in the two groups.The expression levels of CD62p and PAC-1 were not affected by CPET in both groups.A total of 13 patients completed 12 sessions of rehabilitation training,with an average age of 56±7 years,of which 76.9%were males.Cardiac rehabilitation prolonged the exercise time of exercise test in patients with CHD（369±91 v.s.422±85 s,p=0.039）,increased the oxygen uptake at anaerobic threshold（17±3.4 v.s.19.1±3.4 ml/（kg·min）,p=0.021）and at peak exercise（19.3±3.1 v.s.21.2±4 ml/（kg·min）,p=0.005）,increased the Borg score at peak exercise level（16±1 v.s.17±2,p=0.017）,and reduced total cholesterol（3.9±1.2 v.s.3.3±0.7 mmol/l,p=0.015）,triglyceride（1.7±1.1v.s.1.4±0.8 mmol/l,p=0.037）,anxiety（3±2 v.s.1±1,p=0.003）and depression（4±2 v.s.2±1,p=0.004）.Long term CR had a tendency to inhibit platelet aggregation before and after cardiopulmonary test,although not statistically significant.The expressions of CD62p and PAC-1 in platelets decreased after cardiac rehabilitation,but did not reach statistical significance.The effects of two types of cardiac rehabilitation training modes（HIIT and MCT）on platelet function were not discussed in this paper due to lost of follow-up of study subjects.Conclusion:Acute exercise（CPET）can significantly increase the platelet aggregation in patients with coronary heart disease and increase the risk of acute thrombotic events.P2Y12 receptor antagonist significantly inhibited ADP-induced platelet aggregation,while Aspirin had no such effect.Aspirin alone or in combination with P2Y12 receptor antagonist did not inhibit exercise-induced platelet aggregation.The mechanism of increased platelet aggregation induced by sub-maximum acute exercise may be mainly because of platelet recruitment rather than the activation of single platelets.Long-term cardiac rehabilitation training significantly improved the cardiopulmonary fitness of CHD patients,and increased the anaerobic threshold,improved blood lipid metabolism,anxiety and depression in patients with CHD and inhibited platelet activation induced by acute exercise to some extent.The effect of long-term exercise rehabilitation on platelet function may be one of the mechanisms by which cardiac rehabilitation benefits patients with CHD.