The purpose of this study is to determine whether high intensity interval training (INT) is more effective in suppressing platelet reactivity than continuous, moderate intensity training (CONT) in patients undergoing cardiac rehabilitation after percutaneous coronary intervention.
Background: Platelets play an important role in cardiovascular disease: First, they promote the development of atherosclerotic lesions, and second, platelets form vessel occluding thrombi on top of (ruptured) lesions, ultimately leading to thrombotic events like myocardial infarctions (MCI). Whereas acute, strenuous exercise causes platelet activation and transiently increases the risk for MCIs, long-term chronic exercise training results in a clear reduction of both platelet activation and MCI incidence. Exercise training plays a key role in cardiac rehabilitation, since improvements in cardiorespiratory fitness (CRF) are associated with decreased mortality in these patients. With respect to CRF improvements, high-intensity interval training has been demonstrated to be more effective than moderate-intensity continuous exercise. However, the beneficial effect of high-intensity interval training on platelet function in patients with cardiovascular disease has never been investigated. Scientific question: The aim of this study is to determine the effect of interval training in cardiac rehabilitation on platelet function. Hypotheses: Cardiac rehabilitation with interval training components (INT) reduces 1. platelet activation and platelet reactivity at physical rest 2. changes of platelet activation and -reactivity induced by acute, strenuous exercise to a greater extent than cardiac rehabilitation consisting exclusively of moderate-intensity continuous exercise training (CONT). Work program: 80 patients at the beginning of phase II cardiac rehabilitation will be randomly assigned to an interval group or to a control group. In both groups, patients will exercise 4x / week for 12 weeks. At the beginning, after 6 weeks and at the end an exercise test will be carried out. Blood will be taken before (platelet function at rest) and immediately after each exercise test (platelet function after acute, strenuous exercise). Basal platelet activation as well as platelet responsiveness towards a platelet agonist (platelet reactivity) will be analyzed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
82
* 5 min warm-up (40% Pmax\*) * 30 min high intensity interval training (1 min 100% Pmax, 1 min 20% Pmax, in alternating sequence) * 10 min cool-down (30% Pmax) Pmax\*: Maximal power output (Watt) achieved at the end of an incremental exercise test.
* 5 min warm-up (40% Pmax\*) * 30 min moderate intensity continuous training (60% Pmax) * 10 min cool-down (30% Pmax) Pmax\*: Maximal power output (Watt) achieved at the end of an incremental exercise test.
MUVienna
Vienna, Austria
Platelet reactivity at physical rest: EC50 of TRAP-6 in terms of platelet CD62P expression. Unit of Measure: µM (Micromolar)
Platelet reactivity as measured by half maximal effective concentration (EC50) of the platelet agonist TRAP-6 (Thrombin receptor activating peptide-6; SFLLRN) in terms of platelet CD62P (P-selectin) expression, as described in Heber et al. 2016 (PMID: 26909532). The percentage of CD62P expressing platelets is quantified by flow cytometry without and with increasing concentrations of the platelet agonist TRAP-6. EC50 of TRAP-6 is estimated by fitting a four parameter logistic dose-response curve to flow cytometry data as a function of agonist concentration, aggregating multiple measurements to one reported value (EC50) with the unit µM. Treatment effects on platelet reactivity at physical rest after 6 weeks (INT vs. CONT) are estimated by ANCOVA, with baseline values as covariate.
Time frame: 6 weeks
Platelet reactivity at physical rest: EC50 of TRAP-6 in terms of platelet CD62P expression. Unit of Measure: µM
Platelet reactivity as measured by half maximal effective concentration (EC50) of the platelet agonist TRAP-6 (Thrombin receptor activating peptide-6; SFLLRN) in terms of platelet CD62P (P-selectin) expression. The percentage of CD62P expressing platelets is quantified by flow cytometry without and with increasing concentrations of the platelet agonist TRAP-6. EC50 of TRAP-6 is estimated by fitting a four parameter logistic dose-response curve to flow cytometry data as a function of agonist concentration, aggregating multiple measurements to one reported value (EC50) with the unit µM. Treatment effects on platelet reactivity at physical rest after 12 weeks (INT vs. CONT) are estimated by ANCOVA, with baseline values as covariate.
Time frame: 12 weeks
Cardiorespiratory fitness: Maximal power output
Maximal power output (Watt / kg bodyweight) at the end of an incremental exercise test
Time frame: 6 weeks
Cardiorespiratory fitness: Maximal power output
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Maximal power output (Watt / kg bodyweight) at the end of an incremental exercise test
Time frame: 12 weeks
Cardiorespiratory fitness: Maximal oxygen consumption
Maximal oxygen consumption (ml/min/kg bodyweight) at the end of an incremental exercise test
Time frame: 6 weeks
Cardiorespiratory fitness: Maximal oxygen consumption
Maximal oxygen consumption (ml/min/kg bodyweight) at the end of an incremental exercise test
Time frame: 12 weeks