Abstract
Introduction
Regular exercise training is essential in prevention and treatment of cardiovascular disease (CVD), yet the beneficial effects of exercise remain only partly explained. Platelets play a key role in CVD and may be affected by regular exercise training. We aimed to systematically summarise studies investigating the effect of regular exercise training on platelet function in patients with CVD and in healthy individuals.
Methods
Studies were identified by PubMed, Embase and Web of Science May 16, 2022. We selected studies investigating markers of platelet function in relation to regular exercise training in patients with CVD and in healthy individuals. Regular exercise was defined as exercise training for four weeks or more.
Results
Of the included studies, 11 investigated patients with CVD and 29 were on healthy individuals. Studies were heterogeneous regarding design, study population and methodology, and the results were ambiguous. In total, 52 different markers of platelet function were investigated with platelet aggregation, soluble P-selectin, and thromboxane B2 (TXB2) as the most frequently examined. When evaluating between-group changes after regular exercise, two studies found a reduced platelet aggregation in the exercise group whilst three studies did not find a difference between groups. With respect to TXB2, three studies reported a reduction and two studies an increase in the exercise group. There were no between-group differences in the seven studies examining soluble P-selectin.
Conclusion
Regular exercise training has no clear impact on platelet function in patients with CVD or healthy individuals.
Prospero registration
CRD42022350539.
Abbreviations:
6-keto-PGF1α (plasma 6-keto-prostaglandin F1α), AA (arachidonic acid), ADMA (asymmetrical dimethyl arginine), ADP (adenosine diphosphate), CAD (coronary artery disease), CD40L (plasma CD40 ligand), COL (collagen), CVD (cardiovascular disease), EPI (epinephrine), L-arg (L-arginine levels), MPA (monocyte-platelet aggregates), MPV (mean platelet volume), PLT (platelet count), PCT (platelet crit (PLT × MPV / 10,000)), PDGF (platelet derived growth factor beta-1), PDW (platelet distribution width), PRISMA (preferred reporting items for systematic reviews and meta-analyses), P-sel (P-selectin), RCT (randomised controlled trial), S1P (sphingosine-1-phosphate), SA1P (sphinganine-1-phosphate), sICAM-1 (soluble intercellular adhesion molecule-1), SDMA (symmetrical dimethyl arginine), sE-sel (soluble-E-selectin), SphK (sphingosine kinase activity), sP-selectin (soluble-P-selectin), sVCAM-1 (soluble vascular cell adhesion molecule-1), TRAP (thrombin receptor activating peptide), TXA2 (thromboxane A2), TXB2 (thromboxane B2), VCAM-1 (vascular cell adhesion molecule-1), VEGF (vascular endothelial growth factor), VO2max (maximal aerobic capacity), vWf (von Willebrand factor)Keywords
1. Introduction
Cardiovascular disease (CVD) is the leading cause of death worldwide [
[1]
]. Regular exercise training has a high priority in the prevention and treatment of CVD and has been shown to reduce cardiovascular death and rehospitalisation in patients with coronary artery disease (CAD) [2
, - Pelliccia A.
- Sharma S.
- Gati S.
- et al.
2020 ESC guidelines on sports cardiology and exercise in patients with cardiovascular disease.
Eur. Heart J. 2021; 42 ([published Online First: 2020/08/30]): 17-96https://doi.org/10.1093/eurheartj/ehaa605
3
]. In peripheral artery disease, regular exercise training is among first line treatments in order to improve limb symptoms and salvage [- Dibben G.
- Faulkner J.
- Oldridge N.
- et al.
Exercise-based cardiac rehabilitation for coronary heart disease.
Cochrane Database Syst. Rev. 2021; 11 ([published Online First: 20211106])Cd001800https://doi.org/10.1002/14651858.CD001800.pub4
[4]
]. The mechanisms explaining the benefits of regular exercise training are only sparsely understood. Regular exercise training has a wide range of potential benefits on cardiovascular risk factors such as hypertension, dyslipidaemia and overweight [- Aboyans V.
- Ricco J.B.
- Bartelink M.E.L.
- et al.
2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the european Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the european stroke organization (ESO)The task force for the diagnosis and treatment of peripheral arterial diseases of the european Society of Cardiology (ESC) and of the european Society for Vascular Surgery (ESVS).
2
, - Pelliccia A.
- Sharma S.
- Gati S.
- et al.
2020 ESC guidelines on sports cardiology and exercise in patients with cardiovascular disease.
Eur. Heart J. 2021; 42 ([published Online First: 2020/08/30]): 17-96https://doi.org/10.1093/eurheartj/ehaa605
5
, - Alves A.J.
- Wu Y.
- Lopes S.
- et al.
Exercise to treat hypertension: late breaking news on exercise prescriptions that FITT.
Curr. Sports Med. Rep. 2022; 21 ([published Online First: 20220801]): 280-288https://doi.org/10.1249/jsr.0000000000000983
6
] and may possibly also have an impact on platelet function. Platelets play a crucial role in the process of coronary thrombus formation [- Doewes R.I.
- Gharibian G.
- Zadeh F.A.
An updated systematic review on the effects of aerobic exercise on human blood lipid profile.
Curr. Probl. Cardiol. 2022; ([published Online First: 20220108])101108https://doi.org/10.1016/j.cpcardiol.2022.101108
7
, 8
] and thus CVD patients are usually treated with antithrombotic drugs [- Gremmel T.
- Frelinger III, A.L.
- Michelson A.D.
Platelet physiology.
Semin. Thromb. Hemost. 2016; 42 ([published Online First: 20160229]): 191-204https://doi.org/10.1055/s-0035-1564835
3
, - Dibben G.
- Faulkner J.
- Oldridge N.
- et al.
Exercise-based cardiac rehabilitation for coronary heart disease.
Cochrane Database Syst. Rev. 2021; 11 ([published Online First: 20211106])Cd001800https://doi.org/10.1002/14651858.CD001800.pub4
9
]. Paradoxically, some studies have linked acute exercise to an increased risk of thrombosis [- Giannuzzi P.
- Mezzani A.
- Saner H.
- et al.
Physical activity for primary and secondary prevention. Position paper of the working group on cardiac rehabilitation and exercise physiology of the european Society of Cardiology.
Eur. J. Cardiovasc. Prev. Rehabil. 2003; 10: 319-327https://doi.org/10.1097/01.hjr.0000086303.28200.50
10
, - Olsen L.N.
- Fischer M.
- Evans P.A.
Does exercise influence the susceptibility to arterial thrombosis? An integrative perspective.
Front. Physiol. 2021; 12 ([published Online First: 20210223])636027https://doi.org/10.3389/fphys.2021.636027
11
, - Posthuma J.J.
- van der Meijden P.E.
- Ten Cate H.
Short- and Long-term exercise induced alterations in haemostasis: a review of the literature.
Blood Rev. 2015; 29 (10.1016/j.blre.2014.10.005. Epub 2014 Nov 6): 171-178https://doi.org/10.1016/j.blre.2014.10.005
12
], which may be explained by exercise-induced platelet aggregation and activation of coagulation [- Hvas A.M.
- Neergaard-Petersen S.
Influence of exercise on platelet function in patients with cardiovascular disease.
Semin. Thromb. Hemost. 2018; 44 (10.1055/s-0038-1673618. Epub 2018 Sep 28): 802-812https://doi.org/10.1055/s-0038-1673618
11
, - Posthuma J.J.
- van der Meijden P.E.
- Ten Cate H.
Short- and Long-term exercise induced alterations in haemostasis: a review of the literature.
Blood Rev. 2015; 29 (10.1016/j.blre.2014.10.005. Epub 2014 Nov 6): 171-178https://doi.org/10.1016/j.blre.2014.10.005
12
]. Furthermore, untrained people have a higher risk of cardiovascular events following strenuous exercise [- Hvas A.M.
- Neergaard-Petersen S.
Influence of exercise on platelet function in patients with cardiovascular disease.
Semin. Thromb. Hemost. 2018; 44 (10.1055/s-0038-1673618. Epub 2018 Sep 28): 802-812https://doi.org/10.1055/s-0038-1673618
[2]
]. In contrast, regular exercise training may induce changes in the haemostatic system explaining its beneficial effects on cardiovascular health and mortality [- Pelliccia A.
- Sharma S.
- Gati S.
- et al.
2020 ESC guidelines on sports cardiology and exercise in patients with cardiovascular disease.
Eur. Heart J. 2021; 42 ([published Online First: 2020/08/30]): 17-96https://doi.org/10.1093/eurheartj/ehaa605
[3]
]. We aimed to systematically review the literature for studies investigating the effect of regular exercise training on platelet function in patients with CVD and in healthy individuals.- Dibben G.
- Faulkner J.
- Oldridge N.
- et al.
Exercise-based cardiac rehabilitation for coronary heart disease.
Cochrane Database Syst. Rev. 2021; 11 ([published Online First: 20211106])Cd001800https://doi.org/10.1002/14651858.CD001800.pub4
2. Methods
2.1 Eligibility criteria
The present review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines [
[13]
]. Inclusion criteria were: 1) studies including patients with CVD or healthy individuals, 2) performance of regular exercise training (≥4 weeks), 3) evaluation of platelet function (activation, aggregation, and/or platelet turnover), 4) age ≥18 years, 5) English language, 6) randomised controlled trials, cohort, cross-sectional, or case-control studies. Exclusion criteria were: 1) Studies including individuals with risk factors without established CVD, 2) animals or in vitro studies, 3) guidelines, 4) reviews, 5) letters or editorials without original data, 6) case reports, 7) conference abstracts, 8) studies investigating the effect of pharmacotherapy on platelet function during exercise training 9) records with <10 cases that completed the study. The review was registered at PROSPERO (ID: CRD42022350539).- Liberati A.
- Altman D.G.
- Tetzlaff J.
- et al.
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
PLoS Med. 2009; 6e1000100https://doi.org/10.1371/journal.pmed.1000100 [published Online First: 20090721]
2.2 Literature search and data extraction
Literature search was performed in three different databases: PubMed, Embase and web of science. The literature search was performed on May 16th, 2022. The search string for PubMed was: (“Blood Platelets” (Mesh) OR “platelet” OR “thrombocyte” OR “Platelet Function Test” (Mesh) OR “Platelet Activation” (Mesh)) AND (“Exercise” (Mesh) OR “exercise”), Embase: (“exercise”/exp OR “exercise”) AND (“thrombocyte”/exp OR “thrombocyte”) and for web of science: ALL = (exercise) AND (ALL = (thrombocyte) OR ALL = (platelet)). The searches were without time boundaries. After duplicate screening, 30 random abstracts were independently screened by the first and last author (JK and AMH). JK made the remaining abstract screening using the Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). JK and AMH evaluated 30 random full-text records to evaluate the study selection. JK evaluated the remaining full-text records for relevance.
2.3 Data processing
Included records were divided by population in patients with CAD, ischaemic stroke or peripheral artery disease and healthy individuals. The exercise protocol for each study was presented with focus on weekly frequency, length of training period, and supervision status.
3. Results
Fig. 1 shows the flowchart of the literature searches and selection procedure. In total, 8266 records were identified. Before screening, 4178 duplicates were removed. Title and abstract screening was performed on 3312 records of which 3170 were excluded based on inclusion and exclusion criteria. The remaining 142 articles were assessed by full text of which 38 were eligible for inclusion. Furthermore, two additional records were found in the reference list of other studies. Among the included studies, 11 studies included patients with CVD and 29 studies examined healthy individuals. CVD subpopulations included CAD (n = 9) and peripheral artery disease (n = 2).![Fig. 1]()

Fig. 1Flow-diagram for literature search.
3.1 Effect of regular exercise on platelet function in CVD patients and in healthy individuals
Table 1, Table 2 summarise the characteristics and results of all 40 included studies. The total study population consisted of 2238 individuals: 1072 healthy individuals, 1047 patients with CAD and 119 patients with peripheral artery disease. Out of the 40 included studies, 12 were randomised controlled trials, 21 were cohort studies, 4 were cross-sectional studies and 3 were combined cohort- and cross-sectional studies. Randomised controlled studies were employed in 6 (55 %) of the studies on CVD patients and 6 (21 %) of the studies including healthy individuals. The mean age of patients with CVD was 62 years old, compared to 31 years for healthy individuals. Among studies on patients with CVD, 21 % of patients were women, whereas 33 % of healthy individuals were women. In the included studies, 52 different markers of platelet function were investigated, of which 41 were only measured in a few studies. In Table 3, changes of the 11 markers that were assessed in three or more studies are displayed. Some of the studies reported two different results for the same marker; one result on changes from baseline to after exercise training and another result from the comparison of changes in cases and controls.
Table 1Studies investigating the effect of regular exercise on platelet function in patients with cardiovascular disease (n = 11).
Year Author Ref | Design Study population Number of individuals Age Females | Exercise protocol | Blood sampling | Platelet parameters | Results |
---|---|---|---|---|---|
2021 Durmus et al. [41] | Cohort study CAD Cases (n = 203) Controls (n = 97) 57 years Gender: 23 % Aspirin: 98 % P2Y12 inhib: 59 % | 5 times weekly 1.5 months Supervised | Pre 1.5 months | MPV | Cases vs controls:
|
2020 Heber et al. [51]
Effects of high-intensity interval training on platelet function in cardiac rehabilitation: a randomised controlled trial. Heart. 2020; 106 ([published Online First: 2019/07/19]): 69-79https://doi.org/10.1136/heartjnl-2019-315130 | RCT CAD Cases (n = 40) Controls (n = 42) 61 years Gender: 0 % Aspirin: 100 % P2Y12 inhib: 100 % | All: 4 times weekly 3 months Cases: HIIT+MICT Controls: MICT | Pre 1.5 months 3 months | Flow cytometry (TRAP as agonist): P-sel, CD40L, PNA, GPIIb/IIIa. MPV PLT | Cases vs controls:
|
2013 Keating et al. [42] | RCT CAD Cases (n = 21) Controls (n = 25) 64 years Gender: 24 % Aspirin: 98 % P2Y12 inhib: 0 % | 5–7 times weekly 5 months Supervised and unsupervised | Pre 5 months | sP-sel expression (ADP agonist) | Post vs pre, cases:
|
2006 Lee et al. [43] | RCT CAD Cases (n = 81) Controls (n = 20) 60 years Gender: 19 % Aspirin: 98 % P2Y12 inhib: 13 % | 2 times weekly 3 months Supervised vs unsupervised | Pre 3 months | sP-sel vWf | Post vs pre, cases:
|
2021 Liang et al. [44]
Modest gains after an 8-week exercise program correlate with reductions in non-traditional markers of cardiovascular risk. Front. Cardiovasc. Med. 2021; 8 ([published Online First: 2021/07/06])669110https://doi.org/10.3389/fcvm.2021.669110 | Cohort study CAD Cases (n = 35) Controls (n = 17) 67 years Gender: 8 % Aspirin: 36 % P2Y12 inhib: 20 % | 2 months Supervised vs unsupervised | Pre 2 months | PDGF | Post vs pre, cases:
|
2011, Munk et al. [45]
High intensity interval training reduces systemic inflammation in post-PCI patients. Eur. J. Cardiovasc. Prev. Rehabil. 2011; 18 ([published Online First: 20110218]): 850-857https://doi.org/10.1177/1741826710397600 | RCT CAD Cases (n = 18) Controls (n = 18) 60 years Gender: 17 % Aspirin: 100 % P2Y12 inhib: 100 % | 3 times weekly 6 months Supervised | Pre 6 months | sE-sel VCAM-1 vWF sP-sel CD4-Ligand | Post vs pre, cases:
|
1992 Suzuki et al. [46] | Cohort study CAD Cases (n = 56) Controls (n = 30) 60 years Gender: 13 % Aspirin: 51 % P2Y12 inhib: 43 % | 6 times weekly 1 month Supervised | Pre 1 month | PLT vWf antigen | Post vs pre, cases:
|
2017 Toth-Zsamboki et al. [47] | Cohort study CAD Cases (n = 84) Controls (n = 51) 61 years Gender: 22 % Aspirin: 33 % P2Y12 inhib: 20 % | 5 times weekly 3 months Supervised vs unsupervised | Pre 3 months | PLT MPV Platelet aggregation (COL, ADP, EPI and AA as agonists) PDGF Platelet micro particles | Post vs pre, cases:
|
2009 Vona et al. [48] | RCT CAD Cases (n = 159) Controls (n = 50) 57 years Gender: 26 % Aspirin: 100 % P2Y12 inhib: NR | 4 times weekly 1 month Supervised | Pre 1 month | vWf | Post vs pre, cases:
|
2017 Januszek et al. [49]
Soluble endoglin as a prognostic factor of the claudication distance improvement in patients with peripheral artery disease undergoing supervised treadmill training program. J. Am. Soc. Hypertens. 2017; 11 ([published Online First: 20170628]): 553-564https://doi.org/10.1016/j.jash.2017.06.009 | Cohort study Intermittent claudication (n = 66) 65 years Gender: 38 % Aspirin: NR P2Y12 inhib: NR | 3 months Supervised | Pre 3 months | PDGF AA PDGF AB/BB | Post vs pre:
|
2012 Schlager et al. [50]
Impact of exercise training on inflammation and platelet activation in patients with intermittent claudication. Swiss Med. Wkly. 2012; 142 ([published Online First: 20120814])w13623https://doi.org/10.4414/smw.2012.13623 | RCT Intermittent claudication: cases (n = 27) Controls (n = 26) 70 years Gender: 38 % Aspirin: 85 % P2Y12 inhib: 40 % | 2 times weekly 6 months Supervised | Pre 3 months 6 months 12 months | sP-sel MPA | Post vs pre, cases:
|
Studies evaluating two or more subgroups were labelled as cases and controls. Cases were defined as the group who exercised. If both groups exercised, the population termed cases exercised more than controls and we only presented the exercise protocol for the case group.
Abbreviations: AA: arachidonic acid, ADP: adenosine 5′diphosphate, CAD: coronary artery disease, COL: collagen, EPI: epinephrine, Inhib: inhibitor, HIIT: high-intensity interval training, MICT: moderate-intensity continuous training, MPA: monocyte-platelet aggregates, MPV: mean platelet volume, PDGF: platelet derived growth factor beta-1, PLT: platelet count, PNA: platelet–neutrophil aggregates, P-sel: P-selectin, RCT: Randomised controlled trial, sE-sel: soluble E-selectin, sP-sel: soluble P-selectin, VCAM-1: vascular cell adhesion molecule-1, vWf: von Willebrand factor.
Table 2Studies investigating the effect of regular exercise on platelet function in healthy individuals (n = 29).
Year, author Ref. | Design Study population Number of patients Age Gender (%females) | Exercise protocol | Blood sampling | Platelet analysis | Results |
---|---|---|---|---|---|
1991, Ågren et al. [15] | RCT Cases (n = 27) Controls (n = 23) 21 years Gender: 100 % | 3 times weekly 3.5 months Unsupervised | Pre 3.5 months | Platelet aggregation (ADP as agonist) TXB2 6-Keto-PGF1α | Post vs pre, cases:
|
2017, Bachero-Mena et al. [16] | Cohort study Active (n = 13) 23 years Gender 0 % | Daily 8 months NR | Pre 4 months 8 months | PLT MPV | 8 months vs pre:
|
2017, Bittencourt et al. [17] | Cross-sectional study Cases (n = 25) Controls (n = 24) NR NR | Daily NR | Single time point | Platelet micro particles | Cases vs controls:
|
2019, Boyali et al. [18] | Cohort study Active (n = 21) 20 years Gender: 57 % | 5 times weekly 2 months NR | Pre 2 months | PLT MPV PCT PDW | Post vs pre:
|
1996, Burri et al. [19] | Cohort study Inactive (n = 10) 28 years Gender: 100 % | 6 times weekly 3 months Supervised | Pre 1.5 months 3 months | PLT Platelet aggregation (ADP, COL and EPI as agonists) | 1.5 months vs pre:
|
2004, Coppola et al. [20] | Cohort study Cases (n = 15) Controls (n = 15) 43 years Gender: 27 % | 3 times weekly for 3 months Supervised | Pre 3 months | PLT Platelet aggregation (ADP as agonist) | Post vs pre, cases:
|
2004, Di Massimo et al. [21]
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans. Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9 | Cohort study Inactive (n = 12) 25 years Gender: 0 % | 3 times weekly 5 months Supervised | Pre 5 months | Platelet aggregation (ADP and COL as agonists) NOx level | Post vs pre:
|
2020, Erdogan et al. [22] | Cohort study Active (n = 16) NR Gender: 0 % | 3 times weekly for 3 months Supervised | Pre 3 months | PLT PCT MPV PDW | Post vs pre:
|
2018, Haynes et al. [23]
Beneficial impacts of regular exercise on platelet function in sedentary older adults: evidence from a randomized 6-mo walking trial. J. Appl. Physiol. (1985). 2018; 125 ([published Online First: 20180412]): 401-408https://doi.org/10.1152/japplphysiol.00079.2018 | RCT Cases (n = 14) Controls (n = 13) 60 years Gender: 82 % | 3 times weekly for 6 months Supervised | Pre 6 months | MPA (ADP, TRAP, AA as agonists) | 6 months vs pre, cases:
|
2016, Heber et al. [24] |
|
|
| Flow cytometry (P-sel, CD40L, ROS) [unstimulated and TRAP as agonist] |
|
2000, Hilberg et al. [14] | Cohort study Cases (n = 24) Controls (n = 10) 22–38 years Gender: 100 % | 2 times weekly 3 months NR | Pre 3 months | vWf | Post vs pre, cases
|
1997, Kauffman et al. [25] | Cohort study Cases (n = 10) Controls (n = 6) 66 years Gender: 50 % | 3 times weekly 4 months Supervised | Pre 4 months | 6-Keto-PGF1α TXB2 | Post vs pre, cases
|
2018, Książek et al. [26]
Endurance training selectively increases high-density lipoprotein-bound sphingosine-1-phosphate in the plasma. Scand. J. Med. Sci. Sports. 2018; 28 ([published Online First: 20170601]): 57-64https://doi.org/10.1111/sms.12910 | Cohort study Inactive (n = 17) 20 years Gender: 0 % | 3 times weekly 2 months Supervised | Pre 2 months | Sphingosine Sphinganine S1P SA1P Ceramide SphK PLT | Post vs pre
|
2006, Lippi et al. [27] | Cross-sectional study Cases (n = 89) Controls (n = 43) 28 years Gender: 0 % | Daily NR | Single time point | Platelet aggregation (COL-ADP and COL-EPI as agonist) vWf | Cases vs controls:
|
2018, Lundberg Slingsby et al. [29]
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels. Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119] | Cross-sectional study Cases (n = 14) Controls (n = 13) 52 years Gender: 0 % | 2–4 h weekly >15 years Unsupervised | Single time point | Platelet aggregation (AA, ADP, COL, EPI, TRAP, TXA2 as agonists) 6-Keto PGF1α | Cases vs controls:
|
2017, Lundberg Slingsby et al. [28]
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women. J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866 | Cohort study Inactive (n = 49) 51 years Gender: 100 % | 3 times weekly 3 months Supervised | Pre 3 months | Platelet aggregation (ADP, EPI, TRAP, TXA2 and COL as agonists) 6-Keto PGF1α PLT MPV | Post vs pre
|
2021, Medvedev et al. [30] |
|
|
| TXB2 6-Keto-PGF1α |
|
2021, Medvedev et al. [31] |
|
|
| TXB2 6-Keto-PGF1α |
|
2007, Murakami et al. [32]
Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity. Thromb. Res. 2007; 119 ([published Online First: 20060215]): 45-53https://doi.org/10.1016/j.thromres.2005.12.013 | RCT Cases (n = 28) Controls (n = 21) 52 years Gender: 48 % | 3 times weekly 3 months Supervised | Pre 3 months | Platelet microparticles | 3 months vs pre, cases:
|
2017, Podgórska et al. [33]
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity. Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909 | Cross-sectional study Cases (n = 25) Controls (n = 54) 25 years Gender: 0 % | Daily Supervised | Single time point | Platelet aggregation (AA and ADP as agonists) 6-Keto-PGF1α TXB2 Soluble markers (sP-Sel, VEGF, sICAM-1, sVCAM-1, sE-Sel, ADMA, SDMA, L-arg, Serpin E1) | Cases vs controls:
|
1993, Ponjee et al. [34] | Cohort study Inactive (n = 34) 37 years Gender: 41 % | 3 times weekly 9 months Supervised | Pre 6 months 9 months | Platelet factor 4 β-Thrombo-globulin | 6 months vs pre:
|
2013, Santilli et al. [35]
Effects of high-amount-high-intensity exercise on in vivo platelet activation: modulation by lipid peroxidation and AGE/RAGE axis. Thromb. Haemost. 2013; 110 ([published Online First: 20130912]): 1232-1240https://doi.org/10.1160/th13-04-0295 | Cohort study Inactive (n = 22) 51 years Gender: 32 % | 2 times weekly 2 months Supervised | Pre 2 months | 8-iso-PGF2α TXB2 sCD40L sP-sel | 2 months vs pre
|
2018 Tagawa et al. [52] | Cohort study Cases (n = 17) Controls (n = 7) 25 years Gender: 0 % | 3 times weekly 1 month Supervised | Pre 1 month | TXB2 | Post vs pre, cases:
|
2011 Trenerry et al. [53]
Impact of resistance exercise training on interleukin-6 and JAK/STAT in young men. Muscle Nerve. 2011; 43 ([published Online First: 20101209]): 385-392https://doi.org/10.1002/mus.21875 | Cohort study Active (n = 13) 19 years Gender: 0 % | 3 times weekly 3 months Supervised | Pre 3 months | VEGF | Post vs pre:
|
2004 Wang et al. [36] | Cohort study Inactive (n = 10) 22 years Gender: 0 % | 5 times weekly 2 months Supervised | Pre 2 months | PLT Platelet aggregation (ADP as agonist) Platelet [Ca2+]I (unstimulated and ADP) | Post vs pre:
|
1997 Wang et al. [37] | RCT Cases (n = 8) Controls (n = 8) 22 years Gender: 100 % | 5 times weekly 2 months Supervised | Pre 2 months | Platelet adhesiveness Platelet aggregation (ADP as agonist) Platelet [Ca2+]I (unstimulated and ADP) Platelet cGMP | Post vs pre, cases:
|
1995 Wang et al. [38] | RCT Cases (n = 11) Controls (n = 12) 21 years Gender: 0 % | 5 times weekly 2 months Supervised | Pre 2 months | Platelet adhesiveness Platelet aggregation (ADP as agonist) | Post vs pre, cases:
|
2005 Wang et al. [39]
Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arterioscler. Thromb. Vasc. Biol. 2005; 25 ([published Online First: 20041129]): 454-460https://doi.org/10.1161/01.Atv.0000151987.04607.24 | RCT Cases (n = 15) Controls (n = 15) 24 years Gender: 0 % | 5 times weekly 2 months Supervised | Pre 2 months | Platelet aggregation (induced by shear stress) sP-sel vWf | Post vs pre, cases:
|
2010 Zoladz et al. [40] | Cohort study Inactive (n = 12) 23 years Gender: 0 % | 4 times weekly 1 month Supervised | Pre 1 month | 6-Keto-PGF1α | Post vs pre:
|
Cohort studies investigating one group only were labelled active or inactive describing their level of physical activity at inclusion. Studies evaluating two or more subgroups were labelled as cases and controls. Cases were defined as the group who exercised. If both groups exercised, the population termed cases exercised more than controls and we only presented the exercise protocol for the case group.
Abbreviations: 6-keto-PGF1α: plasma 6-keto-prostaglandin F1α, AA: arachidonic acid, ADMA: asymmetrical dimethyl arginine, ADP: adenosine 5′diphosphate, CD40L: plasma CD40 ligand, COL: collagen, EPI: epinephrine, L-arg: L-arginine levels, MPA: monocyte-platelet aggregates, MPV: mean platelet volume, NR: not reported, PLT: platelet count, PCT: platelet crit (PLT × MPV / 10,000), PDW: platelet distribution width, RCT: randomised controlled trial, S1P: sphingosine-1-phosphate, SA1P: sphinganine-1-phosphate, sICAM-1: soluble intercellular adhesion molecule-1, SDMA: symmetrical dimethyl arginine, sE-sel: soluble-E-selectin, SphK: sphingosine kinase activity, sP-selectin: soluble-P-selectin, sVCAM-1: soluble vascular cell adhesion molecule-1, TRAP: thrombin receptor activating peptide, TXA2: thromboxane A2, TXB2: thromboxane B2, VEGF: vascular endothelial growth factor, VO2max: maximal aerobic capacity, vWf: von Willebrand factor.
Table 3Alteration in platelet function following regular exercise training from baseline to after exercise intervention (within-group) and comparing cases and controls (between-group).
Marker | Healthy individuals | Cardiovascular disease | ||
---|---|---|---|---|
Within-group | Between-group | Within-group | Between-group | |
Platelet aggregation (ADP) | ↓ 20 , 21 ,
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans. Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9 36 , 37 , 38 ↔ 15 , 19 , 28
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women. J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866 | ↓ [37] ↔ 20 , 29 ,
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels. Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119] 33 ,
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity. Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909 38 | ↓ [47] | |
Platelet aggregation (COL) | ↓ 19 , 21
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans. Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9 ↔ [28]
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women. J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866 | ↓ [29]
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels. Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119] | ↓ [47] | |
Platelet aggregation (EPI) | ↔ 19 , 28
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women. J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866 | ↓ [29]
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels. Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119] | ↓ [47] | |
TXB2 | ↓ 30 , 31 , 35
Effects of high-amount-high-intensity exercise on in vivo platelet activation: modulation by lipid peroxidation and AGE/RAGE axis. Thromb. Haemost. 2013; 110 ([published Online First: 20130912]): 1232-1240https://doi.org/10.1160/th13-04-0295 ↔ 15 , 25 ↑ [52] | ↓ 30 , 31 , 33
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity. Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909 ↑ 25 , 52 | ||
6-Keto-PGF1α | ↓ [25] ↔ 15 , 28 ,
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women. J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866 40 ↑ 30 , 31 | ↔ 25 , 29 ,
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels. Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119] 33
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity. Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909 ↑ 30 , 31 | ||
Mean platelet volume | ↓ [18] ↔ [28]
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women. J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866 ↑ 16 , 22 | ↔ [47] | ↓ [41] ↔ [51]
Effects of high-intensity interval training on platelet function in cardiac rehabilitation: a randomised controlled trial. Heart. 2020; 106 ([published Online First: 2019/07/19]): 69-79https://doi.org/10.1136/heartjnl-2019-315130 | |
Platelet count | ↓ [19] ↔ 16 , 18 , 20 , 22 , 28 ,
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women. J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866 36 | ↔ [20] | ↓ [46] ↑ [47] | ↓ [46] ↔ [51]
Effects of high-intensity interval training on platelet function in cardiac rehabilitation: a randomised controlled trial. Heart. 2020; 106 ([published Online First: 2019/07/19]): 69-79https://doi.org/10.1136/heartjnl-2019-315130 |
Micro particles | ↓ [32]
Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity. Thromb. Res. 2007; 119 ([published Online First: 20060215]): 45-53https://doi.org/10.1016/j.thromres.2005.12.013 | ↔ 17 , 32
Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity. Thromb. Res. 2007; 119 ([published Online First: 20060215]): 45-53https://doi.org/10.1016/j.thromres.2005.12.013 | ↓ [47] | |
vWf | ↓ [39]
Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arterioscler. Thromb. Vasc. Biol. 2005; 25 ([published Online First: 20041129]): 454-460https://doi.org/10.1161/01.Atv.0000151987.04607.24 ↔ [14] | ↓ [39]
Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arterioscler. Thromb. Vasc. Biol. 2005; 25 ([published Online First: 20041129]): 454-460https://doi.org/10.1161/01.Atv.0000151987.04607.24 ↔ 14 , 27 | ↓ 43 , 46 , 48 ↔ [45]
High intensity interval training reduces systemic inflammation in post-PCI patients. Eur. J. Cardiovasc. Prev. Rehabil. 2011; 18 ([published Online First: 20110218]): 850-857https://doi.org/10.1177/1741826710397600 | ↔ 43 , 45 ,
High intensity interval training reduces systemic inflammation in post-PCI patients. Eur. J. Cardiovasc. Prev. Rehabil. 2011; 18 ([published Online First: 20110218]): 850-857https://doi.org/10.1177/1741826710397600 46 |
sP-selectin | ↓ [35]
Effects of high-amount-high-intensity exercise on in vivo platelet activation: modulation by lipid peroxidation and AGE/RAGE axis. Thromb. Haemost. 2013; 110 ([published Online First: 20130912]): 1232-1240https://doi.org/10.1160/th13-04-0295 ↔ [39]
Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arterioscler. Thromb. Vasc. Biol. 2005; 25 ([published Online First: 20041129]): 454-460https://doi.org/10.1161/01.Atv.0000151987.04607.24 | ↔ 33 ,
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity. Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909 39
Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arterioscler. Thromb. Vasc. Biol. 2005; 25 ([published Online First: 20041129]): 454-460https://doi.org/10.1161/01.Atv.0000151987.04607.24 | ↓ [42] ↔ 43 , 45 ,
High intensity interval training reduces systemic inflammation in post-PCI patients. Eur. J. Cardiovasc. Prev. Rehabil. 2011; 18 ([published Online First: 20110218]): 850-857https://doi.org/10.1177/1741826710397600 50
Impact of exercise training on inflammation and platelet activation in patients with intermittent claudication. Swiss Med. Wkly. 2012; 142 ([published Online First: 20120814])w13623https://doi.org/10.4414/smw.2012.13623 | ↔ 42 , 43 , 45 ,
High intensity interval training reduces systemic inflammation in post-PCI patients. Eur. J. Cardiovasc. Prev. Rehabil. 2011; 18 ([published Online First: 20110218]): 850-857https://doi.org/10.1177/1741826710397600 50 ,
Impact of exercise training on inflammation and platelet activation in patients with intermittent claudication. Swiss Med. Wkly. 2012; 142 ([published Online First: 20120814])w13623https://doi.org/10.4414/smw.2012.13623 51
Effects of high-intensity interval training on platelet function in cardiac rehabilitation: a randomised controlled trial. Heart. 2020; 106 ([published Online First: 2019/07/19]): 69-79https://doi.org/10.1136/heartjnl-2019-315130 |
PDGF | ↓ 44 ,
Modest gains after an 8-week exercise program correlate with reductions in non-traditional markers of cardiovascular risk. Front. Cardiovasc. Med. 2021; 8 ([published Online First: 2021/07/06])669110https://doi.org/10.3389/fcvm.2021.669110 47 ↔ [49]
Soluble endoglin as a prognostic factor of the claudication distance improvement in patients with peripheral artery disease undergoing supervised treadmill training program. J. Am. Soc. Hypertens. 2017; 11 ([published Online First: 20170628]): 553-564https://doi.org/10.1016/j.jash.2017.06.009 | ↓ [44]
Modest gains after an 8-week exercise program correlate with reductions in non-traditional markers of cardiovascular risk. Front. Cardiovasc. Med. 2021; 8 ([published Online First: 2021/07/06])669110https://doi.org/10.3389/fcvm.2021.669110 |
Only platelet activity and aggregation markers examined in at least three studies across study populations are presented.
↑: Higher after exercise or higher in exercise group (cases) than controls.
↓: Lower after exercise or lower in exercise group (cases) than controls.
↔: Unchanged after exercise or no difference between exercise group (cases) and controls.
If markers were measured more than twice during the intervention, we only included comparison between baseline and post intervention blood samples in this table.
Abbreviations: ADP: adenosine diphosphate, COL: collagen, EPI: epinephrine, PDGF: platelet derived growth factor beta, TXB2: thromboxane B2, vWf: von Willebrand factor.
3.2 Exercise intervention characteristics
The included studies were homogeneous concerning the type of exercise intervention. In 38 (95 %) of the studies, aerobic exercise was performed (supervised, unsupervised or retrospectively) [
14
, 15
, 16
, 17
, 18
, 19
, 20
, 21
, - Di Massimo C.
- Scarpelli P.
- Penco M.
- et al.
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.
Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9
22
, 23
, - Haynes A.
- Linden M.D.
- Robey E.
Beneficial impacts of regular exercise on platelet function in sedentary older adults: evidence from a randomized 6-mo walking trial.
J. Appl. Physiol. (1985). 2018; 125 ([published Online First: 20180412]): 401-408https://doi.org/10.1152/japplphysiol.00079.2018
24
, 25
, 26
, - Książek M.
- Charmas M.
- Klusiewicz A.
- et al.
Endurance training selectively increases high-density lipoprotein-bound sphingosine-1-phosphate in the plasma.
Scand. J. Med. Sci. Sports. 2018; 28 ([published Online First: 20170601]): 57-64https://doi.org/10.1111/sms.12910
27
, 28
, - Lundberg Slingsby M.H.
- Nyberg M.
- Egelund J.
- et al.
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women.
J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866
29
, - Lundberg Slingsby M.H.
- Gliemann L.
- Thrane M.
- et al.
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.
Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119]
30
, 31
, 32
, - Murakami T.
- Horigome H.
- Tanaka K.
- et al.
Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity.
Thromb. Res. 2007; 119 ([published Online First: 20060215]): 45-53https://doi.org/10.1016/j.thromres.2005.12.013
33
, - Podgórska K.
- Derkacz A.
- Szahidewicz-Krupska E.
- et al.
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity.
Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909
34
, 35
, - Santilli F.
- Vazzana N.
- Iodice P.
- et al.
Effects of high-amount-high-intensity exercise on in vivo platelet activation: modulation by lipid peroxidation and AGE/RAGE axis.
Thromb. Haemost. 2013; 110 ([published Online First: 20130912]): 1232-1240https://doi.org/10.1160/th13-04-0295
36
, 37
, 38
, 39
, - Wang J.S.
- Li Y.S.
- Chen J.C.
- et al.
Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men.
Arterioscler. Thromb. Vasc. Biol. 2005; 25 ([published Online First: 20041129]): 454-460https://doi.org/10.1161/01.Atv.0000151987.04607.24
40
, 41
, 42
, 43
, 44
, - Liang G.
- Huang X.
- Hirsch J.
- et al.
Modest gains after an 8-week exercise program correlate with reductions in non-traditional markers of cardiovascular risk.
Front. Cardiovasc. Med. 2021; 8 ([published Online First: 2021/07/06])669110https://doi.org/10.3389/fcvm.2021.669110
45
, - Munk P.S.
- Breland U.M.
- Aukrust P.
- et al.
High intensity interval training reduces systemic inflammation in post-PCI patients.
Eur. J. Cardiovasc. Prev. Rehabil. 2011; 18 ([published Online First: 20110218]): 850-857https://doi.org/10.1177/1741826710397600
46
, 47
, 48
, 49
, - Januszek R.
- Mika P.
- Nowobilski R.
- et al.
Soluble endoglin as a prognostic factor of the claudication distance improvement in patients with peripheral artery disease undergoing supervised treadmill training program.
J. Am. Soc. Hypertens. 2017; 11 ([published Online First: 20170628]): 553-564https://doi.org/10.1016/j.jash.2017.06.009
50
, - Schlager O.
- Hammer A.
- Giurgea A.
Impact of exercise training on inflammation and platelet activation in patients with intermittent claudication.
Swiss Med. Wkly. 2012; 142 ([published Online First: 20120814])w13623https://doi.org/10.4414/smw.2012.13623
51
] whilst 2 (5 %) studies performed a resistance training program [- Heber S.
- Fischer B.
- Sallaberger-Lehner M.
- et al.
Effects of high-intensity interval training on platelet function in cardiac rehabilitation: a randomised controlled trial.
Heart. 2020; 106 ([published Online First: 2019/07/19]): 69-79https://doi.org/10.1136/heartjnl-2019-315130
52
, 53
]. Twenty-nine studies (73 %) performed supervised exercise training [- Trenerry M.K.
- Della Gatta P.A.
- Larsen A.E.
- et al.
Impact of resistance exercise training on interleukin-6 and JAK/STAT in young men.
Muscle Nerve. 2011; 43 ([published Online First: 20101209]): 385-392https://doi.org/10.1002/mus.21875
19
, 20
, 21
, - Di Massimo C.
- Scarpelli P.
- Penco M.
- et al.
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.
Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9
22
, 23
, - Haynes A.
- Linden M.D.
- Robey E.
Beneficial impacts of regular exercise on platelet function in sedentary older adults: evidence from a randomized 6-mo walking trial.
J. Appl. Physiol. (1985). 2018; 125 ([published Online First: 20180412]): 401-408https://doi.org/10.1152/japplphysiol.00079.2018
24
, 25
, 26
, - Książek M.
- Charmas M.
- Klusiewicz A.
- et al.
Endurance training selectively increases high-density lipoprotein-bound sphingosine-1-phosphate in the plasma.
Scand. J. Med. Sci. Sports. 2018; 28 ([published Online First: 20170601]): 57-64https://doi.org/10.1111/sms.12910
28
, - Lundberg Slingsby M.H.
- Nyberg M.
- Egelund J.
- et al.
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women.
J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866
32
, - Murakami T.
- Horigome H.
- Tanaka K.
- et al.
Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity.
Thromb. Res. 2007; 119 ([published Online First: 20060215]): 45-53https://doi.org/10.1016/j.thromres.2005.12.013
33
, - Podgórska K.
- Derkacz A.
- Szahidewicz-Krupska E.
- et al.
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity.
Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909
34
, 35
, - Santilli F.
- Vazzana N.
- Iodice P.
- et al.
Effects of high-amount-high-intensity exercise on in vivo platelet activation: modulation by lipid peroxidation and AGE/RAGE axis.
Thromb. Haemost. 2013; 110 ([published Online First: 20130912]): 1232-1240https://doi.org/10.1160/th13-04-0295
36
, 37
, 38
, 39
, - Wang J.S.
- Li Y.S.
- Chen J.C.
- et al.
Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men.
Arterioscler. Thromb. Vasc. Biol. 2005; 25 ([published Online First: 20041129]): 454-460https://doi.org/10.1161/01.Atv.0000151987.04607.24
40
, 41
, 43
, 45
, - Munk P.S.
- Breland U.M.
- Aukrust P.
- et al.
High intensity interval training reduces systemic inflammation in post-PCI patients.
Eur. J. Cardiovasc. Prev. Rehabil. 2011; 18 ([published Online First: 20110218]): 850-857https://doi.org/10.1177/1741826710397600
46
, 47
, 48
, 49
, - Januszek R.
- Mika P.
- Nowobilski R.
- et al.
Soluble endoglin as a prognostic factor of the claudication distance improvement in patients with peripheral artery disease undergoing supervised treadmill training program.
J. Am. Soc. Hypertens. 2017; 11 ([published Online First: 20170628]): 553-564https://doi.org/10.1016/j.jash.2017.06.009
50
, - Schlager O.
- Hammer A.
- Giurgea A.
Impact of exercise training on inflammation and platelet activation in patients with intermittent claudication.
Swiss Med. Wkly. 2012; 142 ([published Online First: 20120814])w13623https://doi.org/10.4414/smw.2012.13623
51
, - Heber S.
- Fischer B.
- Sallaberger-Lehner M.
- et al.
Effects of high-intensity interval training on platelet function in cardiac rehabilitation: a randomised controlled trial.
Heart. 2020; 106 ([published Online First: 2019/07/19]): 69-79https://doi.org/10.1136/heartjnl-2019-315130
52
, 53
], 6 studies (15 %) did not report supervision status [- Trenerry M.K.
- Della Gatta P.A.
- Larsen A.E.
- et al.
Impact of resistance exercise training on interleukin-6 and JAK/STAT in young men.
Muscle Nerve. 2011; 43 ([published Online First: 20101209]): 385-392https://doi.org/10.1002/mus.21875
14
, 16
, 17
, 18
, 27
, 44
] and 5 (13 %) studies performed unsupervised exercise [- Liang G.
- Huang X.
- Hirsch J.
- et al.
Modest gains after an 8-week exercise program correlate with reductions in non-traditional markers of cardiovascular risk.
Front. Cardiovasc. Med. 2021; 8 ([published Online First: 2021/07/06])669110https://doi.org/10.3389/fcvm.2021.669110
15
, 29
, - Lundberg Slingsby M.H.
- Gliemann L.
- Thrane M.
- et al.
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.
Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119]
30
, 31
, 42
]. The length of the exercise intervention was varying from 1 to 9 months. Twenty-six studies (65 %) performed exercise interventions for ≤3 months [14
, 18
, 19
, 20
, 22
, 24
, 26
, - Książek M.
- Charmas M.
- Klusiewicz A.
- et al.
Endurance training selectively increases high-density lipoprotein-bound sphingosine-1-phosphate in the plasma.
Scand. J. Med. Sci. Sports. 2018; 28 ([published Online First: 20170601]): 57-64https://doi.org/10.1111/sms.12910
28
, - Lundberg Slingsby M.H.
- Nyberg M.
- Egelund J.
- et al.
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women.
J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866
32
, - Murakami T.
- Horigome H.
- Tanaka K.
- et al.
Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity.
Thromb. Res. 2007; 119 ([published Online First: 20060215]): 45-53https://doi.org/10.1016/j.thromres.2005.12.013
35
, - Santilli F.
- Vazzana N.
- Iodice P.
- et al.
Effects of high-amount-high-intensity exercise on in vivo platelet activation: modulation by lipid peroxidation and AGE/RAGE axis.
Thromb. Haemost. 2013; 110 ([published Online First: 20130912]): 1232-1240https://doi.org/10.1160/th13-04-0295
36
, 37
, 38
, 39
, - Wang J.S.
- Li Y.S.
- Chen J.C.
- et al.
Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men.
Arterioscler. Thromb. Vasc. Biol. 2005; 25 ([published Online First: 20041129]): 454-460https://doi.org/10.1161/01.Atv.0000151987.04607.24
40
, 41
, 43
, 44
, - Liang G.
- Huang X.
- Hirsch J.
- et al.
Modest gains after an 8-week exercise program correlate with reductions in non-traditional markers of cardiovascular risk.
Front. Cardiovasc. Med. 2021; 8 ([published Online First: 2021/07/06])669110https://doi.org/10.3389/fcvm.2021.669110
46
, 47
, 48
, 49
, - Januszek R.
- Mika P.
- Nowobilski R.
- et al.
Soluble endoglin as a prognostic factor of the claudication distance improvement in patients with peripheral artery disease undergoing supervised treadmill training program.
J. Am. Soc. Hypertens. 2017; 11 ([published Online First: 20170628]): 553-564https://doi.org/10.1016/j.jash.2017.06.009
51
, - Heber S.
- Fischer B.
- Sallaberger-Lehner M.
- et al.
Effects of high-intensity interval training on platelet function in cardiac rehabilitation: a randomised controlled trial.
Heart. 2020; 106 ([published Online First: 2019/07/19]): 69-79https://doi.org/10.1136/heartjnl-2019-315130
52
, 53
], and in 14 studies (35 %) the exercise period lasted for >3 months [- Trenerry M.K.
- Della Gatta P.A.
- Larsen A.E.
- et al.
Impact of resistance exercise training on interleukin-6 and JAK/STAT in young men.
Muscle Nerve. 2011; 43 ([published Online First: 20101209]): 385-392https://doi.org/10.1002/mus.21875
15
, 16
, 17
, 21
, - Di Massimo C.
- Scarpelli P.
- Penco M.
- et al.
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.
Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9
23
, - Haynes A.
- Linden M.D.
- Robey E.
Beneficial impacts of regular exercise on platelet function in sedentary older adults: evidence from a randomized 6-mo walking trial.
J. Appl. Physiol. (1985). 2018; 125 ([published Online First: 20180412]): 401-408https://doi.org/10.1152/japplphysiol.00079.2018
25
, 27
, 29
, - Lundberg Slingsby M.H.
- Gliemann L.
- Thrane M.
- et al.
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.
Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119]
30
, 31
, 33
, - Podgórska K.
- Derkacz A.
- Szahidewicz-Krupska E.
- et al.
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity.
Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909
34
, 42
, 45
, - Munk P.S.
- Breland U.M.
- Aukrust P.
- et al.
High intensity interval training reduces systemic inflammation in post-PCI patients.
Eur. J. Cardiovasc. Prev. Rehabil. 2011; 18 ([published Online First: 20110218]): 850-857https://doi.org/10.1177/1741826710397600
50
]. Changes in platelet function markers following exercise did not differ between studies with ≤3 months' exercise compared with studies with >3 months of exercise training (data not shown).- Schlager O.
- Hammer A.
- Giurgea A.
Impact of exercise training on inflammation and platelet activation in patients with intermittent claudication.
Swiss Med. Wkly. 2012; 142 ([published Online First: 20120814])w13623https://doi.org/10.4414/smw.2012.13623
3.3 Platelet aggregation
Eight studies measured platelet aggregation using light transmittance aggregometry [
15
, 19
, 20
, 21
, - Di Massimo C.
- Scarpelli P.
- Penco M.
- et al.
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.
Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9
36
, 37
, 38
, 47
]. Overall, eight studies reported a reduction [19
, 20
, 21
, - Di Massimo C.
- Scarpelli P.
- Penco M.
- et al.
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.
Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9
29
, - Lundberg Slingsby M.H.
- Gliemann L.
- Thrane M.
- et al.
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.
Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119]
36
, 37
, 38
, 47
] and seven studies reported no changes in platelet aggregation following exercise training [15
, 19
, 20
, 28
, - Lundberg Slingsby M.H.
- Nyberg M.
- Egelund J.
- et al.
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women.
J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866
29
, - Lundberg Slingsby M.H.
- Gliemann L.
- Thrane M.
- et al.
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.
Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119]
33
, - Podgórska K.
- Derkacz A.
- Szahidewicz-Krupska E.
- et al.
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity.
Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909
38
]. The most frequently measured marker was ADP-induced platelet aggregation. When comparing changes from baseline to after the exercise intervention, six studies showed a decline [20
, 21
, - Di Massimo C.
- Scarpelli P.
- Penco M.
- et al.
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.
Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9
36
, 37
, 38
, 47
], whilst three reported no changes in ADP-induced platelet aggregation (Table 3) [15
, 19
, 28
]. When changes in the exercise groups were compared with changes in the control group, one study reported a decrease [- Lundberg Slingsby M.H.
- Nyberg M.
- Egelund J.
- et al.
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women.
J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866
[37]
] and four studies found no differences between the two groups [20
, 29
, - Lundberg Slingsby M.H.
- Gliemann L.
- Thrane M.
- et al.
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.
Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119]
33
, - Podgórska K.
- Derkacz A.
- Szahidewicz-Krupska E.
- et al.
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity.
Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909
38
]. When comparing studies that reported a decrease and studies reporting no change in ADP-induced platelet aggregation following an exercise intervention, age (33 years and 34 years) and body mass index (24 in both) were similar in both groups of studies. On the contrary, there was a noticeable variation in the gender distribution across the groups, with a greater proportion of females (44 % vs 27 %) in the group that did not find any alterations in ADP-induced platelet aggregation (χ2 (1, n = 443) = 13.4, p = 0.0003). COL-induced platelet aggregation was reduced after exercise training in four studies [19
, 21
, - Di Massimo C.
- Scarpelli P.
- Penco M.
- et al.
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.
Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9
29
, - Lundberg Slingsby M.H.
- Gliemann L.
- Thrane M.
- et al.
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.
Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119]
47
], whereas one study did not show any changes [[28]
]. Regarding results on EPI-induced platelet aggregation; two studies reported a reduced aggregation [- Lundberg Slingsby M.H.
- Nyberg M.
- Egelund J.
- et al.
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women.
J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866
29
, - Lundberg Slingsby M.H.
- Gliemann L.
- Thrane M.
- et al.
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.
Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119]
47
] and two studies did not find any changes after regular exercise training [19
, 28
]. All studies on platelet aggregation, with the exception of one [- Lundberg Slingsby M.H.
- Nyberg M.
- Egelund J.
- et al.
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women.
J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866
[47]
], comprised healthy individuals [15
, 19
, 20
, 21
, - Di Massimo C.
- Scarpelli P.
- Penco M.
- et al.
Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.
Eur. J. Appl. Physiol. 2004; 91 ([published Online First: 20031118]): 406-412https://doi.org/10.1007/s00421-003-0998-9
28
, - Lundberg Slingsby M.H.
- Nyberg M.
- Egelund J.
- et al.
Aerobic exercise training lowers platelet reactivity and improves platelet sensitivity to prostacyclin in pre- and postmenopausal women.
J. Thromb. Haemost. 2017; 15 ([published Online First: 20171027]): 2419-2431https://doi.org/10.1111/jth.13866
29
, - Lundberg Slingsby M.H.
- Gliemann L.
- Thrane M.
- et al.
Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels.
Acta Physiol (Oxf). 2018; 223e13028https://doi.org/10.1111/apha.13028 [published Online First: 20180119]
33
, - Podgórska K.
- Derkacz A.
- Szahidewicz-Krupska E.
- et al.
Effect of regular aerobic activity in young healthy athletes on profile of endothelial function and platelet activity.
Biomed. Res. Int. 2017; 2017 ([published Online First: 20170529])8715909https://doi.org/10.1155/2017/8715909
36
, 37
, 38
].3.4 Platelet activation and endothelial activation linked to platelet function
Eight different markers of endothelial and platelet activation were measured in three or more studies and are presented in Table 3 [
14
, 15
, 16
, 17
, 18
, 19
, 20
, 22
- Erdogan R.
Effects of endurance workouts on thyroid hormone metabolism and biochemical markers in athletes.