Endurance training reduces circulating inflammatory markers in persons at risk of coronary events: impact on plaque stabilization?

Inflammatory pathways are involved in destabilization of atherosclerotic plaques. We assessed the hypothesis that endurance training decreases circulating concentrations of inflammatory markers in persons with coronary artery disease (CAD) and cardiovascular risk factors (CVRFs). Thirty-two subjects with CAD and/or CVRFs joined a 12-week supervised endurance training. We found a significant decrease of the chemokines interleukin (IL)-8 (pre: 3.9+/-0.6, change: -1.2+/-0.4 pg/ml, -21%, p=0.002) and monocyte chemoattractant protein-1 (pre: 213+/-9, change: -20.4+/-8.2 pg/ml, -5%, p=0.03). Diabetes mellitus (DM) significantly influenced changes of IL-8 (p=0.002). IL-8 substantially dropped by 39% in diabetics. Moreover, matrix metalloproteinase-9 (MMP-9) highly significantly decreased in response to training (pre: 750+/-98, change: -278+/-77 ng/ml, -18%, p=0.005). Exercise-induced changes of MMP-9 were influenced by concomitant use of statins (p=0.038). We observed a particularly strong MMP-9 reduction of 44% in patients treated with statins. Acute phase reactants IL-6 (pre: 1.7+/-0.3, change: +0.25+/-0.7 pg/ml, +4%, p=0.58) and high sensitivity C-reactive protein (pre: 2.1+/-0.5, change: -0.25+/-0.4 mg/l, -9%, p=0.54) did not change in response to training. In conclusion, endurance training decreased circulating chemokines and MMP-9, which may in part explain its beneficial effect on coronary risk. Patients with DM or treated with statins because of hypercholesterolemia may particularly take advantage.

Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease.

OBJECTIVE: As regular physical exercise improves endothelial dysfunction and promotes cardiovascular health, we investigated the effect of training on angiogenesis by measuring the number of circulating endothelial progenitor cells (EPC), the level of EPC-mobilizing growth factors and tested vascular function by flow-mediated dilation (FMD) in patients with coronary artery disease (CAD) and cardiovascular risk factors (CVRF). In addition, degradation products of the NO pathway (NOx) were determined. METHODS AND RESULTS: Twenty patients with documented CAD and/or CVRF joined a 12-week supervised running training. Circulating EPCs--defined by the surface markers CD34, KDR and CD133--were measured at baseline and after exercise training by flow cytometry. We found a significant increase in circulating EPCs (2.9+/-0.4-fold increase; P < .0001), which was positively correlated with both, the change of FMD (r = .81, P < .001) and the increase of NOx synthesis (r = .83, P < .001). Plasma VEGF and erythropoietin did not change in response to exercise. However, we observed a positive correlation between the number of EPCs and erythropoietin at baseline (r = .70, P < .01) and after training (r = .73, P < .01). CONCLUSIONS: Regular exercise training augments the number of circulating EPCs in patients with CVRF and CAD and is associated with improved vascular function and NO synthesis.

Endurance training reduces circulating asymmetric dimethylarginine and myeloperoxidase levels in persons at risk of coronary events.

Asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and paraoxonase 1 (PON1) are directly involved in the pathogenesis of atherosclerosis by modulation of oxidative stress and/or NO bioavailability. We aimed to assess whether endurance exercise which is known to be cardioprotective could beneficially affect these novel risk markers. Thirty-two subjects (31-68 yrs, 56% males) with elevated cardiovascular risk including ten patients with coronary artery disease volunteered for a supervised 12-week endurance training (196 +/- 15 min/week). Their fitness evaluated by 2 km test runs improved significantly after training (pre: 17.3 +/- 0.8 vs. post: 15.7 +/- 0.9 min, p < 0.001). ADMA (pre: 0.94 +/- 0.03 vs. post: 0.75 +/- 0.04 micromol l(-1)) and MPO (pre: 296.8 +/- 22.2 vs.post: 185.7 +/- 19.5 ng ml(-1)) serum levels decreased significantly by 17.6 +/- 4.6% and 28.5 +/- 7.5%, respectively, after training (both p < 0.001). Their down-regulation was inversely correlated (ADMA: r = -0.609, p < 0.001, MPO: r = -0.437, p = 0.014) with the up-regulation of plasma cGMP levels (Cyclic-guanosine 3',5'-monophosphate; pre: 1.6 +/- 0.12 vs. post: 2.21 +/- 0.2 micromol ml(-1), p = 0.001) reflecting NO production. PON1 activity towards phenylacetate was not significantly influenced by training (pre: 133 +/- 6 vs. post: 130 +/- 5 micromol ml(-1) min(-1), p = 0.375). In a matched inactive control group (n = 16) ADMA, MPO, cGMP levels and PON1 activity did not change over time. ADMA, MPO and cGMP changes were significantly different between participants and controls (all p < 0.05). Regular endurance exercise was successful in reducing the circulating levels of two promising cardiovascular risk markers, ADMA and MPO, in persons prone to cardiac events. These changes may result in numerous antiatherosclerotic effects such as improvement of NO bioavailability, reduction of oxidative stress and lipid peroxidation.