High frequency home-based exercise decreases levels of vascular endothelial growth factor in patients with stable angina pectoris.

BACKGROUND: In coronary artery disease (CAD), circulating angiogenic factors have been seen to increase, possibly as a response to ischaemia. Regular physical activity (PA) is recommended for prevention and treatment of CAD, but more research is needed to optimise PA regimes. We investigated the effect of home-based high frequency exercise (HFE) on angiogenic cytokines and cardiac markers in patients with stable CAD. DESIGN: This was a randomised case-control study METHODS: Sixty-two patients, with stable CAD, were randomised to HFE (n = 33), (aerobic exercise 70% of max, 30 min, five times/week and resistance exercise three times/week), performed at home, or usual lifestyle (control, n = 29). After eight weeks, percutaneous coronary intervention (PCI) was performed in both groups, and the HFE group continued another six months of exercise. Serum vascular endothelial growth factor (VEGF) and stromal derived factor-1 (SDF-1), plasma N-terminal-brain natriuretic peptide (NT-proBNP), high-sensitive troponin T (TnT) and copeptin were analysed. RESULTS: Data are presented as median (25(th), 75(th) percentile) of relative changes (%) from baseline. Values of p are given for the difference between the HFE and controls. HFE decreased circulating VEGF levels, before PCI (-5% (-15%, -2%)), while VEGF levels increased in the control group (5% (-3%, 20%) p = 0.004). A significant difference in VEGF remained at three months post-PCI (HFE (-1%(-12%, 5%), control (7% (0%, 14%), p = 0.04), but not at six months after PCI. SDF-1, NT-proBNP, TnT and copeptin levels did not differ significantly. In addition, VEGF levels were positively correlated to NT pro-BNP. CONCLUSIONS: Home-based HFE decreased circulating VEGF in patients with stable CAD, suggesting a reduced ischaemic burden. HFE does not increase markers of cardiac dysfunction, suggesting that it is a safe therapeutic intervention in these patients.

The effect of physical activity or exercise on key biomarkers in atherosclerosis--a systematic review.

OBJECTIVE: This systematic review aimed to summarize published papers on the effect of physical activity (PA)/exercise on key atherosclerotic factors in patients with risk factors for or established cardiovascular disease (CVD). METHODS: Studies involving PA and cytokines, chemokines, adhesion molecules, CRP and angiogenic factors were searched for in Medline and Cochrane library. Original human studies of more than 2 weeks of PA intervention were included. Study quality was assessed according to the GRADE system of evidence. RESULTS: Twenty-eight papers fulfilled the inclusion criteria. PA decreases the cytokines, tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and interferon-y IFN-y (high, moderate and low evidence, respectively). The effect of PA on chemokines; stromal derived factor-1 (SDF-1), interleukin-8 (IL-8) (insufficient evidence) and monocyte chemoattractant protein-1 (MCP-1) (low evidence) was inconclusive. Aerobic exercise decreased the adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) (moderate and high evidence, respectively), while effects of PA on E- and P-selectin were inconclusive. PA decreases C-reactive protein (CRP) (high evidence). The angiogenic actors, endothelial progenitor cells (EPCs) are increased (high evidence) and VEGF is decreased (moderate evidence) by PA. The effect of PA on these factors seems to depend on the type and duration of exercise intervention and patient factors, such as presence of ischemia. CONCLUSION: As presented in this review, there is a high level of evidence that physical activity positively affects key players in atherosclerosis development. These effects could partly explain the scientifically proven anti-atherogenic effects of PA, and do have important clinical implications.

A single-bout of one-hour spinning exercise increases troponin T in healthy subjects.

OBJECTIVES: While long-term endurance exercise is known to increase cardiac biomarkers, only a few studies on short-term exercise and these markers have been reported. The aim of this study was to investigate the acute effects of a one-hour bicycle spinning on cardiac biomarkers in healthy individuals. DESIGN: Serum levels of high-sensitive troponin T (TnT), creatinine kinase MB fraction (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine kinase (CK) and myoglobin were measured at baseline, 1 and 24 hour after one hour of spinning exercise in ten healthy and fit (age 31.0 ± 6.6 years) individuals. RESULTS: TnT doubled one hour post-exercise (All values ≤ 5 - 9.7 ± 6.0 ng/L, p < 0.001). Two individuals had TnT levels above upper reference limit, URL (20.7 and 20.2 ng/L, URL = 12 ng/L). Myoglobin levels increased 72% one hour post-exercise (38 ± 20 - 66 ± 41 mg/L, p < 0.02). TnT and myoglobin levels returned to baseline 24 hour post-exercise. Serum levels of CK-MB, NT-proBNP and CK were not significantly changed. CONCLUSIONS: A single-bout of one-hour bicycle spinning transiently increases TnT and myoglobin in healthy subjects. Some subjects even have TnT release above URL. Thus, recently performed exercise also of short duration should be taken into consideration in the evaluation of acute chest pain with release of cardiac TnT.

Transcutaneous electrical nerve stimulation induces vasodilation in healthy controls but not in refractory angina patients.

CONTEXT: Transcutaneous electrical nerve stimulation (TENS) is an effective treatment option to relieve ischemic pain in refractory angina pectoris (RAP). In healthy persons, TENS enhances local blood flow, but the mechanism responsible for the anti-ischemic effect in RAP seems to be different. OBJECTIVE: The aim of the present investigation was to compare the difference in blood flow and vasodilatory response to TENS between angina patients and healthy controls and evaluate how vascular response in these groups is affected by amperage dosage above and below motor threshold levels. METHODS: Our study evaluated upper limb vascular responses to low- and high-dose TENS (below and above motor threshold) in RAP patients compared with healthy controls. TENS was applied on the nondominating forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Forearm vascular resistance (FVR) was determined (mean arterial pressure [MAP]/FBF). Measurements were done during baseline, low-dose TENS, high-dose TENS, and during recovery. RESULTS: A significant dose-dependent increase in FBF in response to TENS stimulation was seen in controls (n=18) but not in RAP (n=23) (P=0.008). There was no significant difference in FVR ratio (FVR(stim)/FVR(ctrl)) between control (n=7) and RAP (n=23) groups at low dose (controls, 5.7+/-21%; RAP, 9.7+/-20%) or recovery (controls, -4.6+19%; RAP, 5.9+25%). High-dose TENS resulted in a significantly reduced FVR ratio (-16.8+/-11%) in controls (n=7) compared with RAP (1.6+/-32%, n=23) (P=0.02). CONCLUSION: High-dose TENS induces forearm vasodilation in healthy subjects but not in patients with RAP. These findings suggest that TENS has different vascular effects in patients with severe coronary artery disease compared with healthy controls.

Strenuous exercise increases late outgrowth endothelial cells in healthy subjects.

Endothelial progenitor cells (EPCs) and late outgrowth endothelial cells (OECs) seem to play an important role in vessel formation. While EPCs seem to exert their function mainly through a paracrine effect, the OECs can develop into mature endothelial cells and form tubular structures. Exercise is known to increase angiogenic factors that can mobilize EPCs; however, the effect on OECs is not known. We investigated the response to a single session of strenuous exercise on OECs, vascular endothelial growth factor (VEGF) and inflammatory cell levels in the healthy. Eleven healthy subjects performed 1 h of spinning exercise. Blood samples were collected at 1, 6, 24 and 48 h post-exercise for cell culture and biochemical analysis. OEC colonies doubled one hour after the spinning session (baseline 4.5 +/- 4.3 vs. 9.0 +/- 3.7, P < 0.05). Serum VEGF increased from 194 +/- 107 pg/ml at baseline to 224 +/- 111 pg/ml after 1 h, p = ns and neutrophilic granulocytes increased from 3.73 +/- 1.38 at baseline to 9.08 +/- 10.5 at 1 h (P < 0.01). The increased levels of OECs, VEGF and neutrophilic granulocytes declined gradually at the following time points. VEGF levels and neutrophilic granulocytes were highly correlated to OEC levels, r = 0.903 (VEGF) and r = 0.85 (neutrophilic granulocytes), respectively. Strenuous physical activity increases OEC colonies and is correlated to serum VEGF and neutrophilic granulocytes levels. An acute exercise-induced inflammatory response might be responsible for the VEGF release and subsequent increase of OECs. The clinical importance of these findings remains to be elucidated.