Exercise training reduces high mobility group box-1 protein levels in women with breast cancer: findings from the DIANA-5 study.

PURPOSE: To determine whether exercise training might exert anti-inflammatory effect by reducing HMGB1 levels in women with breast cancer (BC). METHODS: We analyzed monocentric data from the DIANA (DIET AND ANDROGENS)-5 PROJECT. Study population consisted of 94 patients randomized into two groups: 61 patients (53 +/- 8 yrs, training group) were assigned to a structured exercise training intervention (3 times/week for the first 3 months, and once /week for the following 9 months); whereas 33 patients (52 +/- 7 yrs, control group) followed only the general indications to adhere to the life-style intervention suggestions of the DIANA protocol. At study entry and after 12 months, all patients underwent cardiopulmonary exercise testing, biochemical as- sessment [HMGB1, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6)]; and lipid and glycemic profile. RESULTS: There were no significant differences between groups in baseline clinical and inflammatory profile. Among the training group, only 19/61 patients had high adherence to the exercise intervention. After stratifying the study population according to the level of adhesion to the exer- cise intervention, 1-year HMGB1 levels were lower among patients more adherent to exercise (p for trend = 0.001). Further adjusting for age, body mass index and baseline values, 1-year HMGB1 levels remained significantly and inversely associated to the level of adhesion to the exercise intervention (B = -0.97, SE = 0.43, p = 0.01). CONCLUSIONS: Moderate intensity exercise training in BC survivors is associated with reduced HMGB1 levels that are proportional to the level of adhesion to the exercise intervention, independently from other classical inflammatory molecules, suggesting an exercise-induced anti-inflammatory effect mediated by HMGB1.

Exercise training early after acute myocardial infarction reduces stress-induced hypoperfusion and improves left ventricular function.

PURPOSE: Exercise training might exert its beneficial effects on myocardial perfusion by inducing coronary vascular adaptations or enhancing collateralization. We evaluated whether long-term exercise-based cardiac rehabilitation started early after ST-elevation acute myocardial infarction (STEMI) improves myocardial perfusion and left ventricular (LV) function. METHODS: Forty-six patients with recent STEMI and residual inducible hypoperfusion were randomized into two groups: 25 enrolled in a 6-month outpatient exercise-based cardiac rehabilitation programme (group T) and 21 discharged with generic instructions for maintaining physical activity and correct lifestyle (group C). All patients underwent cardiopulmonary exercise test and dipyridamole rest gated myocardial perfusion single photon emission computed tomography within 1 week after STEMI and at 6-month follow-up. RESULTS: At follow-up, group T showed an improvement in peak oxygen consumption, oxygen pulse and in the slope of increase in ventilation over carbon dioxide output (all p < 0.01) associated with a reduction of stress-induced hypoperfusion (p < 0.01) and an improvement in resting and post-stress wall motion score indexes (both p < 0.01), resting and post-stress wall thickening score indexes (both p < 0.05) and resting and post-stress LV ejection fraction (both p < 0.05). On the contrary, no changes in cardiopulmonary indexes, myocardial perfusion and LV function parameters were observed in group C at follow-up. CONCLUSION: Exercise training started early after STEMI reduces stress-induced hypoperfusion and improves LV function and contractility. Exercise-induced changes in myocardial perfusion and function were associated with the absence of unfavourable LV remodelling and with an improvement of cardiovascular functional capacity.

Exercise training improves erectile dysfunction (ED) in patients with metabolic syndrome on phosphodiesterase-5 (PDE-5) inhibitors.

INTRODUCTION: Erectile dysfunction (ED) affects about 50% of males aged 40-70 years old. ED shares with atherosclerotic disease several common risk factors; therefore, it may be considered a surrogate marker of atherosclerosis. Since phosphodiesterase-5 inhibitors are well known pharmacologic agents capable of significant improvement in ED, we designed this study to evaluate whether exercise training is of added value in patients with ED who are already on PDE-5 inhibitors. METHODS: We recruited 20 male patients affected by ED with metabolic syndrome. At baseline, all patients underwent Cardio-Pulmonary Exercise Testing (CPET) and the International Index of Erectile Function (IIEF) test. After the initial evaluation, patients were subdivided into two groups: tadalafil group (group T, n = 10), who were maintained only on tadalafil therapy, and a tadalafil/exercise training group (T/E group, n = 10) who continued tadalafil but in addition underwent a2-month structured exercise training program. RESULTS: Basal anthropometric characteristics of study population showed no significant differences. Although both-groups showed at 2 months an improvement of the IIEF score, this was more evident in the T/E group (T group: 11.2 vs 14.2, P = 0.02; T/E group: 10.8 vs 20.1, P < 0.001). There was an improvement of oxygen consumption at peak exercise (VO(2peak)) only in the T/E group patients (T group: 13.63 +/- 2.03 vs 14.24 +/- 2.98 mL/kg/min; P = 0.521; T/E group: 13.41 +/- 2.97 vs 16.58 +/- 3.17 mL/kg/min; P = 0.006). A significant correlation was found between the changes in VO(2peak) and the modifications in IIEF score (r = 0.575; P = 0.001). CONCLUSION: Exercise training in ED patients treated with PDE-5 inhibitors is of added value since further improves ED, as evaluated by IIEF score, and increases functional capacity.

[Takotsubo syndrome in a young woman during puerperium: case report]. / Sindrome di Takotsubo nel puerperio: caso clinico.

INTRODUCTION: Takotsubo syndrome is a reversibile cardiomyopathy that often occurs during an emotional stress and is more frequent in post-menopausal women. CASE PRESENTATION: We describe a clinic case of a 42 years old woman, admitted to our emergency unit because of a thoracic pain. The ECG showed ST-T elevation in V1-V4, the echocardiography revealed akinesia of apical segment of left ventricle. Coronary arteries were free from significant stenosis and ventriculography showed akinesia of apical segment of left ventricle. In the following days, ECG evolved toward a normalization of ST-T segment with appearance of negative T wave in V2-V6, and also the echocardiography showed a normalized LV wall motion. The patient was discharged and ECG and echocardiography were normal at two months follow up. CONCLUSION: In this case report, a young woman during puerperium presented with a Takotsubo syndrome. We speculate that the high Prolactin level and her emotional state contributed to the clinical manifestation of the syndrome.

Exercise training improves cardiopulmonary and endothelial function in women with breast cancer: findings from the Diana-5 dietary intervention study.

To investigate whether exercise training (ET) improves cardiopulmonary and endothelial function in women with breast cancer (BC). Fifty-one female patients (aged between 39 and 72 years) with a history of primary invasive BC within the previous 5 years and enrolled in the Mediterranean diet-based DIANA (diet and androgens)-5 Trial were subdivided into 2 groups: an ET group (n = 25) followed a formal ET program of moderate intensity (3 session/week on a bicycle at 60-70 % VO2peak for 3 months, followed by one session/week until 1-year follow-up), while a control group (n = 26) did not perform any formal ET. At baseline and at 1-year follow-up, all patients underwent cardiopulmonary exercise stress test (CPET) and measurements of vascular endothelial function by peripheral artery tonometry (Reactive Hyperemia Index, RHI). There were no significant differences between the groups in baseline anthropometrical, BC characteristics, and metabolic profile. No differences in baseline CPET and RHI parameters were found. Peak oxygen consumption (VO2peak) significantly increased in ET group (from 12.4 ± 2.9 to 14.3 ± 3.3 mL/kg/min, p < 0.001) compared to the control group (from 12.8 ± 2.5 to 12.6 ± 2.8 mL/kg/min, p = 0.55; p < 0.001 between groups). Compared to the control group (from 2.0 ± 0.4 to 1.9 ± 0.4, p = 0.62), the ET group showed a significant improvement of RHI after 1 year (from 2.1 ± 0.7 to 2.5 ± 0.8, p < 0.001). Changes in VO2peak were correlated with changes in RHI (ΔVO2peak vs. ΔRHI: r = 0.47, p = 0.017). In BC survivors, ET program improves cardiopulmonary functional capacity and vascular endothelial function after 12 months. Whether these changes may favorably modulate some of the pathophysiological mechanisms implied in cancer evolution should be investigated.

Exercise training improves heart rate recovery in women with breast cancer.

PURPOSE: To determine whether exercise training improves autonomic function in women with breast cancer (BC). METHODS: Fifty-one patients (aged between 39 and 72 years) with a history of primary invasive BC within the previous 5 years and enrolled in the Mediterranean diet-based DIANA (Diet and Androgens)-5 Trial were subdivided in two groups: a ET group (n = 25) followed a formal ET program of moderate intensity (3 session/week on a bicycle at 60-70% VO2peak for 3 months, followed by one session/week until 1-year follow-up), while a control group (n = 26) did not perform any formal ET. At baseline and after 1-year, all patients underwent cardiopulmonary exercise stress test (CPET). Heart rate recovery (HRR) was calculated as the difference between heart rate at peak exercise and heart rate at first minute of the cool-down period. RESULTS: There were no significant differences between groups in baseline anthropometrical, BC characteristics, metabolic profile, CPET parameters and HRR. Compared to controls, at 1-year follow-up ET group showed a significant improvement in VO2peak (from 12.6 ± 3.0 to 14.5 ± 3.3 ml/kg/min, p < 0.001; p < 0.001 between groups); and in HRR (from 17.6 ± 6.4 to 23.0 ± 8.3 beats/min, p < 0.001; p < 0.001 between groups). In ET group the changes in HRR directly correlated with changes in VO2peak (r = 0.58, p = 0.002). CONCLUSIONS: Moderate intensity exercise training in BC survivors is associated with improvement of autonomic function. Whether the improvement of sympatho-vagal balance may favorably modulate some of the pathophysiological mechanisms implied in cancer evolution need further investigation.