Francesco Giallauria

Intermittent versus continuous exercise training in chronic heart failure: A meta-analysis

INTRODUCTION We conducted a meta-analysis of randomized, controlled trials of combined strength and intermittent aerobic training, intermittent aerobic training only and continuous exercise training in heart failure patients. METHODS A systematic search was conducted of Medline (Ovid) (1950-September 2011), Embase.com (1974-September 2011), Cochrane Central Register of Controlled Trials and CINAHL (1981-September 19 2011). The search strategy included a mix of MeSH and free text terms for the key concepts heart failure, exercise training, interval training and intermittent exercise training. RESULTS The included studies contained an aggregate of 446 patients, 212 completed intermittent exercise training, 66 only continuous exercise training, 59 completed combined intermittent and strength training and 109 sedentary controls. Weighted mean difference (MD) in Peak VO2 was 1.04mlkg(-1)min(-1) and (95% C.I.) was 0.42-1.66 (p=0.0009) in intermittent versus continuous exercise training respectively. Weighted mean difference in Peak VO2 was -1.10mlkg(-1)min(-1) (95% C.I.) was -1.83-0.37 p=0.003 for intermittent only versus intermittent and strength (combined) training respectively. In studies reporting VE/VCO2 for intermittent versus control groups, MD was -1.50 [(95% C.I. -2.64, -0.37), p=0.01] and for intermittent versus continuous exercise training MD was -1.35 [(95% C.I. -2.15, -0.55), p=0.001]. Change in peak VO2 was positively correlated with weekly exercise energy expenditure for intermittent exercise groups (r=0.48, p=0.05). CONCLUSIONS Combined strength and intermittent exercise appears superior for peak VO2 changes when compared to intermittent exercise of similar exercise energy expenditure.

Epidemiology of Aging

Over the past century, truly remarkable changes have been observed in the health of older persons throughout the world, and these changes have strongly impacted society. The growth of the older population has resulted mostly from a general increase in the overall population size but is also strongly influenced by major declines in leading causes of mortality. These demographic transformations reverberate in society, increasing medical care and social needs, which are expected to increase steeply in the years to come. Based on demographic and epidemiologic perspectives, these changes were already detectable decades before and should have prompted radical changes in the structure and function of our system of health and social protection at that time. We come to this enormous challenge unprepared.

Arterial stiffness and vitamin D levels: the Baltimore longitudinal study of aging.

CONTEXT The importance of vitamin D for bone health has long been acknowledged. Recent evidence suggests that vitamin D can also play a role in reducing the risk of several other diseases, including cardiovascular disease. OBJECTIVE The aim of this study is to test the hypothesis that 25-hydroxyvitamin D (25-OH D) is an independent cross-sectional correlate of central arterial stiffness in a normative aging study population. DESIGN AND SETTINGS We conducted a cross-sectional analysis. SUBJECTS We studied 1228 healthy volunteers (50% males; age, 70±12 yr) of the Baltimore Longitudinal Study of Aging. MAIN OUTCOME MEASURES We measured carotid-femoral pulse wave velocity (PWV) and 25-OH D levels. RESULTS We found a significant inverse association between PWV and 25-OH D levels (adjusted r2=0.27; β=-0.43; P=0.001). After adjusting for age, gender, ethnicity, season of blood draw, estimated glomerular filtration rate, physical activity level, cardiovascular risk factors score (smoking, visceral obesity, hypercholesterolemia, hypertension, and diabetes), calcium/vitamin D supplementation, serum calcium, and PTH levels, the association between PWV and 25-OH D levels was only slightly reduced and remained statistically significant (adjusted r2=0.34; β=-0.34; P=0.04). CONCLUSIONS Vitamin D levels are inversely associated with increased arterial stiffness in a normative aging population, irrespective of traditional risk factor burden. Further research is needed to understand the mechanism of this association and to test the hypothesis that vitamin D supplementation can reduce arterial stiffness.

Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial

BACKGROUND Clomiphene citrate (CC) is the first-line therapy for the induction of ovulation in infertile women with polycystic ovary syndrome (PCOS), but ∼20% of patients are unresponsive. The aim of the current study was to test the hypothesis that a 6-week intervention that consisted of structured exercise training (SET) and hypocaloric diet increases the probability of ovulation after CC in overweight and obese CC-resistant PCOS patients. METHODS A cohort of 96 overweight and obese CC-resistant PCOS patients was enrolled consecutively in a three-arm randomized, parallel, controlled, assessor-blinded clinical trial. The three interventions were: SET plus hypocaloric diet for 6 weeks (Group A); 2 weeks of observation followed by one cycle of CC therapy (Group B); and SET plus hypocaloric diet for 6 weeks, with one cycle of CC after the first 2 weeks (Group C). The primary end-point was the ovulation rate. Other reproductive data, as well as anthropometric, hormonal and metabolic data, were also collected and considered as secondary end points. RESULTS After 6 weeks of SET plus hypocaloric diet, the ovulation rate was significantly (P =0.008) higher in Group C [12/32 (37.5%)] than in Groups A [4/32 (12.5%)] and B [3/32 (9.4%)] with relative risks of 3.9 [95% confidence interval (CI) 1.1-8.3; P = 0.035] and 4.0 (95% CI 1.2-12.8; P = 0.020) compared with Groups A and B, respectively. Compared with baseline, in Groups A and C, a significant improvement in clinical and biochemical androgen and insulin sensitivity indexes was observed. In the same two groups, the insulin sensitivity index was significantly (P < 0.05) better than that in Group B. CONCLUSIONS In overweight and obese CC-resistant PCOS patients, a 6-week intervention of SET and a hypocaloric diet was effective in increasing the probability of ovulation under CC treatment. The study was registered at Clinicaltrials.gov:NCT0100468.

Long-term effects of cardiac rehabilitation on end-exercise heart rate recovery after myocardial infarction.

Background Heart rate recovery (HRR) is a marker of vagal tone that is a powerful predictor of mortality in patients with coronary artery disease. Design This study aims at evaluating the effects of long-term exercise training on HRR after acute myocardial infarction (AMI), in order to clarify whether prolonged exercise training could maintain a long-term improvement of HRR. Methods Forty-four patients after AMI were enrolled in a 3-month hospital-based exercise training programme. At the end, patients were subdivided into two groups: group A (n = 22), patients discharged with a specific home-based exercise training programme and instructions for improving leisure-time physical activity; group B (n = 22), patients discharged with generic instructions to maintain physical activity. All patients underwent a cardiopulmonary exercise test before, at the end of 3 months exercise training and at 6 months follow-up. Results At the end of the hospital-based exercise training programme we observed an increase in peak oxygen consumption [VO2peak; from 13.9 ± 3.6 to 18 ± 2.7 ml/kg per min (A) and from 14.1 ± 3.9 to 17.9 ± 2.1 ml/kg per min (B), P<0.001] and in HRR [from 17.1 ± 1.8 to 23.4 ± 1.4 beats/min (A), and from 18.8 ± 2.1 to 24.3 ± 1.9 beats/min (B), P<0.001]. At 6 months’ follow-up we observed a further improvement in VO2peak (from 18.0 ± 2.7 to 20.3 ± 2.7 ml/kg per min, P<0.001) and in HRR (from 23.4 ± 1.4 to 27.8 ± 2.1 beats/min, P<0.001) in group A, but a significant decrease in VO2peak and in HRR in group B (P<0.001). Conclusion Long-term exercise training is useful for maintaining or improving the beneficial results of the standard 3-month exercise training programme on cardiovascular capacity and HRR. This observation may bear beneficial prognostic effects on patients after AMI.

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

Aims To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. Methods Sixty-one postinfarction patients were randomized into two groups: group T [n = 30, LV ejection fraction (EF) 41.6 ± 11.3%, mean ± SD] entered a 6-month ET programme, whereas group C (n = 31, EF 42.0 ± 7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. Results At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; −9%, P<0.001), a reduction in NT-proBNP (−71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (−40%, P<0.001; T vs. C group, P<0.001). Conclusions Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

Anabolic and catabolic biomarkers as predictors of muscle strength decline: the InCHIANTI study.

BACKGROUND Poor muscle strength is a major public health concern in older persons, predisposing to functional limitations, increased fall risk, and higher mortality. Understanding risk factors for muscle strength decline may offer opportunities for prevention and treatment. One of the possible causes of muscle strength decline is imbalance between catabolic and anabolic signaling. This study aims to examine whether high levels of multiple catabolic and low levels of multiple anabolic biomarkers predict accelerated decline of muscle strength. METHODS In a representative sample of 716 men and women aged >or=65 years in the InCHIANTI study we measured C-reactive protein, interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-alpha receptor 1 as well as dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1, and bioavailable testosterone. Biomarker values were divided into tertiles and the numbers of catabolic/anabolic biomarkers in the highest/lowest tertile were calculated. Hand-grip strength was measured at baseline and 3- and 6-year follow up. RESULTS In adjusted linear mixed models, higher concentration of IL-6 (p = 0.02) and IL-1RA (p = 0.04) as well as lower levels of DHEA-S (p = 0.01) predicted muscle strength decline. After combining all inflammatory markers, the rate of decline in grip strength was progressively greater with the increasing number of dysregulated catabolic biomarkers (p = 0.01). No effect on accelerated muscle strength decline was seen according to number of dysregulated anabolic hormones. CONCLUSIONS Having multiple elevated catabolic biomarkers is a better predictor of muscle strength decline than a single biomarker alone, suggesting that a catabolic dysregulation is at the core of the mechanism leading to muscle strength decline with aging.

Functional electrical stimulation for chronic heart failure: A meta-analysis

INTRODUCTION We conducted a meta-analysis of randomized, controlled trials of combined electrical stimulation versus conventional exercise training or placebo control in heart failure patients. METHODS A systematic search was conducted of Medline (Ovid) (1950-September 2011), Embase.com (1974-September 2011), Cochrane Central Register of Controlled Trials and CINAHL (1981-September 2011). The search strategy included a mix of MeSH and free text terms for the key concepts heart failure, exercise training and functional electrical stimulation (FES). RESULTS FES produced inferior improvements in peak VO2 when compared to cycle training: mean difference (MD) -0.32 ml.kg(-1).min(-1) (95% C.I. -0.63 to -0.02 ml.kg(-1).min(-1), p=0.04), however FES elicited superior improvements in peak VO2: MD 2.30 ml.kg(-1).min(-1) (95% C.I. 1.98 to 2.62 ml.kg(-1).min(-1), p<0.00001); and six minute walk distance to sedentary care or sham FES; MD 46.9 m (95% C.I. 22.5 to 71.3m, p=0.0002). There was no difference in change in quality of life between cycling and FES, but FES elicited significantly larger improvements in Minnesota Living with Heart Failure score than placebo or sham treatment; MD 1.15 (95% C.I. 0.69 to 1.61, p<0.00001). Moreover, the total FES intervention hours were strongly correlated with change in peak VO2, (r=0.80, p=0.02). CONCLUSIONS Passive or active exercise is beneficial for patients with moderate to severe heart failure, but active cycling, or other aerobic/resistance activity is preferred in patients with heart failure who are able to exercise, and FES is the preferred modality in those unable to actively exercise. The benefits of FES may however, be smaller than those observed in conventional exercise training. Aggregate hours of electrical stimulation therapy were associated with larger improvements in cardio-respiratory fitness.

Efficacy of inspiratory muscle training in chronic heart failure patients: a systematic review and meta-analysis.

INTRODUCTION Inspiratory muscle training (IMT) offers an alternative to exercise training (ExT) in the most severely deconditioned heart failure patients who are unable to exercise. We conducted a meta-analysis to determine magnitude of change in peak VO2, six minute walk distance (6MWD), Quality of Life measured by the Minnesota Living with Heart Failure Questionnaire (MLWHFQ), maximal inspiratory pressure (PI max) and ventilatory equivalent for carbon dioxide (VE/VCO2 slope) with IMT. METHODS A systematic search was conducted of randomized, controlled trials of IMT therapy in CHF patients using Medline (Ovid) (1950-February 2012), Embase.com (1974-February 2012), Cochrane Central Register of Controlled Trials and CINAHL (1981-February 2012). The search strategy included a mix of MeSH and free text terms for the key concepts heart failure, inspiratory or respiratory muscle training, exercise training RESULTS The eleven included studies contained data on 287 participants: 148 IMT participants and 139 sham or sedentary control. Compared to control groups, CHF patients undergoing IMT showed a significant improvement in peak VO2 (+1.83 ml kg(-1) min(-1), 95% C.I. 1.33 to 2.32 ml kg(-1) min(-1), p<0.00001); 6 MWD (+34.35 m, 95% C.I. 22.45 to 46.24 m, p<0.00001); MLWHFQ (-12.25, 95% C.I. -17.08 to -7.43, p<0.00001); PImax (+20.01, 95% C.I. 13.96 to 26.06, p<0.00001); and VE/VCO2 slope (-2.28, 95% C.I. -3.25 to -1.30, p<0.00001). CONCLUSIONS IMT improves cardio-respiratory fitness and quality of life to a similar magnitude to conventional exercise training and may provide an initial alternative to the more severely de-conditioned CHF patients who may then transition to conventional ExT.

Effects of metformin with or without supplementation with folate on homocysteine levels and vascular endothelium of women with polycystic ovary syndrome

OBJECTIVE To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium. RESEARCH DESIGN AND METHODS A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 μg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated. RESULTS After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects. CONCLUSIONS Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.