Pascal Izzicupo

Salivary chromogranin A, but not α-amylase, correlates with cardiovascular parameters during high-intensity exercise

Introduction  Several studies have shown that activation of the sympathetic nervous system results in the increased secretion of α‐amylase (sAA), an enzyme produced by salivary glands. Recently, chromogranin A (CgA), a soluble protein costored and coreleased with catecholamines from the adrenal medulla and sympathetic nerve endings, has been proposed as a marker of sympathoadrenal medullary system (SAM) activity. The aim of this study was to investigate the behaviour of salivary chromogranin A (sCgA) and sAA during high‐intensity exercise and to analyse their possible correlation with cardiovascular and psychological parameters.

Biological function and clinical relevance of chromogranin A and derived peptides

Chromogranin A (CgA (CHGA)) is the major soluble protein co-stored and co-released with catecholamines and can function as a pro-hormone by giving rise to several bioactive peptides. This review summarizes the physiological functions, the pathogenic implications, and the recent use of these molecules as biomarkers in several pathological conditions. A thorough literature review of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized keywords such as chromogranin A, vasostatins 1 and 2, chromofungin, chromacin, pancreastatin, catestatin, WE14, chromostatin, GE25, parastatin, and serpinin and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular, and the immune systems and by affecting the glucose or calcium homeostasis. As some peptides exert similar effects, but others elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumors, but also in cardiovascular, inflammatory, and neuropsychiatric diseases.

Walking training in postmenopause: effects on both spontaneous physical activity and training-induced body adaptations.

ObjectiveBecause physical exercise has been widely used for primary and secondary preventions of cardiometabolic diseases arising with menopause, the aim of our study was to determine whether participation in aerobic physical exercise is linked to the modification of spontaneous physical activity and whether this compensation affects aerobic training–related body adaptations. MethodsBoth before and after a 13-week walking training program, 34 postmenopausal women (mean ± SD age, 55.89 ± 3.57 y) were analyzed for lipids, adipokines, glucose, and insulin plasma levels, as well as for body measures, heart rate and blood pressure at rest, maximal aerobic capacity, total daily energy expenditure, mean intensity of daily physical activities, and time and energy spent on physical activities with an intensity of more than three metabolic equivalents. ResultsAerobic training induced significant reductions in body mass, body mass index, heart rate, systolic blood pressure, basal cardiac double product, plasma glucose, leptin, and resistin. Aerobic fitness, the reserve of the cardiac double product, and the quantitative insulin sensitivity index were significantly improved. Cluster analysis of the variations in the total daily energy expenditure, the mean intensity of daily physical activities, and the time and energy spent on physical activities with an intensity of more than three metabolic equivalents identified two subgroups: one showed reduced spontaneous physical activity (GROUP−), whereas the other did not (GROUP+). The subgroups differed significantly only for plasma lipid variation. GROUP+ showed significantly reduced low-density lipoprotein cholesterol and total cholesterol, whereas GROUP− did not show significantly modified plasma lipids. ConclusionsIn postmenopause, participation in a program of aerobic physical exercise can result in a reduction of spontaneous physical activity, which inhibits the positive effects of the aerobic exercise on plasma lipids and lipoproteins.

A life course examination of the physical environmental determinants of physical activity behaviour: A “Determinants of Diet and Physical Activity” (DEDIPAC) umbrella systematic literature review

Background Participation in regular physical activity is associated with a multitude of health benefits across the life course. However, many people fail to meet PA recommendations. Despite a plethora of studies, the evidence regarding the environmental (physical) determinants of physical activity remains inconclusive. Objective To identify the physical environmental determinants that influence PA across the life course. Methods An online systematic literature search was conducted using MEDLINE, ISI Web of Science, Scopus and SPORTDiscus. The search was limited to studies published in English (January 2004 to April 2016). Only systematic literature reviews (SLRs) and meta-analyses (MAs) of observational studies, that investigated the association between physical determinants and physical activity outcomes, were eligible for inclusion. The extracted data were assessed on the importance of determinants, strength of evidence and methodological quality. Results The literature search identified 28 SLRs and 3 MAs on 67 physical environmental characteristics potentially related to physical activity that were eligible for inclusion. Among preschool children, a positive association was reported between availability of backyard space and outdoor toys/equipment in the home and overall physical activity. The availability of physical activity programs and equipment within schools, and neighbourhood features such as pedestrian and cyclist safety structure were positively associated with physical activity in children and adolescents. Negative street characteristics, for example, lack of sidewalks and streetlights, were negatively associated with physical activity in adults. Inconsistent associations were reported for the majority of reviewed determinants in adults. Conclusion This umbrella SLR provided a comprehensive overview of the physical environment determinants of physical activity across the life course and has highlighted, particularly amongst youth, a number of key determinants that may be associated with overall physical activity. Given the limited evidence drawn mostly from cross-sectional studies, longitudinal studies are needed to further explore these associations. Registration PROSPERO CRD42015010616

ACE and AGTR1 Polymorphisms and Left Ventricular Hypertrophy in Endurance Athletes

OBJECTIVE This study aimed to evaluate the role of angiotensin type 1 receptor gene (AGTR1) polymorphism (A1166C) in left ventricular hypertrophy (LVH) mediated by the angiotensin-converting enzyme (ACE) in endurance athletes. METHODS A group of 74 white, healthy male endurance athletes, aged between 25 and 40 yr, were enrolled in this study. All of them participated primarily in isotonic sports, training for at least >10 h x wk(-1), for at least 5 yr. The ACE genotype (insertion [I] or deletion [D] alleles) was ascertained by polymerase chain reaction (DD in 35, ID in 36, and II in 3). Group II was excluded from the analysis because of its small size. No difference was found between the two groups as regards age, blood pressure, HR, and echocardiographic data. RESULTS The left ventricular mass index (LVMI) was significantly higher in group DD rather than in group ID (P = 0.029). The group DD showed a slightly higher prevalence of subjects with LVH (LVMI > 131 g x m(-2); 62.9%) than group ID (44.4%, P = 0.120). No association was found between ACE-DD and LVH (odds ratio (OR) = 2.12, 95% confidence interval = 0.82-5.46). Concerning the role of AGTR1 polymorphism, the highest LVMI was found in 15 athletes with ACE-DD and AGTR1-AC/CC genotypes (150 +/- 23 g x m(-2)); the lowest value of LVMI was found in the case of ACE-ID and AGTR1-AA (127 g x m(-2) +/- 18 g x m(-2)), whereas LVMI in subjects with ACE-DD + AGTR1-AA was similar to that in the ACE-ID + AGTR1-AC/CC group (134 +/- 18 g x m(-2) vs 133 +/- 20 g x m(-2), P = 0.880). The presence of ACE-DD + AGTR1 + AC/CC was strongly associated with LVH (OR = 4.6, P = 0.029). Moreover, subjects with LVH showed longer left ventricular isovolumetric relaxation time and higher end-systolic wall stress. The latter was strongly correlated to LVMI (r = 0.588), especially in the presence of ACE-DD + AGTR1 + AC/CC (r = 0.728). CONCLUSIONS LVMI may be greater in the presence of ACE- DD and AGTR1-AC/CC polymorphisms.

Walking training affects dehydroepiandrosterone sulfate and inflammation independent of changes in spontaneous physical activity.

ObjectiveWe hypothesized that physical exercise in postmenopausal women could interfere with the molecular interrelationship of the immune-endocrine system and be effective even in women in whom training determined a reduction of spontaneous physical activity (SPA). For this reason, we investigated the effects of an aerobic program on plasma dehydroepiandrosterone sulfate (DHEA-S) and cytokine levels in relationship to SPA modification. MethodsThirty-two postmenopausal women (mean [SD] age, 56.38 [4.33] y) were enrolled in the study. Inclusion criteria were as follows: age younger than 65 years, body mass index higher than 18.5 and lower than 35 kg/m2, no pharmacological treatments, and no history of chronic, cardiovascular, or orthopedic diseases. Before and after 3 months of walking training at moderate intensity (40-50 min, 4 d/wk), they were evaluated for SPA, body composition, energy intake, and levels of plasma cytokines (tumor necrosis factor &agr; [TNF-&agr;], interleukin [IL]-1&agr;, IL-1&bgr;, IL-2, IL-8, and IL-10), C-reactive protein, DHEA-S, cortisol, and estrogen. ResultsAt baseline, SPA did not correlate with either DHEA-S level or cytokine levels. There was negative correlation between DHEA-S and both TNF-&agr; and IL-2. After the intervention program, 16 women showed increased SPA, and 16 women showed decreased SPA. Independent of these changes in SPA, both TNF-&agr; levels and cortisol-to-DHEA-S ratio decreased, whereas DHEA-S levels increased. ConclusionsIn postmenopausal women, walking training, rather than SPA, influences DHEA-S and cytokine concentrations and their correlations, thus interfering with adrenal steroids and the inflammatory markers network. Physical exercise acts in parallel on menopausal neuroendocrine alterations and on the systemic inflammatory profile independent of SPA changes.

Functional mitral regurgitation: from normal to pathological anatomy of mitral valve.

Mitral valve (MV) is composed of several structures working in synchrony to open during diastole and close in systole within the high-pressure systemic environment. Its morphological features ensure a normal leaflet closure that prevents regurgitation of blood back into the left atrium causing loss of ventricular pressure and forward flow. The complex interactions of the normal MV are reliant on each component playing a complete role for the efficient working of the valve. In this review we firstly discuss the overall MV structure in terms of a complex make up of the annulus, the leaflets, their tendinous cords, and the supporting papillary muscles, and then the anatomical changes of each MV components due to left ventricular geometry and function alterations, underlying functional mitral regurgitation.

Behavioral determinants of physical activity across the life course: a “DEterminants of DIet and Physical ACtivity” (DEDIPAC) umbrella systematic literature review

BackgroundLow levels of physical activity (PA) are a global concern and increasing PA engagement is becoming a priority in current public health policies. Despite the large number of studies and reviews available, the evidence regarding the behavioral determinants of PA is still inconclusive. Thus, the aim of this umbrella systematic literature review (SLR) was to summarize the evidence on the behavioral determinants of PA across the life course.MethodsA systematic online search was conducted on MEDLINE, ISI Web of Science, Scopus, and SPORTDiscus databases. The search was limited to studies published in English from January, 2004 to April, 2016. SLRs and meta-analyses (MAs) of observational studies that investigated the behavioral determinants of PA were considered eligible. The extracted data were assessed based on the importance of the determinants, the strength of evidence, and the methodological quality. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42015010616).ResultsSeventeen reviews on 35 behavioral determinants of PA were eligible for this umbrella SLR. Regardless of age, the most investigated determinants were those related with ‘screen use’ and ‘smoking’. For youth, probable positive evidence emerged for ‘previous PA’ and ‘independent mobility and active transport’ among children and adolescents. For the adult population, ‘transition to university’ and ‘pregnancy/having a child’ showed probable negative associations.ConclusionsAlthough the majority of the evidence was limited and most of the determinants were not associated with PA, this umbrella SLR provided a comprehensive overview of the associations between behavioral determinants and PA. Youth should be physically active in the early years and increase active transportation to/from school, independent mobility, and ‘free-range activities’ without adult supervision, whilst adult PA behaviors are mostly influenced by the life events. Finally, more research is needed that incorporates prospective study designs, standardized definitions of PA, objective measurement methods of PA assessment, and the use of interactionist and mediational approaches for the evaluation of different behavioral determinants influencing PA behaviors.

Effects of ACE I/D polymorphism and aerobic training on the immune-endocrine network and cardiovascular parameters of postmenopausal women

CONTEXT Estrogen deficiency, systemic low-grade inflammation, and reduction of adrenal gland function have central roles in noncommunicable chronic disease (NCD) development. With angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism, the deletion variant (DD) is related to higher levels of circulating angiotensin II than I allele carriers (II/ID), which might interact with all of these molecular pathways to increase NCDs risk. On the other hand, physical exercise counteracts the occurrence of NCDs, potentially acting on the same pathways. OBJECTIVES The aim of the study was to investigate the effects of walking training on adrenal steroid and cytokine levels and on cardiovascular parameters in postmenopausal women with ACE I/D genotypes. METHODS Thirty-six (DD = 15, II/ID = 21) sedentary postmenopausal women (mean age, 56 ± 4 y) participated in a 13-week program of walking training at moderate intensity. Heart rate, blood pressure, double product, TNF-α, dehydroepiandrosterone sulfate (DHEA-S), and cortisol were evaluated before and after the intervention program. RESULTS Before walking training, the ACE DD genotype showed significantly higher TNF-α (P = .007) and lower DHEA-S concentrations (P = .022) than the ACE II/ID individuals. After walking training, both subgroups significantly decreased TNF-α plasma levels and cortisol/DHEA-S ratio (P = .001 and P = .016, respectively) and significantly increased DHEA-S levels (P < .001). Moreover, all the cardiovascular parameters were significantly reduced in the ACE DD participants (P ≤ .05), whereas the ACE I-allele carriers showed a decrease in heart rate (P ≤ .05) and the double product (P ≤ .05). CONCLUSION ACE I/D polymorphism is linked to different adrenal steroid and cytokine levels, and ACE I-allele carriers show a better adrenal activity and systemic inflammatory profile. The introduction of walking training positively influences the menopause immune-neuroendocrine changes, independent of ACE I/D genotype.

NAD(P)H oxidase and pro-inflammatory response during maximal exercise: role of C242T polymorphism of the P22PHOX subunit

Intense exercise induces a pro-inflammatory status through a mechanism involving the NAD(P)H oxidase system. We focused our attention on p22phox, a subunit of the NAD(P)H oxidase, and on its allelic polymorphism C242T, which is known to affect the functional activity of the enzyme. We investigated whether the p22phox C242T variants exhibit systemic effects in healthy subjects by analyzing the proinflammatory and cardiocirculatory responses to physical exercise in endurance athletes. The group of study consisted of 97 long distance runners, 37±4.4 yrs of age, with similar training history. The subjects underwent a maximal stress test during which both inflammatory and cardiopulmonary parameters were monitored. Our results demonstrate that T allele deeply influences the neutrophil activation in response to intense exercise, since T carriers were characterized by significantly lower release of myeloperoxidase (MPO), a classical leukocyte derived pro-inflammatory cytokine. In addition, the presence of T allele was associated with a higher cardiopulmonary efficiency as evidenced by a significantly lower Heart Rate (HR) at the peak of exercise and, when a dominant model was assumed, by a higher maximal oxygen uptake (VO2 max). On the other hand, no effects of 242T mutation on the plasmatic total antioxidant capacity (TAC) and on the cortisol responses to the physical exercise were detected. In conclusion, our data support a systemic role for p22phox C242T polymorphism that, modifying the intensity of the inflammatory response, can influence the cardiovascular adaptations elicited by aerobic training. These results contribute to support the hypothesis of a systemic effect for the C242T polymorphism and of its possible functional rebound in healthy subjects.