Guillaume Walther

Subclinical Cardiac Abnormalities in Human Immunodeficiency Virus-Infected Men Receiving Antiretroviral Therapy

Although cardiotoxic effects of highly active antiretroviral therapy (HAART) are a growing concern, there is a lack of prospective studies of subclinical involvement of the heart in human immunodeficiency virus (HIV)-infected patients. This study evaluated noninvasively cardiac morphologic characteristics and function in HIV-positive (HIV(+)) men receiving HAART for > or =2 years with no clinical evidence of cardiovascular disease. Echocardiography at rest, including tissue Doppler imaging and exercise testing, were performed in 30 HIV(+) men (age 42.1 +/- 4.7 years, duration of HIV infection 10.4 +/- 4.7 years, duration of HAART 5.3 +/- 2.1 years) and 26 age-matched healthy controls. At rest, HIV(+) patients had similar left ventricular (LV) mass indexed to height(2.7) (40.6 +/- 9.5 vs 37.5 +/- 9.3 g/m; p >0.05), but a higher prevalence of LV diastolic dysfunction (abnormal relaxation or pseudonormal filling pattern in 64% of patients vs 12% of controls; p <0.001). LV systolic function indexes were significantly lower (ejection fraction 60.4 +/- 8.7% vs 66.9 +/- 6.9%; p <0.01, and tissue Doppler imaging peak systolic velocity 11.4 +/- 1.6 vs 13.5 +/- 2.2 cm/s; p <0.001). Pulmonary artery pressure was higher in patients compared with controls (32.1 +/- 5.4 vs 26.1 +/- 6.5 mm Hg; p <0.001). Exercise testing showed decreased exercise tolerance in HIV(+) patients, with no case of myocardial ischemia. In conclusion, subclinical cardiac abnormalities are frequently observed in HIV(+) patients on HAART. The usefulness of systematic noninvasive screening in this population should be considered. GECEM study no. 30: National Agency for AIDS Research (ANRS).

Flow-mediated dilation and exercise-induced hyperaemia in highly trained athletes: comparison of the upper and lower limb vasculature

Aim:  The main purpose of the present study was to assess whether similar vascular adaptive changes could be obtained by long‐term intensive training involving predominantly either the lower or the upper limb musculature.

Different modalities of exercise to reduce visceral fat mass and cardiovascular risk in metabolic syndrome: the RESOLVE* randomized trial

BACKGROUND Opinions differ over the exercise modalities that best limit cardiovascular risk (CVR) resulting from visceral obesity in individuals with metabolic syndrome (MetS). As little is known about the combined effects of resistance and endurance training at high volumes under sound nutritional conditions, we aimed to analyze the impact of various intensities of physical activity on visceral fat and CVR in individuals with MetS. METHODS 100 participants, aged 50-70 years, underwent a diet restriction (protein intake 1.2g/kg/day) with a high exercise volume (15-20 h/week). They were randomized to three training groups: moderate-resistance-moderate-endurance (re), high-resistance-moderate-endurance (Re), or moderate-resistance-high-endurance (rE). A one-year at-home follow-up (M12) commenced with a three-week residential program (Day 0 to Day 21). We measured the change in visceral fat and body composition by DXA, MetS parameters, fitness, the Framingham score and carotid-intima-media-thickness. RESULTS 78 participants completed the program. At D21, visceral fat loss was highest in Re (-18%, p<.0001) and higher in rE than re (-12% vs. -7%, p<.0001). Similarly, from M3, visceral fat decreased more in high-intensity-groups to reach a visceral fat loss of -21.5% (Re) and -21.1% (rE)>-13.0% (re) at M12 (p<.001). CVR, MetS parameters and fitness improved in all groups. Visceral fat loss correlated with changes in MetS parameters. CONCLUSION Increased intensity in high volume training is efficient in improving visceral fat loss and carotid-intima-media-thickness, and is realistic in community dwelling, moderately obese individuals. High-intensity-resistance training induced a faster visceral fat loss, and thus the potential of resistance training should not be undervalued (ClinicalTrials.gov number: NCT00917917).

Metabolic Syndrome Individuals With and Without Type 2 Diabetes Mellitus Present Generalized Vascular Dysfunction Cross-Sectional Study

Objectives— The first objective of this study was to demonstrate differences within endothelial-dependent and endothelial-independent vasoreactivity in macro- and microcirculation beds among patients with metabolic syndrome (MetS) with and without type 2 diabetes mellitus (T2D) compared with healthy counterparts. The second objective was to determine relationships among the function of macro- and microvascular systems and abdominal adiposity, as well as inflammatory markers in the 3 groups. Approach and Results— Cross-sectional analyses of 53 patients with MetS without T2D and 25 with T2D, as well as aged 40 years and sex-matched healthy controls included microvascular (cutaneous blood flow measured with laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside), and macrovascular reactivity (flow-mediated dilation and nitrate-mediated dilation) along with anthropometric measures, plasma glucose, and insulin and inflammatory markers. Compared with controls, MetS participants showed depressed endothelial function of both micro- and macrocirculation beds. T2D in patients with MetS revealed an exacerbated vascular smooth muscle dysfunction in micro- and macrocirculation compared with MetS without T2D. Indices of micro- and macrocirculation were predominantly inversely related to abdominal fat and inflammatory markers. Conclusions— MetS was associated with endothelial-dependent and endothelial-independent dysfunction, affecting both the macro- and the microvascular systems. Participants with diabetes mellitus demonstrated the most severe smooth muscle dysfunction. The presence of central abdominal fat and systemic inflammation seems implicated in the pathogenesis of vascular dysfunctions in MetS.

Vascular smooth muscle function in type 2 diabetes mellitus: a systematic review and meta-analysis

Aims/hypothesisIn type 2 diabetes, in contrast to the well-documented endothelial dysfunction, studies assessing vascular smooth muscle (VSM) function have yielded discrepant results over the last two decades. We therefore sought to determine whether or not VSM function is impaired in individuals with type 2 diabetes.MethodsWe conducted a systematic search of MEDLINE, Cochrane, Scopus and Web of Science databases, from their respective inceptions until December 2012, for articles evaluating VSM function in individuals with type 2 diabetes. A meta-analysis was performed to compare the standardised mean difference (SMD) in VSM function between individuals with type 2 diabetes and age-matched controls. Subgroup analyses and meta-regression were used to identify sources of heterogeneity.ResultsTwenty-seven articles (1,042 individuals with type 2 diabetes and 601 control subjects) were included in this analysis. VSM function was significantly impaired in diabetic compared with control subjects (SMD −0.68, 95% CI −0.84, −0.52; p < 0.001). Although moderate heterogeneity among studies was found (I2 = 52%), no significant publication bias was detected. Subgroup analyses showed a further decline in VSM function assessed in the microcirculation compared with the macrocirculation of individuals with type 2 diabetes (p = 0.009). In meta-regression, VSM function in the microcirculation was inversely associated with BMI and triacylglycerols and was positively associated with HDL-cholesterol.Conclusions/interpretationIn addition to the endothelium, the VSM is a source of vascular dysfunction in type 2 diabetes. An exacerbation of VSM function in the microcirculation may be a distinctive feature in type 2 diabetes.

Phlebotomy eliminates the maximal cardiac output response to six weeks of exercise training

With this study we tested the hypothesis that 6 wk of endurance training increases maximal cardiac output (Qmax) relatively more by elevating blood volume (BV) than by inducing structural and functional changes within the heart. Nine healthy but untrained volunteers (Vo2max 47 ± 5 ml·min(-1)·kg(-1)) underwent supervised training (60 min; 4 times weekly at 65% Vo2max for 6 wk), and Qmax was determined by inert gas rebreathing during cycle ergometer exercise before and after the training period. After the training period, blood volume (determined in duplicates by CO rebreathing) was reestablished to pretraining values by phlebotomy and Qmax was quantified again. Resting echography revealed no structural heart adaptations as a consequence of the training intervention. After the training period, plasma volume (PV), red blood cell volume (RBCV), and BV increased (P < 0.05) by 147 ± 168 (5 ± 5%), 235 ± 64 (10 ± 3%), and 382 ± 204 ml (7 ± 4%), respectively. Vo2max was augmented (P < 0.05) by 10 ± 7% after the training period and decreased (P < 0.05) by 8 ± 7% with phlebotomy. Concomitantly, Qmax was increased (P < 0.05) from 18.9 ± 2.1 to 20.4 ± 2.3 l/min (9 ± 6%) as a consequence of the training intervention, and after normalization of BV by phlebotomy Qmax returned to pretraining values (18.1 ± 2.5 l/min; 12 ± 5% reversal). Thus the exercise training-induced increase in BV is the main mechanism increasing Qmax after 6 wk of endurance training in previously untrained subjects.

Multilevel Approach of a 1-Year Program of Dietary and Exercise Interventions on Bone Mineral Content and Density in Metabolic Syndrome--the RESOLVE Randomized Controlled Trial.

Background Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome (MetS). However, restrictive diets might induce bone loss. The nature of exercise and whether exercise with weight loss programs can protect against potential bone mass deficits remains unclear. Moreover, compliance is essential in intervention programs. Thus, we aimed to investigate the effects that modality and exercise compliance have on bone mineral content (BMC) and density (BMD). Methods We investigated 90 individuals with MetS who were recruited for the 1-year RESOLVE trial. Community-dwelling seniors with MetS were randomly assigned into three different modalities of exercise (intensive resistance, intensive endurance, moderate mixed) combined with a restrictive diet. They were compared to 44 healthy controls who did not undergo the intervention. Results This intensive lifestyle intervention (15–20 hours of training/week + restrictive diet) resulted in weight loss, body composition changes and health improvements. Baseline BMC and BMD for total body, lumbar spine and femoral neck did not differ between MetS groups and between MetS and controls. Despite changes over time, BMC or BMD did not differ between the three modalities of exercise and when compared with the controls. However, independent of exercise modality, compliant participants increased their BMC and BMD compared with their less compliant peers. Decreases in total body lean mass and negative energy balance significantly and independently contributed to decreases in lumbar spine BMC. Conclusion After the one year intervention, differences relating to exercise modalities were not evident. However, compliance with an intensive exercise program resulted in a significantly higher bone mass during energy restriction than non-compliance. Exercise is therefore beneficial to bone in the context of a weight loss program. Trial Registration ClinicalTrials.gov NCT00917917

Acute Hyperglycemia Impairs Vascular Function in Healthy and Cardiometabolic Diseased Subjects Systematic Review and Meta-Analysis

Objectives—Controversy exists over the effect of acute hyperglycemia on vascular function. In this systematic review, we compared the effect of acute hyperglycemia on endothelial and vascular smooth muscle functions across healthy and cardiometabolic diseased subjects. Approach and Results—A systematic search of MEDLINE, EMBASE, and Web of Science from inception until July 2014 identified articles evaluating endothelial or vascular smooth muscle function during acute hyperglycemia and normoglycemia. Meta-analyses compared the standardized mean difference (SMD) in endothelial and vascular smooth muscle functions between acute hyperglycemia and normoglycemia. Subgroup analyses and metaregression identified sources of heterogeneity. Thirty-nine articles (525 healthy and 540 cardiometabolic subjects) were analyzed. Endothelial function was decreased (39 studies; n=1065; SMD, −1.25; 95% confidence interval, −1.52 to −0.98; P<0.01), whereas vascular smooth muscle function was preserved (6 studies; n=144; SMD, −0.07; 95% confidence interval, −0.30 to 0.16; P=0.55) during acute hyperglycemia compared with normoglycemia. Significant heterogeneity was detected among endothelial function studies (P<0.01). A subgroup analysis revealed that endothelial function was decreased in the macrocirculation (30 studies; n=884; SMD, −1.40; 95% confidence interval, −1.68 to −1.12; P<0.01) but not in the microcirculation (9 studies; n=181; SMD, −0.63; 95% confidence interval, −1.36 to 0.11; P=0.09). Similar results were observed according to health status. Macrovascular endothelial function was inversely associated with age, blood pressure, and low-density lipoprotein cholesterol and was positively associated with the postocclusion interval of vascular assessment. Conclusions—To our knowledge, this is the first systematic review and meta-analysis of its kind. In healthy and diseased subjects, we found evidence for macrovascular but not microvascular endothelial dysfunction during acute hyperglycemia.

Impact of a Lifestyle Program on Vascular Insulin Resistance in Metabolic Syndrome Subjects: The RESOLVE Study

CONTEXT AND OBJECTIVE Impaired insulin-dependent vasodilation might contribute to microvascular dysfunction of metabolic syndrome (MetS). The aims of this study were to assess the insulin vasoreactivity in MetS, and to evaluate the effects of a lifestyle program. DESIGN, SETTING, PARTICIPANTS, AND OUTCOME MEASURES: Laser Doppler measurements were used to assess cutaneous blood flux (CBF) and flowmotion in response to iontophoresis of insulin and acetylcholine (ACh) in 38 MetS and 18 controls. Anthropometric, plasma insulin, glycemia, and inflammatory markers were measured. MetS subjects (n = 24) underwent a 6-month lifestyle intervention (M6) with a 3-week residential program (D21). RESULTS The absolute and relative peak insulin and ACh CBF were significantly higher in controls than in MetS subjects. Significant inverse correlations were found between peak insulin CBF and glycemia, insulin and glycated hemoglobin, active plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), and IL-6. With respect to flowmotion, MetS subjects showed lower values in total spectrum CBF and in all its components (except respiratory one). At D21 and M6, peak insulin CBF increased and was no longer different from control values whereas peak ACh CBF did not change. From D21, all the different components and the total CBF spectrum became similar to the control values. The changes in peak insulin CBF and in endothelial component between M6 and baseline were inversely correlated with the change in CRP and PAI-1. CONCLUSIONS The local vasodilatory effects to insulin and its overall flowmotion are impaired in MetS subjects in relation to inflammation. The lifestyle intervention reversed this insulin-induced vascular dysfunction in parallel to decreased inflammation level.

Flow-Mediated Dilation in Athletes: Influence of Aging.

PURPOSE Controversy exists on whether endothelial function is enhanced in athletes. We sought to systematically review the literature and determine whether endothelial function, as assessed by flow-mediated dilation (FMD), is greater in athletes across all ages relative to that in their age-matched counterparts. METHODS We conducted a systematic search on MEDLINE, Cochrane, Scopus, and Web of Science since their inceptions until July 2013 for articles evaluating FMD in athletes. A meta-analysis was performed to compare the standardized mean difference (SMD) in FMD of the brachial artery between athletes and age-matched control subjects. Subgroup analyses and meta-regression were used to identify sources of heterogeneity. RESULTS Twenty-one articles were included in this analysis, comprising 530 athletes (452 endurance trained, 49 strength trained, and 29 endurance and strength trained) and 376 control subjects. After data pooling, FMD was higher in athletes than that in control groups (SMD, 0.48; P = 0.008). In subgroup analyses, young athletes (<40 yr) presented increased baseline brachial artery diameter (mean difference, 0.40 mm; P < 0.00001) and similar FMD (SMD, 0.27; P = 0.22) compared with those in controls. In contrast, master athletes (>;50 yr) showed similar baseline brachial artery diameter (mean difference, 0.04 mm; P = 0.69) and increased FMD (SMD, 0.99; P = 0.0005) compared with those in controls. CONCLUSIONS The current meta-analysis provides evidence that master athletes but not young athletes exhibit greater FMD compared with that in age-matched healthy controls, thus suggesting that the association between high levels of exercise training and increased FMD is age dependent.