Abstract

Muscle vasodilatation during exercise has been associated with cardiovascular health and may be influenced by genetic variability. The purpose of this study was to evaluate functional genetic polymorphisms of physiologic pathways related to the regulation of the cardiovascular function (alpha-adrenergic receptors, endothelial nitric oxide synthase and bradykinin B2 receptor) and exercise muscle vasodilatation in apparently healthy men and women. We enrolled 689 individuals without established cardiovascular disease that had attended a check-up program. The vasodilatation was studied with venous occlusion plethysmography and determined by the increase of vascular conductance during handgrip exercise. Genotypes for ADRA1A Arg347Cys (rs1048101), ADRA2A 1780 C > T (rs553668), ADRA2B Del 301–303 (rs28365031), eNOS 786 T > C (rs2070744), eNOS Glu298Asp (rs1799983) and BDKRB2 (rs5810761) polymorphisms were assessed by polymerase chain reaction followed by high resolution melting analysis. The eNOS rs2070744 polymorphism was significantly associated with forearm vascular conductance during exercise in women. Women with CC genotype showed higher vasodilatation than carriers of TC and TT genotypes (p = 0.043). The ADRA2A rs553668 polymorphism was significantly associated with forearm vascular conductance during exercise in men. Men with TT genotype had higher vasodilatation than carriers of CT and CC genotypes (p = 0.025). eNOS rs207074 polymorphism in women and ADRA2A rs553668 polymorphism in men were associated with the increase of forearm vascular conductance during handgrip exercise. These findings suggest that eNOS and ADRA2A genetic polymorphisms may be potential markers of exercise muscle vasodilatation.

Abstract

Due to the absence of a sub-pulmonary ventricle, the Fontan circulation is sensitive to respiration-induced changes in intrathoracic pressure. However, the importance of a ‘respiratory pump’ in creating forward flow remains controversial. We aimed at evaluating the effect of respiration on ventricular filling during exercise using clinical data and computational modeling predictions. Ten Fontan patients (6 male, 20 ± 4 years) underwent ungated cardiac magnetic resonance (CMR) imaging at rest and during supine bicycle exercise to evaluate systemic ventricular volumes (end-diastolic volume index (EDVi), end-systolic volume index (ESVi) and stroke volume index (SVi)) during normal respiration and a Valsalva maneuver. Respiratory-dependent SV was calculated. Clinical results were compared to predictions made by a closed-loop lumped-parameter (LPN) computational model of Fontan circulation. Inspiration resulted in increased EDVi (98 ± 16 to 103 ± 15 mL, P = 0.001), SVi (55 ± 9 to 59 ± 9 mL, P = 0.001) and cardiac index (3.9 ± 0.7 to 4.2 ± 0.8 L/min, P = 0.002), whereas ESVi (P = 0.096) remained unchanged. The effect of inspiration on EDVi (mean effect + 6 ± 1 mL, P < 0.0001) and SVi (+ 4 ± 1 mL, P < 0.0001) was maintained during exercise. Respiratory-dependent SVi tended to increase during exercise (3 ± 2% to 5 ± 3%, P = 0.084). Valsalva resulted in decreased EDVi (P = 0.001), ESVi (P = 0.003) and SVi (P = 0.005). Computational modeling indicated higher EDV and SV at end-inspiration and expiration, showing a phased time delay between peak caval vein flow and peak SV. In Fontan patients, inspiration resulted in increased ventricular filling at rest and during exercise. Results were confirmed using a computational model indicating a phased time delay between peak SV and peak caval vein flow.

Abstract

Overweight (OW) and obesity (OB) are endemic in the United States and affect adolescents and adults with congenital heart disease (ACHD). Defining the burden of excess weight on the cardiovascular system in ACHD is the goal of this study. Limitation of exercise capacity due to overweight or obesity might be reversible with weight loss and improve quality of life for ACHD adults. Exercise tests performed using a Bruce protocol and measurement of maximum oxygen consumption were retrospectively reviewed on 418 CHD patients. OW and OB were defined as the 85–95 or > 95 percentile respectively for age and gender or by adult criteria. Severity of CHD was assigned based on criteria published in standard guidelines. 63 patients had mild, 198 moderate, and 157 severe heart disease. Each ACHD group was 32 to 34% OW or OB. Measured exercise time (ET) of CHD patients with moderate or severe heart disease was less than that of controls in each weight categories. However, OB or OW people have shorter ET than their normal weight peers with CHD. Multiple regression using ET as the dependent variable finds that female sex, relative BMI, and VE/VCO2 at peak exercise are all associated with lesser ET with high significance. Peak heart rate is associated with greater ET, with borderline significance. Severity of heart disease is not independently associated with ET. OW and OB are strongly associated with reduced ET in persons with congenital heart disease. Losing weight may improve exercise capacity in ACHD.

Abstract

Background São Paulo city, Brazil, faces challenges caused by rapid urbanization. We illustrate how future travel patterns could lead to different health consequences in the city. Methods We evaluated the health impacts of different travel pattern scenarios for the São Paulo adult population by comparing the travel patterns of São Paulo in 2012 with counterfactual scenarios in which the city adopted travel patterns of i) those living in the city's expanded centre; ii) London (2012); iii) a highly motorized São Paulo (SP California); and iv) a visionary São Paulo (SP 2040), with high levels of walking and cycling and low levels of car and motorcycle use. For each scenario we estimated changes in exposure to air pollution, road injury risk, and physical activity. Health outcomes were estimated using disability adjusted life years (DALYs) and premature deaths averted. Sensitivity analyses were performed to identify the main sources of uncertainty. Results We found considerable health gains in the SP 2040 scenario (total 63.6 k DALYs avoided), with 4.7% of premature deaths from ischemic heart disease avoided from increases in physical activity alone. Conversely, we found substantial health losses in the scenario favouring private transport (SP California, total increase of 54.9 k DALYs), with an increase in road traffic deaths and injuries among pedestrians and motorized vehicles. Parameters related to air pollution had the largest impact on uncertainty. Conclusions Shifting travel patterns towards more sustainable transport can provide major health benefits in São Paulo. Reducing the uncertainties in the findings should be a priority for empirical and modelling research on the health impacts of such shifts. Highlights • There is scarce evidence of transportation impacts on health in developing cities • Comparative risk assessment used to assess impacts on three major risk factors • We found large net health gains in sustainable transport scenario for Sao Paulo, Brazil • We also found large net health losses in a car dependent scenario for Sao Paulo • Physical activity provided the largest health impacts, similar to previous studie Document type: Article