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Congenital aortic stenosis {AS} has long been known to occur predominantly in white male infants, born in rural or suburban areas. We used spatial analysis to explore hypotheses of environmental exposure that might be consistent with the original observations.Using a case control series of congenital cardiovascular malformations and population based controls, we analyzed spatial distribution of aortic stenosis, in infants diagnosed before one year of age. Statistical analysis included spatial distribution and extensive personal sociodemographic, occupational exposures, and life style exposure factors as well as family history of cardiac or other malformations. Cases and controls were mapped in the State of Maryland and the District of Columbia in the United States, including the years 1981 through 1989.60 cases of AS and 1990 controls were included in the analysis. By nonparametric analysis AS was associated with advanced maternal age, a history of previous stillbirths, maternal exposure to laboratory chemicals or solvents in pregnancy, residency in areas of orchards, and nitrate in ground water. Five clusters of aortic stenosis cases were identified by Bernoulli analysis including 15 of 60 cases of aortic stenosis. Individual clusters were not significant by Bernoulli analysis using the spatial distribution method. However, using χ2 for case control ratio within the combined cluster areas, odds of aortic stenosis compared to controls was 40, 18.9-87.7 95% CI. We assessed the characteristics of the combined clusters to determine whether these areas shared features that differentiated them from other regions of the state. Cases of aortic stenosis in these clusters differed from other aortic stenosis cases in having older mothers, mothers with high occupational grade, more frequent gestational diabetes, and, at a less significant level [p.071] residing in orchards. Exposure to pesticides sprayed from planes occurred in two cases of 15 in the clusters compared to no cases outside the clusters, p.059 chi square. To clarify the characteristics of the clusters where aortic stenosis cases were located, we compared the characteristics of controls living in and outside the clusters, using the greater power of the number of controls. The clusters are characterized by ground water risk of nitrate contamination χ2 36.996, p.000; residency in orchard χ2 46.333, p.000; residency in cropland χ2 28.893, p.002; and maternal race χ2 9.410; p.009. When analysis was made for controls in the clusters separately by race, the associations with groundwater risk, orchard, mercury exposure, and cropland were reduced in magnitude but remained highly significant and were ordered the same.One congenital cardiovascular malformation, aortic stenosis, shows spatial distribution consistent with possible environmental exposures and gene environment interactions that may be important in pathogenesis. Further prospective study with both genetic and environmental measures will be important in evaluating these findings. [ABSTRACT FROM AUTHOR]

Left heart obstructive congenital cardiovascular malformations [CCVM], including aortic stenosis [AS], coarctation of the aorta [CoAo], and hypoplastic left heart syndrome [HLH] are thought to have common genetic risks. Using spatial analysis we sought linkage between these groups as well as defining the environmental risk of each group separately.102 CoAo, 60 AS, 77HLH and 1990 population based controls were entered into a spatial database for Maryland and the District of Columbia. Spatial analysis was carried out using Bernoulli method for case control comparisons for each CCVM compared with controls. Spatial analysis was then carried out using the Bernoulli method comparing the distribution of HLH with respect to AS and then with respect to CoAo looking for areas in which HLH was over represented with respect to the other CCVM. Regions and cases identified by spatial analysis were further analyzed using the extensive dataset of sociodemographic, medical, and exposure variables available for all cases and controls.Isolated AS is clustered in Maryland in a region of orchards within the Monocacy watershed. Isolated CoAo is clustered in Maryland in the southern Maryland peninsula with risks for the cluster of maternal exposure to solvents and residency at conception in cropland. HLH occurs in regions of increased prevalence with respect to AS only in regions where AS is not present. HLH occurs in regions of increased prevalence with respect to CoAo in a tightly defined region of Baltimore characterized by TRI release of solvents, and by industrial land use. Within this region concurrent cases of AS and CoAo are present. The cases of AS in this region in association with CoAo are iuncreased with odds of 18.2, 95%CI 4.0, 81.9. Analysis of the HLH cluster with respect to CoAo by racial groups comparing cases to controls confirms the cluster in all groups. Residency in the cluster is associated with later prenatal care and lesser paternal education for white infants but these associations are not present for black infants.We speculate that in areas of environmental exposures a common genetic substrate may result in more severe left heart obstruction based on genetic environmental interactions. This increased severity is expressed as increased prevalence of HLH, association of AS with CoAo in this region, and decreased prevalence of simple CoAo in this region. [ABSTRACT FROM AUTHOR]

Left heart obstructions [LHO] as a subset of congenital cardiovascular malformations [CCVM] are thought to be a group linked by a common genetic substrate. We explored possible gene environment interactions by spatial analysis of the three major LHO, aortic stenosis [AS], coarctation of the aorta [CoAo], and hypoplastic left heart [HLH].Using a case control series of congenital cardiovascular malformations and population based controls, we analyzed spatial distribution of hypoplastic left heart syndrome, in infants diagnosed before one year of age. Statistical analysis included spatial distribution and extensive personal sociodemographic, occupational exposures, and life style exposure factors as well as family history of cardiac or other malformations. Cases and controls were mapped in the State of Maryland and the District of Columbia in the United States, including the years 1981 through 1989.83 cases of hypoplastic left heart and 1990 controls were included. 16 cases of hypoplastic left heart syndrome occurred in clusters identified by spatial scanning using a Bernoulli method with respect to controls. Of these clusters, the largest was significant with chi square 40.3, p.000. Variables significant by non parametric analysis for case control status for HLH were entered into a multiple regression model. Family history of cardiac malformation and maternal exposure to solvents were predictive of case status. The clusters of hypoplastic left heart syndrome were characterized by low levels of paternal education only when assessed using HLH cases only. Only 9 controls were found within the cluster so confirmatory assessment of characteristics of the spatial region of the cluster could not be made using control data. These characteristics of the clusters of HLH differ from our findings for clusters of AS or CoAo. The HLH clusters are geographically distinct from those of AS and overlap with some clusters of CoAo. CoAo and AS are present in clusters characterized by being in regions of cropland or orchard. Both CoAo and AS in this dataset predominantly distributed in white populations.The differences in spatial distribution of HLH compared to AS and CoAo may suggest that the genetic risk for HLH differs from that of AS or CoAo. Alternatively, the environmental exposures in different geographic regions may result in different phenotypes by gene environment interactions with common genes for these three congenital left heart obstructions. [ABSTRACT FROM AUTHOR]

Purpose: We determined if a high-intensity aerobic exercise program would be safe, improve expected fitness and clinical outcomes, and alter exploratory phosphorous magnetic resonance spectroscopy (P MRS) outcomes in persons with multiple sclerosis (PwMS)., Methods: This open-label prospective pilot study compared two cohorts of ambulatory PwMS matched for age, sex and V˙O2max. Cohorts underwent 8 wk of high-intensity aerobic exercise (MS-Ex, n = 10) or guided stretching (MS-Ctr, n = 7). Aerobic exercise consisted of four 30-min sessions per week while maintaining ≥70% maximal HR. Changes in cardiorespiratory fitness, clinical outcomes, and P MRS of tibialis anterior (TA) muscle and brain were compared. Cross-sectional P MRS comparisons were made between all MS participants and a separate matched healthy control population., Results: The MS-Ex cohort achieved target increases in V˙O2max (mean, +12.7%; P = <0.001, between-group improvement, P = 0.03). One participant was withdrawn for exercise-induced syncope. The MS-Ex cohort had within-group improvements in fat mass (-5.8%; P = 0.04), lean muscle mass (+2.6%; P = 0.02), Symbol Digit Modalities Test (+15.1%; P = 0.04), and cognitive subscore of the Modified Fatigue Impact Scale (-26%; P = 0.03), whereas only the physical subscore of the Modified Fatigue Impact Scale improved in MS-Ctr (-16.1%; P = 0.007). P MRS revealed significant within-group increases in MS-Ex participants in TA rate constant of phosphocreatine (PCr) recovery (+31.5%; P = 0.03) and adenosine triphosphate/PCr (+3.2%; P = 0.01), and near significant between-group increases in TA PCr recovery rate constant (P = 0.05) but no significant changes in brain P MRS after exercise. Cross-sectional differences existed between MS and healthy control brain PCr/inorganic phosphate (4.61 ± 0.44, 3.93 ± 0.19; P = 0.0019)., Conclusions: High-intensity aerobic exercise in PwMS improved expected cardiorespiratory and clinical outcomes but provoked one serious adverse event. The P MRS may serve to explore underlying mechanisms by which aerobic exercise exerts cerebral benefits.