Publications

Context Obesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking. Objective To study the association between bariatric surgery, weight loss, and cardiovascular events. Design, Setting, and Participants The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, 2001. Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, 0-20 years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals. Main Outcome Measures The primary end point of the SOS study (total mortality) was published in 2007. Myocardial infarction and stroke were predefined secondary end points, considered separately and combined. Results Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29-0.76; P = .002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P  Conclusion Compared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.

The purpose of the present study was to examine the effects of regular exercise on the abundance of targeted circulating microRNAs (miRNAs). The present analysis examined 20 previously sedentary adults from the HERITAGE Family Study who completed 20 weeks of endurance exercise training. The expression of 53 miRNAs related to cardiovascular disease were measured in serum collected at baseline and post-training by performing RT-qPCR on the Human Cardiovascular Disease miRNA array (Qiagen, Germany). The effect of regular exercise on circulating miRNAs was assessed using paired t-tests of baseline and post-training expression levels. A false discovery rate threshold of 5% was used to determine significance. Regular exercise resulted in significantly decreased mean serum expression of nine miRNAs (miR-486-5p, let-7b-5p, miR-29c-3p, let-7e-5p, miR-93-5p, miR-7-5p, miR-25-3p, miR-92a-3p, and miR-29b-3p; fold change range: 0.64–83, p = 0.0002–0.01) and increased mean expression of five miRNAs (miR-142-3p, miR-221-3p, miR-126-3p, miR-146a-5p, and miR-27b-3p; fold change range: 1.41–3.60, p = 0.001–0.006). Enrichment analysis found that these 14 miRNAs target genes related to over 345 different biological pathways. These results provide further evidence of the effects of regular exercise on the circulating miRNA profile.

Background The implementation of cost-effective surveillance systems is essential for tracking the emerging risk of tick-borne diseases. In Canada, where Lyme disease is a growing public health concern, a national sentinel surveillance network was designed to follow the epidemiological portrait of this tick-borne disease across the country. The surveillance network consists of sentinel regions, with active drag sampling carried out annually in all regions to assess the density of Ixodes spp. ticks and prevalence of various tick-borne pathogens in the tick population. The aim of the present study was to prioritize sentinel regions by integrating different spatial criteria relevant to the surveillance goals. Methods We used spatially-explicit multi-criteria decision analyses (MCDA) to map priority areas for surveillance across Canada, and to evaluate different scenarios using sensitivity analyses. Results were shared with stakeholders to support their decision making for the selection of priority areas to survey during active surveillance activities. Results Weights attributed to criteria by decision-makers were overall consistent. Sensitivity analyses showed that the population criterion had the most impact on rankings. Thirty-seven sentinel regions were identified across Canada using this systematic and transparent approach. Conclusion This novel application of spatial MCDA to surveillance network design favors inclusivity of nationwide partners. We propose that such an approach can support the standardized planning of spatial design of sentinel surveillance not only for vector-borne disease BDs, but more broadly for infectious disease surveillance where spatial design is an important component.

The associations between skeletal muscle morphological and metabolic properties and the changes in body composition and metabolic rates in response to long-term overfeeding were investigated in 24 healthy young male identical twins (12 pairs). The proportions of muscle fiber types (type I, type IIA, and type IIB) and the activities of creatine kinase (CK), oxoglutarate dehydrogenase (OGDH), and phosphofructokinase (PFK) were determined from biopsies of the vastus lateralis before and after the overfeeding protocol. Body weight, fat mass (FM), fat-free mass (FFM), percent body fat (%FAT), resting metabolic rate (RMR), and thermic effect of a standardized meal (TEM) were also measured before and after 100 days of overfeeding. Type I muscle fiber proportions correlated inversely with the changes of FM and %FAT (r = [minus ]0.43, P = .035; r = [minus ]0.49, P = .01), and type IIA positively with the same overfeeding-induced changes (r = 0.43, P = .035; r = 0.47, P = .021). Baseline CK and PFK activities correlated negatively with the changes of RMR (r = [minus ]0.49, P = .017; r = [minus ]0.53, P = .01). OGDH activity at baseline correlated negatively with the changes of FM (r = [minus ]0.47, P = 0.02) but the ratio of PFK/OGDH correlated positively with the change of FM (r = 0.46, P = .02). We conclude that overfeeding induced a lower gain of FM in individuals with higher proportions of type I fiber, lower proportions of type IIA fiber, and higher OGDH activities at baseline. CK and PFK activities at baseline were associated with an attenuated increase in RMR when challenged by overfeeding. The significant correlations range from 0.43 to 0.53, and account for 18% to 28% of the variance in the response to overfeeding. The results suggest that an elevated skeletal muscle oxidative capacity plays a protective role in the response to long-term positive energy balance.

C-reactive protein (CRP) is a sensitive marker of systemic low-grade inflammation. Increased plasma levels of CRP predict the risk of cardiovascular and metabolic diseases. Although genetic factors account for 30-40% of individual differences in plasma CRP levels, genomic regions contributing to CRP levels remain unknown. We performed a genome-wide linkage scan for plasma CRP levels in healthy whites from the HERITAGE Family Study. CRP was measured with a high-sensitivity assay. Multipoint linkage analyses were performed in 280 sibling pairs with 654 markers using regression and variance components-based methods. Data were adjusted for independent correlates of plasma CRP. We showed the strongest evidence of linkage for plasma CRP levels on chromosome 20q13. Markers which gave suggestive linkages in this region were D20S52 [logarithm of odds (LOD) score 3.18, P = 0.00006], D20S857 (LOD score 2.87, P = 0.00014), D20S869 (LOD score 2.75, P = 0.0002), D20S480 (LOD score 2.59, P = 0.0003), D20S501 (LOD score 2.55, P = 0.0003), D20S840 (LOD score 2.18, P = 0.0008), and D20S876 (LOD score 2.07, P = 0.001). We also detected suggestive linkage on chromosome 5p13 for marker D5S1470 (LOD score 2.23, P = 0.0007). Chromosome 20q13 may contribute to plasma CRP levels in healthy whites. This region contains genes that are important in the inflammatory process and may play a role in the development of chronic inflammatory diseases. The present findings may be useful in the ongoing effort to search for genes contributing to inflammation and to identify individuals at an increased risk of chronic inflammatory diseases.

The beta adrenergic system plays a key role in regulating energy balance through the stimulation of both thermogenesis and lipid mobilization in brown and white adipose tissues in human and various animal models. Recent studies have suggested that a missense Trp64Arg mutation in the beta3 adrenergic receptor (ADRB3) gene was involved in obesity and insulin resistance. We have investigated the effect of this mutation on obesity-related phenotypes in two cohorts: the Québec Family Study (QFS) and the Swedish Obese Subjects (SOS). In QFS, no association was found between this mutation and body mass index (BMI), body fat including abdominal visceral fat, resting metabolic rate, various diabetes and cardiovascular risk factors, and changes in body weight and body fat over a 12-yr period. With the exception of RMR (P = 0.04), no evidence of linkage was detected between the mutation and phenotypes of QFS based on sib-pair data. In SOS, the frequency of the Trp64Arg allele was not significantly different between nonobese and obese female subjects and no association was found between the mutation and body weight gain over time. These findings do not support the view that there is an association between the Trp64Arg mutation in the ADRB3 gene and obesity.

Background and aims Previous studies have derived and validated an HDL apolipoproteomic score (pCAD) that predicts coronary artery disease (CAD) risk. However, the associations between pCAD and markers of cardiometabolic health in healthy adults are not known, nor are the effects of regular exercise on pCAD. Methods A total of 641 physically inactive adults free of cardiovascular disease from the HERITAGE Family Study completed 20 weeks of exercise training. The pCAD index (range 0–100) was calculated using measurements of apolipoproteins A-I, C–I, C-II, C-III, and C-IV from ApoA-I-tagged serum (higher index = higher CAD risk). The associations between pCAD index and cardiometabolic traits at baseline and their training responses were assessed with Spearman correlation and general linear models. A Bonferroni correction of p < 8.9 × 10−04 was used to determine statistical significance. Results The mean ± SD baseline pCAD index was 29 ± 32, with 106 (16.5 %) participants classified as high CAD risk. At baseline, pCAD index was positively associated with blood pressure, systemic inflammation, and body composition. HDL size, VO2max, and HDL-C were negatively associated with pCAD index at baseline. Of those classified as high CAD risk at baseline, 52 (49 %) were reclassified as normal risk after training. Following training, pCAD index changes were inversely correlated (p < 1.4 × 10−04) with changes in HDL-C, HDL size, and LDL size. Conclusions A higher pCAD index was associated with a worse cardiometabolic profile at baseline but improved with regular exercise. The results from this study highlight the potential role of HDL apolipoproteins as therapeutic targets for lifestyle interventions, particularly in high-risk individuals.

No abstract is provided for this article.