Publications

Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and low HDL-cholesterol concentrations are common features of a plurimetabolic syndrome, which increases the risk of coronary artery disease. Although it has been proposed that the development of atherosclerosis through alterations in plasma lipid levels could be a postprandial phenomenon, most studies on gender differences in plasma lipoprotein-lipid concentrations have reported fasting levels. Therefore, the aim of our study was to examine the response of postprandial triglyceride-rich lipoproteins to a standardized meal in 63 men and 25 women. In addition to the measurement of fasting and postprandial plasma lipid levels, numerous physical and metabolic variables were assessed, including body composition by underwater weighing and body fat distribution by computed tomography. Although no gender difference was noted in total body fat mass, men were characterized by a preferential accumulation of abdominal adipose tissue as revealed by an increased waist circumference and a greater visceral adipose tissue accumulation (50% difference) compared with women (P<0.001). Men also showed a greater plasma triglyceride response (P<0.005) as well as increased postprandial insulin and free fatty acid levels compared with women (P<0.01). Visceral adipose tissue was significantly associated with the postprandial triglyceride response in both genders (men: r=0.49, P<0. 0001; women: r=0.43, P<0.05). Finally, when men and women were matched for visceral adipose tissue accumulation, the gender difference in postprandial plasma triglyceride response was eliminated. Thus results of the present study suggest that the well known gender difference in visceral adipose tissue accumulation is an important contributing factor involved in the exaggerated postprandial triglyceride-rich lipoprotein response noted in men compared with women.

In many genetic studies of complex traits, sample sizes are often too small to detect linkages of low-to-moderate effects. However, the combined linkage evidence across several studies can be synthesized using meta-analysis with the aim of providing more definitive support of linkage.In the current study using the National Heart, Lung, and Blood Institute (NHLBI) GeneLink Project, a meta-analysis based on a modification of Fisher's method of pooling P values was used to investigate linkage for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values across three studies involving African American and Nigerian families (HyperGEN, Health, Risk Factors, Exercise Training and Genetics [HERITAGE], and Genetics of Hypertension in Blacks).The meta results suggest two regions (2p and 7p) provide enhanced linkage evidence compared with the individual study results. The maximal meta Lod score of 2.9 on 2p14-p13.1 (64-78 cM) represented approximately 1-Lod unit increase over the respective individual study scores. This general region has been implicated previously involving primarily families of white ethnicity and provides confirmatory evidence that this QTL is common across ethnic groups. The second finding at 7p21.3-p15.3 (8-25 cM) provided a meta Lod of 3.5. Although region was implicated primarily in the Nigerian subjects the low-level but consistent support involving the African American families (individual Lod score of 1.0) suggests a novel QTL with respect to BP variation in individuals of black ethnicity.Follow-up studies involving positional cloning efforts of the combined families showing linkage evidence in these regions (particularly 2p) may be warranted to verify these findings and identify the genes and causative variants.

The metabolic syndrome is a prevalent condition in North America, representing a substantial public health problem. PURPOSE The objective of this study was to determine the efficacy of physical activity in treating the metabolic syndrome. METHODS The sample included 621 Black and White participants from the HERITAGE Family Study, selected to be sedentary and apparently healthy (no chronic disease or injury). The metabolic syndrome was defined as having three or more risk factors according to the guidelines of the National Cholesterol Education Program, including elevated waist circumference, blood pressure, triglycerides, blood glucose, and low HDL-cholesterol. The presence of the metabolic syndrome was determined before and after 20 weeks of supervised aerobic exercise training. RESULTS The prevalence of the metabolic syndrome was 16.9% in this sample (105/621) of apparently healthy participants. Of the 105 participants with the metabolic syndrome at baseline, 28.6% (30 participants) no longer were classified as having the metabolic syndrome after the exercise training. Among the 30 participants that improved their metabolic profile, 43% decreased triglycerides, 17% improved HDL-cholesterol, 33% decreased blood pressure, 10% improved fasting plasma glucose, and 30% decreased their waist circumference. There were no sex or race differences in the effectiveness of exercise in treating the metabolic syndrome: 31% of male, 26% of female, 27% of Black, and 29% of White participants with the metabolic syndrome were effectively treated with exercise. CONCLUSION Aerobic exercise training in overtly healthy participants with the metabolic syndrome can be useful as a treatment strategy, and provides support for a role for physical activity in the prevention of chronic disease.

We began this series in 2000 with the aim of making available in an easily accessible format all the advances on the genetic basis of a large family of exercise-related traits. The current review presents the 2004 update of the human gene map for physical performance and health-related fitness phenotypes. It is based on peer-reviewed papers published by the end of 2004. The genes and markers with evidence of association or linkage with a performance or fitness phenotype in sedentary or active people, in adaptation to acute exercise, or for training-induced changes are positioned on the genetic map of all autosomes and the X chromosome. Negative studies are reviewed but a gene or locus must be supported by at least one positive study before being inserted on the map. One new feature is that we have incorporated the genes whose sequence variants have been associated with either the level of physical activity or indicators of sedentarism. By the end of 2000, in the early version of the gene map, 29 loci were depicted. In contrast, the 2004 human gene map for physical performance and health-related phenotypes includes 140 autosomal gene entries and quantitative trait loci, plus four on the X chromosome. Moreover, there are 16 mitochondrial genes in which sequence variants have been shown to influence relevant fitness and performance phenotypes. Thus, the map is growing in complexity and progress is being made. The number of laboratories and scientists concerned by the role of genes and sequence variations in exercise-related traits is rising. But exercise science and sports medicine is generally lagging behind in terms of utilizing the advances in genetic and genomic technologies.

Given the controversy around HDL-C as a therapeutic target, there is a need to investigate other features of HDL and how they respond to various preventive interventions. We tested the hypothesis that regular exercise would have beneficial effects on HDL particle (HDL-P) traits in sedentary adults. Methods: The following HDL-P traits were measured via NMR (Liposcience Inc.) before and after completion of a 20-week exercise program in the HERITAGE Family Study (N=715): concentration of total, large, medium, and small HDL-P and mean HDL-P size. ANCOVA was used to test for aggregation of HDL-P trait responses in families controlling for age, sex, and baseline BMI and trait value. Results: The concentration of large HDL-P significantly increased in response to regular exercise in both Black and White participants, while the increase was significantly larger in females compared to males (Table 1). In general, regular exercise decreased the concentration of medium and small HDL-P. Together, these responses contributed to a significant increase in the average cholesterol content of HDL particles. Exercise-induced changes in large HDL-P were inversely correlated with changes in fat mass and systolic blood pressure. Moreover, changes in BMI were significantly associated with changes in all of the HDL-P traits, but not with HDL-C. We found significant evidence of familial aggregation for the exercise-induced changes in HDL-P traits in both races, as there was 1.4 to 1.6 times more variance between than within families for the changes in total (p=0.02 in Whites) and large HDL-P (p=0.004 in Whites, p=0.02 in Blacks) and HDL-P size (p=0.0009 in Whites, p=0.009 in Blacks). Conclusion: The HDL-P subclass profile favorably responded to regular exercise in sedentary Black and White adults, highlighted by increases in the concentration of large HDL-P, and may be influenced by a significant genetic component. We provide evidence that regular exercise could potentially be used as an HDL-based therapy designed to target beneficial subfractions.

There are considerable interindividual differences in maximal oxygen uptake per kilogram of body weight (VO2 max/kg), maximal heart rate (max HR) and maximal blood lactate (max blood La) measured during a progressive exercise test. The aim of the study was to quantify the familial relationships for these variables. Parents and children of 38 families of French-Canadian descent were submitted to a modified Balke treadmill test. VO2 max/kg and max HR were the highest values reached during the test for 1 min. Max blood La was obtained from a blood sample taken 2 min after the test. The effects of age and sex were significant for max blood La and VO2 max/kg in each generation. Scores were thus adjusted through multiple regression procedures (age + sex + age × sex + age2), yielding residuals which were submitted to further analysis. Intraclass correlations (ri) were significant in pairs of sibs for max blood La and max HR, i.e. 0.28 (p < 0.01) and 0.43 (p < 0.05), respectively. For VO2 max/kg, pairs of spouses and sibs were about similarly correlated (ri = 0.20 and 0.15; p < 0.05). Data suggested that children were more related to their mother than to their father for VO2 max/ kg, VO2 max/kg of fat-free weight, and particularly for max HR. It was concluded that familial resemblance and heritability estimates for maximal aerobic power, max HR and max blood La were quite low and generally nonsignificant. Correlations between biological sibs were, however, consistently significant for max HR and max blood La. The suggestion of a maternal effect in maximal aerobic power should be further investigated.

Total energy intake and intakes of carbohydrate, fat, and protein as well as the percentage of energy derived from these nutrients were calculated from a 3-d dietary record in 1597 subjects living in 375 families of French descent. Familial correlations were computed in pairs of biological relatives and relatives by adoption and used in the path-analysis BETA model to determine the contribution of genetic and nongenetic factors in the familial resemblance observed in energy intake. No significant genetic effect was found for intake of any nutrient tested (h2 less than or equal to 11%) and cultural inheritance was found to be more important than genetic inheritance. Nontransmitted environmental factors, including home environmental effects, were found to account for more than 50% of the variation observed in the energy-intake components. These results suggest that the average genetic influence on nutrient intake is negligible and that nongenetic effects associated mainly with home environmental effects are the major affecters of energy intake.

Cardiovascular reactivity, including responses of systolic blood pressure (SBP) and heart rate (HR) to exercise, has been postulated to be a predictor of future essential hypertension and coronary heart disease. The purpose of this study was to investigate the familial relationship of response of SBP and HR and their product to submaximal cycle ergometer exercise in 474 members of 99 sedentary Caucasian families participating in the HERITAGE Family Study. Familial aggregation due to genetic factors and shared social environment was assessed by analysis of variance and the use of the SEGPATH familial correlation model. Maximal heritability for HR response reached 52% at 50 W and 45% at 60% of maximal oxygen uptake (VO2 max), while estimates for SBP response reached 48% at 50W and 38% at 60% of VO2 max, and the estimates for their product were 56% and 45% at 50 W and 60% of VO2 max, respectively. We conclude that the cardiovascular response to the stress of light-to-moderate-intensity exercise is highly familial and includes a significant genetic component. This research was supported by multiple grants from the NHLBI.

No abstract is provided for this article.

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 relations of physical activity and fibrinogen gene polymorphisms to plasma fibrinogen levels were investigated in 176 postmenopausal women, aged 60 to 69 years. Women using analgesics or who were on anticoagulant or antilipidemic therapy were excluded from the analyses. Plasma fibrinogen level was determined by thrombin time method, the genetic polymorphism of α- and β-fibrinogen genes using PCR and digestion with TaqI (α) and BclI (β) and HindIII (β) restriction enzymes, and physical activity during the month preceding the examination by self-administered questionnaire. The mean fibrinogen level was 3.28 g/l (95%CI 3.21;3.36). There were no differences in plasma fibrinogen levels across the three restriction site polymorphisms when data were analyzed by genotype or carrier status. Physical activity correlated inversely with fibrinogen level (r=-0.24, p=0.001). In multiple regression analyses, both physical activity (p=0.008) and body mass index (p=0.001) were significant determinants of plasma fibrinogen, with the whole adjusted model, including age, explaining 12.6% of the variance of plasma fibrinogen. These data suggest that, in postmenopausal women, TaqI, BclI or HindIII restriction fragment length polymorphisms are not associated with plasma fibrinogen level with or without ajustment for physical activity, body mass index and age.

Familial correlation analyses were used to evaluate the familial aggregation of plasma androgens and androgen glucuronides (testosterone (TESTO), dihydrotestosterone (DHT), androstane-3 alpha,17 beta-diol glucuronide (3 alpha-DIOL-G), and androsterone glucuronide (ADT-G)) in 505 members of 99 white families and 296 members of 111 black families participating in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. Each of these four measures was determined by RIA after separation of conjugated and unconjugated steroid using C18 column chromatography. All participants were sedentary prior to being including in this study. Significant spouse correlations, as well as parent-offspring and sibling correlations, were found for TESTO, DHT, 3 alpha-DIOL-G, and ADT-G in the white sample, suggesting that common familial environments and genes contribute to the familial resemblance. In the black sample, significant sibling and parent-offspring correlations were found for all four phenotypes, while the spouse correlation was marginally significant for 3 alpha-DIOL-G and not significant for TESTO, DHT, and ADT-G. The non-significance of spouse correlations in the black individuals may be due to the small number of spouse pairs. The maximal heritability estimates of TESTO, DHT, 3 alpha-DIOL-G, and ADT-G were 69%, 87%, 74%, and 56% for white individuals and 70%, 73%, 62%, and 48% for black individuals respectively. Sex differences in heritability estimates were found in the white individuals, but they were less dramatic in the black individuals. In conclusion, plasma levels of androgens and androgen glucuronides are highly heritable in both white individuals and black individuals. There are notable sex differences in the white individuals.