Regular exercise and patterns of response across multiple cardiometabolic traits: the HERITAGE family study.

OBJECTIVES: We investigated whether high responsiveness or low responsiveness to exercise training aggregates in the same individuals across seven cardiometabolic traits. METHODS: A total of 564 adults (29.2% black, 53.7% female) from the HERITAGE family study completed a 20-week endurance training programme (at 55%-75% of participants' maximal oxygen uptake (VO2max)) with VO2max, per cent body fat, visceral adipose tissue, fasting levels of insulin, high-density lipoprotein cholesterol, small low-density lipoprotein particles and inflammatory marker GlycA measured before and after training. For each exercise response trait, we created ethnicity-specific, sex-specific and generation-specific quintiles. High responses were defined as those within the 20th percentile representing the favourable end of the response trait distribution, low responses were defined as the 20th percentile from the least favourable end, and the remaining were labelled as average responses. RESULTS: Only one individual had universally high or low responses for all seven cardiometabolic traits. Almost half (49%) of the cohort had at least one high response and one low response across the seven traits. About 24% had at least one high response but no low responses, 24% had one or more low responses but no high responses, and 2.5% had average responses across all traits. CONCLUSIONS: Interindividual variation in exercise responses was evident in all the traits we investigated, and responsiveness did not aggregate consistently in the same individuals. While adherence to an exercise prescription is known to produce health benefits, targeted risk factors may not improve.

Plasma steroids, body composition, and fat distribution: effects of age, sex, and exercise training.

BACKGROUND/OBJECTIVES: Plasma steroid hormone levels vary between men and women, but their associations with BMI and adiposity are controversial. Furthermore, little is known about the role of exercise programs on the relationship between steroid hormones and adiposity. This report evaluates these relationships for plasma levels of adrenal, gonadal, and conjugated steroids with body composition and fat distribution in sedentary men and women, aged 17-65 years, and their responses to an exercise program. SUBJECTS/METHODS: In the sedentary state, 270 men (29% Blacks) and 304 women (34% Blacks) from the HERITAGE Family Study were available. Among them, 242 men and 238 women completed a 20-week fully standardized exercise program. Fourteen steroid hormones and SHBG concentrations were assayed in a fasted state and were compared for their associations with adiposity in men and women and in response to the exercise program. Covariates adjusted for in partial correlation analysis were age, ancestry, menopause status (women), and oral contraceptives/hormone replacement treatment status (women) at baseline, as well as baseline value of the trait for the training response. Differences among normal weight, overweight, and obese subjects were also considered. Statistical significance was set at P < 0.0001. RESULTS: Baseline levels of dihydrotesterone (DHT), 17 hydroxy progesterone (OHPROG), sex hormone-binding globulin (SHBG), and testosterone (TESTO) were negatively associated with fat mass and abdominal fat (P < 0.0001) in men and for SHBG in women (P < 0.0001). TESTO was not correlated with fat-free mass in men or women, but was significantly associated with % fat-free mass in men. No association was detected between baseline steroid hormone levels and changes in adiposity traits in response to 20 weeks of exercise. CONCLUSION: In men, low DHT, OHPROG, SHBG, and TESTO were associated with higher adiposity and abdominal and visceral fat. A similar adiposity profile was observed in women with low SHBG.

Plasma Steroids are Not Associated with Resting and Exercise Blood Pressure.

We investigated the associations between steroid hormones and resting and exercise blood pressure in the sedentary state and in response to an exercise program controlling for sex, body mass, ethnicity, age, oral contraceptives, hormone therapy, smoking and alcohol intake in subjects from the HERITAGE Family Study.: In the sedentary state, 267 men (28% Blacks) and 301 women (37% Blacks) were available, and 241 men and 254 women completed the exercise program. Fourteen steroid hormones and sex hormone-binding globulin concentrations were assayed in a fasted state. Statistical significance was set at a Bonferroni adjusted p<0.0001. After controlling for the various covariates, only testosterone came close to a significant correlation with exercise systolic blood pressure at 50 W (r=-0.21, P=0.0006) in men. No other correlations with resting and exercise blood pressure traits were found at baseline. There were significant changes in blood pressure in response to the exercise program, but none of the correlations with baseline plasma steroids reached statistical significance. Plasma steroids do not correlate with resting and exercise blood pressure in sedentary adults and do not associate with blood pressure changes in response to a 20-week endurance exercise program.

The HERITAGE Family Study: A Review of the Effects of Exercise Training on Cardiometabolic Health, with Insights into Molecular Transducers.

The aim of the HERITAGE Family Study was to investigate individual differences in response to a standardized endurance exercise program, the role of familial aggregation, and the genetics of response levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors. Here we summarize the findings and their potential implications for cardiometabolic health and cardiorespiratory fitness. It begins with overviews of background and planning, recruitment, testing and exercise program protocol, quality control measures, and other relevant organizational issues. A summary of findings is then provided on cardiorespiratory fitness, exercise hemodynamics, insulin and glucose metabolism, lipid and lipoprotein profiles, adiposity and abdominal visceral fat, blood levels of steroids and other hormones, markers of oxidative stress, skeletal muscle morphology and metabolic indicators, and resting metabolic rate. These summaries document the extent of the individual differences in response to a standardized and fully monitored endurance exercise program and document the importance of familial aggregation and heritability level for exercise response traits. Findings from genomic markers, muscle gene expression studies, and proteomic and metabolomics explorations are reviewed, along with lessons learned from a bioinformatics-driven analysis pipeline. The new opportunities being pursued in integrative -omics and physiology have extended considerably the expected life of HERITAGE and are being discussed in relation to the original conceptual model of the study.

Comparison of the effect of upper body-ergometry aerobic training vs treadmill training on central cardiorespiratory improvement and walking distance in patients with claudication.

BACKGROUND: Supervised treadmill-walking exercise programs have been proven to be a highly effective in improving walking distance in peripheral arterial disease (PAD) patients with lifestyle-limiting claudication. Limited information is available on the contributions of central cardiorespiratory functions for improving these patients' walking capacity with exercise training. METHODS: This study randomized 28 participants (21 men; age, 65.6 years; 92.7% smoking history, 36.6% with diabetes) with lifestyle-limiting PAD-related claudication to 3 hours/week of supervised exercise training for 12 weeks, using arm-ergometry (n = 10) or treadmill-walking (n = 10) vs a usual-care control group (n = 8). Cardiorespiratory function measurements were assessed before and after training at a submaximal workload and at the onset of claudication (pain-free walking distance [PFWD]) and at maximal walking distance [(MWD]). Changes in these functions from baseline were analyzed among the groups with analysis of covariance. Associations between variables were determined by Pearson's partial correlations. RESULTS: The mean baseline demographic, medical, and exercise variables were similar among the groups. There were similar significant differences in the submaximal double product (heart rate × systolic blood pressure) and at MWD, ventilatory threshold, ventilatory oxygen uptake (VO(2)) at onset of claudication, and VO(2) peak in response to training in both exercise groups vs the control group. Statistically significant, moderate correlations (r = 0.60-0.68) were found between changes in all cardiorespiratory variables and changes in PFWD or MWD. CONCLUSION: Improvements in cardiorespiratory function after arm-ergometry or treadmill-training were significantly associated with improvements in both PFWD and MWD, providing supporting evidence of systemic contributions to exercise training-related improvements in walking capacity seen in patients with claudication.

The pain trajectory during treadmill testing in peripheral artery disease.

BACKGROUND: Ischemia-induced pain associated with walking (claudication) in peripheral artery disease limits mobility and diminishes quality of life. Self-reports of pain during standardized treadmill testing are used in clinical trials to assess the efficacy of interventions. OBJECTIVES: The aim of this study was to model pain trajectories during a peak walking test after 12 weeks of treatment in participants in four randomly assigned treatment groups (treadmill, arm ergometry, combination, and usual care) compared with baseline pain trajectories. METHODS: Self-reports of pain obtained at baseline and after 12 weeks of supervised exercise training for 41 participants (71% male; age, M = 64 years, SD = 8.6 years) were used. Pain was measured every 30 seconds with a numeric rating scale that had ordinal response options ranging from 0 (no pain) to 5 (severe pain). The test was continued until the maximum level of pain was reached and the participant could no longer walk. Observed responses from individual cases were plotted and patterns of pain were identified. A hierarchical generalized linear model for ordinal data was fit to compare baseline and postintervention trajectories. RESULTS: : Patterns in observed data reflected variations in time to onset of mild pain, acceleration to severe pain, and total walking time. All groups improved at 12 weeks; arm ergometry trajectories showed slower onset of pain, whereas treadmill training produced slower rates of increase to the maximum toward the end of the test. Effects for individuals appear as offsets from personal models at baseline. DISCUSSION: Change in the experienced claudication trajectory varied by type of exercise. Findings can inform design of future trials and aid decision making about exercise interventions for claudication.

HRR and V˙O2R Fractions Are Not Equivalent: Is It Time to Rethink Aerobic Exercise Prescription Methods?

INTRODUCTION: According to current guidelines, the intensity of health-enhancing aerobic exercise should be prescribed using a percentage of heart rate reserve (%HRR), which is considered to be more closely associated (showing a 1:1 relation) with the percentage of oxygen uptake reserve (%V˙O2R) rather than with the percentage of maximal oxygen uptake (%V˙O2max) during incremental exercise. However, the associations between %HRR and %V˙O2R and between %HRR and %V˙O2max are under debate; hence, their actual relationships were investigated in this study. METHODS: Data from each stage of a maximal incremental exercise test performed by 737 healthy and physically inactive participants of the HERITAGE Family Study were screened and filtered then used to calculate the individual linear regressions between %HRR and either %V˙O2R or %V˙O2max. For each relationship, the mean slope and intercept of the individual linear regression were compared with 1 and 0 (i.e., the identity line), respectively, using one-sample t-tests. The individual root mean square errors of the actual versus the 1:1 predicted %HRR were calculated for both relationships and compared using a paired-sample t-test. RESULTS: The mean slopes (%HRR-%V˙O2R, 0.972 ± 0.189; %HRR-%V˙O2max, 1.096 ± 0.216) and intercepts (%HRR-%V˙O2R, 8.855 ± 16.022; %HRR-%V˙O2max, -3.616 ± 18.993) of both relationships were significantly different from 1 and 0, respectively, with high interindividual variability. The average root mean square errors were high and revealed that the %HRR-%V˙O2max relationship was more similar to the identity line (P < 0.001) than the %HRR-%V˙O2R relationship (7.78% ± 4.49% vs 9.25% ± 5.54%). CONCLUSIONS: Because both relationships are different from the identity line and using a single equation may not be appropriate to predict exercise intensity at the individual level, a rethinking of the relationships between the intensity variables may be necessary to ensure that the most suitable health-enhancing aerobic exercise intensity is prescribed.

Effects of regular endurance exercise on GlycA: Combined analysis of 14 exercise interventions.

BACKGROUND AND AIMS: GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions. METHODS: Nuclear magnetic resonance spectroscopy, specifically signal amplitudes originating from the N-acetyl methyl group protons of the N-acetylglucosamine residues on the glycan branches of glycoproteins, was used to quantify GlycA concentrations. GlycA was measured before and after completion of an exercise intervention in 1568 individuals across seven studies and 14 exercise interventions. Random effects inverse variance weighting models were used to pool effects across interventions. RESULTS: Combined analysis of unadjusted data showed that regular exercise significantly (p = 2 × 10-6) reduced plasma GlycA (-8.26 ±â€¯1.8 µmol/L). This reduction remained significant (-9.12 ±â€¯1.9 µmol/L, p = 1.22 × 10-6) following adjustment for age, sex, race, baseline BMI, and baseline GlycA. Changes in GlycA were correlated with changes in traditional inflammatory markers, C-reactive protein, interleukin-6, and fibrinogen, however, these correlations were relatively weak (range r: 0.21-0.38, p < 0.0001). CONCLUSIONS: Regular exercise significantly reduced plasma GlycA across 14 different exercise interventions despite differences in exercise programs and study populations. The current study provides a greater understanding of the use of exercise as a potential therapy for the reduction of systemic inflammation. Further research is needed to understand the mechanisms behind the exercise-related reductions in GlycA.

Adropin: An endocrine link between the biological clock and cholesterol homeostasis.

OBJECTIVE: Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function. METHODS: Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models. RESULTS: In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = 401). Analysis of hepatic Enho expression in male mice suggests control by the biological clock. Expression is rhythmic, peaking during maximal food consumption in the dark correlating with transcriptional activation by RORα/γ. The nadir in the light phase coincides with the rest phase and repression by Rev-erb. Plasma adropin concentrations in nonhuman primates (rhesus monkeys) also exhibit peaks coinciding with feeding times (07:00 h, 15:00 h). The ROR inverse agonists SR1001 and the 7-oxygenated sterols 7-ß-hydroxysterol and 7-ketocholesterol, or the Rev-erb agonist SR9009, suppress ENHO expression in cultured human HepG2 cells. Consumption of high-cholesterol diets suppress expression of the adropin transcript in mouse liver. However, adropin over expression does not prevent hypercholesterolemia resulting from a high cholesterol diet and/or LDL receptor mutations. CONCLUSIONS: In humans, associations between plasma adropin concentrations and LDL-C suggest a link with hepatic lipid metabolism. Mouse studies suggest that the relationship between adropin and cholesterol metabolism is unidirectional, and predominantly involves suppression of adropin expression by cholesterol and 7-oxygenated sterols. Sensing of fatty acids, cholesterol and oxysterols by the RORα/γ ligand-binding domain suggests a plausible functional link between adropin expression and cellular lipid metabolism. Furthermore, the nuclear receptors RORα/γ and Rev-erb may couple adropin synthesis with circadian rhythms in carbohydrate and lipid metabolism.

CETP genotypes and HDL-cholesterol phenotypes in the HERITAGE Family Study.

Associations between cholesteryl ester transfer protein (CETP) polymorphisms and high-density lipoprotein cholesterol (HDL-c) levels before and after 20 wk of endurance training were investigated in the HERITAGE Family Study. Plasma HDL-c, HDL(2)-c, HDL(3)-c, and apolipoprotein (apo)A1 levels were measured, and 13 CETP single nucleotide polymorphisms (SNPs) were genotyped in 265 blacks and 486 whites. Three haplotypes defined by SNPs at the -1337, -971, and -629 sites were strongly associated with baseline HDL-c levels in whites. Both C-1337T and C-629A were associated with baseline HDL-c (P < 0.001) and apoA1 (P < 0.01) when tested separately. However, only C-629A remained significant in a combined model. G-971A was not associated with HDL phenotypes, but showed significant interactions with C-629A (P = 0.002) on baseline traits. Genotype-by-sex interactions were observed at the -629 locus for HDL(3)-c (P = 0.004) and apoA1 (P = 0.02) training responses in whites. In women, the -629 A/A homozygotes showed greater increases in HDL(3)-c (P = 0.02) and apoA1 (P = 0.02) levels than the other genotypes. Finally, apolipoprotein E (APOE) genotype and the CETP C-629A locus contributed independently and in additive fashion to the HDL traits, explaining 6.0-8.8% of the variance. The CETP -1337T and -629A alleles are associated with higher baseline HDL-c and apoA1 levels. The beneficial effects of endurance training on plasma HDL(3)-c and apoA1 levels are evident in white women homozygous for the -629A allele. The CETP and APOE genotypes account for up to 9% of the variance in HDL-c phenotypes in the HERITAGE Family Study.

Effect of exercise training on in vitro LDL oxidation and free radical-induced hemolysis: the HERITAGE Family Study.

Oxidant stress and overproduction of reactive oxygen species (ROS) contribute to the development of cardiovascular disease. Oxidative modifications of low-density lipoproteins (LDL) are thought to play an early and critical role in atherogenesis. LDL oxidation can be reproduced in vitro, but results usually show a large interindividual variation not entirely explained by the environment. Free radical-induced hemolysis is also proposed to reveal the overall antioxidant capacity. The roles of genetic factors and exercise on the variability of both measures were investigated. The study was conducted in 146 healthy individuals from 28 families participating in a 20-week exercise-training program. In addition to important biological and environmental influences on variation, significant familial aggregation was detected in all oxidation measures. Exercise did not significantly modify the LDL oxidation parameters, but significantly increased resistance was observed in the free radical-induced hemolysis, especially in women, this effect was not observed in smokers. In total, the findings suggest the presence of familial effects in the response to ex vivo oxidation. Further, smoking negates the beneficial effect of exercise training on erythrocyte resistance to free radical-induced hemolysis. These observations emphasize the importance of context in the evaluation of exercise and oxidant stress.

Attenuation of Adverse Effects of Aging on Skeletal Muscle by Regular Exercise and Nutritional Support.

Beginning early in midlife, natural/primary aging is inevitably associated with a progressive reduction in muscle mass and function. This process can progress with aging to a substantial loss of strength, particularly in the lower extremities, reducing mobility. This condition, commonly referred to as sarcopenia, can result in frailty, reducing one's ability to live independently. This article reviews the underlying biological process contributing to the development of sarcopenia and the roles of regular exercise and nutritional support for attenuating aging-associated muscle loss as well as risk and management of sarcopenia and associated frailty.

Quantitative trait locus on chromosome 20q13 for plasma levels of C-reactive protein in healthy whites: the HERITAGE Family Study.

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.

Cardiac rehabilitation and secondary prevention of coronary heart disease: an American Heart Association scientific statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), in collaboration with the American association of Cardiovascular and Pulmonary Rehabilitation.

This article updates the 1994 American Heart Association scientific statement on cardiac rehabilitation. It provides a review of recommended components for an effective cardiac rehabilitation/secondary prevention program, alternative ways to deliver these services, recommended future research directions, and the rationale for each component of the rehabilitation/secondary prevention program, with emphasis on the exercise training component.

Hepatic lipase gene variant -514C>T is associated with lipoprotein and insulin sensitivity response to regular exercise: the HERITAGE Family Study.

We investigated the associations between the hepatic lipase gene (LIPC) -514C>T polymorphism and lipases, lipoproteins, and insulin sensitivity (Si) responses to exercise training. Hepatic lipase and lipoprotein lipase activities, plasma lipoprotein levels, and Si were measured in the sedentary state and post-exercise training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study (n=662). The LIPC -514C allele frequency was 0.516 (blacks) and 0.796 (whites). Baseline and post-exercise training hepatic lipase activities were 40% higher in CC homozygotes (P < 0.0001) in both races. Black CC homozygotes had lower baseline lipoprotein lipase activity, HDL cholesterol, HDL3, and apolipoprotein (apo)A-1 concentrations. White CC homozygotes had lower baseline HDL cholesterol, apoA-1, LDL cholesterol, and apoB levels that remained low post-exercise training. Baseline Si was not associated with the LIPC genotypes. However, training-induced improvements in Si both in blacks and whites were greater in CC homozygotes (+1.25 +/- 0.2 and +0.22 +/- 0.2 microU.min(-1).ml(-1)) than in the TT genotype (+0.27 +/- 0.3 and -0.97 +/- 0.3 microU.min(-1).ml(-1)) (P = 0.008 and P = 0.002, respectively). The LIPC -514C allele was associated with higher hepatic lipase activity in sedentary and physically active states and better Si responses to regular exercise both in black and white individuals. The benefits from an exercise program on Si are likely to be substantial in the general population given the high frequency of the LIPC -514C allele, particularly in whites.

Pleiotropic QTL on chromosome 19q13 for triglycerides and adiposity: the HERITAGE Family Study.

Motivated by strong correlations between plasma levels of triglycerides (TG) and adiposity traits, we conducted a series of bivariate genome-wide linkage analyses of TG with body mass index (BMI), total fat mass (FAT), percentage of body fat (FATPC), and abdominal subcutaneous fat (ASF). Maximum lod scores of 3.3, 3.0, 2.2 and 2.4, respectively, were found on chromosome 19q13. This linkage region includes the APOE gene, a predictor of variation in lipid-lipoprotein levels, and the hormone-sensitive lipase (LIPE) gene, a key enzyme in the mobilization of fatty acids from triglyceride stores. In addition, the adiposity measures together with the APOE marker showed significant association with TG levels (p = 0.02 to p = 0.03). In summary, these results suggest that one or more QTLs in the 19q13 region jointly influence TG levels and adiposity. Polymorphisms in the APOE gene, and possibly LIPE gene, appear to be strong candidates for the source of this pleiotropic QTL.

Vascular structure and function in women: relationship with body mass index.

BACKGROUND: The purpose of the present study was to compare endothelial function in lean (body mass index [BMI]=18.0-24.9 kg/m2); overweight (BMI=25-29.9 kg/m2); and obese (BMI>30 kg/m2), healthy, eumenorrheic women. METHODS: Eighteen lean, 22 overweight, and 19 obese eumenorrheic middle-aged women were studied. Vascular structure and function were assessed via non-invasive ultrasound imaging of the carotid and brachial arteries. Body composition, blood pressure, fasting blood lipids, glucose, and insulin also were measured. RESULTS: The groups demonstrated significantly (p<0.001) different mean values for total body, lean body, and fat masses. The obese group demonstrated significantly (p<0.05) elevated fasting glucose and insulin levels and lower high-density lipoprotein levels as compared to the lean group. The overweight group also demonstrated elevated fasting glucose levels as compared to the lean group (p<0.05) with no significant difference from the obese group. Only systolic blood pressure differed among the three groups, being elevated in the obese group compared to the lean group (p<0.05). The obese group demonstrated significantly (p<0.05) elevated carotid artery lumen diameter, carotid artery wall cross-sectional area, and brachial artery lumen diameter with significantly (p<0.05) lower flow-mediated dilation as compared to the lean group. The overweight group demonstrated elevated carotid artery wall cross-sectional area and brachial artery lumen diameter as well as lower flow-mediated dilation as compared to the lean group (p<0.05). CONCLUSIONS: The results of this study support the hypothesis that carotid artery wall cross-sectional area is elevated and flow-mediated dilation reduced in overweight and obese eumennorheic women as compared to lean counterparts in relation to BMI classification.

Moderate resistance training and vascular health in overweight women.

PURPOSE: Impaired endothelial function has been implicated as an initial step in the pathogenesis of atherosclerosis leading to cardiovascular disease (CVD). Aerobic exercise improves vascular function and reduces risk of CVD morbidity and mortality; however, the effects of resistance training on vascular function remains unclear. Thus, the aim of this study was to examine the effects of 1 yr of resistance training (RT) on vascular structure and function in overweight but otherwise healthy eumenorrheic women. METHODS: Study participants consisted of 30 (15 control, 15 RT) overweight (BMI > 25 kg x m(-2)) women, aged 24-44 yr, studied before and after a 1-yr RT intervention. Vascular structure and function were assessed via noninvasive ultrasound imaging of the carotid and brachial arteries, respectively. Body composition, blood pressure, and fasting blood lipids and glucose also were measured. RESULTS: The RT group demonstrated a significant mean improvement in one-repetition maximum bench press following 1 yr of RT (P < 0.05). There also was a significant increase in lean body mass in the RT group compared with the control group (P = 0.04). There were no training-associated changes in blood pressure, fasting blood lipids, glucose, or insulin levels. Although there was no change in carotid artery intimamedia thickness, peak flow-mediated dilation significantly improved in the RT group (P < 0.05). CONCLUSION: The principal significant finding in this study was the initial demonstration that RT alone can improve brachial artery endothelial function in overweight eumenorrheic women.

The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels: the HERITAGE Family Study.

OBJECTIVE: Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), stimulate the release of C-reactive protein (CRP). We investigated the association between the TNF-alpha G-308A polymorphism and plasma CRP levels. METHODS: Subjects were 456 White (225 men, 231 women) and 232 Black (83 men, 149 women) healthy adults who underwent a 20-week standardized exercise program in the HERITAGE Family Study. The TNF-alpha gene promoter polymorphism was determined using PCR amplification followed by NcoI digestion. Plasma CRP was measured using a high-sensitivity assay. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for age, smoking, alcohol consumption, maximal oxygen uptake and, in women, hormone use, the AA homozygotes for the G-308A polymorphism had higher baseline CRP levels than other genotypes in White and Black men (P<0.001 and P = 0.044, respectively) and in Black women (P = 0.032). Body mass index partly explained these associations in Blacks. The exercise program results provided further evidence for an association with the polymorphism. Among those with high CRP at baseline (> or = 3.0 mg/L), regular exercise decreased CRP less in AA homozygotes than in other genotypes (P = 0.043). CONCLUSION: The AA genotype of the TNF-alpha G-308A polymorphism is associated with higher plasma CRP levels and less favorable CRP response to regular exercise.

Effects of exercise training on glucose homeostasis: the HERITAGE Family Study.

OBJECTIVE: To determine the effect of a 20-week endurance training program in healthy, previously sedentary participants on measures derived from an intravenous glucose tolerance test (i.v.GTT). RESEARCH DESIGN AND METHODS: An i.v.GTT was performed before and after a standardized training program in 316 women and 280 men (173 blacks and 423 whites). Participants exercised on cycle ergometers 3 days per week for 60 sessions. The exercise intensity was progressively increased from 55% VO2max for 30 min per session to 75% VO2max for 50 min per session. RESULTS: Mean insulin sensitivity increased by 10% (P < 0.001) following the intervention, but the variability in the changes was high. Men had larger improvements than women (P = 0.02). Improvements in fasting insulin were transitory, disappearing 72 h after the last bout of exercise. There were also significant mean increases in the glucose disappearance index (3%, P = 0.02) and in glucose effectiveness (11%, P < 0.001), measures of glucose tolerance and of the capacity of glucose to mediate its own disposal, respectively. The acute insulin response to glucose, a measure of insulin secretion, increased by 7% in the quartile with the lowest baseline glucose tolerance and decreased by 14% in the quartile with the highest baseline glucose tolerance (P < 0.001). The glucose area below fasting levels during the i.v.GTT was reduced by 7% (P = 0.02). CONCLUSIONS: Although the effects of structured regular exercise were highly variable, there were improvements in virtually all i.v.GTT-derived variables. In the absence of substantial weight loss, regular exercise is required for sustained improvements in glucose homeostasis.