Sex differences in ventricular-vascular coupling following endurance training.

INTRODUCTION: Ventricular and vascular coupling is defined as the ratio of arterial elastance (Ea) to ventricular elastance (Elv) and describes the interaction between the heart and arterial system. There are sex differences in both arterial and ventricular function in response to both acute exercise and aerobic exercise training. PURPOSE: To examine the effects of aerobic exercise training on elastances and the coupling ratio in young adult men and women. We hypothesized a reduction in the coupling ratio in both sexes due to a decrease in Ea that would be more pronounced in men and an increase in Elv that would be larger in women. METHODS: Fifty-three healthy, young adults completed the study. Central pulse wave velocity and heart volumes were measured before and after an 8-week aerobic training intervention. Elastances were calculated as Ea = end-systolic pressure/stroke volume and Elv = end-systolic pressure/end-systolic volume and indexed to body surface area. RESULTS: After the intervention, women augmented indexed and un-indexed Elv from 2.09 ± 0.61 to 2.52 ± 0.80 mmHg/ml, p < 0.05, and reduced the coupling ratio from 0.72 ± 18 to 0.62 ± 15, p < 0.05, while men maintained their pre-training ratio (from 0.66 ± 0.20 to 0.74 ± 0.21, p > 0.05). Women also reduced end-systolic pressure (from 91 ± 10 to 87 ± 10 mmHg), and both groups reduced central pulse wave velocity (from 6.0 ± 1.0 to 5.6 ± 0.6 m/s, p < 0.05). CONCLUSION: We conclude that after 8 weeks of aerobic training, only women reduced their coupling ratio due to an increase in Elv. This suggests that aerobic exercise training elicits sex-dependent changes in the coupling ratio in young, healthy individuals.

Perceptual effects and efficacy of intermittent or continuous blood flow restriction resistance training.

Blood flow restriction (BFR) exercise may be an alternative form of resistance training; however, a side of effect of BFR resistance exercise is acute muscle pain. Typically, BFR exercise studies restrict blood flow with a cuff continuously during the exercise bout, including rest periods. However, others have used intermittent BFR where the cuff is inflated only during sets. We performed two studies to compare intermittent and continuous BFR exercise. In study one, eleven subjects randomly proceeded through three treatments of unilateral leg extensions to failure: (i) continuous BFR, (ii) intermittent BFR and (iii) control (exercise without BFR). Pain measurements were taken immediately after each set. In study two, subjects (n = 32) underwent a 5-week resistance training programme after random assignment to one of the three conditions. Lean mass and strength were assessed at baseline and after training. Continuous BFR resulted in significantly greater pain than intermittent BFR or control. Both BFR conditions resulted in significantly fewer repetitions to failure than control. This suggests that an acute bout of intermittent BFR exercise may produce as much muscle fatigue as an acute bout of continuous BFR exercise, but with less pain. With training, maximal knee extension (P = 0·033) and maximum knee flexion (P = 0·007) strength increased among all groups. There were no significant differences between groups in strength or lean mass. These results suggest that short-term low-load resistance training increases muscle strength to a similar extent as low-load resistance training without BFR.

Effect of sex on wasted left ventricular effort following maximal exercise.

Wasted left ventricular effort (∆Ew) refers to work required of the left ventricle to eject blood that does not result in increased stroke volume and is related to left ventricular hypertrophy. Literature shows that men and women have differing ventricular and vascular responses to and following exercise. Our purpose was to determine how ∆Ew changes post-exercise in men and women and examine potential mechanisms. We hypothesized a reduction in ∆Ew that would be greater in men and that central pulse wave velocity and wave intensity (WIA) would be related to ∆Ew. Blood pressures, central pulse wave velocity (cPWV), and WIA were obtained at rest, 15 and 30 min after maximal exercise. Both sexes reduced ∆Ew post-maximal exercise (p>0.05 for interaction), but women had higher ∆Ew at each time point (p<0.05). The first peak of WIA increased 15 min post-exercise only in women (p<0.05). cPWV was attenuated (p<0.05) in women at 15 min and men at 30 min (p<0.05) post-exercise with a significant time by sex interaction (p<0.05). WIA (1st peak) was correlated (p<0.05) to ∆Ew in both sexes before and 15 min post-exercise, but cPWV was only associated with ∆Ew in men at 30 min post-exercise. We conclude that both sexes decrease ∆Ew after maximal exercise, but vascular and ventricular changes associated with the attenuation of ∆Ew are not uniform between sexes.

Resting and post exercise arterial-ventricular coupling in endurance-trained men and women.

The relationship between effective arterial elastance (EA) and left ventricular end-systolic elastance (ELV) is a determinant of cardiac performance, known as arterial-ventricular coupling (AVC). The purpose of this study was to examine the acute effects of high-intensity interval (HI) and low-intensity steady state (SS) exercise on AVC. Twenty-three (13 men, 10 women) young (26 years), endurance-trained individuals completed a VO2 peak test followed by an acute SS and HI exercise bout on separate visits. Before (Pre) and 30- and 60-min after each bout, measures of aortic end-systolic pressure (ESP), left ventricular end-systolic volume and stroke volume were obtained. Across both conditions (HI and SS) and both sexes, at 30 and 60 min post exercise, ESP and ELV were reduced from Pre 30 and 60-min exercise (ESP: 86±7, 77±8 and 73±8 mm Hg; ELV: 4.93±1.53, 4.19±1.38 and 4.10±1.53 mm Hg ml(-1) m(-2)). EA was only reduced at 60 min post exercise (1.90±0.36, 1.78±0.50 and 1.57±0.36). Both EA and ELV were reduced following acute SS and HI exercise. This is likely because of similar reductions in total peripheral resistance following both exercise bouts. These results suggest that endurance-trained individuals are able to match peripheral vascular changes with changes in left ventricular function following dynamic exercise of different intensities.

Aortic reservoir function, estimated myocardial demand and coronary perfusion pressure following steady-state and interval exercise.

Aortic reservoir function is a measure of the aorta's ability to distribute blood during diastole, attenuating the pulsatility of blood flow, and is important in balancing cardiac flow. Effects of acute high versus moderate exercise intensity on reservoir function and cardiac energetics is unknown. Eighteen athletes completed a interval (INT) and steady-state (SS) cycling bout at 60% of VO(2) peak. Reservoir function was calculated as the ratio of diastolic run-off to stroke volume and expressed as a percentage. Coronary perfusion pressure was derived from tissue Doppler imaging and echocardiography. Systolic tension-time integral (TTI) from the aortic pressure waveform served as a measure of myocardial oxygen consumption. All measures were made at rest, 30-min postexercise and 60-min postexercise. Average reservoir function before SS was 76%, which was reduced to 62% 30-min post-SS and 67% 60-min post-SS (P<0.05). Significantly greater reductions in reservoir function were seen following INT (from 71% pre-INT to 45% 30-min post-INT and 53% 60-min INT, P<0.05). Estimated coronary perfusion pressure was reduced 30 min following INT but not SS; both bouts reduced coronary perfusion pressure at 60-min postexercise (P<0.05). TTI increased following both INT and SS at 30- and 60-min postexercise with greater increases following INT (P<0.05). Following exercise, reservoir function was associated with TTI (P<0.05), but not coronary perfusion pressure (P>0.05). We conclude that reservoir function is attenuated following acute SS and INT, but these reductions were greater post-INT, suggesting that exercise intensity affects reservoir function. Reduction of reservoir function following exercise is related to TTI, a reflection of myocardial oxygen consumption but apparently not associated with coronary perfusion pressure.

Effects of endurance exercise training on markers of cholesterol absorption and synthesis.

Abnormal cholesterol metabolism, including low intestinal cholesterol absorption and elevated synthesis, is prevalent in diabetes, obesity, hyperlipidemia, and the metabolic syndrome. Diet-induced weight loss improves cholesterol absorption in these populations, but it is not known if endurance exercise training also improves cholesterol homeostasis. To examine this, we measured circulating levels of campesterol, sitosterol, and lathosterol in 65 sedentary subjects (average age 59 years; with at least one metabolic syndrome risk factor) before and after 6 months of endurance exercise training. Campesterol and sitosterol are plant sterols that correlate with intestinal cholesterol absorption, while lathosterol is a marker of whole body cholesterol synthesis. Following the intervention, plant sterol levels were increased by 10% (p<0.05), but there was no change in plasma lathosterol. In addition, total and LDL-cholesterol were reduced by 0.16 mmol and 0.10 mmol, respectively (p<0.05), while HDL-C levels increased by 0.09 mmol (p<0.05). Furthermore, the change in plant sterols was positively correlated with the change in VO2max (r=0.310, p=0.004), independent of other metabolic syndrome risk factors. These data indicate that exercise training reduces plasma cholesterol despite increasing cholesterol absorption in subjects with metabolic syndrome risk factors.

The association between regional body composition and metabolic outcomes in athletes with spinal cord injury.

STUDY DESIGN: Cross-sectional study comparing athletes with spinal cord injury (SCI) and age and body mass index matched able-bodied controls (AB). OBJECTIVE: To examine the impact of exercise training on the relation between whole body, regional and intermuscular adipose tissue (IMAT) and glucose tolerance, insulin action and lipid profile. SETTING: University Research Laboratory, USA. METHODS: Fourteen college-aged athletes with SCI (seven men; duration of injury 16.5+/-5.7 years, level of injury T5-L5) and 17 sedentary AB (eight men) were assessed for body composition via dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging. Insulin sensitivity index (ISI) was determined via 2-h oral glucose challenge; standard lipid profile was determined from fasting blood samples. RESULTS: Although ISI was 30% higher in SCI, there were no significant differences between groups in glucose and insulin responses or in lipid measures. Adjusting for absolute and relative thigh IMAT area, fasting insulin (13.8+/-5.3 microIU, 16.3+/-5.6 microIU; P<0.05; SCI vs AB respectively) and ISI (4.0+/-1.4, 3.1+/-1.3; P<0.05) were significantly better among SCI athletes compared to AB. Measures of adiposity did not correlate with glucose response or most lipid measures. Within SCI and AB, respectively, ISI correlated strongly (all P<0.05) with absolute (r = -0.70, -0.54) and relative IMAT (r = -0.54, -0.50), than with trunk (r = -0.62, -0.64) and whole body fat mass (r = -0.61, -0.64). CONCLUSION: Habitual physical activity can maintain insulin sensitivity in SCI compared to sedentary AB controls. Total body fat mass, central adiposity and thigh IMAT appear to impact risk for metabolic disease in SCI individuals with IMAT playing a larger role in SCI than AB.

Physical activity, hormone replacement therapy and plasma lipoprotein-lipid levels in postmenopausal women.

We assessed the cross-sectional associations between hormone replacement therapy (HRT), habitual physical activity levels and plasma lipoprotein-lipid levels in postmenopausal women. Sedentary (n = 19), active nonathlete (n = 20) and endurance-trained (n = 21) postmenopausal women, with half of each group on and half not on HRT, underwent assessments of plasma lipids, VO2max, body composition, diet and common genetic variants. The groups' physical characteristics were generally similar though body weight was higher in the active nonathletes, and body fat was lower and VO2max higher in the athletes. HRT was associated with beneficial total cholesterol, LDL-C and HDL-C levels in sedentary and active nonathlete women. Plasma lipoprotein-lipid profiles were similar in women athletes on and not on HRT, with their profiles being only slightly better than sedentary and physically-active women on HRT. After controlling for HRT status, VO2max was correlated with total cholesterol (r = -0.51, p = 0.0001), LDL-C (r = -0.52, p = 0.0001), HDL-C (r = 0.25, p = 0.055), HDL 2 -C (r = 0.24, p = 0.08) and TG levels (r = -0.46, p = 0.0001). After controlling for HRT status, % body fat was correlated with total cholesterol (r = 0.43, p = 0.001), LDL-C (r = 0.38, p = 0.003), HDL-C (r = -0.29, p = 0.025), HDL 2 -C (r = -0,26, p = 0.07) and TG levels (r = 0.40, p = 0.002). Dietary fat intake was similar among the groups. APO E genotype was only associated with plasma lipid profiles in athletes, as those with at least one APO E2 allele tended to have better lipid profiles than those with only APO E3 or E4 alleles. Thus, HRT, exercise training and body composition are associated with plasma lipid levels in postmenopausal women; common polymorphic variations at key lipid metabolism-related gene loci also may interact with exercise training to affect their plasma lipid profiles.

Acute resistive exercise does not affect ambulatory blood pressure in young men and women.

PURPOSE: Resistive exercise elicits a pressor response that results in a dramatic increase in blood pressure (BP) during the exercise. However, it is not known if the BP elevation persists after resistive exercise. METHODS: This study examined the effects of an acute resistive exercise session on 24-h ambulatory BP in sedentary (5 men, 6 women), resistance-trained (6 men, 6 women), and endurance-trained (4 men, 6 women) young subjects (age 22 +/- 3.2 yr) with normal BP. Two 24-h ambulatory BP recordings were made on each subject, one after two sets of resistive exercise on 12 weight machines and one after 48 h without prior exercise. RESULTS: Systolic, diastolic, and mean arterial BP and heart rate (HR) were not different in the hours after and for up to 24 h after the single resistive exercise session compared with the control day. There also was no difference in the ambulatory BP or HR response after the single session of resistive exercise based on the training status of the subjects. CONCLUSION: Thus, the elevated BP that occurs during resistive exercise does not persist in the 24 h after acute resistive exercise in sedentary, resistance-trained, or endurance-trained, young, normotensive men and women.

Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein.

Atherogenic low density lipoproteins are cleared from the circulation by hepatic low density lipoprotein receptors (LDLR). Two inherited forms of hypercholesterolemia result from loss of LDLR activity: autosomal dominant familial hypercholesterolemia (FH), caused by mutations in the LDLR gene, and autosomal recessive hypercholesterolemia (ARH), of unknown etiology. Here we map the ARH locus to an approximately 1-centimorgan interval on chromosome 1p35 and identify six mutations in a gene encoding a putative adaptor protein (ARH). ARH contains a phosphotyrosine binding (PTB) domain, which in other proteins binds NPXY motifs in the cytoplasmic tails of cell-surface receptors, including the LDLR. ARH appears to have a tissue-specific role in LDLR function, as it is required in liver but not in fibroblasts.

Moderate physical activity is associated with higher bone mineral density in postmenopausal women.

OBJECTIVES: To determine the associations between different levels of habitual physical activity, hormone replacement therapy (HRT), and bone mineral density (BMD) in postmenopausal women. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: Twenty sedentary women, 20 active nonathletic women, and 23 endurance-trained athletes, all of whom were postmenopausal, with half of each group on and half not on HRT. MEASUREMENTS: BMD and body composition determined by dual energy x-ray absorptiometry, maximal oxygen consumption (VO2max), dietary history by questionnaire, and vitamin D receptor (VDR) genotyping on deoxyribonucleic acid. RESULTS: Body weight was higher in the active nonathletic than in the sedentary and athletic women. Body fat was lower and VO2max higher in the athletic women than in the sedentary and the active nonathletic women. Physical activity level was significantly associated with BMD in three of the five measurements taken (L1-L4 lumbar spine, trochanter, total body; all P < .05). These differences were also generally significant after adjusting for body weight. The association between physical activity status and BMD at the neck of the femur and Ward's triangle bordered on significance (P = .07-.09). At most sites, the active nonathletic women had higher BMD than did the sedentary and athletic women. HRT was significantly associated only with total body BMD (P < .05). The groups were similar in terms of dietary habits (protein, calcium, sodium, phosphorus intake); VDR genotypes; and family, smoking, and nutritional histories. CONCLUSION: Given the similarity of the groups with respect to other factors that affect BMD, it appears that prolonged low-to-moderate-intensity physical activity, but not the same number of years of higher-intensity training for competitive events, was independently associated with higher BMD.

APO E gene and gene-environment effects on plasma lipoprotein-lipid levels.

Apolipoprotein E (apo E) is important in plasma lipid metabolism and is a component of several plasma lipoprotein-lipid particles. Three major apo E isoforms are encoded by three common alleles at the APO E locus. The E2 allele is associated with lower and the E4 allele with higher total plasma cholesterol and LDL cholesterol levels compared with the E3 allele. Available data generally indicate that APO E2, and possibly E3, genotype individuals reduce plasma total and low-density lipoprotein (LDL) cholesterol levels more than APO E4 individuals with statin therapy. Some evidence also indicates that APO E2 individuals are more likely to respond favorably to gemfibrozil and cholestyramine. On the other hand, it appears that with probucol, APO E4 genotype individuals may improve plasma lipoprotein-lipid profiles more than APO E3 individuals. APO E2 and E3 genotype perimenopausal women appear to improve plasma lipoprotein-lipid profiles more with hormone replacement therapy than APO E4 women. On the other hand, low-fat diet interventions tend to reduce plasma LDL cholesterol and, perhaps, plasma total cholesterol levels more in APO E4 than in APO E2 or E3 individuals. Both cross-sectional and longitudinal studies generally indicate that APO E2 and E3 individuals improve plasma lipoprotein-lipid profiles more with exercise training than APO E4 individuals. Although these data are hardly definitive, they lend strong support for the possibility that in the near future individuals will be directed to what might be their optimal therapy for improving plasma lipoprotein-lipid profiles and cardiovascular disease risk based partially on APO E genotype.

Determinants of body composition in postmenopausal women.

BACKGROUND: Little is known about the effects of different levels of long-term physical activity on total body and regional fat and whether hormone replacement therapy interacts with physical activity level to affect body composition in postmenopausal women. METHODS: We determined the associations between different levels of habitual physical activity, hormone replacement therapy (HRT), and total and regional body composition in postmenopausal women. Twenty sedentary, 20 active nonathletic, and 23 endurance-trained women (approximately half on HRT) had total and regional body composition assessed by dual-energy x-ray absorptiometry. The athletes and active nonathletic women had been active for the same number of years and the same number of hours per week. RESULTS: The athletes and sedentary women weighed the same, but the active nonathletic groups on and not on HRT weighed 3-12 kg more (p < .05). Athletes had less trunk, arm, leg, and total body fat than sedentary and active nonathletic women (p < .05). Women on HRT tended to have lower total body (p = .07), but not regional, fat values. Linear regression analyses indicated that VO2max in ml/kg/min was the major independent determinant of total and regional body fat accounting for 52% to 70% of their variances. Athletes had greater caloric and carbohydrate intake than their less active peers, but all groups had similar protein, fat, saturated fat, monounsaturated fat, and polyunsaturated fat intakes. CONCLUSIONS: Intense training, but not low- to moderate-intensity physical activity, is associated with markedly lower levels of total and regional body fat in postmenopausal women. HRT has less of an effect on body composition than intense exercise training in postmenopausal women.

Exercise training-induced blood pressure and plasma lipid improvements in hypertensives may be genotype dependent.

Exercise training improves cardiovascular disease risk, but individual responses are highly variable. We hypothesized that common polymorphic gene variations would affect these responses. Sedentary obese hypertensive older men who had undergone exercise training were typed at the apolipoprotein (apo) E, angiotensin-converting enzyme (ACE), and lipoprotein lipase (LPL) loci. Individuals of all genotype subgroups were generally similar before training; they also changed body weight, body composition, and &f1;O(2)max similarly with training. ACE insertion/insertion (II) and insertion/deletion (ID) genotype individuals (n=10) tended to reduce systolic blood pressure more with training than deletion/deletion (DD) individuals (n=8) (-10 versus -5 mm Hg, P=0. 16). ACE II and ID individuals decreased diastolic blood pressure more with training than DD individuals (-10 versus -1 mm Hg, P<0. 005). Systolic blood pressure reductions with training were also larger in apoE3 and E4 (n=15) than apoE2 men (n=3) (-10 versus 0 mm Hg, P<0.05). The same trend was evident for diastolic blood pressure (-7 versus -3 mm Hg), but the difference was not significant. Systolic (14 versus -6 mm Hg, P=0.08) and diastolic (-9 versus -5 mm Hg, P=0.10) blood pressure reductions tended to be greater in LPL PvuII +/+ (n=4) than +/- and -/- individuals (n=14). Systolic (-10 versus 3 mm Hg, P<0.05) and diastolic (-9 versus 2 mm Hg, P<0.05) blood pressure reductions were larger in LPL HindIII +/+ and +/- (n=15) than -/- persons (n=3), respectively. LPL PvuII -/- individuals (n=3) had larger increases in HDL cholesterol (11 versus 2 mg/dL, P<0.05) and HDL(2) cholesterol (8 versus 0 mg/dL, P<0.05) than LPL PvuII +/- and +/+ individuals (n=15). These results are consistent with the possibility that apoE, ACE, and LPL genotypes may identify hypertensives who will improve blood pressure, lipoprotein lipids, and cardiovascular disease risk the most with exercise training.

VO2 max is associated with ACE genotype in postmenopausal women.

Relationships have frequently been found between angiotensin-converting enzyme (ACE) genotype and various pathological and physiological cardiovascular outcomes and functions. Thus we sought to determine whether ACE genotype affected maximal O2 consumption (VO2 max) and maximal exercise hemodynamics in postmenopausal women with different habitual physical activity levels. Age, body composition, and habitual physical activity levels did not differ among ACE genotype groups. However, ACE insertion/insertion (II) genotype carriers had a 6.3 ml . kg-1 . min-1 higher VO2 max (P < 0.05) than the ACE deletion/deletion (DD) genotype group after accounting for the effect of physical activity levels. The ACE II genotype group also had a 3.3 ml . kg-1 . min-1 higher VO2 max (P < 0.05) than the ACE insertion/deletion (ID) genotype group. The ACE ID group tended to have a higher VO2 max than the DD genotype group, but the difference was not significant. ACE genotype accounted for 12% of the variation in VO2 max among women after accounting for the effect of habitual physical activity levels. The entire difference in VO2 max among ACE genotype groups was the result of differences in maximal arteriovenous O2 difference (a-vDO2). ACE genotype accounted for 17% of the variation in maximal a-vDO2 in these women. Maximal cardiac output index did not differ whatsoever among ACE genotype groups. Thus it appears that ACE genotype accounts for a significant portion of the interindividual differences in VO2 max among these women. However, this difference is the result of genotype-dependent differences in maximal a-vDO2 and not of maximal stroke volume and maximal cardiac output.