Successful weight maintenance preserves lower levels of oxidized LDL achieved by weight reduction in obese men.

OBJECTIVE: We studied the association between weight maintenance, oxidized low-density lipoprotein (ox-LDL) and other lipoproteins in obese men. METHODS: A 2-month weight reduction phase (WRP) with a very-low-energy diet was followed by a 6-month weight maintenance period and an unsupervised 2-year follow-up. Ninety men entered and 68 (76%) completed the study. Subjects were analyzed as one group and after division into two subgroups: 20 most successful men in maintaining the lost weight (subgroup 1) and the remaining (n=48) men (subgroup 2). Ox-LDL was measured by quantifying the amount of conjugated dienes in LDL particles. RESULTS: The mean (+/-s.d.) weight reduction at the end of the WRP (n=68) was 14% (confidence interval (CI) 12.9-14.7%, 14.5+/-4.2 kg, P<0.001). Ox-LDL decreased by 22% (CI 16.9-28.1, 12.3+/-15.4 micromol/l, P<0.001). At the end of the 2-year follow-up, the regain in weight from the end of the WRP was 11% (CI 9.0-12.4, 9.6+/-6.2 kg, P<0.001). The regain in ox-LDL was 30% (CI 18.7-41.2, 8.2+/-15.4 micromol/l, P<0.001). In subgroup 1 vs 2, the respective regains were 3% (CI 0.9-4.2, 2.2+/-3.0 kg, P=0.006) vs 14% (CI 12.7-15.6, 12.9+/-4.0 kg, P<0.001) regarding weight and 9% (2.0+/-6.9 micromol/l, P=NS) vs 39% (CI 23.7-53.9, 11.2+/-17.2 micromol/l, P

Circulating oxidized low-density lipoprotein and common carotid artery intima-media thickness in a random sample of middle-aged men.

Circulating oxidized low-density lipoprotein (oxLDL) has been suggested to play an important role in atherosclerosis development. According to previous observations, oxLDL correlates with clinically manifest coronary and carotid artery disease. We investigated the association between the oxLDL concentration measured directly in plasma and common carotid artery intima-media thickness (IMT) in a population-based, case-control study in middle-aged men from Southern Finland. oxLDL was determined in 214 men by a commercially available sandwich ELISA test (Mercodia). Carotid artery IMT was measured at 12 standardized segments by B-mode ultrasonography (at the near and far wall of the left and right common carotid arteries, bifurcations and internal carotid arteries), and the overall mean maximum IMT (MMaxIMT) was calculated. The MMaxIMT of the carotid arteries was significantly associated with circulating oxLDL (r(s) = 0.16, p = 0.018). In a stepwise multiple regression model with MMaxIMT as dependent variable and systolic blood pressure, smoking, oxLDL, HDL cholesterol and apolipoprotein B as covariates, systolic blood pressure (beta = 0.22, p < 0.001), oxLDL (beta = 0.15, p = 0.022) and smoking (beta = 0.17, p = 0.014) showed an independent association with IMT (R(2) = 0.10, p < 0.001). Our results show that oxLDL measured directly from plasma is independently associated with subclinical carotid artery atherosclerosis in middle-aged men.

Walking trials in postmenopausal women: effect of low doses of exercise and exercise fractionization on coronary risk factors.

We studied the fractionization of walking training and searched for the minimum dose to affect coronary risk factors in two randomized controlled trials. Altogether 134 (Study I) and 121 (Study II) healthy, sedentary postmenopausal women started the trials, and 130 (Study I) and 116 (Study II) completed them. In Study I the exercise intensity was 65% of the maximal aerobic power (VO2max) and a total of 300 kcal was expended in one (Group W1) or two (Group W2) daily walking bouts. In Study II the exercise was continuous, and the exercise intensity (% of VO2max) and energy expenditure (kcal session(-1)) were 55% and 300 kcal (Group W3), 45% and 300 kcal (Group W4), 55% and 200 kcal (Group W5) and 45% and 200 kcal (Group W6). All the subjects walked 5 days a week. The outcome measures were blood pressure, serum lipoproteins and blood glucose and plasma insulin in fasting state and also during 2-h oral glucose tolerance test in Study I. There was no change in diastolic pressure in the original study groups, but in the combined exercise group (W1+W2) in Study I, the mean diastolic pressure declined by -3.0 mmHg (95% con-fidence interval (CI) -5.5 to -0.4) (P=0.025) in comparison with that of the controls. The mean blood glucose declined by -0.21 mmol L(-1) (CI -0.33 to -0.09) in Group W1 and -0.13 mmol L(-1) (CI -0.25 to -0.01) in Group W2 compared to controls (P=0.03). Also the 2-h glucose concentration decreased in Groups W1 and W2 compared to controls. Systolic blood pressure, serum lipoproteins and insulin levels did not change in Study I or Study II. We conclude that our training program with the greatest exercise dose, exercise intensity 65% of VO2max and weekly expenditure of 1500 kcal had a minimal, positive effect on diastolic pressure and blood glucose, and the effect was similar in one or two daily exercise session groups. This exercise dose is probably close to the minimum to affect coronary risk factors in healthy postmenopausal women. To get a more pronounced and clinically relevant effect, a greater exercise dose is needed.

Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial.

In this randomized, double-blind, placebo-controlled 12-month trial we evaluated effects of weight- bearing jumping exercise and oral alendronate, alone or in combination, on the mass and structure of bone, risk factors for falling (muscle strength and power, postural sway, and dynamic balance), and cardiorespiratory fitness in postmenopausal women. A total of 164 healthy, sedentary, early postmenopausal women were randomly assigned to one of four experimental groups: (1) 5 mg of alendronate daily plus progressive jumping exercise, (2) 5 mg alendronate, (3) placebo plus progressive jumping exercise, or (4) placebo. The primary endpoint was 12-month change in bone mass and geometry (measured with dual-energy X-ray absorptiometry and peripheral computed tomography at several axial and limb sites) and physical performance; the secondary endpoint was change in biochemical markers of bone turnover. The jumping exercise was conducted an average 1.6 +/- 0.9 (mean +/- SD) times a week. Alendronate daily was effective in increasing bone mass at the lumbar spine (alendronate vs placebo 3.5%; 95% CI, 2.2-4.9%) and femoral neck (1.3%; 95% CI, 0.2-2.4%) but did not affect other bone sites. Exercise alone had no effect on bone mass at the lumbar spine or femoral neck; it had neither an additive nor an interactive effect with alendronate at these bone sites. However, at the distal tibia the mean increase of 3.6% (0.3-7.1%) in the section modulus (that is, bone strength) and 3.7% (0.1-7.3%) increase in the ratio of cortical bone to total bone area were statistically significant in the exercise group compared to the nonexercise group, indicating exercise-induced thickening of the bone cortex. Bone turnover was reduced in alendronate groups only. Alendronate had no effect on physical performance while the jumping exercise improved leg extensor power, dynamic balance, and cardiorespiratory fitness. As conclusion Alendronate is effective in increasing bone mass at the lumbar spine and femoral neck, while exercise is effective in increasing the mechanical properties of bone at some of the most loaded bone sites, as well as improving the participants' muscular performance and dynamic balance. Together alendronate and exercise may effectively decrease the risk of osteoporotic fractures.

Relationship between high-density lipoprotein paraoxonase gene M/L55 polymorphism and carotid atherosclerosis differs in smoking and nonsmoking men.

The enzyme paraoxonase (PON) can eliminate lipid peroxides and is believed to protect against low-density lipoprotein oxidation. A common polymorphism in the PON gene (PON1) causes an amino acid substitution of methionine (M) for leucine (L) at position 55 in the protein, which changes the activity of PON and can affect the risk of atherosclerosis. Because smoking is associated with increased lipid peroxidation, we studied the relationship between PON M/L55 polymorphism and the carotid artery intima-media thickness (IMT) in smokers or previous smokers (n = 112) and nonsmokers (n = 87). IMT was measured at 3 standardized segments by B-mode ultrasonography, and the overall mean IMT value of 199 randomly selected men (mean age 54.2 +/- 3.0 years) was calculated. Subjects with IMT > 1.7 mm in at least 1 standard site were considered to have carotid artery atherosclerotic disease (CAAD). For analysis, L55 homozygotes were compared with the M55 allele carriers. Nonsmoking L55 homozygotes had an 8.9% (95% confidence interval [CI], 1.6 to 16.8) higher overall mean IMT than M55 allele carriers. In smokers, however, the M55 allele carriers tended to have higher overall mean IMT values than L55 homozygotes. There was also a statistically significant interaction between M/L55 genotype and smoking status on CAAD (P =.009) by logistic regression analysis. Among nonsmokers, the L55 homozygotes had an odds ratio of 4.22 (95% CI, 1.06 to 16.8) for CAAD compared with nonsmoking M55 allele carriers. Contrary to nonsmokers, the smoking M55 allele carriers had an odds ratio of 2.22 (95% CI, 0.82 to 6.01) for CAAD when the L55/L55 genotype of smokers was a reference group. These data suggest that in nonsmoking men, a PON L55/L55 genotype may represent a genetic risk factor for CAAD. The reverse effect in smokers implies that the ability of PON to protect against CAAD is influenced by cigarette smoking. The efficiency of this inhibition probably depends on the PON M/L55 genotype.

Reduced oxidized low-density lipoprotein after weight reduction in obese premenopausal women.

BACKGROUND: Several studies support the hypothesis that oxidation of low-density lipoprotein (LDL) promotes atherogenesis. Obesity is one of the risk factors of atherosclerosis, but it is not known whether obesity is related to LDL oxidation. OBJECTIVE AND DESIGN: We investigated the effect of weight reduction and subsequent weight maintenance program on LDL oxidation in 77 obese premenopausal women (BMI 29-46 kg/m(2)). Another group of seven obese women served as a control group. Oxidized LDL was measured as baseline concentration of conjugated dienes in LDL lipids (ox-LDL). The weight reduction was performed in 12 weeks, using a very-low-energy diet. RESULTS: The mean weight loss was 13 kg (92 vs 79 kg). During weight reduction, the concentration of LDL cholesterol decreased by 11%, the concentration of ox-LDL decreased by 40%, and the ratio of ox-LDL to LDL by 33%. The concentration of LDL antioxidant capacity (LDL-TRAP) decreased by 8%, but the decrease was caused by the decrease in LDL. The concentration of LDL, ox-LDL or LDL-TRAP did not change in the control group. The weight reduction correlated with the decrease of ox-LDL. During the subsequent 9 month weight maintenance programme, the concentrations of serum LDL (10%), ox-LDL (11%), LDL-TRAP (29%), and the ratio of LDL-TRAP to LDL (21%) decreased. CONCLUSION: This study strengthens the evidence that the risk of atherogenesis is influenced favourably by weight reduction in obese women. This risk reduction is associated with a reduced oxidation of LDL.

Apolipoprotein E polymorphism and carotid artery intima-media thickness in a random sample of middle-aged men.

Genetic polymorphism of apolipoprotein E (apoE) is an important factor in the development of coronary artery disease but the results concerning apoE genotype and carotid artery atherosclerosis remain controversial. We investigated a random sample of 189 Finnish middle aged men (mean age 54 years, range 50-59) to assess the role of apoE in the process of carotid atherosclerosis. Intima-media thickness (IMT) of the carotid artery wall was measured at three standardised segments (common carotid artery, bifurcation and internal carotid artery) by B-mode ultrasonography. Overall mean IMT value was also calculated. The carriers of E3/2 (n=20) genotype had significantly lower (P<0.01) total cholesterol and LDL cholesterol concentrations than carriers of E3/3 genotype (n=109) or the E4 allele (n=60). ApoE polymorphism was associated with common carotid artery IMT (P=0.034) when adjusted for age and body-mass index (model 1). The carriers of E3/2 had on average 9% (95% CI 0.8-16%, P=0.028) lower common carotid IMT values than the carriers of E3/3. After further adjustment with LDL and HDL cholesterol, systolic blood pressure, lipoprotein (a), apolipoprotein B and pack-years of smoking (model 2) the association was not statistically significant. The overall mean IMT varied significantly with apoE genotype (P=0.03 for model 1 and P=0.07 for model 2), and it was also lowest in the carriers of E3/2 genotype. This suggests that apoE E3/2 genotype is a protective factor in the development of carotid artery atherosclerosis in randomly selected middle-aged men. The favourable effect might be mediated at least partly by the lowering effect of E3/2 genotype on serum cholesterol.

A controlled trial of the health benefits of regular walking on a golf course.

PURPOSE: To study the effects of regular walking during a golf game on various health and fitness indicators in middle-aged men. METHODS: Study subjects were 55 healthy male golfers aged 48 to 64 years who had been sedentary during the 7 months before the study, and 55 age-matched, similarly sedentary controls. During the 20-week study, those in the intervention group were encouraged to play golf two to three times a week; the controls were not. Measurements of body composition, cardiorespiratory performance, motor and musculoskeletal fitness, blood pressure, and serum lipid, glucose, and insulin levels were obtained at baseline and after the 20-week study. RESULTS: Walking during a golf game was a practical and safe form of physical activity with high adherence. It significantly increased aerobic performance and trunk muscle endurance, with a net difference (pretraining to posttraining change between the golfers and controls) of 36 seconds (95% confidence interval [CI]: 19 to 53 seconds, P < 0.001) for treadmill walking time and 13 seconds (95% CI: 2 to 24 seconds, P = 0.02) for static back extension. In addition, regular walking favorably affected body composition, including reductions in weight of 1.4 kg (95% CI: 0.6 to 2.1 kg, P < 0.001), in waist circumference of 2.2 cm (95% CI: 1.0 to 3.3 cm, P < 0.001), and in abdominal skin fold thickness of 2.2 cm (95% CI: 0.9 to 3.4 cm, P = 0.001). Golfers also had significantly greater increases in serum high-density lipoprotein (HDL) cholesterol levels and in the ratio of HDL cholesterol to total cholesterol. CONCLUSIONS: Regular walking had many positive effects on the health and fitness of sedentary middle-aged men. Walking during a golf game is characterized by high adherence and low risk of injury and is therefore a good form of health-enhancing physical activity.

Effects of walking training on weight maintenance after a very-low-energy diet in premenopausal obese women: a randomized controlled trial.

BACKGROUND: Maintenance of weight loss is a core problem in the treatment of obesity. Physical activity may improve maintenance and metabolic risk factors associated with obesity. HYPOTHESES: (1) A walking training program of moderate intensity, started after weight reduction by a very-low-energy diet, improves maintenance of weight loss and obesity-related metabolic disorders; and (2) the effect of the training program is related to the prescribed amount of physical activity, ie, a higher amount (energy expenditure) leads to more favorable results. METHODS: The participants were premenopausal women with a mean body mass index of 34.0 kg/m(2). Eighty-two participants were randomized to this study; 74 participated in the follow-up assessment. A 12-week weight reduction by mostly a very-low-energy diet was followed by a 40-week maintenance program randomized in 3 groups: a control group with no increase in habitual exercise and with counseling on diet and relapse prevention; a walk-1 group, with a walking program targeted to expend 4.2 MJ/wk and diet counseling; and a walk-2 group, with a walking program of 8. 4 MJ/wk and diet counseling. Random permuted blocks within strata were used, with weight loss (in 3 classes) as the stratifying factor. After the intervention, the subjects were followed up for 2 years. MAIN OUTCOME MEASURES: Primary outcomes were body weight, fat mass, and waist circumference at the 2-year follow-up. Secondary outcomes were the levels of serum lipoproteins and lipids, plasma glucose, insulin, and blood pressure. RESULTS: The mean weight loss after weight reduction was 13.1 kg. The main outcome variables remained stable during the maintenance program, but increased during the follow-up period. Compared with the end of weight reduction, weight regain at the 2-year follow-up was 3.5 kg less (95% confidence interval, 0.2-6.8) and waist circumference regain 3.8 cm less (95% confidence interval, 0.3-7.3) in the walk-1 group vs controls. The secondary outcomes showed a partial relapse during the maintenance program, and a further regain during the follow-up period. CONCLUSIONS: Inclusion of a walking program of moderate training regimen into a weight maintenance program improved maintenance of losses in weight and waist circumference.

Relationship of angiotensin-converting enzyme gene polymorphism to carotid wall thickness in middle-aged men.

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. The D allele has been suggested to be a potent risk factor for coronary artery disease; however, the effect of the ACE gene on carotid atherosclerosis remains controversial. We therefore studied the relationship between the ACE gene I/D polymorphism and carotid artery intima-media thickness (IMT). A random sample of 300 men aged 50-59 years living in southern Finland were selected, and 233 agreed to participate (74%). Data were collected in 219 subjects. Quantitative B-mode ultrasonography was used to measure the maximum near and far wall IMT of right and left common, bifurcation, and internal carotid artery. The mean maximum IMT (overall mean) was calculated as the mean of 12 maximum IMTs at 12 standard sites. Patients with an IMT higher than 1.7 mm in at least one of 12 standard sites were assumed to have carotid atherosclerosis. The I/D polymorphism was determined by polymerase chain reaction. Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primer and the inclusion of 5% dimethylsulfoxide. No significant differences were found in carotid wall thickness between the three genotypes; the overall mean IMT were 1.18 +/- 0.30, 1.22 +/- 0.24, and 1.08 +/- 0.40 mm in genotypes of II, ID, and DD, respectively. Similarly, the ACE genotypes and allele frequencies did not differ significantly between the subjects with and those without carotid atherosclerosis. There was no association in the subgroups among only nonsmoking subjects or subjects without chronic medication. The present data indicate that the I/D polymorphism of the ACE gene is not related to carotid IMT and is unlikely to play a major role in carotid atherosclerosis.

Additive effects of the mutations in the beta3-adrenergic receptor and uncoupling protein-1 genes on weight loss and weight maintenance in Finnish women.

This study examined whether the Trp64Arg mutation in the beta3-adrenergic receptor (beta3AR) and the A-->G mutation in the uncoupling protein-1 (UCP-1) genes have associations with weight loss and subsequent weight maintenance. Seventy-seven obese (body mass index range, 29-46 kg/m2), clinically healthy, premenopausal women were studied. A 12-wk weight reduction by very low calorie diet (VLCD) was followed by a 40-wk weight maintenance phase. The subjects were divided into four groups according to their beta3AR and UCP-1 genotype: no mutation (control; n=37), only Trp64Arg mutation in the beta3AR gene (n=12), only A-->G mutation in the UCP-1 gene (n=23), and both mutations (n=5). Subjects with both mutations had a lower weight reduction during VLCD than the controls [-10.5+/-0.6 (+/-SEM) vs. -14.0+/-0.5 kg; P=0.051, by ANOVA]. During the maintenance phase, weight in subjects with both mutations increased by 5.8+/-1.5 kg, but remained unchanged in the controls (-0.5+/-0.8 kg; P=0.041). The changes in weight in subjects with only one of the mutation were close to the results in the controls. Resting energy expenditure, adjusted for fat mass, fat-free mass, and maximal aerobic power, did not change differently between the groups throughout the study. The results suggest that a combination of the Trp64Arg mutation in the beta3AR and the A-->G mutation in the UCP-1 genes may be associated with faster weight gain after a VLCD.

Effects of walking training on health-related fitness in healthy middle-aged adults--a randomized controlled study.

The effects of walking training on VO2max, serum lipoproteins and plasma fibrinogen were studied in 119 healthy middle-aged persons. Training prescription was 65-75% of VO2max, 50 min/session, four times a week for 15 weeks. The net difference (between pre-posttraining changes in the walking and control group) was statistically significant for VO2max (0.14 l .min-1, 95% CI 0.04, 0.23), total cholesterol (-0.20 mmol.l-1, CI -0.34, -0.06), LDL cholesterol (-0.17 mmol.l-1, CI -0.29, -0.05), ratio of HDL cholesterol to total cholesterol (0.014, CI 0.005, 0.023), and triglycerides (-0.15 mmol.l-1, CI -0.26, -0.04). No statistically significant changes occurred in fibrinogen. The findings indicate that walking training of moderate intensity resulted in a modest increase in VO2max and minor but consistently favorable changes in serum lipoproteins.

Vitamin D receptor alleles and bone's response to physical activity.

The objective of this prospective controlled study was to determine whether the osteogenic response of bone to mechanical loading is dependent on the vitamin D receptor (VDR) polymorphism. Thirty-five healthy premenopausal women took part in a progressive, high-impact exercise three times a week for a period of 18 months and 45 women served as nonexercising controls. The trainees were divided into three groups: bb (n = 12, 34%); Bb (n = 16, 46%); BB (n = 7, 20%) according to polymorphism at the gene encoding the VDR (BB representing subjects without the restriction enzyme BsmI sites on the two VDR gene alleles). Bone mineral content (BMC) and areal bone mineral density (BMD) were measured at the lumber spine, proximal femur, knee, calcaneus, and dominant distal radius before the beginning of the exercise regimen and at 12 and 18 months of training using dual-energy x-ray absorptiometry (DXA). As an indicator of the total osteogenic effect of the training, SigmaBMC was derived by summing up the BMC values of the loaded sites (i.e., the lower limb sites and the lumbar spine). The mean SigmaBMC increased 2.0% in the bb group, 3.0% in the Bb group, and 2.8% in the BB group (P = 0.184 for the intergroup difference), but only 0. 8% in the controls (exercisers versus controls, P < 0.001). Individuals with the BB genotype of the VDR gene, subjects with whom the BMC can be lower than normal and whose bones can be less responsive to pharmacological therapies than bones of the other individuals, seem to have as good osteogenic response to mechanical loading as subjects with other VDR genotypes. Thus, irrespective of the VDR genotype, physical activity seems to be beneficial for bones of premenopausal women.