The protective effect of melatonin on smoke‐induced vascular injury in rats and humans: a randomized controlled trial

Smoking is one of the most harmful lifestyles in the world. Very few studies have investigated the effects of melatonin in smoke‐induced vascular injury. This study was designed to investigate whether melatonin could protect rats and humans from smoke‐induced vascular injury. 32 male rats and a double‐blind randomized controlled trial (RCT) containing 63 participants formed the subjects of this study. In rats, 10 mg/kg of melatonin was intraperitoneally injected. Blood samples and abdominal artery were harvested two weeks later. Melatonin decreased the expression of platelet endothelial cell adhesion molecule‐1 (CD31), intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and endothelin‐1 (ET‐1) compared with the smoke exposed group (P < 0.05), whereas endothelial nitric oxide synthase (eNOS), nuclear erythroid 2‐related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO‐1), catalytic glutamate cysteine ligase (GCLC) and heme oxygenase‐1 (HO‐1) recovered markedly (P < 0.05). In humans, 3 mg/day of melatonin was taken orally by the participants. Blood samples were drawn at baseline and after two weeks of treatment. Compared with the oral placebo group, melatonin decreased the concentration of fibrinogen (Fbg) (P = 0.04) and free fatty acids (FFA) (P = 0.04) in smokers, along with the decreased expression of ICAM‐1, VCAM‐1 and ET‐1 (P = 0.004, P = 0.001, P < 0.0001, respectively). In contrast, Nrf2 and HO‐1 expression were markedly increased (P = 0.0001, P = 0.0049, respectively) after smokers took melatonin orally. In summary, our present data suggest that melatonin could ameliorate smoke‐induced vascular injury.     

The effect of hormone replacement therapy on cardiovascular risk factors in type 2 diabetes: a randomized controlled trial

BACKGROUND: Postmenopausal women with diabetes are at high risk for cardiovascular disease, compared with their nondiabetic counterparts. Combined continuous hormone replacement therapy (HRT) is associated with improvements in serum lipoprotein levels in nondiabetic women; however, the effect in women with diabetes has not been determined. We evaluated the effect of combined continuous HRT on lipoprotein and coagulation factor concentrations and glycemic control in postmenopausal women with type 2 diabetes mellitus. METHODS: In a randomized controlled crossover study, 61 subjects received combined continuous HRT or placebo. Each treatment phase was of 6 months' duration, with an 8-week washout phase between treatment phases. RESULTS: Total cholesterol concentration decreased by 7% (95% confidence interval [CI], 4%-11%) during HRT. For low-density lipoprotein concentration, the mean decrease with HRT was 12% (95% CI, 6%-17%). Apolipoprotein B levels decreased in keeping with the reduction in low-density lipoprotein cholesterol concentrations. There were no significant changes in concentrations of high-density lipoprotein, its subfractions, or triglycerides. Lipoprotein(a) and fibrinogen concentrations were reduced by 21% (95% CI, 10%-31%) and 8% (95% CI, 2%-13%), respectively, with HRT. Fructosamine concentrations declined by 5% (95% CI, 2%-9%) during HRT. CONCLUSIONS: In postmenopausal women with type 2 diabetes mellitus, combined continuous HRT has beneficial effects on lipoprotein concentrations and improves some markers of coagulation and glycemic control.     

Effects of intense exercise and moderate caloric restriction on cardiovascular risk factors and inflammation

Background

Obesity is associated with insulin resistance, inflammation, metabolic dysfunction, and atherosclerosis. This study investigates the effects of weight loss, intense exercise, and moderate caloric restriction on insulin resistance, lipids, inflammatory biomarkers, carotid artery distensibility index (CaDI), and carotid intima media thickness (CIMT).

Methods

Seventeen sedentary morbidly obese contestants in the “Biggest Loser” television program completed the 7-month intense-exercise and moderate-restricting calories program; 3 were excluded due to lack of follow-up CIMT. Serum insulin level, glucose, lipid profile, high-sensitivity C-reactive protein (CRP), hemoglobin A1c (HbA1c), resistin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor receptor-II (TNFRII), lipoprotein a (Lp[a]), sex hormone binding globulin (SHBG), blood pressure, body fat, weight, CaDI, and CIMT were measured at baseline and 7-month follow-up. CIMT was measured 5-10 mm below the common carotid bifurcation during mid-diastolic phase. CaDI was defined as: (End-systole – End-diastole common-carotid cross-sectional area)/(End-diastole common-carotid cross-sectional-area × systemic pulse pressure) × 1000. Insulin resistance was calculated by homeostatic model assessment (HOMA) index.

Results

At 7-month follow-up, major reductions in weight (−39%), body fat (−66%), serum insulin level (−52%), glucose (−21%), high-sensitivity CRP (−81%), HbA1c (−11%), PAI-1 (−49%), TNFRII (−12%), and CIMT (−25%), and increases in CaDI (132%), resistin (344%), adiponectin (94%), Lp(a) (73%), and SHBG (94%) were observed. The improvement in CaDI was positively correlated with increases in adiponectin, Lp(a), SBHG, and resistin (r² = 0.86, P = .009), but inversely with PAI-1, TNFRII, CRP, and IR (r² = −0.64, P = .01). Strong inverse correlation was noted between decreases in CIMT and increases in CaDI (r² = 0.65, P = .001).

Conclusion

In morbidly obese individuals, intense exercise with moderate caloric restriction over 7 months is associated with a dramatic improvement in carotid vascular function and atherosclerosis risk factors, as well as a reduction in inflammatory biomarkers, lipids, insulin resistance, and CIMT.     

Transgenerational effects of caloric restriction on appetite: a meta‐analysis

Maternal undernutrition can result in significant alterations to the post‐natal offspring phenotype, including body size and behaviour. For example, maternal food restriction has been implicated in offspring hyperphagia, potentially causing increased weight gain and fat accumulation. This could result in obesity and other adverse long‐term health effects in offspring. We investigated the link between maternal caloric restriction during gestation and offspring appetite by conducting the first meta‐analysis on this topic using experimental data from mammalian laboratory models (i.e. rats and mice). We collected 89 effect sizes from 35 studies, together with relevant moderators. Our analysis revealed weak and statistically non‐significant overall effect on offspring's appetite. However, we found that lower protein content of restricted diets is associated with higher food intake in female offspring. Importantly, we show that a main source of variation among studies arises from whether, and how, food intake was adjusted for body mass. This probably explains many of the contradictory results in the field. Based on our results, we recommend using allometric scaling of food intake to body mass in future studies.     

Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET)

Abstract. Adamsson V, Reumark A, Fredriksson I‐B, Hammarström E, Vessby B, Johansson G, Risérus U (Uppsala University, Uppsala; Lantmännen R&D, Stockholm; Bollnäs Heart Clinic, Mitt Hjärta, Bollnäs; Halmstad University, Halmstad, Sweden). Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET). J Intern Med 2011; 269 : 150–159. Objective. The aim of this study was to investigate the effects of a healthy Nordic diet (ND) on cardiovascular risk factors. Design and subjects. In a randomized controlled trial (NORDIET) conducted in Sweden, 88 mildly hypercholesterolaemic subjects were randomly assigned to an ad libitum ND or control diet (subjects’ usual Western diet) for 6 weeks. Participants in the ND group were provided with all meals and foods. Primary outcome measurements were low‐density lipoprotein (LDL) cholesterol, and secondary outcomes were blood pressure (BP) and insulin sensitivity (fasting insulin and homeostatic model assessment‐insulin resistance). The ND was rich in high‐fibre plant foods, fruits, berries, vegetables, whole grains, rapeseed oil, nuts, fish and low‐fat milk products, but low in salt, added sugars and saturated fats. Results. The ND contained 27%, 52%, 19% and 2% of energy from fat, carbohydrate, protein and alcohol, respectively. In total, 86 of 88 subjects randomly assigned to diet completed the study. Compared with controls, there was a decrease in plasma cholesterol (?16%, P < 0.001), LDL cholesterol (?21%, P < 0.001), high‐density lipoprotein (HDL) cholesterol (?5%, P < 0.01), LDL/HDL (?14%, P < 0.01) and apolipoprotein (apo)B/apoA1 (?1%, P < 0.05) in the ND group. The ND reduced insulin (?9%, P = 0.01) and systolic BP by ?6.6 ± 13.2 mmHg (?5%, P < 0.05) compared with the control diet. Despite the ad libitum nature of the ND, body weight decreased after 6 weeks in the ND compared with the control group (?4%, P < 0.001). After adjustment for weight change, the significant differences between groups remained for blood lipids, but not for insulin sensitivity or BP. There were no significant differences in diastolic BP or triglyceride or glucose concentrations. Conclusions. A healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinically relevant levels in hypercholesterolaemic subjects.     

Minor effects of green tea catechin supplementation on cardiovascular risk markers in active older people: A randomized controlled trial

Aim: Although previous studies have shown that consumption of green tea catechins (GTC) and walking might prevent development of cardiovascular disease (CVD), the effects of GTC supplementation on CVD risk in active older people are unknown. Methods: A total of 52 older adults (male/female 20/32, mean age 69.1 ± 5.9 years) participating in a pedometer‐based walking program were randomly assigned to a GTC group with an intake of 630.9 mg GTC daily (n = 26) or a control group (n = 26) for 14 weeks. Cardiovascular risk markers were measured before and after this trial. Results: In the GTC group, values of the following markers were significantly reduced (P < 0.05) from the beginning to the end of the trial: waist circumference (from 84.2 ± 8.4 to 82.2 ± 8.5 cm), hip circumference (from 95.1 ± 6.9 to 92.2 ± 6.3 cm), total cholesterol (from 233.0 ± 46.3 to 218.8 ± 42.3 mg/dL), low‐density lipoprotein cholesterol (from 130.4 ± 36.2 to 119.1 ± 33.4 mg/dL) and low‐density lipoprotein cholesterol to high‐density lipoprotein cholesterol ratio (from 2.0 ± 1.7 to 1.7 ± 0.5); only hip circumference (from 95.6 ± 8.1 to 94.1 ± 7.6 cm) was significantly reduced (P < 0.05) in the control group. No significant between‐group differences were found for any parameter measured. Conclusions: Although GTC might reduce cholesterol levels, the present randomized control trial suggests that GTC supplementation in active older participants did not significantly affect cardiovascular risk markers. Future studies should identify more effective combinations of GTC supplementation and physical activity. Geriatr Gerontol Int 2013; 13: 622–629.     

Efficacy of weight loss drugs on obesity and cardiovascular risk factors in obese adolescents: a meta‐analysis of randomized controlled trials

Weight loss drugs have been developed to reduce the comorbidities associated with excess weight. We conducted a meta‐analysis of the efficacy of orlistat and sibutramine on weight, body mass index, waist circumference and cardiovascular risk factors in overweight adolescents. MEDLINE and the Cochrane Library were searched for relevant articles using MESH terms and keywords. Studies were included if they had reported quantitative estimates and standard deviations of the association between each weight loss drug and weight, with information on at least one cardiovascular risk factor. A total of eight trials (three orlistat and five sibutramine) with information on 1391 individuals was included in the present analysis. The mean decrease in weight between the intervention and control groups was 5.25 kg (95% confidence interval: 3.03–7.48) after a minimum follow‐up of 6 months. There was evidence of statistical heterogeneity between the studies (I² = 76%) that was no longer apparent after exclusion of trials of orlistat (mean weight decrease = 5.32 kg; I² = 38%). There was little evidence that treatment was associated with adverse effects on cardiovascular risk factors but this requires verification from future large trials with longer study follow‐up.     

The effects of caloric restriction and controlled physical exercise on hypertension in the elderly

The overweight and sedentary life style are associated with elevated blood pressure values in the elderly patients. The first step in the therapy of arterial hypertension should be hygienic-behavioral measures in order to modify the life style of the patients. The present study evaluates the independent effects of caloric restriction and physical exercise on the blood pressure and on the anti-hypertensive treatment in elderely subjects with mild-moderate hypertension. The number of enrolled patients was 74 in the age range of 61-72 years, showing up in our Geriatric Day Hospital. The results obtained confirm that the non-pharmacological measures represent a valid alternative to the pharmacological treatment of hypertension in the elderly patients, or may be applied in combination with the latter, in order to reduce the doses of pharmaca.     

Interventions to maintain cardiac risk control after discharge from a cardiovascular risk reduction clinic: A randomized controlled trial

Aims

To evaluate the efficacy of two maintenance strategies compared to usual care after discharge from a pharmacist-led cardiovascular risk reduction clinic (CRRC).

Methods

Open-label, randomized-controlled trial of 200 consecutive CRRC patients that met clinic discharge criteria (HbA1c ≤7% (53 mmol/mol); blood pressure ≤140/80 mmHg for those with diabetes and ≤140/90 mmHg for those without diabetes; and an LDL-cholesterol ≤2.59 mmol/l). Participants were randomized to either [1] quarterly group medical visits or [2] quarterly CRRC individual clinic visits, or [3] a usual care control arm with the standard primary care alone first in a 1:1:1 ratio, followed by a 2:2:1 ratio after first 100 patients. Primary outcome measures were time to failure for guideline recommended goals of HbA1c and blood pressure over 12-months.

Results

Of the 200 participants randomized, 89% had diabetes and were similar in other cardiovascular risk factors. After 1-year, the HbA1c failure rate was 0.36 [95% CI, 0.28–0.47] per quarter for the group medical visit arm, 0.24 [95% CI, 0.18–0.33] per quarter for the quarterly CRRC individual arm and, 0.82 [95% CI, 0.69–0.96] per quarter for the usual care control arm, p < 0.001. The rate of failure for blood pressure was 0.31 [95% CI, 0.23–0.41] per quarter for the group medical visit arm, 0.22 [95% CI, 0.16–0.30] per quarter for the CRRC individual arm and, 0.53 [95% CI, 0.40–0.71] per quarter the control arm, p < 0.001.

Conclusion

After discharge from a CRRC program, both individual and group interventions are more effective in maintaining glycemia and blood pressure control for patients with diabetes than usual care after 1-year of follow-up.     

The hepatitis C self‐management programme: a randomized controlled trial

Summary. Chronic hepatitis C (HCV) infection afflicts millions of people worldwide. While antiviral treatments are effective for some patients, many either cannot or choose not to receive antiviral treatment. Education about behavioural changes like alcohol avoidance and symptom management, in contrast, is universally recommended, particularly in HCV‐infected persons from disadvantaged groups where liver risk factors are most prevalent. Self‐management interventions are one option for fostering improved HCV knowledge and health‐related quality of life (HRQOL). One hundred and thirty‐two patients with VA with HCV (mean age of 54.6, 95% men, 41% ethnic minority, 83% unmarried, 72% unemployed/disabled, 48% homeless in last 5 years) were randomized to either a 6‐week self‐management workshop or an information‐only intervention. The weekly 2‐h self‐management sessions were based on cognitive‐behavioural principles and were adapted from an existing self‐management programme that has been efficacious with other chronic diseases. HCV‐specific modules were added. Outcomes including HRQOL, HCV knowledge, self‐efficacy, depression, energy and health distress were measured at baseline and 6 weeks later. Data were analysed using ANOVA. When compared to the information‐only group, participants attending the self‐management workshop improved more on HCV knowledge (P < 0.001), HCV self‐efficacy (P = 0.011), and SF‐36 energy/vitality (P = 0.040). Similar trends were found for SF‐36 physical functioning (P = 0.055) and health distress (P = 0.055). Attending the self‐management programme improved disease knowledge and HRQOL 6 weeks later in this disadvantaged population. The intervention can improve the health of people with hepatitis C, independent of antiviral therapy. Future research will study longer‐term outcomes, effects on antiviral treatment and costs.     

Square-stepping exercise and fall risk factors in older adults: a single-blind, randomized controlled trial

BACKGROUND: Decreased fitness of the lower extremities is a potentially modifiable fall risk factor. This study aimed to compare two exercise programs--square-stepping exercise (SSE), which is a low-cost indoor program, and walking--for improving the fitness of the lower extremities. METHODS: We randomly allocated 68 community-dwelling older adults (age 65-74 years) to either the SSE or walking group (W group). During the 12-week regimen, the SSE group participated in 70-minute exercise sessions conducted twice a week at a local health center, and the W group participated in outdoor supervised walking sessions conducted weekly. The W group was instructed to increase the number of daily steps. Prior to and after the program, we obtained information on 11 physical performance tests for known fall risk factors and 3 self-reported scales. The fall incidence was followed-up for 8 months. RESULTS: At 12 weeks postregimen, significant differences were observed between the two exercise groups with respect to leg power (1 item), balance (2 items), agility (2 items), reaction time (2 items), and a self-reported scale (1 item); the SSE group demonstrated a marked improvement in the above-mentioned items with Group x Time interactions. Significant time effects were observed in the tests involving chair stands, functional reach, and standing up from a lying-down position without Group x Time interactions. During the follow-up period, the fall rates per person-year in the SSE and W groups were 23.4% and 33.3%, respectively (p =.31). CONCLUSION: Although further studies are required, SSE is apparently more effective than walking in reducing fall risk factors, and it appears that it may be recommended as a health promotion exercise in older adults.