Effect of smoking cessation on cardiac troponin I concentrations.

Chronic elevation of cardiac troponin I (cTnI) is associated with heart failure and cardiovascular death. Paradoxically, observational studies have indicated that current smokers have lower cTnI concentrations than non-smokers. We examined determinants of cTnI in smokers and the effect of smoking cessation on cTnI. Overweight or obese smokers received motivational support and varenicline to aid cessation and dietary advice to limit weight gain. Quitters were defined according to the Russell standard (≤5 cigarettes after the quit date) and validated with expired breath CO <10 ppm. Of the total 122 participants, 108 completed assessments at 12 weeks and 78 were classified as quitters versus 30 who continued smoking. cTnI was measured with a high-sensitivity assay with a limit of detection of 1.2 ng/L (Abbott Diagnostics), and concentrations (log-transformed) were compared between quitters and continuing smokers. cTnI concentrations were significantly higher in men than women and correlated with age, but not with number of cigarettes/day. Quitters had median baseline and 12-week levels of 1.4 ng/L (interquartile range [IQR] 1.2-2.5) and 1.4 ng/L (IQR 1.2-2.4), respectively, while nonquitters had baseline and 12-week levels of 1.5 ng/L (IQR 1.2-2.9) and 1.8 ng/L (IQR 1.3-3.4), respectively. The change in cTnI concentrations from baseline to 12 weeks did not differ between quitters and continuous smokers (p = .7). The results suggest that smoking cessation does not affect levels of cTnI, a marker of chronic subclinical myocardial injury, in contrast to prior observational data suggesting that tobacco smoking is associated with lower cTn concentrations.

A novel intragastric balloon for treatment of obesity and type 2 diabetes. A two-center pilot trial.

BACKGROUND AND AIMS: Obesity with type-2 diabetes is a global challenge. Lifestyle interventions have limited effect for most patients. Bariatric surgery is highly effective, but resource-demanding, invasive and associated with serious complications. Recently, a new intragastric balloon was introduced, not requiring endoscopy for placement or removal (Elipse™, Allurion Inc., Natick, MA). The balloon is swallowed in a capsule and filled with water once in the stomach. The balloon self-deflates after 4 months and is naturally excreted. The present trial investigated balloon feasibility, safety and efficacy in patients with obesity and type-2 diabetes. PATIENTS AND METHODS: We treated 19 patients, with type-2 diabetes and body mass index (BMI) of 30.0-39.9 kg/m2 at two Norwegian centers with the Elipse balloon. Patient follow-up during balloon treatment mimicked real-world clinical practice, including dietary plan and outpatient visits. The primary efficacy endpoints were total body weight loss (TBWL) and HbA1c at weeks 16 and 52. RESULTS: All patients underwent balloon insertion uneventfully as out-patients. Mean TBWL and HbA1c reduction after 16 and 52 weeks of balloon insertion was 3.9% (95%CI 2.1-5.7) and 0.8% (95%CI 1.9-3.5); and 7 (95%CI 4-10), and 1 (95%CI -6 to 9) mmol/mol, respectively. Adverse events occurred in two patients (10.5%): one developed gastric outlet obstruction, managed by endoscopic balloon removal; the other excessive vomiting and dehydration, managed conservatively. CONCLUSIONS: This first Scandinavian real-world clinical trial with a new minimally invasive intragastric balloon system demonstrated good feasibility, but did not confirm expected efficacy for weight loss and diabetes control.

Diet, eating behaviour and weight gain in men and women with overweight/obesity receiving varenicline for smoking cessation.

Because trying to quit smoking and not gain weight requires changes in two major behaviours simultaneously we explored eating behaviour in smokers with overweight/obesity making a quit attempt using guideline-based treatment. Participants were randomized to a carbohydrate-reduced or fat-reduced diet. The Three Factor Eating Questionnaire and Binge Eating Scale were completed by 48 of 64 participants in the low-carbohydrate and 47 of 58 in the fat-reduced group at randomization, after 6 and 14 weeks. At 6 weeks, no between group differences were seen in eating behaviour scores thus, we combined the sample for further analyses. In the combined sample, restraint increased (3.94 [95% CI 3.05, 4.83]), disinhibition (uncontrolled eating) decreased (-0.86 [95% CI-1.31, -0.41]) and binge eating decreased (-1.95 [95% CI -2.83, -1.06]), while hunger scores did not change (-0.43 [95% CI -0.89, 0.03]) after 14 weeks. In a general linear model, increase in dietary restraint (P = .012) and decrease in binge eating (P = .040) were associated with lower weight gain (model R2 adj = .147). In a smoking cessation program, dietary support regardless of diet was associated with increased dietary restraint and reduced binge eating. Because smoking cessation causes weight gain these results indicate that dietary support leads to eating behaviour changes that may prevent weight gain.

BMI modifies the effect of dietary fat on atherogenic lipids: a randomized clinical trial.

BACKGROUND: SFA intake increases LDL cholesterol whereas PUFA intake lowers it. Whether the lipid response to dietary fat differs between normal-weight and obese persons is of relevance to dietary recommendations for obese populations. OBJECTIVES: We compared the effect of substituting unsaturated fat for saturated fat on LDL cholesterol and apoB concentrations in normal-weight (BMI ≤ 25 kg/m2) and obese (BMI: 30-45) subjects with elevated LDL cholesterol. METHODS: We randomly assigned 83 men and women (aged 21-70 y) stratified by BMI (normal: n = 44; obese: n = 39) and elevated LDL cholesterol (mean ± SD, normal weight 4.6 ± 0.9 mmol/L; obese 4.4 ± 0.8 mmol/L) to either a PUFA diet enriched with oil-based margarine ( n = 42) or an SFA diet enriched with butter (n = 41) for 6 wk. RESULTS: Seven-day dietary records showed differences of ∼9 energy percent (E%) in SFA and ∼4 E% in PUFA between the SFA and PUFA groups. In the total study population, the PUFA diet compared with the SFA diet lowered LDL cholesterol (-0.31 mmol/L; 95% CI: -0.47, -0.15 mmol/L, compared with 0.32 mmol/L; 95% CI: 0.18, 0.47 mmol/L; P < 0.001) and apoB (-0.08 g/L; 95% CI: -0.11, -0.05 g/L, compared with 0.07 g/L; 95% CI: 0.03, 0.10 g/L; P < 0.001). Tests of the BMI × diet interaction were significant for total cholesterol, LDL cholesterol, and apoB ( P values ≤ 0.009). In normal-weight compared with obese participants post-hoc comparisons found that the respective changes in LDL cholesterol were 9.7% (95% CI: 5.3%, 14.2%) compared with 5.3% (95% CI: -0.7%, 11.2%), P = 0.206, in the SFA group, and -10.4% (95% CI: -15.2%, -5.7%) compared with -2.3% (95% CI: -7.4%, 2.8%), P = 0.020, in the PUFA group. ApoB changes were 7.5% (95% CI: 3.5%, 11.4%) compared with 3.0% (95% CI: -1.7%, 7.7%), P = 0.140, in the SFA group, and -8.9% (95% CI: -12.6%, -5.2%) compared with -3.8% (95% CI: -6.3%, -1.2%), P = 0.021, in the PUFA group. Responses to dietary fat were not associated with changes in polyprotein convertase subtisilin/kexin type 9 concentrations. CONCLUSIONS: BMI modifies the effect of PUFAs compared with SFAs, with smaller improvements in atherogenic lipid concentrations in obese than in normal-weight individuals, possibly supporting adjustment of dietary recommendations according to BMI. This trial was registered with www.clinicaltrials.gov as NCT02589769.

Associations of Circulating PYY3-36 Concentrations with Metabolic Syndrome in Extremely Obese Subjects.

BACKGROUND: The gut hormone peptide YY3-36 (PYY3-36) plays major roles in regulation of appetite and energy metabolism, mediates beneficial effects of bariatric surgery, and may be a potential weight-reducing and glucose-modulating therapy. Obesity may influence the metabolic expression of circulating PYY3-36 and metabolic markers. We studied the relationship of PYY3-36 concentrations with metabolic syndrome (MetSyn) components, lipids, insulin resistance, and inflammatory biomarkers in subjects with extreme obesity. METHODS: We measured MetSyn components and PYY3-36, lipids, hormones, homeostasis model assessment (HOMA) index, and inflammatory biomarkers in consecutively referred patients (180 women and 111 men) aged 18-78 years with body mass index (BMI) ≥40 kg/m2. Associations of PYY3-36 to components, insulin resistance, and biomarkers were examined with partial correlations and linear regression. RESULTS: PYY3-36 concentrations were not related to MetSyn components, HOMA index, or to inflammatory biomarker or leptin concentrations. PYY3-36 concentrations correlated with systolic blood pressure (r = 0.21; P < 0.0001) after adjustment for age and gender. In linear regression analysis, PYY3-36 concentrations were associated with systolic blood pressure after adjustment for age, gender, and central obesity in the entire sample (Beta 0.21; 95% CI 0.09-0.34) as well as in subjects not taking blood pressure-lowering medication (Beta 0.19; 95% CI 0.04-0.36). These associations were not statistically significant in the small subset of participants (22%) with type 2 diabetes. CONCLUSIONS: In extremely obese patients, fasting PYY3-36 concentrations were linked to systolic blood pressure, but not to other components of MetSyn, suggesting divergence between pathways of blood pressure and glucose/body weight regulation. However, this finding will need to be further investigated.

Characteristics of Metabolic Syndrome in Morbidly Obese Subjects.

BACKGROUND: Metabolic syndrome (MetSyn) magnifies risks of cardiovascular disease (CVD) and type 2 diabetes, but its expression varies within the obese population. We examined body mass index (BMI), metabolic traits, and fat distribution in morbidly obese individuals. METHODS: Lipids and inflammatory, oxidative stress and hepatic biomarkers in 346 women and 203 men (BMI ≥35 kg/m2 and co-morbidity or ≥40 kg/m2) were stratified by MetSyn components (1-5, excluding diabetes). Age- and smoking-adjusted partial correlations were calculated. Dual-energy X-ray absorptiometry was measured in 206 participants. RESULTS: Apolipoprotein B, ferritin, uric acid, and alanine aminotransferase (ALT) concentrations worsened with increasing MetSyn components (P ≤ 0.0001), while BMI and LDL-cholesterol showed no association. BMI correlated inversely with triglycerides (r = -0.16, P = 0.03) and positively with HDL-cholesterol in men (r = 0.16, P = 0.02), but not in women. BMI correlated with C-reactive protein (CRP) (r = 0.32, P < 0.0001; r = 0.24, P < 0.0001 in men and women, respectively) and white blood cell count (r = 0.24, P = 0.001 in men; r = 0.15, P = 0.008 in women). Truncal fat percentage correlated to CRP (r = 0.31, P = 0.03; r = 0.20, P = 0.02 in men and women, respectively). In women, number of MetSyn components was inversely related to truncal and peripheral fat (r = -0.20, P = 0.02; r = -0.42, P < 0.0001, respectively) as was ALT (r = -0.21, P = 0.009; r = -0.38, P < 0.0001, respectively) and triglycerides with peripheral fat (r = -0.38, P < 0.0001), while HDL cholesterol was positively associated with truncal and peripheral fat (r = 0.26; P = 0.001). CONCLUSIONS: BMI and fat distribution showed expected associations to inflammation biomarkers, but paradoxical relations between fat indices, and MetSyn components and biomarkers were seen. This suggests a need for better markers of CVD risk in morbid obesity.

Low Carbohydrate and Moderately Fat-Reduced Diets Similarly Affected Early Weight Gain in Varenicline-Treated Overweight or Obese Smokers.

INTRODUCTION: Weight gain is common when stopping smoking. This study compared the effect of advising smokers to follow a diet low in carbohydrates versus a usual fat-reduced diet on weight gain and nicotine withdrawal. METHODS: In a randomized clinical trial, 122 men and women smokers with body mass index 25-40kg/m(2) were assigned low-carbohydrate versus moderately fat-reduced diets. Within a week thereafter all participants started treatment with a 12-week course of varenicline 10 days prior to the target quit date. Brief dietary and motivational counseling was given at all visits. Self-reported abstinence was validated. RESULTS: Protein intake in the low-carbohydrate versus fat-reduced diets was 26.4% of total energy versus 20.0%, fat 38.2% versus 30.1%, and carbohydrates 29.0% versus 41.7% (all P < .001). Mean weight changes for the low-carbohydrate versus fat-reduced groups were -1.2 (SD 2.2) versus -0.5 (SD 2.0) kg, -0.2 (SD 3.3) versus 0.5 (SD 2.6) kg, and 2.2 (SD 4.5) versus 2.1 (SD 3.9) kg at 4, 12, and 24 weeks after the target quit date, respectively (not statistically significant). Smoking abstinence rates did not differ between diets. In the combined groups, point prevalence abstinence rates were 71.0% at 12 weeks and 46.3% at 24 weeks. The Minnesota Nicotine Withdrawal Symptoms score was lower in the fat-reduced group compared with the low-carbohydrate group at weeks 4 and 12. CONCLUSIONS: In overweight or obese smokers using varenicline a low-carbohydrate diet was no better than a fat-reduced diet in reducing weight gain but may result in more severe nicotine withdrawal symptoms. Compared to previous studies, cessation rates with varenicline were not impaired by dietary counseling. IMPLICATIONS: The study implies that a popular low-carbohydrate diet does not result in greater weight loss than a moderately fat-reduced diet in overweight and obese smokers who are attempting to quit smoking with the aid of varenicline. Dietary counseling combined with varenicline treatment did not appear to unfavorably influence quit rates compared to previous studies in smokers not selected for overweight or obesity. Notably, the withdrawal symptoms score was lower in the fat-reduced dietary group than the low-carbohydrate group, suggesting a venue for further study.

Effects of margarine enriched with plant sterol esters from rapeseed and tall oils on markers of endothelial function, inflammation and hemostasis.

BACKGROUND AND AIMS: The sterol profile of rapeseed oil differs from that of tall oil with higher contents of campesterol and brassicasterol. We previously found that margarines providing 2 g/day of sterols from rapeseed or tall oil resulted in similar reductions in LDL cholesterol of 8-9%. The aim of the present study was to investigate whether the consumption of these margarines affected markers of endothelial function, inflammation and hemostasis. METHODS: Blood samples were collected from 58 hypercholesterolemic volunteers who completed a double-blinded, randomized, crossover trial. Subjects consumed each of the two sterol margarines and a control non-sterol margarine for 4 weeks separated by one-week washout periods. All the margarines had the same fatty acid composition. Concentrations of vascular cell adhesion molecule-l (VCAM-1), E-selection, circulating tumor necrosis factor α (TNFα) and plasminogen activator inhibitor-1 (total, tPAI-1; active, PAI-1) were quantified. RESULTS: Rapeseed-sterol margarine reduced E-selection concentrations compared to the control margarine (p = 0.012) while tall-sterol margarine had no effect. The rapeseed-sterol margarine also reduced tPAI-1 (p = 0.008) compared to the tall-sterol margarine. No significant changes were observed in TNFα and VCAM-1. No association was found between LDL reduction and changes in E-selection and tPAI-1. CONCLUSION: Rapeseed-sterol margarine demonstrated favorable effects on vascular risk markers.

The effect of kiwifruit consumption on blood pressure in subjects with moderately elevated blood pressure: a randomized, controlled study.

BACKGROUND AND AIMS: Kiwifruit contains bioactive substances that may lower blood pressure (BP) and improve endothelial function. We examined the effects of adding kiwifruit to the usual diet on 24-h ambulatory BP, office BP and endothelial function. METHODS: In a parallel-groups study, 118 subjects with high normal BP or stage 1 hypertension (systolic BP 130-159 mmHg and/or diastolic BP 85-99 mmHg) were randomized to intake of three kiwifruits (intervention) or one apple (control) a day for 8 weeks. Office and 24-h ambulatory BP was measured along with biomarkers of endothelial function including metabolites of nitric oxide (NO) formation and finger photo-plethysmography. RESULTS: At randomization, mean 24-h ambulatory systolic/diastolic BP was 133 ± 13/82 ± 9 mmHg (n = 106). After 8 weeks, BP was lower in the group assigned to kiwifruit versus apple intake (between group difference, - 3.6 mmHg [95% CI - 6.5 to - 0.7], p = 0.017 and - 1.9 mmHg [95% CI - 3.6 to - 0.3]; p = 0.040, for systolic and diastolic BP, respectively). Changes in office BP and endothelial function did not differ between the groups. CONCLUSIONS: Among men and women with moderately elevated BP, intake of three kiwifruits was associated with lower systolic and diastolic 24-h BP compared with one apple a day. The effect may be regulated by mechanisms other than improvement of endothelial function.

Niccine®, a nicotine vaccine, for relapse prevention: a phase II, randomized, placebo-controlled, multicenter clinical trial.

INTRODUCTION: A nicotine vaccine could prevent relapse to smoking by hindering blood nicotine from reaching the brain. Niccine® is a nicotine hapten tetanus-toxoid conjugate vaccine. The present study evaluated the clinical efficacy of Niccine for tobacco smoking relapse prevention. METHODS: Cigarette smokers (n = 355) aged 25-50 years were enrolled in a randomized, double-blind, parallel group 1-year trial encompassing 16 visits and 16 telephone calls. Niccine 40 µg or placebo was administered on Days 0, 28, 56, 90, 150, and 210. Between Days 56-98, subjects were treated with varenicline to aid cessation, targeted for Day 70. Only individuals abstinent between Days 90-98 (n = 265) were allowed to continue to 1 year (n = 219). Relapse to smoking was defined as >5 cigarettes within 7 days or since the last contact, or smoking on >5 occasions within 7 days or since the last contact. RESULTS: At 1 year, nonrelapse was 43.3% in the Niccine versus 51.1% in the placebo groups (difference = -7.9%; 95% CI = -20.6% to 4.9%). There was no benefit of Niccine on smoking status at 6 or 9 months, exhaled carbon monoxide levels, time to relapse, abstinence, withdrawal symptoms, or smoking reinforcement. Nicotine antibody levels increased (mean = 1.34 µg/ml; SD = 2.84 µg/ml) in the Niccine group, but were not related to relapse. Adverse events except hypersensitivity and compensatory smoking did not differ between groups. CONCLUSIONS: This nicotine vaccine appeared well tolerated but did not influence trajectories of relapse possibly because of insufficient antibody levels or lack of efficacy of the vaccine concept for relapse prevention.

Effect of a low-fat versus a low-gycemic-load diet on inflammatory biomarker and adipokine concentrations.

BACKGROUND: Low-grade inflammation is linked to metabolic syndrome and obesity. We studied the effects of weight loss and dietary composition on serum concentrations of biomarkers of inflammation and adipokines. METHODS: Men and women (n=181) aged 30-65 years with a body mass index (BMI) of 28-40 kg/m(2) (28-35 kg/m(2) for women) and one or more components of metabolic syndrome were randomized to follow one of two hypocaloric diets, a low-fat or low-glycemic-load diet for 3 months. Blood samples were taken pre- and postintervention. Serum concentrations of interleukin-6 (IL-6), tumor necrosis factorα (TNF-α), plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), and adipokines (leptin, resistin, and adiponectin) were analyzed using multiplexed microsphere immunoassays. RESULTS: Weight loss was not different in the low-fat (4.4%±3.8%) and low-glycemic-load (4.9%±3.2%) groups. Concentrations of IL-6, TNF-α, PAI-1, and leptin were significantly reduced in both dietary groups with no between-group differences, whereas MCP-1 and adiponectin concentrations did not change. Subjects with full metabolic syndrome (three or more components; n=109) experienced greater weight loss than subjects (n=72) with one to two components and greater reduction in leptin [7.08 (95% confidence interval 5.19, 8.97) vs. 3.46 (0.91, 6.00) ng/mL; p=0.02] and a tendency to greater reduction in TNF-α (1.00 [0.60, 1.44] vs 0.40 [0.02, 0.78] pg/mL; p=0.05). CONCLUSION: Hypocaloric diets improved inflammatory biomarkers and adipokines independently of dietary composition. The response tended to be greater in subjects with three or more components of metabolic syndrome than their counterparts with one to two components.

Treatment with the PPARgamma agonist rosiglitazone downregulates interleukin-1 receptor antagonist in individuals with metabolic syndrome.

OBJECTIVES: Thiazolidinediones (TZDs) reduce insulin resistance, but also have pleiotropic properties including effects on inflammation. The balance between protective and proatherogenic effects may differ in various patient populations. We studied the effect of rosiglitazone on inflammatory markers in patients with metabolic syndrome (MetSyn). METHODS: In a cross-over randomized controlled trial, 23 subjects with MetSyn were assigned to treatment with rosiglitazone that was uptitrated from 4 mg/day for 6 weeks followed by 8 mg/day for 6 weeks or matching placebo for 12 weeks, and then to the opposite treatment for 12 weeks. Plasma levels of inflammatory and metabolic markers were measured during follow-up. RESULTS: Our main findings were i) compared to placebo, rosiglitazone significantly decreased the plasma levels of the naturally occurring interleukin (IL)1 inhibitor, IL1 receptor antagonist (IL1Ra; P=0.001), potentially reflecting inflammatory effects on the IL1 system; ii) parallel to this, rosiglitazone decreased plasma levels of IL10 (P=0.029) further suggesting inflammatory effects; iii) rosiglitazone decreased uric acid levels (P=0.001), and monocyte chemoattractant protein-1 (P=0.05) and C-reactive protein (P=0.06) tended to be lower after rosiglitazone than placebo, suggesting potential pro- and anti-inflammatory effects simultaneously and iv) in vitro, rosiglitazone enhanced IL1Ra and decreased IL1beta in THP-1 monocytes, illustrating the complex effects of these medications, potentially exhibiting anti-inflammatory effects on the IL1 system in certain tissues or cells at least at certain concentrations. CONCLUSION: Our findings suggest inflammatory effects on the IL1 system during rosiglitazone therapy in MetSyn. However, anti-inflammatory effects were also observed, and the net effect of TZDs in MetSyn should be further investigated.