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Biomedical subjects

S Tonstad

Publications and source records attributed to S Tonstad.

At least 19 recordsLinked to original sources
PubMed2007

Effects of an antiatherogenic diet during pregnancy on markers of maternal and fetal endothelial activation and inflammation: the CARRDIP study.

OBJECTIVE: To study the effect of an antiatherogenic diet on maternal and cord blood concentrations of systemic biomarkers of endothelial cell activation, haemostasis and inflammation. DESIGN: Single blinded randomised controlled clinical trial. SETTING: Obstetric outpatient clinic and maternity unit of a university hospital in Norway. POPULATION: Nonsmoking pregnant women aged 21-38 years carrying a single fetus and with no previous pregnancy-related complications. METHODS: Subjects (n = 290) were randomised to continue their usual diet or to adopt a diet low in saturated fat and cholesterol from gestational week 17-20 to birth. Soluble forms of cellular adhesion molecules, high-sensitivity C-reactive protein (CRP) and haemostatic markers were measured at 17-20 weeks of gestation (baseline) and subsequently up to week 36. All the above, except CRP, were also measured in cord blood. MAIN OUTCOME MEASURES: Concentrations of maternal and fetal biomarkers and maternal CRP. RESULTS: All biomarkers except CRP levels increased significantly during the study period in both the intervention and control groups. None of the maternal or fetal biomarkers were influenced by the intervention (P > 0.05) except for a tendency to lower concentrations of cord blood tissue plasminogen activator antigen in the intervention group compared with the control group, median (interquartile range) 5.4 ng/ml (3.1-7.7) versus 5.8 ng/ml (3.5-11.8), P = 0.05. CONCLUSION: An antiatherogenic diet in pregnancy did not significantly influence maternal or fetal blood concentrations of a range of biomarkers for inflammation. Thus, the previously reported effects of a cholesterol-lowering diet on maternal lipid profile and preterm delivery (<37 complete weeks of gestation) do not seem to involve changes in the systemic inflammatory responses of pregnancy.

Adult↗
PubMed2006

Follow-up of diet and cardiovascular risk factors 20 years after cessation of intervention in the Oslo Diet and Antismoking Study.

OBJECTIVE: The Oslo Diet and Antismoking study was a 5-year randomised trial initiated in 1972-1973, which studied the effect of dietary change and smoking cessation for the prevention of coronary heart disease among high-risk middle-aged men. To test the long-term maintenance of lifestyle change, we examined diet and cardiovascular risk factors in subjects initially randomised to the control and intervention groups 20 years after cessation of the intervention. SUBJECTS AND DESIGN: Of the original cohort that included 1232 participants, 910 survivors were identified in 1997 and cardiovascular risk factors were measured in 563 (62%) in 1997-1999. Of these, 558 (99%) also completed questionnaires about their food intake and attitudes to health and diet. RESULTS: Cigarette smoking was nearly halved between baseline and 20-year follow-up in each of the intervention and control groups (P<0.001 within groups), but did not differ between the intervention group (39%) versus the control group (34%); P=0.07. Body mass index increased by 1.4+/-2.6 and 1.6+/-2.6 kg/m(2) between baseline and 20-year follow-up in the intervention and control groups, respectively (P<0.001 within groups; NS between groups). Serum total cholesterol and triglyceride concentrations decreased substantially in subjects treated or untreated with statins (P<0.001 within the intervention and control groups) but did not differ between the groups (total cholesterol change of -1.4+/-1.3 and -1.3+/-1.2 mmol/l, respectively, and triglyceride change of -0.5+/-1.0 mmol/l in both groups). Men in the intervention group reported a less atherogenic fat quality score and lower intakes of fat, saturated fat and cholesterol, higher intakes of long chain polyunsaturated fatty acids, protein and beta-carotene and greater attention to lifestyle and change of diet than the control group (all P<0.05). The fatty acid concentrations did not differ, however, between the intervention and control groups (P>0.05). CONCLUSIONS: No long-term differences in smoking rates or lipid concentrations between the intervention and control groups were observed in the surviving attendees two decades after the end of the trial. Lifestyle intervention still influenced the dietary intake, though modestly.

Aged↗
PubMed2005

Effect of dietary and antismoking advice on the incidence of myocardial infarction: a 16-year follow-up of the Oslo Diet and Antismoking Study after its close.

BACKGROUND AND AIM: The Oslo Diet and Antismoking Study was a 5-year randomised controlled trial initiated in 1972-1973 and ended in 1977-1978, which showed that dietary change and smoking cessation reduced the incidence of coronary heart disease among high risk middle-aged men. In an extended follow-up we studied the incidence of myocardial infarction (MI) 16 years after the end of the trial in the intervention and control groups. METHODS: The primary endpoint was the first occurrence of non-fatal and fatal MI including sudden death up to December 31 1993. Cases of fatal MI were identified by linkage to Statistics Norway using each subject's individual personal number. Cases of non-fatal MI were extracted from the hospital records. Cox proportional hazards regression models estimated relationships between changes in total cholesterol and triglyceride concentrations and smoking status and the primary endpoints up to 16 years following the end of the trial. RESULTS: At 5 and 10 years following the end of the trial the incidence of MI among the 604 men in the intervention (I) and 628 in the control (C) group differed significantly (5-year event rate (I/C) =0.059/0.090; P=0.038 and 10-year event rate (I/C) =0.111/0.155; P=0.023), but the difference faded slowly and subsequently (P=0.069 at 16 years). The reduction in MI in the intervention group was primarily explained by the differences in total cholesterol and triglyceride concentrations between the groups. CONCLUSION: This extended follow-up of the Oslo Diet and Antismoking Study found a prolonged benefit of the intervention lasting for at least a decade after the close of the trial. This finding is in accordance with statin and other studies showing that the effect of cholesterol lowering may be prolonged after the end of the intervention.

Cholesterol↗
PubMed2005

Tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population.

AIMS/HYPOTHESIS: Insulin resistance is associated with abnormalities in lipid and glucose metabolism, which are major components of metabolic syndrome and risk factors for vascular disease. This study examined the effect of tesaglitazar (Galida), a novel, dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist, on lipid and glucose metabolism in patients with evidence of insulin resistance. METHODS: A 12-week, multicentre, randomised, double-blind, placebo-controlled, dose-finding study compared the efficacy and safety of oral tesaglitazar (0.1, 0.25, 0.5 and 1.0 mg/day) and placebo in 390 non-diabetic patients with hypertriglyceridaemia (plasma triglyceride concentration >1.7 mmol/l) and abdominal obesity (waist-to-hip ratio >0.90 for men and >0.85 for women). RESULTS: A 1.0-mg dose of tesaglitazar reduced fasting triglycerides (the primary endpoint) by 37% (95% CI: -43% to -30%; p<0.0001), non-HDL-cholesterol by 15% (95% CI: -20% to -10%; p<0.0001) and NEFA by 40% (95% CI: -51% to -27%; p<0.0001), and increased HDL-cholesterol by 16% (95% CI: 8 to -24%; p<0.0001). At the end of treatment there was a dose-dependent increase in patients with pattern A LDL particle diameter (40% at baseline vs 87% at 12 weeks for tesaglitazar 1.0 mg). Tesaglitazar produced significant reductions in fasting insulin concentration (-35%; p<0.0001) and plasma glucose concentration (-0.47 mmol/l; p<0.0001). Respiratory infection and gastrointestinal symptoms were the most common adverse events and were similarly frequent in all groups. CONCLUSIONS/INTERPRETATION: Tesaglitazar was well tolerated and produced significant, dose-dependent improvements in lipid and glucose metabolism and insulin sensitivity. Tesaglitazar may have the potential to prevent vascular complications and delay progression to diabetes in these patients.

Alkanesulfonates↗
PubMed2004

Elevated Framingham risk score in HIV-positive patients on highly active antiretroviral therapy: results from a Norwegian study of 721 subjects.

Highly active antiretroviral therapy (HAART) may induce dyslipidemia and thus increase the risk of future cardiovascular heart disease (CHD). In this cross-sectional study performed in 2000-2001, the prevalence of a Framingham CHD risk score of >20% in HIV-positive individuals treated or not treated with HAART was compared with that in age- and gender-matched controls. The study included 721 subjects: 219 HIV-positive individuals on HAART, 64 HIV-positive, HAART-naïve individuals, and 438 age- and gender-matched controls randomly selected from a simultaneous health survey. The prevalence of a 10-year estimated CHD risk of >20% was 11.9% in patients on HAART compared to 5.3% in controls ( P=0.004). The main contributors to the increased CHD risk in patients on HAART were increased prevalence of daily smoking (54.5% vs 30.1%; P<0.001), total cholesterol of >6.2 mmol/l (36.1% vs 21.7%; P<0.001), and HDL cholesterol of < 0.9 mmol/l (20.9% vs 8.0%; P<0.001). In HAART-naïve patients, the prevalence of a 10-year estimated CHD risk of >20% was 6.3% ( P=0.25 vs HAART patients, P=0.76 vs controls), the prevalence of daily smoking was 56.3% ( P=0.89 vs HAART patients, P<0.001 vs controls), the prevalence of total cholesterol >6.2 mmol/l was 9.4% ( P<0.001 vs HAART patients, P=0.019 vs controls), and the prevalence of HDL cholesterol of <0.9 mmol/l was 30.9% ( P=0.16 vs HAART patients, P<0.001 vs controls). The results show that, compared to controls, twice as many patients on HAART have an estimated 10-year CHD risk above 20%. These patients are candidates for intensive interventions. HAART patients should be encouraged to permanently stop smoking, make healthy food choices, and increase physical activity. In patients with elevated lipid levels, a change in the HAART regimen or treatment with lipid-lowering drugs should be considered.

Adult↗
PubMed2004

8-isoprostane increases scavenger receptor A and matrix metalloproteinase activity in THP-1 macrophages, resulting in long-lived foam cells.

BACKGROUND: Oxidative stress is a key factor in atherogenesis, in which it is closely associated with the inflammation and formation of bioactive lipids. Although 8-isoprostane is regarded as a reliable marker of oxidative stress in vivo, the pathogenic role of this F(2)-isoprostane in atherogenesis is far from clear. Based on the important role of foam cells in the initiation and progression of atherosclerosis we hereby examined the ability of 8-isoprostane to modulate oxidized (ox)LDL-induced foam cell formation and the function of these cells, particularly focusing on the effect on matrix degradation. METHODS AND RESULTS: 8-isoprostane (10 micro M) augmented the oxLDL-induced (20 micro g mL(-1)) lipid accumulation of THP-1 macrophages evaluated by Oil-Red-O staining and lipid mass quantification (colourimetric assay). Additionally, 8-isoprostane induced the expression of the scavenger receptor A type 1 (MSR-1) [mRNA and protein level], assessed by RT-PCR and Western blotting, respectively. Moreover, 8-isoprostane counteracted the oxLDL-induced apoptosis of these cells, involving both mitochondrial-protective and caspase-suppressive mechanisms. Along with these changes, 8-isoprostane increased the oxLDL-induced gene expression of matrix metalloproteinase (MMP)-9 and its endogenous inhibitor [i.e. tissue inhibitor of MMP (TIMP)-1] accompanied by enhanced total MMP activity. CONCLUSIONS: We show that 8-isoprostane increases foam cell formation at least partly by enhancing MSR-1 expression and by inhibiting apoptosis of these cells, inducing long-lived foam cells with enhanced matrix degrading capacity. Our findings further support a role for 8-isoprostane not only as a marker of oxidative stress in patients with atherosclerotic disorders, but also as a mediator in atherogenesis and plaque destabilization.

Apoptosis↗
PubMed2004

Undertreatment and overtreatment with statins: the Oslo Health Study 2000-2001.

OBJECTIVE: We examined the prevalence and factors associated with use of cholesterol-lowering statins in the population. METHODS: Demographic, medical, anthropometric and lifestyle data was obtained from 6233 men and 7521 women born in 1924/25, 1940/41, 1955 and 1960 that participated in the Oslo Health Study 2000-2001. A nonfasting blood sample was collected. RESULTS: Of subjects with a heart attack, angina, stroke or diabetes 45% of men and 35% of women were taking a statin (P < 0.001). Of subjects with cardiovascular disease (CVD) or diabetes taking statins 61% of men and 40% of women achieved total serum cholesterol levels < or =5 mmol L(-1). The odds ratio for taking a statin was increased amongst subjects who also took antihypertensive drug(s) or acetylsalicylic acid, subjects with a family history of coronary heart disease (CHD) and women who had visited the general practitioner within the last year. Amongst presumed healthy subjects use of statins increased from about 1% in women aged 40-45 years, to 7% at age 60 and to 12% at age 75 whilst the corresponding figures for men were 3%, 8% and 9%, respectively. About 22% of men but <2% of women aged 60 who were not taking statins had a 10-year Framingham CHD risk score >20%. Determinants of statin use were similar to those amongst subjects with CVD or diabetes. CONCLUSION: People with CVD or diabetes remain undertreated with statins, women more so than men. Use of other preventive drugs, the family history and recent contact with the general practitioner were the most important determinants of statin use in primary and secondary prevention. Amongst healthy subjects aged 60 or 75 years women received statins disproportionately to their low CHD risk compared with men.

Adult↗
PubMed2004

Hormone therapy and mortality during a 14-year follow-up of 14 324 Norwegian women.

OBJECTIVES: We evaluated mortality from cardiovascular disease (CVD), coronary heart disease (CHD) and all causes in relation to use of any hormone therapy (HT) and HT with oestradiol and norethisterone or levonorgestrel. DESIGN: Population-based cohort study. SETTING AND SUBJECTS: Women in three Norwegian counties were invited to a health survey in 1985-88 and 82.8% participated. In all 14 324 post- or perimenopausal women aged 35-62 years, including 702 HT users with a mean age of 48.8 years, were followed for 14 years. RESULTS: Women using HT had mortality from all causes and CVD comparable with that of nonusers. The relative risk (RRs) for CVD mortality amongst all women were 0.69 (95% CI: 0.35-1.33) for users of HT, and 0.96 (95% CI: 0.43-2.17) for users of HT with norethisterone or levonorgestrel. Amongst women free of self-reported cardiovascular health problems at baseline all-cause, CVD and CHD mortality tended to be lower amongst users of HT whilst HT use was linked with increased mortality amongst women with cardiovascular health problems. CONCLUSIONS: In this cohort of women around the usual age of menopause all-cause or CVD mortality amongst users of HT, most often oestradiol combined with norethisterone or levonorgestrel, was not markedly different from that of nonusers. Early CHD events amongst HT users prior to the baseline survey, together with selective inclusion of healthy subjects, may in part explain protective effects of HT on CHD reported from previous observational studies.

Adult↗
PubMed2003

Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study.

AIMS: To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD). METHODS: Six hundred twenty-nine subjects with CVD who smoked >/=10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150 mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study. RESULTS: Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; P<0.001). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, P<0.001). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 (P<0.001). In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants (n=36) discontinued study medication due to an adverse event (bupropion SR, n=17; placebo, n=19). CONCLUSIONS: After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations.

Adult↗
PubMed2003

Choices for treatment of hyperlipidaemia.

A number of studies have established that lowering of serum cholesterol levels leads to striking reductions in cardiovascular events. Although children almost never experience myocardial infarction, stroke or coronary death, paediatric autopsy studies suggest that atherosclerosis starts in childhood. Moreover, the extent of atherosclerotic change in children can be correlated with the same risk factors, including serum cholesterol level, as identified in adults. As a result of these lines of evidence, the paediatric health care community has produced guidelines for treatment of children with hypercholesterolaemia, but has also debated the pros and cons of treatment. This controversy is unlikely to be resolved completely, because definitive studies would require several decades of follow-up and would raise serious ethical concerns. The purpose of this review is to summarize current views on the optimal approach to management of hyperlipidaemia in children, given current knowledge. We suggest that the child's sex, serum cholesterol level and family history of premature cardiovascular disease may be used to stratify risk. Children at exceptional high risk may be considered for pharmacological treatment.

Anticholesteremic Agents↗
PubMed2003

A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation.

BACKGROUND: Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies. OBJECTIVE: To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes. RESULTS: Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89-4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29-3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%). CONCLUSION: Bupropion SR in combination with counselling increased the abstinence rate compared with placebo, and was well tolerated.

Adult↗
PubMed2003

Children and statins.

UNLABELLED: Use of statins is increasing among children with familial hypercholesterolaemia who previously have had to take unpalatable resins. In a selected group with no controls, children taking statins had similar scores for quality of life and anxiety as normative scores. The question that remains is how to improve dietary and disease information. CONCLUSION: Children with familial hypercholesterolaemia who are taking statins have no reduction in quality of life or increase in anxiety.

Adolescent↗
PubMed2002

Does short-term smoking cessation reduce plasma total homocysteine concentrations?

Both elevated plasma total homocysteine and cigarette smoking are associated with an increased risk of occlusive cardiovascular disease. We examined whether smoking cessation for a mean time of 10-11 weeks lowered plasma total homocysteine concentrations in men and women with (n=59) and without (n=55) established cardiovascular disease. Blood tests were available for 58 quitters and 29 subjects who did not stop smoking. Compared with subjects who continued to smoke, quitters had statistically significant higher HDL cholesterol concentrations, but plasma total homocysteine concentrations did not differ between the two groups. Likewise, no differences were found between quitters and non-quitters whose baseline homocysteine concentrations were above the 75th percentile.

Adult↗
PubMed2001

[Diet and secondary prevention of coronary heart disease--are our recommendations good enough?].

BACKGROUND: Dietary treatment plays an important role in prevention of coronary heart disease. In Norway as in other European countries, patients with established coronary heart disease are advised to follow a cholesterol-lowering diet. However, epidemiological observations have suggested that Mediterranean and other diets may have cardioprotective characteristics beyond their effects on serum total and LDL cholesterol levels. MATERIAL AND METHODS: We describe the results of randomised, controlled clinical trials that have investigated the effect of diet on secondary prevention of coronary heart disease. RESULTS: Diets characterised by high contents of oleic acid (18: 1n-9), alpha-linolenic acid (18: 3n-3) and fish or fish oil and near-vegetarian diets have reduced cardiovascular morbidity and mortality in patients with coronary heart disease. INTERPRETATION: Several characteristics of the Mediterranean diet seem to have additional anti-atherothrombogenic effects beyond those observed with the usually recommended cholesterol-lowering diet. We ask whether Norwegian dietary recommendations for secondary prevention, should emphasise more strongly the type of fat used and fruit and vegetable intake, in line with the principles of the Mediterranean diet. Such dietary advice should be incorporated into the medical treatment given to all patients with coronary heart disease, regardless of their lipid profile.

Coronary Disease↗