Biomedical subjects

S Tonstad

Publications and source records attributed to S Tonstad.

At least 37 records · Page 2Linked to original sources

PubMed2001

Action levels for obesity treatment in 40 to 42-y-old men and women compared with action levels for prevention of coronary heart disease.

BACKGROUND: Guidelines for treating overweight and obesity have been suggested by the World Health Organization and other expert groups. We asked whether most men and women targeted in obesity guidelines would already be included in existing clinical recommendations for the prevention of coronary heart disease (CHD) or whether a new group of patients would be added to current workloads. SUBJECTS AND METHODS: In 1997 the Norwegian National Health Screening Service examined CHD risk factors in subjects aged 40-42 y living in three counties. We studied 6911 men and 7992 women who did not report treatment for diabetes, hypertension or the presence of cardiovascular disease. Estimated 10 y risk of CHD was calculated using the Framingham equation. RESULTS: The prevalence of single risk factors (systolic blood pressure > or =160 mmHg, diastolic blood pressure > or =95 mmHg, total cholesterol level > or =7.8 mmol/l and nonfasting glucose > or =11.1 mmol/l) ranged between 0 and 11% among subjects with body mass index > or =25 kg/m2. Adding low HDL cholesterol (<1.0 mmol/l for men, <1.1 mmol/l for women) and 10 y risk CHD risk to the classical risk factors increased prevalence to 16-50% (one or more risk factors or 10 y risk > or =10%). Sensitivities and specificities of using body mass index (BMI) or BMI and waist circumference as a screen for elevated CHD risk ranged between 22 and 91%. Screening for 10 y CHD risk of > or =10% or one or more risk factors among men and screening for one or more risk factors among women gave positive predictive values of 19-50%; however, the positive predictive value of screening for 10 y CHD risk of > or =10% was only 1-2% among women. Compared with men with BMI<30 kg/m2 or waist circumference <102 cm, those with measurements equal to or above these levels had statistically significantly higher adjusted odds ratios of elevated CHD risk (1.49, 95% CI 1.24-1.79 and 1.48, 95% CI 1.22-1.80, respectively); these associations were not observed among women. CONCLUSION: Using BMI and waist circumference to screen for CHD risk yields low positive prediction values, thus doubling the number of men and adding even more to the number of women seen by the practitioner for prevention of CHD.

Abdomen↗

PubMed2001

Serum cholesterol response to replacing butter with a new trans-free margarine in hypercholesterolemic subjects.

UNLABELLED: Margarine leads to lower total and LDL cholesterol (LDL-C) levels than butter but may contain trans fatty acids that increase atherogenic lipids. A food company has used data concerning the cholesterolemic effects of individual fatty acids, including trans fatty acids, to develop a commercially available and virtually trans-free margarine. OBJECTIVE: The effect of this novel margarine on serum lipids and lipoproteins was compared with that of butter in free-living, hypercholesterolemic subjects. DESIGN AND SETTING: A two-period, outpatient cross-over trial at a university hospital lipid clinic. SUBJECTS: The study involved 77 subjects, and was completed by 53 men and 19 women aged 35-65 years with total serum cholesterol levels of between 6.0 and 7.9 mmol/L. INTERVENTION: Two 23-day regimens, separated by a 4-week washout period, included individualised dietary prescriptions supplemented with butter or margarine designed to provide 15% of total dietary energy. RESULTS: In comparison with butter, margarine intake lowered total and LDL-C levels by respectively 11.1% (99% CI: 8.1-14.1) and 11.3% (99% CI: 7.6-15.1). The reduction in LDL-C was < 3% in nearly one-fifth of the subjects despite appropriate changes in serum triglyceride fatty acids. Of the tested clinical and demographic variables, only the percentage of energy obtained from saturated fat during the margarine intake period was associated with dietary responsiveness (explaining 12% of the variation; p < 0.01). CONCLUSION: Our results suggest that a margarine designed to meet nutritional recommendations for hypercholesterolemia is more efficacious than butter in reducing atherogenic lipid levels in hypercholesterolemic subjects.

Adult↗

PubMed2001

Stratification of risk in children with familial hypercholesterolemia with focus on psychosocial issues.

AIM: This paper discusses the clinical implications of making a diagnosis of familial hypercholesterolemia (FH) in children and data on psychosocial issues. DATA SUMMARY: The case for treating FH in children is based on pathophysiological considerations. Some authors claim that treatment may be harmful, partly because the psychosocial risks have not been assessed. The available data indicate that psychological distress does not seem to be a problem in testing and treating most children for FH, although a few may develop social and emotional problems, experience family conflicts, or have problems with the diet or bile acid binding resins. CONCLUSIONS: Parental preferences and the psychosocial function of the child should be considered and a complete assessment should be made of the potential risk of coronary heart disease (CHD) on the basis of established CHD risk factors. Boys and girls with total cholesterol concentrations of > 7.0 mmol/L and a family history of early CHD (first or second degree relatives with CHD, in males before the age of 40 and in females before the age of 50 years), and boys with cholesterol concentrations of > 10.0 mmol/L regardless of family history, should be considered at high risk and start dietary treatment as early as possible (preferable before the age of ten years). Girls at high risk may start statins by the age of 18 years, whereas starting statins should be considered in boys between the ages of 10 and 18 years. Children with FH at low to moderate risk of CHD may wait until adulthood or start treatment depending on an individualized evaluation.

Adolescent↗

PubMed2000

[The obesity epidemics--do diet pills have a place in the treatment?].

BACKGROUND: Many experts consider obesity a chronic disease that may require long-term therapy. A loss of 5-15% of body weight is associated with improvements in cardiovascular risk factors and morbidity. However, most studies show that the majority of patients who lose weight relapse. Patients may be unable to maintain a low energy intake when confronted with an almost limitless supply of food. Moreover, a number of physiological mechanisms favour a set point for body weight, that may be altered with anti-obesity drugs. MATERIAL AND RESULTS: In the current paper we describe actions and effects of current anti-obesity drugs. The centrally acting drug, sibutramine, is an adrenaline and serotonine re-uptake inhibitor which was recently approved in the USA for obesity. The USA, the European Union and Norway have approved orlistat, a pancreatic lipase inhibitor for weight reduction for up to two years. Patients must maintain a low fat intake in order to avoid gastrointestinal discomfort. In recent studies, orlistat and diet reduced body weight by 9% versus 6% on placebo and diet. No studies have documented long-term safety of anti-obesity drugs. INTERPRETATION: Treatment of a lifestyle-related disease like obesity with medications is controversial, however, such treatment may not differ substantially from treatment of type II diabetes, hyperlipidaemia or hypertension.

Anti-Obesity Agents↗

PubMed2000

[Does postmenopausal hormone replacement therapy have a place in treatment of hyperlipidemia?].

Postmenopausal women experience increases in total cholesterol, triglyceride and lipoprotein (a) levels, decreased HDL cholesterol level and a shift in the LDL particle distribution toward a more dense subtype. Postmenopausal hormone substitution lowers LDL cholesterol level by 12-13%, also in women with hyperlipidaemia, and lowers lipoprotein (a) level. The effect on subtype of LDL has been variable in studies to date. The type, dose and mode of administration of the gestagen as well as the choice of oestrogen (conjugated equine oestrogen versus oestradiol) may affect triglyceride and/or HDL cholesterol levels. The first randomised study of postmenopausal hormone substitution in women with cardiovascular disease (Heart and Estrogen/progestin Replacement Study) showed an increase in cardiovascular events during the first year of therapy with a decrease by the fourth year, thus, there was no overall effect. Several new studies including the Women's Health Initiative and the Women's International Study of long Duration Oestrogen after Menopause should have the power to show the effect of postmenopausal hormone substitution on cardiovascular endpoints in primary prevention, however, the results of these studies will not be available for several years.

Aged↗

PubMed2000

Cardiovascular risk factors and testing of relatives amongst patients with familial hyperlipidaemia one decade after a clinical trial.

OBJECTIVES: We examined the cardiovascular disease risk factor status of men and women with familial hyperlipidaemia (FH) 10-11 years after a clinical trial and asked whether first-degree relatives had undergone lipid testing. DESIGN SETTING AND SUBJECTS: Subjects started lipid-lowering drugs in 1987-88. Of 60 subjects, 12 had died, one emigrated and 35 men and 12 women took part in a follow-up clinical examination in 1998. RESULTS: Total cholesterol level was reduced by 41% and high-density lipoprotein (HDL) cholesterol level increased by 13% compared with baseline (diet alone). Low-density lipoprotein (LDL) cholesterol level was lower at the end of the trial than at follow-up (3.6 +/- 1.5 vs. 4.6 +/- 2.2 mmol L-1; P = 0.01) and was higher in the group taking a low dose of a statin alone compared with other drug groups. Thus, two-thirds of the subjects required adjustment of lipid-lowering drugs to reach target lipid levels. One-fifth consumed at least two food groups rich in saturated fat regularly. Body mass index (BMI) increased from 25.6 +/- 2.9 to 26.8 +/- 3.3 kg m-2 (P < 0.001). Five subjects compared with one at baseline had type II diabetes or glucose intolerance; 12 compared with four at baseline had a blood pressure of >/= 160 mmHg systolic or >/= 95 mmHg diastolic. Plasma total homocysteine was higher in subjects with coronary artery disease than in subjects without disease (11.7 +/- 3.9 vs. 9.0 +/- 2.3 micromol L-1; P = 0.01). Barriers to testing for lipids amongst children or siblings included family feuds, fear of increased insurance and psychiatric disease. CONCLUSION: The majority of subjects were undertreated. Increases in BMI, blood pressure and glucose levels and the diet posed challenges to risk reduction. Plasma homocysteine levels should be considered in this group. Testing of all first-degree relatives may not be achievable because of psychological barriers.

Adult↗

PubMed2000

Does maternal or paternal heredity affect carotid atherosclerosis in children with familial hypercholesterolaemia?

Maternal hypercholesterolaemia has recently been shown to increase the number of fatty streaks in the foetal aorta, as well as subsequent progression of fatty streaks to more advanced lesions. We compared carotid intima-media thickness by B-mode ultrasonography in children who inherited familial hypercholesterolaemia from their mothers or fathers, hypothesizing that children whose mothers were hypercholesterolaemic during pregnancy had increased atherogenesis compared with children whose mothers did not have familial hypercholesterolaemia. We found that carotid intima-media thickness and prevalence of plaque did not differ between children with familial hypercholesterolaemia who inherited FH maternally or paternally.

Adolescent↗

PubMed1999

[Nicotine preparations and other preparations for smoking cessation].

Nicotine replacement therapy doubles quit rates in smoking cessation with or without adjunct behavioural therapy; however, absolute quit rates are higher with adjunct therapy. Effective therapies include the nicotine gum, transdermal preparations, inhaler and spray. Highly dependent smokers should be offered high dose gum (4 mg) or nicotine spray. The nicotine inhaler offers more habit replacement than any of the other forms of nicotine administration and is appropriate for smokers who are moderately addicted and need something to do with their hands. Use of nicotine replacement therapy is safe for most patients with cardiovascular disease, but should probably be restricted in pregnancy to heavy smokers who are unable to quit. Bupropion, a modest dopamine and noradrenaline reuptake inhibitor, increases quit rates compared with placebo. Future therapies will include combinations of nicotine replacement products, and combinations of nicotine products with other medications. Some smokers may benefit from longer treatment and more gradual withdrawal than present treatment regimens imply.

Female↗

PubMed1999

Mutant transcripts of the LDL receptor gene: mRNA structure and quantity.

mRNA of the low-density lipoprotein receptor (LDLR) gene from 22 heterozygous familial hypercholesterolemic subjects possessing different mutations in this gene was analyzed by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) in order to detect abnormally spliced transcripts. These analyses revealed abnormally spliced transcripts for the two splice-site mutations 1359-1G-->A and 1705 + 1G-->T. The abnormally spliced transcript for mutation 1359-1G-->A was caused by activation of a cryptic acceptor splice site in exon 10. As a result, seven nucleotides of exon 10 were deleted. For mutation 1705 + 1G-->T, two mutant transcripts were observed. In the first transcript, exon 10 was spliced to exon 13, and in the second transcript intron 11 was retained. The relative amount of mutant transcripts from 14 of the 22 subjects was determined by use of an RT-PCR-based method. Quantitation of the relative amounts of mutant transcripts for five missense mutations resulted in a mean value (+/-SD) of 52.8% (+/-4.55). In comparison, quantitation of the relative amounts of mutant transcripts for five nonsense mutations resulted in a mean value of 31.8% (+/-6.91). This value was significantly lower than the value of 54.2% (+/-2.38) obtained for nine healthy subjects (P < 0.0001). The relative amount of mutant transcripts for the 1705 + 1G-->T mutation was 36%. Thus, transcripts from alleles containing premature stop codons are present in reduced amounts, whereas transcripts from alleles containing missense mutations are present in normal amounts. These findings underscore the importance of determining how mutations affect mRNA structure and quantity in order to understand how mutations cause disease.

Alleles↗

PubMed1999

Under-reporting of dietary intake by smoking and non-smoking subjects counselled for hypercholesterolaemia.

OBJECTIVES: We asked whether under-reporting of energy and cigarette smoking were associated with choice of foods and dietary composition amongst subjects with hypercholesterolaemia who had received dietary instruction to lower serum cholesterol. DESIGN, SETTING AND SUBJECTS: Dietary intake was assessed with a 4-day weighed food record in 205 women and 141 men, aged 20-73 years, being treated at a lipid clinic (tertiary referral centre). Under-reporting was assessed by calculating the ratio of energy intake (EI) to estimated basal metabolic rate (BMR). RESULTS: The median EI/BMR was 1.1 for both men and women. EI/BMR did not differ according to smoking status, but correlated negatively with body mass index (Spearman's rho = -0.32, P = 0.0001). EI/BMR was inversely associated with energy-adjusted intakes of potatoes, vegetables, fish and low-fat meats, and positively associated with intakes of nuts, potato crisps, chocolate, sour and ice cream, oils, fatty meat spreads, cakes and biscuits, and with alcohol. Thus, low EI/BMR was associated with increased energy-adjusted intakes of protein, thiamine, riboflavin, niacin, iron and cholesterol and with decreased intakes of sugar, poly- and monounsaturated fats and vitamin E (all P < 0.05). Cigarette smokers had a higher energy percentage (E%) from fat than non-smokers (29 +/- 6 vs. 26 +/- 6), a lower E% from carbohydrates (50 +/- 7 vs. 54 +/- 7) and a lower intake of vitamin C (11 +/- 7 vs. 16 +/- 9 mg MJ-1; all P = 0.0001), reflecting an increased intake of fatty meats and a decreased intake of skimmed cheese, fruit, rice and pasta, and cakes and biscuits (all P < 0.05). CONCLUSION: Weighed dietary records reflected a 'healthier' intake of fat, protein, sugar, alcohol and some micronutrients amongst under-reporters, suggesting that self-reported dietary intakes are biased in patients with hypercholesterolaemia. Lack of responsiveness to the diet should not be assumed when dietary data are based on self-report. Smokers report a higher intake of fat and lower intake of vitamin C than non-smokers, even after dietary counsel, and may require more intensive interventions to optimize the diet.

Adult↗

PubMed1999

DNA polymorphisms of the apolipoprotein B gene (XbaI, EcoRI, and MspI RFLPs) in Norwegians at risk of atherosclerosis and healthy controls.

OBJECTIVES: Apo B is the exclusive protein constituent of LDL and is ligand on LDL, recognized and bound by the LDL receptor. Several restriction fragment length polymorphisms (RFLPs) of the apo B gene have been shown to be associated with variation in serum lipid levels in different populations. In this study we sought to determine the frequency of XbaI, EcoRI, and MspI polymorphisms and the haplotypes generated by these three polymorphic sites of the apo B gene and their influence on lipid levels in a sample of Norwegian subjects at risk of atherosclerosis and healthy control subjects. METHODS AND RESULTS: 108 White Norwegians at risk of atherosclerosis (cases) and 64 healthy individuals (controls) were examined for possible association between the alleles at the XbaI (X), EcoRI (R), and MspI (M) polymorphic restriction sites of the apolipoprotein B gene and serum lipid levels. The frequency of the M allele (absence of restriction site) was significantly higher in cases with high total cholesterol (TC), high low-density lipoprotein cholesterol (LDLC), and high apolipoprotein B (apo B) than in controls with normal TC, LDLC, and apo B (P < 0.04, P < 0.02, and P < 0.01, respectively). The frequencies of apo B genotypes detected with XbaI, EcoRI, and MspI did not differ significantly between cases and control subjects. A significant association between MspI genotypes and TC (P < 0.02), LDLC (P = 0.03), and apo B (P = 0.001) was observed only in cases. However, cases with the genotype M+/M+ had the lowest and those with the genotype M+/M- had the highest levels of serum TC, LDLC, and apo B. We did not observe any significant association between the alleles or genotypes detected with XbaI or EcoRI and serum lipid levels. In cases, genotypes defined by EcoRI and MspI RFLP paired loci differed significantly for apo B (chi 2 = 19; P = 0.007) but not for other blood lipids. EcoRI and MspI RFLPs change glutamic acid (Glu) 4154 to lysine (Lys) and arginine (Arg) 3611 to glutamine (Gln), respectively, which lie near the low density lipoprotein receptor binding region of apo B. Haplotypes containing "Lys/Arg Lys/Arg" (all basic amino acids) in cases were associated with low serum TC, LDLC, and apo B. In individuals at risk of atherosclerosis the concentration of serum lipids tends to be inversely related to the number of lysine and arginine. CONCLUSION: We conclude that variations in the apo B gene, resulting in changes of charged amino acids, affect the circulating blood lipids and that these may contribute to the risk of atherosclerosis.

Adult↗

PubMed1999

Phenotypic consequences of a deletion of exons 2 and 3 of the LDL receptor gene.

Screening for structural alterations of the low density lipoprotein (LDL) receptor gene by Southern blot analysis revealed an abnormal band pattern in one subject with a clinical diagnosis of homozygous familial hypercholesterolemia (FH). The molecular defect was further characterized by polymerase chain reaction and cDNA sequencing. These analyses identified a 4.8 kb in-frame deletion of exons 2 and 3, where exon 1 was spliced to exon 4. This deletion is expected to produce a receptor that has lost the two first cysteine-rich repeats of the ligand-binding domain. Previously published data of in vitro site-directed mutagenesis has shown that binding of LDL to such a receptor is reduced to 70% of normal. A mild phenotype in our FH homozygote is consistent with that observation. In contrast, heterozygotes carrying this deletion have a relatively more severe phenotype that is comparable to that of heterozygotes carrying a null-allele. A severe phenotype was also found in a compound heterozygote carrying this deletion. Possible mechanisms for this phenotypic variability are discussed.-Rødningen, O. K., S. Tonstad, J. D. Medh, D. A. Chappell, L. Ose, and T. P. Leren. Phenotypic consequences of a deletion of exons 2 and 3 of the LDL receptor gene.

Base Sequence↗

PubMed1998

[Should treatment of risk factors of cardiovascular diseases be directed only by absolute risk?].

Consensus groups have recommended using the baseline absolute risk of disease over five to ten years rather than relative risk when treatment with lipid-lowering or antihypertensive drugs is considered. Targeting patients with a coronary event rate of 20% over ten years ensures that society's investment in drugs yields substantial benefits by reducing the incidence of premature disease. However, the use of absolute risk is most appropriate among the middle-aged. Because all elderly persons have a high absolute risk of disease, almost all may be eligible for drug treatment. The costs of postponing death after the age of 70 are therefore substantial. Among young persons with familial hypercholesterolemia on the other hand, the consequences of a death before middle-age are so enormous that most patients are treated with drugs even though absolute risk is very low. An additional problem with using absolute risk is that the risk of atherosclerotic disease accumulates over time. Calculation of benefit on the basis of short-term trials might underestimate long-term benefit. In the future, non-invasive measures of atherosclerosis and new markers of risk may provide valuable information on risk stratification in primary prevention.

Antihypertensive Agents↗

PubMed1998

[Attitude to genetic screening for familial hypercholesterolemia].

Familial hypercholesterolemia causes premature cardiovascular disease. Genetic screening of patients' relatives who have already been diagnosed has proved to be more efficient than screening in a general population. Privacy laws in Norway forbid physicians to directly contact persons with genetic disorders who are not their own patients. We examined attitudes towards this type of screening in a representative sample of the Norwegian population and a group of patients with familial hypercholesterolaemia. In both groups the majority showed a positive attitude towards physicians contacting relatives directly to detect individuals with familial hypercholesterolaemia. In both groups the majority wanted to know whether, based on the diagnosis of relatives, they might also be affected. Both groups wanted this information regardless of the risk of their being affected. We conclude that the privacy laws should be amended to conform with the attitudes of the population and the patients, thus enabling physicians to contact relatives directly.

Attitude to Health↗

PubMed1998

[Do women need different strategies than men to prevent cardiovascular diseases?].

Though women have a lower absolute risk of disease than men at all ages, almost all the risk factors for cardiovascular disease carry the same or higher relative risk for women as for men. Moreover, the attributable risk is higher in older women than in men. Epidemiologic studies show that recent decreases in coronary heart disease mortality are in some cases greater among women than men. Interventional studies show that women appear to have as good or better a response than men to cholesterol-lowering in secondary prevention. Antihypertensive drug therapy is effective in preventing clinical endpoints in elderly women. These observations imply that an overall estimation of cardiovascular risk in women needs careful consideration. Because established therapies appear to be effective in high risk women, postmenopausal and probably also elderly women are important target groups for preventive efforts. The value of prevention for premenopausal women should not be underestimated, but should on the whole be approached through population-based strategies.

Cardiovascular Diseases↗

PubMed1998

[Referrals to the Lipid clinic--"appropriate" patients with inadequate anamnesis].

We examined 199 consecutive referrals to the Lipid Clinic at the National hospital in 1995 in order to compare referral- and chart data on familial hyperlipidaemia, familial cardiovascular disease, diagnosis, and lifestyle. 78% of referrals were from general practitioners. Most of the referrals included information on familial hyperlipidaemia and cardiovascular disease and on diet, but did not specify a lipid diagnosis. Less than half of the referrals included information on smoking habits (which was almost always specified in the chart). Up to 80% did not include information on alcohol, body mass index and physical activity, which was also often missing in the chart. We conclude that the referring doctors, and to some extent the clinic physicians, identified patients with a familial risk of cardiovascular disease, but they did not appear to characterise important lifestyle habits related to cardiovascular risk.

Adult↗

PubMed1998

Effects of a 9.6-kb deletion of the LDL receptor gene (FH Helsinki) on structure and levels of mRNA.

FH Helsinki is a deletion of the low-density lipoprotein receptor (LDLR) gene that deletes 9.6 kb from intron 15 to exon 18. Screening for mutant transcripts by Northern blot analysis from a patient heterozygous for FH Helsinki revealed two mutant transcripts. One was a transcript where the proximal part of intron 15 was retained in mRNA. The second was a transcript where exon 15 was spliced to nucleotide 4186 of exon 18. Thus, this transcript was generated using the normal donor splice site in intron 15, and a cryptic AG acceptor splice site in exon 18. Translation of the two mutant transcripts is predicted to give nonfunctional proteins, as both the membrane-spanning domain and the cytoplasmic domain of the receptor are deleted. Scanning of the autoradiograms showed that the amounts of each of the two mutant transcripts were approximately 10 times higher than that of the normal transcript in our heterozygous patient. The finding of higher levels of mutant transcripts was confirmed by an allele-specific transcript quantitation method, in which the amount of the two mutant transcripts together was approximately 5 times higher than the amount of the normal transcript. Deletion of destabilizing elements (AU-rich elements) by FH Helsinki are proposed to cause the increased levels of mutant transcripts.

Base Sequence↗

PubMed1998

The C677T mutation in the methylenetetrahydrofolate reductase gene predisposes to hyperhomocysteinemia in children with familial hypercholesterolemia treated with cholestyramine.

In children with familial hypercholesterolemia, heterozygosity and homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase gene was associated with low serum folate and increased susceptibility to elevation of plasma total homocysteine during cholestyramine treatment. Because of the independent relationship between elevated plasma total homocysteine and cardiovascular disease, folate supplementation may be prudent in these children.

Anticholesteremic Agents↗