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S Tonstad

Publications and source records attributed to S Tonstad.

At least 55 records · Page 3Linked to original sources
PubMed1998

Carotid intima-media thickness and plaque in patients with familial hypercholesterolaemia mutations and control subjects.

BACKGROUND: In individuals with familial hypercholesterolaemia (FH), ultrasonographic measurement of carotid intima-media thickness (IMT) and plaque may provide a non-invasive assessment of cardiovascular risk. METHODS: We examined carotid artery IMT and its determinants in 79 non-smoking, normotensive, treated men and women with FH aged 26-46 years, and in 79 non-smoking, normotensive sex-, age- and body mass index-matched control subjects. FH was verified by molecular genetic analyses. The underlying mutation in the low-destiny lipoprotein receptor gene included a splice-site mutation, mutations predicted or shown to lead to class 2B mutations or other mutations that probably represent class I mutations (null alleles). RESULTS: The carotid bifurcation and common carotid artery IMT was increased in men with FH compared with control subjects (0.81 +/- 0.15 mm vs. 0.74 +/- 0.19 mm and 0.61 +/- 0.13 mm vs. 0.55 +/- 0.14 mm respectively; P < 0.05). The carotid bifurcation IMT was increased in women with FH compared with control subjects (0.74 +/- 0.17 vs. 0. 66 +/- 0.15; P = 0.005). More subjects with FH had carotid plaque (54% vs. 14%; P = 0.0001). In multivariate analysis, male gender, level of low-density lipoprotein-cholesterol, cholesterol-years score and xanthoma were associated with IMT and plaque in subjects with FH. FH subjects with class 2B mutations had lower cholesterol levels than subjects with mutations belonging to the other classes. They also had a tendency towards a decreased common carotid artery IMT. CONCLUSION: These findings confirm the importance of gender, xanthoma and lifetime cholesterol levels in relation to carotid atherosclerosis in FH. Whether the type of mutation causing FH modulates carotid artery IMT and plaque requires further study.

Adult↗
PubMed1998

Do genetic determinates of ischaemic heart disease imply that prevention may become more difficult?

Favourable changes in environment and lifestyle in the community may lead to a situation in which genetic determinants of ischaemic heart disease assume greater importance. Does this imply that ischaemic heart disease becomes more difficult to prevent? Much of the role of the family history as a risk factor within populations may be explained by new genetic mutations. However, differences between populations are generally attributable to environmental differences. A model of gene-environment interaction implies that individuals or populations with genetic risk markers are both more susceptible and more responsive to environmental changes, including lifestyle and drugs, and thus, may be eminently treatable.

Humans↗
PubMed1997

[Diagnosis and treatment of severe hyperlipidemia].

Though severe hyperlipidaemia (total cholesterol level > or = 13 mmol/l in this study) is uncommon, it is important to make a precise diagnosis. We examined 57 patients with isolated severe hypercholesterolaemia. Of these, four were homozygotes for familial hypercholesterolaemia, 48 were heterozygotes for familial hypercholesterolacmia and one had sitosterolemia. The heterozygotes carried 15 different LDL receptor mutations, with no one mutation predominating. When the diagnosis is made, relatives should be given the opportunity to be tested. Combined severe hyperlipidaemia is usually due to a secondary cause, at our clinic, the most common cause is diabetes mellitus. The underlying disease should be treated first. However, many patients will require additional lipid-lowering drugs because the underlying disease may be associated with an increased risk of cardiovascular disease. With the exception of fish oil capsules, drugs that reduce serum triglyceride levels substantially are not registered in Norway at present.

Adult↗
PubMed1997

[What happens with patients after participation in a clinical trial?].

107 patients with primary hypercholesterolaemia participated for five years in a clinical trial with dietary and drug treatment (a statin) at the Lipid Clinic. At the end of the study the patients were referred back to their own physicians, with written advice on diet and drug therapy. At a recall two years later we studied to what extent recommended therapy and follow-up had been implemented. 15% had no follow-up after participating in the study and 18% had not measured their cholesterol for one year or more. The majority of the patients did not follow the recommended diet and level of physical activity satisfactorily, and 20% had stopped their lipid-lowering medication. In general they had been prescribed too low doses of the lipid-lowering agent, and 70% of the patients had not reached the target of the LDL-cholesterol. In conclusion, adequate treatment and a five-year follow-up is not sufficient to keep the patient compliant when the follow-up becomes less intensive. When a clinical trial is terminated, greater efforts should be made to secure better compliance to therapy.

Adult↗
PubMed1997

Flow cytometric measurement of low density lipoprotein receptor activity validated by DNA analysis in diagnosing heterozygous familial hypercholesterolemia.

We have evaluated whether low density lipoprotein (LDL) receptor activity of stimulated lymphocytes, as measured by an improved flow cytometric assay, may be used to diagnose familial hypercholesterolemia (FH). Cells were isolated from 75 children suspected from strict clinical criteria to be FH heterozygotes and from 29 normal children. DNA from the FH patients were also subjected to molecular genetic analysis of the LDL receptor gene in order to confirm the clinical diagnosis. A molecular genetic diagnosis of FH was obtained in 68 of the 75 patients; 67 of these had a low (below 70% of normal) receptor activity and 1 had a borderline (71%) activity. By contrast, 28 of the normal children showed a normal (above 80%) and 1 a borderline (78%) receptor activity. Of the 7 patients in whom no mutation in the LDL receptor gene was found, 4 showed a normal, 1 a borderline, and 2 showed a low activity. In summary, measurement of LDL receptor activity allowed us to separate between genetically diagnosed FH heterozygotes and healthy children. The combined use of LDL receptor activity measurements and molecular genetic analysis allows us both to diagnose and exclude FH in children suspected to suffer from this disease.

Child↗
PubMed1997

Association between plasma total homocysteine and parental history of cardiovascular disease in children with familial hypercholesterolemia.

BACKGROUND: Recently, we reported a relation between plasma total homocysteine (tHcy) in children and cardiovascular disease (CVD) in their male relatives, suggesting that tHcy may partly explain the increased risk related to a family history of CVD. Because individuals with familial hyperlipidemias have an exceptionally high risk of premature CVD, we explored the relationship between tHcy and parental history of CVD in children with familial hypercholesterolemia (FH). METHODS AND RESULTS: Study subjects were 91 boys and 64 girls (age range, 7 to 17 years) with FH who were treated with a standard lipid-lowering diet at a tertiary care lipid clinic. We conducted a cross-sectional analysis of demographics, the diet, tHcy level, presence of the C677T mutation in the methylenetetrahydrofolate reductase gene (a common genetic cause of elevated tHcy) in children, and the prevalence of parental CVD. tHcy increased after puberty and was inversely related to parental educational level. Intakes of folate, vitamin C, and fruits and vegetables were inversely associated with tHcy, as were serum folate and vitamin B12 (Spearman's rho, -0.2 to 0.4; P<.05). tHcy was increased in children whose parent with FH had experienced CVD compared with children without parental CVD (median [interquartile range], 6.6 [5.3, 8.0] micromol/L versus 5.6 [4.7, 6.8] micromol/L; P=.01). This difference remained significant in multivariate regression analysis. Homozygosity for the C677T mutation was associated with a higher tHcy level and tended to be more frequent in the group with than in the group without a parental history of CVD (18% versus 8%; P=.07). CONCLUSIONS: These findings suggest that a moderately elevated tHcy level may partly account for the contribution of the family history to risk of CVD in FH. Dietary recommendations for FH should include nutrients that affect homocysteine metabolism.

Adolescent↗
PubMed1997

[Zocor and Sotacor].

Explore the source record for details and available documents.

Anti-Arrhythmia Agents↗
PubMed1997

[Drug therapy of hyperlipidemia--unanswered questions].

The use of lipid-lowering drugs is now established clinical practice. However, not all patient categories have been covered in the landmark studies (4S, WOSCOPS and CARE), leaving the arena open for widely differing opinions. Dyslipidoemia in patients with diabetes mellitus and arteriosclerotic disease of the aorta, limb arteries or carotid arteries should be corrected. The benefit remains unproven for patients with coronary artery disease and normal lipid levels, and for the elderly. Omega-3 supplements are approved in Norway for hypertriglyceridoemia, but clinical benefit has not been established for this treatment, in contrast to treatment with gemfibrosil. Hormone replacement therapy for postmenopausal women effectively lowers LDL cholesterol levels and the results of randomised studies with clinical endpoints are awaited. The rapid effect (within six months) of lowered cholesterol on coronary events suggests that starting treatment during middle age is adequate for many patients, except for those with familial hyperlipidemias.

Adult↗
PubMed1997

[Application of gene technology in the diagnosis of familial hypercholesterolemia].

Familial hypercholesterolaemia is an autosomal dominant disorder characterized by hypercholesterolaemia, xanthomas and premature coronary heart disease. Treatment of hypercholesterolemia is effective and consists of dietary changes and lipid lowering drugs. Only a minor proportion of familial hypercholesterolaemia patients are adequately treated, however. One explanation for this is assumed to be the relatively vague clinical diagnostic criteria applied. Because familial hypercholesterolaemia is caused by a mutation in the gene encoding the low density lipoprotein (LDL) receptor, mutation analysis of this gene could form the basis for specific diagnosis. 29 different mutations in the LDL receptor gene have been found to cause familial hypercholesterolaemia among Norwegian patients, and a total of 681 patients from 322 unrelated families have been provided with a molecular genetic diagnosis. We conclude that the use of molecular genetic analysis is feasible, and should be used clinically.

DNA Mutational Analysis↗
PubMed1997

Fat-soluble vitamin levels in familial hypercholesterolemia.

OBJECTIVE: To examine serum levels of retinol, 25-hydroxyvitamin D, and alpha-tocopherol and their potential determinants in familial hypercholesterolemia (FH). SUBJECTS: Study 1: 151 boys and girls with FH aged 7 to 16 years who were following a lipid-reduced diet but not taking lipid-lowering drugs. Study 2: 87 boys and girls with FH, of whom 24 were taking bile acid-binding resins in addition to the diet, and 30 age- and sex-matched control subjects. DESIGN: Cross-sectional survey. SETTING: Lipid referral clinic. RESULTS: None of the subjects had suboptimal retinol or 25-hydroxyvitamin D levels. Only one girl had a low alpha-tocopherol level and alpha-tocopherol/lipid ratio. In multiple regression analysis, pubertal onset and gender were associated with retinol and 25-hydroxyvitamin D levels. The triglyceride level was positively related to level of retinol, and body mass index was inversely related to 25-hydroxyvitamin D level. Vitamin supplementation was positively related to 25-hydroxyvitamin D level and the alpha-tocopherol/lipid ratio. This ratio was lower in subjects whose total cholesterol level was above the median (8.0 mmol/L (310 mg/dl)) than in subjects whose cholesterol level was below the median (p = 0.01). In study 2, the alpha-tocopherol/lipid ratio in control subjects (median, 5.1 mumol/mmol) was higher than in subjects with FH who were not taking resins (median, 3.3 mumol/mmol; p < 0.05) but similar to the ratio in treated subjects (median, 5.4 mumol/mmol). CONCLUSIONS: Pubertal onset, gender, lipid levels, vitamin supplementation, and body mass index are significant predictors of fat-soluble vitamin levels in children with FH. Though children following a lipid-lowering diet have normal serum levels of fat-soluble vitamins, the alpha-tocopherol level does not appear to increase proportionately to the increase in cholesterol level. Treatment with resins may restore a normal alpha-tocopherol/lipid ratio.

Adolescent↗
PubMed1997

Correlates of plasma total homocysteine in patients with hyperlipidaemia.

The study sought to define the relation of plasma total homocysteine to biological and clinical variables and to serum vitamin concentrations in patients with primary hyperlipidaemia. Fasting plasma total homocysteine was measured in 219 men and 159 women; vitamin concentrations were available for about 60% of the sample. Men had significantly higher plasma total homocysteine than women [median (25th, 75th percentiles) 9.4 (8.2, 11.5) mumol L-1 vs. 8.5 (7.0, 10.2) mumol L-1; P = 0.0001]. Plasma total homocysteine was lower in women taking lipid-lowering drugs than in women who were not taking drugs. Serum folate and vitamin B12 concentrations were normal for all but one and four subjects respectively. Correlations (P < or = 0.06) were found between plasma total homocysteine and age, triglyceride concentration in women, uric acid concentration in men, serum folate, vitamin B12 and creatinine concentrations. In multiple regression analysis, the association between plasma total homocysteine and sex and between plasma total homocysteine and use of lipid-lowering drugs disappeared when creatinine concentration was entered into the analysis. This study shows that plasma total homocysteine is related to vitamin concentrations within the normal range, suggesting that plasma total homocysteine may be modifiable by diet in hyperlipidaemic subjects with normal vitamin nutrition. Sex-related differences appear to be related to men's higher creatinine concentration. Whether lipid-lowering drugs interact with total homocysteine concentration requires further study.

Adult↗
PubMed1997

Molecular genetics of familial hypercholesterolaemia in Norway.

OBJECTIVES: To characterize mutations in the low density lipoprotein (LDL) receptor gene causing familial hypercholesterolaemia (FH) amongst Norwegian patients. DESIGN: Molecular genetic analyses of the LDL receptor gene have been performed in patients with a clinical diagnosis of FH. SUBJECTS: A total of 742 probands have been studied. Of these, 476 had a diagnosis of definite FH. The rest had a diagnosis of possible FH. RESULTS: Twenty-three different mutations in the LDL receptor gene as well as the apolipoprotein B-3500 mutation have been found. Six of the mutations in the LDL receptor gene are novel mutations. A molecular genetic diagnosis was achieved in 295 of the probands with definite FH (62%) and in 317 probands total. Of the 317 probands, 3% carried the apolipoprotein B-3500 mutation. When family members were included, a total of 624 persons carried a mutation in the LDL receptor gene and 20 carried the apolipoprotein B-3500 mutation. CONCLUSIONS: Approximately 5% of Norwegian FH patients have been provided with a molecular genetic diagnosis. Our data suggest that molecular diagnosis of FH in Norway is feasible and should be implemented in clinical medicine.

Adult↗
PubMed1997

Dietary adherence in children with familial hypercholesterolemia.

We examined nutritional and psychosocial factors associated with adherence to the recommended diet (< or = 30% of energy from fat and < 10% from saturated fat) in children with familial hypercholesterolemia. Ninety-eight boys and 74 girls aged 7-17 y treated for > or = 18 mo responded to a quantitative food-frequency questionnaire that was self- (ages 13-17 y) or dietitian-(ages 7-12 y) administered. One hundred nine subjects also completed a weighed food record. Psychosocial assessments included the Child Behavior Checklist, Youth Self Report, and Children's Global Assessment Scale. The weighed record showed better adherence to dietary guidelines than the food-frequency questionnaire, but energy intake was underestimated. Low energy reporters had a healthier diet than the rest with the weighed record. According to the questionnaire, energy intake was underreported in only 9% of subjects and was not associated with a healthier diet, thus, further analyses were based on the questionnaire. Intakes of vitamin C (P = 0.0001), folate (P = 0.0001), riboflavin (P = 0.03), thiamine (P = 0.0001), and magnesium (P = 0.0001) per megajoule increased as quartile of total fat intake (as a % of total energy) decreased, reflecting increased intakes of cereals (P = 0.002), pasta (P = 0.01), fruit (P = 0.0001), pure meat (not minced or meat products; P = 0.047), skim milk (P = 0.0001), and skim cheese (P = 0.005). Energy and sugar (% of total energy) intakes were not significantly different across all fat intakes; energy density decreased with decreasing fat quartile. Overall psychosocial function score and parental educational level were associated with lower fat intake in multivariate analysis, explaining 11% of the variance in fat intake. We conclude that adherence to fat restriction among children treated for familial hypercholesterolemia is associated with increased micronutrient density, decreased energy density, and psychosocial factors that facilitate adherence.

Adolescent↗
PubMed1997

Relation between dietary fat and energy and micronutrient intakes.

Concern has been raised about the energy and nutrient adequacy of low fat diets for children that aim to prevent cardiovascular disease in Western populations. The diets of 174 randomly chosen schoolchildren aged 8-12 years from middle and high socioeconomic groups were analysed to determine their nutrient composition in relation to fat intake. The mean percentages of energy intake from fat and saturated fat were 31 and 13%, respectively, and 44% of all children reported consuming < 30% of their energy from fat. The energy intake did not change across the spectrum of fat intake. A decreased fat intake was associated with an increased sugar intake, but also with increased nutrient densities of thiamin, niacin, folate, vitamin C, magnesium, and iron, reflecting an increased intake of fruit, vegetables, and grains. Parental educational level was the most important determinant of fat intake (inverse relation). It is concluded that a self selected low fat intake among children from average to high socioeconomic backgrounds does not compromise their intake of major nutrients or energy.

Child↗
PubMed1997

A rational approach to treating hypercholesterolaemia in children. Weighing the risks and benefits.

Because atherosclerosis is a continuous process throughout life, expert panels have suggested guidelines to reduce the risk of cardiovascular disease, starting from childhood. The guidelines focus on population-based measures and on treating hypercholesterolaemia in individual children. Low-fat diets in children have been widely debated. There is little evidence that growth is stunted or that nutritional deficiencies arise if the energy that is lost by limiting fat intake is substituted with other nutrients. Dietary fibre, plant sterols and fish oils have been used to modify lipid levels in children; however, the efficacy of these dietary adjuncts is limited. Bile acid-binding resins are the only approved drugs to lower cholesterol levels in children and appear to be well tolerated. However, compliance with resins is low because of unpalatability, so low dosages are preferred and vitamin supplementation is prudent. Data on HMG CoA reductase inhibitors and fibrates are insufficient to recommend these drugs at present. Drug treatment should be restricted to children who are at exceptionally high risk of disease, usually those with genetic dyslipidaemias.

Anion Exchange Resins↗
PubMed1996

Efficacy and safety of cholestyramine therapy in peripubertal and prepubertal children with familial hypercholesterolemia.

OBJECTIVE: To determine the efficacy and safety of cholestyramine therapy in young children with familial hypercholesterolemia. SUBJECTS: Boys aged 6 to 11 years (n = 57) and girls aged 6 to 10 years (n = 39) with familial hypercholesterolemia. DESIGN: After 1 year of a low-fat, low-cholesterol diet, children with low-density lipoprotein (LDL) cholesterol levels > or = 4.9 mmol/L (190 mg/di) or < or = 4.1 mmol/L (160 mg/dl) in the presence of familial premature cardiovascular disease were randomly assigned to a double-blind comparison of 8 gm cholestyramine (n = 36) and placebo (n = 36) for 1 year. OUTCOME MEASURES: The primary efficacy and safety outcomes were serum LDL cholesterol levels and height velocity, respectively. Secondary safety outcomes were erythrocyte folate, total plasma homocysteine, serum fat-soluble vitamins, and side effects. RESULTS: Twenty-two subjects in the cholestyramine group and 26 in the placebo group completed the 1-year study. Most withdrawals from the study were related to unpalatability of the study drug or placebo. The LDL cholesterol levels changed by -16.9% (95% confidence interval, -10.8% to -22.9%) in the cholestyramine group compared with 1.4% (95% confidence interval, -4.4% to 7.2%) in the placebo group. Mean height velocity standard deviation scores during 1 year for the children in the cholestyramine and the placebo groups who had not started puberty were 0.24 +/- 1.14 and 0.11 +/- 0.68, respectively (not significant). In the cholestyramine group, mean levels of 25-hydroxyvitamin D decreased. One girl had low folate and elevated homocysteine levels, and there was one case of intestinal obstruction caused by adhesions. CONCLUSIONS: Significant reductions in LDL cholesterol are achievable during treatment with cholestyramine in about half of eligible children. Growth is not adversely affected. Folate deficiency may occur, even with a low dose of cholestyramine, and vitamin D supplements should be considered. Caution should possibly be exercised in starting cholestyramine therapy within 3 months of abdominal surgery in children.

Anticholesteremic Agents↗