[Protective effects of pravastatin against atherosclerosis in children with familial hypercholesterolemia].
Explore the source record for details and available documents.
Child↗
Biomedical subjects
W F Riesen
Publications and source records attributed to W F Riesen.
Hypertriglyceridemia as a possible risk factor for prostate cancer.
We retrospectively studied anthropometric and laboratory parameters (including serum triglycerides, cholesterol), as well as comedication in 504 patients diagnosed with prostate cancer between January 1997 and August 2002 at a single referral center, and compared these patients with 565 age-matched patients with benign prostatic hyperplasia. A positive correlation was found between serum triglycerides and prostate cancer (odds ratio: 1.148/mmol/l; 95% confidence interval (CI) 1.003-1.315; P<0.05) after correcting for age, body mass index, diabetes and comedication with statins. Hypertriglyceridemia may increase the risk of prostate cancer, and the prognostic relevancy of serum triglycerides should be studied prospectively.
Adult↗
Short-term effects of atorvastatin on C-reactive protein.
AIM: To study the short-term effect of atorvastatin on C-reactive protein (CRP) in patients with or at risk for coronary heart disease. METHODS AND RESULTS: One hundred and fifty-five randomly selected patients from the SWiss Intervention Trial for lowering CHolesterol (SWITCH) were assessed for high sensitivity CRP, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides at baseline, and after 1 and 3 months of treatment with atorvastatin at various doses to reach pre-defined lipid target values. The median decrease of cholesterol was 28% after 1 month and 35% after 3 months. LDL-cholesterol was decreased by 37% and 45%, HDL-cholesterol was increased by 7% and 8%, respectively. Patients with a low CRP baseline concentration (lowest quartile <1.34 mg. l(-1)) displayed no significant change, whereas patients in the other quartiles showed a significant decrease, of 22% to 40% (P -value <0.05 to <0.001) at 1 month and of 32% to 36% after 3 months compared to baseline. The decrease in CRP lowering was thus fully established by 1 month and this response was independent of lipid and lipoprotein changes as well as atorvastatin doses. CONCLUSION: Atorvastatin significantly decreases CRP concentrations after 4 weeks of therapy. These results may be important with respect to the early benefit of statin therapy.
Anticholesteremic Agents↗
Increased lipoprotein(a) levels are not a steady prothrombotic defect.
Explore the source record for details and available documents.
Child↗
Comparability of serum and plasma concentrations of haemostasis activation markers.
Since serum and plasma D-dimer concentrations correlate very well, we evaluated the comparability of other haemostasis activation markers in plasma and serum. Prothrombin fragment F1+2, fibrin monomer and D-dimer concentrations were measured with commercially available immunoassays in serum and plasma. Serum to plasma ratios were evaluated to determine the direct (prothrombin fragment F1+2) and indirect (fibrin monomer, D-dimer) downstream influence of prothrombinase on the serum to plasma comparability. Prothrombin fragment F1+2 serum and plasma concentrations did not correlate (R2 = 0.09, ns), while an unexpected high degree of correlation was found for fibrin monomer (R2 = 0.66, p < 0.001), and, as expected, a very good correlation was found for D-dimer (R2 = 0.94, p < 0.001). Median serum to plasma ratios decreased from prothrombin fragment F1+2 (16.26) to fibrin monomer (2.24, p < 0.001) and D-dimer (1.00, p < 0.001), following a highly linear relationship (R2 = 0.93) Plasma and serum concentrations of the evaluated markers correlate the better the farther from prothrombinase activity the respective marker is generated. Serum is not suitable for prothrombin fragment F1+2 measurements, whereas fibrin monomer serum concentrations seem of value for research applications. With the used assay, serum seems an appropriate matrix for clinical D-dimer measurements. This would considerably simplify testing strategies. Validation in further clinical trials is needed.
Blood↗
Acid-base and endocrine effects of aldosterone and angiotensin II inhibition in metabolic acidosis in human patients.
Chronic metabolic acidosis (CMA) in human beings is characterized by increased renin-angiotensin-aldosterone (RAA) activity and cortisol secretion as well as nitrogen wasting. The purpose of this study was to examine whether and to what extent increased RAA activity (i.e., angiotensin II or aldosterone) regulates acid-base equilibrium in CMA and thus might co-determine the severity of acidosis. CMA was induced in 8 normal subjects by oral NH4Cl administration (2.1 mmol/kg body weight per day) for 7 days, followed by a 7-day period of spironolactone (100 mg, 4 times a day by mouth), followed by a 4-day period of spironolactone and losartan (100 mg, every day by mouth). NH4Cl feeding was continued during all study periods. Spironolactone resulted in exacerbation of acidosis ((HCO3)p decreased from 19.8+/-0.4 mmol/L to 17.7+/-0.6 mmol/L, P<.005) because of a large increase in endogenous acid production, as evidenced by significant increases in net acid excretion (116 to 185 mmol/day, P<.005), urinary anion gap (+31 mEq/day, P<.05), and sulfate excretion (+32 mEq/day, P<.05). Plasma potassium increased from 4.2 to 4.6 mmol/L (P<.05) because of decreased urinary potassium excretion (from 108 to 92 mmol/day, P<.05). Plasma angiotensin II, cortisol, aldosterone, urinary aldosterone, urinary tetrahydrocortisol, free cortisol, and nitrogen excretion increased significantly. The subsequent addition of losartan to spironolactone administration resulted in further exacerbation of acidosis ((HCO3)p decreased to 15.7+/-0.4 mmol/L, P<.05) and hyperkalemia (5.0 mmol/L, P<.05) with no change in plasma anion gap. Renal potassium excretion decreased from 92 to 73 mmol/day (P<.05) on day 1. Exacerbation of acidosis was accounted for by a renal mechanism, as evidenced by the significant decrease in net acid excretion and unchanged urinary unmeasured anion and nitrogen excretion. We conclude the following: (1) AT-1 blockade by losartan exacerbates acidosis by inducing a distal-tubular acidification defect. Angiotensin II is an important modulator of the renal acid excretory response to CMA in human beings. (2) Inhibition of aldosterone action by spironolactone in CMA results in an increase in endogenous acid production and exacerbates acidosis by a non-renal mechanism that is mediated, at least in part, by exacerbated hyperglucocorticoidism.
Acid-Base Equilibrium↗
Biochemical markers of bone turnover in patients with thyroid dysfunctions and in euthyroid controls: a cross-sectional study.
Hyperthyroidism is associated with reduced bone mineral density. Conflicting data exist regarding the effects of thyroxine therapy on bone metabolism. The aim of the present study was to assess changes in markers of bone turnover in thyroid dysfunction. A total of 28 patients with overt hyperthyroidism, eight patients with suppressed TSH levels (thyroid hormones within the euthyroid range, no T4 therapy), 25 euthyroid and four hypothyroid patients were included in the present study. Hyperthyroidism resulted in increased bone metabolism, as reflected by increased bone resorption and bone formation parameters. No significant differences in mean levels between patients with TSH supression and those with euthyroidism could be observed; however, a higher frequency of elevated urinary PYD- and DPD excretion rates were noted in patients with TSH suppression. Regression analysis revealed highly significant correlations between bone resorption markers and thyroid parameters, suggesting, that even a mild thyroid hormone excess may lead to an increase in bone resorption. In subjects with suppressed TSH levels and peripheral thyroid hormone levels within the euthyroid range, elevated bone resorption markers point to subclinical hyperthyroidism, if other reasons for an increase in bone turnover rates can be excluded.
Adult↗
[Cholesterol reducing therapy--new aspects in stroke and diabetes].
Explore the source record for details and available documents.
Anticholesteremic Agents↗
Effect of thyroid hormones on Lp(a) and lipid metabolism.
The effect of thyroid hormones on lipoprotein(a) plasma concentrations and the other parameters of lipoprotein metabolism was studied in 158 patients with thyroid dysfunction and in 37 euthyroid controls (cross-sectional study). Multiple regression analysis revealed that 65.5% of the variability in lipoprotein(a) levels were predicted by changes in lipoprotein(a) phenotypes (60.5%), thyrotropin (3.5%), and age (0.8%). The lipid parameters, however, showed no significant effect on lipoprotein(a). A subgroup analysis on samples from patients with large lipoprotein(a) isoforms showed that 28% of the variability in lipoprotein(a) concentrations could be explained by changes in thyroid function (19.1%), age (6.5%) and triglycerides (3.5%). Much stronger correlations were found between thyrotropin and total cholesterol, low density lipoprotein cholesterol or apolipoprotein B respectively (R2=0.951 for low density lipoprotein cholesterol, R2=0.801 for apolipoprotein B). Our data suggest that thyroid hormone is a significant modulator of lipoprotein(a) metabolism. However, different mechanisms are responsible for the change in lipoprotein(a) levels and for the decrease in total- and low density lipoprotein cholesterol levels.
Adult↗
Diagnostic and prognostic value of biochemical markers in malignant bone disease: a prospective study on the effect of bisphosphonate on pain intensity and progression of malignant bone disease.
Seventy cancer patients with malignant osteolytic bone disease received pamidronate every three weeks for a maximum of six cycles. Bone resorption parameters, urinary calcium excretion, and pain parameters were assessed at baseline and throughout the study. At baseline, 80-95% of patients showed elevated urinary pyridinoline, deoxypyridinoline, Osteomark NTx and serum ICTP levels, whereas only 35% of patients had elevated urinary CrossLaps excretion rates. During bisphosphonate therapy, significant decreases in Osteomark NTx, CrossLaps and calcium excretion were observed, which were not related to the clinical outcome. The baseline levels of bone resorption markers were used to predict the probability of non-progressive bone disease or reduction in pain intensity during bisphosphonate therapy. Significant predictors of non-progressive bone disease were urinary pyridinoline and serum ICTP levels; significant predictors of reduction in pain intensity were urinary free deoxypyridinoline and serum ICTP levels. Our data indicate that serum ICTP levels predict significantly the response to bisphosphonate therapy in patients with advanced malignant osteolytic bone disease. CrossLaps did not predict the clinical outcome, but decreased significantly during bisphosphonate therapy. Our data demonstrate that the different bone resorption markers are reflecting different aspects of bone metabolism, and therefore differ in their diagnostic and prognostic properties.
Aged↗
Comparison of bezafibrate and simvastatin in the treatment of dyslipidaemia in patients with NIDDM.
Fibrates and HMG CoA reductase inhibitors are commonly used in the treatment of diabetic dyslipidaemia. However, these two groups of drugs have not been compared in diabetic patients in a randomized controlled trial. Therefore, a multicentre study was performed in 73 subjects with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and combined hyperlipidaemia (serum cholesterol 6.2-10.0 mmol l(-1), serum triglycerides 2.3-10.0 mmol l(-1)), comparing the efficacy of 400 mg bezafibrate with 10 mg simvastatin in a double-blind fashion. Treatment with bezafibrate during 12 weeks reduced serum triglycerides significantly more than simvastatin (-41% vs -22%, p < 0.001) and increased HDL cholesterol more (bezafibrate: + 17% vs simvastatin: + 9%, p < 0.05). LDL cholesterol levels decreased by 14% (p < 0.001) during simvastatin and increased by 21% (p < 0.01) during bezafibrate. This increase in LDL cholesterol was positively correlated with fasting serum triglycerides (p < 0.001) and was associated with a reduction of the serum apolipoprotein B concentration, suggesting an increase in LDL particle size. Metabolic control of diabetes (fasting glycaemia; HbA1c) and insulin secretion (C-peptide levels) were unaffected by both treatments. The incidence of side-effects during treatment was similar for both drugs. Thus, 400 mg bezafibrate mainly increases HDL cholesterol and lowers serum triglycerides but at the expense of an increase in LDL cholesterol; 10 mg simvastatin lowers LDL cholesterin more effectively but has a smaller effect on HDL cholesterol and triglycerides.
Aged↗
[Lipoprotein(a) and hemostasis activation markers in angina pectoris].
STATEMENT OF PROBLEM: To analyse whether lipoprotein(a) is a risk factor for myocardial infarction, stroke and acute peripheral arterial occlusion in coronary heart disease and whether this risk can be assessed by clotting activation markers. PATIENTS AND METHODS: A partly prospective, partly retrospective study of data on 237 consecutive patients (201 men, 36 women; mean age 55 [24-76] years) who had undergone coronary arteriography because of severe angina. Concentrations were measured for: beta-thromboglobulin, platelet factor 4, fibrinopeptide A, D-dimers, thrombin-antithrombin III factor (TAT), prothrombin fragments 1 + 2, lipoprotein(a), apolipoprotein A-I (apoA-I), cholesterol and triglycerides. Analysis of any relationship between the findings on coronary arteriography (degree of stenosis) and the occurrence of myocardial infarction, stroke and acute peripheral arterial occlusion before and during the 2 years after the arteriography. RESULTS: There was no correlation between lipid parameters and clotting or platelet activation markers. Patients with a history of acute peripheral arterial occlusion had raised values for lipoprotein(a) and TAT. In the prospective part of the study (i.e. during the first 2 years after blood samples had been taken), there was no correlation. CONCLUSIONS: In patients with coronary artery disease and angina pectoris no correlation was found between lipoprotein(a) and haemostasis activation markers. None of these parameters--prospectively evaluated--could predict risk of thromboembolism.
Adult↗
[Tumor-induced anemia and markers of inflammation].
Anemia of cancer patients is multifactorial but often resembles anemia of chronic inflammatory disorders. We investigated the possibility of measurably increased parameters of inflammation in the serum of cancer patients and examined the correlation of hemoglobin levels, serum iron, and markers of inflammatory response in 201 cancer patients. Serum levels of CRP, ferritin, s-IL-2R, neopterin levels and TNF were assayed with ELISA tests. Statistically significant correlations were found between hemoglobin levels, CRP (Pearson's R = -0.451; p < 0.0001), serum iron (R = 0.326) and ferritin levels (R = -0.449). No significant correlations were seen between hemoglobin levels and neopterin or s-IL-2R. The correlation between hemoglobin levels in cancer patients and elevated markers of inflammatory responses, such as CRP, suggest that cytokines involved in the inflammatory responses may be at least partially responsible, directly or indirectly, for anemia in cancer patients.
Adult↗
Anti-thyroid peroxidase (anti-TPO) antibodies in thyroid diseases, non-thyroidal illness and controls. Clinical validity of a new commercial method for detection of anti-TPO (thyroid microsomal) autoantibodies.
The identification of the thyroid peroxidase (TPO) as the main antigen of the thyroid microsomal fraction has enabled the development of a sensitive and specific assay for detection of the corresponding autoantibodies. We evaluated the diagnostic validity of the anti-TPO assay in 303 patients with different types of thyroid disease and in controls. Clearly elevated anti-TPO values (anti-TPO > 500 units/ml) were found in 59% of patients with thyroiditis but in none of the controls or the patients with non-thyroidal illness. The mean anti-TPO levels in these two control groups were 26 +/- 31 units/ml (mean +/- S.D.) and 39 +/- 34 units/ml, respectively. The highest frequency of positive results (88%) was obtained in patients with auto-immune hypothyroidism (clinical diagnosis: Hashimoto's thyroiditis) followed by patients with Graves' disease (53%). With a cut-off point of 200 units/ml, a sensitivity of 96% was obtained for Hashimoto's thyroiditis and of 59% for Graves' disease with a specificity of 100% (50 cases). The new method (anti-TPO, Dynotest) was compared with three conventional methods (35 samples). The results for all measurements were in general agreement. In two cases the results were clearly discordant: one sample contained high anti-thyroglobulin antibody concentrations, the other was obtained from a patient with non-thyroidal illness. In both instances the 'classical' assays yielded false-positive results. Treatment of autoimmune hyperthyroidism resulted in a median decrease in anti-TPO levels of over 50% after reaching the euthyroid state (P < 0.05), whereas in persistent hyperthyroidism no consistent changes were observed. In autoimmune hypothyroidism a marked variability in anti-TPO levels was noted. Some patients showed a clear decrease in anti-TPO levels during T4 substitution whereas in others no consistent changes were observed.
Autoantibodies↗
Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A.
Severe insulin resistance type A is due to mutations in the insulin receptor gene and is characterized by glucose intolerance or diabetes mellitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recently, we showed that glucose levels in three such patients are promptly lowered by an i.v. bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare patients again and determined fasting and postprandial glucose, insulin, C-peptide, proinsulin and lipid levels during five control, five treatment and three wash-out days while on a constant diet. Treatment consisted of 2 x 150 micrograms rhIGF-I/kg sc per day, which elevated total IGF-I levels 4.5-fold above the control. Fasting glucose levels (days 1-5) in the two patients were 9.6 +/- 1.3 and 9.2 +/- 1.2 mmol/l, respectively, and fell to 4.4 +/- 0.4 and 5.1 +/- 0.5 mmol/l on treatment days 8-10. Fasting insulin (2950 +/- 450 and 690 +/- 125 pmol/l), C-peptide (2217 +/- 183 and 1317 +/- 235 pmol/l) and proinsulin control levels (125 +/- 35 and 66 +/- 0 pmol/l) also decreased by approximately 65% during rhIGH-I treatment, as did the respective postprandial levels. Lipid levels hardly changed at all. In conclusion, IGF-I appears to correct partially some metabolic sequelae of severe insulin resistance and may, hence, be used as a new therapeutic agent.
Adolescent↗
[Pravastatin in the treatment of primary hypercholesterolemia: a Swiss multicenter study].
Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects. Pravastatin is a new potent cholesterol-lowering agent, which selectively inhibits hepatic HMG-CoA-reductase. In a double-blind, placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory, the efficacy and safety of 6 months' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors. Compared to baseline and after 26 weeks' therapy, pravastatin significantly reduced total cholesterol (pravastatin vs placebo, -17% vs +7%, p < 0.0001) and LDL cholesterol (-26 vs +2%, p < 0.0001). The total/HDL cholesterol ratio ( = "atherogenic index") was comparable in the two groups at baseline (5.9 +/- 1.1 vs 6.3 +/- 0.9), and was distinctly lowered by pravastatin but not placebo (-20 vs 0%, p < 0.0001). In 11 patients in whom the reduction of serum total cholesterol after 13 weeks' treatment with 20 mg pravastatin was still below target (on average -9.1%), doubling of the dose produced a further decrease of 4.3%. Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo. Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects. There were 5 dropouts during the study, 2 patients in the pravastatin group and 3 in the placebo group. These findings document that pravastatin, administered in a single daily dose of 20 to 40 mg, effectively lowers serum cholesterol and total-/HDL-cholesterol improving action and is well tolerated.
Cholesterol, HDL↗
Improvement of lipid profile in type 2 (non-insulin-dependent) diabetes mellitus by insulin-like growth factor I.
Type 2 (non-insulin-dependent) diabetes mellitus is associated with increased glucose, insulin, total and VLDL-triglyceride, and often total and LDL-cholesterol levels which promote vascular disease. Recombinant human insulin-like growth factor-I which mimics many effects of insulin, decreased insulin, total and VLDL-triglyceride, and total and LDL-cholesterol levels in healthy man as well as glucose and insulin levels in Type 2 diabetic patients. We, therefore, investigated total and fractionated triglyceride and cholesterol levels, lipoprotein(a), non-esterified fatty acid, and apolipoprotein levels in eight Type 2 diabetic patients during five control, five treatment, and three wash-out days. They received a constant diet throughout and daily 2 x 120 micrograms insulin-like growth factor-I/kg s.c. during the treatment period. Fasting total and VLDL-triglyceride, total and LDL-cholesterol control levels were (mean +/- SD) 3.1 +/- 2.6, 1.3 +/- 1.0, 6.3 +/- 1.3, and 4.5 +/- 1.1 mmol/l and decreased to 1.6 +/- 0.8, 0.6 +/- 0.4, 5.0 +/- 1.0, and 3.5 +/- 1.1 mmol/l, respectively, on the last treatment day (p < 0.01). During therapy, fasting lipoprotein(a) levels and the postprandial area under the triglyceride curve decreased by 48 +/- 22 and 32 +/- 18% of control (p < 0.01), respectively. In conclusion, insulin-like growth factor-I lowered lipid levels in Type 2 diabetic patients directly or indirectly or both because of decreased glucose and insulin levels. Long-term trials would be of interest with respect to the cardiovascular risk in Type 2 diabetes and patients with hyperlipidaemia.
Adult↗