Hypercholesterolemia: Schuster H

Schuster H, Anonymous00170. · Humboldt University Berlin, Droysenstr. 1, 10629 Berlin, Germany. · Atheroscler Suppl. · Pubmed #12714033 No free full text.

Abstract: Populations of patients at high risk of coronary heart disease (CHD) include those with type 2 diabetes and those with heterozygous familial hypercholesterolemia (HeFH). Despite benefits of statin lipid-lowering therapy in reducing CHD risk in diabetic patients, screening for dyslipidemia in such patients is inadequate, and patients frequently fail to achieve recommended low-density lipoprotein goals. Diagnosis of HeFH is also suboptimal, despite the reliability of family lipid screening in confirming clinical diagnosis and utility of screening in identifying other family members who are at risk. Patients with HeFH frequently require large reductions in low-density lipoprotein (LDL) cholesterol to achieve target levels. In both of these populations, statins that produce large reductions in LDL cholesterol offer advantages in achieving lipid-lowering goals and in simplifying medical therapy to reduce CHD risk.

Dallongeville J, Ferrières J, Schuster H, Farnier M, Lepen C. · INSERM U508, Institut Pasteur, Lille, France. · Presse Med. · Pubmed #15523276 No free full text.

This publication has no abstract.

Schuster H. · Humboldt University, Berlin, Germany. · Int J Clin Pract. · Pubmed #15311726 No free full text.

Abstract: Despite the benefits of statin therapy, cholesterol management remains suboptimal and many patients do not achieve their recommended low-density lipoprotein cholesterol (LDL-C) goals. The use of insufficient doses, limited drug effectiveness and poor patient compliance may contribute to the treatment gap. Options for improving lipid management include dose titration, combination therapy or prescribing a more efficacious statin. LDL-C reductions are generally modest when patients' current statin dose is titrated, and there may be an increased potential for adverse effects. Combining statin therapy with another lipid-modifying agent can provide additional LDL-C reductions, but cost, tolerability and compliance should be considered. In general, switching to a more efficacious statin is a cost-effective way of enabling more patients to achieve recommended targets without increasing dosages. When considering the options available, physicians should balance efficacy, cost and safety to enable more patients to attain LDL-C goals and achieve greater therapeutic gain from statin treatment.

Schuster H. · MDC, Humboldt University, Berlin, Germany. · Cardiology. · Pubmed #12824720 No free full text.

Abstract: Rosuvastatin (Crestor; licensed to AstraZeneca, Macclesfield, UK from Shionogi, Osaka, Japan) is a new statin with pharmacologic characteristics that translate into selectivity of effect in hepatic cells and enhanced potency in 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition. It is approved for use at doses of 10-40 mg once daily to reduce low-density lipoprotein (LDL) cholesterol, increase high-density lipoprotein (HDL) cholesterol and improve other lipid measures in dyslipidemic patients. In a dose-ranging study in mild/moderate hypercholesterolemia, rosuvastatin reduced LDL cholesterol by 52-63% at 10-40 mg. Rosuvastatin 10 mg reduces LDL cholesterol significantly more than atorvastatin 10 mg, simvastatin 10-40 mg and pravastatin 10-40 mg, and enables significantly more patients to achieve National Cholesterol Education Program and Joint European Societies LDL cholesterol goals compared with each of these statins. Rosuvastatin also produces marked elevations in HDL cholesterol and maintains this effect across the dose range. Rosuvastatin favorably modifies triglycerides, LDL cholesterol and other lipid measures in patients with hypertriglyceridemia or mixed dyslipidemia, including diabetic patients, and may constitute a monotherapy option for many such patients. Rosuvastatin is well tolerated when used alone or in combination, exhibiting a safety profile similar to that of other available statins. Rosuvastatin offers considerable advantages for use in routine clinical practice.

Vergopoulos A, Knoblauch H, Schuster H. · Max Delbruck Center for Molecular Medicine, University Hospital Charité, Humboldt University of Berlin, Berlin, Germany. · Am J Pharmacogenomics. · Pubmed #12421096 No free full text.

Abstract: Cardiovascular disease is the leading cause of death worldwide and, like most chronic diseases, it has major genetic and environmental components. Among patients with coronary heart disease onset before the age of 55, about 5% of cases are attributable to heterozygous familial hypercholesterolemia (FH), a disease following autosomal dominant inheritance. About 50% of individuals with FH die before the age of 60 due to myocardial infarction. The frequency of FH is estimated to be 1 : 500. FH is related to mutations in the low-density lipoprotein (LDL)-cholesterol LDL-receptor gene and apolipoprotein B (apoB) gene. The identification of individuals with FH has been based on lipid levels and segregation of lipid levels within the family. However, phenotypes are overlapping and family history is not always informative. Therefore, a DNA-based genetic test for FH appears to offer the best alternative. The DNA test gives a simple yes/no answer. The FH test is a definitive tool for the identification of affected family members. The approach of targeted family genetic screening to find new patients is faster and more reliable compared with a biochemical form of screening. Early identification and efficient treatment of such patients is important and highly cost effective. There is evidence to suggest that the nature of the LDL-receptor (LDLR) mutation influences the degree of cholesterol lowering achieved by HMG-CoA reductase inhibitors (statins). The observed differences in the LDL-cholesterol (LDL-C) responses to these drugs among the various LDLR gene mutations are not yet completely understood. The relationships shown between LDLR mutation types and lipid levels, and the response of lipid levels to HMG-CoA reductase inhibitor treatment, will have to be investigated within the framework of pharmacogenetic studies. The variables, which are important in determining the overall atherosclerosis risk, are the result of combined activity in a dynamic network of numerous genes and environment. Candidate genes for atherosclerosis need to be further tested and validated. Future research should be directed at determining the significance of such targets, which patients with FH are at particularly high risk of premature cardiovascular disease, and which environmental factors are effective in modulating this risk. Genetics-based diagnostics will complement identification of FH while improving cardiovascular risk prediction, prevention of disease and treatment efficacy.

Schuster H. · Humboldt University, Berlin, Germany. · Int J Clin Pract Suppl. · Pubmed #12296604 No free full text.

This publication has no abstract.

Schuster H. · Infogen GmbH and Max Delbruck Center, Humboldt University, Berlin, Germany. · Atheroscler Suppl. · Pubmed #11976074 No free full text.

Abstract: Familial hypercholesterolemia provides an excellent model for demonstrating how disease prevention can be facilitated by molecular characterization of a genetic disease. To achieve the most efficient yield in terms of patient identification and coronary heart disease prevention, family information should be obtained in the primary care setting. In the majority of cases, measurement of cholesterol levels in a patient's relatives is sufficient to determine presence or absence of familial hypercholesterolemia, and DNA testing may be used in those cases in which cholesterol level is not diagnostic. DNA testing has enabled a more refined assessment of the absolute cardiovascular risks associated with familial hypercholesterolemia, which is currently estimated to have a 50% mortality rate by age 60. Recent investigations using DNA testing have suggested that familial hypercholesterolemia is implicated in one of 12 cases of cardiovascular disease in individuals aged <65 years. Only the most potent lipid-modifying therapies should be used in those found to be affected by this disorder. In this regard, it is noteworthy that the new statin rosuvastatin (Crestor; AstraZeneca) was recently shown to produce significantly greater low-density lipoprotein (LDL) cholesterol reductions and high-density lipoprotein (HDL) cholesterol increases than atorvastatin in a large study in patients with familial hypercholesterolemia, while bringing more of these patients to LDL cholesterol goals. Familial hypercholesterolemia should serve as a paradigm of molecular medicine: we understand the genetic defect, we have the tools to identify the individuals who are at high risk of disease because they have the defect, and we have therapies that can prevent clinical disease. It nevertheless requires effort on the part of clinicians to ensure that optimal risk assessment is performed and optimal treatment provided.

Cheung RC, Morrell JM, Kallend D, Watkins C, Schuster H. · Southwestern Ontario Medical Education Network Windsor, Schulich School of Medicine, University of Western Ontario, Canada. · Int J Cardiol. · Pubmed #15823640 No free full text.

Abstract: BACKGROUND: Lipid ratios are clinically useful markers of coronary artery disease (CAD) risk. The effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on lipid ratios were investigated in the Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY (MERCURY) I trial. METHODS: This trial was conducted in 3140 hypercholesterolemic patients with CAD, atherosclerosis, type 2 diabetes mellitus, or a 20% 10-year risk for CAD. Patients were randomized to rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks; all patients except those receiving rosuvastatin 10 mg either were switched to rosuvastatin 10 or 20 mg or remained on initial treatment for 8 more weeks. RESULTS: At 8 weeks, reductions in total cholesterol (TC):high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol:HDL-C, non-HDL-C:HDL-C, and apolipoprotein (apo) B:apo A-I ratios with rosuvastatin 10 mg were significantly greater than those with atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, and pravastatin 40 mg (P<0.0001 for all). At week 16, switching to rosuvastatin 10 mg from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg and to rosuvastatin 20 mg from atorvastatin 20 mg produced significantly greater reductions in all lipid ratios (P< or =0.0001 for all). Switching to rosuvastatin 10 mg from atorvastatin 20 mg produced significantly greater reductions in TC:HDL-C (P<0.025) and apo B:apo A-I (P<0.01). CONCLUSIONS: Rosuvastatin 10 mg reduces lipid ratios more than equivalent and higher doses of other statins; switching to equal or lower doses of rosuvastatin produces significantly improved reductions in lipid ratios.

Schuster H, Barter PJ, Stender S, Cheung RC, Bonnet J, Morrell JM, Watkins C, Kallend D, Raza A, Anonymous00057. · Humboldt University, Berlin, Germany. · Am Heart J. · Pubmed #15077101 No free full text.

Abstract: BACKGROUND: In a multinational trial (4522IL/0081), we assessed the effects of switching to low doses of rosuvastatin from commonly used doses of atorvastatin, simvastatin, and pravastatin on low-density lipoprotein cholesterol (LDL-C) goal achievement in high-risk patients. METHODS: Hypercholesterolemic patients (n = 3140) with coronary heart disease, atherosclerosis, or type 2 diabetes were randomized to open-label rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks. Patients either remained on these treatments for another 8 weeks or switched treatments from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg to rosuvastatin 10 mg or from atorvastatin 20 mg to rosuvastatin 10 or 20 mg. The primary efficacy measure was the proportion of patients reaching the Joint European Societies' LDL-C goal (<116 mg/dL) at week 16. For measures of cholesterol goal achievement, treatment arms were compared using logistic-regression analysis. RESULTS: Significant improvement in LDL-C goal achievement was found for patients who switched to rosuvastatin 10 mg, compared with patients who remained on atorvastatin 10 mg (86% vs 80%, P <.05), simvastatin 20 mg (86% vs 72%, P <.0001), and pravastatin 40 mg (88% vs 66%, P <.0001), and between patients switched to rosuvastatin 20 mg and those who remained on atorvastatin 20 mg (90% vs 84%, P <.01). Similar results were found for achievement of the European combined LDL-C and total cholesterol goals and National Cholesterol Education Program Adult Treatment Panel III LDL-C goals. All statins were well tolerated over 16 weeks. CONCLUSIONS: We demonstrated that switching to a more efficacious statin is an effective strategy to improve lipid goal achievement in patients requiring lipid-lowering therapy.

Fonseca FA, Izar MC, Silva MA, Karapanos A, Schuster H, Singh D. · Atherosclerosis and Vascular Biology Laboratory, Federal University of Sao Paulo, Brazil. · Evid Based Cardiovasc Med. · Pubmed #16753506 No free full text.

This publication has no abstract.

Stender S, Schuster H, Barter P, Watkins C, Kallend D, Anonymous00101. · Department of Clinical Biochemistry, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. · Diabetes Obes Metab. · Pubmed #15955130 No free full text.

Abstract: AIM: The metabolic syndrome (MS) increases the risk of coronary heart disease, yet few data are available on the effects of statin treatment in improving lipid measures in patients with the syndrome. This analysis compares the effects of statin therapy on plasma low-density lipoprotein cholesterol (LDL-C) goal achievement and lipid levels in hypercholesterolaemic patients with or without the MS. METHODS: The Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY I (MERCURY I) trial compared rosuvastatin 10 mg with atorvastatin 10 mg and 20 mg, simvastatin 20 mg and pravastatin 40 mg over 8 weeks in patients with coronary or other atherosclerotic diseases or diabetes who had fasting levels of LDL-C of >or=2.99 mmol/l and triglycerides of <4.52 mmol/l. Modified National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria for the MS were met by 1342 (43%) of 3140 patients. RESULTS: LDL-C goal achievement rates and reductions in LDL-C, total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) were similar in patients with and without the MS within statin treatment groups; triglycerides were reduced more and HDL-C tended to be increased more in patients with the MS, as expected. Treatment with rosuvastatin 10 mg was more effective in allowing patients with and without the MS to reach European and ATP III LDL-C goals, compared to atorvastatin 10 mg, simvastatin 20 mg and pravastatin 40 mg (p < 0.0001 for all comparisons); consistently produced greater reductions in LDL-C, total cholesterol and non-HDL-C, compared to these treatments; and produced similar or greater reductions in triglycerides and increases in HDL-C, compared to the other treatments. CONCLUSIONS: Statin therapy is effective in allowing LDL-C goal achievement and improving the lipid profile in hypercholesterolaemic high-risk patients with the MS. Rosuvastatin 10 mg presents significant advantages in goal achievement and lipid lowering over other statins at commonly used doses in patients both with and without the MS.

Schuster H. · INFOGEN, Berlin, Germany. · Am J Med. · Pubmed #15050189 No free full text.

Abstract: Coronary heart disease (CHD) risk assessment to establish risk category and appropriate plasma lipid goals as well as achievement of those lipid goals, are important elements of treatment for dyslipidemia in clinical practice. Cases from clinical practice are presented to illustrate risk assessment and treatment in the settings of peripheral arterial disease (PAD) and heterozygous familial hypercholesterolemia (hFH). Patients with PAD are at high risk of CHD and cardiovascular mortality and may require aggressive lipid-lowering therapy irrespective of the degree of hypercholesterolemia at presentation. Risk in patients with hFH is not adequately reflected in population-based risk algorithms. Patients who have hFH should be considered at high risk for developing CHD and given aggressive lipid-modifying therapy, and family screening should be undertaken for additional case finding.

Schuster H. · Humboldt University, Berlin. · Am J Manag Care. · Pubmed #13678396 links to  free full text

This publication has no abstract.

Knoblauch H, Müller-Myhsok B, Busjahn A, Ben Avi L, Bähring S, Baron H, Heath SC, Uhlmann R, Faulhaber HD, Shpitzen S, Aydin A, Reshef A, Rosenthal M, Eliav O, Mühl A, Lowe A, Schurr D, Harats D, Jeschke E, Friedlander Y, Schuster H, Luft FC, Leitersdorf E. · Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine and Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. · Am J Hum Genet. · Pubmed #10631147 links to  free full text

Abstract: A cholesterol-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to those in persons with heterozygous FH. We studied such a family with FH that also had members without FH and with lower-than-normal LDL levels. We performed linkage analyses and identified a locus at 13q, defined by markers D13S156 and D13S158. FASTLINK and GENEHUNTER yielded LOD scores >5 and >4, respectively, whereas an affected-sib-pair analysis gave a peak multipoint LOD score of 4.8, corresponding to a P value of 1.26x10-6. A multipoint quantitative-trait-locus (QTL) linkage analysis with maximum-likelihood binomial QTL verified this locus as a QTL for LDL levels. To test the relevance of this QTL in an independent normal population, we studied MZ and DZ twin subjects. An MZ-DZ comparison confirmed genetic variance with regard to lipid concentrations. We then performed an identity-by-descent linkage analysis on the DZ twins, with markers at the 13q locus. We found strong evidence for linkage at this locus with LDL (P<.0002), HDL (P<.004), total cholesterol (P<.0002), and body-mass index (P<.0001). These data provide support for the existence of a new gene influencing lipid concentrations in humans.