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Biomedical subjects

R S Scott

Publications and source records attributed to R S Scott.

At least 19 recordsLinked to original sources
PubMed2006

Short-term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non-ischaemic heart failure.

OBJECTIVES: To investigate the effect of short-term statin treatment on impaired endothelium-dependent vasodilatation and haemodynamic abnormalities typically occurring in chronic heart failure (CHF). METHODS: In a double-blind, crossover study endothelium-dependent vasodilatation was measured in conduit and resistance vessels of 23 patients with non-ischaemic CHF after 6 weeks of placebo and 40 mg atorvastatin. The haemodynamic impact was assessed by cardioendocrine hormones, echocardiography and clinical indicators of CHF. RESULTS: Cholesterol concentrations were population average (low density lipoprotein 3.56 (SEM 0.16) mmol/l, triglycerides 1.70 (0.20) mmol/l and high density lipoprotein 1.17 (0.07) mmol/l). In resistance vessels, the area under the curve ratio during acetylcholine infusion increased from 9.2 (1.9) with placebo to 12.2 (2.1) with statin (p < 0.01). This improvement was reversed during co-infusion with the nitric oxide antagonist N(G)-monomethyl-L-arginine. In conduit arteries, flow-mediated dilatation increased from 5.64 (SEM 0.88)% with placebo to 6.83 (0.97)% with statin (p < 0.05). Endothelium-independent vasodilatation did not change (p = 0.68 for conduit and p = 0.45 for resistance vessels). Endothelin 1 and atrial natriuretic peptide (ANP) decreased from 1.57 (0.08) and 51.3 (1.0) with placebo to 1.42 (0.09) pg/ml (p < 0.05) and 42.1 (7.5) pmol/l (p < 0.05), respectively, with statin. CONCLUSIONS: In patients with non-ischaemic CHF and population-average cholesterol concentrations, short-term statin treatment improves endothelial function in conduit and resistance vessels and lowers plasma endothelin 1 and ANP concentrations.

Atorvastatin↗
PubMed2006

Epstein-Barr virus shed in saliva is high in B-cell-tropic glycoprotein gp42.

Epstein-Barr virus is an orally transmitted human herpesvirus that infects epithelial cells and establishes latency in memory B lymphocytes. Movement of virus between the two cell types is facilitated by changes in amounts of an envelope glycoprotein, gp42, which are effected by interaction of gp42 with HLA class II in a B cell. Here we used the differential ability of virus to bind to CD21-positive B cells and CD21-negative epithelial cells, which is also influenced by levels of gp42, to determine that the majority of virus shed in saliva is derived from an HLA class II-negative cell.

B-Lymphocytes↗
PubMed2004

The postprandial state does not impair endothelial function in women with type 2 diabetes irrespective of glycaemic control.

AIMS/HYPOTHESIS: The postprandial state has been shown to be associated with endothelial dysfunction, a predictor of cardiovascular morbidity. In type 2 diabetes, postprandial metabolic excursions are prolonged and exaggerated, but less pronounced if glycaemic control is optimised. We investigated the impact of improved glycaemic control on endothelial function in the postprandial state. METHODS: We studied 19 postmenopausal women with type 2 diabetes and ten non-diabetic subjects. Participants with diabetes were re-studied 3 months after intensive glucose regulation. We measured forearm blood flow by strain gauge plethysmography during rest, during acetylcholine infusion and post ischaemia in the fasting state, and again 3 hours after a mixed meal (660 kcal, 55% fat). RESULTS: Endothelium-dependent vasodilation was impaired in the diabetic group (p<0.005) and improved following an HbA1c reduction of 0.96% (p<0.05 for high-dose acetylcholine infusion). Postprandial metabolic excursions were higher in the diabetic group (p<0.001, p<0.01 and p<0.05 for glucose, insulin and triglycerides respectively). Resting forearm blood flow increased in all groups after the meal (p<0.005). There was no difference in fasting and postprandial endothelium-dependent vasodilation before and after improved glucose regulation in either group. CONCLUSIONS/INTERPRETATION: The postprandial state does not impair endothelial function in non-diabetic women and does not make pre-existing endothelial dysfunction worse in women with type 2 diabetes, irrespective of glycaemic control.

Aged↗
PubMed2004

Genetic screening of patients with familial hypercholesterolaemia (FH): a New Zealand perspective.

Using denaturing high performance liquid chromatography (DHPLC) to screen the LDL receptor gene of people with familial hypercholesterolaemia (FH) in Christchurch, New Zealand, we have identified mutations in 65 patients (44 different mutations, of which 15 are novel). We also test family members of probands for the mutation identified in their relative, allowing diagnosis of affected children and those without classical FH symptoms. This screening programme is helpful to clinicians and benefits FH patients and their families, and has provided us with a pool of LDL receptor variants on which to base research into this disease.

Chromatography, High Pressure Liquid↗
PubMed2004

Prospective audit of conversion from regular to lispro insulin during routine clinical care.

BACKGROUND: Randomized controlled trials show that lispro insulin has the potential to improve glycaemic control. Observational, practice-based studies provide information that is complementary to that obtained from randomized controlled trials and results of both types of studies are of relevance when advising patients of likely outcomes during routine clinical care. AIMS: This prospective audit aimed to determine whether conversion from regular (short-acting, soluble) preprandial insulin to lispro during routine clinical care improved glycated haemoglobin. METHODS: Eligible patients were those using regular insulin before main meals and a basal neutral protamine Hagedorn (NPH) insulin. Study group patients were those who chose to convert to lispro insulin. Patients who elected not to change their regimen were used as a comparison group. Follow up was for a minimum of 1 year. RESULTS: Glycated haemoglobin (HbA(1c)) and body mass index showed no change in either the study or comparison groups. Post-hoc analysis revealed that the patients most likely to improve their HbA(1c) on lispro were those with a higher baseline HbA(1c). Patients using lispro reported a decreased frequency of hypoglycaemia and improved convenience of use. CONCLUSIONS: Administration of lispro insulin was perceived by patients as convenient to use and was also associated with less hypoglycaemia when compared with the use of regular insulin. There was, however, no improvement in HbA(1c). This finding may be informative when advising patients during routine clinical care of the likely metabolic outcome of changing their insulin regimen.

Body Mass Index↗
PubMed2004

Plasma sex hormone-binding globulin rather than corticosteroid-binding globulin is a marker of insulin resistance in obese adult males.

AIM: Plasma levels of corticosteroid-binding globulin (CBG) and sex hormone-binding globulin (SHBG) may be regulated by insulin. The aim of this study was to test the hypothesis that these steroid-binding proteins are markers of insulin resistance and obesity in adult patients with the metabolic syndrome. METHODS: Fasting blood samples were obtained from 108 male and 88 female overweight adult patients who had varying degrees of dyslipidaemia, adiposity and insulin resistance. We measured plasma levels of SHBG and CBG and investigated their correlation with insulin resistance [homeostasis model assessment (HOMA) % sensitivity] and anthropometric markers of adiposity. RESULTS: In male patients, plasma SHBG correlated positively with HOMA (% sensitivity) and negatively with anthropometric measurements, including body mass index, waist circumference (cm) and percentage body fat. There was no correlation with CBG and any other parameter in the male patients. The female patients were treated as two groups, those not using oral contraceptives or hormone replacement therapy (n = 67) and those taking steroid medications (n = 21). Female patients using steroid medications had significantly higher SHBG levels but neither group showed any correlation between SHBG, insulin resistance and adiposity. Correlation studies of CBG with other parameters in the female subgroups did not reach statistical significance. CONCLUSIONS: We conclude that plasma SHBG is another surrogate marker for insulin resistance in obese males but not in obese females. It also appears that plasma CBG is not a useful marker of insulin resistance in patients with the metabolic syndrome.

Biomarkers↗
PubMed2003

Plasma adiponectin in overweight, nondiabetic individuals with or without insulin resistance.

AIM: Adiponectin is a protein produced exclusively by adipocytes with putative insulin-sensitizing and anti-atherogenic properties. This cross-sectional study investigated the relationship between plasma adiponectin and a range of anthropometric, glycaemic, lipid and inflammatory parameters in overweight and obese subjects expressing characteristics of the metabolic syndrome. METHODS: Subjects were selected for the study from a clinical database, if they were non-diabetic, overweight [body mass index (BMI) > 25] and had features of the metabolic syndrome. The subjects were grouped according to BMI (25-30, 31-35 and >35 kg/m2) and then stratified for insulin resistance [homeostasis model assessment (HOMA) %S]. One hundred and ninety-seven patients (109 males and 88 females) were selected for the study by taking an equal number with the highest and lowest HOMA indices from each of the three BMI groups. Plasma adiponectin concentration was measured in duplicate by radioimmunoassay, and the relationship between these levels and the other parameters was investigated using correlation and multiple linear regression analyses. RESULTS: Plasma adiponectin concentration was higher in females than males (median 10.3 vs. 7.1 micro g/ml, p < 0.001) despite being matched for BMI. In both genders, adiponectin levels were inversely related to BMI, waist circumference, percentage body fat, insulin resistance and the fasting plasma concentration of leptin. A direct correlation in both sexes was found between adiponectin levels and high-density lipoprotein (HDL)-cholesterol, apolipoprotein A1 and age. Multiple linear regression analyses showed that the independent determinants of low plasma adiponectin concentrations were gender, age, BMI, insulin resistance and HDL-cholesterol. An association between reduced adiponectin and increased high-sensitivity plasma C-reactive protein concentration was observed only in female subjects and was independent of anthropometric variables. Our observation that adiponectin levels increase with age differs from the majority of other studies and may simply reflect the demographics of the population studied. CONCLUSIONS: This study shows that adiponectin is an important molecular link between obesity, insulin resistance and atherogenic lipoproteins. It is possible that plasma adiponectin concentration may be a convenient marker for identifying subjects with the metabolic syndrome who may progress to impaired glucose tolerance. Longitudinal studies are required in order to verify this clinical application of adiponectin.

Adiponectin↗
PubMed2003

Cause-specific and total mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population: a 15-year follow-up study.

AIMS: To establish all-cause and cause-specific death rates, and risk factors for mortality in insulin-treated diabetic individuals living in the province of Canterbury, New Zealand. METHODS: Insulin-treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time. RESULTS: There were 419 deaths in 11 226.3 person-years of follow-up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8-2.2). Relative mortality was greatest for the group aged 0-29 years (SMR 3.0 (95% CI 2.4-3.7)). After controlling for diabetes duration and gender, a 10-year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29-36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10-year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24-29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis. CONCLUSIONS: Mortality rates are high for insulin-treated diabetic individuals relative to the general population.

Adolescent↗
PubMed2001

Implementation of evidence based cardiovascular risk treatments by general practitioners.

AIM: To review general practitioner (GP) implementation of evidence based cardiovascular risk reducing strategies in subjects with coronary heart disease (CHD). METHODS: Audit of patient records of randomly selected GPs. RESULTS: There were 326 subjects with CHD under the care of 21 doctors. Except for smoking, details of lifestyle measures were rarely found in the notes. Advice on diet and exercise was mentioned in 51% and 23.3% of records respectively. Aspirin and beta-blockers were widely used. Of patients with drug untreated values of total cholesterol (TC) and/or TC/HDL exceeding National Heart Foundation (NHF) guidelines, 71% were prescribed lipid-modifying drugs. NHF targets for TC (< or = 5.0 mmol/l) were achieved by 37% and for TC/HDL (< or = 4.5) by 60%. TC remained above 5.5 mmol/L in 120 cases. Lipid results from tests within the last 12 months were found in 60% of cases. CONCLUSIONS: Recording of lifestyle treatments in subjects with CHD appears to be assigned low priority. Cardioprotective treatments were widely used. Cholesterol levels were recorded frequently and of those with values exceeding NHF guidelines, nearly 3/4 were on medication. Recommended targets for lipid parameters were being achieved by <50% of patients. More frequent monitoring could improve this outcome

Adrenergic beta-Antagonists↗
PubMed2001

Phagocytosis and clearance of apoptotic cells is mediated by MER.

Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens. Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family. mer(kd) mice with a cytoplasmic truncation of Mer had macrophages deficient in the clearance of apoptotic thymocytes. This was corrected in chimaeric mice reconstituted with bone marrow from wild-type animals. Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles. The inability to clear apoptotic cells adequately may be linked to an increased number of nuclear autoantibodies in mer(kd) mice. Thus, the Mer receptor tyrosine kinase seems to be critical for the engulfment and efficient clearance of apoptotic cells. This has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus.

Animals↗
PubMed2001

Age at diagnosis, glycaemic control and the development of retinopathy in a population-based cohort of Type 1 diabetic subjects in Canterbury, New Zealand.

The aim was to determine the relationship between age at diagnosis, glycaemic control and the development of retinopathy in a population-based cohort of Type 1 diabetic subjects. At 1 January 1984, there were 286 individuals with Type 1 diabetes (and age of onset<20 years) on the Canterbury, New Zealand population register who had at least 2 prospective HbA(1c) readings (from 1 January 1984). Of these, 107 already had retinopathy. Of the 179 subjects without retinopathy at baseline 63 developed retinopathy during follow-up. After controlling for duration of diabetes (in the whole group), age at diagnosis was found to be a significant predictor of HbA(1c) level (P=0.001), with higher (mean+/-SD) baseline HbA(1c) in the 10-14 age group (7.95+/-2.14%), compared with (7.62+/-1.77%) in the <10 year group and (7.39+/-2.57%) in the >14 year group. The major predictors of retinopathy (in those without retinopathy at baseline), however were duration of diabetes (mean time to development of retinopathy decreases by 14% (95% CI 10-17%) for each year), baseline HbA(1c) (for each unit increase, mean time to development of retinopathy decreased by 23% (95%CI 13-32%) and HbA(1c) slope (average annual change). Peri-pubertal age at diagnosis (10-14 years) did not influence the time to onset of retinopathy over and above that attributed to duration of diabetes and glycaemic control.

Adolescent↗
PubMed2001

Predictors of mortality from type 2 diabetes mellitus in Canterbury, New Zealand; a ten-year cohort study.

The aim was to establish mortality rates in a cohort of subjects with type 2 diabetes mellitus over 10 years in Canterbury, New Zealand (NZ) and to determine baseline prognostic factors. Subjects (447) with type 2 diabetes (208 male, 239 female; age range 30-82 years, median 62 years; of predominantly European origin) were characterised in a clinic survey in 1989. Individual status (dead or alive) at June 1 1999 (10 year follow-up) was ascertained. Mortality rates were compared with the general NZ population and the relative risk (RR) of baseline prognostic factors evaluated with Cox's proportional hazards model. At 10 years, 232 subjects were confirmed as alive and 187 as dead - only 28 were untraceable. Ten year survival was 55% (95% CI: 50-60) for the cohort, compared with 70% (95% CI: 65-75) at 6 years. Factors assessed at baseline (1989), that were independently prognostic of total mortality, included age (RR 2.0, 95% CI: 1.6-2.5), pre-existing coronary artery disease (CAD; RR 1.7, 95% CI: 1.2-2.4) and albuminuria (RR 1.58, 95% CI: 1.1-2.3). Glycated haemoglobin was not a significant predictor of total mortality, although was a predictor of CAD mortality in those subjects free of CAD in 1989 (RR 1.6, 95% CI: 1.1-2.3). In the latter subset, independent prognostic factors for CAD mortality also included age (RR 2.5, 95% CI: 1.7-3.8), hypertension (RR 1.9, 95% CI: 1.0-3.7), peripheral vascular disease (RR 2.4, 95% CI: 1.3-4.5) and smoking (RR 2.6, 95% CI: 1.2-5.8). Increased mortality in type 2 diabetic subjects is therefore attributable to multiple risk factors. Improved outcomes will depend on interventions targeted at glycaemic and all other remediable factors.

Adult↗
PubMed2001

All-cause mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population.

OBJECTIVE: To establish all-cause death rates and life expectancies of and risk factors for mortality in insulin-treated diabetic individuals living in Canterbury, New Zealand. RESEARCH DESIGN AND METHODS: Insulin-treated diabetic subjects (n = 1,008) on the Canterbury Diabetes Registry were tracked over 9 years, and their vital status was determined. Death rates were standardized using direct and indirect methods. Cox proportional hazard regression was used to model the effects of demographic and clinical covariates on survival time. RESULTS: At study entry, age ranged from 2.9 to 92.7 years, with mean 48.7 +/- 20.4 years; age at diagnosis was 0.2-88.9 years, mean 34.5 +/- 20.0 years; and duration of diabetes was 0.1-58.5 years, mean 14.0 +/- 10.6 years. There were 303 deaths in 7,372 person-years of follow-up with a standardized mortality ratio (SMR) of 2.6 (95% CI 2.4-3.0). Relative mortality was greatest for those aged 30-39 years (SMR 9.2 [4.8-16.2]). The death rate for the diabetic cohort standardized against the Segi world standard population was 16.2 per 1,000. Attained age, sex, and clinical subtype were significant predictors of mortality The SMR for subjects with type 1 diabetes and age at onset <30 years was 3.7 (CI 2.7-5.0), 2.2 (1.8-2.6) for those with onset > or =30 years, and 3.1 (2.5-3.7) for subjects suspected of having latent autoimmune diabetes in adulthood or insulin-treated type 2 diabetes. Life expectancy was reduced for both sexes at all ages. CONCLUSIONS: Mortality rates for insulin-treated diabetic individuals remain high, resulting in shortened life spans relative to the general population. Marked differences in mortality exist between clinical groups of subjects. Further research is needed to improve diabetes classification and to clarify differences in health outcomes.

Adolescent↗
PubMed2001

A comparison of post-prandial changes in flow-mediated dilatation in patients with type 2 diabetes with and without macroalbuminuria.

During the post-prandial period there is a decrease in systemic vascular resistance. This study compared meal-induced changes in flow-mediated dilatation (FMD) in patients with Type 2 diabetes with and without evidence of diabetic nephropathy as defined by the presence of macroalbuminuria. The effects on FMD of other factors such as smoking history, antihypertensive treatment and insulin use were also examined. Twelve patients with macroalbuminuria (>300 mg albumin/day) and 12 age- and sex-matched patients with normoalbuminuria (<50 mg albumin/day) participated in the study. Following a 12-hr overnight fast, forearm basal and reactive hyperaemic blood flow was assessed by venous occlusion plethysmography before and 2-hr after ingestion of a meal (2750 kJ) consisting of 56% fat, 26% carbohydrate and 16% protein. Plasma lipid and glycaemic indices were measured at the same times. The combined and grouped data was analysed using paired t tests and correlation and regression analyses. The meal resulted in significant increases in plasma glucose and triglyceride concentrations. While the meal resulted in a similar increase in basal blood flow rate in both patient groups, post-meal reactive hyperaemic flow increased significantly (p=0.04) in normoalbuminuric patients (mean individual increase: 33%) but remained unchanged in patients with macroalbuminuria (mean individual increase: 4%). The use of antihypertensive agents and insulin was also associated with an attenuated post-prandial hyperaemic response. In summary, our study demonstrated that the degree of renal impairment in patients with Type 2 diabetes may influence vasoactivity following a meal. Patients with evidence of diabetic nephropathy had a decreased post-prandial hyperaemic response, a result that indicated a reduced vasodilator reserve. The mechanism of this reduction in vasodilatation of peripheral vessels during the post-prandial period is probably multifactorial. These changes in vasoactivity have the potential to combine with other cardiovascular risk factors to enhance the development of atheroma.

Aged↗
PubMed2000

Lipid-altering efficacy and safety of simvastatin 80 mg/day: long-term experience in a large group of patients with hypercholesterolemia. World Wide Expanded Dose Simvastatin Study Group.

BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol promote the development of atherosclerosis and coronary heart disease. HYPOTHESIS: Simvastatin 80 mg/day will be more effective than simvastatin 40 mg/day at reducing LDL cholesterol and will be well tolerated. METHODS: Two similar, randomized, multicenter, controlled, double-blind, parallel-group, 48-week studies were performed to evaluate the long-term lipid-altering efficacy and safety of simvastatin 80 mg/day in patients with hypercholesterolemia. One study conducted in the US enrolled patients meeting the National Cholesterol Education Program (NCEP) LDL cholesterol criteria for pharmacologic treatment. In the other multinational study, patients with LDL cholesterol levels > or = 4.2 mmol/l were enrolled. At 20 centers in the US and 19 countries world-wide, 1,105 hypercholesterolemic patients, while on a lipid-lowering diet, were randomly assigned at a ratio of 2:3 to receive simvastatin 40 mg (n = 436) or 80 mg (n = 669) once daily for 24 weeks. Those patients completing an initial 24-week base study were enrolled in a 24-week blinded extension. Patients who had started on the 80 mg dose in the base study continued on the same dose in the extension, while those who had started on the 40 mg dose were rerandomized at a 1:1 ratio to simvastatin 40 or 80 mg in the extension. RESULTS: There was a significant advantage in the LDL cholesterol-lowering effect of the 80 mg dose compared with that of the 40 mg dose, which was maintained over the 48 weeks of treatment. The mean percentage reductions (95% confidence intervals) from baseline in LDL cholesterol for the 40 and 80 mg groups were 41% (42, 39) and 47% (48, 46), respectively, for the 24-week base study, and 41% (43, 39) and 46% (47, 45), respectively, after 48 weeks of treatment (p < 0.001 between groups). Larger reductions in total cholesterol and triglycerides were also observed with the 80 mg dose compared with the 40 mg dose at Weeks 24 and 48. Both doses were well tolerated, with close to 95% of patients enrolled completing the entire 48 weeks of treatment. Myopathy (muscle symptoms plus creatine kinase increase > 10 fold upper limit of normal) and clinically significant hepatic transaminase increases (> 3 times the upper limit of normal) occurred infrequently with both doses. There was no significant difference between the groups in the number of patients with such increases, although there were more cases for both with the 80 mg dose. CONCLUSIONS: Compared with the 40 mg dose, simvastatin 80 mg produced greater reductions in LDL cholesterol, total cholesterol, and triglycerides. Both doses were well tolerated.

Adult↗
PubMed2000

Mutation analysis in a small cohort of New Zealand patients originating from the United Kingdom demonstrates genetic heterogeneity in familial hypercholesterolemia.

Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are relatively common lipid disorders caused by mutations in the low-density lipoprotein receptor (LDLR) and apolipoprotein B (apo B) genes, respectively. Molecular analysis at these loci was performed in eight New Zealand subjects with clinical features of heterozygous FH. Utilization of an in vitro lymphocyte receptor assay demonstrated normal receptor function in four patients, three of whom screened positive for the founder-type apo B mutation, R3500Q, causing FDB. Four patients with reduced LDLR function, consistent with heterozygous FH, revealed three previously documented mutations in exons 3 (W66X), 6 (C292Y) and 7 (G322S) of the LDLR gene and, a novel 2-bp deletion (TC or CT) after nucleotide 1204 (or 1205) in exon 9. The remaining patient was found to be FH/FDB negative after extensive mutation screening using both denaturing gradient gel electrophoresis and heteroduplex-single strand conformation polymorphism analysis. Haplotype analysis at the LDLR and apo B loci finally excluded the likelihood that mutations in these two genes underlie the FH phenotype in the molecularly uncharacterized New Zealand family originating from the United Kingdom. This family represents a valuable source of material for future genetic dissection of autosomal dominant hypercholesterolemia (ADH), shown to be a heterogeneous disease through molecular analysis.

Adult↗
PubMed2000

Lipid-altering efficacy and safety of simvastatin 80 mg/day: worldwide long-term experience in patients with hypercholesterolemia.

BACKGROUND AND AIM: Clinical data suggesting that larger decreases in low density lipoprotein cholesterol (LDL-C) result in greater reductions in coronary heart disease events have led to the establishment of aggressive LDL-C targets for the treatment of hypercholesterolemia. In view of this, the efficacy and safety of a new maximum dose of simvastatin, 80 mg, were evaluated in 9 studies involving 2819 hypercholesterolemic patients. This report focuses on the combined results from the 4 main or Pivotal studies in which a total of 1936 patients received simvastatin 40 or 80 mg for 36 to 48 weeks. METHODS AND RESULTS: The Pivotal studies had similar randomized, multicenter, controlled, double-blind, parallel-group designs. Their combined results demonstrated a significant advantage in the LDL-C-lowering effect for the 80 mg dose. At week 24, the mean percentage reductions (95% confidence intervals) from baseline in LDL-C for the 40 and 80 mg groups were -39.8% (-40.9, -38.7) and -45.7% (-46.5, -45.0) respectively (p < 0.001, between groups), and larger reductions in total cholesterol and triglycerides were also observed in the 80 mg group. Both doses were well tolerated. No new or unexpected adverse events were observed and the overall clinical event profiles were similar in the two groups. Clinically significant hepatic transaminase increases (> 3 times the upper limit of normal/ULN) and myopathy (muscle symptoms plus creatine kinase increase > 10 times ULN) occurred infrequently with both doses. Simvastatin 80 mg had a comparable efficacy and safety profile in women and men as well as in non-elderly and elderly patients. CONCLUSIONS: Simvastatin 80 mg provides additional LDL-C and triglyceride reductions compared to the 40 mg dose and has an excellent safety and tolerability profile.

Adolescent↗