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Biomedical subjects

A G Olsson

Publications and source records attributed to A G Olsson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.

CONTEXT: Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. OBJECTIVE: To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. DESIGN AND SETTING: A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. PATIENTS: A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. INTERVENTIONS: Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. MAIN OUTCOME MEASURES: Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. RESULTS: A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12 vs 24 events; P =.045). In the atorvastatin group, mean low-density lipoprotein cholesterol level declined from 124 mg/dL (3.2 mmol/L) to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P<.001). CONCLUSION: For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.

Aged↗
PubMed2001

Statin therapy and reductions in low-density lipoprotein cholesterol: initial clinical data on the potent new statin Rosuvastatin.

The utility of statins with increased potency in reducing low-density lipoprotein cholesterol (LDL-C) is indicated by evidence that aggressive LDL-C lowering is associated with increased reduction in coronary artery disease risk, and the need for such agents is illustrated by the fact that many patients currently fail to achieve LDL-C target levels during treatment with available drugs. In dose-ranging studies of patients with hypercholesterolemia, the new synthetic statin rosuvastatin (formerly ZD4522) produced significant, dose-dependent reductions in LDL-C compared with placebo across a range of doses. Reductions ranged from 34% at 1 mg per day to 65% at 80 mg per day, with linear regression analysis indicating an additional 4.5% reduction in LDL-C with each doubling of the rosuvastatin dose. Rosuvastatin treatment was well tolerated. Phase 3 clinical trials of this agent are under way.

Cholesterol, LDL↗
PubMed2001

A new statin: a new standard.

Numerous studies have demonstrated that treatments designed to reduce low-density lipoprotein cholesterol (LDL-C) can reduce the risk of coronary heart disease (CHD) events in the setting of either primary or secondary prevention. The rationale for aggressive lowering of LDL-C, supported by large observational studies, is the concept that no threshold exists below which reductions fail to provide additional benefit. The statins are widely considered first-line therapy for preventing CHD events because these agents yield the greatest reductions in LDL-C. However, many patients do not achieve target LDL-C levels with the currently available statins. Newer, more effective statins may permit the benefits of aggressive LDL-C reduction to be extended to larger numbers of patients. A novel, highly efficacious statin, rosuvastatin (Crestor, AstraZeneca group of companies), is currently undergoing clinical investigation. Dose-ranging studies in hypercholesterolemic patients have shdwn that rosuvastatin produces significant, dose-dependent decreases in LDL-C when compared with placebo. Reductions have ranged from 34% at a dose of 1 mg/day to 65% at 80 mg/day. This agent has been found to be well tolerated across the range of doses studied. Phase III studies indicate that rosuvastatin is more effective than atorvastatin, pravastatin, and simvastatin in improving the atherogenic lipid profiles of hypercholesterolemic patients, and more effective than atorvastatin in improving the atherogenic lipid profiles of patients with heterozygous familial hypercholesterolemia. Overall, these findings suggest that rosuvastatin is a promising new medication for the treatment of dyslipidemias.

Anticholesteremic Agents↗
PubMed2001

Comparison of the efficacy and tolerability of fluvastatin extended-release and immediate-release formulations in the treatment of primary hypercholesterolemia: a randomized trial.

BACKGROUND: A new extended-release (ER) formulation of fluvastatin 80 mg has been developed for once-daily treatment of primary hypercholesterolemia. OBJECTIVE: The purpose of this study was to compare the lipid-lowering efficacy and tolerability of fluvastatin ER (80 mg once daily) versus fluvastatin immediate-release (IR) (40 mg once or twice daily). METHODS: Following a 4-week placebo/dietary run-in period, patients with primary hypercholesterolemia type IIa or IIb (low-density lipoprotein cholesterol ILDL-C] > or = 160 mg/dL and triglycerides [TG] < or = 400 mg/dL) were randomized (2:1:1) to receive fluvastatin ER 80 mg once daily at bedtime (QPM), fluvastatin IR 40 mg QPM, or fluvastatin IR 40 mg BID for 24 weeks. Patients who had homozygous familial hypercholesterolemia; type I, III, IV, V, or secondary hyperlipoproteinemia; diabetes; or evidence of liver or renal impairment were excluded. At weeks 0, 2, 4, 8, 12, 16, 20, and 24 of the active-treatment period, levels of LDL-C, high-density lipoprotein cholesterol (HDL-C), TG, and total cholesterol (TC) were measured. RESULTS: Of the 1183 patients enrolled, 695 were randomly assigned to treatment--346 to fluvastatin ER 80 mg QPM, 174 to fluvastatin IR 40 mg QPM, and 175 to fluvastatin IR 40 mg BID. Patients were well matched between groups, with a mean age of approximately 56 years and body mass index of 27 kg/m2; 56.0% of patients (389/695) were female and 97.7% (679/695) were white. Fluvastatin ER 80 mg QPM lowered LDL-C levels significantly more than did fluvastatin IR 40 mg QPM (33.7% vs 24.4%; P < 0.001) and as effectively as fluvastatin IR 40 mg BID (33.9%). More than half of the patients administered fluvastatin ER 80 mg QPM and IR 40 mg BID achieved reductions in LDL-C levels of > or = 35%; more than half of those administered fluvastatin IR 40 mg QPM experienced reductions in LDL-C levels of > or = 25%. The mean reductions in LDL:HDL ratio, TC, and apolipoprotein B levels in the fluvastatin ER 80 mg QPM group were significantly greater than the reductions in the IR 40 mg QPM group (P < 0.001). In patients with mixed dyslipidemia, fluvastatin ER 80 mg reduced triglycerides by 21.8% (median 28%) and increased HDL-C by 14.5%. Fluvastatin ER 80 mg QPM was well tolerated, with incidences of clinically notable elevations in alanine aminotransferase, aspartate aminotransferase, and creatine kinase levels and musculoskeletal adverse events comparable to those in the IR 40 mg QPM group. CONCLUSION: The ER 80-mg formulation of fluvastatin is effective and well tolerated as a once-daily starting and maintenance treatment for primary hypercholesterolemia.

Adult↗
PubMed2001

Effects of fluvastatin on cardiac events in renal transplant patients: ALERT (Assessment of Lescol in Renal Transplantation) study design and baseline data.

BACKGROUND: Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ('statins') reduces morbidity and mortality from coronary heart disease in diverse patient populations. STUDY AIMS: The aim of the present ALERT (Assessment of Lescol in Renal Transplantation) study is to determine whether renal transplant recipients would also benefit from statin therapy. ALERT is a multicentre, randomized, double-blind, placebo-controlled trial to assess the effect of fluvastatin in renal transplant recipients with mild-to-moderate hypercholesterolaemia. The primary objective is to investigate the effects of fluvastatin on major adverse cardiac events (MACE). In addition, the effects on cardiovascular and all-cause mortality, as well as renal function, will be addressed. STUDY POPULATION: The study population contains patients with functioning renal allografts of more than 6 months' duration, recruited from 75 centres in Northern Europe and Canada. Patients of both sexes, aged 30-75 years, with a total cholesterol level of 4.0-9.0 mmol/l (155-348 mg/dl) were included, except for those with a history of myocardial infarction, where the upper limit for inclusion was 7.0 mmol/l (270 mg/dl). STUDY DESIGN: A total of 2100 patients were recruited by the end of October 1997 and will be followed for up to 6 years. This report presents the design features of the study (recruitment, follow-up, sample size, data analysis and study organization), along with baseline results. ALERT is the first large-scale prospective, randomized, double-blind study to address the prevention of cardiovascular mortality in renal transplant patients receiving an HMGCoA reductase inhibitor.

Adult↗
PubMed2001

A new statin: a new standard.

In a 2-stage, placebo-controlled, Phase 2 dose-ranging trial evaluating the new statin rosuvastatin in men and postmenopausal women with hypercholesterolemia, the agent was found to reduce low-density lipoprotein cholesterol (LDL-C) levels in a dose-related manner. With each doubling of the rosuvastatin dose (1, 2.5, 5, 10, 20, 40, and 80 mg/day), there was an additional 4.5% reduction in LDL-C. Reductions in LDL-C were statistically significant across all doses and ranged from 35% to 65%. The latter percent reduction surpasses the maximal reductions reported for all other statins when used for monotherapy and suggests that rosuvastatin might enable more patients with hypercholesterolemia to achieve target LDL-C levels. Across all doses, the new statin also had favorable effects on other lipid parameters and was well tolerated, with the incidence of adverse events similar to placebo.

Adolescent↗
PubMed2000

Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering.

The Scandinavian Simvastatin Survival Study (4S) and other randomized clinical trials have demonstrated that cholesterol-lowering treatment with statins improves prognosis in patients with coronary atherosclerosis compared with placebo. The effect of therapy with statins beyond the typical 5 to 6 years' duration of the trials, in particular regarding the risk of cancer, has not been investigated. This study examines the long-term effects of simvastatin for up to 8 years on cause-specific mortality in patients with coronary heart disease (CHD). We performed an observational, government registry-based study of mortality in the groups originally randomized to simvastatin or placebo in the 4S over an additional 2-year follow-up period, so that the median total follow-up period was 7.4 years (range 6.9 to 8.3 in surviving patients). Randomization took place at outpatient clinics at 94 clinical centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 1989. Of 4,444 patients with CHD, 2,223 and 2,221 were randomized to treatment with placebo or simvastatin therapy, respectively. Patients received treatment with simvastatin, starting at 20 mg/day, with titration to 40 mg/day at 12 or 24 weeks if total cholesterol was >5.2 mmol/L (200 mg/dl), or placebo. After the double-blind period, most patients in both treatment groups received simvastatin as open-label prescription. Of the 1,967 patients originally treated with placebo and surviving the double-blind period, 97 (4.9%) died during the following 2 years. In the group randomized to simvastatin the corresponding number was 74 of the 2, 039 survivors (3.6%). Adding these deaths to those occurring during the original trial, the total was 353 (15.9%) and 256 (11.5%) deaths in the groups originally randomized to placebo and simvastatin, respectively. The relative risk was 0.70 (95% confidence interval 0. 60 to 0.82, p = 0.00002). The total number of cancer deaths was 68 (3.1%) in the placebo group and 52 (2.3%) in the simvastatin group (relative risk 0.73, 95% confidence interval 0.51 to 0.05, p = 0. 087), and the numbers of noncardiovascular and other deaths were similar in both groups. We therefore conclude that treatment with simvastatin for up to 8 years in patients with CHD is safe and yields continued survival benefit.

Adult↗
PubMed2000

Ultrasound determined carotid and femoral atherosclerosis in Lithuanian and Swedish men: the LiVicordia study.

Coronary heart disease mortality is four times higher in Lithuanian compared to Swedish middle-aged men. Using the same equipment (Acuson XP10 with 5 MHz linear transducer) and staff, we compared the amount of atherosclerosis in carotid and femoral arteries in 100 randomly sampled 50-year-old men in each of the cities Vilnius, Lithuania and Linköping, Sweden. Atherosclerotic plaques were more abundant in Vilnius men compared to Linköping men (53 versus 28% in the common carotid artery, 73 versus 37% in the common femoral artery, P < 0.001 for both). Plaques were thicker and more extended in arteries of Vilnius men, and an ultrasound atherosclerosis score was higher in both carotid and femoral arteries (P < 0.001 for all). More Vilnius men had a maximal intima-media thickness of the common femoral artery above 1 mm (P<0.005). Stiffness in the common carotid artery was higher in Vilnius men (P<0.001). In a linear regression model of the pooled material, after adjustment for city was made, smoking, systolic blood pressure, low density lipoprotein cholesterol and beta-carotene (inversely) significantly contributed to a high total ultrasound score (r2 = 0.32). These findings show that the higher coronary mortality noted in Lithuanian men goes together with a higher prevalence of early peripheral atherosclerosis.

Arteriosclerosis↗
PubMed2000

Plasma lipoprotein particle concentrations in postmenopausal women with unstable coronary artery disease. Analysis of diagnostic accuracy using receiver operating characteristics.

BACKGROUND: The contribution of plasma lipids to cardiovascular risk is usually evaluated by measuring plasma concentrations of total cholesterol, triglycerides and HDL cholesterol, and calculating LDL cholesterol concentration. We investigated plasma concentrations of apolipoproteins and lipoprotein particles in women with unstable coronary artery disease (CAD) to evaluate whether these, better than the routine lipid status, could differentiate women with and without coronary atherosclerosis. METHODS: Blood samples for lipid analyses were collected from 119 angiographically examined postmenopausal 49-79-year-old women with unstable CAD, and from 101 age-matched controls. Mean plasma concentrations were compared and the discriminatory ability of the different variables were tested using receiver operating characteristics (ROC). RESULTS: At coronary angiography 19% had normal vessels and 81% had coronary atherosclerosis. A disturbed triglyceride metabolism was the most pronounced lipid abnormality in women with unstable CAD and coronary atherosclerosis. ROC showed that none of the evaluated variables had a particularly high discriminatory power regarding unstable CAD or coronary atherosclerosis. The ratio cholesterol/HDL cholesterol was best with an ROC area of 0.79. Furthermore, the newer lipid variables, i.e. lipoprotein particles and apolipoproteins, were no better than the traditional variables. CONCLUSION: Lipoprotein changes reflecting a disturbed triglyceride metabolism are most pronounced in women with unstable CAD and coronary atherosclerosis. Lipoprotein particles and apolipoproteins alone were no better than lipids and lipoproteins in separating women with from those without coronary atherosclerosis. Our study does not support the measurement of apolipoproteins and lipoprotein particles on the basis of diagnostic accuracy alone.

Aged↗
PubMed1999

Efficacy and safety of simvastatin for high-risk hypercholesterolemia.

Ten years' experience of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin in 45 hypercholesterolemic high-risk patients is reported. All patients started with 20 mg simvastatin/day. The simvastatin dose was increased to 40 mg in 22 patients. Fourteen patients needed further addition of cholestyramine. Simvastatin reduced plasma cholesterol by 33% after 1 month and was further reduced after adjustment of the lipid-lowering treatment. The mean reduction in plasma cholesterol varied between 30% and 35% in 2 to 10 years. Low-density lipoprotein cholesterol demonstrated mean reductions of 34% to 42%. Mean plasma triglycerides were reduced by 26% after 1 month and by 1% to 19% the following years. High-density lipoprotein (HDL) cholesterol increased initially by 8% and remained elevated at 7% to 11% during the first 6 years, but then dropped slightly below baseline. HDL2 cholesterol increased by 9% to 25% the first 6 years and then decreased. HDL3 cholesterol showed a persistent elevation during simvastatin treatment. About half of the subjects had minor transient but clinical insignificant increases in creatine kinase. No cases of myopathy were seen. Mean serum aspartate aminotransferase and alanine aminotransferase increased significantly but within the normal ranges during the 10 years. The tolerability and compliance of simvastatin treatment was excellent as judged from patients' reports and from analyses of low-density lipoprotein cholesterol. This 10-year study demonstrates that simvastatin is an effective and safe drug with excellent tolerability with only few minor side effects, and causes a pronounced and persistent cholesterol-lowering effect during long-term treatment of hypercholesterolemic patients at risk.

Alanine Transaminase↗
PubMed1999

The lipoprotein profile differs during insulin treatment alone and combination therapy with insulin and sulphonylureas in patients with Type 2 diabetes mellitus.

AIMS: To study whether changes in endogenous insulin secretion at the same glycaemic control affect the plasma concentrations of lipoproteins in patients with Type 2 diabetes mellitus. METHODS: Fifteen patients, age 59+/-2 years (mean +/- SEM), body weight 86.3+/-3.0kg, body mass index 29.6+/-0.9 kg/m2 were treated with sulphonylurea and insulin in combination or with insulin alone in a randomized, double-blind, crossover study. All patients were treated with a multiple daily injection regimen with the addition of glibenclamide 10.5 mg daily or placebo tablets. RESULTS: During combination therapy, the dose of insulin was 25% less (P < 0.002) and there was a 29% increase in plasma C-peptide concentration (P = 0.01). Plasma levels of free insulin were not changed. Plasma levels of sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding protein (IGFBP)-1 were lowered. There were no differences in the 24-h blood glucose profiles or HbA1c (6.0+/-0.2 vs. 6.3+/-0.2%; P = 0.16). Body weight was similar. There was a significant decrease in plasma LDL cholesterol (3.04+/-0.24 vs. 3.41+/-0.21 mmol/l; P = 0.04), apolipoprotein A1 and of lipoprotein(a) but an increase in VLDL-triglycerides (1.36+/-0.31 vs. 0.96+/-0.16 mmol/l; P = 0.02) during combination therapy. The ratio between LDL cholesterol and apolipoprotein B concentrations was significantly lower during combination therapy (P < 0.01). CONCLUSIONS: Combination therapy with insulin and sulphonylureas increases portal insulin supply and thereby alters liver lipoprotein metabolism when compared with insulin therapy alone.

Aged↗
PubMed1999

Adipose tissue fatty acids in men from two populations with different cardiovascular risk: the LiVicordia study.

The LiVicordia study was set up to investigate possible causes for coronary heart disease mortality in middle-aged Lithuanian men being four times higher than in Swedish men. In a previous part of this study we found lower total and low density lipoprotein (LDL) cholesterol in the Lithuanian men in spite of them having a higher fat intake than in the Swedish men. Their LDL was also more susceptible to oxidation in vitro than was that of the Swedish men. Fat quality can influence LDL oxidation. In order to obtain data on long-term fat quality intake we measured the fatty acid composition of abdominal wall adipose tissue by gas chromatography in men aged 50 years from Vilnius, Lithuania (n=50) and Linköping, Sweden (n=50). Men from Vilnius had a significantly higher percentage of adipose tissue long chain polyunsaturated fatty acids (PUFA) (20:4n6, 20:5n3, 22:5n5, 22:6n3) and lower percentage of saturated fatty acids, especially myristic acid (14:0), 3.4+/-0.7 versus 4.6+/-0.8, p<0.0001. The percentage content of adipose tissue linoleic acid (18:2n6) was 11.5+/-2.1 versus 11.0+/-1.4 (n.s.) and of linolenic acid (18:3n3) 0.7+/-0.3 versus 0.6+/-0.2 (n.s.) in men from Vilnius and Linköping, respectively. It is concluded that the adipose tissue content of essential fatty acids is similar in men from Vilnius and men from Linköping and therefore the intake is also likely to be similar. The higher contents of long chain highly unsaturated fatty acids in men from Vilnius may be of importance in the oxidation process of LDL.

Adipose Tissue↗
PubMed1999

Increased plasma 7 beta-hydroxycholesterol concentrations in a population with a high risk for cardiovascular disease.

The mortality in coronary heart disease among 50- to 54-year-old men is 4 times higher in Lithuania than in Sweden. It was recently suggested that traditional risk factors could not explain this mortality difference. LDL of Lithuanian men showed, however, a lower resistance to oxidation than that of Swedish men. In addition, the plasma concentration of gamma-tocopherol, lycopene, and beta-carotene were lower in Lithuanian men. In the present investigation, we determined plasma oxysterols in men from Lithuania and Sweden and found that the plasma concentration of 7 beta-hydroxycholesterol was higher in Lithuanian men, 12+/-5 versus 9+/-8 (SD) ng/mL (P=0.0011). This oxysterol is a cholesterol autoxidation product and there is no indication that it should have an enzymatic origin. Mean LDL oxidation lag time was shorter in Lithuanian men (75+/-14 versus 90+/-13 minutes, P<0.0001) and the concentration of LDL linoleic acid was lower (249+/-56 versus 292+/-54 microgram/mg of LDL protein, P<0.0001). Lipid corrected gamma-tocopherol was 0.07+/-0.02 mg/mL in Vilnius men and 0.12+/-0. 04 mg/mL (P<0.0001) in Linköping men. There was a negative correlation between the concentration of 7 beta-hydroxycholesterol and lag time (R=-0.31, P=0.0023). It is suggested that the higher 7 beta-hydroxycholesterol concentration in Lithuanian men is an indication of an increased in vivo lipid peroxidation.

Biomarkers↗