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Anders G Olsson

Publications and source records attributed to Anders G Olsson.

At least 19 recordsLinked to original sources
PubMed2006

Are lower levels of low-density lipoprotein cholesterol beneficial? a review of recent data.

In the 1960s, epidemiologic studies established a link between elevated serum cholesterol and increased risk of cardiovascular events. Extensive clinical trial data subsequently highlighted 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (ie, statins) as the most effective pharmacotherapy for lowering low-density lipoprotein (LDL) cholesterol, and showed that statin-mediated LDL cholesterol reductions were associated with significant improvements in cardiovascular outcomes. Such findings are reflected in current cardiovascular disease management guidelines, which focus on LDL cholesterol as the primary therapeutic target. These guidelines recommend target LDL cholesterol levels. However, a number of clinical trials have failed to identify an LDL cholesterol threshold level below which no further cardiovascular risk reduction occurs. Such findings suggest that optimal risk reduction may require greater reductions in LDL cholesterol than are currently being achieved. This review examines recent data highlighting the benefits of more pronounced LDL cholesterol reductions and considers how this could be achieved in clinical practice when many patients are not even reaching current targets.

Anticholesteremic Agents↗
PubMed2006

Expanding options with a wider range of rosuvastatin doses.

BACKGROUND: The dose range for rosuvastatin in Europe has recently been expanded to 5 to 40 mg and is now in line with the dose range currently available in the United States. OBJECTIVE: The goal of this article was to review the efficacy and safety data available for the rosuvastatin 5-mg dose and discuss these data in the context of the full 5- to 40-mg dose range. METHODS: Articles referring to clinical efficacy or safety data for the 5-mg dose of rosuvastatin were identified and reviewed after a search of the MEDLINE database (2000-August 2006; English language only) using the search term rosuvastatin. Proceedings from major cardiology congresses (2000-2006) were also searched for additional information. RESULTS: Rosuvastatin 5 mg is significantly (P < 0.001) more effective at reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol (42% and 30%) levels compared with atorvastatin 10 mg (36% and 27%), simvastatin 20 mg (36% and 25%), and pravastatin 20 mg (27% and 19%). Rosuvastatin 5 mg allows significantly more patients to reach their LDL-C goals as recommended by the 2003 European guidelines and the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (49%-52% and 67%-71%) than atorvastatin 10 mg (36%, P < 0.001; 53%, P < 0.01), simvastatin 20 mg (37%, P < 0.001; 64%, P < 0.05), and pravastatin 20 mg (12%, P < 0.001; 49%, P < 0.001). Rosuvastatin is well tolerated across the 5- to 40-mg dose range, with a type and incidence of adverse events similar to the other commonly available, but less effective, statins. The introduction of a 5-mg dose offers greater flexibility to prescribing physicians in that it provides an additional dosing option for those patients who are at a lower cardiovascular risk or who have an increased potential for developing myopathy with statin therapy. CONCLUSIONS: Rosuvastatin 5 mg is well tolerated and has beneficial effects across the atherogenic lipid profile by reducing LDL-C and total cholesterol, raising high-density lipoprotein cholesterol, and helping a greater proportion of patients reach their LDL-C goals.

Arteriosclerosis↗
PubMed2005

High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial.

CONTEXT: Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. OBJECTIVE: To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI). DESIGN, SETTING, AND PARTICIPANTS: The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. INTERVENTIONS: Patients were randomly assigned to receive a high dose of atorvastatin (80 mg/d; n = 4439), or usual-dose simvastatin (20 mg/d; n = 4449). MAIN OUTCOME MEASURE: Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation. RESULTS: During treatment, mean LDL-C levels were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% CI, 0.78-1.01; P = .07). Nonfatal acute MI occurred in 321 (7.2%) and 267 (6.0%) in the 2 groups (HR, 0.83; 95% CI, 0.71-0.98; P = .02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% CI, 0.77-0.98; P = .02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% CI, 0.76-0.91; P<.001). Noncardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% CI, 0.73-1.15; P = .47). Death from any cause occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% CI, 0.85-1.13; P = .81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (P<.001). Serious myopathy and rhabdomyolysis were rare in both groups. CONCLUSIONS: In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions.Trial Registration ClinicalTrials.gov Identifier: NCT00159835.

Aged↗
PubMed2005

The case for intensive statin therapy after acute coronary syndromes.

Acute coronary syndromes (ACS) consist of unstable angina or acute myocardial infarction and are associated with a high risk of early recurrent ischemic events. Revascularization procedures do not modify underlying pathophysiology and only modestly reduce early ischemic events after an index episode of ACS. Although statins improve dyslipidemia and cardiovascular risk over the long term, efforts to identify new ACS treatments are focusing on the ability of statins to modify the arterial wall-blood interface and reduce the risk of early recurrent ischemic events. Statins have been shown to reduce circulating markers of inflammation within days of an acute ischemic event. Short-term statin therapy also has been associated with improved coronary endothelial function, reversal of prothrombotic states, and reduction in atherosclerotic plaque volume. Findings from 6 randomized, controlled intervention trials were evaluated to determine if risk reduction is associated with the intensity of statin therapy. In addition, the predictive ability of baseline lipid levels and inflammatory markers were examined. High-intensity statin therapy (atorvastatin 80 mg) reduced early recurrent ischemic events after ACS compared with moderate-intensity treatment (eg, pravastatin 40 mg) or placebo. Moderate-intensity regimens (simvastatin 40 mg, pravastatin 20 to 40 mg, fluvastatin 80 mg, cerivastatin 0.4 mg) provided minimal benefit compared with placebo. Although there was no apparent relation between low-density lipoprotein (LDL) cholesterol levels before or during randomized treatment and short-term (4-month) risk of recurrent events, the degree of LDL cholesterol reduction with statin treatment after ACS may be related to longer-term event reduction. Moreover, evidence suggests that anti-inflammatory effects of high-intensity statin treatment are associated with clinical benefit.

Humans↗
PubMed2005

High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial.

AIMS: Patients with acute coronary syndrome (ACS) in the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study had diminished cardiovascular events after 16 weeks of treatment of atorvastatin 80 mg daily. We determined whether plasma lipoproteins at baseline and then at 6 weeks after randomization predicted clinical outcome. METHODS AND RESULTS: Cox proportional hazards models were constructed to determine relations between lipoproteins and clinical endpoint events. Baseline LDL cholesterol (LDL-C) did not predict outcome. In contrast, baseline HDL-C predicted outcome with a hazard ratio of 0.986 per mg/dL increment in HDL-C, P<0.001, indicating 1.4% reduction in risk for each 1 mg/dL increase in HDL-C. Atorvastatin treatment profoundly lowered LDL-C, but had minimal effect on HDL-C. Neither Week 6 LDL-C nor absolute change of LDL-C from baseline by Week 6 had any significant impact on clinical endpoints occurring between Week 6 and Week 16 after randomization. CONCLUSION: Plasma HDL-C, but not LDL-C, measured in the initial stage of ACS predicts the risk of recurrent cardiovascular events over the ensuing 16 weeks. LDL-C reduction does not account for the clinical risk reduction with atorvastatin treatment after ACS. This finding may suggest that the clinical benefit of atorvastatin after ACS is mediated by qualitative changes in the LDL particle and/or by non-lipid (pleiotropic) effects of the drug.

Aged↗
PubMed2005

Circulating levels of proinflammatory cytokines and neutrophil-platelet aggregates in patients with coronary artery disease.

Several lines of evidence indicate that increased inflammatory activity in peripheral blood is associated with the acute coronary syndrome. Systemic inflammation in clinically stable conditions of coronary artery disease has been less studied. We examined cytokine profiles in 20 patients who had acute coronary syndrome, 45 who had angiographically verified coronary artery disease and stable angina pectoris, and 45 healthy controls. Circulating levels of C-reactive protein, interleukin-1 receptor antagonist, interleukin-2 receptor, interleukin-6, interleukin-10, and interleukin-18 were determined. Subpopulations of peripheral immune cells, including neutrophil-platelet aggregates, were analyzed by 3-color flow cytometry using a panel of monoclonal antibodies. Patients who had acute coronary syndrome and stable angina pectoris had significantly higher levels of C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist than did controls, whereas levels of interleukin-2 receptor, interleukin-10, and interleukin-18 were similar across groups. Patients had significantly more neutrophils, and the numbers of neutrophil-platelet aggregates were particularly large in patients who had stable angina pectoris. High levels of C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist in patients were significantly related to numbers of neutrophils and neutrophil-platelet aggregates but not to other immune cell subpopulations. The data suggest that the interaction between neutrophils and platelets is an important component of proinflammatory activity seen in peripheral blood of stable and unstable forms of coronary artery disease.

Angina Pectoris↗
PubMed2005

Risk factors for reaching renal endpoints in the assessment of Lescol in renal transplantation (ALERT) trial.

BACKGROUND: The aim of the study was to identity risk factors for long-term renal transplant function and development of chronic allograft nephropathy (CAN) in renal transplant recipients included in the Assessment of Lescol in Renal Transplantation (ALERT) trial. METHODS: The ALERT trial was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 and 80 mg/day, in renal transplant recipients who were randomized to receive fluvastatin (Lescol) (n = 1,050) or placebo (n = 1,052) over 5 to 6 years of follow-up. Renal endpoints including graft loss or doubling of serum creatinine or death were analyzed by univariate and multivariate regression analysis in the placebo group. RESULTS: There were 137 graft losses (13.5%) in the placebo group, mainly caused by CAN (82%). Univariate risk factors for graft loss or doubling of serum creatinine were as follows: serum creatinine, proteinuria, hypertension, pulse pressure, time since transplantation, donor age, human leukocyte antigen-DR mismatches, treatment for rejection, low high-density lipoprotein cholesterol, and smoking. Multivariate analysis revealed independent risk factors for graft loss as follows: serum creatinine (relative risk [RR], 3.12 per 100-microM increase), proteinuria (RR, 1.64 per 1-g/24 hr increase), and pulse pressure (RR, 1.12 per 10 mm Hg), whereas age was a protective factor. With patient death in the composite endpoint, diabetes mellitus, smoking, age, and number of transplantations were also risk factors. CONCLUSIONS: Independent risk factors for graft loss or doubling of serum creatinine or patient death are mainly related to renal transplant function, proteinuria, and blood pressure, which emphasizes the importance of renoprotective treatment regimens in this population.

Adult↗
PubMed2005

The role of statins in the prevention of ischemic stroke.

Statin treatment has been demonstrated to diminish the risk for stroke in patients with coronary heart disease, hypercholesterolemia, normocholesterolemia, in the elderly, and among hypertensive and diabetic patients. Stroke incidence in patients on statin treatment has been reduced in all these clinical settings involving both primary and secondary prevention but not in patients with previous stroke. Two recent meta-analyses confirm this conclusion. The mechanism by which statins provide benefit against stroke is likely multifactorial, involving both the low-density lipoprotein cholesterol-lowering effect with stabilization of vulnerable plaques, and pleiotropic effects such as improvement of endothelial function, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory responses, immunomodulatory actions, and regulation of progenitor cells.

Anticholesteremic Agents↗
PubMed2005

Cardiovascular risk and renal transplantation: post hoc analyses of the Assessment of Lescol in Renal Transplantation (ALERT) Study.

BACKGROUND: Renal transplantation is associated with an increased risk for premature cardiovascular disease. We analyzed the data in the placebo arm of Assessment of Lescol in Renal Transplantation (ALERT) to improve our understanding of the relationship between cardiovascular risk factors and outcomes in this unique population. METHODS: We performed Cox survival analysis for myocardial infarction, cardiac death, and noncardiac death in 1,052 patients recruited to the placebo arm of ALERT. These subjects were aged 30 to 75 years, had stable graft function at least 6 months after transplantation, had a serum total cholesterol level between 155 and 348 mg/dL (4 and 9 mmol/L), and were receiving cyclosporine-based immunosuppression. RESULTS: The results confirm previous studies. In multivariate analysis, preexisting coronary heart disease (hazard ratio [HR], 3.69; P < 0.001), total cholesterol level (HR, 1.55 per 50 mg/dL; P = 0.0045), and prior acute rejection (HR, 2.36; P = 0.0023) were independent risk factors. Conversely, independent risk factors for cardiac death were age (HR, 1.58 per decade; P = 0.0033), diabetes (HR, 3.35; P = 0.0002), ST-T changes on the ECG (HR, 3.17; P = 0.0004), and serum creatinine level (HR, 2.65 per milligram per deciliter; P < 0.0001). CONCLUSION: This analysis confirms that renal transplant recipients share risk factors for myocardial infarction and cardiac death with the general population. However, the pattern of risk factors and their relationship with outcomes is atypical, highlighting the unique nature of cardiovascular risk in transplant recipients.

Adult↗
PubMed2005

Good self-rated health is related to psychosocial resources and a strong cortisol response to acute stress: the LiVicordia study of middle-aged men.

Self-rated health (SRH) is a strong predictor for disease and death. The relations among SRH, psychosocial factors, and cortisol dynamics were tested using pooled data from the LiVicordia study of 50-year-old men in Lithuania (n = 94) and Sweden (n = 89), controlling for effect of residence. SRH was assessed by "How would you assess your own health?" A standardized laboratory stress test included measures of cortisol in serum and saliva. Good SRH related to high scale scores of decision latitude, social support at work, coping, self-esteem, and sense of coherence; to low scores of overcommitment (all p < .01) and vital exhaustion (r = -0.40, p < 0.001); to low concentrations of saliva baseline cortisol (r = -.26, p = .001); and to a strong cortisol response to stress (r = .27, p = .001). Findings that good SRH related to favorable psychosocial characteristics and to a dynamic cortisol stress response indicate a possible explanation for observed lower risk for disease and death in this state.

Cross-Sectional Studies↗
PubMed2005

Relation of characteristics of metabolic syndrome to short-term prognosis and effects of intensive statin therapy after acute coronary syndrome: an analysis of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial.

OBJECTIVE: We examined relations between characteristics of the metabolic syndrome, early cardiovascular risk, and effect of early, intensive statin therapy after acute coronary syndrome. RESEARCH DESIGN AND METHODS: A total of 3,038 patients in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial were characterized by the presence or absence of a history of diabetes, a history of hypertension and/or blood pressure > or = 130/> or = 85, BMI >30 kg/m2, HDL cholesterol <40 mg/dl (men) or <50 mg/dl (women), and triglycerides > or = 150 mg/dl. Patients with three or more of these characteristics were categorized as having metabolic syndrome. RESULTS: A total of 38% of patients (n = 1,161) met criteria for metabolic syndrome as defined in this study and had a 19% incidence of a primary end point event (death, nonfatal myocardial infarction, cardiac arrest, or recurrent unstable myocardial ischemia) during the 16-week trial. Patients with two or fewer characteristics (n = 1,877) were classified as not having metabolic syndrome and had a 14% incidence of a primary end point event. In univariate analysis, the individual characteristics that bore a significant relation to risk were diabetes and low HDL cholesterol. In a multivariable model including age, sex, and randomized treatment assignment, presence of metabolic syndrome was associated with a hazard ratio of 1.49 (95% CI 1.24-1.79, P < 0.0001). Relative risk reduction with 80 mg atorvastatin daily compared with placebo was similar in patients with and without metabolic syndrome. CONCLUSIONS: Metabolic syndrome, as defined in the context of this clinical trial, is a strong predictor of early recurrent ischemic events after acute coronary syndrome.

Acute Disease↗
PubMed2004

Design and baseline characteristics of the Incremental Decrease in End Points through Aggressive Lipid Lowering study.

The Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) study is an investigator-initiated trial designed to determine whether additional clinical benefit might be gained through a strategy that decreases levels of low-density lipoprotein cholesterol levels better than those currently achieved with established statin therapy in patients who have coronary heart disease. IDEAL is a multicenter prospective, randomized, open-label, blinded, end point classification study. Patients who had myocardial infarction were randomized to prescription treatment with 80 mg/day of atorvastatin or 20 mg/day of simvastatin (the dose was increased to 40 mg/day at week 24 in those patients whose plasma total cholesterol remained >5.0 mmol/L, or 190 mg/dl, or whose low-density lipoprotein cholesterol remained >3.0 mmol/L, or 115 mg/dl). The primary clinical outcome variable is the time to initial occurrence of a major coronary event, which is defined as nonfatal acute myocardial infarction, coronary death, or resuscitated cardiac arrest. The study is designed to have a power of 90% to detect a relative decrease of 20% in the atorvastatin-group compared with the simvastatin-group in the number of major events caused by coronary heart disease over approximately 5.5 years. The 8,888 randomized patients had the following characteristics: mean age 61.7 +/- 9.5 years, 19.1% women (mean age 64.0 +/- 9.5 years), baseline total cholesterol 5.1 +/- 1.0 mmol/L (197 mg/dl), low-density lipoprotein cholesterol 3.2 +/- 0.9 mmol/L (124 mg/dl), and high-density lipoprotein cholesterol 1.2 +/- 0.3 mmol/L (46 mg/dl). Drug treatment before randomization consisted of statins in 77% of patients, aspirin in 78.9%, beta blockers in 75.1%, and angiotensin-converting enzyme inhibitors in 30%.

Adult↗
PubMed2004

High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial.

BACKGROUND: Oxidized phospholipids (OxPL) are present within atherosclerotic plaques and bound by lipoprotein (a) [Lp(a)] in plasma. This study evaluated the impact of atorvastatin on oxidized LDL (OxLDL) in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: OxLDL-E06 (OxPL content on apolipoprotein B-100 [apoB] detected by antibody E06), apoB-100 immune complexes (apoB-IC), OxLDL autoantibodies, and Lp(a) levels were measured in 2341 patients at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. The OxLDL-E06 and apoB-IC data are reported per apoB-100 particle (OxPL/apoB, IC/apoB) and as total levels on all apoB-100 particles (total apoB-OxPL and total apoB-IC [eg, OxPL/apoB or IC/apoBxapoB-100 levels]). Compared with baseline values, atorvastatin reduced apoB-100 (-33%), total apoB-OxPL (-29.7%), total apoB-IC IgG (-29.5%), and IgM (-25.7%) (P<0.0001 for all), whereas no change or an increase was observed with placebo. When normalized per apoB-100, compared with placebo, atorvastatin increased OxPL/apoB (9.5% versus -3.9%, P<0.0001) and Lp(a) (8.8% versus -0.7%, (P<0.0001). A strong correlation was noted between OxPL/apoB and Lp(a) (R=0.85, P<0.0001), consistent with previous data that Lp(a) binds OxPL. CONCLUSIONS: After atorvastatin treatment, total OxPL on all apoB-100 particles was decreased. However, there was enrichment of OxPL on a smaller pool of apoB-100 particles, in parallel with similar increases in Lp(a), suggesting binding by Lp(a). These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL, which may contribute to a reduction in ischemic events after ACS.

Aged↗
PubMed2004

Effect of atorvastatin on risk of recurrent cardiovascular events after an acute coronary syndrome associated with high soluble CD40 ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study.

BACKGROUND: Patients with acute coronary syndromes have elevated plasma levels of the proinflammatory, prothrombotic cytokine CD40 ligand (sCD40L). Statins inhibit CD40L signaling in vitro, but there are no prospective studies of statins and sCD40L in acute coronary syndromes. METHODS AND RESULTS: We measured sCD40L in subjects with an acute coronary syndrome enrolled in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects were randomized in this double-blind trial to atorvastatin 80 mg/d or placebo for 16 weeks. Plasma CD40L was measured from 2908 (94%) of 3086 subjects at baseline and 2352 (76%) at 16 weeks. Odds ratios (ORs) and 95% CIs from logistic regression models assessed the risk of recurrent cardiovascular events over 16 weeks (death, nonfatal myocardial infarction, cardiac arrest, and worsening angina requiring rehospitalization) in the placebo group from baseline sCD40L and the effect of atorvastatin on the risk associated with CD40L in all subjects. The effects of atorvastatin on plasma concentrations of CD40L were assessed by Wilcoxon tests. There was a threshold effect, with only high sCD40L (>90th centile) being a risk factor for a recurrent cardiovascular event (OR 1.86, 95% CI 1.25 to 2.77). This risk was abolished by atorvastatin (OR 1.09, 95% CI 0.69 to 1.76), which reduced the risk by 48%. Atorvastatin had only a modest effect on sCD40L (P=0.08). CONCLUSIONS: In patients with acute coronary syndromes, atorvastatin abrogated the risk of recurrent cardiovascular events associated with high sCD40L. Early statin therapy after acute coronary syndromes counters the risk associated with elevated sCD40L.

Aged↗
PubMed2004

[Apolipoprotein A-I can be a new tool in the treatment of atherosclerosis].

Five weekly infusions of apolipoprotein A-IMilano/phospholipid complex decreased mean percent coronary atheroma volume as estimated with intravascular ultrasound. The mechanism of action may be through reverse cholesterol transport or through an anti-inflammatory effect. Treatment with high-dose atorvastatin during 18 months did not decrease percent coronary atheroma volume as measured with the same technique. Large-scale efficacy and safety studies will be necessary in order to establish apolipoprotein A-I as the next tool to fight coronary heart disease. The study is in line with the cholesterol hypothesis.

Apolipoprotein A-I↗
PubMed2004

Effects of alpha-tocopherol and astaxanthin on LDL oxidation and atherosclerosis in WHHL rabbits.

The aim of this study was to evaluate the influence of -tocopherol and astaxanthin on low-density lipoprotein (LDL) oxidation lag time and atherosclerotic lesion formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one, 3-month-old WHHL rabbits were divided into three experimental groups. One group (n=10) was fed standard rabbit feed alone and served as a control, a second group (n=11) was supplied with the same feed containing 500 mg alpha-tocopherol/kg and a third group (n=10) was given a feed containing 100 mg astaxanthin/kg. Plasma lipids, lipoproteins and LDL oxidation lag time were followed for 24 weeks. At the end of the treatment period, the animals were killed and the thoracic aorta was used for evaluation of the degree of atherosclerosis. Colour photographs of the intimal surface of the vessel were taken for determination of the atherosclerotic area. Cross-sections of the thoracic aorta were used for histological examination and for determination of intimal thickening. Specimens of the vessel were used for determination of the tissue cholesterol content. Plasma cholesterol remained at a high level during the time of the experiment and there were no differences between the experimental groups. After 24 weeks, the LDL oxidation lag time was 53.7+/-1.7 min, 109+/-4 min (P<0.001) and 56.4+/-3.4 min (P=0.47) in the control, alpha-tocopherol and astaxanthin groups, respectively. In the thoracic aorta, the atherosclerotic area was 80.7+/-5.1%, 67.1+/-6.7% (P=0.13) and 75.2+/-5.7% (P=0.49) in the control, alpha-tocopherol and astaxanthin groups, respectively. The intimal thickening was 45.6+/-3.2%, 44.0+/-4.1% (P=0.89) and 40.0+/-4.5% (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. Finally, the cholesterol content was 107+/-9 mol/g, 95.7+/-11.5 mol/g (P=0.31) and 101+/-5 mol/g (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. It can be concluded that alpha-tocopherol but not astaxanthin prolonged the LDL oxidation lag time. The two antioxidative substances did not prevent atherogenesis in WHHL rabbits in this setting.

Animals↗