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Biomedical subjects

A G Olsson

Publications and source records attributed to A G Olsson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Cholesterol lowering and the use of healthcare resources. Results of the Scandinavian Simvastatin Survival Study.

BACKGROUND: Advances in the treatment of cardiovascular disease have increased costs; annual cardiovascular healthcare expenditure in the United States currently exceeds $100 billion. Physicians and third-party payers need to assess the economic impact of treatments that reduce cardiovascular morbidity and mortality. METHODS AND RESULTS: The Scandinavian Simvastatin Survival Study is a randomized, double-blind, placebo-controlled trial in which simvastatin reduced the risk of death by 30% (P=.0003) over the median follow-up period of 5.4 years in patients with previous myocardial infarction or stable angina pectoris as a result of a 42% reduction in the risk of coronary deaths (P=.00001). In the present report, data prospectively collected from hospital admissions were analyzed to evaluate the impact of simvastatin on healthcare resource use and perform a cost-minimization analysis. In the placebo group (n=2223), there were 1905 hospitalizations (average duration, 7.9 days) for acute cardiovascular events or coronary revascularization procedures among 937 patients, whereas in the simvastatin group (n=2221), there were 1403 such hospitalizations (average duration, 7.1 days) among 720 patients (all differences, P<.0001). The corresponding number of hospital days was 15089 and 9951 in the two groups, respectively (34% reduction,P<.0001). In the United States, the resulting reduction in hospitalization costs over the 5.4 years of the trial would be $3872 per patient, reducing the effective cost of simvastatin by 88% to $0.28 per day. CONCLUSIONS: In addition to reducing mortality and morbidity in coronary heart disease patients, simvastatin markedly reduces use of hospital services, thus offsetting most of its cost.

Adult↗
PubMed1996

Iron in human atheroma and LDL oxidation by macrophages following erythrophagocytosis.

The oxidative modification of low density lipoprotein (LDL) has been implicated as an early step in the formation of atheromatous lesions. In vitro studies suggest it to be accelerated, or even initiated, by transition metals such as iron or copper in combination with a reducing agent. Even if such metals have been demonstrated in atheroma gruels, their origin and precise localisation within human atheroma are presently unknown. In the initial part of this study we applied Pearl's method, energy dispersive X-ray microanalysis, and a modified Timm sulphide silver method (SSM) to demonstrate the occurrence of iron in early atherosclerotic lesions from a number of consecutive autopsy cases with evident, general atheromatosis. With the very sensitive SSM, but not with the other techniques, we found foam cells to contain heavy metals with a mainly lysosomal localization. On the basis of the hypothesis that such a lysosomal accumulation of iron might be due to erythrophagocytosis by migrating tissue-bound macrophages that later develop into foam cells, we designed an in vitro model system where human monocyte-derived macrophages were exposed to artificially aged, UV-exposed erythrocytes. The macrophages were then exposed to LDL in serum-and iron-free RPMI medium, occasionally in the presence of the potent iron-chelator desferrioxamine. The capacity of macrophages to oxidise LDL was much enhanced following erythrophagocytosis, and the process was shown to involve secretion of iron. Consequently, LDL oxidation was greatly inhibited by desferrioxamine. We conclude that iron may be exocytosed by macrophages that previously had their lysosomal apparatus enriched with iron, e.g. due to erythrophagocytosis. Oxidation of LDL may result in ensuing foam cell-formation secondary to scavenger-receptor mediated endocytosis by macrophages.

Aged↗
PubMed1996

Cost-effectiveness of cholesterol lowering. Results from the Scandinavian Simvastatin Survival Study (4S)

An analysis of the cost-effectiveness of simvastatin was conducted, based on the Scandinavian Simvastatin Survival Study (4S). The total cost of hospitalization in the placebo group was 52.8 million Swedish kronor (SEK) (5.15 million pounds), compared with SEK 36.0 million (3.51 million pounds) in the simvastatin group. This amounts to a 32% reduction, or a saving of SEK 16.8 million (1.6 million pounds) or SEK 7560 (738 pounds) per patient. The net cost per patient for the duration of the study (5.4 years) was SEK 13,540 (1324 pounds). Simvastatin treatment saved an estimated 0.377 undiscounted life years (0.240 life years discounted at 5% per annum). The cost of simvastatin therapy per discounted life-year saved was therefore SEK 56,400 (5502 pounds). Sensitivity analysis, examining the effect of different life expectancies, costs of initiation and monitoring of simvastatin therapy, and discount rates, showed the results to be stable. Conclusion. The cost per life-year saved of simvastatin in the treatment of post-myocardial infarction and angina patients, as determined from 4S data, is well within the range normally considered cost-effective.

Anticholesteremic Agents↗
PubMed1996

Antioxidants in the prevention of atherosclerosis.

Four antioxidant treatment modalities against atherosclerosis and coronary heart disease are scrutinized: probucol, beta-carotene, alpha-tocopherol and anti-iron treatment. A pattern seems to have emerged in which some treatments look promising, but others are disappointing. Most published studies of antioxidation in atherosclerosis have been ad-hoc in that the primary endpoint of the study has not been a diagnosis related to atherosclerosis; this may be misleading. The most promising antioxidant seems to be alpha-tocopherol, supported by the results of the Cambridge Heart Antioxidant Study. Probucol has the drawback of decreasing high density lipoprotein concentration and is therefore unlikely to influence atheroma in people. beta-Carotene has been repeatedly shown to be ineffective against coronary heart disease. Anti-iron treatment has not yet been tested in animal models or in man. More has to be learned of the role of antioxidation in atherosclerosis before the effectiveness of this treatment modality can be established.

Anticholesteremic Agents↗
PubMed1996

A population study of plasma neuropeptide Y: correlations with components of the metabolic syndrome.

UNLABELLED: To study the relations between neuropeptide Y (NPY) and age, gender, blood pressure (BP) and risk factors for cardiovascular disease and the renin angiotensin system, we performed a population-based study through random selection of 220 subjects (49% men). Subjects on antihypertensive therapy were excluded and participation rate was 67%. Venous blood was drawn at 08.00 h in the fasting state and a Spacelab 90202/90207 ambulatory BP device was then fitted. Plasma NPY levels were normally distributed and the mean level was 144 +/- 17 pmol/L (mean +/- SD). There was a trend towards higher levels in women than in men (147 +/- 17 pmol/L and 142 +/- 17 pmol/L, respectively, p = 0.053). No correlations were found between NPY and ambulatory BP or clinic BP in either gender. Angiotensin II correlated positively with NPY in men but not in women (r = 0.27, p = 0.007). There were no correlations between NPY and body mass index, waist/hip ratio, BP or C-peptide in either gender. Total cholesterol (r = 0.39, p < 0.0001) and LDL-cholesterol (r = 0.35, p = 0.0001) were positively correlated with NPY in women only. The correlation remained in multiple regression analysis with plasma total or LDL- cholesterol as second independent variable to age, and NPY as dependent variable (total cholesterol: standardised r = 0.43, p = 0.0002, LDL-cholesterol: standardised r = 0.34, p = 0.002, respectively). CONCLUSION: The positive correlation between LDL-cholesterol and NPY in women, independent of age, and components of the metabolic syndrome, makes it a possible gender-specific cardiovascular riskmarker.

Blood Pressure↗
PubMed1996

Copper-induced low density lipoprotein oxidation is not a risk discriminator for intermittent claudication.

Oxidative modification of low density lipoprotein (LDL) is supposed to be important in atherogenesis. Recently it was shown that subjects with coronary atherosclerosis have an increased susceptibility of their LDL to copper-induced oxidation. We investigated if patients with intermittent claudication (IC) might have an increased susceptibility of LDL to copper-induced oxidation. Fifty-eight males were randomly selected from an epidemiological study of IC, 29 with IC and 29 healthy controls matched for age, sex and smoking habits. All subjects performed a standard exercise test to confirm or exclude peripheral atherosclerosis. Claudicants had a lag phase of 99.7 +/- 14.8 minutes (mean +/- SD) and in healthy controls it was 104.6 +/- 12.9 minutes. The difference between the groups was not significant and neither was there any association between lag phase and degree of peripheral atherosclerosis in IC. Lag phase showed a positive and significant correlation to the plasma concentration of high density lipoprotein-2 (HDL2-) cholesterol. The correlation for the whole group was r = 0.41, p < 0.01. We conclude that the susceptibility of LDL to copper-oxidation does not discriminate between claudicants and healthy controls. The results also suggest that high plasma concentrations of HDL2-cholesterol may have a protective effect on LDL against oxidation.

Arteriosclerosis↗
PubMed1995

Trials of lipid-lowering therapy in secondary prevention of coronary heart disease.

The Scandinavian Simvastatin Survival Study showed that a 35% decrease in LDL-cholesterol was accompanied by a 42% reduction in coronary mortality. Even if the period of time is longer than 1 year for the divergence of survival curves in the simvastatin and placebo groups there are reasons to believe that the beneficial effect of lipid lowering is rapid. The effect may be mediated by stabilization of lipid-rich coronary lesions or by effects on endothelium. Lipid-lowering studies in the acute stage of coronary heart disease are suggested.

Anticholesteremic Agents↗
PubMed1995

Effects of in vitro addition of captopril on copper-induced low density lipoprotein oxidation.

Low density lipoprotein (LDL) was incubated with 20 microM of the angiotensin converting enzyme (ACE) inhibitors captopril, fosinopril and quinapril or ethanol. Oxidation of LDL was initiated by addition of CuSO4 and monitored for production of conjugated dienes, thiobarbituric acid reactive substances (TBARS) and lipid peroxides. The inhibition of production of conjugated dienes was expressed as the lag phase in minutes. The lag phase for control samples was 55.2 +/- 6.1 (mean +/- s.e. mean) min and for captopril 86.4 +/- 7.0 min (P = 0.0058). Quinapril had a small but nonsignificant effect, fosinopril and ethanol had no effect. LDL incubated with captopril showed only 13.8% of TBARS and 22.7% of lipid peroxides produced by control (100%) after 1 h. Increasing concentrations of captopril showed a linear increase in the lag phase. We conclude that captopril increases the resistance of LDL to copper-induced oxidation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Predilection of atherosclerosis for the inner curvature in the femoral artery. A digitized angiography study.

The degree of atherosclerosis in the inner and outer curvature of the femoral artery was studied by using digitized angiography and edge-roughness calculations in 301 hyperlipidemic patients. When the two edges of the vessel were compared no significant difference was seen, but when the local curvature was taken into account, inner curves were found to be more atherosclerotic than outer curves, and both inner and outer curves were more affected than straight segments. The same pattern was encountered in subpopulations defined by clinical or blood lipid criteria. The suggested explanation is that flow disturbances such as low shear rates or separated flow, which tend to arise along the inner curvature, promote the development of atherosclerosis.

Adult↗
PubMed1995

Lowering of HDL2b by probucol partly explains the failure of the drug to affect femoral atherosclerosis in subjects with hypercholesterolemia. A Probucol Quantitative Regression Swedish Trial (PQRST) Report.

The aim of the Probucol Quantitative Regression Swedish Trial (PQRST) (n = 303) was to investigate whether probucol (0.5 g BID) added to diet and cholestyramine (8 g BID) could retard progression or induce regression of femoral atherosclerosis in hypercholesterolemic (> 6.86 mmol/L) subjects. Probucol did not induce regression over the 3-year trial period as estimated by change in lumen volume on quantitative arteriography of a 20-cm segment of the femoral artery. In this report we studied in a representative subgroup (n = 72) whether the reduction in HDL concentrations induced by probucol could explain the failure of the drug to be effective. We analyzed the effects of treatment on HDL particle size subclasses. Probucol lowered the relative level of HDL2b, comprising the largest HDL particles, by 53% and the protein concentration of HDL2b by 67%. The protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety. The change in lumen volume correlated significantly with change in HDL, ie, HDL cholesterol (r = .34, P < .01), HDL2 cholesterol (r = .37, P < .01), HDL2b protein (r = .44, P < .001), and the relative HDL2b value (r = .51, P < .001). The corresponding values for relative HDL2b, distribution calculated on the active (n = 35) and placebo (n = 37) groups separately were also significant (r = .39 and .32, respectively; both P < .05). The correlation between drug-induced change in the relative HDL2b concentration and change in atherosclerosis was independent of the alteration in triglyceride concentration and could not be explained by treatment interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗
PubMed1995

Probucol treatment decreases serum concentrations of diet-derived antioxidants.

The effect of probucol, which is both a cholesterol-lowering drug and an antioxidant, on the serum concentrations of diet-derived antioxidants vitamin E, beta-carotene, lycopene, and vitamin A was studied in 303 hypercholesterolemic subjects. In a 3-year, double-blind, randomized trial we investigated to determine whether combined treatment with diet, cholestyramine, and probucol could reduce the progression of femoral atherosclerosis. Serum and lipoprotein antioxidant levels were measured by reverse-phase high-performance liquid chromatography. Cholestyramine significantly lowered serum concentrations of vitamin E by 7%, beta-carotene by 40%, and lycopene by 30% (all P < .001) due to impairment of gastrointestinal absorption and to serum cholesterol lowering. Probucol reduced serum vitamin E by 14% (P < .001) secondary to cholesterol and triglyceride lowering. The carotenoids were reduced by probucol by 30% to 40% (P < .001) most probably due to reductions in lipoprotein particle size and to competition with these substances for incorporation into VLDL during its assembly in the liver. This study shows that the use of a lipid-soluble antioxidant and cholesterol-lowering drug may have unfavorable effects on blood levels of diet-derived antioxidants.

Antioxidants↗
PubMed1995

Effects of iron- and hemoglobin-loaded human monocyte-derived macrophages on oxidation and uptake of LDL.

It is generally accepted that transition metals are required for cellular LDL oxidation. LDL may also be oxidized by iron and reducing agents in cell-free systems. We hypothesized that lysosomal iron may be exocytosed from macrophages that have been iron loaded by phagocytosis and degradation of iron-rich structures, eg, erythrocytes, and that such released iron may promote LDL oxidation and uptake by macrophages. Human monocyte-derived macrophages (HMDMs) were isolated and cultured for 7 days and then exposed to FeCl3, Fe-ADP, or Fe-EDTA (100 mumol/L) or hemoglobin (25 or 50 micrograms/mL) for 24 hours. After rinsing, LDL (50 to 150 micrograms/mL) was added in fresh culture medium without serum. After another 24 hours the media concentrations of iron and thiobarbituric acid-reacting substances as well as the electrophoretic mobility of LDL were increased, while the cells showed only minimal signs of decreased viability. Lipofuscin, neutral lipids, and phospholipids accumulated in a granular, lysosome-like pattern, and the cells acquired a foam cell-like morphology. There was a strong correlation (r = .87, P = .005) between the amount of iron added during the pre-exposure period and lipofuscin accumulation during the ensuing exposure to LDL in fresh, serum-free medium. Our results support our hypothesis and indicate that lysosomal iron may be exocytosed from HMDMs and promote oxidation and uptake of LDL and thus induce foam cell formation.

Cell Survival↗
PubMed1995

Effects of gemfibrozil (Lopid) on hyperlipidemia in acitretin-treated patients. Results of a double-blind cross-over study.

Hyperlipidemia is a common side-effect of oral retinoid treatment, which sometimes interferes with long-term therapy. To evaluate the safety and efficacy of the lipid-lowering drug gemfibrozil on retinoid-associated hyperlipidemia, we studied the clinical response and the plasma lipoprotein levels in 22 acitretin-treated (0.25-0.75 mg/kg) patients mainly suffering from psoriasis. Gemfibrozil or placebo was given in a double-blind cross-over fashion to 14 patients, who after 8 weeks of acitretin therapy and dietary advice exhibited hyperlipidemia (triglyceride levels > or = 50% above baseline and/or > or = 2.0 mmol/l). Serum triglycerides remained high (3.7 +/- 2.4 mmol/l) during placebo treatment but were reduced after 8 weeks of gemfibrozil treatment (p < 0.01). The total cholesterol level decreased slightly (p < 0.05) during gemfibrozil treatment, but the LDL/HDL ratio did not change significantly. No untoward effects of gemfibrozil on acitretin dose-response and clinical side-effects were noted. Gemfibrozil thus appears useful in patients prone to retinoid-induced hyperlipidemia unresponsive to dietary treatment and acitretin dose reductions.

Acitretin↗
PubMed1994

The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST).

The Probucol Quantitative Regression Swedish Trial tested whether treatment of hypercholesterolemic persons with probucol for 3 years affected femoral atherosclerosis. The primary end point was the change in atheroma volume estimated as change in lumen volume of the femoral artery assessed by quantitative arteriography. Three hundred three patients with visible atherosclerosis were randomized to probucol 0.5 g, twice daily, or to placebo. All patients were given diet and cholestyramine, 8 to 16 g/day. Twenty-nine patients were excluded because of inadequate primary end point measurements. The mean age of the remaining 274 subjects (158 were men) was 55 years. Seventeen percent had intermittent claudication and 24% had angina pectoris. After 3 years, the probucol-treated patients had 17% lower serum cholesterol, 12% lower low-density lipoprotein cholesterol, 24% lower total high-density lipoprotein cholesterol, and 34% lower high-density lipoprotein2 cholesterol levels than control subjects. All lipoprotein differences between the treatment groups remained highly significant during the trial. There was no statistically significant change in lumen volume between the probucol and the control group. Furthermore, there was no difference between the treatment groups with regard to change in arterial edge roughness or amount of aorto-femoral atherosclerosis; neither were there any differences between the treatment groups with regard to change in ST-segment depressions on exercise tests or ankle/arm blood pressure (secondary end points). In the control group, lumen volume increased (p < 0.001) and roughness of the femoral artery decreased (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1994

Influence of lipoprotein lipids, dietary fat and smoking on macrophage degradation of native and oxidized low density lipoprotein.

Relatively little is known about the biological mechanisms by which lipoproteins promote atherogenesis. It has, however, been shown that structural modification of low density lipoprotein (LDL), such as by oxidation, results in their uptake and degradation by intimal macrophages and consequently leads to formation of lipid-rich atherosclerotic lesions. The aim of the present investigation was to study the influence of dietary intake of fat, lipoprotein lipid composition, smoking and gender on macrophage degradation of LDL before and after oxidation. The study group consisted of 48 males and 56 females with hyperlipidemia taking part in the open prerandomization phase of the Probucol Quantitative Regression Swedish Trial (PQRST). Analysis including lipoprotein determinations, dietary and smoking habit interviews, LDL degradation by macrophages, LDL receptor binding and LDL thiobarbituric acid reactive substance (TBARS) levels before and after copper ion-induced oxidation was done during the pre-andomization phase of the study. Increased plasma and very low density lipoprotein (VLDL) triglyceride levels were associated with an increased macrophage degradation of native LDL, whereas no such association was found after oxidation of LDL. The dietary intake of polyunsaturated fatty acids (PUFA) was also inversely related to the degradation of native LDL by macrophages, but increased the rate at which oxidized LDL was degraded. Smoking and gender did not influence the rate of macrophage degradation of native or oxidized LDL. It is concluded that hypertriglyceridemia is associated with an increased macrophage degradation of LDL. This may represent a mechanism by which hypertriglyceridemia promotes atherosclerosis.

Adult↗
PubMed1994

Antiatherosclerotic effects of the angiotensin-converting enzyme inhibitors captopril and fosinopril in hypercholesterolemic minipigs.

We evaluated the two angiotensin-converting enzyme (ACE) inhibitors captopril and fosinopril with regard to possible antiatherosclerotic effects in minipigs. Experimental hypercholesterolemia and atherosclerosis was produced in 33 minipigs of the Göttingen strain by an egg yolk/cholesterol-enriched diet for 1 year. One group (n = 11) was fed the atherogenic diet alone and served as a control. A second group (n = 11) received captopril (80 mg/kg/day) added to the atherogenic diet, and a third group (n = 11) was treated in the same manner but with fosinopril (8 mg/kg/day). The drug treatments produced significant reduction in serum ACE activity associated with a reactive increase in plasma renin activity (PRA), but had only minor effects on plasma lipids and lipoproteins. At the end of the treatment period, all animals were killed and examined for degree of atherosclerosis. The percentage of atherosclerotic area in the abdominal aorta was significantly lower in both drug-treated groups as compared with controls. Furthermore, accumulation of cholesterol in the thoracic and abdominal aorta was inhibited by drug treatment. Finally, the percentage of intimal thickening in abdominal aorta was significantly reduced in the drug-treated groups. In conclusion, the ACE inhibitors captopril and fosinopril inhibited development of atherosclerosis in hypercholesterolemic minipigs.

Aldosterone↗
PubMed1994

The relation of coronary and peripheral arterial disease to the severity of femoral atherosclerosis in hypercholesterolaemia.

OBJECTIVES: The extent of atherosclerosis in the superficial femoral artery and the severity of arterial disease in the aorto-iliac and femoro-popliteal arterial districts were related to clinical diagnosis of coronary and peripheral atherosclerosis in hypercholesterolaemic patients. DESIGN: The study constitutes baseline cross-sectional data of a randomized double-blind clinical trial on Probucol, using both computer based and visual estimations of angiographies as endpoints. SUBJECTS: Two hundred and ninety men and women (mean age 54 years) with hypercholesterolaemia. MAIN OUTCOME MEASURES: Atherosclerosis was estimated with arteriographies. Lumen volume and edge roughness (vessel inner wall irregularity) of a 20 cm segment of the femoral artery were estimated by computer. A visual atherosclerosis score of the abdominal aorta to the popliteal arteries was made on both sides. RESULTS: Patients with peripheral arterial disease had significantly more advanced disease according to all three angiographic variables than those without symptoms of peripheral vascular disease. Both men and women with coronary artery disease had significantly lower femoral lumen volume and higher roughness values than patients without. Men with previous myocardial infarction had significantly higher mean visual scores of atherosclerosis than those without, while lumen volume and roughness did not differ in either sex. CONCLUSIONS: Femoral atherosclerosis is an expression of a generalized disease, associated with clinical symptoms of coronary artery disease. Femoral atherosclerosis is often accompanied by atherosclerosis also in the coronary arteries.

Adult↗