BACKGROUND: Anecdotal evidence indicates that significant lowering of LDL-cholesterol by means of LDL apheresis may reduce the level of microalbuminuria in heterozygous familial hypercholesterolemia. We therefore examined whether treatment with the most potent LDL-lowering drug available (atorvastatin) has a similar effect on the level of microalbuminuria. MATERIAL/METHODS: In a case series, 100 patients with familial heterozygous hypercholesterolemia were started on 10 mg atorvastatin. 62 patients were switched to 40 mg atorvastatin once in the evening when the LDL-cholesterol treatment goals were not reached within 1 month. RESULTS: Baseline serum creatinine clearance significantly improved after 1, 3 and 6 months, while serum urea and serum creatinine were unchanged. Blood pressure exhibited a lowering trend. After one month of treatment, the mean level of microalbuminuria was significantly improved in both dose regimens, showing further improvement after 3 months and stabilizing thereafter. CONCLUSIONS: These data indicate that significant lowering of LDL-cholesterol with atorvastatin may favorably affect kidney function, in particular microalbuminuria as a measure of endothelial function. It remains to be seen whether this effect can be attributed to lipid lowering alone.

Adult↗

PubMed2002

Correlation of lipoprotein(a) levels and myocardial stress thallium scintigraphy pattern in different entities of CHD severity.

BACKGROUND: Higher levels of lipoprotein(a) confer an increased risk for coronary heart disease (CHD). Apo-E genotype (APO-E) also plays a role, the APO-E epsilon 4 allele being associated with CHD. Furthermore, higher Lp(a) concentrations are correlated with APO-E epsilon 4 allele presence. The study was performed to investigate the relationship of Lp(a) and APO-E with the functional status of coronary arteries as evaluated by myocardial scintigraphy. PATIENTS AND METHODS: We studied 70 patients (27 F and 43 M; mean age: 55 +/- 6 yrs.) consecutively referred for CHD, and 50 normal sex and age-matched controls. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo-AI, apo-B, Lp(a) levels (ELISA), Lp(a) isoforms (Immuno Blotting) and APO-E (PCR) were measured in all subjects. Only CHD patients underwent a myocardial tomographic stress thallium scintigraphy (201Tl-SPECT); the SPECT pattern was classified as follows: no perfusion defects (unstable angina group = 1), reversible defects at stress images (ischemia group = 2), fixed defects (infarction group = 3). RESULTS: Lp(a) medians were significantly higher than controls in group 1 (p < 0.05), 2 (p < 0.001) and 3 (p = 0.00). Low molecular weight isoforms (B, S1, S2) were significantly more frequent in all CHD-patients vs. controls (p < 0.05), whereas APO-E genotypes did not differ among controls and patients. Multiple regression analysis showed family history (p < 0.001) to be the only independent predictive variable of CHD severity correlated to the scintigraphic pattern. CONCLUSION: Among the considered biological parameters in our patients only Lp(a) plasma levels are related to the entity of ischemic cardiac wall damage as evaluated by 201Tl-SPECT.

Alleles↗

PubMed2002

Side effects of statins--prevalence, relevance, consequences.

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Alanine Transaminase↗

PubMed2002

Statin-induced myositis migrans.

Muscle related side effects of statins might be more frequent than once considered. Without affecting CK, they appear in various forms. Here, for the first time, we describe a new appearance we call "Statin-induced myositis migrans" in a 74-year-old female. Symptoms appeared more during the day and were not related to exercise. They were seen after simvastatin, pravastatin and--most intensively--after atorvastatin, but not on lovastatin, which the patient took for about 7 years without any problem. The clinical consequence (to withdraw the drug or not) of these milder statin side effects are discussed.

Aged↗

PubMed2002

Effect of prickly pear (Opuntia robusta) on glucose- and lipid-metabolism in non-diabetics with hyperlipidemia--a pilot study.

BACKGROUND: Besides others pectin, a soluble fibre, has been reported to be effective in lowering cholesterol levels in both animals and man with hyperlipidemia as well as being able to slow carbohydrate absorption and hence reduce the postprandial rise in blood glucose and serum insulin in patients with type-II diabetes. Aim of this pilot study was to assess the effect of prickly pear consumption on glucose- and lipid metabolism. DESIGN: In 24 non-diabetic, non-obese males (aged 37-55 years) suffering from primary isolated hypercholesterolemia (n = 12; group A) or combined hyperlipidemia (n = 12; group B) respectively, the influence of prickly pear pectin (Opuntia robusta)-intake on glucose- and lipid metabolism was examined. After an 8 week pre-running phase with a 7506 KJ step-I diet (phase I), 625 KJ were replaced by prickly pear edible pulp (250 g/day) for 8 further weeks (phase II). RESULTS: Prickly pear leads to a decrease of total cholesterol (12%), low-density lipoprotein-cholesterol (15%), apolipoprotein B (9%), triglycerides (12%), fibrinogen (11%), blood glucose (11%), insulin (11%) and uric acid (10%), while body weight, high-density lipoprotein-cholesterol, apolipoprotein A-I, and lipoprotein(a) remained unchanged. CONCLUSION: The hypocholesterolemic action of prickly pear may be partly explained by the fibre (pectin) content, but the hypoglycaemic actions (improvement of insulin sensitivity) in the non-obese, non-diabetic need further investigation to get more insights on the potential advantage of treating the metabolic syndrome.

Adult↗

PubMed2002

Awareness of Austrian physicians of risk factors for the development of atherosclerosis.

OBJECTIVE: In industrialised countries, coronary heart- (CHD) and other atherosclerosis-associated diseases (AAD) are, with an increasing incidence, responsible for almost half of the deaths among their respective populations. There is unequivocal evidence that medicine should try to achieve a reduction in manifestations of atherosclerosis by efficient preventive strategies. A variety of guidelines have been published during the last decades; nevertheless there is a gap between established recommendations and its application in everyday practice by Austrian physicians. The aim of this survey was to investigate physicians' knowledge of and attitude towards risk factors, preventive strategies and therapy of CHD and other AAD. METHODS: The self-administered questionnaire was mailed to 1000 physicians. We obtained an answer from a total of 286 physicians (general practitioners, GP) and specialists in internal medicine, IMS), who were asked about selected items concerning CHD and other AAD and an eventual modification in attitude towards diagnosis and treatment according to their own, personal risk profile. RESULTS: Risk factors for developing AAD such as elevated CH was identified in 77% (74% GP vs. 84% IMS), hypertension in 77% (76% GP vs. 81% IMS), elevated TG in 37% (40% GP vs. 26% IMS), excess alcohol consumption in 14% of all interrogated physicians (16% GP vs. 9% IMS) respectively. 77% (75% GP vs. 81% IMS) of the physicians considered the CH/HDL-ratio to be important in primary prevention and 83% (81% GP vs. 87% IMS) in secondary prevention; Lipoprotein(a) was considered important in only 9% (8% GP vs. 14% IMS) and 24% (19% GP vs. 41% IMS), respectively. CONCLUSION: In summary, all mentioned risk factors were heavily underestimated by Austrian physicians, partly leading to insufficient evaluation and therapeutic interventions. Secondary prevention was managed quite satisfactorily by both GP and IMS according to the Austrian guidelines. The knowledge about primary prevention strategies was significantly worse in GP compared to IMS. There is still a great need for information and training-programs for Austrian physicians to make primary and secondary prevention strategies work more effectively.

Adult↗

PubMed2002

Direct association between high-density lipoprotein cholesterol and endothelial function in hyperlipemia.

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Adult↗

PubMed2002

[DRGs--sword of Damocles or silver strip?].

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Austria↗

PubMed2002

Antiplatelet activity of semotiadil fumarate.

Calcium antagonists are known to exert antiplatelet activity. Semotiadil fumarate (SD-3211), a new benzothiazine, was therefore examined for its antiplatelet activity. The inhibitory activity on adenosine diphosphate (ADP)-, collagen-, arachidonic acid (AA)-, and platelet activating factor (PAF)-induced platelet aggregation after the 1-, 30-, 60- and 120-min incubation at concentrations ranging from 1 x 10(-3), 1 x 10(-4), 1 x 10(-5), 1 x 10(-6) and 1 x 10(-7) was examined. The data were compared with those using diltiazem, nifedipine and amlodipine under identical conditions in blood from eight healthy volunteers (four males, four females; aged 23-36 years) and eight hypertensive patients (four males, four females; aged 31-46 years). Semotiadil showed a dose-dependent inhibition of platelet aggregation in vitro with all the agents examined. Using the various aggregation-inducing agents, the dose-dependent inhibitory action was comparable for all the compounds tested. The antiaggregatory potency was in the order diltiazem, semotiadil, amlodipine and nifedipine. The incubation period did not significantly affect the antiaggregatory effect. No difference between platelets derived from healthy volunteers and hypertensive patients was noted. These findings indicate potent antiplatelet activity of the new calcium antagonist semotiadil.

Adenosine Diphosphate↗

PubMed2002

Muscular side effects of statins.

Lipid lowering has been shown to be effective in preventing primary and recurrent cardiovascular events and to save life. Statins almost exclusively used for this purpose meanwhile became one of the most widely prescribed families of drugs world-wide. Myopathies--mainly not well characterized--are the major group of side effects. We here review different types of clinical appearances, localizations, symptoms and the biochemical background. The data indicate that severe muscular side effects are rare. Patients and their doctors, however, easily overlook mild ones. Myopathic symptoms without any known biochemical correlate are not rare. No general guideline exists about exact diagnosis and differential diagnosis. Strict adherence to the measures of life-style change and performance of regular exercise can even further enhance significantly these side effects. Much more research should be directed onto the pathophysiological (genetic?) background to finally evaluate possible therapeutic consequences rather than simply to withdraw or change the respective statin.

Adult↗

PubMed2002

Antioxidant status in thyroid dysfunction.

Our study was designed to test and compare the levels of enzymatic antioxidants (ARS), endogenous peroxides (POX), non-enzymatic antioxidants (Antiox-cap) and anti-oxidized low-density lipoprotein (LDL) antibody titers (oLAb) in hyperthyroid and hypothyroid patients. We measured POX, ARS, Antiox-cap and oLAb in the plasma from 68 patients (34 patients with hyperthyroidism, thyroid-stimulating hormone (TSH) <0.04; and 34 patients with hypothyroidism, TSH >4.0) and 34 healthy euthyroid controls. POX were highest in hyperthyroid patients, but differences between hyperthyroid and hypothyroid patients and controls were not significant. ARS were significantly higher in patients compared to controls. Antiox-cap were significantly lower in patients compared to controls. oLAb were significantly higher in hypothyroid patients compared to controls and hyperthyroid patients. Our study shows that both hyperthyroidism and hypothyroidism are associated with enhanced oxidative stress involving enzymatic and non-enzymatic antioxidants. Higher POX in hyperthyroid patients might reflect the hypermetabolic state of these patients. oLAb, indicating progression of atherosclerosis, were highest in hypothyroid patients.

Adult↗

PubMed2002

Oxidation injury in patients receiving HMG-CoA reductase inhibitors: occurrence in patients without enzyme elevation or myopathy.

BACKGROUND: Myopathy in its severe forms including rhabdomyolysis is a very rare adverse effect occurring during monotherapy with the HMG-CoA reductase inhibitors ('statins') and is associated with pronounced signs of oxidation injury. This has been found at a local (muscle) as well as at a systemic level (blood). Several lines of evidence indicate that even mild forms of myopathy during statin treatment may be associated with in vivo oxidation injury. In contrast, statin therapy has been shown to be associated with a decrease in oxidation injury. OBJECTIVE: The aim of this study was to investigate whether patients with heterozygous familial hypercholesterolaemia who did not exhibit any symptoms or abnormalities in safety parameters during 6 months of treatment with various statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) did exhibit a change in oxidation injury as assessed by the isoprostane levels. METHODS: Blood (plasma and serum) as well as urine was tested before and 1, 3 and 6 months after starting statin therapy. RESULTS: Out of 111 treated patients (63 males, 48 females; aged 19 to 58 years) who did not experience any adverse effects during statin treatment, 11 (seven males, four females; aged 24 to 51 years) showed a pronounced increase in 8-epi-prostaglandin (PG) F(2alpha) in all the compartments examined. In the remaining 100 patients (56 males, 44 females; aged 19 to 58 years) there was either no change in or even an apparent decrease in 8-epi-PGF(2alpha). This increase was monitored with all the statins administered. If elevated, the increase in 8-epi-PGF(2alpha) remained without change throughout the entire follow-up period. No sex difference or differential response between smokers and nonsmokers was observed. DISCUSSION: These findings indicate that in the absence of other clinically observable adverse effects, in some of the patients, for an as yet unknown reason, statin therapy may be associated with increased oxidation injury. The fact that changing to another statin is apparently not necessarily associated with an identical response raises the question of a specific predisposition for certain compounds in a given patient. These data add a further piece of evidence that mild adverse effects of statins that are difficult to assess might be much more prevalent than widely considered. The clinical relevance and consequence of these findings still remains to be assessed.

Adult↗

PubMed2002

Flu-like response on statins.

BACKGROUND: Statins became one of the most widely used family of drugs meanwhile. Myopathy in various forms is among the most prevalent side effects. Only few attention has been paid to its various forms of appearance. We are reporting on a so far unknown flu-like response on statins with very severe symptoms of exhaustion, weakness, aching muscles and joints elevated acute phase response markers and sometimes even subfebrile body temperature. MATERIAL/METHODS: The 5 patients (4 males, 1 female) we monitored showed this response to some but not all the available statins with an onset of latest 3 weeks after starting therapy. RESULTS: Symptoms appeared already at the lowest available dose of the respective statin. Only in 3 of the patients, CK-elevation was noted, while 4 of them exhibited a severe increase in 8-epi-prostaglandin-F(2 alpha), an in-vivo oxidation injury marker. Latest 5 weeks after statin withdrawal the symptoms completely disappeared. Liver function parameters remained normal in all the patients at all time. CONCLUSIONS: Misinterpretation of this flu-like response is particularly dangerous as the treatment with antibiotics initiated in one of the patients may have had deleterious consequences. The pathophysiological background of this response remains to be assessed.

Acute-Phase Reaction↗

PubMed2002

Radioiodine therapy induces dose-dependent in vivo oxidation injury: evidence by increased isoprostane 8-epi-PGF(2 alpha).

UNLABELLED: 131I is the treatment of choice for differentiated thyroid cancer and hyperthyroidism. A relationship between low-density lipoprotein oxidation and radioiodine therapy-related side effects, consequently inducing increased formation of 8-epi-prostaglandin F(2 alpha) (PGF(2 alpha)) in situ, has recently been reported by several investigators. Isoprostanes, among them 8-epi-PGF(2 alpha), have been associated with increased oxidation injury due to various pathologic conditions in vivo. The aim of this study was to investigate the possible induction of oxidative stress as a consequence of (131)I therapy. METHODS: 8-epi-PGF(2 alpha) was examined in plasma, serum, and urine in 42 patients undergoing radioiodine treatment of hyperthyroidism or thyroid cancer. The 8-epi-PGF(2 alpha) levels were analyzed daily for 1 wk and thereafter at different points up to 12 wk after treatment. RESULTS: The isoprostane levels showed an increase after application of radioiodine in all investigated compartments. The effect was significantly higher and longer lasting after higher-activity therapy (2,960 or 7,400 MBq) than after lower-activity therapy (185 or 740 MBq). CONCLUSION: These findings document a significant, dose-dependent in vivo oxidation injury as a consequence of therapeutic radioiodine application to the salivary gland.

Adult↗