Peer supporters for cardiac patients with diabetes: a randomized controlled trial.

AIMS: To determine whether incorporation of patient peer supporters in a Cardiac-Diabetes Self-Management Program (Peer-CDSMP) led to greater improvement in self-efficacy, knowledge and self-management behaviour in the intervention group compared to a control group. BACKGROUND: Promoting improved self-management for those with diabetes and a cardiac condition is enhanced by raising motivation and providing a model. Peer support from former patients who are able to successfully manage similar conditions could enhance patient motivation to achieve better health outcomes and provide a model of how such management can be achieved. While studies on peer support have demonstrated the potential of peers in promoting self-management, none have examined the impact on patients with two co-morbidities. METHODS: A randomized controlled trial was used to develop and evaluate the effectiveness of the Peer-CDSMP from August 2009 to December 2010. Thirty cardiac patients with type 2 diabetes were recruited. The study commenced in an acute hospital, follow-up at participants' homes in Brisbane, Australia. RESULTS: While both the control and intervention groups had improved self-care behaviour, self-efficacy and knowledge, the improvement in knowledge was significantly greater for the intervention group. CONCLUSIONS: Significant improvement in knowledge was achieved for the intervention group. Absence of significant improvements in self-efficacy and self-care behaviour represents an inconclusive effect; further studies with larger sample sizes are recommended.

Expression of fat mobilizing genes in human epicardial adipose tissue.

BACKGROUND: Epicardial adipose tissue (EAT) mass correlates with metabolic syndrome and coronary artery disease (CAD). However, little is known about the expression of genes involved in triglyceride (TG) storage and mobilization in EAT. We therefore analyzed the expression of genes involved in fat mobilization in EAT in comparison to subcutaneous abdominal adipose tissue (AAT) in CAD patients and in controls. METHODS: EAT and AAT were obtained during coronary artery bypass graft (CABG) surgery from 16 CAD patients and from 14 non-CAD patients presenting for valve surgery. The state of atherosclerosis was assessed by angiography. RNA from tissues were extracted, reversibly transcribed and quantified by real time polymerase chain reaction (RT-PCR). The following genes were analyzed: perilipin-1 and -5 (PLIN1, PLIN5), lipoprotein lipase (LPL), hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL), comparative gene identification-58 (CIG-58), angiopoietin like protein 4 (ANGPTL4), in addition to interleukine-6 (IL-6), leptin (LEP) and adiponectin (ADPN). RESULTS: A significant expression of all listed genes could be observed in EAT. The relative expression pattern of the 10 genes in EAT was comparable to the expression in AAT, yet there was a significantly higher overall expression in AAT. The expression of the listed genes was not different between CAD patients and controls. CONCLUSION: It is suggested that the postulated difference in EAT volume between CAD patients and non-CAD patients is not caused by a differential mRNA expression of fat mobilizing genes. Further work on protein levels and enzyme activities will be necessary to get a complete picture.

Short-term infliximab therapy improves symptoms of psoriatic arthritis and decreases concentrations of cartilage oligomeric matrix protein.

OBJECTIVE: The aim of the current study was to evaluate the short-term effects of anti-tumour necrosis factor alpha (infliximab) therapy on serum cartilage oligomeric matrix protein (COMP) levels, a possible biomarker of cartilage destruction. METHODS: Nine consecutive patients with active psoriatic arthritis (PsA) were treated with infliximab for 6 weeks. Serum COMP levels were measured and correlated to pre-established disease activity outcome variables: pain as assessed by the patient, using the 100 mm visual analogue scale (VAS), duration of morning stiffness (MGST), swollen joint count (SJC), tender joint count (TJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: Significant improvements in MGST, VAS, SJC and TJC values were observed after 6 weeks of therapy. Similar significant improvements were demonstrated in the ACR response rate and in eight (89%) patients the ACR20 was achieved. ESR and CRP decreased significantly over 6 weeks. Serum COMP levels also decreased significantly after 6 weeks of treatment (12.99 +/- 1.71 baseline, 10.22 +/- 1.1 after 6 weeks, P < 0.008). CONCLUSION: The results of our study suggest that short-term therapy with infliximab leads to decreased COMP levels in patients with PsA. COMP seems to be a good candidate for a biomarker reflecting cartilage response to this treatment in PsA patients.

The ability of statins to protect low density lipoprotein from oxidation in hypercholesterolemic patients.

OBJECTIVE: It is unclear at the present time whether hydroxy-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA reductase inhibitors; statins) exert a protective effect on low-density lipoproteins (LDL) oxidation in vivo. In addition, it is speculated that pharmacological differences between statins may account for differences in their antioxidative capacities. This is of clinical relevance, because there is strong evidence that oxidized LDL initiates the atherosclerosis process. MATERIAL AND METHODS: In a controlled, randomized, double-blind study we compared the effects of three different statins (simvastatin, pravastatin and atorvastatin) on the ability to protect LDL from oxidation in 70 hypercholesterolemic but otherwise healthy subjects. Statins were administered in doses which were nearly equi-effective in lowering LDL-cholesterol. Changes in LDL oxidation were measured using diene conjugation (DIENES) and thiobarbituric acid reactive substances (TBARS) at entry and three months after beginning therapy with the statins. RESULTS: Levels of DIENES, usually generated during the early phases of lipid peroxidation, were significantly reduced by 10.2 +/- 5.5% (mean +/- SEM; p < 0.03), 6.0 +/- 2.0% (p < 0.005) versus baseline in the case of pravastatin and atorvastatin but simvastatin had no significant effect with a mean reduction of 5.5 +/- 6.4% (p > 0.23). Levels of TBARS, reflecting late phases of LDL oxidation, showed no significant changes against baseline (p > 0.34). Pooled data (n = 70) indicated that statins reduce DIENES levels by approximately 9% versus baseline (p < 0.005) but had no significant effect on TBARS levels (p > 0.29) after three months of therapy. CONCLUSION: This study showed that atorvastatin and pravastatin were capable of protecting LDL from oxidation in vivo in the early treatment phase. Pooled data levels of DIENES were significantly affected by statin therapy over a period of 3 months. No protective effect appeared to be present in the late phases of oxidation evaluated using measurement of TBARS but it should be noted that the clinical impact of such observations are currently discussed controversially in the literature.

Strength and endurance training lead to different post exercise glucose profiles in diabetic participants using a continuous subcutaneous glucose monitoring system.

BACKGROUND: Although both strength training (ST) and endurance training (ET) seem to be beneficial in type 2 diabetes mellitus (T2D), little is known about post-exercise glucose profiles. The objective of the study was to report changes in blood glucose (BG) values after a 4-month ET and ST programme now that a device for continuous glucose monitoring has become available. MATERIALS AND METHODS: Fifteen participants, comprising four men age 56.5 +/- 0.9 years and 11 women age 57.4 +/- 0.9 years with T2D, were monitored with the MiniMed (Northridge, CA, USA) continuous glucose monitoring system (CGMS) for 48 h before and after 4 months of ET or ST. The ST consisted of three sets at the beginning, increasing to six sets per week at the end of the training period, including all major muscle groups and ET performed with an intensity of maximal oxygen uptake of 60% and a volume beginning at 15 min and advancing to a maximum of 30 min three times a week. RESULTS: A total of 17,549 single BG measurements pretraining (619.7 +/- 39.8) and post-training (550.3 +/- 30.1) were recorded, correlating to an average of 585 +/- 25.3 potential measurements per participant at the beginning and at the end of the study. The change in BG-value between the beginning (132 mg dL(-1)) and the end (118 mg dL(-1)) for all participants was significant (P = 0.028). The improvement in BG-value for the ST programme was significant (P = 0.02) but for the ET no significant change was measured (P = 0.48). Glycaemic control improved in the ST group and the mean BG was reduced by 15.6% (Cl 3-25%). CONCLUSION: In conclusion, the CGMS may be a useful tool in monitoring improvements in glycaemic control after different exercise programmes. Additionally, the CGMS may help to identify asymptomatic hypoglycaemia or hyperglycaemia after training programmes.

Continuous glucose monitoring in diabetic long distance runners.

Marathon running is growing in popularity, and many diabetic patients are participating in various marathon races all over the world each year. This study aimed to investigate the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) during a marathon run in patients with well-controlled diabetes mellitus using a continuous glucose monitoring system (CGMS). Five subjects with type 1 and one patient with type 2 diabetes mellitus were monitored with the Medtronic MiniMed CGMS during the 2002 Vienna City Marathon (n = 3) or the "Fernwärme run" (n = 3) long distance runs of 42.19/15.8 km. All six patients finished their course. The CGSM system was well tolerated in all patients over an average duration of 34 +/- 4.0 hours and it did not limit the patients' activities. The mean running time for the Vienna city marathon was 257 +/- 8 min (247 to 274 min) and for the Fernwärme run 134 +/- 118 min (113 to 150 min). A total of 1470 blood glucose measurements (mean 245 readings per subject) were performed. During and after the marathons frequent hypo- and hyperglycemic episodes with and without clinical symptoms were measured. Our data confirm that the CGMS may help to identify asymptomatic hypoglycemia or hyperglycemia during and after a long distance run. The system may also be helpful to improve our understanding about the individual changes of glucose during and after a marathon and may protect hypoglycemic or hyperglycemic periods in future races.

Plasma delipidation process induces rapid regression of atherosclerosis and mobilisation of adipose tissue.

Cholesterol is a major component of atherosclerotic plaques. Cholesterol accumulation within the arterial intima and atherosclerotic plaques is determined by the difference of cellular cholesterol synthesis and/or influx from apo B-containing lipoproteins and cholesterol efflux. In humans, apo A-1 Milano infusion has led to rapid regression of atherosclerosis in coronary arteries. We hypothesised that a multifunctional plasma delipidation process (PDP) would lead to rapid regression of experimental atherosclerosis and probably impact on adipose tissue lipids. In hyperlipidemic animals, the plasma concentrations of cholesterol, triglyceride and phospholipid were, respectively, 6-, 157-, and 18-fold higher than control animals, which consequently resulted in atherosclerosis. PDP consisted of delipidation of plasma with a mixture of butanol-diisopropyl ether (DIPE). PDP removed considerably more lipid from the hyperlipidemic animals than in normolipidemic animals. PDP treatment of hyperlipidemic animals markedly reduced intensity of lipid staining materials in the arterial wall and led to dramatic reduction of lipid in the adipose tissue. Five PDP treatments increased apolipoprotein A1 concentrations in all animals. Biochemical and hematological parameters were unaffected during PDP treatment. These results show that five PDP treatments led to marked reduction in avian atherosclerosis and removal of lipid from adipose tissue. PDP is a highly effective method for rapid regression of atherosclerosis.

Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans.

BACKGROUND: As statin therapy has been reported to reduce antioxidants such as vitamin E and coenzyme Q10 and there are indications that this reduction may cause impairment of left ventricular function (LVF), we studied the influence of simvastatin on LVF and serum vitamin E and coenzyme Q10 levels in humans. MATERIAL AND METHODS: We assessed the effect of simvastatin on left ventricular function and coenzyme Q10 levels in 21 (11 male, 10 female) hypercholesterolaemic subjects (mean age = 56 years) with normal LVF, over a period of 6 months. Subjects were re-tested after a 1-month wash-out period (7 months). Echocardiography was performed on all subjects before commencement of simvastatin (20 mg day(-1)), and at 1, 3, 6 and 7 months after initiation of treatment. Fasting blood samples were also collected at these intervals to assess lipids, apoproteins, vitamin E and coenzyme Q10. RESULTS: Serum lipids showed the expected reductions. Plasma vitamin E and coenzyme Q10 levels were reduced by 17 +/- 4% (P < 0.01) and 12 +/- 4% (P < 0.03) at 6 months. However, the coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio increased significantly. Left ventricular ejection fraction (EF) decreased transiently after 1 month, while no significant change was observed at 3 and 6 months. Other markers of left ventricular function did not change significantly at any time point. CONCLUSION: Despite reduced plasma vitamin E and coenzyme Q10, 20 mg of simvastatin therapy is associated with a significantly increased coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio. Simvastatin treatment is not associated with impairment in left ventricular systolic or diastolic function in hypercholesterolaemic subjects after 6 months of treatment.

HFE genotyping demonstrates a significant incidence of hemochromatosis in undifferentiated arthritis.

OBJECTIVE: Hereditary hemochromatosis is a common autosomal recessive disorder of iron metabolism. Among Northern Europeans the carrier frequency is estimated to be 1 in 10, while up to 1 in 200 is affected by the disease. Arthropathy is one early clinical manifestation of this disease, but the articular features are often misdiagnosed. In this study the two frequent mutations of the HLA-linked hemochromatosis gene (HFE) were investigated in a rheumatology clinic population. METHODS: Two hundred and six consecutive patients (mean age 57.7 years; 38 male/168 female) attending a rheumatology clinic over a period of 14 months were screened for HFE mutations (C282Y and H63D). All standard diagnostic procedures were used to identify the aetiology of the arthropathy. Mutations were evaluated by separation on PAGE of digested PCR amplificates of DNA (by SnapI and Bcl-I, for C282Y and H63D, respectively) obtained from PBMCs. RESULTS: The C282Y and H63D allele frequencies were 4.5 and 12.8 in patients with rheumatic diseases. Five patients were homozygote for H63D (2.4%), and one for C282Y (0.5%). Five patients were compound heterozygous (2.4%). The observed C282Y allele frequency in rheumatic patients with undifferentiated arthritis was 12.9 and exceeded that of healthy subjects (p = 0.01). CONCLUSIONS: Determination of the HFE genotype is clinically useful in patients with arthritis of unknown origin, to allow early diagnosis of hemochromatosis.

Therapy of hyper-Lp(a).

Lipoprotein (a) [Lp(a)] appears to be one of the most atherogenic lipoproteins. It consists of a low-density lipoprotein (LDL) core in addition to a covalently bound glycoprotein, apolipoprotein (a) [apo(a)]. Apo(a) exists in numerous polymorphic forms. The size polymorphism is mediated by the variable number of kringle-4 Type-II repeats found in apo(a). Plasma Lp(a) levels are determined to more than 90% by genetic factors. Plasma Lp(a) levels in healthy individuals correlate significantly high with apo(a) biosynthesis and not with its catabolism. There are several hormones known to have a strong impact on Lp(a) metabolism. In certain diseases, such as kidney disease, Lp(a) catabolism is impaired leading to up to fivefold elevations. Lp(a) levels rise with age but are otherwise influenced only little by diet and lifestyle. There is no safe and efficient way of treating individuals with elevated plasma Lp(a) concentrations. Most of the lipid-lowering drugs have either no significant influence on Lp(a) or exhibit a variable effect in patients with different forms of primary and secondary hyperlipoproteinemia. There is without doubt a strong need to concentrate on the development of specific medications to selectively target Lp(a) biosynthesis, Lp(a) assembly and Lp(a) catabolism. So far only anabolic steroids were found to drastically reduce Lp(a) plasma levels. This class of substance cannot, of course, be used for treatment of patients with hyper-Lp(a). We recommend that the mechanism of action of these drugs be studied in more detail and that the possibility of synthesizing derivatives which may have a more specific effect on Lp(a) without having any side effects be pursued. Other strategies that may be of use in the development of drugs for treatment of patients with hyper-Lp(a) are discussed in this review.

The effects of ACE inhibitor therapy on left ventricular myocardial mass and diastolic filling in previously untreated hypertensive patients: a cine MRI study.

Cardiac remodeling in case of hypertension induces hypertrophy of myocytes and elevated collagen content and, subsequently, impaired diastolic filling of the left ventricle. The purpose of this prospective study was to evaluate changes of left ventricular (LV) myocardial mass, as well as diastolic filling properties, in hypertensive patients treated with the ACE inhibitor fosinopril. Sixteen hypertensive patients with echocardiographically documented LV hypertrophy and diastolic dysfunction received fosinopril (10-20 mg daily). Measurements of LV myocardial mass and properties of diastolic filling (peak filling fraction (PFF); peak filling rate (PFR)) were performed prior to medication, as well as after 3 and 6 months of therapy using cine magnetic resonance imaging (MRI). Ten healthy subjects served as a control group. LV myocardial mass (g/m2) decreased continuously within 3-6 months of follow-up by 32% (148 +/- 40 vs. 120 +/- 26 vs. 101 +/- 22 g/m2; P < 0.0001/0.005). The extent of regression correlated to the severity of LV hypertrophy at baseline (r = 0.77; P < 0.004). Early diastolic filling increased significantly within 6 months of therapy (PFF (%): 36 +/- 6 vs. 61 +/- 7, P < 0.0001; PFR (mL/second): 211 +/- 48 vs. 282 +/- 48, P < 0.001). Cine MRI can be used to assess the time course of pharmacological effects on cardiac remodeling in the course of hypertension. ACE inhibitor therapy results in a significant reduction of LV mass within 3 months and is accompanied by a normalization of diastolic filling that is completed after 6 months.

Quantification of coronary artery calcification in patients with FH using EBCT.

BACKGROUND: Calcification of the coronary vessel wall is regarded as a marker of advanced coronary atherosclerosis. METHODS: To test whether patients with heterozygous familial hypercholesterolemia (FH) exhibit excessive calcification of the coronary vessel wall, we quantified coronary artery calcium in LDL-apheresis treated FH-patients with known severe coronary artery disease (CAD) (n = 10), in patients with moderate hypercholesterolemia and known severe CAD (n = 10), and in asymptomatic controls (n = 10) using electronic beam CT. The total coronary calcium score (Agatston-Score), the number of calcified lesions and the calcified plaque volume were evaluated for this study. RESULTS: CAD-patients with FH, although on average 10 years younger, had a significantly higher total coronary calcium score (702/2018/2890), number of lesions (34/43/49) and calcified plaque volume (700/1818/2313) compared to patients with CAD only (480/641/1362, 10/16.5/22, 480/588/1209, respectively) and controls (10/47/137, 2/4/10, 15/50/144, respectively). Furthermore, we observed a significant correlation (r = 0.93; P < 0.01) between LDL-cholesterol levels (pretreatment levels of the CAD-FH group) and the total coronary calcium score in all three groups. Our results demonstrate that coronary artery calcification is more extensive in CAD-patients with FH than in CAD-patients with moderate hypercholesterolemia. In addition, we provide evidence that the amount of calcium in the coronary vessel wall in FH patients result from a long lasting history of elevated LDL-Cholesterol levels. CONCLUSION: These findings emphasize the significance of LDL-cholesterol as a risk factor for atherosclerosis and underline the importance of early diagnosis of CAD and early cholesterol lowering therapy in FH patients.

Urinary excretion of apolipoprotein(a): relation to other plasma proteins.

The atherogenic lipoprotein Lp(a) consists of an LDL-like core and apo(a), linked to apoB via a thiol bridge. Apo(a) fragments ranging in size from 60 to 220 kDa are excreted into urine and the excretion rate correlates significantly with the plasma levels of Lp(a). In order to study the interrelationship of apo(a) secretion with that of other plasma proteins, urinary apo(a) and protein secretion of five probands were followed for 24 h at different urinary densities. The excretion rate of apo(a) fragments, despite their high molecular weight, was highest, followed by apoD, orosomucoid, albumin and beta(2)-glycoprotein-I (beta2-GI) and plasminogen (1.58, 0.87, 0.095, 0.027, 0.013 and <0.001%/day, respectively). There was a highly significant correlation between apo(a), apoD and beta2-GI concentrations but not with albumin and orosomucoid concentrations in urine. The only protein that was fragmented in urine was apo(a) while the other proteins had molecular weights comparable to those in plasma. We conclude that a previously suggested fragmentation of apo(a) by the kidney is not a rate-limiting step in its excretion. Since plasminogen, another kringle-IV-containing plasma compound, and fragments thereof, are undetectable in urine under identical experimental conditions, it is very unlikely that the characteristic kringle structure is responsible for the high excretion rate of apo(a).

Urinary apo(a) excretion is not altered by changes in glomerular filtration rate and renal plasma flow in healthy males.

Lipoprotein(a) (Lp(a)) is an independent risk factor for atherosclerotic disease. However, information concerning the site of Lp(a) catabolism and breakdown is scarce. Several studies have shown that, in renal insufficiency, plasma Lp(a) levels are elevated, and that after normalisation of kidney function they return to normal. We have recently shown that fragments of apo(a) are found in the urine of healthy individuals. Despite this evidence that apo (a) is excreted into the urine, the mode of excretion of apo(a) remains unclear. Since it has been reported that intravenous infusion of somatostatin can reduce glomerular filtration rate (GFR) and renal plasma flow (RPF), we analysed urinary apo(a) excretion in ten healthy volunteers receiving somatostatin infusions. The infusion of somatostatin led to reversible changes in GFR and RPF. Apo(a) excretion was constant in all 10 individuals over the entire time course when normalised for creatinine. There was a highly significant correlation between plasma Lp(a) levels and urinary apo(a) values. Changes in renal plasma flow and glomerular filtration rate did not alter urinary apo(a) excretion. We conclude that a constant amount of apo(a) is excreted into urine, depending on plasma Lp(a) levels, and that urinary apo(a) excretion is not altered by changes in GFR and RPF in healthy males.

Effects of vitamin E on chronic and acute endothelial dysfunction in smokers.

OBJECTIVES: The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation (FMD) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin E. BACKGROUND: Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress. METHODS: We studied 22 healthy male smokers (mean +/- SD, 23 +/- 9 cigarettes per day) randomly assigned to receive either 600 IU vitamin E per day (n = 11, age 28 +/- 6 years) or placebo (n = 11, age 27 +/- 6 years) for four weeks and 11 age-matched healthy male nonsmokers. Flow mediated vasodilation and endothelium-independent, nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound (7.5 MHz) at baseline and after therapy. Subjects stopped smoking 2 h before the ultrasound examinations. At the end of the treatment period, a third scan was obtained 20 min after smoking a cigarette (0.6 mg nicotine, 7 mg tar) to estimate transient impairment of FMD. RESULTS: Flow mediated vasodilation at baseline was abnormal in the vitamin E (5.3 +/- 3.8, p < 0.01) and in the placebo group (6.4 +/- 3.5, p < 0.05) compared with nonsmoking controls (11.6 +/- 4.7). Using a two-way repeated measures analysis of variance (ANOVA) to examine the effects of vitamin E on FMD, we found no effect for the grouping factor (p = 0.5834) in the ANOVA over time but a highly significant difference with respect to time (p = 0.0065). The interaction of the time factor and the grouping factor also proved to be significant (p = 0.0318). Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin E (p values from successive differences for the time/group factor: 0.0001/0.0017). The transient attenuation of FMD (calculated as the percent change in FMD) was related to the improvement of the antioxidant status, estimated as percent changes in thiobarbituric acid-reactive substances (r = -0.67, p = 0.0024). Nitroglycerin-induced dilation did not differ between study groups at baseline or after therapy. CONCLUSIONS: These results demonstrate that oral supplementation of vitamin E can attenuate transient impairment of endothelial function after heavy smoking due to an improvement of the oxidative status but cannot restore chronic endothelial dysfunction within four weeks in healthy male smokers.

Low density lipoprotein immunoapheresis does not increase plasma lipid peroxidation products in vivo.

Extracorporeal elimination of low density lipoprotein (LDL) is frequently used in drug-resistant hypercholesterolemia. LDL-immunoapheresis selectively removes LDL and lipoprotein(a) [Lp(a)] from plasma. Lipid peroxidation is one unwanted side effect, that occurs during extracorporeal plasma treatment. The purpose of this study was to investigate the effect of LDL immunoapheresis on lipid peroxidation. Before and after a single LDL-immunoapheresis treatment, plasma concentrations of lipid hydroperoxides, determined with two different spectophotometric assays, thiobarbituric acid-reacting substances (TBARS), determined spectrophotometrically and malondialdehyde (MDA), determined by an MDA-TBA/HPLC method, were measured in 13 hypercholesterolemic patients. In addition MDA was also determined in the eluate of the apheresis column. Before treatment, plasma cholesterol and LDL cholesterol concentrations were significantly higher in patients than in healthy control subjects, as were the lipid peroxidation products. LDL-immunoapheresis treatment of the patients led to significant decreases in total cholesterol (69+/-8%), LDL-cholesterol (79+/-7%), HDL-cholesterol (35+/-17%), triglycerides (38+/-21%), apolipoprotein-B (77+/-6%), apolipoprotein-A1 (25+/-5%) and Lp(a) concentrations (76+/-10%). Changes in plasma lipid peroxide concentrations (17+/-8 nmol/l before vs. 14+/-5 nmol/l after treatment) were not significant, neither were those in TBARS (3. 0+/-2.6 micromol/l vs. 2.3+/-1.3 micromol/l) or MDA concentrations (1.03+/-0.17 micromol/l vs. 1.0+/-0.20 micromol/l). Patients with high baseline values showed a decrease, whereas others did not. MDA was present (0.57+/-0.13 micromol/l) in the eluate of the apheresis column, suggesting that, along with LDL, lipid peroxidation products are also removed. From these results we conclude that a single LDL-immunoapheresis treatment effectively reduces LDL and Lp(a) in the absence of increases in plasma lipid peroxidation products.

[Aggressive therapy and combination therapy in severe hyperlipidemia]. / Aggressive Therapie und Kombinationstherapie bei schweren Hyperlipidämien.

In cases of severe hyperlipidemia, we have very effective therapeutic tools nowadays. LDL-apheresis is still the most effective therapy for familial hypercholesterolemia, especially in its homocygous form. In combination with statins, LDL-cholesterol can be lowered by 80%. Most other genetic and secondary hyperlipidemias can effectively be treated by lipid lowering drugs. This aggressive treatment gains more and more on importance in view of the tough recommendations of specific scientific societies. Atorvastatin and simvastatin can lower LDL-cholesterol by 60%. In this report different therapies and combination therapies for hyperlipidemia are discussed.