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.

Effect of tranexamic acid and delta-aminovaleric acid on lipoprotein(a) metabolism in transgenic mice.

The assembly of lipoprotein(a) (Lp(a)) is a two-step process which involves the interaction of kringle-4 (K-IV) domains in apolipoprotein(a) (apo(a)) with Lys groups in apoB-100. Lys analogues such as tranexamic acid (TXA) or delta-aminovaleric acid (delta-AVA) proved to prevent the Lp(a) assembly in vitro. In order to study the in vivo effect of Lys analogues, transgenic apo(a) or Lp(a) mice were treated with TXA or delta-AVA and plasma levels of free and low density lipoprotein bound apo(a) were measured. In parallel experiments, McA-RH 7777 cells, stably transfected with apo(a), were also treated with these substances and apo(a) secretion was followed. Treatment of transgenic mice with Lys analogues caused a doubling of plasma Lp(a) levels, while the ratio of free:apoB-100 bound apo(a) remained unchanged. In transgenic apo(a) mice a 1. 5-fold increase in plasma apo(a) levels was noticed. TXA significantly increased Lp(a) half-life from 6 h to 8 h. Incubation of McA-RH 7777 cells with Lys analogues resulted in an up to 1. 4-fold increase in apo(a) in the medium. The amount of intracellular low molecular weight apo(a) precursor remained unchanged. We hypothesize that Lys analogues increase plasma Lp(a) levels by increasing the dissociation of cell bound apo(a) in combination with reducing Lp(a) catabolism.

Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men.

OBJECTIVES: The aim of this study was to determine whether the combination of lipid-lowering therapy and vitamin E supplementation improves peripheral endothelial function and whether it is more effective than lipid-lowering therapy alone. BACKGROUND: Endothelium-dependent vasodilation is impaired in coronary and peripheral arteries of patients with hypercholesterolemia. Coronary endothelial function has been shown to improve under lipid-lowering and antioxidant therapy, but the effect of additive vitamin E supplementation in the brachial artery is unknown. METHODS: Seven patients with hypercholesterolemia (mean+/-SD; age 51+/-10 yr) were studied. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent nitroglycerin-induced dilation (NMD) were assessed in the brachial artery using high resolution ultrasound 1) at baseline (BL I), 2) after 8 weeks of simvastatin (20 mg) and vitamin E (300 IU) therapy (Comb I), 3) after withdrawal of vitamin E for 4 weeks (Statin), 4) after therapy as in #2 for 4 weeks (Comb II) and 5) after withdrawal of both drugs for 4 weeks (BL II). RESULTS: Combined simvastatin and vitamin E therapy reduced total cholesterol (Comb I vs. BL I: 276+/-22 vs. 190+/-14 mg/dl, p < 0.0001) and low-density lipoprotein (LDL)-C (197+/-22 vs. 106+/-22 mg/dl, p < 0.00001), augmented alpha tocopherol levels normalized to LDL (12.2+/-4.1 vs. 4.9+/-0.9 microg alpha-T/100 mg% LDL-C, p < 0.01) and resulted in significant improvements in FMD (16.4+/-4.7 vs. 4.9+/-2.5%, p < 0.001) as well as NMD (17.9+/-4.3 vs. 11.2+/-2.8%, p < 0.01). The ratio of FMD to NMD (0.92+/-0.17 vs. 0.46+/-0.24%, p < 0.05) also increased under combination therapy, indicating a greater improvement of FMD than that of NMD. After withdrawal of vitamin E, both FMD (Comb I vs. Statin: 16.4+/-4.7 vs. 7.9+/-4.7%, p < 0.01) and NMD (17.9+/-4.3 vs. 10.9+/-4.5%, p < 0.05) decreased significantly such that simvastatin alone only tended to improve FMD and did not change NMD. Results under combination therapy (Comb II vs. BL II) were reproducible. CONCLUSIONS: Combined vitamin E and simvastatin therapy leads to an improvement of FMD and NMD in the brachial artery of patients with hypercholesterolemia. The improvement of FMD is more pronounced after combination therapy than after lipid-lowering therapy alone, similar to previous findings in the coronary circulation.

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.

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.

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.

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.

Impairment of endothelium-independent vasodilation in patients with hypercalcemia.

OBJECTIVE: Patients with primary hyperparathyroidism (PHPT) and/or hypercalcemia are at increased risk for myocardial ischemia. Whether PHPT is associated with altered endothelium-dependent dilation, vascular smooth muscle cell function, or both is unknown. This study was performed to test the hypothesis that endothelium-dependent, flow-mediated dilation (FMD) and/or endothelium-independent, nitroglycerin-induced dilation (NMD) is impaired in the preclinical phase of vascular disease in patients with PHPT. METHODS: Twenty-six PHPT patients (mean +/- SD; age 55 +/- 15 y, serum calcium 3.00 +/- 0.37 mmol/l, serum phosphate 0.79 +/- 0.21 mmol/l, iPTH 249 +/- 262 pg/ml) with no evidence of coronary artery disease (CAD) as well as 26 normocalcemic control subjects (CTL; age 51 +/- 12 y) were studied. FMD following reactive hyperemia and NMD after 0.8 mg nitroglycerin (NTG) were assessed in the brachial artery by using high resolution ultrasound (7 MHz). RESULTS: NMD was impaired in PHPT patients compared to CTL (11.9 +/- 3.9% vs. 15.6 +/- 5.7%; p = 0.012). FMD was similar in both study groups (11.6 +/- 4.6% vs. 12.6 +/- 4.9; NS). The ratio of FMD to NMD was significantly different between PHPT patients and CTL (0.98 +/- 0.19 vs 0.81 +/- 0.25, p = 0.0009). On multiple stepwise regression analysis serum calcium was independently associated with the FMD/NMD ratio (r = 0.34, p = 0.017). CONCLUSIONS: Endothelium-independent vasodilation is impaired in PHPT patients without clinical evidence of coronary artery disease compared to normocalcemic CTL, while endothelium-dependent dilation was similar in both study groups. Thus, altered arterial reactivity in the course of PHPT may predominantly involve the arterial media and not the endothelium as observed previously in patients with various stages of atherosclerosis.

Is oxidative stress causally linked to unstable angina pectoris? A study in 100 CAD patients and matched controls.

OBJECTIVE: Unstable angina pectoris often leads to acute myocardial infarction. Since lipid peroxidation is thought to be causally related to chronic and acute events in atherosclerosis and coronary artery disease, we measured lipid peroxidation products and vitamin E in 100 patients with coronary artery disease and compared them to a matched control group. METHODS: 50 consecutive patients with stable angina pectoris (SAP) and 50 consecutive patients with unstable angina pectoris (UAP) were studied and compared to 100 clinically healthy individuals. In addition to conventional lipid and lipoprotein analysis, malondialdehydes were measured as thiobarbituric acid reactive substances (TBARS). Lipid hydroperoxides were assayed with the colorimetric methylene blue method. alpha-Tocopherol was quantitated by HPLC after extraction of serum with hexane-ethanol. In the patient group conjugated dienes were also measured. RESULTS: As expected, patients had significantly higher cholesterol, triglyceride LDL-C and Lp(a) values and lower HDL-C values than controls. When patients were divided into groups with SAP and UAP respectively, peroxides and TBARS were significantly higher in the latter group as compared to patients with SAP and to controls. Conjugated dienes were also significantly higher in patients with UAP as compared to patients with SAP. Total plasma alpha-tocopherol was comparable in all three groups, whereas the alpha-tocopherol content per LDL particle was lowest in patients with UAP, followed by patients with SAP and then controls. CONCLUSION: It is concluded that lipid peroxidation parameters are increased in patients with UAP and discriminate SAP from UAP patients.

Urinary apo(a) discriminates coronary artery disease patients from controls.

Increased plasma lipoprotein (a) (Lp(a)) levels are associated with premature cardiovascular diseases and stroke. Since Lp(a) immune reactivity is found in urine we compared urinary apolipoprotein (a) (apo(a)) with plasma Lp(a) levels in 116 patients suffering from angiographically proven coronary artery diseases with that of 109 controls. Urinary apo(a) investigated by immuno blotting, revealed a distinct apo(a) fragmentation pattern with molecular weights between 50 and 160 kDa. Apolipoprotein B however was not secreted into urine. Lp(a) and apo(a) were measured by a fluorescence immuno assay. Within single individuals, urinary apo(a) levels correlated significantly with creatinine (Rho, 0.98; P < 0.0005). Medians and 25/75 percentiles of urinary apo(a) in coronary artery disease (CAD) patients were 5.70, 3.25 and 10.35 microg/dl and in controls 2.64, 1.43 and 3.50 microg/dl respectively. At cut-off levels of 30 mg/dl for plasma Lp(a) and 10 microg/dl of urinary apo(a) respectively, both paramenters showed comparable sensitivities (33.8% vs. 26.7%), yet the specificity (76.1% vs. 91.7%) and the positive predictive value (60.0% vs.76.4%) of urinary apo(a) were much higher. In receiver-operating characteristic plots, urinary apo(a) was much more sensitive at high specificities i.e. greater than 60% as compared to Lp(a). Urinary secretion of apo(a) fragments normalized to creatinine is stable in a given individual and significantly associated with coronary artery disease.

Plasma Lp(a) levels are increased in patients with chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease resulting from the thromboembolic obstruction of the segmental and/or large size pulmonary arteries, subsequently leading to pulmonary arterial hypertension. Incomplete resolution of acute pulmonary emboli and thrombus organization are believed to be important for the development of the disease. Primary pulmonary hypertension (PPH) is a further disease that at present is poorly understood but shows a clinical picture similar to CTEPH. Since lipoprotein(a) [Lp(a)]. a genetically determined risk factor for atherosclerosis and thrombosis, has been found increased in plasma of patients with deep vein thrombosis and pulmonary embolism, we measured plasma Lp(a) levels in 40 patients with CTEPH and 50 patients with PPH and compared them to 50 matched controls. The median for Lp(a) plasma levels was significantly higher in CTEPH patients (26.6 mg/dl) than in PPH patients (9.6 mg/dl) and controls (7.2 mg/dl). Increased plasma Lp(a) could, therefore. play a significant role in the mechanisms of ongoing thrombosis and thrombus organization in CTEPH, while its possible role in PPH can be limited to a small number of patients.

Urinary excretion of apolipoprotein(a) fragments in type 1 diabetes mellitus patients.

High levels of plasma lipoprotein(a) [Lp(a)] represent an independent risk factor for cardiovascular morbidity; however, Lp(a) has not yet been identified as a risk factor for type 1 diabetic patients. Results from the limited number of available studies on plasma Lp(a) levels in relation to renal function in type 1 diabetes mellitus are inconclusive. We hypothesized that only type 1 diabetes mellitus patients with impaired renal function show increased plasma Lp(a) levels, due to decreased urinary apolipoprotein(a) [apo(a)] excretion. We therefore measured urinary apo(a) levels in 52 type 1 diabetes mellitus patients and 52 matched controls, and related the urinary apo(a) concentration to the plasma Lp(a) level, kidney function, and metabolic control. Our findings indicate that patients with incipient diabetic nephropathy as evidenced by microalbuminuria (20 to 200 microg/min) exhibit significantly higher plasma Lp(a) levels (median, 15.6 mg/dL) in comparison to normoalbuminuric patients (median, 10.3 mg/dL) and healthy controls (median, 12.0 mg/dL). Urinary apo(a) normalized to creatinine excretion was significantly elevated in both normoalbuminuric (median, 22.3 microg/dL) and microalbuminuric type 1 diabetic patients (median, 29.1 microg/dL) compared with healthy subjects (median, 16.0 microg/dL) and correlated significantly with Lp(a) plasma levels in both patient and control groups (P < .003). No correlation existed between the Lp(a) plasma level or urinary apo(a) concentration and metabolic control in type 1 diabetes mellitus patients. From these studies, we conclude that urinary apo(a) excretion is significantly increased in type 1 diabetic patients and correlates with plasma Lp(a) levels, and only type 1 diabetic patients with microalbuminuria have higher plasma levels of Lp(a) compared with patients with normoalbuminuria and healthy controls.

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).

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.

[Lowering cholesterol 1998. Cholesterol synthesis inhibitors compared]. / Cholesterinsenkung 1998. Cholesterinsynthese-Hemmer im Vergleich.

Large scale primary and secondary prevention trials in recent years have revealed that the effective lipid reducing therapy with statins can reduce mortality of coronary heart disease by up to 30%. For the first time it has become possible to reduce LDL-cholesterol pharmacologically by more than 50%, a reduction that was only achieved by LDL-apheresis so far. Cost-effectiveness is becoming an important issue since this varies widely between patients according to the coronary risk. Treating the patients with the highest coronary risk is most cost effective. Currently, there are six statins on the market. Reduction of LDL-cholesterol is mainly mediated by the induction of LDL-receptor activity in the liver. In addition, some statins at high doses also reduce LDL-cholesterol synthesis. Due to variations in the molecular structure of the active compounds these 6 statins have important pharmacological differences, such as their capacity to reduce plasma triglycerides, their interaction with other drugs. The daily recommended doses of the statins range from 0.1 mg (cerivastatin) to 80 mg (atorvastatin). In this review the differences in the pharmacological and clinical actions of the statins are analyzed.

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.

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.

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.