The recent effects of small dose of folic acid on lipoprotein-associated phospholipase A2 and systolic blood pressure variability in coronary heart disease patients with hyperhomocysteinemia: A single-center prospective cohort study.

ABSTRACT: To Investigate the recent effects of small dose of folic acid on lipoprotein-associated phospholipase A2 (LP-PLA2) and systolic blood pressure variability in coronary heart disease (CHD) patients with hyperhomocysteinemia.In this prospective cohort study, a total of 167 CHD patients with hyperhomocysteinemia were consecutively enrolled, and they were divided into Group A (without folic acid intervention, n = 99), Group B (with 0.4 mg of folic acid intervention, n = 34), Group C (0.8 mg of folic acid intervention, n = 34). General information, fasting blood glucose, and blood lipid, folic acid, homocysteine, Lp-PLA2, and blood pressure variability were compared among 3 groups. The above indicators were reviewed after 3 months of treatment.There were no statistically significant differences of age, gender, blood pressure, incidence of type 2 diabetes mellitus, fasting blood glucose, folic acid, homocysteine, Lp-PLA2, total cholesterol, 3 acyl glycerin, apolipoprotein B, lipoprotein (a), high density lipoprotein cholesterol, and low density lipoprotein cholesterol were found among 3 groups (P > .05); however, after being treated for 3 months, there was statistically significant difference in folic acid among 3 groups (P < .05), there was statistically significant difference in apolipoprotein A between Group A and Group B (t = 0.505, P = .039), and also between Group A and Group C (t = 0.052, P = .017). There were statistically significant differences in Lp-PLA2 (t = 24.320, P = .016) and systolic blood pressure variability (t = 0.154, P = .018) between Group A and Group C.For CHD patients with hyperhomocysteinemia, the higher dose (0.8 mg) of folic acid supplement was beneficial for increasing the apolipoprotein A, reducing the Lp-PLA2, and improving the systolic blood pressure variation, which might help to improve the prognosis in these patients.

Differential protein analysis of serum exosomes post-intravenous immunoglobulin therapy in patients with Kawasaki disease.

BACKGROUND: Kawasaki disease, which is characterised by systemic vasculitides accompanied by acute fever, is regularly treated by intravenous immunoglobulin to avoid lesion formation in the coronary artery; however, the mechanism of intravenous immunoglobulin therapy is unclear. Hence, we aimed to analyse the global expression profile of serum exosomal proteins before and after administering intravenous immunoglobulin. METHODS: Two-dimensional electrophoresis coupled with mass spectrometry analysis was used to identify the differentially expressed proteome of serum exosomes in patients with Kawasaki disease before and after intravenous immunoglobulin therapy. RESULTS: Our analysis revealed 69 differential protein spots in the Kawasaki disease group with changes larger than 1.5-fold and 59 differential ones in patients after intravenous immunoglobulin therapy compared with the control group. Gene ontology analysis revealed that the acute-phase response disappeared, the functions of the complement system and innate immune response were enhanced, and the antibacterial humoral response pathway of corticosteroids and cardioprotection emerged after administration of intravenous immunoglobulin. Further, we showed that complement C3 and apolipoprotein A-IV levels increased before and decreased after intravenous immunoglobulin therapy and that the insulin-like growth factor-binding protein complex acid labile subunit displayed reverse alteration before and after intravenous immunoglobulin therapy. These observations might be potential indicators of intravenous immunoglobulin function. CONCLUSIONS: Our results show the differential proteomic profile of serum exosomes of patients with Kawasaki disease before and after intravenous immunoglobulin therapy, such as complement C3, apolipoprotein A-IV, and insulin-like growth factor-binding protein complex acid labile subunit. These results may be useful in the identification of markers for monitoring intravenous immunoglobulin therapy in patients with Kawasaki disease.

1 and 2 mg 17beta-estradiol combined with sequential dydrogesterone have similar effects on the serum lipid profile of postmenopausal women.

OBJECTIVES: The aim of this study was to assess the effects of 1 and 2 mg 17beta-estradiol on serum lipid profile. Beneficial effects have been clearly established in previous studies with a 2 mg dose; further evidence was required to confirm the beneficial effects of a 1 mg dose. METHODS: This double-blind, placebo-controlled study involved 579 postmenopausal women randomized to oral treatment with placebo, 1 mg/day 17beta-estradiol sequentially combined with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle, or 2 mg/day 17beta-estradiol sequentially combined with 10 or 20 mg/day dydrogesterone for the last 14 days of each 28-day cycle. Treatment was continued for 26 cycles. RESULTS: High density lipoprotein (HDL) cholesterol levels were significantly (p<0.05) increased after 26 cycles in all active treatment groups compared with placebo. In addition, low density lipoprotein (LDL) cholesterol and lipoprotein(a) levels were significantly reduced, and apolipoprotein A1 and triglyceride levels were significantly increased, in all active treatment groups after 13 and 26 cycles. CONCLUSIONS: The results of this study clearly indicate that sequential combinations of either 1 or 2 mg 17beta-estradiol with dydrogesterone are associated with long-term, favorable changes in the serum lipid profile. There was no evidence that dydrogesterone compromised the 17beta-estradiol-induced improvements in lipid profile.

Red-wine beneficial long-term effect on lipids but not on antioxidant characteristics in plasma in a study comparing three types of wine--description of two O-methylated derivatives of gallic acid in humans.

The purpose of this double clinical study was (1) to evaluate the effect of one single intake (300 ml) of red wine (RW) on the plasma antioxidant capacity (pAOC) and plasma phenolics over the 24-h time period following the intake, and (2) to compare the long-term effects of daily intakes (250 ml/d) of RW, white wine (WW) and Champagne (CH) on the plasma and LDL characteristics of healthy subjects. In the first part, blood samples were collected just before and after wine consumption. In the second part, subjects received the 3 types of wine successively, only at the mealtime, over 3-week periods separated by a 3-week wash out. Blood samples were drawn in fasting condition before and after each 3-week wine consumption period. The peak of pAOC was at 3-4 h following the single intake of RW, that of catechin was at 4 h (0.13 micromol/l) and that of gallic acid and caffeic acid was earlier (< or = 1.5 and 0.3 micromol/l, respectively). In plasma, the major form of gallic acid was 4-O-methylated, but a minor form (the 3-O-methyl derivative) appeared. In the long term study, no wine was able to change LDL oxidizability, but some other parameters were modified specifically: RW decreased pAOC (without changing TBARS and uric acid plasma levels), LDL lipids and total cholesterol (TC), and increased plasma apoA1, whereas CH increased plasma vitamin A. The beneficial effect of RW seems to mainly be explained by its action on lipid and lipoprotein constants, and not by its antioxidant one.

Atorvastatin lowers lipoprotein(a) but not apolipoprotein(a) fragment levels in hypercholesterolemic subjects at high cardiovascular risk.

The effect of statins on Lp(a) levels is controversial; furthermore, the potential action of statins on apo(a) fragmentation is indeterminate. We therefore determined the circulating levels of Lp(a) and of apo(a) fragments in hypercholesterolemic patients before and after treatment (6 weeks) with Atorvastatin 10 mg/day (A10) or Simvastatin 20 mg/day (S20). In a double blind study, hypercholesterolemic patients (n=391) at high cardiovascular risk (LDL-C>=4.13 mmol/l; TG<2.24 mmol/l; 34% with documented CHD; 45% hypertensive; and 29% current smokers) were assigned to treatment with A10 (n=199) or S20 (n=192). Plasma Lp(a) and apo(a) fragment levels (n=206) were measured prior to and after treatment. At baseline, A10 and S20 groups did not differ in plasma levels of lipids, Lp(a) (A10: 0.45+/-0.48 mg/ml, S20: 0.46+/-0.5), and apo(a) fragments (A10: 3.88+/-5.22 microg/ml; S20: 3.25+/-3), and equally in apo(a) isoform size (A10: 26+/-5 kr, S20: 25.5+/-5.3). After treatment, both statins significantly reduced Lp(a) levels (A10: 0.42+/-0.47 mg/ml, 6% variation, P<0.001; S20: 0.45+/-0.53 mg/ml, 0.02% variation, P=0.046). A10 and S20 did not significantly differ in their efficacy to lower Lp(a) levels. In a multivariate logistic regression analysis, the reduction of Lp(a) levels was independently associated with Lp(a) baseline concentration, but not to other variables, including LDL-C reduction. Plasma levels of apo(a) fragments were not modified by either statin. In conclusion, both A10 and S20 significantly lowered Lp(a), although this effect was of greater magnitude in atorvastatin-treated patients.

Vitamin C intake and apolipoproteins in a healthy elderly Japanese population.

BACKGROUND: Adequate vitamin C (AsA) intake may lower the risk of arteriosclerotic cardiovascular disease, but little is known about its influence on the progression of atherogenic disease in the elderly. METHODS: We examined whether AsA intake was associated with serum lipids, apolipoprotein A-1 (ApoA1) and apolipoprotein B (ApoB), in 680 Japanese elderly persons. RESULTS: There were no significant gender differences among mean serum lipids and apolipoprotein concentrations and intakes of macronutrients. AsA intake had a significant positive association with serum concentrations of high-density cholesterol and ApoA1, but an inverse association with serum concentrations of low-density cholesterol and ApoB, after adjusting for age, body mass index, total energy, and macronutrients. AsA intake was strongly inversely related to ApoA1/ApoB. CONCLUSION: Increased AsA intake could play an important role in lipid composition and could be of potential importance in the genesis and prevention of atherogenic disease in the elderly.

Butyrate stimulates ApoA-IV-containing lipoprotein secretion in differentiated Caco-2 cells: role in cholesterol efflux.

The aim of this study was to determine: (1) whether the Short Chain Fatty Acids (SCFA) Acetate, Propionate, and Butyrate enhance the synthesis and secretion of intestinal apolipoprotein A-IV-containing lipoproteins and (2) if so, whether these particles are able to promote cholesterol efflux in vitro. For this purpose Caco-2 cells were used for their functional properties of differentiated enterocytes. They were incubated with the three SCFA (2, 4, and 8 mM) for 48 h. Only butyrate stimulated apoA-IV gene expression and this was associated with an increase in apoA-IV secretion. A nondenaturing 2D-PAGE (agarose gel was followed by PAGE) was used to identify apoA-IV-containing lipoproteins in various media, and showed that butyrate stimulated the secretion of two small HDL sized particles. The influence of these secreted particles on cholesterol efflux was investigated using incubation of media with (3)H-cholesterol-labeled Fu5AH cells. The data indicate that conditioned media from Caco-2 cells treated with butyrate resulted in an increase of 20-30% in cholesterol efflux. We conclude that butyrate may regulate apoA-IV secretion and, therefore, modulate reverse cholesterol transport.

Enhancement of the cAMP-induced apolipoprotein-mediated cellular lipid release by calmodulin inhibitors W7 and W5 from RAW 264 mouse macrophage cell line cells.

Apolipoprotein (apo) A-I generates high-density lipoprotein (HDL) by removing cellular cholesterol and phospholipid on the interaction with cells as a main source of plasma HDL. The reaction is induced by dibutylyl cyclic (dbc) adenosine monophosphate (AMP) in RAW 264, mouse macrophage cell line cells, and we investigated its pharmacologic modulation using this cell model. Release of cellular cholesterol and choline phospholipid by apoA-I was increased 9.9 and 4.2 times, respectively, by pretreatment of the cells with 300 microM dbcAMP for 24 h. Calmodulin inhibitors, W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide) and W5 (N(6-aminohexyl)-1-naphthalenesulfonamide), increased the apoA-I-mediated lipid release by 3 times from the dbcAMP-treated cells. The optimal drug concentrations (80 and 160 microM for W7 and W5, respectively) were not parallel with those reported for in vitro calmodulin inhibition (IC50, 28 and 240 microM for W7 and W5, respectively, toward phosphodiesterase activity), and in fact 40 microM W7 showed much stronger intracellular calmodulin inhibition than did 300 microM W5 using S7AAS2, a fluorescent peptide probe. Other calmodulin inhibitors such as amitriptyline, chlorpromazine, and trifluoperazine showed no effect on the apoA-I-mediated cholesterol release. In contrast to these results, neither dbcAMP nor W7 influenced the diffusion-mediated nonspecific cholesterol efflux to lipid microemulsion. We concluded that W7 and W5 increased the interaction of apoA-I with RAW 264 cells to generate more HDL. The effect did not seem directly correlated to their cal modulin inhibition or modulation of cAMP and protein kinase C.

Intravenous infusion of hexamethonium and atropine but not propranolol diminishes apolipoprotein A-IV gene expression in rat ileum.

To clarify the role of neural factors in the regulation of apolipoprotein (apo) A-IV expression in the small intestine, we investigated the effect of neural blockers on mRNA levels of apo A-IV in rat small intestine. Either ganglionic blocker (hexamethonium), cholinergic blocker (atropine) or beta-adrenergic blocker (propranolol) was infused intravenously to unrestrained conscious rats for 8 h, and then total RNA was isolated from the small intestine and analyzed using Northern hybridization. Apo A-IV mRNA levels in the ileum were significantly lower in hexamethonium- or atropine-infused rats than in saline- (control) or propranolol-infused rats. Immunoblot analysis showed no difference in plasma apo A-IV concentrations between hexamethonium- and saline-infused groups. The lower mRNA levels of apo A-IV in the ileum of hexamethonium-infused rats were observed even in bile-drained rats, indicating that the lower expression was not due to any changes in bile availability. The ileal apo A-IV mRNA levels were significantly higher in rats infused with lipid emulsion into the ileum than in rats infused with glucose-saline, and the concomitant infusion of intravenous hexamethonium did not affect the higher levels of apo A-IV mRNA. These results suggest that the basal expression of the ileal A-IV gene is at least partially regulated in a site-specific manner by cholinergic neurons.

Aspirin reduces apolipoprotein(a) (apo(a)) production in human hepatocytes by suppression of apo(a) gene transcription.

High serum lipoprotein(a) (Lp(a)) is a risk factor for vascular disorders. Our preliminary observations suggest that, in some patients with coronary heart disease with high serum Lp(a) levels, administration of aspirin reduced Lp(a) levels. Therefore, we aimed to analyze the effects of aspirin on the production of apo(a), the expression of apolipoprotein(a) (apo(a)) mRNA and the transcriptional activity of apo(a) gene promoter. Aspirin (5 mM) reduced the apo(a) levels in culture medium of human hepatocytes and suppressed apo(a) mRNA expression to 73% and 85% of the controls, respectively. Aspirin also reduced the transcriptional activity of apo(a) gene transfected into HepG2 hepatoma cells in a dose-dependent manner, with a maximal effect at 5 mM (44.3 +/- 1.5% of the control). Sodium salicylate (5 mM) also reduced apo(a) gene transcription, whereas indomethacin (10 microM) had no effect. Deletion analysis of apo(a) gene promoter showed that promoter region extending from -30 to +138 is critical for the effect of aspirin. Furthermore, enhanced production, mRNA expression, and gene transcription of apo(a) by interleukin-6 were also inhibited by aspirin. These results demonstrate that aspirin reduces apo(a) production from hepatocytes via reduction of the transcriptional activity of apo(a) gene with suppression of apo(a) mRNA expression. The suppression of apo(a) production by aspirin may at least in part play a role in the anti-atherogenic effect of aspirin in vascular disorders.

The effect of 24 months recombinant human growth hormone (rh-GH) on LDL cholesterol, triglyceride-rich lipoproteins and apo [a] in hypopituitary adults previously treated with conventional replacement therapy.

Hypopituitary adults receiving conventional hormone replacement therapy are reported to have increased cardiovascular mortality. Previous studies indicate that these patients have several abnormalities in lipoprotein metabolism, including reduced low density lipoprotein (LDL) uptake and impaired metabolism of triglyceride-rich lipoproteins. The effects of 24 months of 0.21 IU/kg per week recombinant growth hormone (rh-GH) on the lipoprotein profiles of 22 GH-deficient adults were studied. Samples were collected after a 12-h fast at baseline and 24 months. Total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, apolipoprotein (apo) A, apo B and apo [a] were determined by routine laboratory methods. LDL particle size was determined by non-denaturing gradient gel electrophoresis. Visceral adiposity was determined by dual energy X-ray absorptiometry (DEXA). Insulin sensitivity was measured in a subset of 17 subjects using a two-stage hyperinsulinaemic-euglycaemic clamp. Significant reductions were observed in total cholesterol (5.3 +/- 0. 17 vs 4.9 +/- 0.23 mmol/l;P<0.05) and LDL cholesterol (3.4 +/- 0.17 vs 2.9 +/- 0.17 mmol/l; P<0.001) at 24 months when compared to baseline. No significant changes were observed in triglyceride level, HDL cholesterol level, apo B, apo A and LDL size. A significant increase in apo [a] [160 (96-416) vs 204 (127-534) U/l;P<0.05] was observed which appeared to be dose-dependent. Visceral adiposity was reduced significantly. Insulin sensitivity did not alter significantly. Replacement for 24 months with rh-GH has a differential effect on the lipid profile with a decrease in LDL, but little effect upon the metabolism of triglyceride-rich lipoproteins, manifested by unchanged triglyceride, HDL cholesterol levels and LDL size, despite the reduction in visceral adiposity. Conversely, apo [a], an independent risk factor for cardiovascular disease was increased. The ultimate effect of GH therapy upon cardiovascular mortality remains to be determined and may be dose-related.

Two-year prospective and comparative study on the effects of tibolone on lipid pattern, behavior of apolipoproteins AI and B.

OBJECTIVE: To investigate long-term lipid and lipoprotein changes in postmenopausal women treated with tibolone in a prospective study using appropriate control groups. DESIGN: Seventy-six of 105 postmenopausal women initially selected for this study completed the 2-year follow-up. Patients were allocated into three groups. The first received 2.5 mg/day tibolone continuously (n = 27; group T), the second received 0.625 mg/day conjugated equine estrogen plus 2.5 mg/day of medroxyprogesterone (group E-P) continuously (n = 25), and a third group contained an additional 24 women who did not receive replacement therapy; these constituted the untreated control group (group C). Plasma lipids and lipoproteins were determined in all patients before joining the study and also at 12 and 24 months after being included. RESULTS: Women treated with tibolone experienced the greatest decreases in cholesterol, both total and high density lipoprotein (HDL), and triglycerides (TG), whereas the highest increase in HDL was observed in the group E-P. A decrease in low density lipoprotein levels was detected in both therapy groups, whereas a significant increase was observed in the control group. TG were increased after E-P therapy. In all the groups, apolipoprotein AI showed parallel trends to HDL and apolipoprotein B to low density lipoprotein. CONCLUSIONS: Both therapy groups, tibolone and E-P, induced changes in levels of plasma lipids, lipoproteins and apolipoproteins. Long-term tibolone treatment is associated with a marked and significant decrease in HDL apolipoprotein AI and TG, an effect that defines the major difference with standard HRT. Clearly, further studies are necessary to establish the definite risk/benefit ratio of tibolone with respect to its overall effect on lipid metabolism.

Plant monoterpenes do not raise plasma high-density-lipoprotein concentrations in humans.

BACKGROUND: Low plasma concentrations of HDLs are associated with an increased risk of coronary artery disease. Two uncontrolled studies suggested that plant monoterpenes may have substantial HDL-cholesterol-elevating activity in humans. Each study used a proprietary mixture of 6 monoterpenes in olive oil. OBJECTIVE: The present study was undertaken to test more rigorously the hypothesis that monoterpenes raise HDL concentrations in men with hypoalphalipoproteinemia. DESIGN: A double-blind, placebo-controlled crossover design was used. Twenty-four men aged 58-68 y (x: 62.3 y) with plasma HDL cholesterol <1.1 mmol/L, plasma triacylglycerols <3.5 mmol/L, and plasma total cholesterol <5.5 mmol/L at recruitment were randomly assigned to 6 capsules daily of a proprietary mixture of 6 monoterpenes in olive oil or 6 capsules daily of olive oil alone for 24 wk, followed by a washout period of 8 wk, and then the alternative capsules for 24 wk. RESULTS: Five men dropped out. In the others, compliance was excellent as judged by capsule counts and urinary menthol glucuronide concentrations. No significant effects were observed on plasma HDL-cholesterol or apolipoprotein A-I concentrations, nor on plasma triacylglycerol, LDL-cholesterol, or apolipoprotein B concentrations. CONCLUSIONS: Plant monoterpenes have no HDL-elevating activity of potential value for coronary artery disease prevention.

Statin therapy in a kindred with both apolipoprotein B and low density lipoprotein receptor gene defects.

We studied an extended family of similar genetic and environmental background to determine whether there is a difference in response to statin therapy in those subjects with heterozygous familial hypercholesterolaemia (FH Afrikaner-1 (FH1) or FH Afrikaner-2 (FH2)) compared to those with familial defective apo B-100 (FDB), or both FH plus FDB. Fasting lipid profiles and Lp(a) levels were done on 18 members of the family and then repeated following 6 weeks of therapy with simvastatin 20 mg daily. Statin therapy reduced LDL-cholesterol (LDL-C) by 31% in those with FH (n = 7); 29.8% in FDB (n = 5) and 25.4% in those with both FDB and FH (n = 5). There was no response to statin therapy in the single subject with both FH1, FH2, as well as FDB. Lp(a) levels did not change significantly either within or between any of the groups following statin therapy (FH from 6.5 (1.2-72.3) to 5.3 (1.2-52.3), FDB from 6.1 (4.70-71) to 8.2 (5.7 79) and FDB plus FH from 4.5 (2.6-17.4) to 3.1 (1.9-24) mg/dl). Statins are equally effective in lowering LDL-C in related subjects with heterozygous FH, FDB or both FDB plus FH. The ability of statins to lower LDL-C in FDB is probably due to increased hepatic uptake of lipoprotein precursors of LDL that can bind via apo E receptors. Lp(a) concentration is not reduced by drugs that stimulate LDL receptor activity implying that LDL receptors do not contribute greatly to normal clearance of Lp(a) in hypercholesterolaemic subjects with defects in receptor-mediated endocytosis of LDL.

Bezafibrate. An update of its pharmacology and use in the management of dyslipidaemia.

The lipid-modifying profile of bezafibrate is characterised by marked decreases in elevated triglyceride levels, increases in high density lipoprotein (HDL) cholesterol levels and decreases in total and low density lipoprotein (LDL) cholesterol levels. Bezafibrate also reduces elevated levels of lipoprotein(a) [Lp(a)] and fibrinogen, which are independent cardiovascular risk factors. Bezafibrate is effective in most types of primary and secondary dyslipidaemia. It is of greatest benefit in conditions featuring hypertriglyceridaemia and/or HDL cholesterol deficiency. This is particularly true for patients with diabetes mellitus, notably those with non-insulin-dependent diabetes mellitus (NIDDM) who are also likely to have increased fibrinogen levels. In the limited comparisons available, there appear to be few consistent differences in lipid-modifying effects between bezafibrate and other fibrates. Compared with HMG-CoA reductase inhibitors, bezafibrate causes larger changes in triglyceride and, in general, HDL cholesterol levels, and has a lesser influence on LDL and total cholesterol levels. These differences are advantageous when bezafibrate and HMG-CoA reductase inhibitors are used as combined therapy in patients with severe dyslipidaemia unresponsive to either modality alone. The combination of bezafibrate plus an HMG-CoA reductase inhibitor in clinical trials has not led to the predicted increase in myalgia. Indeed, bezafibrate is generally free of serious unwanted effects: rhabdomyolysis is rare and has occurred mainly in patients with renal dysfunction given excessive dosages. Other patient groups in whom bezafibrate has improved serum lipid profiles are those with isolated HDL cholesterol deficiency, dyslipidaemia secondary to renal insufficiency, and following cardiac surgery or other procedures. However, data for these indications are not extensive. Evidence is now available to show a beneficial effect of bezafibrate on retarding atherosclerotic processes and in reducing risk of coronary heart disease. The 5-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) in young male survivors of myocardial infarction demonstrated a smaller decrease in luminal diameter and a reduction in coronary events with bezafibrate compared with placebo. The Bezafibrate Infarction Prevention (BIP) study is expected to provide mortality data which is currently lacking for bezafibrate. In conclusion, bezafibrate is a useful and well-tolerated lipid-modifying agent in the management of primary and secondary dyslipidaemia. It has particularly beneficial effects in patients with hypertriglyceridaemia and/or low HDL cholesterol levels, and reduces fibrinogen levels. Together with its ability to sustain or improve glycaemic control, these properties make it a logical choice for treating patients with diabetes mellitus and dyslipidaemia. Additionally, the drug may be of value as combination therapy in patients with severe dyslipidaemia. Importantly, there is evidence that the drug can slow the atherosclerotic process and reduce cardiovascular morbidity. The ongoing BIP secondary intervention study and other investigations will help clarify the effects of bezafibrate on cardiovascular mortality and morbidity.

Oral physiological magnesium supplementation for 6 weeks with 1 g/d magnesium oxide does not affect increased Lp(a) levels in hypercholesterolaemic subjects.

Twenty hyperlipidaemic patients on a cholesterol-poor diet were selected on the basis of a raised lipoprotein (a) (Lp(a); apo (a) > 300 U/litre) and treated with 1000 mg MgO per day during 6 weeks. Serum magnesium slightly increased compared to pretreatment levels (P < 0.001). Serum apo(a) concentrations (mean +/- S.D.) were not affected: pretreatment level 963 +/- 552 U/litre; during treatment 999 +/- 536 U/litre; and after washout 995 +/- 524 U/litre. Serum cholesterol increased slightly during MgO treatment because of an increase in LDL-cholesterol (10 per cent) and returned to pretreatment levels after a washout period.

La terapia hormonal sustitutiva modifica la composición en ácidos grasos de fosfolípidos de HDL / Hormone replacement therapy modifies the fatty-acid composition of HDL phospholipids

Las mujeres postmenospáusicas tienen un riesgo aumentado de padecer enfermedad coronaria en comparación con las premenospáusicas. Sin embargo, el riesgo disminuye cuando se realiza terapia hormonal sustitutiva. El objetivo de este estudio es investigar el posible efecto de la terapia con 17 ß Estradiol (E2) o de la combinación de 17 ß Estradiol y Acetato de Medroxiprogesterona (AMP), sobre las concentraciones plásmicas de colesterol total, colesterol HDL, colesterol LDL, colesterol VLDL y triglicéridos, fracciones de conocida participación en la aterogénesis. También se estudió la composición de ácidos grasos de fosfolípidos de la fracción no retenida obtenida por cromatografía de afinidad con Concanavalina A. Al cabo de 30 días de tratamiento con E2, el colesterol total disminuyó desde 226,0 ñ 54,4 mg/dl hasta 202,0 ñ 51,7 mg/dl; los niveles de triglicéridos descendieron desde 106,3 ñ 31,3 mg/dl hasta 80,6 ñ 13,9 mg/dl (p < 0,05), posiblemente a expensas de la fracción VLDL (21,3 ñ 6,2 mg/dl vs. 16,9 ñ 2,5 mg/dl); los fosfolípidos de la fracción no retenida de Concanavalina A mostraron una disminución de los ácidos grasos mirístico, palmítico y esteárico, y un aumento concomitante de los ácidos grasos oleico y linoleico. Los cambios observados con la administración de E2 tendieron a anularse cuando se agregó Acetato de Medroxiprogesterona (AU)

Effect of immunosuppressive drug regime on cardiovascular risk profile following kidney transplantation.

We have previously studied cardiovascular risk markers apolipoprotein (a) (apo(a)) and plasma fibrinogen in 146 control, 60 haemodialysis (HD), 53 continuous ambulatory peritoneal dialysis (CAPD) and 66 renal transplant subjects. Fibrinogen concentration was higher in all 3 renal replacement groups compared to controls. Apo(a) was higher in the CAPD group only. We have now restudied those dialysis patients (24 HD, 16 CAPD) who have since undergone transplantation. Fibrinogen concentration remained elevated in CAPD patients (mean (SE) 3.9 (0.17) vs. 3.77 (0.20) grams/l) and increased in HD patients (2.88 (0.16) vs. 3.72 (0.13) grams/l, P < 0.0001). Apo(a) fell in both groups (CAPD, geometric mean 287 vs. 151 U/l, P = 0.008; HD, 230 vs. 179 U/l, P = 0.013). Fibrinogen concentration was higher in the recent group compared to the original group (3.74 (0.11) vs. 3.19 (0.12) grams/l, P = 0.001). None of the 66 original patients received cyclosporin (cyA) compared to 35 of the 40 in the present study. In this recent group, patients maintained on prednisolone and azathioprine alone had significantly lower fibrinogen levels than those receiving cyA. Furthermore, the fall in apo(a) was smaller (31% vs. 74%) and the increase in apolipoprotein B (apo B) greater (0.55 (0.15) vs. 0.18 (0.05) grams/l, P = 0.014) in cyA-treated patients. CyA may have an adverse effect on cardiovascular risk profile in renal transplant recipients.

Comparison of Lp(a) concentrations and some potential effects in hemodialysis, CAPD, transplantation, and control groups, and review of the literature.

Apolipoprotein (a)-Lp(a)-is reported to be an independent risk factor for coronary artery disease and for hemodialysis (HD) access occlusion. Homology with plasminogen may predispose to thrombosis. High concentrations usually have been reported in patients on HD and on continuous ambulatory peritoneal dialysis (CAPD), but near-normal values in many kidney transplants (TP). We used Pharmacia immunoradiometric assay in 52 patients on HD, 58 on CAPD, 94 after TP, and 56 controls. The Lp(a) mean levels for CAPD, HD, TP, and control groups were 738, 647, 348, and 368 U/l and the medians were 542, 537, 96 and 143 U/l, respectively. The means and medians for CAPD and HD were significantly greater than those for TP and controls (p < 0.003 for means and < 0.005 for medians). We found no significant difference between: (1) Lp(a) means or medians comparing HD and CAPD or TP and controls; (2) Lp(a) means for the 33 patients with insulin-dependent diabetes mellitus and the 171 without; (3) number of occlusions of HD fistulae or grafts in patients with high Lp(a) values and without; (4) mean Lp(a) for CAPD patients on gemfibrozil and also for TP patients on 3-hydroxy-methylglutaryl coenzyme 1 reductase inhibitors, or diet alone, before and after treatment, and (5) mean Lp(a) values for HD and CAPD patients with and without myocardial infarction. Lp(a) did not correlate significantly with fractional shortening or left ventricular end systolic or diastolic diameter by echocardiogram or with ejection fraction. For TP patients, Lp(a) and serum creatinine correlated (p = 0.004), and mean Lp(a) for 71 TP on ciclosporin A exceeded that for the other 23 patients (p < 0.03). Lp(a) fell in 13 of 14 patients after TP (mean fall 77%). The dominant Apo(a) isoform in 10 of 13 patients on CAPD or HD with high Lp(a) values was the equivalent of S2 (Utermann). Lp(a) in HD or CAPD is often elevated and regulated by both genetic and renal failure factors, but falls after TP with return of renal function and mainly genetic regulation. Lp(a) was not a risk factor for coronary artery disease in HD or CAPD patients and did not fall significantly with two drugs or diet.

The effect of a thromboxane A2 synthase inhibitor on the dyslipoproteinemia of an inbred rat strain with spontaneous age-related nephrotic syndrome.

We have previously shown that the administration of a thromboxane A2 (TXA2) synthase inhibitor (FCE 22178) reduced the progression of glomerular lesions and proteinuria in MNS rats, an inbred strain which develops an age-related nephrotic syndrome. In the present study we investigated the effect of FCE 22178 on the plasma lipoproteins of MNS rats at 28 weeks of age (with mild proteinuria and moderate dyslipoproteinemia) and at 48 weeks of age (with heavy proteinuria and severe dyslipoproteinemia). Drug treatment reduced proteinuria (by 70% and 36% at 28 and 48 weeks of age, respectively) plasma cholesterol (by 36% and 27% at 28 and 48 weeks of age, respectively) and prevented the decrease of plasma albumin observed in untreated rats (C-MNS) 48 weeks old. In treated rats (T-MNS), the decrease of proteinuria was positively correlated with that of plasma cholesterol. FCE 22178 reduced the elevation in plasma HDL1 (by 17.4%) and HDL2 levels (by 30%), a key feature of nephrotic dyslipoproteinemia in the rat. From 28 to 48 weeks of age plasma apo A-I and apo E increased 217% and 128%, respectively, in C-MNS rats and 191% and 121%, respectively, in T-MNS rats. A significant increase of apo A-I/apo E ratio was found in C-MNS rats from 28 (2.28 +/- 0.36) to 48 weeks of age (3.84 +/- 0.9) but not in T-MNS rats. FCE 22178 altered the lipid composition of VLDL and HDL2 by reducing the content of cholesteryl esters and increasing that of free cholesterol and phospholipids. These findings suggest that the beneficial effect of FCE 22178 on the dyslipoproteinemia of nephrotic MNS rats is secondary to the amelioration in kidney function and to the reduction of proteinuria produced by this drug.