Conservative therapeutic approaches in terminal coronary heart disease. Chronic intermittent urokinase therapy

The plasma concentration of lipoprotein(a) [Lp(a)] is highly correlated with the incidence of cardiovascular and peripheral vascular disease. A positive physiological role for Lp(a) has not yet been clearly identified, although elevated plasma levels in pregnant women, long-distance runners, subjects given growth hormone, patients after cardiovascular surgery, and patients with cancer, diabetes, or renal disease suggest its involvement in tissue synthesis and repair. The hypothesis that Lp(a) is involved in repair/reinforcement of the aorta was tested in 38 patients undergoing surgery for aortic aneurysm. In 29 patients 1 day before surgery, the mean plasma Lp(a) protein level was 10.7 mg/dl. At about 1, 2, and 8 weeks after surgery, the level was 14.1, 15.1, and 15.2 mg/dl, respectively. These levels are significantly higher than those of a comparable group of normal subjects (6.4 mg/dl; n = 274). Specimens of resected aortic aneurysm showed extensive medial degeneration, discontinuous elastic fibers, and deposition of mucopolysaccharides; these specimens were treated with a detergent-containing buffer to extract entrapped lipoproteins. The mean Lp(a) protein level in aortic wall extracts was 14.6 ng/mg tissue; these individual values were significantly associated with plasma Lp(a) levels before surgery (r2 = 0.31, p = 0.0003). The mean Lp(a) protein level in aortic thrombus extracts was substantially higher at 69.6 ng/mg tissue; these individual levels also were significantly associated with plasma Lp(a) concentrations before surgery (r2 = 0.68, p < 0.0001). The observations that: (i) plasma Lp(a) protein is about 1.7-fold higher in patients with aortic aneurysms than in normal subjects; and (ii) that Lp(a) protein in the aneurysmic thrombus is about 4.8-fold higher than in the aortic wall suggest that this lipoprotein plays a significant and direct role in thrombus formation and in reinforcement of the aneurysmic aortic wall.     

Different change in lipoprotein(a) levels from lipid levels of other lipoproteins with improved glycemic control in patients with NIDDM

OBJECTIVE: To evaluate change both in lipoprotein(a) [Lp(a)] and lipid levels in other lipoproteins in non-insulin-dependent diabetes mellitus (NIDDM) after short-term improvement of glycemic control. RESEARCH DESIGN AND METHODS: We compared Lp(a) levels in 210 NIDDM patients with those in 46 control subjects and evaluated the relationship between glycemic control and Lp(a) levels in diabetic patients. In addition, changes in Lp(a) levels and lipid levels were assessed after the improvement of glycemic control in 54 poorly controlled NIDDM patients. RESULTS: In NIDDM, Lp(a) levels in all patients, 62 patients with HbA1c < 6.0%, and 75 patients with HbA1c between 6.0 and 8.0%, were significantly higher than those in control subjects (19.1 [1.7-106.6], 19.2 [6.0-106.6], and 20.3 [2.7-75.3] vs. 15.4 [2.0-61.7] mg/dl, median [range], P < 0.05). Lp(a) levels in 73 patients with HbA1c of > or = 8.0% (18.7 [1.7-58.8] mg/dl) were not significantly different from those in control subjects. After glycemic control, lipid levels in plasma and in other lipoproteins fell significantly, but Lp(a) did not change (from 18.3 [1.7-58.8] to 18.4 [6.6-95.3] mg/dl). Changes in lipid levels, including Lp(a), did not correlate with those in fasting plasma glucose or HbA1c. CONCLUSIONS: These results suggest that elevated Lp(a) levels do not reflect poor glycemic control and that Lp(a) levels are independent of lipid levels in other lipoproteins after improved glycemic control in NIDDM.     

LDL-unbound apolipoprotein(a) and carotid atherosclerosis in hemodialysis patients

High lipoprotein(a) [Lp(a)] plasma concentrations, which are genetically determined by apo(a) size polymorphism, are directly associated with an increased risk for atherosclerosis. Patients with end-stage renal disease (ESRD), who show an enormous prevalence of cardiovascular disease, have elevated plasma concentrations of Lp(a). In recent studies we were able to show that apo(a) size polymorphism is a better predictor for carotid atherosclerosis and coronary artery disease in hemodialysis patients than concentrations of Lp(a) and other lipoproteins. Less than 5% of apo(a) in plasma exists in a low-density lipoprotein (LDL)-unbound form. This "free" apo(a) consists mainly of disintegrated apo(a) molecules of different molecular weight, ranging from about 125 to 360 kDa. LDL-unbound apo(a) molecules are elevated in patients with ESRD. The aim of this study was therefore to investigate whether the LDL-unbound form of apo(a) contributes to the prediction of carotid atherosclerosis in a group of 153 hemodialysis patients. The absolute amount of LDL-unbound apo(a) showed a trend to increasing values with the degree of carotid atherosclerosis, but the correlation of Lp(a) plasma concentrations with atherosclerosis was more pronounced. In multivariate analysis the two variables were related to neither the presence nor the degree of atherosclerosis. Instead, the apo(a) phenotype took the place of Lp(a) and LDL-unbound apo(a). After adjustment for other variables, the odds ratio for carotid atherosclerosis in patients with a low molecular weight apo(a) phenotype was about 5 (p<0.01). This indicates a strong association between the apo(a) phenotype and the prevalence of carotid atherosclerosis. Finally, multivariate regression analysis revealed age, angina pectoris and the apo(a) phenotype as the only significant predictors of the degree of atherosclerosis in these patients. In summary, it seems that LDL-unbound apo(a) levels do not contribute to the prediction of carotid atherosclerosis in hemodialysis patients. However, this does not mean that "free", mainly disintegrated, apo(a) has no atherogenic potential.     

The genomes of three of four novel HPV types, defined by differences of their L1 genes, show high conservation of the E7 gene and the URR

OBJECTIVES: This study was undertaken to test the hypothesis that lipoprotein(a) [Lp(a)] impairs endothelial function. BACKGROUND: Elevated Lp(a) plasma levels have been demonstrated to be associated with an increased risk of coronary heart disease. In atherosclerosis, endothelial dysfunction is known to be an early indicator of vascular changes. However, the effect of Lp(a) on nitric oxide (NO)-dependent vasodilator response has not yet been determined. We therefore examined the influence of Lp(a) on basal and stimulated NO-mediated vasodilator response in the forearm vascular bed. METHODS: Strain gauge plethysmography was used to measure changes in forearm blood flow produced by intraarterial infusion of increasing doses of acetylcholine (3, 12, 24 and 48 microg/min), sodium nitroprusside (200, 800 and 3,200 ng/min) and N-monomethyl L-arginine (L-NMMA) (1, 2 and 4 micromol/min) in 57 white subjects (mean age +/- SD 37 +/- 14 years). Lp(a) plasma concentrations were determined by rocket immunoelectrophoresis. RESULTS: Endothelium-dependent vasodilation tested by intraarterial acetylcholine and endothelium-independent vascular relaxation tested by intraarterial sodium nitroprusside were not correlated with Lp(a). Similarly, no significant differences in forearm blood flow changes were observed when patients were classified into tertiles according to their individual Lp(a) concentration. In contrast, changes in forearm blood flow after intraarterial L-NMMA indicating basal production and release of NO differed significantly among tertiles. Patients in the highest Lp(a) tertile (49.2 +/- 20.3 mg/dl) had a much greater vasoconstrictive response to L-NMMA than patients in the lowest Lp(a) tertile (4.8 +/- 2.5 mg/dl): 2 micromol/min of L-NMMA, -23.6 +/- 22.5% vs. -10.4 +/- 9.1% (p < 0.02); 4 micromol/min of L-NMMA, -27.8 +/- 10.3% vs. -17.6 +/- 9.9% (p < 0.03). Lp(a) plasma level consistently correlated negatively with the forearm blood flow responses to 4 micromol/min of intraarterial L-NMMA (r = -0.38, p < 0.01). Multiple stepwise regression analysis of variables, including total and high and low density lipoprotein cholesterol, further confirmed that plasma Lp(a) remained a significant independent determinant of forearm blood flow changes in response to L-NMMA (p < 0.02). CONCLUSIONS: The endothelium-dependent vasoconstrictive response to L-NMMA was enhanced in subjects with relatively high Lp(a) plasma levels, suggesting an increased basal production and release of NO. This response seemed to reflect a compensatory mechanism of the endothelium to yet unknown Lp(a)-induced atherosclerotic effects.     

Urinary excretion of apo(a) fragments in NIDDM patients

Lp(a), one of the most atherogenic lipoproteins, is believed to contribute significantly to vascular diseases in non-insulin-dependent diabetic (NIDDM) patients. Contradictive data have been published on these patients concerning plasma concentrations of Lp(a) and their relation to renal function. Since apo(a) fragments appear in urine, we measured urinary apo(a) in 134 NIDDM patients and 100 matched controls and related urinary apo(a) concentrations to plasma Lp(a) levels and kidney function. Plasma Lp(a) values were found to be significantly higher in NIDDM patients. NIDDM patients also secreted significantly more apo(a) into their urine as compared to control subjects. There was no correlation between creatinine clearance or albumin excretion and urinary apo(a) concentrations. Patients with macroalbuminuria exhibited a twofold higher apparent fractional excretion of apo(a) in comparison to patients with normal renal function. Urinary apo(a) values in both patients and control subjects were highly correlated to plasma Lp(a), yet no correlation was found with HbA1c or serum lipoproteins. It is concluded that urinary apo(a) excretion is correlated to plasma Lp(a) levels but not to creatinine clearance in patients suffering from NIDDM.     

Paradigms for clinical ethics consultation practice

The effects of lipoproteins on ion channel-mediated catecholamine secretion were investigated in cultured bovine adrenal medullary cells. Low density lipoprotein (LDL: 20-80 mg/dl) and lipoprotein(a) [Lp(a); 10-80 mg/dl] inhibited catecholamine secretion induced by carbachol, an activator of nicotinic acetylcholine receptor-ion channels. LDL and Lp(a) suppressed carbachol-induced 22Na+ influx as well as 45Ca2+ influx in a concentration-dependent manner similar to that of catecholamine secretion. The inhibition of catecholamine secretion by Lp(a) was not overcome by increasing the concentration of carbachol. On the other hand, high density lipoprotein (HDL; < 150 mg/dl) had no effect on 22Na+ influx, 45Ca2+ influx, and catecholamine secretion. Like LDL and Lp(a), a synthetic peptide homologous to human plasma apolipoprotein B (apoB), apoB fragment(3358-3372)-amide (3-60 microM), attenuated 22Na+ influx, 45Ca2+ influx, and catecholamine secretion caused by carbachol. The apoB fragment also suppressed 22Na+ influx induced by veratridine (an activator of voltage-dependent Na+ channels) and 45Ca2+ influx induced by 56 mM K+ (an indirect activator of voltage-dependent Ca2+ channels). These findings suggest that atherogenic lipoproteins such as LDL and Lp(a) suppress catecholamine secretion by interfering with Na+ influx through nicotinic acetylcholine receptor-ion channels, in which apoB, a structural component common to both LDL and Lp(a), plays an important role. The inhibition by atherogenic lipoproteins of catecholamine secretion may influence the progression of atherosclerosis induced by these lipoproteins.     

Plasma lipoprotein distribution of apoC-III in normolipidemic and hypertriglyceridemic subjects: comparison of the apoC-III to apoE ratio in different lipoprotein fractions

In order to assess the relationship between plasma accumulation of triglyceride-rich lipoproteins (TRL) and lipoprotein levels of apoC-III and apoE, we have measured apoC-III and apoE in lipoproteins separated according to size (by automated gel filtration chromatography) from plasma of normolipidemic subjects (plasma triglyceride (TG): 0.84 +/- 0.10 mmol/l; mean +/- SE, n = 8), and from type III (n = 8) and type IV (n = 8) hyperlipoproteinemic patients, matched for plasma TG (5.76 +/- 0.62 v 5.55 +/- 0.45 mmol/l, resp.). Total plasma apoC-III concentration was similar in type III and type IV patients (33.1 +/- 3.4 v 37.6 +/- 4.4 mg/dl, respectively), but was significantly increased compared to normolipidemic controls (10.0 +/- 1.0 mg/dl, P < 0.001). TRL apoC-III was lower and high density lipoprotein (HDL) apoC-III was significantly higher in type III versus type IV subjects (14.8 +/- 3.2 vs. 22.8 +/- 3.0 mg/dl, P < 0.05; 8.3 +/- 1.0 vs. 5.2 +/- 0.5 mg/dl, P < 0.05). Plasma concentration of apoC-III in lipoproteins that eluted between TRL and HDL (intermediate-sized lipoproteins, ISL) was similar in the two hypertriglyceridemic groups (10.1 +/- 1.3 vs. 9.7 +/- 1.6 mg/dl), but was significantly higher (P< 0.05) than controls (2.2 +/- 0.3 mg/dl). TRL, ISL, and HDL apoE concentrations were significantly higher in type III versus type IV subjects (P < 0.05). All lipoprotein fractions in type III patients were characterized by lower apoC-III to apoE ratios. In contrast, the TRL apoC-III to apoE ratio of type IV patients was similar and the ISL apoC-III to apoE ratio was significantly higher, compared to normolipidemic individuals. These results indicate that compared to normolipidemic individuals, remnant-like lipoproteins in the ISL fraction of type IV patients are enriched in apoC-III relative to apoE, whereas those of type III patients are enriched in apoE relative to apoC-III.     

Monocyte expression of tissue factor and adhesion molecules: the link with accelerated coronary artery disease in patients with chronic renal failure

OBJECTIVE: To investigate the expression of monocyte tissue factor (MTF) and adhesion molecules in patients with chronic renal failure (CRF) and to look for any correlation with thrombin generation and Lp(a) lipoprotein. DESIGN: A study of MTF expression and adhesion molecules, prothrombin fragments 1+2 (PTf1+2), an index of thrombin generation, and lipoproteins in patients with CRF and in normal control subjects. BACKGROUND: Patients with end stage renal failure have an increased risk of coronary artery disease despite advances in therapy. Stimulated monocytes are potent activators of blood coagulation through the generation of MTF, which was recently implicated in the aetiology of acute coronary ischaemic syndromes. METHODS: MTF expression and adhesion molecules were measured in whole blood using immunofluorescence of monocytes labelled with anti-tissue factor antibody and CD11b and c by flow cytometry. PTf1+2 and Lp(a) lipoprotein in plasma were measured by enzyme linked immunosorbent assay (ELISA). PATIENTS: 70 patients with CRF without documented coronary artery disease (30 patients with CRF undialysed, 20 patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and 20 undergoing haemodialysis (HD)), together with 20 normal controls, were studied. RESULTS: The (mean (SD)) increased MTF of CRF (48.0 (29) v 33.3 (7.2) mesf unit/100 monocytes in controls, p = 0.04) was more pronounced in patients undergoing dialysis (HD 73.1 (32.8) (p < 0.003) and CAPD 62.8 (28.9) mesf unit/100 monocytes, p < 0.04). MTF activity showed a positive correlation with both PTf1+2 and serum creatinine (p < 0.003) but not with Lp(a) lipoprotein. Lp(a) lipoprotein was significantly increased in both dialysis groups compared with controls (p < 0.005) and non-dialysis CRF groups (p < 0.02). Monocyte adhesion molecule (CD11b) was significantly higher in all three CRF groups than in the controls (p = 0.006). Conclusion: This study has demonstrated a hypercoagulable state in patients with CRF. This was especially pronounced in the dialysis patients. These findings provide a possible explanation for the increased cardiovascular and cerebrovascular morbidity and mortality in these patients.     

An efficient chromatographic system for lipoprotein fractionation using whole plasma

We have validated a semi-automatic procedure for the efficient isolation of plasma lipoproteins from 300 microl of whole plasma (actual injection volume 200 microl) by Fast Phase Liquid Chromatography (FPLC). Modified enzymatic assays were established to allow the determination of low concentrations (1-20 mg/dl) of triglycerides and cholesterol using the Beckman CX-5 Autoanalyzer. The sum of the cholesterol contents in the fractions corresponding to low density (LDL) and high density lipoprotein (HDL) can be demonstrated to be highly correlated to values obtained with dextran sulfate/MgCl2 precipitation for HDLc (slope = 0.98, r2 = 0.997) and ultracentrifugation (beta-quant) for LDLc (slope = 1.03, r2 = 0.988). Using pure lipoprotein fractions isolated by ultracentrifugation, linear ranges of detection for HDLc and HDL apoA-I were performed at 18-95 mg/dl and 59-262 mg/dl, respectively. The ranges for LDLc were 41-435 mg/dl and 21-280 mg/dl for LDL apoB. The mean (range) fractional standard deviations for quadruplicate runs for 15 individual plasma samples ranging widely in lipoprotein concentrations were 0.97 (0.29-2.86%) for LDLc (range: 101.5-258.5 mg/dl), 3.67 (0.62-14.11%) for HDLc (range: 27.1-85.1 mg/dl) and 2.19 (0.16-6.56%) for VLDL-TG (range: 6.1-515.0 mg/dl).     

Elevated lipoprotein (a) levels in primary nephrotic syndrome

Elevated plasma levels of total cholesterol and increase in the hepatic synthesis of some apo B-containing lipoproteins have been noted in the nephrotic syndrome. Apoprotein (a), the apolipoprotein distinguishing lipoprotein (a) [Lp(a)] from low-density lipoprotein, is equally of hepatic origin, and Lp(a) recently has been shown to possess both atherogenic and thrombogenic activities. However, little is known of Lp(a) levels in nephrotic patients. We measured plasma Lp(a) concentrations in 11 patients with primary nephrotic syndrome in the absence of hematuria, hypertension, and renal insufficiency. Histologic lesions were minimal-change disease in five cases, membranous glomerulopathy in four cases, and focal and segmental glomerulosclerosis in two cases. Mean levels of Lp(a) (98 +/- 92 mg/dL [mean +/- SD]) were markedly elevated in the nephrotic patients as compared with the controls (14 +/- 13 mg/dL). No correlation was noted between plasma Lp(a) and proteinuria, albuminemia, total cholesterolemia, low-density lipoprotein cholesterol, apoprotein B100, or plasminogen. Furthermore, there was no correlation between Lp(a) levels and apoprotein (a) isoform size. In four patients, the level of Lp(a) decreased approximately fourfold after remission of the nephrotic syndrome under corticosteroid treatment. Our observation that Lp(a) levels are elevated in the nephrotic syndrome is consistent with the hypothesis that these patients may be at an increased risk of cardiovascular and thrombotic complications.     

Effects of apoE gene polymorphism on Lp(a) concentrations depend on the size of apo(a): a study of 466 white men

Polymorphisms in the genes for the low-density lipoprotein (LDL) receptor ligands, apolipoprotein E (apoE), and apolipoprotein B (apoB) are associated with variation in plasma levels of LDL cholesterol. Lp(a) lipoprotein(a) [Lp(a)] is LDL in which apoB is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined isoforms differing in molecular weight, which are inversely correlated with Lp(a) concentrations in blood. The interaction of apo(a) with triglyceride-rich lipoproteins differs with the size of apo(a), and therefore the effects of apoE gene polymorphism on Lp(a) levels could also depend on apo(a) size. We have investigated the possible effect of genetic variation in the apoE and apoB genes on plasma Lp(a) concentrations in 466 white men with different apo(a) phenotypes. Overall there was no significant association between the common apoE polymorphism and Lp(a), but in the subgroup with apo(a)-S4, concentrations of Lp(a) differed significantly among the apoE genotypes (P = 0.05). Lp(a) was highest in the apoE genotypes epsilon 2 epsilon 3 and epsilon 3 epsilon 3 and lowest in genotype epsilon 3 epsilon 4, and the apoE polymorphism was estimated to account for about 2.4% of the variation in Lp(a). In contrast, in the subgroup with apo(a)-S2 Lp(a) was significantly lower (P = 0.04) in apoE genotype epsilon 2 epsilon 3 than in genotype epsilon 3 epsilon 3. Lp(a) concentrations did not differ among the XbaI (P = 0.65) or SP 24/27 (P = 0.26) polymorphisms of the apoB gene. The expected effects of both apoE and apoB polymorphism on LDL levels were significant in the whole population sample and in subjects with large-sized apo(a) isoforms (P < 0.01), whereas no effect was seen in those with low molecular weight apo(a) isoforms. We conclude that the influence of apoE genotypes on Lp(a) concentrations depends on the size of the apo(a) molecule in Lp(a), possibly because both apo(a)-S4 and apoE4 have high affinity for triglyceride-rich lipoproteins and may be taken up and degraded rapidly by remnant receptors.     

Lipoprotein(a) in android obesity and NIDDM

OBJECTIVE: To assess the level of serum lipoprotein(a) [Lp(a)] in nonobese and obese NIDDM subjects with android body distribution. RESEARCH DESIGN AND METHODS: Serum Lp(a) levels were measured in 30 long-standing NIDDM patients (duration of diabetes 12.5 +/- 3 years, mean +/- SD), with 15 of the patients being obese of android distribution (BMI > 30 kg/m2 and waist-to-hip ratio > 0.8). In addition, there were 15 android obese nondiabetic subjects and 10 healthy subjects serving as the control group. RESULTS: All groups of patients in this study (diabetic, obese, and obese diabetic) showed significantly higher levels of Lp(a) than the healthy control group. Lp(a) concentrations were significantly higher in NIDDM patients with android type of obesity than in nondiabetic androids (24.1 +/- 5.6 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Significantly greater levels of Lp(a) were found in nonobese subjects with diabetes when compared with obese subjects without diabetes (22.3 +/- 4.1 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Furthermore, Lp(a) serum concentrations were not dependent on the degree of glycemic control (controlled NIDDM 23.6 +/- 5.0 vs. uncontrolled NIDDM 21.4 +/- 2.7 mg/dl, NS), but were much greater in subjects with diabetes complicated by vascular disease (complicated 26.3 +/- 5.0 vs. uncomplicated 20.5 +/- 2.7 mg/dl, P < 0.001). No correlation was found between Lp(a) and other lipid parameters in this study. CONCLUSIONS: Lp(a) levels are significantly elevated in both android-obese and nonobese NIDDM patients regardless of the degree of glycemic control. Lp(a) is an independent risk factor showing greater elevations in those subjects complicated with diabetic vascular diseases.     

Measurement of oxidation in plasma Lp(a) in CAPD patients using a novel ELISA

BACKGROUND: LGE2 is produced by the cyclooxygenase- or free radical-mediated modification of arachidonate and is formed during the oxidation of low density lipoprotein (LDL) with subsequent adduction to lysine residues in apo B. We have developed a sensitive enzyme-linked sandwich immunosorbent assay (ELISA) for detection and measurement of LGE2-protein adducts as an estimate of oxidation of plasma LDL and Lp(a). METHODS: The assay employs rabbit polyclonal antibodies directed against LGE2-protein adducts that form pyrroles, and alkaline phosphatase-conjugated polyclonal antibodies specific for apo B or apo (a). It demonstrates a high degree of specificity, sensitivity and validity. RESULTS: Epitopes characteristic for LGE2-pyrroles were quantified in patients with end-stage renal disease (ESRD) that had undergone continuous ambulatory peritoneal dialysis (CAPD) and in a gender- and age-matched control population. In addition to finding that both LDL and Lp(a) levels were elevated in CAPD patients, we also found that plasma Lp(a) but not LDL was more oxidized in CAPD patients when compared to corresponding lipoproteins from healthy subjects. Using density gradient ultra-centrifugation of plasma samples, we found that modified Lp(a) floats at the same density as total Lp(a). CONCLUSIONS: The results of this study demonstrate that oxidation of plasma Lp(a) is a characteristic of ESRD patients undergoing CAPD. This ELISA may be useful for further investigations on oxidation of lipoproteins in the circulation of specific patient populations.     

Effects of gender and menopausal status on plasma lipoprotein subspecies and particle sizes

The risk of coronary heart disease (CHD) is lower in women than in men, but increases in women after menopause. Some of the gender, age, and menopausal-related differences in CHD risk may relate to differences in lipoprotein subspecies. We therefore examined these subspecies in three groups of healthy subjects: premenopausal women (W, n = 72, mean age 41.2 +/- 6.5), postmenopausal women (PMW, n = 74, 55.8 +/- 7.4), and men (M, n = 139, 48.8 +/- 10.7). We measured plasma levels of lipids, lipoprotein cholesterol, apolipoproteins A-I, A-IV, B, C-III, and E, and lipoprotein subspecies Lp A-I, Lp A-I:A-II, Lp B, Lp B:C-III, and Lp B:E, as well as LDL and HDL particle sizes. Our data indicate that women have significantly higher values of HDL-C, apoA-I, apoE, and Lp A-I; larger LDL and HDL particle sizes; and lower values of triglyceride, apoB, and Lp B:C-III particles than men, with no difference in Lp A-I:A-II. Postmenopausal status was associated with significantly higher values of total cholesterol, triglyceride, VLDL-C, and LDL-C; increased levels of apoB, C-III, and E; elevated values of Lp B, Lp B:C-III, and Lp B:E; and lower levels of HDL-C along with smaller HDL particle size. Moreover, we noted a strong correlation between LDL and HDL particle size. Our data are consistent with the concepts that male gender confers decreases in HDL subspecies due to lower Lp A-I levels; while postmenopausal status results in higher levels of all apoB-containing lipoproteins (Lp B, Lp B:C-III, and Lp B:E). The lipoprotein alterations associated with male gender and postmenopausal status would be expected to increase CHD risk.     

DALI-the first human whole-blood low-density lipoprotein and lipoprotein (a) apheresis system in clinical use: procedure and clinical results

BACKGROUND: The DALI low-density lipoprotein (LDL) apheresis system is the first whole-blood apheresis system in regular clinical use. DALI stands for direct adsorption of lipoproteins, which describes the basic principle of operation of this newly developed LDL apheresis procedure. METHODS: The selective removal of LDLs and lipoprotein (a) [Lp(a)] is performed in human whole blood by adsorption onto polyacrylate-coated polyacrylamide beads in an adsorber. This article describes the results of the first open multicentre clinical trial in 14 patients in whom the safety and the efficacy of the system were tested. All patients were treated on average 17 times on a weekly basis. In total, 238 sessions were carried out during the study without severe side-effects. On average, 7675 mL of the patients' whole blood was processed in about 2 h. Anticoagulation in the extracorporeal system was carried out by first giving a heparin bolus followed by continuous addition of an acid citrate dextrose (ACD-A) infusion during the treatment. RESULTS: The processing of nearly 1.6 times the patient blood volumes resulted in a reduction in the median LDL-cholesterol level by 66-77% (dependent on the system configuration). The Lp(a) concentrations were reduced by 59-73% (dependent on the system configuration). HDL-cholesterol, blood cell count and the other clinical parameters were not significantly affected. CONCLUSION: Based on this short-term evaluation, the DALI apheresis system is a well-tolerated, effective and simple way of reducing LDL and Lp(a) in human whole blood. The system has been introduced to clinical practice. However, to use the DALI apheresis system in clinical routine, further evaluation of long-term effects is required.     

Bioplastique as a complement in conventional plastic surgery

BACKGROUND: Calcified aortic value disease is increasing with explosively in the elderly. Elevated serum lipoprotein(a) (Lp(a) plays an important role in the pathogenesis of atherosclerosis. Thus, we investigated the relationship between aortic valve sclerosis and serum Lp(a) levels in elderly patients. METHODS: Echocardiography was performed in 97 subjects (77 +/- 7 years, 48 males and 49 females), Lp(a), fasting plasma glucose, and blood pressure were measured at the time of the study. Aortic valve sclerosis was assessed using echocardiography. RESULTS: Aortic valve sclerosis was observed in 63 patients (sclerosis group; 24 males and 39 females) and not in 34 subjects (non-sclerosis group; 24 males and 10 females). Univariable analysis revealed that age, Lp(a) level, and the number of females were higher in the sclerosis group than in the non-sclerosis group (age; 78 +/- 7 vs 74 +/- 7 years, p = 0.0090, Lp(a); cholesterol, triglyceride, and fasting blood glucose did not seem to affect aortic valve sclerosis. In all of 9 patients with serum Lp(a) greater than 60mg/dl aortic valve sclerosis was present. In discriminative analysis, gender (female) (lambda = 0.9038, p = 0.0020) and Lp(a) (lambda = 0.8316, p = 0.0053) were related to aortic valve sclerosis. CONCLUSION: Elevated serum Lp(a) was observed in elderly patients with aortic valve sclerosis.     

Polymorphism of apolipoprotein E, lipoprotein(a), and other lipoproteins in children with type I diabetes

We assessed the effect of particular apolipoprotein (apo) E phenotypes, lipoprotein(a) [Lp(a)], and other lipoproteins on the development of dyslipoproteinemia in 450 patients with type I diabetes, ages 13-14 years. The control group consisted of 450 healthy school children of both sexes, ages 13-14 years. Both groups were found to be normolipidemic, but the concentration of Lp(a) was significantly (P < 0.05) higher in the diabetic children than in the control group. Apo E 3/2 and apo E 4/4 phenotypes were more frequent in the group of diabetics. Diabetics with the apo E 3/3 phenotype had higher concentrations of very-low-density lipoprotein (VLDL) and Lp(a), and lower concentrations of low-density lipoprotein (LDL) than the apo E 3/3 nondiabetics. For apo E 3/2 phenotypes, total cholesterol, LDL cholesterol, LDL, apo A-I, and Lp(a) concentrations were higher in the diabetic children than in the control group; for apo E 4/3 phenotypes, this was true for triglycerides and VLDL cholesterol. The distribution of Lp(a) lipoprotein concentrations between 0.01 and > 0.5 g/L indicated a more frequent occurrence of higher Lp(a) values in diabetic children than in the control group. Results of this study indicate that an increased concentration of Lp(a) lipoprotein and apo E 3/2 and apo E 4/3 phenotypes contribute to the expression of dyslipoproteinemia in type I diabetes in childhood.     

Lipoprotein(a) in endurance athletes, power athletes, and sedentary controls

Elevated concentrations of lipoprotein(a) [Lp(a)] have been shown to be an independent risk factor for atherosclerotic disease. Physical activity and physical fitness have been shown to improve lipoprotein metabolism and reduce the risk of coronary artery disease. Studies on the influence of physical activity and physical fitness on Lp(a) levels including a large number of endurance as well as power athletes have not been performed before. Therefore, we determined parameters of physical fitness (maximal oxygen consumption), physical activity, and lipoproteins in 105 endurance athletes, 57 power athletes, and 87 sedentary young men. As expected, we found that endurance athletes with a good physical fitness had significantly higher concentrations of high-density lipoprotein cholesterol than power athletes and sedentary controls. Regarding mean Lp(a) levels (rocket immunoelectrophoresis), however, there were no significant differences between endurance athletes, power athletes, and sedentary controls. Even when including only those with Lp(a) values > 10 mg.dl-1, no differences were observed between the groups. These findings indicate that intensive training over years and good aerobic fitness improve the ratio of low-density lipoprotein to high-density lipoprotein cholesterol but have no or only minor effects on Lp(a) concentrations.     

The use of an interactive computer program for the education of parents of asthmatic children

OBJECTIVES: To evaluate the effect of a single evening meal (gorging) on plasma lipids and lipoproteins in normal individuals observing the Ramadan Fast. During the Ramadan month, Muslims refrain from food and liquids during the day and eat a large meal after sundown. DESIGN: Sequential measurement of plasma lipids and lipoproteins in Muslims observing the Ramadan Fast and non-fasting individuals. SETTING: The study was conducted in the Bedouin town of Rahat, in the northern Negev area of Israel. SUBJECTS: Twenty-two healthy subjects who fasted during Ramadan and 16 non-fasting laboratory workers, were studied before Ramadan, at week 1, 2 and 4 of the Ramadan month, and again four weeks after the end of Ramadan. RESULTS: Plasma high-density lipoprotein cholesterol (HDL) rose significantly (P < 0.001) at the week 4 measurement, returning to basal levels 4 weeks after the end of Ramadan. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), very-low density lipoprotein cholesterol (VLDL), and lipoprotein (a) [Lp(a)] did not change significantly. CONCLUSIONS: Plasma HDL increased by 23% after four weeks of gorging. The dietary change did not affect the composition of other lipoproteins, such as LDL, VLDL or Lp(a), other plasma biochemical parameters, or BMI. Prolonged gorging, well tolerated by all individuals, is a very effective non-pharmacological method to increase plasma HDL-cholesterol.     

Human submandibular saliva specifically inhibits HIV type 1

This study was performed to investigate the possible association between preeclampsia and the plasma concentrations of Lp(a) lipoprotein and TGF-beta1 in a large series of patients. Additionally, correlation between the concentrations of these molecules and the severity of preeclampsia or fetal growth retardation was evaluated. Following clinical examination and biochemical analyses, both electroimmunoassay and RIA technique were used for quantitative determinations of plasma Lp(a) lipoprotein. ELISA technique was used to measure the active form of TGF-beta1 in plasma of pregnant normotensive and preeclamptic women. We examined 154 women with preeclampsia (preeclampsia group) and 76 healthy, pregnant normotensive women (control group). The preeclampsia group was further divided into the following subgroups: mild preeclampsia, severe preeclampsia and preeclampsia with fetal growth retardation. Plasma levels of Lp(a) lipoprotein were lower in the total preeclampsia group as well as in all preeclampsia subgroups (5.45+/-7.41, 5.58+/-8.02, 5.08+/-5.38, and 4.32+/-5.28 mg/dl in the total preeclampsia group, and in subgroups with mild preeclampsia, severe preeclampsia, and preeclampsia with fetal growth retardation, respectively) than in the control group (7.84+/-9.26 mg/dl) as determined by quantitative electroimmunoassay. Corresponding results were obtained with a radioimmunoassay (166.03+/-200.2 U/l in the total preeclampsia group vs. 229.18+/-257.7 U/l in controls). There was good correlation between the two methods used for Lp(a) lipoprotein measurement. The differences between controls and the total preeclampsia group as well as each preeclampsia subgroup were statistically significant by a non-parametric test (one-way Kruskal-Wallis test). Plasma concentrations of the active form of TGF-beta1 were increased in all preeclampsia subgroups as well as in the total group (5.63+/-1.68 ng/ml) compared to controls (4.67+/-1.33 ng/ml). This increase in TGF-beta1 was statistically highly significant. Plasma concentrations of Lp(a) lipoprotein and the active form of TGF-beta1 did not differ significantly between the preeclampsia subgroups. The outcome of this study may suggest involvement of both parameters in the pathophysiology of preeclampsia and may substantiate the notion of a multifactorial etiology of the disease.