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J Ordóñez-Llanos

Publications and source records attributed to J Ordóñez-Llanos.

At least 19 recordsLinked to original sources
PubMed2005

The inflammatory properties of electronegative low-density lipoprotein from type 1 diabetic patients are related to increased platelet-activating factor acetylhydrolase activity.

AIMS/HYPOTHESIS: Chemical and biological characteristics of LDL(-) from type 1 diabetic subjects were analysed. The diabetic patients were studied during poor and optimised glycaemic control. MATERIALS AND METHODS: Total LDL was subfractionated into electropositive LDL(+) and electronegative LDL(-) by anion exchange chromatography and the lipid and protein composition of the two determined. RESULTS: LDL(-) differed from LDL(+) in that it had higher triglyceride, non-esterified fatty acids, apoE, apoC-III and platelet-activating factor acetylhydrolase (PAF-AH), as well as lower apoB relative content. No evidence of increased oxidation was observed in LDL(-). LDL(-) increased two-fold the release of interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells, suggesting an inflammatory role. Optimisation of glycaemic control after insulin therapy decreased the proportion of LDL(-), but did not modify the composition of LDL subfractions, except for a decrease in PAF-AH activity in LDL(-). The possibility that LDL(-) could be generated by non-enzymatic glycosylation was studied. Fructosamine and glycated LDL content in LDL subfractions from type 1 diabetic patients was greater than in LDL subfractions isolated from normoglycaemic subjects, and decreased after glycaemic optimisation in both subfractions. However, no difference was observed between LDL(+) and LDL(-) before and after insulin therapy. CONCLUSIONS/INTERPRETATION: These results provide evidence that LDL(-) is not produced by glycosylation. Nevertheless, LDL(-) from diabetic patients displays inflammatory potential reflected by the induction of chemokine release in endothelial cells. This proatherogenic effect could be related to the high PAF-AH activity in LDL(-).

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Quantitative effect of glycaemic improvement on the components of diabetic dyslipidaemia: a longitudinal study.

In order to assess the effect of glycaemic improvement on lipoprotein concentrations, we studied 73 type 2 diabetic subjects before (HbA1c 10.1 (6.2-16)%) and after (HbA1c 6.6 (3.8-8.0)%) glycaemic improvement. Total triglyceride and cholesterol (c), LDLc, HDLc, non-HDLc and apolipoproteins AI (apoAI) and B (apoB) were measured. Bivariate correlations and step-wise, multivariate analysis were performed to find predictors of change in the different components of diabetic dyslipidaemia. Changes in HDLc (r = -0.358, P = 0.001), apoAI (r = -0.355, P = 0.003), apoAI/apoB ratio (r = -0.333, P = 0.005), weight (r = -0.245, P = 0.046) and BMI (r = -0.253, P = 0.039) correlated with that of HbA1c, but, in multivariate analysis, only changes in HDLc, apoAI and apoAI/apoB ratio were predicted by the decrease in HbA1c. For the median observed change in HbA1c (-3.3 percentage-points), the estimated changes were +0.14 mmol/l, +0.12 g/l and +0.20 for HDLc, apoAI and apoAI/apoB ratio, respectively, accounting for 81, 92 and 80% of the observed changes. In conclusion, for the component of diabetic dyslipidaemia for which less therapeutic tools are available, glycaemic improvement is most effective.

Aged↗
PubMed2002

LDL-cholesterol/apolipoprotein B ratio is a good predictor of LDL phenotype B in type 2 diabetes.

LDL phenotype B is a component of diabetic dyslipidaemia, but its diagnosis is cumbersome. Our aim was to find easily available markers of phenotype B in a group of type 2 diabetic subjects. We studied 123 type 2 diabetic patients (67.5% male, aged 59.3+/-10.1 years, mean HbA1c 7.4%). Clinical features and fasting total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol (LDLc, using Friedewald's equation and an alternative formula), apolipoprotein B (apoB), lipoprotein (a) and LDL particle size (on gradient polyacrylamide gel electrophoresis) were assessed. Patients with phenotypes A (predominant LDL size > or =25.5 nm) and B (<25.5 nm) were compared, and regression analysis was performed to find the best markers of LDL particle. Cut-off points were obtained and evaluated as predictors of phenotype B (kappa index). Patients with phenotype B (36%) showed higher total cholesterol, triglyceride and apolipoprotein B, and lower HDL cholesterol and LDLc/apoB ratio. Triglyceride was the best predictor of LDL particle size (r=-0.632, p<0.01), but an LDLc/apoB ratio below 1.297 mmol/g detected phenotype B best (sensitivity 65.9%, specificity 92.4%, kappa=0.611). Although triglyceride concentration is the best predictor of LDL size in type 2 diabetes, LDLcholesterol/apolipoproteinB ratio is the best tool to detect phenotype B.

Aged↗
PubMed2001

Apo(B)-dependent dyslipidemic phenotypes in type 1 diabetic patients.

BACKGROUND: The prevalence of apo(B)-dependent dyslipidemic phenotypes, which are associated with cardiovascular disease, is increased in normocholesterolemic type 2 diabetic patients. Our aim was to determine the impact of including apo(B) in the evaluation of normocholesterolemic type 1 diabetic patients. METHODS: A total of 123 type 1 diabetic patients (47% male, age 36.6+/-12.5 years) were included. The apo(B) cut-off point (1.14 g/l) was obtained from a group of 53 normolipidemic control subjects of similar age and gender distribution; for low density lipoprotein cholesterol (LDLc), triglycerides, and high density lipoprotein cholesterol (HDLc), we used the cut-off points recommended by the National Cholesterol Education Program. LDLc was determined by ultracentrifugation or Friedewald's equation, depending on triglyceride concentrations, and apo(B) by immunoturbidimetry. RESULTS: A total of 113 (92%) type 1 diabetic patients were normocholesterolemic, and 13% of these were dyslipidemic. The frequency of hyperapo(B) was similar in normocholesterolemic patients and controls (6.2 vs. 9.4%, respectively). Diabetic patients with hyperapo(B) had poorer glycemic control, higher total cholesterol, triglycerides, and LDLc, and a lower HDLc and LDLc/apo(B) ratio. CONCLUSIONS: Unlike type 2 diabetes, type 1 diabetes is not associated with an increased prevalence of hyperapo(B)-dependent dyslipidemic phenotypes. Thus, only in patients with poor glycemic control who display other components of diabetic dyslipidemia, typical for type 2 diabetes, does determining apo(B) concentrations provide additional information in type 1 diabetes.

Journal Article↗
PubMed2001

Low-density lipoprotein particle size, triglyceride-rich lipoproteins, and glucose tolerance in non-diabetic men with essential hypertension.

The aim of the study is to investigate serum lipoproteins abnormalities including low-density lipoprotein (LDL) particle size, and their relationship with other cardiovascular risk factors in men with essential hypertension. Plasma glucose and serum insulin levels during oral glucose tolerance test (OGTT), serum lipoprotein(a), apolipoprotein (apo) A-I. apo B. cholesterol and triglycerides in serum and in lipoproteins, and LDL particle diameter were measured in thirty-eight consecutive newly-diagnosed non-diabetic untreated hypertensive men and 38 healthy male controls. Plasma glucose at baseline, 60 and 120 min during OGTT was significantly higher in patients than controls whereas serum insulin levels did not differ between patients and controls. Serum apo B and triglycerides were significantly raised in patients compared with controls (1.08 +/- 0.17 g/L [mean +/- SD] vs 0.97 +/- 0.22 g/L. p < 0.05, and 1.56 +/- 0.90 mmol/L vs 1.15 +/- 0.57 mmol/L, p < 0.05, respectively). Very-low-density lipoprotein (VLDL) triglycerides and LDL-cholesterol were increased in patients compared with controls (0.89 +/- 0.79 mmol/L and 0.54 +/- 0.35 mmol/L, p < 0.05, and 4.08 +/- 0.85 mmol/L and 3.60 +/- 0.92 mmol/L, p < 0.05, respectively) whereas high-density lipoprotein (HDL) cholesterol was lower in patients compared with controls 0.95 +/- 0.22 mmol/L and 1.07 +/- 0.20 mmol/L, p < 0.05). Adjustment for body mass index, abdominal/hip perimeter ratio and area under the glucose curve did not attenuate the relationship between hypertension and VLDL-triglycerides. Six patients and two controls had a mean LDL diameter < or = 25.5 nm and in the former serum triglycerides ranged from 1.86 mmol/L to 2.37 mmol/L. Mean LDL particle diameter in both patients and controls showed an inverse relationship with log-transformed serum triglycerides (r = - 0.51, p < 0.001 and r = - 0.47, p < 0.005, respectively). Among patients, those with serum triglycerides > or = [corrected] 1.58 mmol/L had a lesser mean LDL diameter than those with triglycerides above this threshold (25.78 +/- 0.47 nm vs 26.30 +/- 0.35 nm, p < 0.001). Higher plasma glucose, serum apo B and LDL-cholesterol as well as the decrease in serum HDL-cholesterol in patients with hypertension are consistent with high coronary heart disease risk. Not only mild hypertriglyceridemia but also high-normal serum triglycerides in themselves or as a surrogate of a predominance of small dense LDL particles in plasma convey an additional risk for cardiovascular disease in hypertensive patients even though routine plasma lipids are within or near normal range.

Adult↗
PubMed2001

Effect of glycemic optimization on electronegative low-density lipoprotein in diabetes: relation to nonenzymatic glycosylation and oxidative modification.

The effect of insulin therapy on low-density lipoprotein (LDL) oxidizability, proportion of electronegative LDL [LDL(-)] and LDL composition was studied in 33 type 2 diabetic patients. Before glycemic control improvement, type 2 diabetic subjects presented higher triglyceride and very low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol than 25 healthy matched subjects. Furthermore, their LDL was more susceptible to oxidation (lag phase 45.9 +/- 5.4 min vs. 49.7 +/- 7.6 min, P < 0.05), contained a higher proportion of LDL(-) (19.0 +/- 8.7% vs. 14.3 +/- 5.5%, P < 0.05), and was enriched in triglyceride and depleted in cholesterol and phopholipids. Lipoprotein profile improved after glycemic optimization but failed to change either LDL oxidizability (45.3 +/- 6.2 min) or LDL(-) (17.9 +/- 8.2%). These data suggest that oxidation rather than nonenzymatic glycosylation could be related to the high LDL(-) found in these patients and disagree with results obtained in a previous study of type 1 diabetic patients. A second study was conducted in 10 type 1 and 10 type 2 diabetic subjects under insulin therapy, and the proportions of glycated LDL (gLDL) and LDL(-) were determined. Basal gLDL (2.8 +/- 0.6%) and LDL(-) (20.7 +/- 6.1%) decreased in type 1 diabetics after glycemic optimization (1.9 +/- 0.6% and 15.4 +/- 3.4%, respectively; P < 0.05). In type 2 patients, even though gLDL decreased (from 2.2 +/- 0.6% to 1.6 +/- 0.6%, P < 0.05) no effect was observed on LDL(-) (from 17.3 +/- 2.9% to 16.0 +/- 4.3%). We conclude that nonenzymatic glycosylation, which appears as a determinant of the high proportion of LDL(-) in type 1 diabetes, does not play a major role in LDL(-) generation in type 2 diabetes.

Adult↗
PubMed2001

ApoA-II expression in CETP transgenic mice increases VLDL production and impairs VLDL clearance.

Apolipoprotein (apo)A-II is a major high density lipoprotein (HDL) protein; however, its role in lipoprotein metabolism is largely unknown. Transgenic (Tg) mice that overexpress human apoA-II present functional lecithin: cholesterol acyltransferase deficiency, HDL deficiency, hypertriglyceridemia and, when fed an atherogenic diet, increased non-HDL cholesterol and increased susceptibility to atherosclerosis. In contrast to humans, mice do not present cholesteryl ester transfer protein (CETP) activity in plasma. To study the in vivo interaction of these two proteins, we crossbred human apoA-II and CETP-Tg mice. CETP x apoA-II-Tg mice fed an atherogenic diet, compared with CETP-Tg mice presented a 2-fold decrease in HDL cholesterol and a quantitatively similar increase in total plasma cholesterol and percentage of free cholesterol, non-HDL cholesterol, and free fatty acids, together with a remarkable 112-fold increase in plasma triglycerides. Plasma triglycerides in CETP x apoA-II-Tg mice were mainly associated with very low density lipoproteins (VLDL), which were also enriched in protein content, and resulted from a combination of higher production rate compared with both of their progenitors and non-Tg control mice, and decreased catabolism compared only with CETP-Tg mice. These results show CETP x apoA-II-Tg mice to be a good model with which to study mechanisms leading to VLDL overproduction and suggest that CETP and, in particular apoA-II, may play a role in the regulation of VLDL metabolism.

Animals↗
PubMed2000

Increased production of very-low-density lipoproteins in transgenic mice overexpressing human apolipoprotein A-II and fed with a high-fat diet.

We investigated the mechanisms that lead to combined hyperlipidemia in transgenic mice that overexpress human apolipoprotein (apo) A-II (line 11.1). The 11.1 transgenic mice develop pronounced hypertriglyceridemia, and a moderate increase in free fatty acid (FFA) and plasma cholesterol, especially when fed a high-fat/high-cholesterol diet. Post-heparin plasma lipoprotein lipase and hepatic lipase activities (using artificial or natural autologous substrates), the decay of plasma triglycerides with fasting, and the fractional catabolic rate of the radiolabeled VLDL-triglyceride (both fasting and postprandial) were similar in 11. 1 transgenic mice and in control mice. In contrast, a 2.5-fold increase in hepatic VLDL-triglyceride production was observed in 11. 1 transgenic mice in a period of 2 h in which blood lipolysis was inhibited. This increased synthesis of hepatic VLDL-triglyceride used preformed FFA rather than FFA of de novo hepatic synthesis. The 11.1 transgenic mice also presented reduced epididymal/parametrial white adipose tissue weight (1.5-fold), increased rate of epididymal/parametrial hormone-sensitive lipase-mediated lipolysis (1.2-fold) and an increase in cholesterol and, especially, in triglyceride liver content, suggesting an enhanced mobilization of fat as the source of preformed FFA reaching the liver. Increased plasma FFA was reverted by insulin, demonstrating that 11.1 transgenic mice are not insulin resistant. We conclude that the overexpression of human apoA-II in transgenic mice induces combined hyperlipidemia through an increase in VLDL production. These mice will be useful in the study of molecular mechanisms that regulate the overproduction of VLDL, a situation of major pathophysiological interest since it is the basic mechanism underlying familial combined hyperlipidemia.

Animals↗
PubMed2000

Determinants of plasma homocyst(e)ine in patients with nephrotic syndrome.

Hyperhomocyst(e)inemia is an independent risk factor for atherothrombosis in several clinical settings in which renal function is impaired, but its prevalence in the nephrotic syndrome has not been investigated in detail, even though this syndrome provides an excellent model in which to study a possible link between albuminuria, proteinuria, and hyperhomocyst(e)inemia. We obtained plasma and urine from 27 patients with biopsy-confirmed membranous glomerulonephritis presenting nephrotic syndrome and 27 matched controls and determined the concentrations of homocyst(e)ine and proteins considered putative markers of glomerular and tubular function. Hyperhomocyst(e)inemia, defined as the mean +SD of the plasma homocyst(e)ine concentration of the controls [plasma homocyst(e)ine concentration >10.8 micromol/l] was present in 26% of the patients with nephrotic syndrome but in only 7.4% of the controls. Furthermore, the degree of hyperhomocyst(e)inemia was more severe in the nephrotic patients than in the controls. The existence of renal failure, tubular damage, and, interestingly, relatively well conserved glomerular function barrier were the main predictors of increased levels of plasma homocyst(e)ine. In conclusion, hyperhomocyst(e)inemia is a frequent cardiovascular risk factor present in patients with nephrotic syndrome and renal failure, but it is not directly associated with proteinuria.

Adult↗
PubMed2000

Effect of physical exercise on lipoprotein(a) and low-density lipoprotein modifications in type 1 and type 2 diabetic patients.

To evaluate the effect of physical exercise on blood pressure, the lipid profile, lipoprotein(a) (Lp(a)), and low-density lipoprotein (LDL) modifications in untrained diabetics, 27 diabetic patients (14 type 1 and 13 type 2) under acceptable and stable glycemic control were studied before and after a supervised 3-month physical exercise program. Anthropometric parameters, insulin requirements, blood pressure, the lipid profile, Lp(a), LDL composition, size, and susceptibility to oxidation, and the proportion of electronegative LDL (LDL(-)) were measured. After 3 months of physical exercise, physical fitness improved (maximal O2 consumption [VO2max], 29.6 +/- 6.8 v 33.0 +/- 8.4 mL/kg/min, P < .01). The body mass index (BMI) did not change, but the waist circumference (83.2 +/- 11.8 to 81.4 +/- 11.2 cm, P < .05) decreased significantly. An increase in the subscapular to triceps skinfold ratio (0.91 +/- 0.37 v 1.12 +/- 0.47 cm, P < .01) and midarm muscle circumference ([MMC], 23.1 +/- 3.4 v 24.4 +/- 3.7 cm, P < .001) were observed after exercise. Insulin requirements (0.40 +/- 0.18 v 0.31 +/- 0.19 U/kg/d, P < .05) and diastolic blood pressure (80.2 +/- 10 v 73.8 +/- 5 mm Hg, P < .01) decreased in type 2 diabetic patients. High-density lipoprotein cholesterol (HDL-C) increased in type 1 patients (1.48 +/- 0.45 v1.66 +/- 0.6 mmol/L, P < .05), while LDL cholesterol (LDL-C) decreased in type 2 patients (3.6 +/- 1.0 v3.4 +/- 0.9 mmol/L, P < .01). Although Lp(a) levels did not vary in the whole group, a significant decrease was noted in patients with baseline Lp(a) above 300 mg/L (mean decrease, -13%). A relationship between baseline Lp(a) and the change in Lp(a) (r = -.718, P < .0001) was also observed. After the exercise program, 3 of 4 patients with LDL phenotype B changed to LDL phenotype A, and the proportion of LDL(-) tended to decrease (16.5% +/- 7.4% v 14.0% +/- 5.1%, P = .06). No changes were observed for LDL composition or susceptibility to oxidation. In addition to its known beneficial effects on the classic cardiovascular risk factors, regular physical exercise may reduce the risk of cardiovascular disease in diabetic patients by reducing Lp(a) levels in those with elevated Lp(a) and producing favorable qualitative LDL modifications.

Adolescent↗
PubMed2000

Electronegative LDL from normolipemic subjects induces IL-8 and monocyte chemotactic protein secretion by human endothelial cells.

The presence in plasma of an electronegative LDL subfraction [LDL(-)] cytotoxic for endothelial cells (ECs) has been reported. We studied the effect of LDL(-) on the release by ECs of molecules implicated in leukocyte recruitment [interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1)] and in the plasminogen activator inhibitor-1 (PAI-1). LDL(-), isolated by anion-exchange chromatography, differed from nonelectronegative LDL [LDL(+)] in its higher triglyceride, nonesterified fatty acid, apoprotein E and apoprotein C-III, and sialic acid contents. No evidence of extensive oxidation was found in LDL(-); its antioxidant and thiobarbituric acid-reactive substances contents were similar to those of LDL(+). However, conjugated dienes were increased in LDL(-), which suggests that mild oxidation might affect these particles. LDL(-) increased, in a concentration-dependent manner, the release of IL-8 and MCP-1 by ECs and was a stronger inductor of both chemokines than oxidized LDL (oxLDL) or LDL(+). PAI-1 release increased slightly in ECs incubated with both LDL(-) and oxLDL but not with LDL(+). However, no cytotoxic effects of LDL(-) were observed on ECs. Actinomycin D inhibited the release of IL-8 and MCP-1 induced by LDL(-) and oxLDL by up to 80%, indicating that their production is mediated by protein synthesis. Incubation of ECs with N:-acetyl cysteine inhibited production of IL-8 and MCP-1 induced by LDL(-) and oxLDL by >50%. The free radical scavenger butylated hydroxytoluene slightly inhibited the effect of oxLDL but did not modify the effect of LDL(-). An antagonist (BN-50730) of the platelet-activating factor receptor inhibited production of both chemokines by LDL(-) and oxLDL in a concentration-dependent manner. Our results indicate that LDL(-) shows proinflammatory activity on ECs and may contribute to early atherosclerotic events.

Acetylcysteine↗
PubMed2000

Comparison of the Abbott IMx and a high-performance liquid chromatography method for measuring total plasma homocysteine.

The determination of the total concentration of plasma homocysteine is of interest in a variety of clinical circumstances, especially, in the evaluation of the risk of cardiovascular disease. However, most of the methods available to date, many of them chromatographic, are not well suited for the majority of clinical laboratories. Several automated methods are now or will be, shortly, commercially available. We have compared one of them, the fluorescence polarization immunoassay (FPIA) adapted to the IMx analyzer (Abbott Laboratories), with the high-performance liquid chromatography (HPLC) method with fluorescent detection currently used in our laboratory. The results show that the FPIA-IMx method is less imprecise and slightly more sensitive than the HPLC. The comparison of 67 clinical plasma specimens indicated that there is a proportional error disagreement between FPIA-IMx and HPLC (FPIA=1.19 HPLC + 0.92; confidence region for slope and y-intercept were, respectively, from 1.06 to 1.31 and from -0.06 to 2.32). The nature of this error is not explained by the experiments performed to study the inaccuracy of both methods, which included the investigation of dilution parallelism, analytical recovery and cross-reactivity. The different results of homocysteine concentration obtained with FPIA-IMx and HPLC must be taken into account when a change of methodology is under consideration.

Chromatography, High Pressure Liquid↗
PubMed2000

Expression of human apolipoprotein A-II in apolipoprotein E-deficient mice induces features of familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common inherited hyperlipidemia and a major risk factor for atherothrombotic cardiovascular disease. The cause(s) leading to FCHL are largely unknown, but the existence of unidentified "major" genes that would increase VLDL production and of "modifier" genes that would influence the phenotype of the disease has been proposed. Expression of apolipoprotein A-II (apoA-II), a high density lipoprotein (HDL) of unknown function, in transgenic mice produced increased concentration of apoB-containing lipoproteins and decreased HDL. Here we show that expression of human apoA-II in apoE-deficient mice induces a dose-dependent increase in VLDL, resulting in plasma triglyceride elevations of up to 24-fold in a mouse line that has 2-fold the concentration of human apoA-II of normolipidemic humans, as well as other well-known characteristics of FCHL: increased concentrations of cholesterol, triglyceride, and apoB in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL), reduced HDL cholesterol, normal lipoprotein lipase and hepatic lipase activities, increased production of VLDL triglycerides, and increased susceptibility to atherosclerosis. However, FCHL patients do not have plasma concentrations of human apoA-II as high as those of apoE-deficient mice overexpressing human apoA-II, and the apoA-II gene has not been linked to FCHL in genome-wide scans. Therefore, the apoA-II gene could be a "modifier" FCHL gene influencing the phenotype of the disease in some individuals through unkown mechanisms including an action on a "major" FCHL gene. We conclude that apoE-deficient mice overexpressing human apoA-II constitute useful animal models with which to study the mechanisms leading to overproduction of VLDL, and that apoA-II may function to regulate VLDL production.

Animals↗
PubMed1999

Effect of simvastatin treatment on the electronegative low-density lipoprotein present in patients with heterozygous familial hypercholesterolemia.

Most described modifications of low-density lipoprotein (LDL) cholesterol share an increase in its negative electric charge; in fact, an electronegative form of LDL can be identified and isolated from plasma. Although the exact nature of the chemical modification of electronegative LDL is still controversial, its toxicity on endothelial cells has been demonstrated. Statins have protective effects against cardiovascular disease that are independent of their lipid-lowering action and which could be due, at least in part, to the prevention of LDL modification. We evaluated the effect of 6 months of simvastatin therapy (40 mg/day) on electronegative LDL proportion and LDL susceptibility to in vitro induced oxidation in 21 patients with heterozygous familial hypercholesterolemia (FH). Eleven normolipemic subjects were analyzed as a control group. Total cholesterol as well as LDL and very low density lipoprotein cholesterol, triglycerides, and apoprotein B decreased 30% after the first month of therapy, with no further decreases thereafter. LDL susceptibility to oxidation was similar in FH patients and controls and did not change throughout the treatment. Electronegative LDL proportion was 35.1 +/- 9.9% in FH patients and 9.1 +/- 2.4% in control subjects (p <0.0001) but, in contrast to total LDL cholesterol and the rest of lipid parameters, it decreased to 28.6 +/- 9.1% in the third month and to 21.2 +/- 7.7% in the sixth month of therapy. The decrease in these cytotoxic particles may be a relevant mechanism by which simvastatin protects against cardiovascular disease.

Adult↗