Visceral leishmaniasis is associated with marked changes in serum lipid profile.

BACKGROUND: Infection is often accompanied by lipid profile alterations. The aim of this study was to evaluate the lipid profile changes in patients with visceral leishmaniasis (VL). MATERIALS AND METHODS: We included 15 patients [10 men, aged 50 (24-82) years old] with VL and 15 age- and sex-matched controls. The parameters estimated at diagnosis and 4 months after VL resolution were total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoproteins (apo) A-Ι, B, E, C-II, C-III, lipoprotein (a) [Lp(a)], activities of lipoprotein-associated phospholipase A2 (Lp-PLA2), HDL-Lp-PLA2, PON1 (paraoxonase 1) and cholesterol ester transfer protein (CETP), cytokines (interleukins 1ß and 6 and tumour necrosis factor α), as well as LDL subfraction profile. RESULTS: Patients with VL at diagnosis had lower levels of TC, LDL-C, apoΒ and Lp(a), and higher TG and apoE concentrations compared with 4 months after VL resolution. The activities of Lp-PLA2, HDL-Lp-PLA2 and ΡΟΝ1 were reduced at diagnosis compared with post-treatment values. VL patients had decreased levels of both large and sdLDL-C at diagnosis; no effect on mean LDL particle size was observed. Patients with VL at diagnosis had decreased HDL-C and apoA-I concentrations; these increased 4 months after VL resolution, but remained lower compared with controls. The activities of HDL-Lp-PLA2 and PON1 remained lower in patients after VL resolution compared with controls. CONCLUSIONS: Patients with VL exhibit increased TG levels and decreased cholesterol subclasses at diagnosis. HDL-C, apoA-I and associated enzymes remain lower 4 months after VL resolution compared with controls.

Differences in metabolic parameters and cardiovascular risk between American Diabetes Association and World Health Organization definition of impaired fasting glucose in European Caucasian subjects: a cross-sectional study.

INTRODUCTION: The American Diabetes Association (ADA) defines impaired fasting glucose (IFG) as fasting plasma glucose concentration of 100-125 mg/dl, whereas the World Health Organization (WHO) and the International Diabetes Federation (IDF) define IFG as fasting plasma glucose levels of 110-125 mg/dl. We identified differences in metabolic parameters and cardiovascular disease (CVD) risk according to the ADA or WHO/IDF definition of IFG. MATERIAL AND METHODS: Healthy drug-naive Caucasian (Greek) subjects (n = 396; age 55 ±12 years) participated in this cross-sectional study. RESULTS: Diastolic blood pressure (DBP) and uric acid levels were higher in the subjects with glucose 100-109 mg/dl compared with those with glucose < 100 mg/dl (87 ±9 mm Hg vs. 84 ±11 mm Hg, p = 0.004 for DBP, 5.6 ±1.5 mg/dl vs. 5.0 ±1.0 mg/dl, p = 0.002 for uric acid), whereas triglyceride levels were lower in subjects with glucose 100-109 mg/dl compared with those with glucose ≥ 110 mg/dl (169 mg/dl (interquartile range (IQR) = 102-186) vs. 186 mg/dl (IQR = 115-242), p = 0.002). Only the ADA definition recognized subjects with significantly increased 10-year CVD risk estimation (SCORE risk calculation) compared with their respective controls (5.4% (IQR = 0.9-7.3) vs. 4.1% (IQR = 0.7-5.8), p = 0.002). CONCLUSIONS: The ADA IFG definition recognized more subjects with significantly increased CVD risk (SCORE model) compared with the WHO/IDF definition.

Small high-density lipoprotein (HDL) subclasses are increased with decreased activity of HDL-associated phospholipase A2 in subjects with prediabetes.

Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL cholesterol (HDL-C) was significantly increased in prediabetic subjects compared with their controls (p < 0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A2 (HDL-LpPLA2) was significantly lower in subjects with prediabetes (p < 0.05), whereas the activity of paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA2.

The relationship of vitamin D with non-traditional risk factors for cardiovascular disease in subjects with metabolic syndrome.

INTRODUCTION: Several studies implicate an inverse relationship between 25-hydroxy vitamin D (25(OH)Vit D) serum levels and metabolic syndrome (MetS). We sought to investigate a possible relationship between 25(OH)Vit D and emerging risk factors associated with MetS, such as small dense low-density lipoprotein cholesterol (sdLDL-C) concentration, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity and high-sensitivity C-reactive protein (hsCRP) levels. MATERIAL AND METHODS: We studied 110 consecutive otherwise healthy individuals. Of these, 52 were diagnosed with MetS and 58 who did not meet the MetS criteria served as controls. Low-density lipoprotein (LDL) subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA(2) activity was determined in total plasma by the trichloroacetic acid precipitation procedure. Serum 25(OH)Vit D was determined quantitatively by an enzyme immunoassay method. RESULTS: Metabolic syndrome subjects had significantly lower 25(OH)Vit D levels (11.8 [0.6-48.3] ng/ml; 29.5 [1.5-120.75] nmol/l) compared with controls (17.2 [4.8-62.4] ng/ml; 43 [12-156] nmol/l, p = 0.027). Univariate regression analysis showed that 25(OH)Vit D concentration was inversely related to triglycerides (r= - 0.416, p = 0.003) and sdLDL-C (r= - 0.305, p = 0.004). There was no association of 25(OH)Vit D with waist circumference, blood pressure, high-density lipoprotein cholesterol (HDL-C), fasting glucose, Lp-PLA(2) and hsCRP. In multivariate regression analysis the relationship between 25(OH)Vit D and sdLDL-C became insignificant when triglycerides were included in the model. CONCLUSIONS: Subjects with MetS exhibit lower 25(OH)Vit D serum levels compared with non-MetS individuals. Low 25(OH)Vit D is associated with higher sdLDL-C levels possibly through elevated triglycerides. No association between 25(OH)Vit D and Lp-PLA(2) or hsCRP was found.

High-dose intravenous immunoglobulin in the treatment of adult patients with bullous pemphigoid.

High-dose intravenous immunoglobulin (IVIg) has only been sporadically used in the treatment of bullous pemphigoid (BP), as it is suggested as an adjuvant to systemic corticosteroids in progressive disease or when life-threatening complications are of concern with other therapeutic interventions. The aim of the present study was to report our observations in the treatment of adult BP patients with IVIg, in association with a focused literature review. In our Department we identified five patients (4 women, 1 man) who had received IVIg for BP relatively early in the course of their disease. These cases were added to the 36 adequately documented ones reported in the literature. Most of these patients (33/41) responded to treatment with IVIg and 7/33 responders remained clear one year after the onset of IVIg. However, the time for effective disease control after IVIg treatment depended positively on disease duration before treatment (P<0.01). In conclusion, despite the limited experience with its use, IVIg seems to be a useful therapeutic alternative to conventional modalities for selected BP patients, particularly if it is initiated promptly after BP diagnosis.

The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study.

This study examined the association among serum adiponectin levels, a single nucleotide polymorphism (SNP) of the adiponectin gene, and the size of serum high-density lipoprotein (HDL) particles in a general population. A total of 275 subjects were examined as part of the community-based Mima study. Serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Serum small-sized HDL was measured with the electrophoretic separation of lipoproteins using the Lipoprint system. Single nucleotide polymorphism G276T (rs1501299, SNP276) of the adiponectin gene was determined with a fluorescent allele-specific DNA primer assay system. Age- and sex-adjusted correlation test revealed a significant inverse relationship between small-sized HDL and adiponectin levels (r = -0.236, P < .001). More percentages of small-sized HDL were observed in the subjects with the SNP276 G/G and G/T genotypes than in those with the T/T genotype (5.5% ± 5.0% vs 3.0% ± 2.9%, P = .016). In a multiple regression analysis, small-sized HDL was significantly and independently correlated with triglycerides levels (ß = 0.133, P = .030), adiponectin levels (ß = -0.242, P < .001), and the SNP276 G allele (ß = -0.142, P = .014). Our findings indicated that adiponectin and SNP276 of the adiponectin gene may modify the size of HDL particles.

Leptospirosis is associated with markedly increased triglycerides and small dense low-density lipoprotein and decreased high-density lipoprotein.

The objective of the present study was to evaluate the effects of acute infection with Leptospira interrogans on lipids, lipoproteins and associated enzymes. Fasting serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins (apo) A-Ι, B, E, C-II, C-III and lipoprotein (a) [Lp(a)] were determined in patients with Leptospirosis on diagnosis and 4 months after recovery as well as in age- and sex-matched controls. Activities of cholesteryl-ester transfer protein (CETP) and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) as well as paraoxonase 1 (PON1) hydrolysing activity and levels of cytokines were determined. LDL subclass analysis was performed with Lipoprint LDL System. Eleven patients (10 men, mean age 49.5 ± 8.4 years) and 11 controls were included. TC, HDL-C, LDL-C, apoA-I, apoB and Lp(a) levels were lower at baseline, whereas TG and apoE levels were elevated compared with 4 months later. At baseline, higher levels of cytokines and cholesterol concentration of small dense LDL particles (sdLDL-C) were noticed, whereas LDL particle size was lower compared with follow-up. Activities of plasma Lp-PLA(2) and HDL-associated Lp-PLA(2) were lower at baseline compared with post treatment values, whereas PON1 activity was similar at baseline and 4 months later. 4 months after recovery, the levels of all lipid parameters evaluated did not differ compared with controls, except for HDL-C which remained lower. PON1 activity both at baseline and 4 months later was lower in patients compared with controls. Leptospirosis is associated with atherogenic changes of lipids, lipoproteins and associated enzymes.

Ezetimibe treatment lowers indicators of oxidative stress in hypercholesterolemic subjects with high oxidative stress.

Ezetimibe effectively reduces low-density lipoprotein cholesterol (LDL-C). In this study, we tested the hypothesis that ezetimibe monotherapy may also decrease markers of oxidative stress in subjects with hypercholesterolemia. Subjects with hypercholesterolemia and no evidence of cardiovascular disease were randomly allocated to open-label ezetimibe monotherapy 10 mg/day (EZT group) or therapeutic lifestyle changes (TLC group). At baseline and 12 weeks post-treatment serum lipoprotein and apolipoprotein levels as well as oxidative stress parameters, including oxidized LDL (ox-LDL), 8-isoprostanes (8-epiPGF2a) and reactive oxygen metabolites (d-ROMs) levels, were blindly determined. A total of 60 patients were included; 30 in each group. Despite a significant decrease in ox-LDL levels (by 20.8%, p < 0.001 vs. baseline; p < 0.001 vs. TLC group) in the EZT group no change in the ratio ox-LDL to LDL-C was noticed following ezetimibe treatment. No significant change in 8-epiPGF2a and d-ROMs levels was observed in the EZT group. Of note, a significant decrease in 8-epiPGF2a and d-ROMs levels (by 20.4% and 18.2%, respectively, p < 0.01 vs. baseline for both), was noted among patients in the EZT group who exhibited 'high oxidative stress' at baseline. No change in any of oxidative stress parameters was noted in the TLC group. Ezetimibe may decrease markers of oxidative stress in hypercholesterolemic subjects. This benefit may be more profound among patients who exhibit 'high oxidative stress' at baseline.

Plasma triglyceride levels and body mass index values are the most important determinants of prebeta-1 HDL concentrations in patients with various types of primary dyslipidemia.

OBJECTIVE: Experimental studies have shown that the prebeta-1 subclass of high-density lipoprotein particles (prebeta-1 HDL) may play an important role in the reverse cholesterol transport pathway as the initial acceptors of cellular cholesterol. The aim of the present study was the direct comparison of prebeta-1 HDL values in individuals with various types of primary dyslipidemias. METHODS: Four hundred and eighty-six unrelated individuals were included in the study. According to their lipid values study participants were subdivided into four groups: control group (n=206), type IIA dyslipidemia group (n=148), type IIB dyslipidemia group (n=49) and type IV dyslipidemia group (n=83). RESULTS: All dyslipidemic patients displayed higher concentrations of prebeta-1 HDL compared to control individuals. However, patients with dyslipidemias characterized by an abnormal catabolism of triglyceride-rich lipoproteins (such as dyslipidemias of type IIB and IV) tend to have higher prebeta-1 HDL values compared to patients with hypercholesterolemia, and this increase is proportional to the degree of hypertriglyceridemia. In addition, patients with metabolic syndrome exhibited significantly higher levels of prebeta-1 HDL compared to individuals that do not fulfill the criteria for the diagnosis of this syndrome. Multiple regression analysis revealed that serum triglyceride concentrations and body mass index (BMI) values were the most important determinants of prebeta-1 HDL levels in our population. CONCLUSION: All dyslipidemic patients exhibit increased prebeta-1 HDL concentrations as compared to normolipidemic individuals. Whether this increase represents a defensive mechanism against atherosclerosis or it is indicative of impaired maturation of HDL particles and thus of a defective reverse cholesterol transport mechanism remains to be established.

Kidney function and estimated vascular risk in patients with primary dyslipidemia.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased vascular risk. Some studies suggested that considering markers of CKD might improve the predictive accuracy of the Framingham risk equation. AIM: To evaluate the links between kidney function and risk stratification in patients with primary dyslipidemia. METHODS: Dyslipidemic patients (n = 156; 83 men) who were non-smokers, did not have diabetes mellitus or evident vascular disease and were not on lipid-lowering or antihypertensive agents were recruited. Creatinine clearance (CrCl) was estimated using the Cockcroft-Gault equation. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation. We estimated vascular risk using the Framingham equation. RESULTS: In both men and women, there was a significant negative correlation between estimated Framingham risk and both eGFR and CrCl (p < 0.001 for all correlations). When men were divided according to creatinine tertiles, there were no significant differences in any parameter between groups. When men were divided according to either eGFR or CrCl tertiles, all estimated Framingham risks significantly increased as renal function declined (p<0.001 for all trends). When women were divided according to creatinine tertiles, all estimated Framingham risks except for stroke significantly increased as creatinine levels increased. When women were divided according to either eGFR or CrCl tertiles, all estimated Framingham risks significantly increased as renal function declined. CONCLUSIONS: Estimated vascular risk increases as renal function declines. The possibility that incorporating kidney function in the Framingham equation will improve risk stratification requires further evaluation.

Orlistat-associated adverse effects and drug interactions: a critical review.

Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

Hypertriglyceridaemic waist phenotype criteria and prevalent metabolic triad in women.

BACKGROUND: To assess the metabolic profile and the prevalence of the metabolic triad (i.e. hyperinsulinaemia, hyperapobetalipoproteinaemia, and decreased low-density lipoprotein particle size) in women characterized by the hypertriglyceridaemic waist (HTGW) phenotype and to identify cut-off values for triglycerides and waist circumference, effectively discriminating women with the metabolic triad. METHODS: Two hundred and twenty-eight female subjects without any history of vascular disease or diabetes mellitus attending an Outpatient Lipid Clinic setting at the University Hospital of Ioannina, Greece were studied. RESULTS: Currently available HTGW criteria for women were unable to detect any significant differences in the metabolic profile either in the pre- or post-menopausal women, and proved similar in terms of sensitivity and specificity in identifying women with the metabolic triad. A cut-off value of 1.26 mmol/L for triglycerides and 84.5 cm for waist circumference were determined by Receiver-operating Curve evaluation. Women with both triglycerides and waist circumference above these thresholds had four-fold higher odds of presenting with the metabolic triad compared with women with non-HTGW phenotype. CONCLUSIONS: A HTGW phenotype definition of 1.26 mmol/L for triglycerides and 84.5 cm for waist circumference may effectively identify Mediterranean women with the atherogenic metabolic triad. Whether these criteria are also associated with a higher incidence of vascular disease and/or new-onset diabetes in women remains to be investigated.

Gender-related and age-related urinalysis of healthy subjects by NMR-based metabonomics.

NMR-based metabonomic analysis is a well-established approach to characterizing healthy and diseased states. The aim of this study was to investigate inter-individual variability in the metabolic urinary profile of a healthy Greek population, not subjected to strict dietary limitations, by NMR-based metabonomics. The overall metabonomic urinalysis showed a homogeneous distribution among the population. The metabolic profile was examined in relation to gender and age, and reference intervals of major metabolites were determined. Multivariate data analysis led to the construction of two robust models that were able to predict the class membership of the subjects studied according to their gender and age. The most influential low molecular weight metabolites responsible for the differences in gender groups were citrate, creatinine, trimethylamine N-oxide, glycine, creatine and taurine, and for the differences in age groups they were citrate, creatinine, trimethylamine N-oxide and an unidentified metabolite (delta 3.78).

Fibrinogen, lipoprotein (a), albumin and bilirubin (F-L-A-B) levels and cardiovascular risk calculated using the Framingham equation.

OBJECTIVES: To determine the correlation between cardiovascular risk calculated using the Framingham equation and the circulating levels of 4 'emerging'predictors of vascular events: fibrinogen (Fib), lipoprotein (a) (Lp(a)), albumin (Alb) and bilirubin (Bil) (F-L-A-B). PATIENTS AND METHODS: A retrospective survey was carried out using patients referred to a specialist university-based clinic. A total of 376 patients with primary dyslipidaemia (209 men), without overt vascular disease, had their cardiovascular risk estimated using the Framingham equation. RESULTS: Among the men, smokers (n=45) were significantly younger (p =0.014) than non-smokers (n=164). Smokers when compared with non-smokers had significantly higher median Fib levels (3.84 (1.15-5.87) vs. 3.08 (1.44-5.47) g/l; p<0.0001) and lower median Bil levels (8 (3-17) vs. 10 (1-28) micromol/l; p=0.016). When non-smoker men without clinically evident vascular disease were considered, there was a significant positive Fib and negative Alb correlation with calculated risk, whether the family history was considered or not. Moreover in smokers, the only significant correlation was a negative one between Bil and cardiovascular disease risk. Lp(a) correlated with risk for stroke in women non-smokers whether the family history was considered or not, while Alb correlated with risk for stroke in women non-smokers without family history. CONCLUSION: Fib, Lp(a), Alb and Bil (F-L-A-B) may be predictors of vascular events in high-risk populations. Prospective studies should evaluate whether the F-L-A-B markers are useful in the assessment of cardiovascular risk load. Such an advantage would make treatment more cost effective by improving patient targeting. The F-L-A-B markers could eventually become targets for new drugs.

Effect of ezetimibe in patients who cannot tolerate statins or cannot get to the low density lipoprotein cholesterol target despite taking a statin.

BACKGROUND: Recent guidelines underline the need for high-risk patients to reach strict low density lipoprotein cholesterol (LDL-C) targets (1.8-2.6 mmol/L; 70-100 mg/dL), and specifically mention the possible use of combination therapy (e.g.statin + ezetimibe) to achieve these goals. METHODS: A retrospective case-note audit was carried out to assess the response to administering ezetimibe in patients unable to tolerate statins (Group 1), or high dose of statins (Group 2) and patients who cannot achieve the LDL-C target (2.6 mmol/L; 100 mg/dL) despite taking a statin (Group 3). RESULTS: Ezetimibe lowered LDL-C levels by 20-29% across the 3 patient groups after 2-3 months of treatment. High density lipoprotein cholesterol (HDL-C) levels tended to remain unchanged, although there was a consistent trend for a fall if baseline values were 'high'. However, the LDL-C/HDL-C ratio changed significantly and favourably in all groups. The fall in fasting triglyceride levels in all groups was greater (reaching 19-25%) when baseline levels were > or = 1.5 or 1.7 mmol/L (136-150 mg/dL). There were no marked abnormalities in liver function tests or creatine kinase activity. In Group 3 there was a significant trend for a fall in serum creatinine levels across the tertiles of baseline creatinine values. Limitations of the present study include the small sample size (especially in Groups 1 and 2), its short-term duration and the absence of event-based end-points. Therefore, the results are hypothesis-generating rather than conclusive. CONCLUSIONS: When used alone or added to a statin, ezetimibe favourably altered the LDL-C/HDL-C ratio and lowered triglyceride levels. Ezetimibe was well tolerated in patients with statin intolerance and was associated with a 26% fall in LDL-C. An additional action may be some degree of improved renal function. Further studies are needed to confirm these findings.

Differential effect of hypolipidemic drugs on lipoprotein-associated phospholipase A2.

OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor for incident atherosclerotic disease. We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA2 activity and mass. METHODS AND RESULTS: In 50 patients with Type IIA dyslipidemia were administered rosuvastatin (10 mg daily), whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy (10 mg daily). Fifty patients with Type IV dyslipidemia were given micronised fenofibrate (200 mg daily). Low- and high-density lipoprotein (LDL and HDL, respectively) subclass analysis was performed electrophoretically, whereas lipoprotein subfractions were isolated by ultracentrifugation. Ezetimibe reduced plasma Lp-PLA2 activity and mass attributable to the reduction in plasma levels of all LDL subfractions. Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA2 on dense LDL subfraction (LDL-5). Fenofibrate preferentially reduced the Lp-PLA2 activity and mass associated with the VLDL+IDL and LDL-5 subfractions. Among studied drugs only fenofibrate increased HDL-associated Lp-PLA2 (HDL-Lp-PLA2) activity and mass attributable to a preferential increase in Lp-PLA2 associated with the HDL-3c subfraction. CONCLUSIONS: Ezetimibe, rosuvastatin, and fenofibrate reduce Lp-PLA2 activity and mass associated with the atherogenic apoB-lipoproteins. Furthermore, fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA2. The clinical implications of these effects remain to be established.

Effect of ezetimibe monotherapy on the concentration of lipoprotein subfractions in patients with primary dyslipidaemia.

BACKGROUND: Recent studies suggest that the distribution of lipoprotein subfractions is an independent predictor of vascular events. Therefore, we evaluated the effect of ezetimibe (a selective cholesterol transport inhibitor) on the concentrations of lipoprotein subfractions in patients with primary dyslipidaemia. MATERIALS AND METHODS: Patients (n = 50) with primary dyslipidaemias were recruited. The concentrations of the individual lipoprotein subfractions were measured using the Lipoprint system at baseline and after 16 weeks of treatment. RESULTS: Ezetimibe reduced total, low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) values as well as apolipoprotein B concentrations. Subfractionation of apolipoprotein B-containing lipoproteins showed that the reduction in LDL-C values was due to a fall in the concentrations of all LDL subfractions. However, a more pronounced trend towards a decrease in the concentrations of dense LDL subfractions was observed. Patients with triglyceride values >1.7 mmol/L had significantly greater reductions in the concentrations of small, dense LDL particles compared with those with normal triglyceride levels (49 vs. 19%, respectively; p < 0.05). Ezetimibe decreased the concentrations of HDL-C mainly due to a fall in the concentration of dense HDL subfractions. CONCLUSION: Ezetimibe can favourably affect the distribution of LDL subfractions, especially in patients with elevated triglyceride values. Further studies are needed to clarify the significance of the ezetimibe-induced reduction in the concentrations of dense HDL particles.

Plasma lipoproteins and triacylglycerol are predictors of small, dense LDL particles.

Recently published data suggest that the assessment of LDL subfraction profiles may contribute to the determination of the cardiovascular risk. In this study, we tested the ability of various metabolic parameters to estimate the presence or the preponderance of small, dense LDL particles (sdLDL). One hundred and fifty individuals attending the Outpatient Clinics of the University Hospital of Ioannina for suspected metabolic abnormalities were included in the study. Individuals were excluded if they were found to be diabetic or if they had a history of cardiovascular disease. Patients with thyroid dysfunction, liver or kidney diseases as well as those receiving drugs that may interfere with lipids or glucose metabolism were also excluded from the study. The ability of the various parameters to identify individuals with pattern B LDL phenotype or, alternatively, with measurable quantities of sdLDL particles was tested with the calculation of the areas under the ROC curves. The ratio of triglycerides to HDL-C was the best predictor of the presence of the pattern B LDL phenotype. Nevertheless, when the variable of interest was the presence of measurable quantities of sdLDL subfractions, the ratio of apoB to apoAI had the best predictive ability. In conclusion the ratios of apoB to apoAI and of triglycerides to HDL-C can reliably predict the presence of measurable quantities of sdLDL particles and of the pattern B LDL phenotype, respectively. However, since the quantitative determination of sdLDL concentrations may contribute to the determination of the cardiovascular risk, whereas the role of the LDL particle size remains controversial, apoB to apoAI ratio could provide more valuable information compared to markers that simply predict the presence of the pattern B LDL phenotype.

Clinical importance and therapeutic modulation of small dense low-density lipoprotein particles.

The National Cholesterol Education Programme Adult Treatment Panel III accepted the predominance of small dense low-density lipoprotein (sdLDL) as an emerging cardiovascular disease (CVD) risk factor. Most studies suggest that measuring low-density lipoprotein (LDL) particle size, sdLDL cholesterol content and LDL particle number provides additional assessment of CVD risk. Therapeutic modulation of small LDL size, number and distribution may decrease CVD risk; however, no definitive causal relationship is established, probably due to the close association between sdLDL and triglycerides and other risk factors (e.g., high-density lipoprotein, insulin resistance and diabetes). This review addresses the formation and measurement of sdLDL, as well as the relationship between sdLDL particles and CVD. The effect of hypolipidaemic (statins, fibrates and ezetimibe) and hypoglycaemic (glitazones) agents on LDL size and distribution is also discussed.

LDL-cholesterol calculation formulas in patients with or without the metabolic syndrome.

The present study compares the low-density lipoprotein cholesterol (LDL-C) values obtained by the Friedewald formula (LDL-F) with those derived from a new equation that uses only the concentrations of total cholesterol and triglycerides (LDL-A) in patients with the metabolic syndrome (MS) (n=118) and in age- and sex-matched controls (n=112). According to our results, LDL-A was correlated with LDL-F in the MS as well as in the control group (p for both <0.001). However, LDL-A slightly overestimated the LDL-C levels compared with LDL-F in the control group, possible due to the higher high-density lipoprotein cholesterol (HDL-C) levels in these individuals. Importantly, no difference was observed between the two equations in the MS group. LDL-A may be useful for the calculation of LDL-C levels when HDL-C level are not easily available.