Atherogenic dyslipidemia and oxidative stress: a new look

Although results from in vitro studies and clinical trials demonstrate strong associations between oxidative stress and cardiovascular risk, to date still no convincing data are available to suggest that treatment with antioxidants might reduce vascular events. Oxidative modifications of low-density lipoproteins (LDL) represent an early stage of atherosclerosis, and small, dense LDL are more susceptible to oxidation than larger, more buoyant particles. Oxidized LDL are independent predictors of subclinical and clinical atherosclerosis. Recent studies suggested that novel therapeutic strategies may take into account the removal of such particles from circulation. Future research is required …

Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome.

OBJECTIVE: Dyslipidaemia is very common in patients with polycystic ovary syndrome (PCOS) but, beyond plasma lipids, atherogenic lipoprotein (Lp) and apolipoprotein (apo) alterations are still ill defined. DESIGN: We measured concentrations of apoB, Lp(a) and small, dense low-density lipoprotein (LDL) in 42 patients with PCOS [age: 28 +/- 7 years, body mass index (BMI): 27 +/- 5 kg/m(2)] vs. 37 age- and BMI-matched healthy controls. METHODS: Elevated Lp(a) levels considered were those > 30 mg/dl while elevated apoB concentrations were those > 100 g/l. RESULTS: Polycystic ovary syndrome showed increased triglycerides levels (p = 0.0011) and lower high-density lipoprotein (HDL)-cholesterol co…

Is diabetes the cost to pay for a greater cardiovascular prevention?

The recent JUPITER (Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin) trial is another study providing evidence about the effectiveness of statin therapy in reducing cardiovascular risk. Yet, in this study significantly higher glycated hemoglobin levels and incidence rates of diabetes were observed in persons treated with rosuvastatin than the placebo group. It should be noted that adverse effects on glucose metabolism have already been reported, albeit rarely, in previous trials with statins. Although the exact mechanisms involved are unknown, it seems that statins may deteriorate glycemic control by decreasing different metabolites,…

Quantitative and qualitative effects of rosuvastatin on LDL-cholesterol: what is the clinical significance ?

Summary Background:  Statins have emerged as the global leader in pharmacologic therapy for dyslipidaemia, and rosuvastatin has demonstrated clinical efficacy as well as safety in several clinical trials and postmarketing analyses. Aim:  The present article reviewed the effects of rosuvastatin on the quantity and the quality of low-density lipoproteins (LDL). Methods:  We searched for and reviewed all the available evidence in a systematic way. A literature search (by Medline and Scopus) was performed using the following headings: ‘LDL-cholesterol’, ‘LDL size’, ‘LDL subclasses’, ‘small dense LDL’, ‘apolipoprotein B, apo B’ and ‘rosuvastatin’ up to 11 November 2008. The authors also manually…

Small, dense low-density lipoproteins (LDL) are predictors of cardio- and cerebro-vascular events in subjects with the metabolic syndrome

Summary Objective  Small, dense low-density lipoproteins (LDL) are a feature of the metabolic syndrome (MS) but their predictive role still remains to be established. We performed a 2-year follow-up study in 124 subjects with MS (63 ± 6 years), as defined by the American Heart Association/National Heart, Lung and Blood Institute guidelines, to assess clinical and biochemical predictors of cerebro- and cardio-vascular events. Methods and results  Beyond traditional cardiovascular risk factors, we measured LDL size and subclasses by gradient gel electrophoresis. Clinical events were registered in the 25% of subjects. At univariate analysis subjects with events had increased prevalence of elev…

Milder forms of atherogenic dyslipidemia in ovulatory versus anovulatory polycystic ovary syndrome phenotype

BACKGROUND: Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) but its prevalence in different PCOS phenotypes is still largely unknown. METHODS: We measured plasma lipids and lipoproteins in 35 anovulatory PCOS (age: 25 ± 6 years, BMI: 28 ± 6 kg/m2), 15 ovulatory PCOS (age: 30 ± 6 years, BMI: 25 ± 3 kg/m2) and 27 healthy women (controls) age- and BMI-matched with ovulatory PCOS. PCOS was diagnosed by the presence of clinical or biologic hyperandrogenism associated with chronic anovulation and/or polycystic ovaries at ultrasound. In women with normal menses chronic anovulation was indicated by low serum progesterone levels (<9.54 nmol/l) during midluteal phase (days 21…

“European Panel on Low Density Lipoprotein (LDL) Subclasses”: A Statement on the Pathophysiology, Atherogenicity and Clinical Significance of LDL Subclasses

Aim of the present Consensus Statement is to provide a comprehensive and up to-date document on the pathophysiology, atherogenicity and clinical significance of low density lipoproteins (LDL) subclasses. We sub-divided our Statement in 2 sections: section I discusses the pathophysiology, atherogenicity and measurement issues, while section II is focused on the effects of drugs and lifestlyle modifications. Suggestions for future research in the field are highlighted at the end of section II. Each section includes Conclusions.

Ethnic differences in serum lipoproteins and their determinants in South African women.

The objective of the study was to characterize ethnic differences in lipid levels and low-density lipoprotein (LDL) particle size and subclasses in black and white South African women and to explore the associations with insulin sensitivity (S(I)), body composition, and lifestyle factors. Fasting serum lipids and LDL size and subclasses, body composition (dual-energy x-ray absorptiometry), and S(I) (frequently sampled intravenous glucose tolerance test) were measured in normal-weight (body mass index25 kg/m(2)) black (n = 15) and white (n = 15), and obese (body mass index30 kg/m(2)) black (n = 13) and white (n = 13) women. Normal-weight and obese black women had lower triglycerides (0.59 +/…

Atherogenic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes.

AIMS: Women with gestational diabetes are more likely to develop Type 2 diabetes and cardiovascular disease after pregnancy; however, the exact nature of the lipid alterations present is not clear. In Mediterranean women with gestational diabetes, we measured low-density lipoprotein (LDL) size and all seven subclasses, as well as the 'atherogenic-lipoprotein phenotype'[ALP, e.g. concomitant presence of elevated triglycerides, reduced high-density lipoprotein (HDL)-cholesterol and increased small, dense LDL]. METHODS: In 27 women with gestational diabetes and 23 healthy pregnant women matched for age, weeks of gestation and body mass index, we measured plasma lipids and LDL size and subclass…

Atherogenic lipoprotein phenotype and LDL size and subclasses in drug-naïve patients with early rheumatoid arthritis.

Abstract Objective : Subjects with rheumatoid arthritis (RA) have increased cardiovascular risk and may show atherogenic forms of dyslipidemia. The present study investigated whether patients with early RA, beyond alterations in plasma lipids, also show lower LDL size and altered LDL subclass distribution. Design and Methods We identified 25 subjects with RA (47±8 years, body mass index (BMI) 25±4kg/m 2 ) by the American College of Rheumatology diagnostic criteria, with a disease durations Results As compared to controls RA patients had higher plasma triglycerides (1.8±0.5 vs. 1.0±0.5mmol/L, p p =0.0027), while total- and LDL-cholesterol concentrations were similar. LDL particle size was lo…

Size and subclasses of low-density lipoproteins in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) have proatherogenic dyslipidemia. We analyzed predictors of low-density lipoproteins' (LDLs) size in patients with OSA. In a cross-sectional study including 58 participants with OSA (30 without the metabolic syndrome [MetS] and 28 with MetS), we evaluated the size of LDL by gradient gel electrophoresis. Compared with patients without the MetS, those with MetS showed lower LDL size ( P = .007), due to a reduction in large LDL-I particles ( P = .002) and an increase in small, dense LDL-IIIA ( P = .048) and LDL-IIIB ( P = .037). The size of LDL correlated inversely with age ( r = −.268, P = .042) and serum triglycerides ( r = −.364, P = .005), and p…

Ezetimibe alone or in combination with simvastatin increases small, dense low-density lipoproteins in healthy men: a randomized trial

Aims The predominance of small dense low-density lipoproteins (sdLDLs) has been associated with increased cardiovascular risk. The effect of ezetimibe on LDL subfraction distribution has not been fully elucidated. This study assessed by gradient gel electrophoresis the effects of ezetimibe alone, simvastatin alone, and their combination on sdLDL subfraction distribution. Methods and results A single-centre, randomized, parallel three-group open-label study was performed in 72 healthy men with a baseline LDL-cholesterol (LDL-C) concentration of 111 ± 30 mg/dL (2.9 ± 0.8 mmol/L). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24), or their combination ( n = …

The differential effects of thiazolidindiones on atherogenic dyslipidemia in type 2 diabetes: what is the clinical significance?

Diabetic dyslipidemia is typically characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein cholesterol and a concomitant increase in atherogenic small dense low-density lipoproteins. Thiazolidindiones are able to lower the levels of fasting glucose and glycated hemoglobin significantly by improving insulin sensitivity, as well as improving some aspects of diabetic dyslipidemia: total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol tend to increase while triglycerides are generally decreased.This paper reviewed the effects of pioglitazone and rosiglitazone on atherogenic diabetic dyslipidemia, in particular on sma…

“European Panel On Low Density Lipoprotein (LDL) Subclasses”: A Statement on the Pathophysiology, Atherogenicity and Clinical Significance of LDL Subclasses: Executive Summary

Glucose lowering and anti-atherogenic effects of incretin-based therapies: GLP-1 analogues and DPP-4-inhibitors

Type 2 diabetes is a chronic, progressive disease with a multi-faceted pathophysiology. Beyond the known defects of insulin resistance and beta-cell insufficiency, derangement of incretin hormones normally produced from the gut wall in response to food intake play an important role. In recent years, the 'incretin-based' therapies (IBTs) have been developed to address hyperglycemia through either mimicking the action of the endogenous incretin glucagon-like polypeptide (GLP-1) (GLP-1 receptor agonists) or by inhibiting the activity of the enzyme that degrades GLP-1 (the dipeptyl peptidase-4 inhibitors).We reviewed available evidence on the glucose lowering and anti-atherogenic effects of IBT…

Long-term consequences of polycystic ovary syndrome on cardiovascular risk

Most available data suggest that the prevalence of cardiovascular diseases in women with polycystic ovary syndrome (PCOS) is smaller than expected based on risk calculations during fertile years; therefore, more studies are needed on long-term cardiovascular consequences. Evidence is accumulating that postmenopausal women with PCOS have an increased risk of cerebrovascular events and cardiovascular morbidity. These events are partially related to persisting hyperandrogenism but are mostly correlated with excessive body weight (mainly visceral obesity); this suggests that our best long-term strategy is to ensure that women with PCOS are informed about their high risk for metabolic and cardio…

The effects of ezetimibe on LDL-cholesterol: quantitative or qualitative changes ?

Ezetimibe represents the first of a new class of agents, the cholesterol absorption inhibitors, able to reduce low-density lipoproteins (LDL)-cholesterol by 15-25% from baseline in monotherapy and on top of statins and fibrates. To-date all the data regarding the efficacy of ezetimibe comes from the studies of its lipid-lowering power. Yet, recent findings from the ENHANCE study on atherosclerosis progression showed that the addition of ezetimibe to simvastatin in patients with heterozygous familial hypercholesterolemia did not affect the mean change in carotid intima-media thickness, although a significant reduction in LDL-cholesterol levels was present. Therefore, we cannot exclude that e…

The Association of Basal Insulin Glargine and/or n-3 Fatty Acids With Incident Cancers in Patients With Dysglycemia

OBJECTIVE Epidemiologic studies linking insulin glargine and glucose-lowering therapies to cancers and n-3 fatty acids to cancer prevention have not been confirmed. We aimed to assess the effect of insulin glargine and n-3 fatty acids on incident cancers within the context of the ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial. RESEARCH DESIGN AND METHODS The ORIGIN trial is an international, long-term, randomized two-by-two factorial study comparing insulin glargine with standard care and n-3 fatty acids with placebo (double blind) in people with dysglycemia at high risk for cardiovascular events. The primary outcome measure (cancer substudy) was the occurrence of any …

The predictive role of atherogenic dyslipidemia in subjects with non-coronary atherosclerosis

Abstract Background Recent findings have suggested that subjects with non-coronary atherosclerosis may show elevated prevalence of atherogenic dyslipidemia, including higher triglyceride levels, reduced HDL-cholesterol concentrations and increased levels of small, dense low-density lipoproteins (LDL). These three lipid abnormalities constitute the so-called “atherogenic-lipoprotein-phenotype” (ALP) but its predictive role in these patients still remains to be established. Methods We performed a 2-year follow-up study to assess clinical and biochemical predictors of cardiovascular events in 44 male patients (64 ± 5 years, BMI: 27 ± 3), 26 with peripheral arterial disease and 18 with abdomina…

Interleukin-18 levels are associated with low-density lipoproteins size

INTRODUCTION: Both low-density lipoproteins (LDL) size and serum interleukin (IL)-18 levels have been shown to be predictors of cardiovascular morbidity and mortality. However, it is still unknown whether IL-18 levels are independently associated with LDL size. METHODS: In this cross-sectional study including 53 premenopausal women (18-45 years), LDL size (by gradient gel electrophoresis), serum IL-18, high-sensitivity C-reactive protein (hs-CRP), serum lipids, insulin sensitivity (S(I), by frequently sampled intravenous glucose tolerance test) were measured. RESULTS: LDL size correlated with IL-18 (r = -0.38, P = 0.006), hs-CRP (r = -0.40, P = 0.003), S(I) (r = 0.36, P = 0.011), serum trig…