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ABSTRACT: Beyond low-density lipoprotein (LDL)-cholesterol concentrations, in recent years, several clinical studies have shown that both oxidised and small, dense LDL have a strong predictive role for the presence of vascular atherosclerosis. These two lipid parameters seem to have a synergistic impact on cardiovascular risk, with a greater importance in patients at higher-risk, such as those with type-2 diabetes. Increased levels of oxidised and small, dense LDL levels are a feature of diabetic dyslipidaemia, and small, dense LDL have been shown to be a good predictor of future cardiovascular events, at both univariate and multivariate analyses. On the other hand, although the association of oxidised LDL with surrogate markers of atherosclerosis is consistent, the correlation with hard clinical end points seems to be smaller. Yet, measurement of these two lipid parameters has not been widely used in daily practice because of the limited availability of clinical data and methodological problems: lack of availability of easy, cheap and reproducible essays for measurement of oxidised and, particularly, small, dense LDL has reduced their assessment in large clinical end-points trials. However, on the basis of available data, the therapeutic modulation of small, dense LDL is significantly associated with reduced cardiovascular risk, even after adjustment for confounding factors. In conclusion, the routine measurement of oxidised and small, dense LDL in patients with type-2 diabetes cannot be recommended in daily clinical practice so far; yet, their measurement is strongly encouraged to better understand their role on the cardiovascular risk of patients with type-2 diabetes.
International Journal of Clinical Practice 11/2010; 64(12):1632-42. · 2.41 Impact Factor
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ABSTRACT: 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.
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.
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 triglycerides (r = -0.32, P = 0.018) and high-density lipoproteins (HDL)-cholesterol (r = 0.40, P = 0.003). When these variables were entered into a regression model, serum IL-18 (beta = -0.26, P = 0.04), triglycerides (beta = -0.29, P = 0.02) and HDL-cholesterol (beta = 0.34, P = 0.01) levels were independently associated with LDL size, accounting for 42% of the variance (P < 0.001). Serum hs-CRP levels and S(I) were not significant independent predictors of LDL size in this model.
This is the first report showing that elevated IL-18 levels are associated with reduced LDL size, independent of other inflammatory and metabolic risk factors. Future prospective studies are needed to evaluate the predictive role of IL-18 as an inflammatory marker of LDL size and the development of subclinical and/or clinical atherosclerosis.
European Journal of Clinical Investigation 11/2009; 40(1):54-5. · 3.02 Impact Factor
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ABSTRACT: 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.
The present article reviewed the effects of rosuvastatin on the quantity and the quality of low-density lipoproteins (LDL).
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 reviewed the references of selected articles for any pertinent material.
Rosuvastatin reduces LDL-cholesterol levels to a greater extent than other statins and is able to modulate significantly LDL size and subclasses towards less atherogenic particles as well as the LDL particle number, as indirectly measured by the levels of apo B.
The recent Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin study provides more evidence about the effectiveness of rosuvastatin therapy in reducing cardiovascular risk, even among persons who would not currently be considered for pharmacotherapy. Further insights on cardiovascular outcomes will be available by the on-going trials included in the GALAXY program that includes subjects with type-2 diabetes, haemodialysis recipients, patients with congestive heart failure and specific ethnic groups, such as African American, Hispanic and South Asian populations.
International Journal of Clinical Practice 04/2009; 63(3):478-85. · 2.41 Impact Factor
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ABSTRACT: 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].
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 subclasses by gradient gel electrophoresis between 24 and 28 weeks of gestation.
Although no significant differences were found in the concentrations of any of the plasma lipids, compared with control subjects women with gestational diabetes had lower LDL size (P = 0.0007) due to reduced LDL-I (P = 0.0074) and increased LDL-IVA (P = 0.0146) and -IVB (P < 0.0001) subclasses. Correlation analysis revealed that fasting glucose, homeostasis model assessment and glycated haemoglobin were inversely correlated with LDL-I and positively with LDL-IVA and -IVB (all P < 0.05). ALP due to high HDL-cholesterol levels was not seen in either group, whereas elevated small, dense LDL were more common in women with gestational diabetes than control subjects (33% vs. 4%, P = 0.0107).
Increased levels of small, dense LDL are common in Mediterranean women with gestational diabetes. Whether these findings affect the atherogenic process and clinical end-points in these women remains to be determined by future prospective studies.
Diabetic Medicine 01/2009; 25(12):1406-11. · 2.90 Impact Factor
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ABSTRACT: 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.
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.
Elevated Lp(a) levels considered were those > 30 mg/dl while elevated apoB concentrations were those > 100 g/l.
Polycystic ovary syndrome showed increased triglycerides levels (p = 0.0011) and lower high-density lipoprotein (HDL)-cholesterol concentrations (p = 0.0131) while total- and LDL cholesterol were similar. PCOS also showed smaller LDL size (p = 0.0005), higher levels of total small, dense LDL (p < 0.0001), higher concentrations of Lp(a), as considered as absolute values (p = 0.0143) and log-transformed (p = 0.0014), while no differences were found in apoB levels. Elevated Lp(a) concentrations were found in 24% of PCOS, while elevated apoB levels were relatively uncommon (14%). Spearman correlation analysis revealed that Lp(a) concentrations were weakly correlated only with HDL-cholesterol levels (r = -0.378, p = 0.0431). In addition, 36% of patients with PCOS with normal plasma lipid profile showed elevated levels of Lp(a), apoB or small, dense LDL.
Atherogenic Lp abnormalities may be found in one-third of women with PCOS who have a normal lipid pattern. Future prospective studies are needed to test to which extent such atherogenic forms of dyslipidaemia may contribute to the increased cardiovascular risk in young women with PCOS.
International Journal of Clinical Practice 01/2009; 63(1):56-62. · 2.41 Impact Factor
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ABSTRACT: 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 ezetimibe is treating mainly LDL-cholesterol and not the underlying dyslipidemia. Reviewing all available evidences on the effects on atherogenic small, dense LDL, it seems that ezetimibe produce quantitative rather than qualitative changes in LDL, with small net effects on LDL subclass distribution. Yet, we cannot exclude that clinical and laboratory factors influenced this result. We found important differences in the methodology used to measure LDL size and subfractions and this represents a crucial point, since these methods cannot be fully used interchangeably. In addition, it is reasonable to imagine that ezetimibe may be more effective on small, dense LDL in subjects with hypertriglyceridemia. Further formal cardiovascular event outcome trials are underway and this will provide additional insights into the long-term effects of ezetimibe. Future prospective studies are also needed to clarify to which extent ezetimibe is able to reduce atherogenic dyslipidemia, beyond LDL-cholesterol levels.
Atherosclerosis 11/2008; · 3.79 Impact Factor
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ABSTRACT: BACKGROUND: 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. OBJECTIVE: This paper reviewed the effects of pioglitazone and rosiglitazone on atherogenic diabetic dyslipidemia, in particular on small dense low-density lipoprotein particles. Methods: A literature search (by Medline and Scopus) was performed up to 15 March 2008. The authors also manually reviewed the references of selected articles for any pertinent material. RESULTS: Pioglitazone showed an additional beneficial effect on triglycerides, high-density lipoprotein cholesterol and the levels of small dense low-density lipoprotein compared to rosiglitazone. CONCLUSIONS: Since recent studies have suggested that these agents may also have a differential effect on long-term cardiovascular end-points despite similar improvements in glycated hemoglobin and insulin sensitivity, the different impact on atherogenic diabetic dyslipidemia may help to explain these findings.
Expert Opinion on Pharmacotherapy 10/2008; · 3.20 Impact Factor
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ABSTRACT: OBJECTIVE: Several studies have suggested that lipoproteins generated during the post-prandial phase are highly atherogenic, with modifications in low-density lipoproteins (LDL) size and density. In the present study we assessed post-prandial variations in LDL size and subclasses in patients with growth hormone deficiency (GHD). DESIGN: We studied in 12 hypopituitary patients with GHD and 10 healthy control subjects matched for gender, age and body mass index (BMI) post-prandial variations after a standardized meal consisting of 35% fat, 45% carbohydrate and 20% of protein (Clinutren Mix, Nestlé) and containing calories corresponding to 1/3 of estimated basal metabolic rate. Blood samples were collected at baseline and after 2 and 4h to measure plasma lipids and LDL size and subclasses by nondenaturing polyacrylamide gradient gel electrophoresis. RESULTS: At baseline patients had similar plasma lipids than controls, with the exception of higher triglycerides (1.2+/-0.8 vs. 0.7+/-0.4mmol/L, p=.0024). Baseline LDL size was similar between the two groups and LDL subclass analysis revealed a small increase in LDL-IIIA (p=.0046). During post-prandial phase no significant differences were found in LDL size and subclasses in patients vs. controls with the sole exception of increased levels of LDL-IVB after 2h (p=.0295) and LDL-IIIB after 4h (p=.0478). CONCLUSIONS: It is, therefore, unlikely that a post-prandial variation in levels of small, dense LDL may significantly contribute to the atherogenic potential in hypopituitary patients with GHD.
Growth Hormone & IGF Research 07/2008; · 2.16 Impact Factor
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ABSTRACT: Despite their young age, women with polycystic ovary syndrome (PCOS) have increased cardiovascular risk. Besides normal concentrations of low-density lipoprotein (LDL) cholesterol, dyslipidemia is very common and includes elevated triglyceride levels and low high-density lipoprotein cholesterol concentrations. Recent findings also showed that women with PCOS have qualitative LDL alterations, with increased levels of atherogenic small, dense LDL particles. Such lipid abnormalities constitute a common form of dyslipidemia, the so-called atherogenic lipoprotein phenotype (ALP), associated with a greater cardiovascular risk. Weight reduction and increased physical activity may constitute first-line therapy for ALP in PCOS, and lipid lowering drugs, particularly nicotinic acid and fibrates, should be used in patients with severe dyslipidemia. Statins have usually a lower impact on ALP, and their beneficial effect is often moderate. Insulin-sensitizing medications favorably alter each component of ALP and combined therapy with these agents remains an option; in particular, the combination pioglitazone plus metformin seems to be particularly beneficial.
American journal of obstetrics and gynecology 02/2008; · 3.28 Impact Factor
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ABSTRACT: Increasing evidence suggest that the 'quality' rather than only the 'quantity' of low-density lipoprotein (LDL) exerts a great influence on the cardiovascular risk. Small, dense LDL seem to be an important predictor of cardiovascular events and progression of coronary artery disease (CAD) and their predominance has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III.
Some studies showed in past years that small, dense LDL are usually elevated in patients at very high cardiovascular risk, such as those with CAD and type 2 diabetes. More recently elevated levels of these particles have been found in other categories of patients at high cardiovascular risk, such as those with non-coronary forms of atherosclerosis (e.g. with carotid artery disease, aortic abdominal aneurysm and peripheral arterial disease) and metabolic diseases (with polycystic ovary syndrome and growth hormone deficiency); notably, in most of them, the predominance of small, dense LDL characterised their type of dyslipidaemia, alone or in combination with elevated triglycerides and reduced high-density lipoproteins cholesterol concentrations.
The therapeutical modulation of small, dense LDL have been shown to significantly reduce cardiovascular risk and weight reduction and increased physical activity may constitute first-line therapy. In addition, lipid-lowering drugs are able to favourably alter these particles and fibrates and nicotinic acid seem to be the most effective agents. Promising data are also available with the use of rosuvastatin, the latest statin introduced in the market, and ezetimibe, a cholesterol absorption inhibitor.
International Journal of Clinical Practice 12/2007; 61(11):1949-56. · 2.41 Impact Factor
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ABSTRACT: Increasing evidence suggest that the "quality" rather than only the "quantity" of low density lipoproteins (LDL) exerts a great influence on the cardiovascular risk. Hypertriglyceridemia, low HDL-cholesterol and increased levels of small dense LDL characterise diabetic dyslipidemia. In subjects with type-2 diabetes LDL size seems also to represent a good marker of clinical apparent and non-apparent atherosclerosis. Recently, the Coordinating Committee of the National Cholesterol Education Program stated that high-risk patients may benefit of stronger therapeutical approaches, a category of subjects that include those with type-2 diabetes. Screening for the presence of small, dense LDL may potentially identify those with even higher risk and may contribute in directing specific treatments in order to prevent new cardiovascular events. Hypolipidemic treatments are able to favourably modulate LDL size and subclasses in patients at higher cardiovascular risk. Regarding subjects with type-2 diabetes this seems particularly true for fibrates and less for statins. Analysis of all published studies revealed that atorvastatin represents the most effective agent among statins, while fenofibrate, bezafibrate and gemfibrozil are all very beneficial in modifying LDL size and subclasses towards less atherogenic particles. Nicotinic acid has been found also effective but the extended-release form should be preferred for the reduced intolerance, while fish oils have been shown to be less beneficial. Promising data are also available with the use of ezetimibe, a cholesterol absorption inhibitor.
Experimental and Clinical Endocrinology & Diabetes 10/2007; 115(8):477-82. · 1.69 Impact Factor
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ABSTRACT: Low density lipoproteins (LDL) comprise in humans two different main fractions: large, buoyant and small, dense particles. Small, dense LDL particles correlate negatively with plasma HDL levels and positively with plasma triglyceride concentrations and are associated with the metabolic syndrome and increased risk for cardiovascular disease. LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart disease (CHD). In addition, several studies have suggested that therapeutic modulation of specific LDL subclasses may be of great benefit in reducing the atherosclerotic risk. Therefore, LDL size measurement may be of potential value in the clinical assessment and management of patients at high risk of CHD, a category that comprises individuals with non-coronary forms of atherosclerosis: peripheral arterial disease, carotid artery disease, abdominal aortic aneurysm. Potentially, screening for the presence of small, dense LDL in patients with those clinical forms of atherosclerosis may identify those with even higher vascular risk and may contribute in directing specific anti-atherosclerotic treatments in order to prevent new vascular events in the same or another district. However, to-date, not so many studies have investigated the LDL size in patients with non-coronary forms of atherosclerosis and we need to wait for further contributions with larger number of patients, even if available data seem to suggest an association between small, dense LDL and such diseases. The predominance of small dense LDL particles has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III but screening for the presence of small, dense LDL particles in patients with non-coronary forms of atherosclerosis has not been so far recommended.
International angiology: a journal of the International Union of Angiology 04/2006; 25(1):4-9. · 1.65 Impact Factor
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ABSTRACT: A predominance of small, dense low-density lipoproteins (LDL) has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart disease and evidences suggests that both quality (particularly small, dense LDL) and quantity may increase cardiovascular risk. However, other authors have suggested that LDL size measurement does not add information beyond that obtained by measuring LDL concentration, triglyceride levels and HDL concentrations. Therefore, it remains debatable whether to measure LDL particle size in cardiovascular risk assessment and, if so, in which categories of patient. Therapeutic modulation of LDL particle size or number appears beneficial in reducing the risk of cardiovascular events, but no clear causal relationship has been shown, because of confounding factors, including lipid and non-lipid variables. Studies are needed to investigate the clinical significance of LDL size measurements in patients with coronary and non-coronary forms of atherosclerosis; in particular, to test whether LDL size is associated with even higher vascular risk, and whether LDL size modification may contribute to secondary prevention in such patients.
QJM: monthly journal of the Association of Physicians 02/2006; 99(1):1-14. · 2.33 Impact Factor
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ABSTRACT: The atherogenic lipoprotein phenotype is characterised by a moderate increase in plasma triglycerides, a decrease in high density lipoprotein cholesterol and the prevalence of smaller denser low density lipoprotein particles. The prevalence of this partially inheritable phenotype is approximately 30% and is a feature of the metabolic syndrome associated with an increased risk for cardiovascular events. The predominance of small dense LDL has been accepted as an emerging cardiovascular risk factor by the adult treatment panel (ATP) III.
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 01/2005; 134(49-50):720-4. · 1.89 Impact Factor
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ABSTRACT: Background: High amounts of dietary fructose may contribute to dyslipidemia in adults, but there are few data in children. Childhood adiposity is associated with smaller LDL particle size, but the dietary predictors of LDL size in overweight children have not been studied. Objectives: We aimed to determine whether LDL particle size is associated with dietary factors and specifically with fructose intake in normal-weight and overweight children. Design: In a cross-sectional study of normal-weight and overweight 6¿14 y-old Swiss children (n = 74), dietary intakes were assessed by using two 24-h-recalls and a 1-d dietary record. Body mass index (BMI) and waist-hip ratio (WHR) were measured, and plasma lipid profile and LDL particle size were determined. Results: Compared with the normal-weight group, overweight children had significantly higher plasma triacylglycerol concentrations, lower HDL-cholesterol concentrations, and smaller LDL particle size (P < 0.05). LDL particle size was inversely correlated to BMI SD scores and WHR (P = 0.007). Although there were no significant differences in total fructose intake, the overweight children consumed a significantly (P < 0.05) higher percentage of fructose from sweets and sweetened drinks than did the normal-weight children. After control for adiposity, the only dietary factor that was a significant predictor of LDL particle size was total fructose intake (P = 0.024). Conclusions: In school-age children, greater total and central adiposity are associated with smaller LDL particle size and lower HDL cholesterol. Overweight children consume more fructose from sweets and sweetened drinks than do normal-weight children, and higher fructose intake predicts smaller LDL particle size
American Journal of Clinical Nutrition 86 (2007) 4.
