Ezetimibe/simvastatin (INEGY) in the treatment of hyperlipidaemia

Ezetimibe/simvastatin (INEGY), a dual inhibitor of both cholesterol production and absorption, is a new approach to the management of hyperlipidaemia. Recent studies have shown that it produces greater reductions in low-density lipoprotein (LDL) cholesterol than the single inhibition of statin therapy, enabling many more patients to achieve their LDL cholesterol treatment goals. With ezetimibe/simvastatin therapy, reductions of up to 61% from baseline have been seen in LDL cholesterol, with clear improvements in other associated lipid fractions. It has been well tolerated across all studies, with a safety profile similar to that of statin therapy. This article will review clinical experience to date with ezetimibe/simvastatin, commenting upon its place and potential value in the prevention of cardiovascular disease.     

Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels

OBJECTIVE: In patients with type 2 diabetes, a normal HDL cholesterol level does not rule out that LDL particles may be small. Although techniques for analyzing LDL subfractions are not likely to be used in clinical practice, a prediction of LDL size based on a regular lipid profile may be useful for assessment of cardiovascular risk. RESEARCH DESIGN AND METHODS: Sixty patients with type 2 diabetes with acceptable glycemic control and an HDL cholesterol level > or = 1 mmol/l were recruited after cessation of lipid-altering treatments. LDL size was determined by 2-20% PAGE; patients having small LDL (n = 30) were compared with those having intermediate or large LDL (n = 30). RESULTS: Clinical characteristics, pharmacological therapies, lifestyle, and prevalence of diabetes-related complications were similar in both patient groups. LDL size correlated negatively with plasma triglycerides (TGs) (R2 = 0.52) and positively with HDL cholesterol (R2 = 0.14). However, an inverse correlation between the TG-to-HDL cholesterol molar ratio and LDL size was even stronger (R2 = 0.59). The ratio was > 1.33 in 90% of the patients with small LDL particles (95% CI 79.3-100) and 16.5% of those with larger LDL particles. A cutoff point of 1.33 for the TG-to-HDL cholesterol ratio distinguishes between patients having small LDL values better than TG cutoff of 1.70 and 1.45 mmol/l. CONCLUSIONS: The TG-to-HDL cholesterol ratio may be related to the processes involved in LDL size pathophysiology and relevant with regard to the risk of clinical vascular disease. It may be suitable for the selection of patients needing an earlier and aggressive treatment of lipid abnormalities.     

Asessing coronary heart disease risk and managing lipids.

Elevated low-density lipoprotein (LDL) and below normal high-density lipoprotein (HDL) cholesterol are risk factors for coronary heart disease (CHD). According to clinical guidelines, LDL cholesterol is the primary target for lipid-altering therapy. Many patients who develop CHD have LDL and HDL cholesterol levels that fall within the desirable or low-risk category; consequently, conventional measurements of plasma lipids may not accurately detect high-risk patients. This article discusses the clinical significance of lipoprotein subclasses and methods of measurement. Assessing lipoprotein subclasses provides a more comprehensive and efficacious therapeutic approach compared with the standard lipid profile.     

Differing associations of lipid and lipoprotein disturbances with the macrovascular and microvascular complications of type 1 diabetes.

OBJECTIVE: Cardiovascular disease (CVD) is increased in patients with type 1 diabetes, but lipid and lipoprotein patterns remain favorable. In contrast, nephropathy is associated with an adverse distribution. We compared the associations and predictive power of lipid and lipoprotein disturbances with these complications. RESEARCH DESIGN AND METHODS: A nested case-control study from the EURODIAB cohort of 140 case subjects with evidence of at least one complication and 84 control subjects with no complications were analyzed. Conventional and unconventional lipid and lipoprotein fractions, including apolipoprotein (apo)-A1, lipoprotein (Lp)-A1, LpA1/A2, apoB, and LDL particle size were measured centrally. RESULTS: CVD was only associated with increased LDL cholesterol (3.6 vs. 3.0 mmol/l, P = 0.02). In contrast, albuminuria was associated with elevated cholesterol, triglyceride, LDL, and apoB and with diminished LDL particle size. No disturbances in HDL and related lipoproteins were noted. In normoalbuminuric patients, CVD was not associated with any significant changes in lipids. CVD in macroalbuminuric patients was associated with increased triglyceride level (2.37 vs. 1.07 mmol/l, P = 0.001; P = 0.02 for CVD/albuminuria interaction) and LDL cholesterol (5.4 vs. 3.3 mmol/l, P = 0.005; P = 0.004 for interaction). Independent associations were observed for total cholesterol and for LDL particle size and albuminuria. CONCLUSIONS: Abnormalities in lipid and lipoprotein disturbances are more closely related to albuminuria than to CVD in patients with type 1 diabetes. Measurement of conventional parameters provide sufficient risk information. ApoB and LDL particle size offer limited extra information. HDL metabolism remains undisturbed in the presence of complications. These changes reflect associations with glycemic control, which is the key to understanding lipid and lipoprotein disturbances.     

The nuclear magnetic resonance metabolic profile: Impact of fasting status

IntroductionMeasurement of lipoprotein subclass concentration (-c), particle number (-p), and size (-s) by nuclear magnetic resonance (NMR) has gained traction in the clinical laboratory due to associations between smaller lipid particle sizes and atherogenic risk, especially for LDL-p. The standard protocols for lipoprotein measurements by NMR require fasting blood samples; however, patients may not fast properly before sample collection. The study objective was to evaluate the impact of fasting status on the NMR-based lipid profile and to identify key parameters differentiating between fasting and post-meal specimens.MethodsForty-eight self-reported healthy male and female participants were recruited. Blood was collected after a 12 h fast and 4 h after a high fat meal. Samples were analyzed using the AXINON LipoFIT by NMR assay. The measurements included triglyceride, total cholesterol, IDL-c, and LDL, HDL, VLDL concentration, particle number, and size, as well as glucose, and four amino acids (alanine, valine, leucine and isoleucine).ResultsAs expected, triglycerides increased after the meal (58%, p < 0.0001). Significant changes were also observed for VLDL, LDL, and HDL parameters, and the branched chain amino acids. The ratio of Valine*VLDL-c/LDL-c or Isoleucine*VLDL-c/LDL-c provided equally effective differentiation of fasting and post-meal samples. The ratio cutoffs (79.1 and 23.6 when calculated using valine and isoleucine, respectively) had sensitivities of 86% and specificities of 93–95%.ConclusionsThe clinical impact on NMR results from post-meal samples warrants further evaluation. Algorithms to differentiate fasting and post-meal specimens may be useful in identifying suboptimal specimens.     

Low-density lipoprotein size and cardiovascular risk assessment

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.     

Lipid and Lipoprotein Profiles in Youth With and Without Type 1 Diabetes: The SEARCH for Diabetes in Youth Case-Control Study

OBJECTIVE—The purpose of this study was to compare the lipid profile and the prevalence of lipid abnormalities in youth with and without type 1 diabetes and explore the role of glycemic control on the hypothesized altered lipid profile in youth with type 1 diabetes.RESEARCH DESIGN AND METHODS—We conducted a cross-sectional analysis of 512 youth with type 1 diabetes (mean duration 4.22 years) and 188 healthy control subjects aged 10–22 years in Colorado and South Carolina. SEARCH for Diabetes in Youth (SEARCH) participants with type 1 diabetes and healthy control subjects recruited from primary care offices in the same geographic regions were invited to attend a research visit. Fasting lipid profiles were compared between youth with type 1 diabetes (stratified according to categories of optimal [A1C <7.5%] and suboptimal [A1C ≥7.5%] glycemic control) and healthy nondiabetic youth, using multiple linear and logistic regression.RESULTS—Youth with type 1 diabetes and optimal A1C had lipid concentrations that were similar (total cholesterol, LDL cholesterol, and LDL particle size) or even less atherogenic (HDL cholesterol, non-HDL cholesterol, triglyceride, and triglyceride–to–HDL cholesterol ratio) than those observed in nondiabetic youth, whereas youth with suboptimal glycemic control had elevated standard lipid levels (total cholesterol, LDL cholesterol, and non-HDL cholesterol). Youth with type 1 diabetes also had significantly elevated apolipoprotein B levels and more small, dense LDL particles than nondiabetic youth, regardless of glycemic control.CONCLUSIONS—Youth with type 1 diabetes have abnormal lipid levels and atherogenic changes in lipoprotein composition, even after a relatively short disease duration. As in adults, glycemic control is an important mediator of these abnormalities.Diabetes is a major risk factor for cardiovascular disease (CVD) (1). In patients with type 1 diabetes, atherosclerosis occurs earlier in life, leading to increased morbidity and mortality compared with those in the general population (2). Moreover, studies of the natural history of atherosclerosis development point to an origin of the lesions in childhood and adolescence (3).Lipid concentrations are strongly related to the risk of CVD in adults with diabetes (4), Although lipid levels in adults with type 1 diabetes have been described as comparable to those in nondiabetic individuals (5), adults with type 1 diabetes are known to have a higher risk for atherosclerotic disease compared with that of the general population (2). The SEARCH for Diabetes in Youth (SEARCH) study recently showed that a substantial proportion of youth aged 10–22 years with type 1 diabetes had lipid levels outside the recommended targets (6). However, it is not known whether the lipid profile (lipid concentrations and lipoprotein composition) in youth with type 1 diabetes is proatherogenic compared with that in healthy nondiabetic youth. Some data suggest that, in adults with diabetes, lipoprotein composition is more atherogenic (7) and is substantially influenced by glycemic control (8). The goals of this study were to compare the lipid and lipoprotein profile, as measured by total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, non-HDL cholesterol, the triglyceride–to–HDL cholesterol ratio, apolipoprotein B (apoB), and LDL particle size and density in youth with and without type 1 diabetes, and to explore the role of glycemic control, as measured by A1C, on the hypothesized altered lipid profile in type 1 diabetic youth.     

Apolipoproteins as markers and managers of coronary risk

Coronary artery disease (CAD) is a major cause of morbidity and mortality in Western communities. Reliable indices of coronary risk assessment and targets for drug treatment are important to the management of patients. Although plasma LDL cholesterol is well established as a predictor of CAD, it may not be the best circulatory marker. Results from recent epidemiological studies and statin trials suggest that apolipoprotein B-100 (apoB), with or without apoA-I, is superior to LDL cholesterol in predicting coronary events. Measurements of apolipoproteins are internationally standardized, automated, cost-effective and more convenient and precise than those for LDL cholesterol. ApoB may also be preferable to the measurement of non-HDL cholesterol. Measurement of apolipoproteins (apoB and possibly apoA-I) should be routinely added to the routine lipid profile (cholesterol, triglycerides and high-density lipoprotein cholesterol) to assess the atherogenic potential of lipid disorders. This is particularly relevant to dyslipidaemias characterized by an elevation in plasma triglycerides. Apolipoproteins, especially apoB, could also replace the standard "lipid profile" as a target for therapy in at-risk patients.     

A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia

OBJECTIVE: Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS: We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. RESULTS: Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005). CONCLUSIONS: Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.     

Serum lipoproteins in the diabetes control and complications trial/epidemiology of diabetes intervention and complications cohort: associations with gender and glycemia

OBJECTIVE: To relate the nuclear magnetic resonance (NMR)-determined lipoprotein profile, conventional lipid and apolipoprotein measures, and in vitro oxidizibility of LDL with gender and glycemia in type 1 diabetes. RESEARCH DESIGN AND METHODS: In the 1997-1999 Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort, serum from 428 women and 540 men were characterized by conventional lipids, NMR, apolipoprotein levels, and LDL susceptibility to in vitro oxidation. Simple and partial correlation coefficients were calculated for each lipoprotein-related parameter versus gender, with and without covariates (age, diabetes duration, concurrent HbA(1c), DCCT randomization, hypertension, BMI, waist-to-hip ratio, and albuminuria). For concurrent HbA(1c), data were analyzed as above, exchanging gender for HbA(1c). Associations were significant if P < 0.05. RESULTS: Although men and women had similar total and LDL cholesterol and triglycerides, men exhibited the following significant percent differences in NMR profiles versus women: small VLDL 41; IDL -30; medium LDL 39; small LDL 21; large HDL -32; small HDL 35; LDL particle concentration 4; VLDL and HDL diameters -8 and -4, respectively. Small VLDL, small HDL, medium LDL (women only), small LDL (men only), and LDL particle concentration were positively correlated, and HDL size was inversely correlated, with concurrent HbA(1c). NMR profile was unrelated to prior DCCT randomization. Susceptibility of LDL to oxidation was unrelated to gender and glycemia. CONCLUSIONS: Male gender and poor glycemia are associated with a potentially more atherogenic NMR lipoprotein profile. Neither gender nor glycemia influence LDL oxidation in vitro.     

Cholesterol profile measurement by vertical auto profile method

Vertical auto profile (VAP) method is a direct single test for measuring comprehensive lipoprotein cholesterol profile. It is based on a well-established method of ultracentrifugation that uses vertical rotor and single density gradient spin. VAP provides cholesterol concentrations of total lipoprotein, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), lipoprotein(a) (Lp(a)), intermediate-density lipoprotein (IDL), HDL subclasses (HDL2 and HDL3), LDL subclasses (LDL1, LDL2, LDL3, and LDL4), VLDL subclasses (VLDL1, VLDL2, and VLDL3), and LDL maximum time, which is directly proportional to LDL size. Because VAP measures additional lipoprotein classes, such as Lp(a), IDL, and subclasses of HDL, LDL, and VLDL, it can identify patients at high risk for coronary heart disease who cannot be identified using the standard lipid panel. In addition, the VAP method is compliant with the National Cholesterol Education Program's Adult Treatment Panel III guidelines.     

Cardiovascular risk reduction: What do recent trials with rosuvastatin tell us?

Abundant evidence from large-scale clinical trials supports the importance of lowering low-density lipoprotein cholesterol (LDL-C) to decrease the risk of cardiovascular disease (CVD) events. The LDL-C targets in various guidelines remain important treatment goals but, even in trials where statin therapy achieves substantial reduction of LDL-C, a significant number of CVD events still occur and the residual risk remains high. These findings suggest that lipid parameters other than LDL-C, such as high-density lipoprotein cholesterol (HDL-C), triglycerides, and LDL particle size, can influence the risk of CVD. On this basis, other strategies that can alter the lipid profile, in particular raising HDL.C, may provide additional benefits. Other factors such as HDL-C functionality and susceptibility to oxidation and inflammatory factors can also influence cardiovascular risk. In addition to the modifications of the lipid profile, statins have cholesterolindependent beneficial pleiotropic effects. The contribution of these effects to event reduction is not yet fully understood. Recently, the body of evidence has expanded to support the use of intensive statin therapy in broader patient populations. The JUPITER trial has shown the benefit of intensive statin treatment in low-risk subjects with high levels of high-sensitivity C-reactive protein and average levels of LDL-C. Unlike the setting of primary and secondary prevention, the results of statin trials in patients with heart failure have shown no clear benefit in terms of survival. The recently published AURORA trial was carried out to investigate the effect of rosuvastatin in patients with end-stage renal disease undergoing chronic hemodialysis. In this trial no benefit on cardiovascular events was shown with statin therapy. In conclusion, large outcomes trials have clearly shown that statin treatments have a favorable benefit/risk profile in a large range of patients at different levels of risk, with the exception of patients with heart failure and those with renal disease undergoing dialysis. Further evidence is needed on the role of therapeutic strategies on the so-called residual risk.     

Development of a pharmacist-managed lipid clinic

OBJECTIVE: To describe the development of a pharmacist-managed lipid clinic within a primary care medical clinic and review its results after approximately 12 months of operation. METHODS: A pharmacist-managed lipid clinic was developed at Naval Medical Center San Diego. Administrative background, treatment algorithm development, operational issues, clinical activities, and barriers to the clinic are discussed. For intermediate outcomes, data from patients who had at least 1 intervention by the pharmacist and 1 follow-up lipid panel were analyzed for medication use, changes in lipid parameters, and percent reaching the low-density-lipoprotein (LDL) target goal. Modified National Cholesterol Education Program-Adult Treatment Panel II guidelines were used to determine the LDL goal. RESULTS: Following approximately 12 months of operation, the clinic received 204 referrals and consisted of 146 active patients. A brief study was conducted to assess clinical outcomes. Of 115 patients who were seen in the clinic and met inclusion criteria, 57% were receiving treatment with a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) and 17% were receiving fibrates; 17% of the patients were not receiving lipid-lowering medications. Relative to baseline, LDL cholesterol concentrations decreased 20%, high-density-lipoprotein cholesterol increased 11%, and triglycerides decreased 19%. Overall, LDL goals were reached in 77% of the patients. LDL goals were attained by 63%, 79%, and 93% of patients with targets of <100, <130, and <160 mg/dL, respectively. Results are compared with other studies regarding lipid goal attainment. CONCLUSIONS: A pharmacist-managed lipid clinic can be developed and integrated into a primary care medical clinic. Pharmacists can effectively manage lipid-lowering therapy, helping to achieve LDL goals.     

Adverse change in low-density lipoprotein subfractions profile with oestrogen-only hormone replacement therapy

In a prospective longitudinal study in 17 women, we investigated the effects of surgical menopause and subsequent oestrogen-only hormone replacement therapy (HRT) on plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and LDL subfractions profile. Plasma LDL is a heterogeneous population of particles of varying size, density and chemical composition. The predominance of small LDL particles is a newly-recognized risk factor for coronary artery disease. The LDL score is used to describe LDL subfractions profile and the greater the score, the higher the proportion of small LDL particles. Six weeks after hysterectomy and bilateral oopherectomy, total cholesterol and triglyceride concentrations were significantly increased (p < 0.01) as well as the LDL score (p < 0.05). After 6 weeks of oestrogen-only HRT, total cholesterol concentration was significantly lower and HDL cholesterol concentration significantly higher than before the treatment (p < 0.05). At the same time, mean LDL score significantly increased and in none of the women did LDL subfractions profile change favourably.      

The effect of selective low-density lipoprotein apheresis on plasma lipoperoxides and antioxidant vitamins in familial hypercholesterolemic patients.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by a lifelong elevation in the concentration of low-density lipoprotein (LDL) bound cholesterol in blood by cholesterol deposits and by early coronary artery disease. The LDL apheresis technique has been introduced with the goal of reducing LDL cholesterol levels, thereby preventing the development of atherosclerosis. The literature on LDL apheresis reports 2 different facets, the therapeutic aspect associated with the lessening of LDL concentration and the initiation of a peroxidation process associated with the biocompatibility of the artificial membrane. Lipid and protein peroxidation gives rise to toxic and atherogenic hydroperoxide, mostly lipid hydroperoxides, and derivative compounds, which may offset the benefit of the procedure. In this paper, plasma hydroperoxide levels are determined along with the elevation of the serum and LDL antioxidant status in hypercholesterolemic patients before and following repeated LDL apheresis sessions. Hydroperoxide concentration has been expressed both in terms of plasma volume and LDL concentration. A highly significant increase in LDL lipid hydroperoxides is demonstrated when expressed in terms of LDL concentration and is associated with the LDL apheresis procedure. The usefulness of antioxidant supplementation in LDL apheresis is discussed.     

Hypertriglyceridemic hyperapoB in type 2 diabetes

OBJECTIVES: Much less attention has been paid to LDL in type 2 diabetes than to VLDL or HDL. In particular, there are few data on apoB levels in these patients. Moreover, most reports have focused on mean lipoprotein levels and consequently there is little information on the frequencies of the various dyslipidemic phenotypes. RESEARCH DESIGN AND METHODS: Plasma and lipoprotein lipids, apoB and apoA1 were measured by standardized methods. LDL particle size was determined by PAGE. The total cohort was divided into phenotypes by two different methods. The first was based on triglycerides (> or = or <1.5 mmol/l) and LDL cholesterol (> or = or <4 mmol/l), whereas the second was based on triglycerides (> or = or <1.5 mmol/l) and apoB (> or = or <120 mg/dl). RESULTS: For the overall cohort, plasma triglycerides were elevated (2.13 +/- 1.6 mmol/l), total and LDL cholesterol were normal (5.34 +/- 1.1 and 3.28 +/- 0.88 mmol/l, respectively), and peak LDL size was reduced (252.9 +/- 5.8 A). HDL cholesterol was between the 25th and 50th percentiles of the general population (1.12 +/- 0.36 mmol/l). The average level of apoB was 114 +/- 29 mg/dl, a value that is between the 50th and 75th percentiles of the general population and is higher than that for LDL cholesterol, which was between the 25th and the 50th percentiles of the population. The results of the phenotyping analysis were as follows. Using the conventional approach, only 23% has abnormal LDL, i.e., an elevated LDL cholesterol level. Using the new approach, almost 40% has an elevated apoB and therefore an elevated LDL particle number. Only 12.8% has combined hyperlipidemia based on the conventional approach, whereas almost one-third had the equivalent, hypertriglyceridemic hyperapoB-based on the new algorithm. The severity of the dyslipoproteinemia in this group was noteworthy. Although the average LDL cholesterol was 3.91 mmol/l, a value just below the 75th percentile of the general population, the average apoB was 145 mg/dl, a value that approximates the 95th percentile of the population. CONCLUSIONS: The dyslipidemic profile of patients with type 2 diabetes is not uniform. A substantial group have normal lipids and normal LDL particle number and size whereas others have markedly abnormal profiles. Diagnosis based on triglycerides and apoB rather than triglycerides and LDL cholesterol revealed that more than one in five had hypertriglyceridemic hyperapoB, which is characterized by hypertriglyceridemia, marked elevation of LDL particle number, small dense LDL, and low HDL, a constellation of abnormalities that is associated with markedly accelerated atherogenesis and therefore justifies intensive medical therapy.     

Effects of atorvastatin 10 mg and fenofibrate 200 mg on the low-density lipoprotein profile in dyslipidemic patients: A 12-week, multicenter, randomized, open-label, parallel-group study

Background: Elevated plasma low-density lipoprotein cholesterol (LDL-C) concentrations are highly atherogenic, especially the small, dense LDL (sdLDL) species. Fenofibrate has been reported to shift the LDL profile by decreasing the sdLDL subfraction and increasing larger LDL subclasses. Atorvastatin, anantihyperlipidemic agent, has been reported to reduce plasma total cholesterol (TC) and triglyceride (TG) concentrations and thus could modify the LDL profile.Objective: The aim of this study was to compare the effects of fenofi brate and atorvastatin on standard lipid concentrations and the LDL profile.Methods: In this randomized, open-label, parallel-group study, men and women aged 18 to 79 years with type II primary dyslipidemia, defined as LDL-C ≥160 and TG 150 to 400 mg/dL, after a 4- to 6-week washout period while eating an appropriate diet, were randomized to receive either atorvastatin 10 mg once daily or fenofi-brate 200 mg once daily. Plasma lipid concentrations and cholesterol and apolipoprotein (apo) B (reflecting the LDL particle number) in each LDL subfraction prepared by ultracentrifiigation were determined at baseline and after 12 weeks of treatment. Tolerability was assessed using adverse events (AEs) obtained on laboratory analysis and vital sign measurement. Adherence was assessed by counting unused drug supplies.Results: A total of 165 patients (117 men, 48 women; mean [SD] age, 50.1 [10.7] years; mean TC concentration, 289 mg/dL) were randomized to receive atorvastatin (n = 81) or fenofibrate (n = 84). Compared with fenofibrate, atorvastatin was associated with a significantly greater mean (SD) percentage decrease in TC (27.0% [12.3%] vs 16.5% [12.9%]; P < 0.001), calculated LDL-C (35.4% [15.8%] vs 17.3% [17.2%]; P < 0.001), TC/high-density lipoprotein cholesterol (HDL-C) ratio (29.1% [16.3%] vs 22.9% [15.9%]; P = 0.001), and apoB (30.3% [12.7%] vs 19.6% [15.5%]; P < 0.001). Compared with atorvastatin, fenofibrate was associated with a significantly greater decrease in TG (37.2% [25.9%] vs 20.2% [27.3%]; P < 0.001) and a significantly greater increase in HDL-C concentration (10.4% [15.7%] vs 4.6% [12.1%]; P = 0.017). Fibrinogen concentration was significantly different between the 2 groups (P = 0.002); it was decreased with fenofibrate use (4.6% [23.7%]) and was increased with atorvastatin use (5.7% [23.5%]). Atorvastatin did not markedly affect the LDL distribution; it was associated with a homogeneous decrease in cholesterol and apoB concentrations in all subfractions, whereas fenofibrate was associated with a marked movement toward a normalized LDL profile, shifting the sdLDL subfractions toward larger and less atherogenic particles, particularly in those patients with baseline TG ≥200 mg/dL. No serious AEs related to the study treatments were reported. A total of 5 AEs were observed in 8 patients, including: abdominal pain, 3 patients (2 in the atorvastatin group and 1 in the fenofibrate group); abnormal liver function test results, 1 (fenofibrate); increased creatine Phosphokinase activity, 2 (atorvastatin); gastrointestinal disorders, 1 (fenofibrate); and vertigo, 1 (fenofibrate).Conclusion: In these dyslipidemic patients, fenofibrate treatment was associated with an improved LDL subfraction profile beyond reduction in LDL-C, particularly in patients with elevated TG concentration, whereas atorvastatin was associated with equally reduced concentrations of cholesterol and apoB in all LDL subfractions independent of TG concentrations.     

Distribution of LDL particle size in a population-based sample of children and adolescents and relationship with other cardiovascular risk factors

BACKGROUND: Smaller, denser LDL particles are associated with an increased risk for cardiovascular diseases (CVD). In youths, data on the distribution of LDL particle size and on its association with other CVD risk factors are limited. METHODS: We determined LDL peak particle size by nondenaturing 2%-16% gradient gel electrophoresis in a representative sample of 2249 youths 9, 13, and 16 years of age who participated in a school-based survey conducted in 1999 in the province of Quebec, Canada. Standardized clinical measurements and fasting plasma lipid, glucose, and insulin concentrations were available. RESULTS: The LDL peak particle size distribution was gaussian. The 5th, 50th (median), and 95th percentiles by age and sex were 255.5-258.6, 262.1-263.2, and 268.1-269.5 A, respectively. The prevalence of the small, dense LDL phenotype (LDL peak particle size 相似文献   

The impact of whole-body cryotherapy on lipid profile: A systematic review and meta-analysis

PurposeWhole-body cryotherapy (WBC) is an already proven method of supportive therapy in somatic medicine. Emerging evidence suggests that WBC might exert beneficial effects on lipid profile; however, studies in this field have provided mixed findings.ObjectiveWe aimed to perform a systematic review and meta-analysis of studies investigating the impact of WBC on lipid profile.MethodsElectronic databases (the MEDLINE, the ERIC, the CINAHL Complete, the International Pharmaceutical Abstracts as well as the Academic Search Ultimate and the Health Source: Nursing/Academic Edition) were searched from their inception until 25th April 2020. Meta-analysis was performed using random-effects models and Hedges g’ was calculated as the effect size estimate.ResultsWe identified seven eligible studies. Pooled data analysis revealed significantly lower levels of triglycerides after WBC. Sensitivity analysis also demonstrated significantly lower levels of total cholesterol and low-density lipoproteins (LDL) after removing single studies. Meta-regression analysis showed that lower baseline body mass index (BMI) was significantly associated with greater changes in the levels of total cholesterol and LDL during WBC.ConclusionsOur findings imply that WBC may exert beneficial effects on the lipid profile in terms of lowering the levels of total cholesterol, LDL and triglycerides. Lower BMI may predict a greater improvement of lipid profile during WBC. However, caution should be taken as to the way our results are being interpreted due to low number of studies and considerable methodological heterogeneity of studies included in our meta-analysis.     

Studies on the Structure of Low Density Lipoproteins Isolated from Macaca Fascicularis Fed an Atherogenic Diet

Cynomolgus monkeys, Macaca fascicularis, fed cholesterol-containing saturated-fat diets develop increased levels of high molecular weight plasma low density lipoproteins (LDL), associated with accelerated atherosclerosis. To study the composition and structure of these abnormal particles, LDL from monkeys, fed atherogenic and control diets, were characterized chemically and examined by differential scanning calorimetry and low-angle X-ray scattering. LDL from animals on the experimental diet showed an increase in molecular weight (4.0 to 7.0 x 10(6), experimental diet compared with 3.0 to 3.7 x 10(6), control diet) associated with a large increase in cholesterol ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. There was a strong positive correlation between molecular weight and the number of saturated and monounsaturated cholesterol esters in the particle. In contrast, particle content of polyunsaturated cholesterol esters remained constant despite large changes in total particle cholesterol esters.When examined by calorimetry and X-ray scattering, LDL from monkeys on both diets diplayed a reversible transition of cholesterol esters from an ordered smeticlike (layered) structure to a more disordered state. For all animals on the experimental diet, the peak temperature of the cholesterol-ester transition (42-48 degrees C) was above body temperature (39 degrees C), but below body temperature on the control diet (34-38.5 degrees C). In the experimental group, the transition temperature was correlated with the LDL molecular weight. However, after thermal disruption of LDL, liquid-crystalline transitions of LDL cholesterol esters were observed in the same temperature range as in the intact lipoprotein, which shows that changes in particle size had little effect on the cholesterol-ester transition temperature. Rather, the transition temperature was determined by the degree of saturation of the LDL cholesterol ester fatty acids and the LDL cholesterol ester: triglyceride ratio, both of which correlated with increased LDL molecular weight.The existence of smectic-like cholesterol ester in LDL at body temperature was clearly a discriminating feature between monkeys on control and experimental diets. Diet-induced changes in the lipid composition of precursor lipoproteins of LDL appeared to lead to the existence of smectic-like cholesterol ester in LDL above body temperature. The altered composition and structure of the core lipids of high molecular weight LDL probably account, in part, for the previously documented correlation between increased LDL molecular weight and atherosclerosis in this species.