Low-density Lipoprotein Cholesterol Particle Size Research Articles

Effects of pemafibrate on lipid metabolism in patients with type 2 diabetes and hypertriglyceridemia: A multi-center prospective observational study, the PARM-T2D study

AimsPemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, was shown to ameliorate lipid abnormalities in a phase III clinical trial of patients with type 2 diabetes mellitus (T2DM). However, its efficacy has not been demonstrated in real-world clinical practice in patients with T2DM. MethodsWe performed a multi-center prospective observational study of the use of pemafibrate in patients with T2DM and hypertriglyceridemia versus conventional therapy, with or without a fibrate. The primary outcomes were the changes from baseline in fasting serum triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) concentrations at week 52. ResultsWe recruited 650 patients, and data from 504 (252 per group) were analyzed after propensity score matching. In the pemafibrate group, both TG and HDL-C showed significant improvements (p < 0.001), and several indices reflecting TG-rich lipoproteins, low-density lipoprotein-cholesterol particle size, and liver enzyme elevations were significantly ameliorated compared with the control group, but there was no difference in glycemic control markers. One of the key secondary endpoints showed that switching from conventional fibrates to pemafibrate improved eGFR but increased uric acid concentration. ConclusionsIn patients with T2DM, pemafibrate has superior effects on lipid profile as well as liver and renal dysfunction to conventional fibrates.

Brief Report: Progression of Atherosclerosis in HIV-Infected Individuals-Prospective Data From an Asian Cohort.

The magnitude and risk factors of progression of atherosclerosis in Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1) the rate of progression of atherosclerosis in HIV-infected individuals, and (2) metabolic and inflammatory parameters that may predict atherosclerosis progression in HIV-infected individuals in an Asian cohort. A prospective, longitudinal study was performed among adults attending an HIV Metabolic clinic in Hong Kong. Carotid intima media thickness (cIMT) was measured at baseline and 24 months. Body composition, metabolic, and inflammatory biomarkers [including homeostasis model assessment of insulin resistance, LDL (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive protein, adiponectin] associated with cIMT change were analyzed; their predictive performances were estimated using receiver operating characteristic analyses. Sixty-one HIV-infected individuals (mean ± SD age 49.8 ± 11.4 years, 89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were recruited. Annual rate of change of cIMT was +0.0075 (0.0000-0.0163) mm/yr, and 19% developed new plaque at 24 months. Two patients died during the study period, 1 because of sudden cardiac death. Using receiver operating characteristic analyses, combination of lower limb fat percentage, LDL cholesterol subclass pattern B, and lower adiponectin level, but not Framingham score, predicted greater cIMT progression in HIV-infected individuals. Asian HIV-infected individuals had atherosclerosis progression. Limb fat percentage, LDL cholesterol particle size, and adiponectin level may identify at-risk Asian HIV-infected individuals for early intervention.

An Evidence-Based Review of Exercise and Metabolic Syndrome

An Evidence-Based Review of Exercise and Metabolic Syndrome

LDL particle size and number compared with LDL cholesterol and risk categorization in end-stage renal disease patients

Few studies have been conducted that make comparisons between traditional measures of cholesterol and cholesterol subfractions, and only one study has compared low-density lipoprotein cholesterol (LDL-C) particle number, LDL-C particle size and LDL-C among end-stage renal disease (ESRD) patients. The purpose of this study was to examine the relationships between cholesterol measures and differences in risk stratification when using ATP-III guidelines compared with cholesterol particle number and size in ESRD patients. ESRD patients (n=1,092) from clinics associated with the Central Texas Nephrology Associates were recruited to participate in this study. LDL particle size categorized more patients at-risk when compared with LDL-C, non-HDL-C and triglycerides. Pearson correlation coefficients revealed a strong significant correlation between LDL-C and LDL particle number (r2=0.908, p=0.0001) and a significant correlation between LDL particle number and LDL particle size (r2=-0.290, p=0.0001). A significant but weak correlation existed between LDL-C and LDL particle size (r2=0.107, p=0.0001). A significant correlation existed between LDL particle number and triglycerides (r2=0.335, p=0.0001) and a significant inverse relationship between LDL particle size and triglycerides (r2=-0.500, p=0.0001). Our study seems to suggest that using LDL particle size may help to identify those who would not be considered at-risk using LDL-C, non-HDL-C or triglycerides alone, and can be used as a further screening measure that may be more predictive of coronary heart disease outcomes.

Serum lipid responses to phytosterol-enriched milk in a moderate hypercholesterolemic population is not affected by apolipoprotein E polymorphism or diameter of low-density lipoprotein particles

The importance of both low-density lipoprotein cholesterol (LDLc) size and the apolipoprotein E (Apo E) in the atherogenic process is known, but there is little information with regard to the effect of phytosterols (PS) on these parameters. The aim of this study was to evaluate the influence of PS on lipid profile and LDLc size according to Apo E genotype. This was a randomized parallel trial employing 75 mild-hypercholesterolemic subjects and consisting of two 3-month intervention phases. After 3 months of receiving a standard healthy diet, subjects were divided into two intervention groups: a diet group (n=34) and a diet+PS group (n=41) that received 2 g/day of PS. Total cholesterol (TC), triacylglycerols, LDLc, high-density lipoprotein cholesterol (HDLc), non-HDLc, Apo A-I and B-100, LDLc size and Apo E genotype were determined. Patients receiving PS exhibited a significant decrease in TC (5.1%), LDLc (8.1%), non-HDLc (7.4%) and Apo B-100/Apo A-I ratio (7.7%), but these effects did not depend on Apo E genotype. No significant changes were found in lipid profile according to Apo E genotype when patients following dietary recommendations were considered as a whole population or separately. No variations in LDLc size were observed in any of the intervention groups. The results of this study show that Apo E genotype does not have an impact on the lipid response to PS as a cholesterol-lowering agent in mild-hypercholesterolemic patients. Furthermore, the evidence obtained confirms that LDLc particle size is not modified when PS are added to a standard healthy diet.

Effects of ezetimibe/simvastatin on lipoprotein subfractions in patients with primary hypercholesterolemia: An exploratory analysis of archived samples using two commercially available techniques

Background:Cholesterol-rich lipoproteins, including low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol (IDL-C), and very-low-density lipoprotein cholesterol (VLDL-C), are known to promote atherosclerosis. Ezetimibe/ simvastatin (E/S) is an efficacious lipid-lowering treatment that inhibits both the intestinal absorption and biosynthesis of cholesterol. Objective:The aim of the current analysis was to compare the effects of ezetimibe and simvastatin monotherapy and E/S treatment on lipoprotein subffactions and LDL particle size in patients with primary hypercholesterolemia. Methods:This was an exploratory (hypothesis generating) analysis of archived plasma samples drawn from patients in a multicenter, randomized, double-blind, placebo-controlled, parallel-arm study. After a washout and diet/placebo run-in, patients with hypercholes- terolemia (LDL-C, ≥145-≤250 mg/dL; triglycerides, ≤350 mg/dL) were randomized equally to 1 of 10 daily treatments for 12 weeks: E/S (10/10, 10/20, 10/40, or 10/80 rag), simvastatin monotherapy (10, 20, 40, or 80 rag), ezetimibe monotherapy (10 rag), or placebo. A subset of patients had lipid subfraction measurements taken at baseline (week 0) and postrandomization (week 12). Plasma samples were used to quantify cho- lesterol associated with VLDL subfractions (VLDLI+2 and VLDL3), IDL, and 4 LDL subfractions (LDL1-4) via the Vertical Auto Profile II method. LDL-C particle size was determined using segmented gradient gel elec- trophoresis. The primary end point was median percent change in subfraction cholesterol for E/S versus ezetimibe or simvastatin monotherapy, pooled across doses. Results:Of the 1528 patients randomized in the original study, 1397 (91%) had lipid subfraction measurements taken. E/S was associated with significant reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe, simvastatin, and placebo. E/S resulted in near-additive reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe and simvastatin monotherapy. Of the subfractions examined, with regard to E/S, the greatest reductions were observed in IDL-C and LDL-C1, LDL-C2, and LDL-C3. When compared with placebo, ezetimibe, simvastatin, and E/S did not shift the distribution of LDL particles toward a larger, more buoyant LDL subclass pattern. Conclusion:E/S was more effective than ezetimibe and simvastatin monotherapy in reducing atherogenic lipoprotein subffactions in these patients with primary hypercholesterolemia. (Clin Ther. 2007;29:2419- 2432)

Analysis of Recent Papers in Hypertension

Analysis of Recent Papers in Hypertension

Effects of Atorvastatin on Low-Density Lipoprotein Cholesterol Phenotype and C-Reactive Protein Levels in Patients Undergoing Long-Term Dialysis

To determine the effects of atorvastatin on low-density lipoprotein cholesterol (LDL) particle size and C-reactive protein (CRP) concentrations in patients undergoing long-term hemodialysis. Another objective was to compare the effects of atorvastatin on lipoprotein profiles as determined by direct versus indirect assessment of lipoprotein composition. Randomized, parallel-group substudy. Two university-affiliated outpatient hemodialysis centers. Nineteen patients with LDL levels above 100 mg/dl and with at least two cardiovascular risk factors. Patients were randomized in a 1:1 ratio to atorvastatin 10 mg/day or no treatment (control) for 20 weeks. We compared the differences between LDL particle size and CRP levels at baseline and 20 weeks in the atorvastatin versus control groups. Baseline demographic characteristics were similar between the two groups. Atorvastatin therapy was associated with no change in mean LDL particle size (p=0.23) and with a 90% decrease in mean CRP level (p=0.52). When evaluated by standard chemical analysis, atorvastatin therapy reduced total cholesterol levels by 29% (p=0.025) and resulted in nonsignificant reductions in LDL, high-density lipoprotein cholesterol, and triglyceride levels. Treatment with atorvastatin was not associated with significant changes in lipoprotein profile as determined by nuclear magnetic resonance (NMR) spectroscopy. Treatment with atorvastatin did not affect LDL particle size but was associated with a sizable, yet nonsignificant, reduction in CRP concentrations. The drug had variable effects on lipoprotein concentrations as determined by chemical and NMR analytical methods. A larger study is necessary to provide definitive information on the effects of atorvastatin on LDL phenotype and CRP in patients with kidney disease.

The metabolic syndrome: pathophysiology, clinical relevance, and use of niacin.

To review the pathophysiology and clinical relevance for using niacin to treat the metabolic syndrome. Primary articles were identified through a MEDLINE search (1966-January 2003), and recommendations for treatment were obtained from the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III guidelines. Published studies showing the effects of the metabolic syndrome, atherogenic dyslipidemia, and niacin were evaluated and reviewed. The metabolic syndrome is a highly prevalent condition that affects 24% of American adults and significantly increases the risk of coronary heart disease (CHD). Most patients with metabolic syndrome have atherogenic dyslipidemia characterized by elevated triglycerides, low high-density-lipoprotein cholesterol (HDL-C), and small, dense low-density-lipoprotein cholesterol (LDL-C) particles. The NCEP-ATP III identifies patients with the metabolic syndrome as candidates for intensified therapy. Lifestyle modifications and drug therapy are recommended. Niacin represents a good option for treating the triad of lipid abnormalities seen in the metabolic syndrome because it raises HDL-C, lowers triglycerides, and increases LDL-C particle size. Treatment of the metabolic syndrome is recommended by NCEP-ATP III to further reduce CHD risk after the LDL-C target has been met. Prospective clinical studies are needed to define the impact of niacin and other lipid-modifying agents on CHD morbidity and mortality in patients with the metabolic syndrome.

Peroxisome Proliferator-Activated Receptor-γ Agonist Increases Both Low-Density Lipoprotein Cholesterol Particle Size and Small High-Density Lipoprotein Cholesterol in Patients with Type 2 Diabetes Independent of Diabetic Control

To ascertain whether troglitazone, independent of control of diabetes, increases low-density lipoprotein (LDL) particle size. We administered 600 mg of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist) daily for 8 weeks to 10 patients with type 2 diabetes (8 of whom completed the study). Then troglitazone therapy was discontinued, and alternative medication for diabetic control was used for another 4 weeks. The LDL, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations and subpopulations, as well as blood glucose and hemoglobin A1c (HbA1c), were determined at weeks 0, 4, 8, and 12 and analyzed statistically. Small, dense LDL cholesterol is commonly seen in patients with diabetes and is thought to be associated with an increased risk for coronary artery disease. After both 4 and 8 weeks of troglitazone therapy, control of diabetes was significantly improved (mean HbA1c values at baseline, week 4, and week 8 were 8.0 +/- 0.7%, 7.4 +/- 0.5%, and 7.0 +/- 0.7%, respectively; P<0.05). HbA1c (6.5 +/- 0.6% at 12 weeks) and blood glucose levels (126 +/- 19 mg/dL at 8 weeks versus 145 +/- 9 mg/dL at 12 weeks) were not significantly different 4 weeks after troglitazone therapy was discontinued. Troglitazone treatment increased the large LDL particle at 4 and 8 weeks, a change that significantly (P<0.05) enlarged the LDL particle size (20.5 +/- 0.3 nm, 21.2 +/- 0.3 nm, and 21.3 +/- 0.2 nm at baseline, week 4, and week 8, respectively). After 8 weeks of troglitazone therapy, VLDL triglycerides were reduced (195 +/- 37 mg/dL versus 136 +/- 28 mg/dL; P<0.05) and HDL was increased (31.6 +/- 2.4 mg/dL versus 35.5 +/- 2.9 mg/dL; P<0.05). This greater HDL value was due to an increase in the small HDL particles. A decrease in the larger VLDL particles (V5 and V6) resulted in a reduction in the mean VLDL particle size (59 +/- 3 nm versus 46 +/- 2 nm; P<0.05). Despite the fact that control of diabetes remained significantly improved after troglitazone therapy was discontinued, the LDL particle size decreased to the baseline value. This change was due to a reduction in the large LDL cholesterol particle (L3). This study shows that troglitazone therapy increases LDL particle size, reduces VLDL particle size, and increases small HDL particles. These changes may lower the risk for coronary artery disease.