Mean Low-density Lipoprotein Particle Size Research Articles

Association between triglyceride-glucose index and low-density lipoprotein particle size in korean obese adults

BackgroundSmall dense low-density lipoprotein cholesterol (sdLDL-C) is the lipoprotein marker among the various lipoproteins that is most strongly related to atherosclerosis. Insulin resistance (IR) can alter lipid metabolism, and sdLDL-C is characteristic of diabetic dyslipidemia. Therefore, this study sought to inspect the relationship between the triglyceride-glucose (TyG) index and mean low-density lipoprotein (LDL) particle size.MethodsIn this study, a total of 128 adults participated. The correlation coefficients between various lipoproteins and the TyG index were compared using Steiger’s Z test and the Spearman correlation. The independent link between the TyG index and mean LDL particle size was demonstrated by multiple linear regression analysis. To identify the TyG index cutoff value for the predominance of sdLDL particles, receiver operating characteristic curves were plotted.ResultsMean LDL particle size correlated more strongly with the TyG index than did very low-density lipoprotein, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Regression analysis demonstrated that mean LDL particle size had a strong association with the TyG index (β coefficient = -0.038, P-value < 0.001). The TyG index optimal cutoff value for sdLDL particle predominance and the corresponding area under the curve (standard error: 0.028, 95% confidence interval: 0.842–0.952) were 8.72 and 0.897, respectively, which were close to the cutoff value of diabetes risk in Koreans.ConclusionsMean LDL particle size is more strongly correlated with the TyG index than do other lipid parameters. After correcting for confounding variables, mean LDL particle size is independently linked with the TyG index. The study indicates that the TyG index is strongly related to atherogenic sdLDL particles predominance.

High-Dose DHA Has More Profound Effects on LDL-Related Features Than High-Dose EPA: The ComparED Study.

Supplementation with high-dose docosahexaenoic acid (DHA) increases serum low-density lipoprotein (LDL) cholesterol (LDL-C) concentrations more than high-dose eicosapentaenoic acid (EPA). The mechanisms underlying this difference are unknown. To examine the phenotypic change in LDL and mechanisms responsible for the differential LDL-C response to EPA and DHA supplementation in men and women at risk of cardiovascular disease. In a double-blind, controlled, crossover study, 48 men and 106 women with abdominal obesity and subclinical inflammation were randomized to a sequence of three treatment phases: phase 1, 2.7 g/d of EPA; phase 2, 2.7 g/d of DHA; and phase 3, 3 g/d of corn oil. All supplements were provided as three 1-g capsules for a total of 3 g/d. The 10-week treatment phases were separated by a 9-week washout period. In vivo kinetics of apolipoprotein (apo)B100-containing lipoproteins were assessed using primed-constant infusion of deuterated leucine at the end of each treatment in a subset of participants (n = 19). Compared with EPA, DHA increased LDL-C concentrations (+3.3%; P = 0.038) and mean LDL particle size (+0.7 Å; P < 0.001) and reduced the proportion of small LDL (-3.2%; P < 0.01). Both EPA and DHA decreased proprotein convertase subtilisin/kexin type 9 concentrations similarly (-18.2% vs -25.0%; P < 0.0001 vs control). Compared with EPA, DHA supplementation increased both the LDL apoB100 fractional catabolic rate (+11.4%; P = 0.008) and the production rate (+9.4%; P = 0.03). The results of the present study have shown that supplementation with high-dose DHA increases LDL turnover and contributes to larger LDL particles compared with EPA.

Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia

Background and aimsSitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported. MethodsSitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis. ResultsEZE reduced (p < 0.05) total sterols (−12.5 ± 4.1%) and LDL-sterol (−22.7 ± 5.7%) and its sterol mass of large VLDL (−24.4 ± 4.5%), VLDL remnants (−21.1 ± 7.9%) and large IDL (−22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (−21.8± 5.0%), total sterols/HDL (−28.2 ± 5.5%) and TG/HDL (−27.4 ± 6.5%, all p < 0.01). ConclusionsEZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction.

SUBFRACTION DISTRIBUTION OF APO B-CONTAINING LIPOPROTEINS DEPENDING ON THE ACHIEVEMENT OF THE TARGET LEVEL OF LOW DENSITY LIPOPROTEINS UNDER STATINS THERAPY IN PATIENTS WITH CORONARY ATHEROSCLEROSIS

Aim. To reveal whether there are differences in subfractional distribution of apo B-containing lipoproteins in men and women with coronary atherosclerosis treated with statins depending on low density lipoprotein (LDL) cholesterol level. Material and methods . Patients aged 33-85 years with angiography documented coronary atherosclerosis were included into the study (n=133): 97 men (mean age 61±9.0 years) and 36 postmenopausal women (mean age 65±9.3 years). Patients were on statin therapy at least 6 months before admission: atorvastatin (10-40 mg/day), simvastatin (20-40 mg/day), rosuvastatin (10-40 mg/day) and pravastatin (20 mg/day). Subfractional apo B-containing lipoproteins distribution was analyzed by electrophoresis in a 3% polyacrylamide gel. Results. Men achieving target LDL cholesterol level (<2.5 mmol/l) as compared with those with higher LDL cholesterol level alongside with decreased proatherogenic lipids and apolipoproteins, had less atherogenic LDL subfractional profile: lower portion of LDL 2 (7.3±3.4 и 9.9±3.9%, p<0.01), small dense LDL 3 (1.3±1.2 и 2.2±2.2%, р<0.05), LDL 4 (0.2±0.2 и 0.3±0.5%, p<0.05), and concentration of cholesterol in this subfrtactions. These differences were associated with elevated mean size of LDL particles (270.8±3.0 vs 268.8±3.9 A, p<0,01). On the other hand, women, despite achieving target LDL cholesterol level, had elevated apo B level and apo B/AI ratio without any differences in subfractional profile of low densities lipoproteins. Conclusion. In patients with coronary atherosclerosis treated with statins, antiatherogenic shifts in apo B-containing lipoproteins, decrease of cholesterol concentration subfractions coupled by elevation of mean LDL particle size were found only in men who reached target LDL cholesterol level.

Circulating non–HDL-C levels were more relevant to atherogenic lipoprotein subfractions compared with LDL-C in patients with stable coronary artery disease

Conflicting results have been yielded as to whether low-density lipoprotein (LDL) cholesterol (LDL-C) or non-high-density lipoprotein (HDL) cholesterol (non-HDL-C) is a better marker of coronary artery disease (CAD) risk. Recently, plasma LDL and HDL subfractions have been suggested to be more accurately reflecting the lipoproteins' atherogenicity. We sought to compare the relationship between LDL-C or non-HDL-C and lipoprotein subfractions. We conducted a cross-sectional study in 351 consecutive stable CAD patients without lipid-lowering therapy. The LDL and HDL separations were performed using the Lipoprint System. The LDL-C levels were measured directly, and the non-HDL-C levels were calculated. The cholesterol concentrations of LDL (large, medium, and small) and HDL (small) particles were increased (all P<.001) by non-HDL-C or LDL-C quartiles, whereas the mean LDL particle size and cholesterol concentrations of HDL (large) were decreased (both P<.001) by non-HDL-C quartiles. In age- and gender-adjusted analysis, the cholesterol in small LDL was much strongly related to non-HDL-C than to LDL-C (r=0.539 vs 0.397, both P<.001). Meanwhile, the mean LDL particle size was more closely associated with non-HDL-C than LDL-C (r=-0.336 vs r=-0.136, both P<.05). Significantly, the cholesterol in large HDL was negatively correlated with non-HDL-C (r=-0223, P<.001) but not with LDL-C. These correlations were further confirmed by the fully adjusted multivariable linear regression analysis. Non-HDL-C, in comparison to LDL-C, was more relevant to atherogenic lipoprotein subfractions in patients with stable CAD, supporting that it may be better in assessing cardiovascular risk.

Differential Genetic Effects on Statin-Induced Changes Across Low-Density Lipoprotein-Related Measures.

Statin therapy influences not only low-density lipoprotein (LDL) cholesterol levels but also LDL-related biomarkers, including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total number of LDL particles, and mean LDL particle size. Recent studies have identified many genetic loci influencing circulating lipid levels and statin-induced LDL cholesterol reduction. However, it is unknown how these genetic variants influence statin-induced changes in LDL subfractions and non-HDL-C. One hundred sixty candidate single-nucleotide polymorphisms for effects on circulating lipid levels or statin-induced LDL-cholesterol lowering were tested for association with response of LDL subfractions and non-HDL-C to rosuvastatin or placebo for 1 year among 7046 participants from the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Of the 51 single-nucleotide polymorphisms associated with statin response for ≥ 1 of the LDL subfractions or non-HDL-C, 20 single-nucleotide polymorphisms could be clustered according to effects predominantly on LDL particle size, predominantly on LDL particle number, and on apolipoprotein B but not on LDL cholesterol or non-HDL-C. These differential associations point to pathways of LDL response to statin therapy and possibly to mechanisms of statin-dependent cardiovascular disease risk reduction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Analysis of Lipoprotein Subfractions in Chinese Han Patients with Stable Coronary Artery Disease

The relation of lipoprotein subfractions with stable coronary artery disease (CAD) has not been fully investigated in the Chinese Han population. Four-hundred-and-thirteen consecutive patients without any lipid-lowering drug treatment were investigated. Patients were classified into two groups according to the angiographic results: CAD group (n=293) and non-CAD group (n=120). The high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subfractions were analysed using the Quantimetrix Lipoprint system. The data showed that the large HDL-cholesterol (HDL-C) level, large HDL subfraction percentage, and mean LDL particle size were significantly lower, while the small HDL-C level and HDL subfraction percentage, intermediate and small LDL-cholesterol (LDL-C) levels, and LDL subfraction percentages were higher in the CAD group compared with those in the non-CAD group. Interestingly, our results suggested that the small HDL-C level and HDL subfraction percentage as well as mean LDL particle size were independently associated with the presence of CAD assessed by logistic regression analysis (OR=1.136, 95%CI=1.018-1.268, p=0.022; OR=1.076, 95%CI=1.021-1.134, p=0.007; OR=0.946, 95%CI=0.898-0.997, p=0.040; respectively). Similar to previous Western population studies, our data suggested a clear association between the lipoprotein subfractions and stable CAD presented as higher small HDL subfraction and smaller mean LDL particle size in Chinese Han patients.

Systemic Inflammatory Markers Are Closely Associated with Atherogenic Lipoprotein Subfractions in Patients Undergoing Coronary Angiography.

Objective. To investigate the relationship between inflammatory markers and atherogenic lipoprotein subfractions. Methods. We studied 520 eligible subjects who were not receiving any lipid-lowering therapy. The inflammatory markers including white blood cell (WBC) count, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR), and D-dimer were measured. A multimarker inflammatory index was developed. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) separation processes were performed using Lipoprint System. Results. In age- and sex-adjusted analysis, several inflammatory markers (WBC count, hs-CRP, fibrinogen, and ESR) were positively related to circulating non-HDL cholesterol and remnant cholesterol (p < 0.05, all). Among lipoprotein subfractions, we observed a positive association of inflammatory markers with very low-density lipoprotein cholesterol, small LDL cholesterol, and LDL score (p < 0.05, all). Meanwhile, a negative association was detected between inflammatory markers and mean LDL particle size (p < 0.05) or large HDL cholesterol (p < 0.05). Moreover, we found that the relationships between multimarker index quartiles and small LDL cholesterol, LDL score, and mean LDL particle size were slightly stronger in patients with CAD. Conclusions. Systemic inflammatory markers are positively correlated with small LDL cholesterol and LDL score while being negatively linked with mean LDL particle size and large HDL cholesterol, highlighting the potential contribution to increased cardiovascular risk.

Relation of plasma PCSK9 levels to lipoprotein subfractions in patients with stable coronary artery disease.

BackgroundPlasma PCSK9 levels was positively associated with low-density lipoprotein (LDL) cholesterol (LDL-C) and atherosclerosis, while PCSK9 may also be implicated in the metabolism of lipoprotein subfractions. The study was to examine the association of plasma PCSK9 with lipoprotein subfractions in patients with stable coronary artery disease (CAD).MethodsA total of 281 consecutive, stable CAD patients who were not treated with lipid-lowering drugs were enrolled. The baseline clinical characteristics were collected, the plasma PCSK9 levels were determined using ELISA, and the LDL and high-density lipoprotein (HDL) subfractions were analyzed by Lipoprint System. The association of plasma PCSK9 levels with the lipoprotein subfractions was investigated.ResultsIn the overall population, plasma PCSK9 levels were positively associated with the concentration of LDL-C, intermediate LDL-C, small LDL-C, and LDL score, while negatively correlated with mean LDL particle size. PCSK9 levels were positively associated with the concentration of HDL-C, intermediate HDL-C and small HDL-C. Multivariable regression analysis revealed that the plasma PCSK9 levels were significantly and independently associated with the concentration of intermediate LDL-C (β = 0.152, p = 0.013), small LDL-C (β = 0.179, p = 0.004), LDL score (β = 0.121, p = 0.043), and mean LDL particle size (β = -0.130, p = 0.035), while not HDL subfractions. Interestingly, when investigated in male and female patients separately, these relationships were only found in male but not in female, and the small HDL-C exhibited an association with PCSK9 levels in male patients (β = 0.149, p = 0.045).ConclusionsPCSK9 levels were independently associated with the changes of lipoprotein subfractions, suggesting a potential interaction between PCSK9 and lipoprotein subfractions in CAD.

Participation in a Social-Support Physical Activity Intervention Modestly Improves Lipoprotein Cholesterol Distribution Among Postpartum Sedentary Hispanic Women.

The effects of moderate intensity walking on lipoprotein remodeling in postpartum Hispanic women are unknown. Sedentary postpartum Hispanic women (28.2 ± 5.6 y; BMI = 29.3 ± 3.3 kg/m2) participating in a social support physical activity (PA) intervention, were randomly assigned to a 12-month walking program (walkers; n = 22; target 150 min/wk, moderate intensity) or a control group (nonwalkers; n = 22). Fasting lipids and cholesterol distribution within low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles were measured at baseline (BL), 6 months, and 12 months. Walkers had an 11% increase and nonwalkers a 7% decrease in HDL cholesterol from 6 to 12 months (P = .0367) without an effect on LDL cholesterol. Whereas nonwalkers had virtually no change in mean LDL particle size, walkers had a borderline reduction in LDL size from BL (268.7 ± 4.1 Å) to 6 months (266.9 ± 4.9 Å), followed by a significant increase in size by 12 months (269.7 ± 4.1 Å; P = .011). The proportion of cholesterol in large LDL particles decreased by 15% from BL to 6 months, but subsequently increased 25% by 12 months among walkers; changes among nonwalkers were smaller and in opposite direction (4% and -3%, respectively; P = .0004). Participation in the social-support PA intervention resulted in slightly increased HDL cholesterol concentrations and a modest and beneficial shift toward larger, less atherogenic LDL particles.

Impact of short-term low-dose atorvastatin on low-density lipoprotein and high-density lipoprotein subfraction phenotype.

Statins can significantly reduce low-density lipoprotein-cholesterol (LDL-C) and modestly raise or not alter high-density lipoprotein-cholesterol (HDL-C). However, their impact on high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subfractions has been less examined. The aim of the present study was to investigate the short-term impact of low-dose atorvastatin on HDL and LDL subfractions in humans. In this randomized study, data from 52 subjects were analysed. Thirty-seven patients with atherosclerosis were randomized to treatment with atorvastatin 10 mg/day (n = 17) or 20 mg/day (n = 20) for 8 weeks, with 15 healthy subjects without therapy used as a control group. The lipid profile and lipoprotein subfractions were determined using the Lipoprint system at baseline and at 8 weeks. The data suggest that atorvastatin treatment (10 and 20 mg/day) for 8 weeks significantly decreases LDL-C levels and reduces the cholesterol concentration of all LDL subfractions, which is accompanied by an increase of the mean LDL particle size. Although 10 mg/day atorvastatin treatment for 8 weeks had no impact on the HDL subfraction, 20 mg/day atorvastatin for 8 weeks significantly increased the cholesterol concentration of large HDL particles and decreased the cholesterol concentration of small HDL particles without changing serum HDL-C levels in patients with atherosclerosis. Therefore, the results suggest that 20 mg/day atorvastatin treatment for 8 weeks may result in a favourable modification of the HDL subfraction phenotype in addition to its effects on the cholesterol concentration of all LDL subfractions and mean LDL particle size.

Heterogeneous properties of intermediate- and low-density lipoprotein subpopulations

ObjectiveIntermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) consist of heterogeneous particles whose subpopulations may have different atherogenic characteristics. This study investigated the associations between these subpopulations and other lipids, lipoproteins and atherosclerosis-related markers. Design and methodsA total of 416 subjects (124 males and 292 females, mean age: 50.8years) were enrolled in this study. Using polyacrylamide gel electrophoresis, serum lipoproteins were separated according to their specific electrophoretic mobility based on particle size. The IDL particles were separated into three midbands (MID-A to C), and the LDL particles were separated into seven subfractions (LDL1 to 7). ResultsMID-B, MID-C, LDL2 and LDL3 to 6 (as a small LDL fraction) were significantly and positively correlated with very LDL (VLDL), while MID-A and LDL1 were significantly and inversely correlated with VLDL. MID-A and LDL1 were significantly and positively correlated with high-density lipoprotein (HDL). The correlation patterns between MID-A or LDL1 and triglycerides, apolipoprotein A-I, glucose, the insulin resistance index, creatinine and the mean LDL particle size had similar trends to those between HDL and these parameters. ConclusionsThe respective subpopulations of IDL and LDL particles can vary in their ability to predict cardiovascular disease risks. These variations may partially explain why quantitative assessments using LDL-cholesterol concentrations, as typically performed in conventional practice, are not perfect predictors of cardiovascular disease. Further studies are required to determine the clinical relevance of analyzing the IDL and LDL subpopulations.

Lifestyle intervention improves lipoprotein particle size and distribution without weight loss in obese Latino adolescents

Childhood obesity is associated with a pro-atherogenic phenotype contributing to increased cardiovascular disease (CVD) risk. This single-arm pilot study examined the effects of a lifestyle intervention on lipoprotein particle size and cholesterol distribution in obese Latino adolescents. Fifteen obese Latino adolescents (15.0 ± 1.0 years) completed a 12-week nutrition education and exercise intervention. Low-density lipoprotein (LDL) particle size and distribution of cholesterol in lipoprotein subclasses were determined via polyacrylamide gel electrophoresis. The intervention resulted in increases in mean LDL particle size (269.3 ± 3.4 to 271.6 ± 2.9 Å, P = 0.0003) and cholesterol in large high-density lipoprotein (HDL) subfractions (22.4 ± 11.2 to 26.8 ± 10.6% area, P = 0.007) along with decreases of cholesterol in small LDL (1.6 ± 2.0 to 0.6 ± 1.2% area, P < 0.01) and HDL subfractions (23.2 ± 9.4 to 19.0 ± 6.7% area, P = 0.05). These improvements were observed independent of changes in weight (90.7 ± 26.2 to 89.9 ± 27.8 kg, P > 0.05) and suggest that lifestyle modification in obese youth may reduce cardiovascular risk by shifting lipoprotein particle size and cholesterol distribution to a less atherogenic phenotype.

Effects of patient-tailored atorvastatin therapy on ameliorating the levels of atherogenic lipids and inflammation beyond lowering low-density lipoprotein cholesterol in patients with type2 diabetes.

Recently, patient-tailored statin therapy was proven effective for achieving target low-density lipoprotein (LDL) cholesterol levels. It is unclear, however, whether this therapeutic modality would be effective for atherogenic lipid profiles and inflammation in patients with type2 diabetes. The present study was an 8-week, multicenter, single-step titration trial of patient-tailored atorvastatin therapy (10, 20 and 40mg) according to baseline LDL cholesterol levels in 440 patients with type2 diabetes. We measured the LDL particle size by polyacrylamide gel electrophoresis, and used high-sensitivity C-reactive protein (hsCRP) and adiponectin as surrogate markers of inflammation. In the intention-to-treat analysis, 91% of the patients achieved their LDL cholesterol targets (<2.6mmol/L) at week8. There were significant reductions at week8 in total cholesterol, triglycerides, non-high-density lipoprotein cholesterol (HDL) cholesterol, and the total cholesterol:HDL cholesterol ratio compared with the baseline values for all of the doses. The mean LDL particle size was significantly increased, and the small, dense LDL cholesterol levels were decreased in a dose-dependent manner over the study period. In addition, the hsCRP levels were decreased in those high-risk patients with baseline hsCRP levels over 3mg/L (P<0.001), and the adiponectin levels tended to increase with all of the doses (P=0.004) at 8weeks. Patient-tailored atorvastatin therapy based on LDL cholesterol at baseline was effective in ameliorating atherogenic LDL particle size and inflammation, in addition to achieving the target LDL cholesterol level without an undesirable effect on glycemic control in patients with type2 diabetes. This trial was registered with ClinicalTrials.gov (no. NCT01239849).

Low-density lipoprotein subfraction, carotid artery intima-media thickness, nitric oxide, and tumor necrosis factor alpha are associated with newly diagnosed ischemic stroke

Objectives:Small dense (sd) low-density lipoprotein (LDL), tumor necrosis factor (TNF) alpha (α), and nitric oxide (NO) have recently emerged as important stroke risk factors. The aim of the study was to investigate the effects of increased levels of small LDL particle size, TNF-α and NO on the developed ischemic stroke and increased carotid artery intima-media thickness (CIMT).Materials and Methods:A total of 29 women and 25 men (a total of 54 ischemic stroke patients) and a similar age group of 50 controls (29 females and 21 males) were included in the study. CIMT, C-reactive protein (CRP), TNF-α, NO, and lipid subfraction test of the two groups were measured.Results:The mean LDL particle size was smaller in patients with stroke than in the controls (26.8 ± 0.31 nm vs. 27.0 ± 0.31 nm, P = 0.003). sd-LDL, TNF-α, NO, CRP, right CIMT, and left CIMT were higher in patients with stroke than in the controls (respectively; 8.2 ± 7.8 mg/dL vs. 3.3 ± 3.5 mg/dL, P < 0.001;75.6 ± 25.0 pg/mL vs. 65.4 ± 9.1 pg/mL, P = 0.009;76.4 ± 53.3 mmol/L vs. 41.5 ± 27.0 mmol/L, P < 0.001;1.9 ± 2.6 mm vs. 0.4 ± 0.3 mm P < 0.001;0.97 ± 0.38 mm vs. 0.83 ± 0.15 mm, P = 0.007;1.04 ± 0.44 mm vs. 0.87 ± 0.19 mm, P = 0.010).Conclusion:These results show that sd-LDL is independently associated with the incidence of stroke and may be a risk factor in the development of stroke. In addition, TNF-α, NO, right CIMT, and left CIMT may be a risk factor in the development of ischemic stroke.

Dyslipidemia in women with polycystic ovary syndrome

Dyslipidemia is a very common metabolic abnormality in women with polycystic ovary syndrome (PCOS). Insulin resistance is a key pathophysiology of PCOS, thus dyslipidemia in women with PCOS may be consistent with those found in an insulin resistant state. In recent meta-analysis, triglycerides and low-density lipoprotein (LDL) cholesterol levels were 26 mg/dL and 12 mg/dL higher, and high-density lipoprotein cholesterol concentration was 6 mg/dL lower in women with PCOS than those of controls. Alterations in LDL quality also have been reported in women with PCOS: women with PCOS have an increased proportion of atherogenic small dense LDL or decreased mean LDL particle size. However, in a recent Korean study, non-obese Korean women with PCOS had no significant quantitative or qualitative changes in LDL cholesterol profile. Lipoprotein (a) has been identified as an independent risk factor for coronary heart disease, and its elevation in PCOS patients has been consistently reported in diverse studies including non-obese Korean population. Some studies have investigated apolipoprotein (Apo) A-I and ApoC-I levels in women with PCOS and levels of ApoA-I, which has cardio-protective effects, were significantly lower in women with PCOS than those of controls. ApoC-I is known to increase the postprandial serum lipid level that is common in coronary artery disease patients, and one study reported that such an elevation may be the earliest variation of lipid abnormality in women with PCOS. In conclusion, women with PCOS should receive a complete lipid test, and lifestyle modification, including diet and exercise, is the first line therapy for all women with PCOS and is particularly important for those with dyslipidemia.

Reduced growth hormone secretion in obesity is associated with smaller LDL and HDL particle size

Reduced growth hormone (GH) secretion is observed in obesity and may contribute to increases in cardiovascular disease (CVD) risk. Lipoprotein characteristics including increased small dense low-density lipoprotein (LDL) particles are known independent risk factors for CVD. We hypothesized that reduced GH secretion in obesity would be associated with a more atherogenic lipid profile including increased small dense LDL particles. To evaluate this hypothesis, we studied 102 normal weight and obese men and women using standard GH stimulation testing to assess GH secretory capacity and performed comprehensive lipoprotein analyses including determination of lipoprotein particle size and subclass concentrations using proton NMR spectroscopy. Obese subjects were stratified into reduced or sufficient GH secretion based on the median peak-stimulated GH (≤6·25 μg/l). Obese subjects with reduced GH secretion (n = 35) demonstrated a smaller mean LDL and HDL particle size in comparison to normal weight subjects (n = 33) or obese subjects with sufficient GH (n = 34) by ANOVA (P < 0·0001). Univariate analyses demonstrated peak-stimulated GH was positively associated with LDL (r = 0·50; P < 0·0001) and HDL (r = 0·57; P < 0·0001), but not VLDL (P = 0·06) particle size. Multivariate regression analysis controlling for age, gender, race, ethnicity, tobacco, use of lipid-lowering medication, BMI and HOMA demonstrated peak-stimulated GH remained significantly associated with LDL particle size (β = 0·01; P = 0·01; R(2) = 0·42; P < 0·0001 for overall model) and HDL particle size (β = 0·008; P = 0·001; R(2) = 0·44; P < 0·0001 for overall model). These results suggest reduced peak-stimulated GH in obesity is independently associated with a more atherogenic lipoprotein profile defined in terms of particle size.

Distinct effects of fixed combinations of valsartan with either amlodipine or hydrochlorothiazide on lipoprotein subfraction profile in patients with hypertension

The effect of antihypertensive drugs on lipoprotein subfraction profile is still under investigation. In this study the effects of fixed combination of valsartan with either amlodipine (V-A) or hydrochlorothiazide (V-H) on low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) subfraction profile of patients with stage 2 or 3 hypertension were assessed. A total of 60 drug-naive patients were randomized to either V-A (160/5 mg, n=30) or V-H (160/12.5 mg, n=30). At baseline as well as 16 weeks post-treatment analysis of the LDL and HDL subfraction profile was conducted by using LDL Lipoprint System. Both V-A and V-H effectively reduced blood pressure (BP) to similar levels. An increase in the cholesterol concentration of small-dense LDL subfractions (by 18.2%, P<0.05) was observed in the V-H group, whereas this parameter remained unchanged in the V-A group. Therefore, mean LDL particle size was decreased in the V-H group (from 267 ± 5 to 266 ± 5Å, P<0.05). HDL-Cholesterol (HDL-C) levels were reduced by 4.7% (P<0.05) in the V-H group, mirrored by a reduction in the cholesterol mass of small and intermediate HDL particles. In conclusion, despite similar reductions in BP, V-H combination may adversely affect serum lipids as well as LDL and HDL subfraction profile as compared with V-A.

Apolipoprotein B, oxidized low-density lipoprotein, and LDL particle size in predicting the incidence of metabolic syndrome: the Cardiovascular Risk in Young Finns study

To test whether serum apolipoprotein B (apoB) and low-density lipoprotein (LDL) particle characteristics (oxidation and mean particle size) predict the incidence of metabolic syndrome (MetS). The 6-year follow-up study included 1429 adults (baseline mean age 31.5). Lipids, apoB, and apoA1 were measured at baseline in 2001. LDL oxidation was measured with monoclonal antibody-based enzyme-linked immunosorbent assay (oxLDL-prot) and with a method measuring oxidized lipids in LDL (oxLDL-lipids). Mean LDL particle size was calculated from proton nuclear magnetic resonance spectroscopy data. Increased concentrations of both oxLDL-measures were associated with increased apoB levels but not with LDL particle size. The odds ratios (95% confidence intervals) for MetS incidence during a 6-year follow up by quartiles of apoB were 2.0 (1.0-3.8) for the second quartile, 3.1 (1.7-5.7) for the third quartile, and 4.2 (2.3-7.6) for the fourth quartile. This association remained after adjusting for age, sex, body mass index, homeostasis model assessment for insulin resistance, C-reactive protein, smoking, LDL cholesterol, oxidized LDL measures (p ≤ 0.01) in addition to risk factors comprising the MetS (p = 0.03). OxLDL-prot and oxLDL-lipids levels were not independently associated with incident MetS after adjusting for apoB. Mean LDL particle size was not associated with the incidence of MetS. ApoB is associated with increased risk of MetS incidence. We found no clear evidence to suggest that increased LDL oxidation or small mean LDL particle size would facilitate the development of MetS.

Cholesteryl ester transfer protein, low density lipoprotein particle size and intima media thickness in patients with coronary heart disease

Cholesteryl ester transfer protein (CETP) plays a key role in reverse cholesterol transport and high density lipoprotein (HDL) metabolism. Predominance of small, dense LDL particles is associated with an increased risk of atherosclerosis and coronary heart disease (CHD).The aim of the study was to determine the potential relationship between the CETP concentration and low density lipoprotein (LDL) particle size and their association with intima media thickness (IMT) in patients with CHD. Lipid parameters, CETP concentration and LDL particle size were determined in 100 healthy subjects (control group) and in 100 patients with CHD, aged 43 to 77 years. Plasma CETP concentrations were measured by an enzyme-linked immuno-sorbent assay with two different monoclonal antibodies. LDL subclasses were separated by nondenaturing polyacrilamide 3-31% gradient gel electrophoresis. CETP concentration was higher in patients compared to controls (2.02 ± 0.75 mg/ml vs. 1.74 ± 0.63 mg/ml, p<0.01). Mean LDL particle size (nm) was significantly smaller in patients than in controls (24.5 ± 1.1 vs. 26.1 ± 0.9; p<0.001). There was no relation between LDL particle size and CETP concentration (r=-0.1807, p=0.072). Age, diastolic blood pressure, CETP concentration and LDL particle size were independent factors for determing IMT by multiple linear regression analysis. They accounted for 35.2 % of the observed variability in IMT. CETP is not an independent contributor of LDL particle size. CETP might play a role in determining lipoprotein distributions, but did not seem to be the sole factor in the formation of small LDL particles.