Dense Low-density Lipoprotein Cholesterol Levels Research Articles

Specific Increase in Small Dense Low-Density Lipoprotein-Cholesterol Levels beyond Triglycerides in Patients with Diabetes: Implications for Cardiovascular Risk of MAFLD.

Small dense (sd) low-density lipoprotein (LDL)-cholesterol (C) is the most powerful predictor of cardiovascular (CV) disease among lipid biomarkers and is generated by hypertriglyceridemia and insulin resistance. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed liver disease with a high CV risk. We investigated the specific association of sdLDL-C with MAFLD beyond triglycerides (TG) and obesityMethods: Participants were 839 non-alcoholic drinkers with type 2 diabetes enrolled in a regional diabetes cohort. Fatty liver (FL) and visceral fat area (VFA) was detected by computed tomography scan. sdLDL-C and LDL-TG were measured by our established homogeneous assay. TG rich lipoprotein (TRL) was calculated by subtracting LDL-C plus HDL-C from total-C. Grade of sdLDL-C (≤ 24, 25-34, 35-44, and ≥ 45 mg/dL) was classified according to the Hisayama study. Compared to non-FL counterparts, FL subjects were younger, predominantly male and smokers; and had higher body mass index (BMI), VFA, hemoglobin A1c, C-peptide, TG, and sdLDL-C, while had similar levels of LDL-C, LDL-TG, and TRL-C. Multivariate logistic analysis revealed that sdLDL-C was the most powerful lipid parameter for identifying FL, independent of TG, HDL-C, BMI, and VFA. The independent association between TG and FL was lost when sdLDL-C was added to the analysis. These results remained the same when lipid-lowering drug users were excluded. After adjustment for confounders, the odds ratio for FL was 2.4-2.7 at sdLDL ≥ 35 mg/dL based on sdLDL ≤ 24 mg/dL. sdLDL-C levels are specifically elevated in patients with diabetes and MAFLD, independent of TG and VFA, suggesting liver-centered metabolic abnormalities.

Small Dense Low-Density Lipoprotein Cholesterol Levels in Breakfast Skippers and Staple Foods Skippers.

Skipping breakfast is known as a cardiovascular disease (CVD) risk. Recently, eating and dietary patterns have been varied in many countries, however, the mechanisms of promoting CVD are still unclear. Our goal was to assess the effects of eating and dietary patterns on CVD risk factors, with a focus on lipid parameters including serum concentration of small dense low-density lipoprotein cholesterol (sdLDL-C). Subjects consisted of 27,997 Japanese men and women, who had medical check-up. Lipid parameters including sdLDL-C levels in breakfast skippers were compared with those in breakfast eaters. Lipid parameters in staple foods skippers were also compared with those in staple foods eaters. Breakfast skippers had significantly (p＜0.01) higher serum levels of median sdLDL-C than breakfast eaters in both genders (34.7 versus 32.0 mg/dL in men, 25.4 versus 24.9 mg/dL in women, respectively), and the same was true for sdLDL-C/LDL-C ratio (0.276 versus 0.260 in men, 0.218 versus 0.209 in women, respectively). Similarly, staple foods skippers had significantly higher sdLDL-C level than staple foods eaters in both genders (34.1 versus 31.6 mg/dL in men, 25.8 versus 24.7 mg/dL in women), and the same went for sdLDL-C/LDL-C ratio (0.278 versus 0.256 in men, 0.215 versus 0.208 mg/dL in women, respectively). Our data indicate that both skipping breakfast and having meals without staple foods increase serum sdLDL-C concentration and cause unfavorable lipid profiles, and then may promote CVD. These finding provide evidence for the importance of having breakfast and meals with staple foods for preventing CVD.

The influence of triglycerides on small dense low-density lipoprotein cholesterol levels is attenuated in low low-density lipoprotein-cholesterol range: Implications for the negative results of the PROMINENT trial.

The Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) trial failed to show the preventive effects of pemafibrate, a triglyceride (TG)-lowering drug, on atherosclerotic cardiovascular disease in patients with type 2 diabetes and dyslipidemia. We recently reported that TG-lowering with pemafibrate did not decrease the calculated small dense (sd) low-density lipoprotein cholesterol (LDL-C), and speculated that the effect of TG on sdLDL-C is attenuated in low LDL-C levels. This report examined this possibility in 1,508 patients with type 2 diabetes and 670 healthy controls. LDL-C ranges were classified as ≤69, 70-99, 100-139 and 140≤ mg/dL. The slope of the regression curve between sdLDL-C and TG was found to flatten as LDL-C decreased; 0.18, 0.13, 0.10 and 0.04 for controls, and 0.18, 0.13, 0.09 and 0.07 for diabetes patients. Correspondingly, the lower the LDL-C range, the lower the sdLDL-C/TG ratio. These results suggest that when LDL-C is tightly controlled, TG-lowering has only a weak inhibitory effect on sdLDL-C.

Small Dense Low-Density Lipoprotein Cholesterol as a Novel Biomarker of Coronary Heart Disease

Objective: To compare serum small dense low-density lipoprotein cholesterol levels in coronary heart disease (CHD) patients and healthy controls.
 Study Design: Comparative cross-sectional study.
 Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), Rawalpindi Pakistan, in collaboration with AFIC Rawalpindi from Feb to Dec 2021.
 Methodology: A total of 220 participants were selected for the study, 120 healthy controls and 100 CHD patients. Fasting blood samples after 12 hours of fast were collected for lipid profile and small dense low-density lipoprotein cholesterol (sdLDL-C) levels. SdLDL-C levels were analyzed by automated, standardized enzymatic assay on Siemens Advia 1800 automated chemistry analyzer using Ex Denka Seiken kits.
 Results: Among the total participants, 154 (70%) were males, and 66(30%) were females. The median age of all participants was 55(IQR: 52 -56) years, while their median sdLDL-C was 0.93 (IQR: 0.56-1.08) mmol/L. Results showed that small, dense LDL cholesterol serum levels were significantly raised in CHD patients compared to healthy controls (p-value <0.05).
 Conclusion: The current study showed that patients with CHD had elevated small, dense LDL-C levels compared to the healthy control group.

Ipragliflozin lowers small, dense low-density lipoprotein cholesterol levels in Japanese patients with type 2 diabetes mellitus

AimsThis preliminary randomized, parallel-group comparative study evaluated the efficacy of ipragliflozin for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). MethodsSixty-two patients with T2DM (age, 56 ± 8 years; hemoglobin A1c levels, 8.1 ± 0.9%; BMI, 27.5 ± 3.3 kg/m2) were randomly assigned in a 2:1 ratio to receive ipragliflozin (50 mg/day) (treatment group; n = 40) or continued treatment (control group; n = 22) for 12 weeks.The primary endpoints were changes in sd LDL-C levels detected using the LipoPhor AS® system; the secondary endpoints included changes in the sd LDL-C/large buoyant LDL-C (lb LDL-C) ratio, a surrogate marker for LDL particle size, and percent changes in routine lipid parameters. ResultsThe treatment group exhibited a statistically significant reduction from baseline for LDL-C levels (−0.37 mg/dL vs. 14.4 mg/dL, p = 0.038), sd LDL-C levels (−1.28 mg/dL vs. 2.81 mg/dL, p = 0.012), and sd LDL-C/lb LDL-C ratio (−3.20% vs. 4.58%, p = 0.040) compared with the control group. Multiple regression analysis among all subjects revealed change in TG levels (p = 0.011) and LDL-C levels (p = 0.024) as well as change in body weight (p = 0.006) as independent factors contributing to the reduction in sd LDL-C. ConclusionsIpragliflozin may have a potential for lowering sd LDL-C levels associated with increasing LDL particle size in Japanese patients with T2DM.

Switching from atorvastatin to rosuvastatin lowers small, dense low-density lipoprotein cholesterol levels in Japanese hypercholesterolemic patients with type 2 diabetes mellitus

AimsThis open-label, randomized, parallel-group comparative study compared the efficacy of rosuvastatin (5mg/day) and atorvastatin (10mg/day) for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). MethodsPatients with T2DM and hypercholesterolemia with detectable sd LDL-C after receiving 10mg/day atorvastatin for ≥24 weeks were randomly assigned to receive rosuvastatin (5mg/day; switched treatment) or atorvastatin (10mg/day; continued treatment) for 12 weeks. The primary endpoints were changes in sd LDL-C levels and sd LDL-C/total LDL-C ratio evaluated using the LipoPhor AS® system. ResultsThere were no significant percent changes from baseline for LDL-C levels between the switched (n=55) and the continued treatment group (n=56). However, the former group exhibited a statistically significant reduction from baseline of sd LDL-C levels, sd LDL-C/total LDL-C ratio compared with the latter group (−3.8mg/dL vs. −1.4mg/dL, p=0.014; −2.3% vs. −0.6%, p=0.004, respectively). Multiple regression analysis among all subjects revealed that independent factors contributing to the reduction in sd LDL-C levels were a change in LDL-C (p=0.003) and triglyceride (TG) levels (p=0.006), treatment group (the switched group=1, the continued group=0; standard coefficient=−1.2, p=0.034) and baseline glycated hemoglobin A1c (HbA1c) (p=0.045), respectively. ConclusionSwitching from 10mg atorvastatin to 5mg rosuvastatin may be a useful therapeutic option to reduce sd LDL-C levels in Japanese hypercholesterolemic patients with T2DM.

Small High‐Density Lipoprotein (HDL) Subclasses are Increased with Decreased Activity of HDL‐Associated Phospholipase A2 in Subjects with Prediabetes

Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL cholesterol (HDL-C) was significantly increased in prediabetic subjects compared with their controls (p < 0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A₂ (HDL-LpPLA₂) was significantly lower in subjects with prediabetes (p < 0.05), whereas the activity of paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA₂.

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).

Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women

Background Serum retinol-binding protein 4 (RBP4) and small dense low-density lipoprotein (sdLDL) have been suggested to be associated with insulin resistance, but no information is available on the relationship between RBP4 and sdLDL. Methods We determined serum RBP4, sdLDL-cholesterol, and other metabolic variables on 38 young women, aged 19–29 years. The homeostatic model assessment of insulin resistance (HOMA-IR) was used for the estimation of insulin resistance. Results In simple regression analyses, RBP4 levels had significant correlations with total cholesterol ( r = 0.354, P = 0.029), LDL-cholesterol ( r = 0.396, P = 0.014), and sdLDL-cholesterol ( r = 0.510, P = 0.001) levels. The sdLDL-cholesterol levels also correlated significantly with total cholesterol ( r = 0.402, P = 0.012), LDL-cholesterol ( r = 0.627, P < 0.001) and triglycerides ( r = 0.449, P = 0.005). Stepwise multiple regression analyses showed only sdLDL-cholesterol (β coefficient ( ß) = 0.510, P = 0.001) level was a significant independent predictor of RBP4 levels (adjusted R 2 = 0.240), whereas RBP4 ( ß = 0.289, P = 0.026) level was one of major factors affecting sdLDL-cholesterol levels (adjusted R 2 = 0.519). There was no significant association of HOMA-IR with RBP4 or sdLDL levels. Conclusions We showed an independent linkage between serum RBP4 and sdLDL-cholesterol levels in young adult women. These findings may contribute to understanding of lipoprotein metabolisms involved in diabetes and cardiovascular disease.