Serum Small Dense Low-density Lipoprotein Research Articles

Role of Small Dense Low-density Lipoprotein Cholesterol in Cardiovascular Events in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Receiving Statin Treatment.

There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL. Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ＜150 mg/dL.

Correlations of Estimated Serum Small Dense Low-Density Lipoprotein and Isoprostane with Metabolic Syndrome Criteria between Metabolic Syndrome and Non-Metabolic Syndrome Subjects in Selangor

Introduction: Metabolic syndrome (MetS) is a global healthcare burden associated with increased risk of atherosclerosis (ATH). The relationship between atherogenic lipoprotein and oxidative stress biomarkers with clinical risk factors of MetS have not been fully explored. Therefore, the objective of this study is to determine the correlation between small dense low-density lipoprotein (sdLDL-c) and isoprostane (ISP) with MetS criteria and comparing these biomarkers between MetS and non-MetS. Materials and Methods: This was a cross sectional study involving 67 MetS and 43 non-MetS diagnosed by JIS criteria 2009. Demographic details and anthropometric measurements were recorded. Blood samples were collected to analyse serum plasma glucose, direct LDL, calculated sdLDL-c and ISP. Results: Mean serum sdLDL-c and ISP levels were significantly higher among those with MetS compared to non-MetS (1.14+0.44 mmol/L vs 0.87±0.38 mmol/L respectively, p=0.005). Similarly, mean serum ISP concentration was higher among MetS compared to non-MetS (884.40+602.69 ng/L vs 657.89±616.42 ng/L respectively, p= 0.054). sdLDL-c was positively correlated with TG in the MetS (Pearson correlation 0.501, p<.001) whilst HDL-c was positively correlated with sdLDL-c among the non-MetS (Pearson Correlation 0.422, p<.005). Conclusion: This study highlights the correlation between sdLDL-c and TG in among MetS, emphasizing the need to closely monitor and manage TG among this cohort to reduce the risk of ATH. It was also noted that HDL-c showed positive correlation with sdLDL-c among non-MetS. This discordant finding suggests that HDL-c itself may not be causally associated with cardiovascular benefits and that perhaps HDL-c subfractions may be a better approach to determine cardioprotective effects of HDL-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.

Serum concentrations of small dense low‐density lipoprotein cholesterol and lipoprotein(a) are related to coronary arteriostenosis in Takayasu arteritis

BackgroundSerum small dense low‐density lipoprotein cholesterol (sdLDL‐C) and lipoprotein(a) [Lp(a)] levels are related to coronary disease, but their specific associations with coronary arteriostenosis in Takayasu arteritis (TA) have not been ascertained. This study explored the correlations between serum sdLDL‐C and Lp(a) levels and coronary arteriostenosis in TA patients as well as the degree of artery stenosis.MethodsThis retrospective study included 190 TA patients and 154 healthy subjects. TA patients were divided into three categories based on the degree of coronary stenosis: Group I, stenosis >50%; Group II, stenosis 1%–50%; and Group III, stenosis 0%. Independent risk factors for coronary arteriostenosis in TA were identified by logistic regression, followed by receiver operating characteristic curve analysis to determine the specificity and sensitivity of risk factors and Youden's Index score calculation to determine the cutoff points.ResultsTakayasu arteritis patients had significantly higher serum levels of sdLDL‐C and Lp(a) than healthy controls (p < 0.0001). The total cholesterol, triglyceride, LDL‐C, sdLDL‐C, and Lp(a) levels and the sdLDL‐C/LDL‐C ratio in Group I were significantly higher than those in Groups II and III (p < 0.05). An elevated serum sdLDL‐C level elevated the risk of coronary arteriostenosis by 5‐fold (cutoff value, 0.605 mmol/l). An increased serum Lp(a) level increased the risk of coronary arteriostenosis by 3.9‐fold (cutoff value, 0.045 g/l). An elevated sdLDL‐C/LDL‐C ratio increased the risk of coronary arteriostenosis by 2.1‐fold (cutoff value, 0.258).ConclusionsSerum sdLDL‐C and Lp(a) levels and sdLDL‐C/LDL‐C ratio may be used as diagnostic factors for coronary arteriostenosis in TA patients.

Treatment of Hepatitis C Virus Infection with Direct-acting Antiviral Agents Elevates the Serum Small-dense Low-density Lipoprotein Cholesterol Level.

Objective The low-density lipoprotein cholesterol (LDL) level is known to increase following the treatment of hepatitis C virus (HCV) infection using direct-acting antiviral agents (DAAs). This study aimed to investigate the changes in the lipid profiles, including small-dense LDL cholesterol (sdLDL), in HCV patients treated with DAAs. Patients We retrospectively assessed 67 HCV patients who achieved sustained virological response with DAA administration and were observed for more than 2 years, of whom 32 were on daclatasvir/asunaprevir, 14 were on sofosbuvir/ledipasvir, and 21 were on sofosbuvir/ribavirin. Methods We evaluated the lipid profiles, including sdLDL, every 6 months until 2 years after the start of treatment and analyzed the factors related to changes in the sdLDL level. Results The median sdLDL value at baseline was 12.8 mg/dL, which increased to 19.5 mg/dL at 6 months (p<0.001) and remained elevated at 25.4 mg/dL at 2 years later (p<0.001). The Kaplan-Meier curve indicated that patients with high values of LDL, albumin, muscle attenuation and visceral to subcutaneous adipose tissue area ratio were at increased risk for elevation of sdLDL over 35 mg/dL (log-rank test: p<0.001; p=0.008, p=0.002 and p=0.042, respectively). A multivariate analysis performed on the factors contributing to elevation of sdLDL 2 years after DAA treatment (≥35.0 mg/dL) revealed pretreatment LDL (≥91.0 mg/dL) and muscle attenuation (≥33.7 HU) as significant factors (p=0.007 and p=0.032, respectively). Conclusion SdLDL increased continuously after DAA treatment, and high LDL levels and low intramuscular fat deposition before treatment contributed to elevated sdLDL levels after treatment.

The Association of Small Dense Low-Density Lipoprotein Cholesterol and Coronary Heart Disease in Subjects at High Cardiovascular Risk.

Aim: The present study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in subjects at high cardiovascular risk.Methods: A total of 3,080 participants without prior cardiovascular disease (CVD), aged ≥ 40 years, were followed up for a median of 8.3 years, which were divided into two groups, those with serum sdLDL cholesterol levels of < 35 mg/dL or ≥ 35 mg/dL. Then, subjects were stratified by the status of diabetes, CVD-related comorbidities (defined as the presence of diabetes, chronic kidney disease, or peripheral artery disease), and the CVD risk assessment according to the Japan Atherosclerosis Society Guidelines. The hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using a Cox proportional hazards model.Results: During the follow-up, 79 subjects developed CHD. The risk for incident CHD was higher in subjects with serum sdLDL cholesterol of ≥ 35 mg/dL than those with sdLDL cholesterol of < 35 mg/dL (HR 2.09, 95%CI 1.26–3.45) after adjusting for traditional risk factors. In the subgroup analyses, the multivariable-adjusted HR for incident CHD increased significantly in those with serum sdLDL cholesterol of ≥ 35 mg/dL among subjects with diabetes (HR 2.76, 95%CI 1.09–7.01), subjects with CVD-related comorbidities (HR 2.60, 95%CI 1.21–5.58), and high-risk category defined as the presence of CVD-related comorbidities or a Suita score of ≥ 56 points (HR 1.93, 95%CI 1.02–3.65).Conclusions: Elevated serum sdLDL cholesterol was associated with the development of CHD even in subjects at high cardiovascular risk.

Small Dense Low-Density Lipoprotein Cholesterol and the Risk of Coronary Heart Disease in a Japanese Community.

Aims: This study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in a Japanese community.Methods: A total of 3,080 participants without prior cardiovascular disease, aged 40 years or older, were followed up for 8 years. The participants were divided into the quartiles of serum sdLDL cholesterol levels. The risk estimates were computed using a Cox proportional hazards model.Results: During the follow-up period, 79 subjects developed CHD. Subjects in the highest quartile had a 5.41-fold (95% confidence interval, 2.12–13.82) higher risk of CHD than those in the lowest quartile after controlling for confounders. In the analysis classifying the participants into four groups according to the levels of serum sdLDL cholesterol and serum low-density lipoprotein (LDL) cholesterol levels, the risk of CHD almost doubled in subjects with sdLDL cholesterol of ≥ 32.9 mg/dL (median), regardless of serum LDL cholesterol levels, as compared with subjects with serum sdLDL cholesterol of < 32.9 mg/dL and serum LDL cholesterol of < 120.1 mg/dL (median). When serum sdLDL cholesterol levels were incorporated into a model with known cardiovascular risk factors, c-statistics was significantly increased (from 0.77 to 0.79; p = 0.02), and the net reclassification improvement was also significant (0.40; p < 0.001).Conclusions: The present findings suggest that the serum sdLDL cholesterol level is a relevant biomarker for the future development of CHD that offers benefit beyond the serum LDL cholesterol level and a possible therapeutic target to reduce the burden of CHD in a Japanese community.

The inreased level of serum small dense low-density lipoprotein cholesterol in patients with transient ischemic attacks and its correlation with recurrent stroke

Objective To investigate serum levels of small dense low-density lipoprotein cholesterol (sdLDL-C) in transient ischemic attacks (TIA) patients and assess their predictive values for subsequent stroke risk after TIA. Methods Clinical case-control study. Serum sdLDL-C levels were determined in 96 TIA patients who were admitted to Jinling Hospital from January 2016 to December 2016 and 44 healthy controls who had contemporaneously visited Jinling Hospital For a routine or the routine. ABCD3-I scores in TIA patients were calculated. All TIA patients were classified into three subgroups: high-risk (8≤ABCD3-I≤ 13, n=23), moderate-risk (4≤ABCD3-I≤ 7, n=36) and low-risk (0≤ABCD3-I≤ 3, n=37). Total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and other lipid/lipoprotein parameters in TIA patients and controls were also analyzed. Spearman correlation analyses and multivariate linear regression analyses were performed to investigate the association of serum sdLDL-C levels with ABCD3-I scores. Logistic regression analyses were performed to investigate the predictive values of serum sdLDL-C for TIA patients. Results Serum sdLDL-C levels were significantly increased in TIA patients compared with controls (t=-5.202, P<0.001). Furthermore, sdLDL-C levels in high-risk patients were significantly higher than that in moderate-risk (t=3.534, P=0.001) and low-risk (t=4.154, P<0.001) patients. Serum sdLDL-C levels were positively correlated with ABCD3-I scores (r=0.317, P=0.002) in TIA patients. The stepwise multiple regression analysis showed that only sdLDL-C was a significant independent predictor of ABCD3-I scores (β=0.481, P=0.032, adjusted R2=0.189), after adjusting for age, gender, blood pressure and other lipid/lipoprotein parameters. Binary Logistic analyses indicated that serum sdLDL-C levels were closely associated with TIA presence (OR=2.84, 95% CI=1.42-5.70, P=0.003), after adjustment with age, gender, blood pressure and other lipid/lipoprotein parameters. Conclusions Serum sdLDL-C levels were increased in TIA patients. The significantly independent associations of sdLDL-C levels with ABCD3-I scores were observed. Serum sdLDL-C levels may contribute to assessing subsequent stroke risk after TIA.(Chin J Lab Med, 2018, 41: 316-320) Key words: Ischemic attack, transient; Cholesterol, LDL; Stroke; Risk factors; Biomarkers

Evaluation of a novel small dense low-density lipoprotein cholesterol kit and investigate the clinical value in the population of coronary heart disease

Objective To evaluate the performance of serum small dense low-density lipoprotein cholesterol(sdLDL-C)kit using enzymic method and investigate the clinical value in coronary heart disease(CHD). Methods According to the standard of Clinical and Laboratory Standards Institute(CLSI ), evaluae the precision, linearity ranges, reportable range and accuracy of sdLDL-C kit. The 683 patients with coronary heart disease ( CHD, 423 men and 260 women, age 35-79 years) who were diagnosed at the people′s hospital of Peking university from October 2015 to October 2016 were divided into two groups. The treated group include 571 patients( CHD1, 342 men and 229 women, age 40-79 years) which taking lipid-lowering drugs and the other include 112 cases ( CHD2, 81 men and 31 women, age 35-70 years ) without Lipid-lowing treatment. Besides, the Control group contains 472 healthy persons(274 men and 198 women, age 41-75 years), were collected from the people′s hospital of Peking university between April and August 2016. The liver function, renal function, blood glucose and blood lipid in CHD group(CHD1, CHD2) and healthy control group were detected. The new enzyme assay kit was used for the determination of sdLDL-C. The data of normal distribution were compared by independent t test between the two groups. The Mann-Whitney U nonparametric test was used for comparison between two groups. Results The precision of sdLDL-C kit examination was in compliance with manufacturer′ statement. The linearity was good in 0.11-2.42 mmol/L(Y=1.008 9X+ 0.024 8, R2=0.998 2), the scope of the report is 0.11-4.84 mmol/L. The level of sdLDL-C in CHD group was significantly higher than that in healthy control group, it has a statistical significance[0.824(0.443) mmol/L, 0.609(0.361) mmol/L; Z=-5.603, P<0.001]. The level of sdLDL-C in (CHD 1) was lower than (CHD 2)[0.761(0.479) mmol/L, 0.888(0. 426) mmol/L; Z=-2.304, P<0.021]. After additional adjustment for various tradition cardiovascular risk factor, including ages, sex, CHO, TG, Hs-CRP, Lp(a), and GLU, the highest quartile of sdLDL-C comparison to the bottom quartile, the OR was 3.02, (95% CI, 1.15-9.05)for CHD. Conclusions Experiment data demonstrated that sdLDL-C kit using enzymic method has good performance in the precision, linearity ranges, reportable range and accuracy, sdLDL-C serum level was significantly higher in CHD group.(Chin J Lab Med, 2017, 40: 716-720) Key words: Coronary disease; Lipoproteins, LDL; Reagent kits, diagnostic; Reproducibility of results

Serum small dense low-density lipoprotein cholesterol and performance evaluation of commercial detection kits and its relationship with the severity of coronary heart disease

Objective To evaluate the performance of serum small dense low-density lipoprotein cholesterol(sdLDL-C)kit using enzymic method and evaluate the relationship with the severity of coronary heart disease. Methods Performance verification methodology. The analytical performance consisted of accuracy, precision and linearity of serum sdLDL-C kit using enzymic method was assessed. One hundred and twenty healthy persons were recruited to establish serum sdLDL-C reference interval. Two hundred and twelve patients underwent coronary angiography were enrolled in the study. Among them 110 cases were positive for coronary angiography, where as 102 cases were negative. We examined serum levels of sdLDL-C in 110 patients with positive angiography, 102 patients with negative angiography and 120 healthy volunteers. Positive group was classfied into severe group(Gensini score>30) and mild group (Gensini score≤30). Results The accuracy and precision of sdLDL-C examination were in compliance with manufacturer's statement and there was a good linear correlation(Y=0.9937X-0.1063, R2=0.99) in range of 0.06-2.45 mmol/L. The reference interval of sdLDL-C was 0.15-0.97 mmol/L and without gender and age specificity. The level of sdLDL-C was higher in positive angiography group than in negative angiography group and healthy control group(P<0.01). The level of sdLDL-C was higher in severe group than in mild group(P<0.05). Binary stepwise regression analysis demonstrated that sdLDL-C was independently associated with the severity of coronary heart disease(OR=3.101, P<0.05). Conclusions Experiment data demonstrated that serum sdLDL-C kit using enzymic method has good performance in the accuracy, precision and linearity. SdLDL-C that plays an important role in the occurrence and progression of coronary heart disease, is an independent important risk of the severity of coronary heart disease.(Chin J Lab Med, 2017, 40: 425-430) Key words: Coronary heart disease; Cholesterol, LDL; Reagent kits, diagnostic

Flaxseed oil intake reduces serum small dense low-density lipoprotein concentrations in Japanese men: a randomized, double blind, crossover study.

BackgroundThe effects of alpha-linolenic acid (ALA) on cardiovascular risk factors considerably vary between published reports. Therefore, we investigated the effects of 12-week supplementation with flaxseed oil (FO), which is a rich source of ALA, on cardiovascular risk factors such as serum small dense low-density lipoprotein (sd-LDL) concentrations.MethodsIn a randomized, double blind, crossover study, 15 subjects ingested 10 g of FO or corn oil (CO), containing 5.49 g and 0.09 g of ALA, respectively, once daily with dinner. Blood samples were collected at 0, 4 and 12 weeks, and were used for analysis of serum lipid, lipid-related proteins, serum fatty acids and serum sd-LDL cholesterol. Differences during the test period were identified using a repeated-measures analysis of variance (ANOVA) for within-group effects. Group differences were identified using paired t-test at each blood sampling time point.ResultsALA and eicosapentaenoic acid concentrations were significantly higher in the FO period at 4 and 12 weeks than in the CO period. No significant differences in docosahexaenoic acid concentrations were observed between two periods, and cholesteryl ester transfer protein and apolipoprotein B concentrations were significantly lower in the FO period than in the CO period at 12 weeks. FO supplementation was associated with a significant decrease in sd-LDL concentrations at 4 and 12 weeks, and CO supplementation had no effect. Moreover, sd-LDL concentrations were significantly lower in the FO period than in the CO period at 4 weeks. Among subjects with triglyceride (TG) concentrations of >100 mg/dl, FO supplementation markedly reduced sd-LDL concentrations at 4 and 12 weeks compared with baseline. Sd-LDL concentrations significantly differed between the periods at both 4 and 12 weeks.ConclusionThis study indicates that the FO, which is a rich source of ALA, leads to lower sd-LDL cholesterol concentrations.

Small dense LDL is more susceptible to glycation than more buoyant LDL in Type 2 diabetes

Glycation of apoB (apolipoprotein B) of LDL (low-density lipoprotein) increases its atherogenicity. Concentrations of both serum glyc-apoB (glycated apoB) and SD-LDL (small dense LDL) (syn LDL3; D=1.044-1.063 g/ml) are increased in diabetes and are closely correlated. We studied whether SD-LDL is more susceptible to glycation in vitro than more buoyant LDL in statin- and non-statin-treated Type 2 diabetes mellitus. Serum SD-LDL apoB and glyc-apoB on statins was 20±2 (means±S.D.) and 3.6±0.41 compared with 47±3 and 5.89±0.68 mg/dl in those not receiving statins (P<0.001 and <0.01, respectively). There was a dose-dependent increase in glycation on incubation of LDL subfractions with glucose, which was accompanied by an increase in LPO (lipid peroxide) and electrophoretic mobility and a decrease in free amino groups. SD-LDL was more susceptible to these changes than more buoyant LDL. Both SD-LDL and more buoyant LDL from statin-treated patients were less susceptible to glycation. There were fewer free amino groups on LDL subfractions from statin-treated patients, which may contribute to this resistance. In conclusion, greater susceptibility of SD-LDL to glycation is likely to contribute to the raised levels of circulating glyc-apoB in diabetes. Statins are associated with lower levels of both SD-LDL and glyc-apoB.

Serum Small Dense Low‐density Lipoprotein Concentrations are Elevated in Patients with Significant Coronary Artery Stenosis and are Related to Features of the Metabolic Syndrome

Serum small dense low-density lipoprotein (sd-LDL) concentrations were measured in patients with angiographically defined coronary artery disease (CAD) and compared to concentrations in healthy subjects. Five hundred and seventy patients with stable CAD were divided into CAD- and CAD+ based on angiography. Patients in whom stenosis was <50% in diameter were classified as having a 'normal' angiogram (CAD-), otherwise the patients were allocated to the CAD+ group. The CAD+ group was further subcategorized into single-, double- and triple-vessel disease (VD). Serum sd-LDL concentrations were significantly lower in controls compared with CAD+ and CAD- patients (P<0.001). Moreover, CAD+ patients had higher concentrations of sd-LDL than CAD- patients (P<0.01). sd-LDL levels were not significantly associated with severity of CAD defined by the number of stenosed coronary arteries (P=0.245). All participants were also categorized into subgroups with or without metabolic syndrome. Subjects with metabolic syndrome had higher levels of sd-LDL than subjects without metabolic syndrome (P<0.01). Multiple linear regressions showed that in CAD patients, triacylglycerol, total-cholesterol, body mass index, and waist circumferences were the most important determinants of serum sd-LDL concentrations. We found that sd-LDL levels were significantly higher in patients presenting with symptoms of CAD. Moreover, patients with significant stenosis of their coronary arteries (>50% stenosis) had higher levels of sd-LDL compared to patients without significant lesions.