Small Dense LDL Research Articles

MiR-122 dysregulation is associated with type 2 diabetes mellitus-induced dyslipidemia and hyperglycemia independently of its rs17669 variant

miR-122 is a liver specific micro-RNA that participates in the regulation of carbohydrate and lipid metabolism. The rs17669 variant of miR-122 is positioned at the flanking region of miR-122 and may affect its stability and maturation. Therefore, this study was aimed to investigate the association of the rs17669 polymorphism with the miR-122 circulating level, risk of type 2 diabetes mellitus (T2DM) development, and biochemical parameters in T2DM patients and matched healthy controls. This study involved 295 subjects (controls: n = 145 and T2DM: n = 150). The rs17669 variant genotyping was done by ARMS-PCR. Serum biochemical parameters including lipid profile, small-dense low density lipoprotein (sdLDL) and glucose were measured by colorimetric kits. Insulin and Glycated hemoglobin (HbA1c) were assayed using ELISA and capillary electrophoresis methods, respectively. miR-122 expression was measured by real-time PCR. There was no significant difference between study groups in terms of allele and genotype distribution (P > 0.05). The rs17669 variant did not have any significant association with miR-122 gene expression and biochemical parameters (P > 0.05). miR-122 expression level in T2DM patients was significantly higher than that in control subjects (5.7 ± 2.4 vs. 1.4 ± 0.78) (P < 0.001). Furthermore, miR-122 fold change had a positive and significant correlation with low-density lipoprotein cholesterol (LDL-C), sdLDL, fasting blood sugar (FBS), and insulin resistance (P < 0.05). It can be concluded that the rs17669 variant of miR-122 is not associated with the miR-122 expression and T2DM-associated serum parameters. Furthermore, it can be suggested that miR-122 dysregulation is involved in T2DM development through inducing dyslipidemia, hyperglycemia, and resistance to insulin.

To Compare the Pattern of Serum Non HDL, HDL Levels in Type 2 Diabetes Subjects With and Without Ischemic Heart Disease

Individuals with DM may have several forms of dyslipidemia. Because of the additive cardiovascular risk of hyperglycemia and hyperlipidemia, lipid abnormalities should be assessed aggressively and treated as part of comprehensive diabetes care. The most common pattern of dyslipidemia is hypertriglyceridemia and reduced HDL cholesterol levels. DM itself does not increase levels of LDL, but the small dense LDL particles found in type 2 DM are more atherogenic because they are more easily glycated and susceptible to oxidation. Low HDL cholesterol as an independent risk factor for CHD Strong epidemiological evidence links low levels of serum HDL cholesterol to increased CHD morbidity and mortality. High HDL-cholesterol levels conversely convey reduced risk. Epidemiological data taken as a whole signify that a 1 percent decrease in HDL cholesterol is associated with a 2–3 percent increase in CHD risk. Epidemiological studies consistently show low HDL cholesterol to be an independent risk factor for CHD. Objective: To compare the pattern of serum non HDL, HDL levels in type 2 diabetes subjects with and without Ischemic Heart Disease. A descriptive study was carried out. Source of Data: Primary observed data of subjects with type 2 diabetes admitted to Medicine wards for ischemic heart disease. Control group of Type 2DM without IHD. Statistical Tests: Chi square test, students T test Bar and Pie chart. Related statistical techniques using SPSS version 21.0. Results: Among the 100 subjects chosen for the study, 59 subjects were males (59%) and remaining 41 subjects were females (41%). Majority of the subjects were in the age group of 50-69 years (60%). Mean non HDL value among non IHD was 67.1+14.6 and among IHD cases were at higher level i.e 176.4+18.7. p value showed statistical significance. Conclusion: UACR is statistically different among subjects with IHD compared to subjects without IHD. Hence subjects with Type 2 DM with IHD have been found to have higher total ....

Significance of Circulating Remnant Lipoprotein Cholesterol Levels Measured by Homogeneous Assay in Patients with Type 2 Diabetes

Remnant lipoproteins (RLs), which are typically present at high concentrations in patients with type 2 diabetes mellitus (T2DM), are associated with cardiovascular disease (CVD). Although an RL cholesterol homogeneous assay (RemL-C) is available for the measurement of RL concentrations, there have been no studies of the relationship between RemL-C and clinical parameters in T2DM. Therefore, we evaluated the relationships between RemL-C and CVD-related parameters in patients with T2DM. We performed a cross-sectional study of 169 patients with T2DM who were hospitalized at Kumamoto University Hospital. Compared with those with low RemL-C, those with higher RemL-C had higher fasting plasma glucose, homeostasis model assessment for insulin resistance (HOMA-R), total cholesterol, triglyceride, small dense low-density lipoprotein cholesterol (sdLDL-C), and urinary albumin-creatinine ratio; and lower high-density lipoprotein cholesterol, adiponectin, and ankle brachial pressure index (ABI). Multivariate logistic regression analysis showed that sdLDL-C and ABI were significantly and independently associated with high RemL-C. Although LDL-C was lower in participants with CVD, there was no difference in RemL-C between participants with or without CVD. Thus, RemL-C may represent a useful index of lipid and glucose metabolism, and that may be a marker of peripheral atherosclerotic disease (PAD) in male patients with T2DM.

Small Dense Low-Density Lipoprotein Cholesterol and Ischemic Stroke.

For decades, it has been suggested that small dense low-density lipoprotein (sdLDL) may be particularly atherogenic. High levels of sdLDL are associated with an increased risk of ischemic heart disease; however, the association of sdLDL with ischemic stroke has not been explored in a large prospective study on the general population. We tested the hypothesis that high sdLDL cholesterol levels are associated with an increased risk of ischemic stroke. This prospective study included 38,319 individuals from the Copenhagen General Population Study with fresh sample measurements of sdLDL cholesterol. Median follow-up time was 3.1 years. We observed 302 and 74 ischemic and hemorrhagic strokes from baseline in 2013 to 2017 to the end of follow-up in 2018. For comparison, we included estimates for large buoyant LDL cholesterol and total LDL cholesterol. Higher levels of sdLDL cholesterol were log-linearly associated with increased risk of ischemic stroke. Compared with individuals with sdLDL cholesterol in the lowest tertile (≤0.60 mmol/l; ≤23 mg/dl) the multivariable adjusted hazard ratio for ischemic stroke was 1.79 (95% confidence interval=1.31-2.43) for the highest tertile (≥0.86 mmol/l; ≥33 mg/dl). Multivariable adjusted hazard ratios for ischemic stroke per 1 mmol/l (38.7mg/dl) higher levels were 1.69 (1.28-2.22) for sdLDL cholesterol, 0.95 (0.78-1.16) for large buoyant LDL cholesterol, and 1.08 (0.93-1.25) for total LDL cholesterol. Hazard ratios were similar when further adjusting for body mass index (BMI) and diabetes mellitus in the biological pathway in combination with related lipids and lipoproteins. Higher sdLDL cholesterol levels were robustly associated with increased risk of ischemic stroke. ANN NEUROL 2023;93:952-964.

Atherosclerotic cardiovascular disease risk and small dense low-density lipoprotein cholesterol in men, women, African Americans and non-African Americans: The pooling project

Background and aimsElevated small dense low-density lipoprotein-cholesterol (sdLDL-C) has been reported to be associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. Our aims were to determine whether direct and calculated sdLDL-C were significant independent ASCVD risk factors in sex and race subgroups. MethodsIn a total of 15,933 participants free of ASCVD at baseline (median age 62 years, 56.7% female, 19.7% African American) fasting plasma lipids and sdLDL-C were measured by standardized automated methods. All subjects were followed for 10 years for incident ASCVD, which developed in 9.7% of subjects. SdLDL-C values were also calculated. Univariate and multivariate analyses were carried out to assess for independent associations with incident ASCVD after adjustment for all standard risk factors. ResultsAll standard risk factors were significantly associated with incident ASCVD on univariate analysis, as were direct and calculated sdLDL-C. These latter parameters were also significant when added to the pooled cohort risk equation. However, associations were significantly stronger for direct sdLDL-C and were not significant for calculated values once direct values were in the model. In contrast to calculated values, top quartile direct sdLDL-C was significantly independently associated with incident ASCVD versus bottom quartile values in all subjects and subgroups, except African Americans (hazard ratios ≥1.50, p < 0.01). Subjects with direct values ≥ 50 mg/dL versus <25 mg/dL had significantly higher independent ASCVD risk in all groups (hazard ratios >1.49, all p < 0.01). ConclusionsHaving a direct small dense low-density lipoprotein cholesterol value ≥ 50 mg/dL is a significant independent ASCVD risk-enhancer.

Small Dense Low-Density Lipoprotein Level in Newly Diagnosed Type 2 Diabetes Mellitus Patients With Normal Low-Density Lipoprotein.

Background and objective There are three subtypes of low-density lipoprotein (LDL): large buoyant (lb), intermediate, and small dense (sd). Among these LDL subtypes, small dense low-density lipoprotein (sdLDL) has been proven to be an independent risk factor for atherosclerosis. Type 2 diabetes mellitus (T2DM) encompasses several metabolic abnormalities and patients suffering from T2DM without good glycemic control are prone to develop atherosclerosis. Hence, in T2DM, it is recommended to evaluate blood lipids for early detection of hyperlipidemia to identify the risk. A larger percentage of sdLDL in T2DM patients with an optimal or near-optimal LDL level might be a hidden risk factor for atherosclerosis. Hence, we aimed to find the level of sdLDL cholesterol (sdLDL-C) among newly diagnosed T2DM patients with optimal or near-optimal blood lipids and to compare it with age and sex-matched controls. Materials and methods In this study, we enrolled newly diagnosed T2DM patients from the diabetic clinic of a tertiary care hospital. The patients were then tested for blood lipids, namely, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C), including sdLDL-C. Then, age and sex-matched controls with similar baseline lipid levels to the T2DM group (without sdLDL-C) were recruited. After recruitment, both groups were measured for blood lipids including sdLDL-C in a single day. The level of sdLDL-C between the groups was tested statistically by the Mann-Whitney U test. Results A total of 50 T2DM patients with a median age of 36 years (Q1-Q3: 33.75-41) were included as the study group and 50 ageand sex-matched controls with a median age of 34 years (32-37.25; p = 0.09) were recruited. The median fasting glucose was 165 (Q1-Q3: 145-199.25) mg/dL and 90.5 (Q1-Q3: 87.75-95.25) mg/dL (p < 0.0001) in the study and control groups, respectively. The LDL-C was 109.9 (Q1-Q3: 99.4-119.4) mg/dL and 108.5 (Q1-Q3: 87.55-124.1) mg/dL (p = 0.94) in the study and control groups, respectively. The sdLDL-C was 40.11 (Q1-Q3: 36.28-43.58) mg/dL and 24.64 (Q1-Q3: 22-32.49) mg/dL (p < 0.0001) in the study and control groups, respectively. Conclusion Newly diagnosed T2DM patients with blood lipids within an optimum or near-optimum level may have a higher percentage of sdLDL-C when compared with healthy controls. Hence, they may have a higher risk of atherosclerosis and cardiovascular diseases. Clinicians may miss the potential risks if they do not advise the sdLDL-C component of LDL-C while advising for the test for blood lipid.

Prognostic Implication of Small Dense LDL-Cholesterol Levels following Acute Coronary Syndrome.

Background and Objectives: Small dense LDL cholesterol is a strong risk factor for atherosclerosis. However, few studies have investigated the impacts of this specific lipid profile on the incident risk of adverse cardiovascular events in patients with acute coronary syndrome. Materials and Methods: Patients with acute coronary syndrome, who underwent revascularization, were included and followed for 2 years. The levels of small dense LDL cholesterol were measured at index discharge (day 0) in the setting of newly administered therapies for secondary prevention, including aspirin and statins, during the index hospitalization. The prognostic impact of small dense LDL-cholesterol levels on the risk of a primary composite endpoint, including cardiac death, non-fatal myocardial infarction, unstable angina pectoris, stroke, and heart failure, was investigated. Results: In total, 46 patients (median 75 (59, 83) years old, 63% men) were included. Median small dense LDL cholesterol was 19.4 (13.5, 23.8) mg/dL at index discharge. All patients initiated statin treatment before the index discharge, with a median LDL-cholesterol level of 77 (64, 109) mg/dL. Small dense LDL-cholesterol level was independently associated with an incremental risk for the primary endpoint (p &lt; 0.05 by adjusting for several potential risk factors, including LDL cholesterol) with a cutoff of 32.6 mg/dL. Conclusions: Small dense LDL-cholesterol level was a significant risk factor for cardiovascular events following presentations of acute coronary syndrome.

Effect of evolocumab on the progression of intraplaque neovascularization of the carotid based on contrast-enhanced ultrasonography (EPIC study): A prospective single-arm, open-label study.

Background and Purpose: The aim of this study was to explore the effect of half a year of evolocumab plus moderate-intensity statin treatment on carotid intraplaque neovascularization (IPN) and blood lipid levels. Methods: A total of 31 patients with 33 carotid plaques who received evolocumab plus statin treatment were included. Blood lipid levels, B-mode ultrasound and contrast-enhanced ultrasonography (CEUS) at baseline and after half a year of evolocumab plus statin therapy were collected. The area under the curve (AUC) reflected the total amount of acoustic developer entering the plaque or lumen within the 180s measurement period. The enhanced intensity reflected the peak blood flow intensity during the monitoring period, and the contrast agent area reflected the area of vessels in the plaques. Results: Except for high-density lipoprotein cholesterol (HDL-c), all other lipid indices decreased. Compared with baseline, low-density lipoprotein cholesterol (LDL-c) decreased by approximately 57% (p < 0.001); total cholesterol (TC) decreased by approximately 34% (p < 0.001); small dense low-density lipoprotein (sd-LDL) decreased by approximately 52% (p < 0.001); and HDL-c increased by approximately 20% (p < 0.001). B-mode ultrasonography showed that the length and thickness of the plaque and the hypoechoic area ratio were reduced (p < 0.05). The plaque area, calcified area ratio, and lumen cross-sectional area changed little (p > 0.05). CEUS revealed that the area under the curve of plaque/lumen [AUC (P/L)] decreased from 0.27 ± 0.13 to 0.19 ± 0.11 (p < 0.001). The enhanced intensity ratio of plaque/lumen [intensity ratio (P/L)] decreased from 0.37 ± 0.16 to 0.31 ± 0.14 (p = 0.009). The contrast agent area in plaque/area of plaque decreased from 19.20 ± 13.23 to 12.66 ± 9.59 (p = 0.003). The neovascularization score decreased from 2.64 ± 0.54 to 2.06 ± 0.86 (p < 0.001). Subgroup analysis based on statin duration (<6months and ≥6months) showed that there was no significant difference in the AUC (P/L) or intensity ratio (P/L) at baseline or after half a year of evolocumab treatment. Conclusion: This study found that evolocumab combined with moderate-intensity statins significantly improved the blood lipid profile and reduced carotid IPN. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT04423406.

Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development.

We sought to explore biomarkers of coronary atherosclerosis in an unbiased fashion. We analyzed 665 patients (mean ± SD age, 56 ± 11 years; 47% male) from the GLOBAL clinical study (NCT01738828). Cases were defined by the presence of any discernable atherosclerotic plaque based on comprehensive cardiac computed tomography (CT). De novo Bayesian networks built out of 37,000 molecular measurements and 99 conventional biomarkers per patient examined the potential causality of specific biomarkers. Most highly ranked biomarkers by gradient boosting were interleukin-6, symmetric dimethylarginine, LDL-triglycerides [LDL-TG], apolipoprotein B48, palmitoleic acid, small dense LDL, alkaline phosphatase, and asymmetric dimethylarginine. In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95% of the ensembles. Genetic variants in the genomic region encoding hepatic lipase (LIPC) were associated with LIPC gene expression, LDL-TG levels and with atherosclerosis. Triglyceride-rich LDL particles, which can now be routinely measured with a direct homogenous assay, may play an important role in atherosclerosis development. GLOBAL clinical study (Genetic Loci and the Burden of Atherosclerotic Lesions); [https://clinicaltrials.gov/ct2/show/NCT01738828?term=NCT01738828&rank=1], identifier [NCT01738828].

Automated On-Line Isolation and Fractionation Method for Subpopulations of Extracellular Vesicles.

Immunoaffinity chromatography (IAC) with selective antibodies immobilized on polymeric monolithic disk columns enables selective isolation of biomacromolecules from human plasma, while asymmetrical flow field-flow fractionation (AsFlFFF or AF4) can be used for further fractionation of relevant subpopulations of biomacromolecules (e.g., small dense low-density lipoproteins, exomeres, and exosomes) from the isolates. Here we describe how the isolation and fractionation of subpopulations of extracellular vesicles can be achieved without the presence of lipoproteins using on-line coupled IAC-AsFlFFF. With the developed methodology, it is possible to have fast, reliable, and reproducible automated isolation and fractionation of challenging biomacromolecules from human plasma with a high purity and high yields of subpopulations.

Validation of Estimated Small Dense Low-Density Lipoprotein Cholesterol Concentration in a Japanese General Population.

A high level of directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for atherosclerotic cardiovascular disease. A method for estimating sdLDL-C by using Sampson's equation that includes levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C and triglycerides (TG) has recently been proposed. We investigated the validation and exploration of estimated sdLDL-C level. The associations between measured and estimated sdLDL-C levels were investigated in 605 Japanese subjects (men/women: 280/325; mean age: 65±15 years) who received annual health check-ups in the Tanno-Sobetsu Study, a population-based cohort. Estimated sdLDL-C level was highly correlated with measured sdLDL-C level in all subjects (R2=0.701), nondiabetic subjects without any medication (n=254, R2=0.686) and subjects with diabetes mellitus (n=128, R2=0.721). Multivariable regression analysis showed that levels of non-HDL-C, TG and γ-glutamyl transpeptidase (γGTP) were independent predictors of measured sdLDL-C level. In a stratification of the LDL window, all of the subjects with a combination of high non-HDL-C (≥ 170 mg/dL) and high TG (≥ 150 mg/dL) had high levels of measured and estimated sdLDL-C (≥ 35 mg/dL). Furthermore, machine learning-based estimation of sdLDL-C level by artificial intelligence software, Prediction One, was substantially improved by using components of Sampson's equation (R2=0.803) and by using those components with the addition of γGTP and deletion of TC (R2=0.929). sdLDL-C level estimated by Sampson's equation can be used instead of measured sdLDL-C level in general practice. By building multiple machine learning models of artificial intelligence, a more accurate and practical estimation of sdLDL-C level might be possible.

Circadian Rhythm of Subspecies of Low-Density Lipoprotein-Cholesterol and High-Density Lipoprotein-Cholesterol in Healthy Subjects and Patients with Type 2 Diabetes.

We established automated assay kits for quantifying small dense low-density lipoprotein (sdLDL)-cholesterol (C), LDL-triglyceride (TG), and high-density lipoprotein (HDL)3-C, and apolipoprotein (apo)E-rich HDL-C, and these have been recognized as sensitive biomarkers for predicting coronary artery disease. We investigated the circadian rhythms of these novel lipids to determine if fasting is required to determine basal levels. Forty-eight inpatients with type 2 diabetes and 19 healthy volunteers were studied. Blood samples were collected at seven time points, which were obtained after an overnight fast, before and 2 h after each meal, and before the next breakfast. sdLDL-C, LDL-TG, remnant-like particle (RLP)-C, TG-rich lipoprotein (TRL-C), HDL3-C, and apoE-rich HDL-C were measured by the homogeneous methods. NonHDL-C, large buoyant (lb) LDL-C and HDL2-C were calculated by subtracting sdLDL-C from LDL-C or HDL3-C from HDL-C, respectively. Serum TG levels were significantly increased after meals in both healthy participants and patients with diabetes. RLP-C and TRL-C were also increased postprandially. LDL-TG, LDL-C, nonHDL-C, HDL2,3-C, and apoE-rich HDL-C did not exhibit significant fluctuation during the day in healthy participants and patients with diabetes. sdLDL-C was slightly increased postprandially in subjects with diabetes (1-2 mg/dl, 3%-9%), though its increase was not significant compared to the baseline (fasting) level. Significant postprandial reduction was observed with LDL-C and lbLDL-C. There was no influence of statin therapy or oral anti-diabetes drugs on the circadian rhythm of LDL-C subspecies. Subtle postprandial increase in sdLDL-C is considered a negligible level in general clinical practice. Fasting is not mandatory to measure basal concentrations of LDL and HDL subspecies.

Predictive value of SII and sd-LDL for contrast-induced acute kidney injury in STEMI patients undergoing percutaneous coronary intervention

Aim: To investigate the relationship between the incidence of contrast-induced acute kidney injury (CI-AKI) and the level of small dense low-density lipoprotein (sd-LDL) and systemic immune-inflammation index (SII) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI), and to further compare the predictive values of SII, sd-LDL and their combination for CI-AKI. Methods: A total of 674 patients were assigned to a training and a validation cohort according to their chronological sequence. The baseline characteristics of the 450 patients in the training cohort were considered as candidate univariate predictors of CI-AKI. Multivariate logistic regression was then used to identify predictors of CI-AKI and develop a prediction model. The predictive values of SII, sd-LDL and their combination for CI-AKI were also evaluated. Results: Multivariate logistic regression analysis showed that age, left ventricular ejection fraction (LVEF), sd-LDL, uric acid, estimated glomerular filtration rate (eGFR) and SII were predictors of CI-AKI. The area under the curve (AUC) of the prediction model based on the above factors was 0.846 [95% confidence interval (CI) 0.808–0.884], and the Hosmer-Lemeshow test (P = 0.587, χ2 = 6.543) proved the goodness of fit of the model. The AUC combining SII with sd-LDL to predict CI-AKI was 0.785 (95% CI 0.735–0.836), with a sensitivity of 72.8% and a specificity of 79.8%, and was statistically significant when compared with SII and sd-LDL, respectively. The predictive efficiency of combining SII with sd-LDL and SII were evaluated by improved net reclassification improvement (NRI, 0.325, P &lt; 0.001) and integrated discrimination improvement (IDI, 0.07, P &lt; 0.001). Conclusions: Both SII and sd-LDL can be used as predictors of CI-AKI in STEMI patients undergoing emergency PCI, and their combination can provide more useful value for early assessment of CI-AKI.

CYP2C19 metabolizer phenotypes may affect the efficacy of statins on lowering small dense low-density lipoprotein cholesterol of patients with coronary artery disease.

Dyslipidemia is a major cause of arteriosclerotic cardiovascular disease (ASCVD), and low-density lipoprotein cholesterol (LDL-C) is the profile to be reduced to prevent disease progression. Small dense low-density lipoprotein cholesterol (sdLDL-C) has been proven to be a more effective biomarker than LDL-C for ASCVD primary and secondary prevention. CYP2C19 is an important drug metabolism gene. This study aimed to investigate the relationship between sdLDL-C and coronary artery disease (CAD) risk factors and explore the influence of CYP2C19 metabolizer phenotypes on the sdLDL-C lowering efficacy of statins. This study recruited 182 patients with CAD and 200 non-CAD controls. Baseline laboratory indices of fasting blood were detected, including blood lipids, glucose, and creatinine. In addition, LDL-C subfractions were separated and quantified. Gene polymorphisms of SLCO1B1 and CYP2C19 were detected in patients with CAD. The LDL-C subfractions levels of patients with CAD were followed up after statin drug treatment. Total cholesterol, LDL-C, LDLC-2, LDLC-3, LDLC-4, LDLC-5, LDLC-6, LDLC-7, and sdLDL-C levels of patients with CAD were significantly higher than those in non-CAD controls. Meanwhile, sdLDL-C (AUC = 0.838) and LDLC-4 (AUC = 0.835) performed outstandingly in distinguishing patients with CAD from controls. Based on CYP2C19 metabolizer phenotypes, 113 patients with CAD were divided into the extensive metabolizer (EM, n = 49), intermediate metabolizer (IM, n = 52), and poor metabolizer (PM, n = 12) groups. The patients with IM and PM metabolizer phenotypes had better sdLDL-C lowering efficacy after taking statin drugs than patients with EM phenotype (P = 0.0268, FDR = 0.0536). The SLCO1B1 genotype had no significant impact on the efficacy of statins (P = 0.1611, FDR = 0.1611). sdLDL-C and LDLC-4 outperformed other blood lipids such as LDL-C for CAD risk screening. CYP2C19 metabolizer phenotypes had the potential to predict the efficacy of statins in lowering sdLDL-C.

Association between measured or calculated small dense low-density lipoprotein cholesterol and oxidized low-density lipoprotein in subjects with or without type 2 diabetes mellitus.

Small dense low-density lipoprotein (sdLDL) possesses atherogenic potential and is predicted to be susceptible to atherogenic modifications, which further increases its atherogenicity. However, studies on the association between measured or estimated sdLDL cholesterol (sdLDL-C) levels and atherogenic modification in diverse population groups are lacking. Surplus serum samples were collected from male subjects with type 2 diabetes mellitus (DM) under treatment (n= 300) and without DM (non-DM; n= 150). sdLDL and oxidized LDL (oxLDL) levels were measured using the Lipoprint LDL subfractions kit (Quantimetrix Corporation) and the Mercodia oxidized LDL competitive enzyme-linked immunosorbent assay kit (Mercodia), respectively. The estimated sdLDL-Cs were calculated from two relevant equations. The effects of sdLDL-C on oxLDL were assessed using multiple linear regression (MLR) models. The mean (±SD) of measured sdLDL-C and oxLDL concentrations were 11.8± 10.0mg/dl and 53.4± 14.2U/L in the non-DM group and 0.20 ± 0.81 mg/dl and 46.0± 15.3U/L in the DM group, respectively. The effects of measured sdLDL-Cs were significant (p= 0.031), whereas those of estimated sdLDL-Cs were not (p= 0.060, p= 0.116) in the non-DM group in the MLR models. The effects of sdLDL-Cs in the DM group were not significant. In the general population, high level of sdLDL-C appeared to be associated with high level of oxLDL. The equation for estimating sdLDL-C developed from a general population should be applied with caution to a special population, such as patients with DM on treatment.

Small dense low-density lipoprotein cholesterol compared to other lipoprotein biomarkers for predicting coronary heart disease among individuals with normal fasting glucose: The Multi-Ethnic Study of Atherosclerosis

ObjectiveThis study compared small dense low-density lipoprotein cholesterol (sdLDL-C) with apolipoprotein B (apo B), and low-density lipoprotein particles (LDL-P) in predicting CHD risk in generally healthy adults with normal fasting glucose (NFG). MethodsThis study was conducted among participants with NFG in the Multi-Ethnic Study of Atherosclerosis (MESA) prospective cohort with measurements of sdLDL-C, LDL-P, and apo B available at baseline (2000–2002) and follow-up CHD data (through 2015) (N = 3,258). Biomarkers were evaluated as quartiles, and in categories using clinically and 75th percentile-defined cut-points. Discordance/concordance of sdLDL-C relative to other biomarkers was calculated using 75th percentile cut-points and linear regression residuals. Associations between individual biomarkers, sdLDL-C discordance and CHD incidence were evaluated using Cox proportional hazards regression. ResultsThere were 241 incident CHD events in this population through 2015. Higher sdLDL-C, apo B, LDL-P were similarly associated with increased CHD in individuals with NFG. Discordance of sdLDL-C with apo B or LDL-P by 75th percentiles was not significantly associated with CHD. Residuals discordantly higher/lower sdLDL-C relative to apo B (discordant high HR=1.26, 95% CI: 0.89, 1.78; discordant low HR=0.94, 95% CI: 0.68, 1.29) and LDL-P (discordant high HR=1.25, 95% CI: 0.88, 1.75; discordant low HR=0.84, 95% CI:0.60, 1.16), compared to those with concordant measures, had non-statistically significant higher/lower risk of CHD. ConclusionsResults suggest sdLDL-C, apo B and LDL-P are generally comparable for predicting CHD events in normoglycemic individuals. Larger studies are needed to confirm findings and to investigate whether measurement of sdLDL-C may be beneficial to evaluate as an additional risk-enhancing factor.

Evaluation of (sdLDLc*HCYc)/HDLc ratio in clinical auxiliary diagnosis of primary cerebral infarction

BackgroundTimely detection of cerebral infarction is of vital importance in planning intervention effect of rapid rehabilitation. The clinical auxiliary diagnosis value of single biomarker, including small dense low-density lipoprotein concentration (sdLDLc), homocysteine concentration (HCYc) and high-density lipoprotein cholesterol concentration (HDLc) for cerebral infarction has been confirmed by many studies. Whether the use of three biomarkers in combination by calculating (sdLDLc*HCYc)/HDLc ratio could improve the diagnosis ability for primary cerebral infarction remains to be unclear. In the present study, we conducted a cross-sectional study to evaluate the value of (sdLDLc*HCYc)/HDLc ratio in clinical auxiliary diagnosis of primary cerebral infarction.MethodsA total of 583 participants, including 299 healthy participants as control group and 284 participants diagnosed with first cerebral infarction as experiment group, were included in this respective study. The serum sdLDLc, HDLc and HCYc were measured by peroxidase method, enzyme‐linked immunosorbent assay and an enzymatic method, respectively.ResultsThe average concentration of sdLDL and HCY (0.69 ± 0.29 mmol/L and 18.14 ± 6.62 μmol/L) in experiment group was significantly higher than those in the control group (0.55 ± 0.22 mmol/L and 10.77 ± 2.67 μmol/L, P < 0.05). However, the average concentration of HDL (1.47 ± 0.25 mmol/L) in the control group was higher than that in the experiment group (1.33 ± 0.28 mmol/L, P < 0.05). Spearman correlation coefficient showed the three indicators are independent of each other. The positive predictive value of (sdLDLc*HCYc)/HDLc ratio (61.27%, 95% CI: 55.31–66.92) is higher than that in single biomarker (sdLDLc: 6.69 95% CI: 4.19–10.42, HCYc: 38.38%, 95% CI: 32.75–44.33, HDLc: 3.87%, 95% CI: 2.05–7.02). Receiver-operating characteristic curve (ROC) analysis illustrated that predictive power of (sdLDLc*HCYc)/HDLc was higher than single biomarker, including sdLDLc, HCYc and HDLc, in primary cerebral infarction.ConclusionsTherefore, (sdLDLc*HCYc)/HDLc ratio might be a better new indicator in clinical auxiliary diagnosis of primary cerebral infarction, which could be contributed to predicting cerebral infarction occurrence and provide a scientific basis for early prevention.

Association of small dense low-density lipoprotein cholesterol with H-type hypertension and MTHFR gene polymorphism

To investigate the expression of small dense low-density lipoprotein cholesterol (sdLDL-C) in patients with H-type hypertension and its association with H-type hypertension and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. The retrospective study method was used,and a total of 207 hospitalized hypertensive patients (76 males and 131 females, aged 40-82 years, median age 66 years) admitted to the Zibo First Hospital from March 2021 to March 2022 were enrolled in this study. The levels of homocysteine (Hcy), sdLDL-C, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein (a) [Lp(a)] were measured. The patients were divided into H-type hypertensive group (n=105, 40 males and 65 females) and non-H-type hypertensive group (n=102, 36 males and 66 females) according to Hcy levels. The C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene was detected in each group. Logistic regression analysis was performed for the related factors of H-type hypertension. The serum sdLDL-C levels were (0.92±0.31) and (0.65±0.28) mmol/L in H-type hypertension group and non-H-type hypertension group, respectively. The sdLDL-C levels in H-type hypertension group were significantly higher than those in non-H-type hypertension group (t=6.500, P<0.01). There was no significant difference in the serum sdLDL-C levels between males and females in H-type hypertension group (t=-1.543, P=0.129). The CC, CT, TT genotypes and C and T allele frequencies of MTHFR C677T in H-type hypertension group were significantly different from those in non-H-type hypertension group (P<0.05). The Hcy and sdLDL-C levels in different genotypes of MTHFR in H-type hypertension group were significantly different (H=12.742, P=0.002; F=3.345, P=0.042). Among them, Hcy levels were higher in TT genotype than in CT and CC genotypes, respectively (Z=-28.099, P=0.003; Z=-16.112, P=0.040), and sdLDL-C levels were higher in TT genotype than in CC genotype (t=-2.587, P=0.012). Logistic regression analysis showed that age, sdLDL-C, and MTHFRC677T TT genotypes were associated with the development for H-type hypertension. In conclusion, the level of sdLDL-C is associated with MTHFR gene polymorphisms and may be associated with the development of H-type hypertension.

Small dense low-density lipoprotein and clinical factors factors associated with early onset acute coronary syndrome

Small Dense LDL (sdLDL) has grown in consensus to be the more specific atherogenic subclass of LDL-C in the pathogenesis of atherosclerosis and coronary artery disease. Measurement of sdLDL could potentially improve the management of risk populations in primary and secondary prevention.

Lipid Profile and Small Dense Low-Density Lipoprotein in Acute Coronary Syndrome Patients: Relationships to Demographic, Clinical, Angiographic, and Therapeutic Variables.

Several lines of evidence have supported small dense low-density lipoproteins (sd-LDL) as a marker of cardiovascular disease. The present study assessed the relationship between lipid profile and sd-LDL levels with demographic, clinical, angiographic, and therapeutic variables in acute coronary syndrome (ACS) patients. This was a single-centre, prospective, cross-sectional study conducted from September 2014 to September 2015. Patients with a diagnosis of ACS were included in this study. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were determined by direct homogenous assay and sd-LDL levels were calculated using an earlier described equation by Srisawadi et al. Results: A total of 200 patients with a diagnosis of ACS were studied. Males constituted 78% of the population cohort and almost 45% of participants were aged &lt;45 years. Patients aged ≤45 years displayed higher mean sd-LDL levels of 30.40 ± 14.18 mg/dL versus patients aged &gt;45 years with mean sd-LDL levels of 28.01 ± 11.58 mg/dL, but the difference was not statistically significant (p = 0.19). Females also displayed higher mean sd-LDL levels, but the difference also failed to achieve statistical significance (30.95 ± 13.44 mg/dL and 28.54 ± 12.64, respectively; p = 0.185). Diabetics had higher mean sd-LDL levels (33.64 ± 13.01 mg/dL and 28.07 ± 12.60 mg/dL; p = 0.273) whilst smokers had lower mean levels (27.21 ± 12.12 mg/dL and 30.51 ± 13.21 mg/dL, respectively; p = 0.071). However, the ratio of sd-LDL/lb-LDL (large buoyant LDL) was significantly higher in diabetics (0.48 vs. 0.39; p = 0.023). In the angiography cohort (n = 88), single-vessel disease was the most predominant overall while among patients aged &gt;45 years, triple-vessel disease was significantly higher (p = 0.005). Similarly, the sd-LDL levels were 33.12 ± 11.13 mg/dL, 27.68 ± 9.80 mg/dL, and 31.65 ± 15.26 mg/dL among patients with single, double, and triple-vessel disease and did not differ significantly (p = 0.262). Prior statin users had significantly lower mean sd-LDL levels of 24.79 ± 12.23 mg/dL compared to statin-naïve patients with a mean sd-LDL of 30.01 ± 12.79 mg/dL (p = 0.027). Non-HDL levels were also significantly lower in prior statin users (112.83 mg/dL vs. 128.9 mg/dL; p = 0.017). In this cohort of ACS patients, age, sex, diabetes, smoking, and the angiographic severity of coronary artery disease had no significant impact on sd-LDL levels, while prior statin usage led to significantly lower sd-LDL levels. Diabetic patients, however, did have significantly higher sd-LDL/lb-LDL ratios.