sdLDL-C Levels Research Articles

An equation for calculating small dense low-density lipoprotein cholesterol

ObjectiveSmall dense low-density lipoprotein cholesterol (sdLDL-C), as an emerging atherogenic factor of cardiovascular diseases, requires additional tests. We aimed to establish a sdLDL-C equation using standard lipid profile and evaluate its capacity of identifying the residual cardiovascular risk beyond LDL-C and apolipoprotein B (ApoB).MethodsThis cross-sectional study included 25 435 participants from Health Management Cohort and 11 628 participants from China Health and Retirement Longitudinal Study (CHARLS) to construct and evaluate the sdLDL-C equation by least-squares regression model. The equation for sdLDL-C depended on low-density lipoprotein cholesterol (LDL-C) and an interaction term between LDL-C and the natural log of triglycerides (TG).ResultsThe modified equation (sdLDL-C = 0.14*ln(TG)*LDL-C − 0.45*LDL-C + 10.88) was more accurate than the original equation in validation set (slope = 0.783 vs. 0.776, MAD = 5.228 vs. 5.396). Using the 80th percentile (50 mg/dL) as a risk-enhancer rule for sdLDL-C, accuracy of the modified equation was higher than the original equation in validation set (90.47% vs. 89.73%). The estimated sdLDL-C identified an additional proportion of high-risk individuals in BHMC (4.93%) and CHARLS (1.84%).ConclusionThe newly developed equation in our study provided an accurate tool for estimating sdLDL-C level among the Chinese population as a potential cardiovascular risk-enhancer.

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.

Calculated Small Dense Low-Density Lipoprotein Cholesterol Level is A Predominant Predictor for New Onset of Ischemic Heart Disease.

A high level of directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for ischemic heart disease (IHD). However, it remains unclear whether estimated sdLDL-C level is a predictor for IHD. We investigated the associations of new onset of IHD with levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), LDL-C and calculated sdLDL-C by Sampson's equation. After exclusion of subjects with IHD or those with TG ≥ 800 mg/dL, a total of 18,176 subjects (men/women: 11,712/6,464, mean age: 46 years) were recruited among 28,990 Japanese individuals who received annual health checkups. During the 10-year follow-up period, 456 men (3.9%) and 121 women (1.9%) newly developed IHD. Multivariable Cox proportional hazard analyses after adjustment of age, sex, obesity, smoking habit, family history of IHD, estimated glomerular filtration rate, hypertension and diabetes mellitus at baseline showed that the hazard ratio (HR) (1.38 [95% confidence interval: 1.03-1.85]) for new onset of IHD in subjects with the 4th quartile (Q4) of sdLDL-C (≥ 42 mg/dL) was significantly higher than that in subjects with the 1st quartile (Q1) (≤ 24 mg/dL) as the reference, though the adjusted HRs in subjects with Q2-Q4 of TC, HDL-C, non-HDL-C, LDL-C and TG were comparable with those in subjects with Q1 of the respective lipid fractions. The adjusted HR with a restricted cubic spline increased with a higher level of calculated sdLDL-C as a continuous value at baseline. sdLDL-C level calculated by Sampson's equation is a predominant predictor for the development of IHD in a general Japanese population.

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.

Detailed Lipid Profiles and Lipid-related Residual Risk after 12-week 10 mg Rosuvastatin Treatment for Acute Myocardial Infarction.

Objective We aimed to reveal detailed on-treatment lipid profiles, lipid-related surrogate markers, and factors predicting failure to achieve the guideline-recommended lipid management goal following guideline-recommended statin treatment in Japanese patients with acute myocardial infarction (AMI). Methods and Results Sixty AMI patients who underwent coronary intervention and had received rosuvastatin 10 mg/day since the start of their hospitalization were assessed for on-treatment lipid-related profiles, including high-sensitivity C-reactive protein, small dense low-density lipoprotein cholesterol (sd LDL-C), and lipoprotein (a), at the 12-week follow-up. Patients who failed to achieve the guideline-recommended lipid management at 12 weeks were defined as the "unachieved group." Univariate and multivariate logistic regression analyses were performed to evaluate the predictors of inclusion in the unachieved group after high-dose statin treatment. Despite the use of high-dose rosuvastatin, 61.7% of the enrolled AMI patients were included in the unachieved group. In addition, the unachieved group had higher sd LDL-C and lipoprotein (a) levels than the achieved group. Logistic regression analyses demonstrated that low baseline high-density lipoprotein cholesterol (HDL-C) levels and the absence of diabetes were predictors of inclusion in the unachieved group. Conclusion More than half of the Japanese AMI patients treated with rosuvastatin 10 mg/day did not achieve the guideline-recommended goal of lipid management and still had lipid-related residual risk at 12 weeks. Particular attention should be paid to patients with low baseline HDL-C levels and those without diabetes with regard to their on-treatment lipid profiles.

A Study Assessing the Correlation of Atherogenic Index of Plasma with Severity of Coronary Artery Disease by Modified Gensini Score in Postmenopausal Women

ABSTRACT Introduction: The latest area of interest in lipids is small dense low-density lipoprotein cholesterol (sdLDL-C). They are highly atherogenic. There is no effective way of estimating them convetionally. Atherogenic index of plasma (AIP) reflects the level of sdLDL-C. The postmenopausal women have increased likelihood for coronary artery disease (CAD). In this study, the correlation between AIP and severity of CAD in postmenopausal women was assessed. Materials and Methods: A total of 448 postmenopausal women with chest pain were screened, of which 252 had a provisional diagnosis of CAD. Of them, 148 patients satisfying inclusion criteria were enrolled. Routine investigations, electrocardiogram, echocardiography, and coronary angiogram (CAG) were performed. Modified Gensini score (mGS) was used for severity of CAD. Chi-square test and Spearman correlation were used to analyze the correlation. Results: The mean age was 57 ± 8.3 years. The most common presentation was STEMI (32.4%), followed by unstable angina (28.4%). Patients already on statin therapy were 26.4%. Hypertension (HTN) was the most common risk factor (38.5%), followed by diabetes with HTN (23%). The mean AIP and mGS score were 0.23 ± 0.16 and 99.66 ± 65.61, respectively. Higher AIP values were seen in patients with higher mGS. Patients on statins and with normal lipid parameters showed higher mGS and AIP. There was a positive correlation of AIP with diabetes, HTN, Vitamin-D deficiency, C-reactive protein, body mass index, waist-circumference, waist-hip ratio, and waist-height ratio. Conclusion: AIP is a novel indicator and a strong marker for predicting the severity of CAD in postmenopausal women. In postmenopausal women with recurrent CAD and on statin therapy previously, AIP levels were high, implying that they need further management.

Value evaluation of serum (sdLDLc*HCYc)/HDLc ratio in the stability of intracranial arterial plaques in patients with acute cerebral infarction.

We aimed to analyze the value of serum (sdLDLc*HCYc)/HDLc ratio in the stability of intracranial arterial plaques among patients with acute cerebral infarction. A retrospective analysis was conducted on 140 patients with acute cerebral infarction admitted to the neurology department and 101 healthy individuals for regular examinations in our hospital from 2013 to 2019, who were respectively allocated into the study group and the control group. Participants in both groups were measured for serum sdLDLc, HDLc, and HCYc using peroxidase method, enzyme-linked immunosorbent assay, and enzyme method, respectively. The laboratory indexes of the two groups were compared. The multivariate logistic regression analysis was done to analyze the influencing factors of the stability of intracranial artery plaque in patients with acute cerebral infarction. The value of high-density lipoprotein cholesterol (HDL-C), homocysteine, sdLDLc, (sdLDLc*HCYc)/HDLc in diagnosing the stability of intracranial artery plaque was also evaluated in patients with acute cerebral infarction. There was no distinct difference in height, hypertension, diabetes, coronary heart disease, smoking history and drinking history between the two groups (P>0.05). The study group showed statistically significant differences in age, gender, weight, and BMI (P<0.05). The current study demonstrated no statistical difference in the levels of TG, low-density lipoprotein cholesterol (LDL-C), α-lipoprotein, and HCYc between the two groups (P>0.05). However, the levels of TC, HDL-C, sdLDLc, (sdLDLc*HCYc)/HDLc in the study group were significantly different when comparing with the control group (P<0.05). No statistically significant difference was found in the levels of TG, triglycerides, LDL-C, α-lipoprotein, and HCYc among patients with different degrees of stenosis in the study group (P>0.05). The level of HDL-C was significantly lower in cases of severe stenosis compared to no stenosis, mild stenosis and moderate stenosis, with severe stenosis showing the lowest levels; mild stenosis had lower levels than no stenosis, while moderate stenosis had lower levels than both no stenosis and mild stenosis (P<0.05). The levels of sdLDLc, (sdLDLc*HCYc)/HDLc exhibited a significant increase in cases of severe stenosis as compared tono stenosis, mild stenosis, and moderate stenosis. Furthermore, the levels of sdLDLc, (sdLDLc*HCYc)/HDLc were found to be higher in moderate stenosis as compared to no stenosis and mild stenosis. Similarly, the levels of sdLDLc, (sdLDLc*HCYc)/HDLc were observed to be higher in mild stenosis than no stenosis (P<0.05).The independent variables were set as the indicators with difference in single factor comparison, including age, gender, BMI, TC, LDL-C, HDL-C, HCYc, sdLDLc, (sdLDLc*HCYc)/HDLc. The dependent variable was the stability of intracranial artery plaque in patients with acute cerebral infarction. After variable selection, the results showed that the factors influencing the stability of intracranial artery plaque in patients with acute cerebral infarction were age, BMI, (sdLDLc*HCYc)/HDLc. The degree of plaque enhancement was used as a criterion to reflect the stability of plaque. ROC curve analysis showed that (sdLDLc*HCYc)/HDLc had a higher evaluation value for the stability of intracranial artery plaque than HDL-C, homocysteine, and sdLDLc in patients with acute cerebral infarction. The serum (sdLDLc*HCYc)/HDLc ratio was found to have potential in evaluating the stability of intracranial arterial plaques in patients with acute cerebral infarction.

Red Blood Cells' Omega-6 and Omega-3 Polyunsaturated Fatty Acids Have a Distinct Influence on LDL Particle Size and its Structural Modifications.

While Omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) have established effects on cardiovascular disease (CVD) risk factors, little is known about their impacts on LDL quality markers. To assess the associations of n-3 and n-6 PUFA within red blood cells (RBC) with LDL particle size, small dense LDL-c (sdLDL-c), and electronegative LDL [LDL(-)] in adults with CVD risk factors. Cross-sectional study involving 335 men and women aged 30 to 74 with at least one cardiovascular risk factor. Analyses were conducted on biochemical parameters, such as glucose, insulin, HbA1c, C-reactive protein (CRP), lipid profile, lipoprotein subfractions, electronegative LDL particle [LDL(-)] and its autoantibody, and RBC n-3 and n-6 PUFAs. Independent t-test/Mann-Whitney test, one-way ANOVA/Kruskal-Wallis test, and multiple linear regressions were applied. All tests were two-sided, and a p-value of less than 0.05 was considered statistically significant. The RBC n-6/n-3 ratio was associated with increased LDL(-) (β = 4.064; 95% CI = 1.381 - 6.748) and sdLDL-c (β = 1.905; 95% CI = 0.863 - 2.947) levels, and reduced LDL particle size (β = -1.032; 95% CI = -1.585 - -0.478). Separately, n-6 and n-3 PUFAs had opposing associations with those parameters, reinforcing the protective effects of n-3 and showing the potential negative effects of n-6 on LDL particle quality. RBC n-6 PUFA was associated with increased cardiometabolic risk and atherogenicity of LDL particles, while n-3 PUFA was associated with better cardiometabolic parameters and LDL particle quality.

Effect of PCSK9 inhibition on plasma levels of small dense low density lipoprotein-cholesterol and 7-ketocholesterol

Oxidized forms of cholesterol (oxysterols) are implicated in atherogenesis and can accumulate in the body via direct absorption from food or through oxidative reactions of endogenous cholesterol, inducing the formation of LDL particles loaded with oxidized cholesterol. It remains unknown whether drastic reductions in LDL-cholesterol (LDL-C) are associated with changes in circulating oxysterols and whether small dense LDL (sdLDL) are more likely to carry these oxysterols and susceptible to the effects of PCSK9 inhibition (PCSK9i). We investigate the effect of LDL-C reduction accomplished via PCSK9i on changes in plasma levels of sdLDL-cholesterol (sdLDL-C) and a common, stable oxysterol, 7-ketocholesterol (7-KC), among 134 patients referred to our Preventive Cardiology clinic. Plasma lipid panel, sdLDL-C, and 7-KC measurements were obtained from patients before and after initiation of PCSK9i. The intervention caused a significant lowering of LDL-C (-55.4 %). The changes in sdLDL-C levels (mean reduction 51.4 %) were highly correlated with the reductions in LDL-C levels (R = 0.829, p < 0.001). Interestingly, whereas changes in plasma free 7-KC levels with PCSK9i treatment were much smaller than (-6.6 %) and did not parallel those of LDL-C and sdLDL-C levels, they did significantly correlate with changes in triglycerides and very low-density lipoprotein-cholesterol (VLDL-C) levels (R = 0.219, p = 0.025). Our findings suggest a non-preferential clearance of LDL subparticles as a consequence of LDL receptor upregulation caused by PCSK9 inhibition. Moreover, the lack of significant reduction in 7-KC with PCSK9i suggests that 7-KC may be in part carried by VLDL and lost during lipoprotein processing leading to LDL formation.

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.

An increase in calculated small dense low-density lipoprotein cholesterol predicts new onset of hypertension in a Japanese cohort.

A disorder of lipid metabolism is involved in cardiovascular diseases including hypertension. A high level of small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for atherosclerotic cardiovascular disease. However, the association between sdLDL-C and hypertension has not been fully investigated. We investigated the associations between the development of hypertension during a 10-year period and levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), and LDL-C and sdLDL-C calculated by using the Sampson equations in 28,990 Japanese subjects who received annual health examinations. After exclusion of subjects with missing data, those with hypertension, and those with TG ≥ 800 mg/dL at baseline, a total of 15,177 subjects (men/women: 9374/5803, mean age: 46 years) were recruited. During the 10-year period, 2379 men (25.4%) and 724 women (12.5%) had new onset of hypertension. Multivariable Cox proportional hazard model analyses showed that levels of HDL-C, non-HDL-C, TG and sdLDL-C, but not levels of TC and LDL-C, were independent risk factors for the development of hypertension after adjustment of age, sex, family history of hypertension, systolic blood pressure, obesity, current smoking habit, alcohol drinking habit, estimated glomerular filtration rate, diagnosis of diabetes mellitus and use of lipid-lowering drugs and that the adjusted risk of sdLDL-C (per 1-standard deviation) was highest (hazard ratio [95% confidence interval: 1.09 [1.05-1.13]). The addition of sdLDL-C to traditional risk factors for hypertension significantly improved the discriminatory capability, which was better than that of other lipid fractions. In conclusion, a high level of calculated sdLDL-C predicts the development of hypertension.

SMALL DENSE LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND CENTRAL OBESITY ASSOCIATED WITH DIABETES MELLITUS AMONG INDONESIAN ADULTS

ABSTRACTBackground: Small dense low-density lipoprotein (sdLDL-C) is an atherogenic lipoprotein. Increased sdLDL-C concentration was hypothesized to be associated with obesity and diabetes mellitus (DM).Objectives: The study aimed to determine the association between sdLDL-C, central obesity, and DM among Indonesian adults, controlled by personal and clinical parameters.Materials and Methods: This study used secondary data from Basic Health Research 2013 of the Ministry of Health, which applied a cross-sectional study design. For this purpose, 30,548 subjects aged 19-79 were analyzed. The sdLDL-C was performed by using Sampson Formula derived from conventional lipid panels. As investigated by Sampson, the formula referred to cLDL-C (calculated LDL-C) and ElbLDL-C (estimated large buoyant LDL-C).Results: There was a positive association between sdLDL-C and central obesity (OR: 3.94; 95% CI: 3.13-3.89), as well as sdLDL-C and DM status (OR: 1.98; 95% CI; 1.43-2.75) after adjusting the personal and clinical parameters.Conclusion: This study demonstrated that the increment of sdLDL-C level and central obesity affected DM status in Indonesian adults. It implies that the sdLDL-C was a potential biomarker to assess the risk of DM.Keywords: Central obesity, Diabetes mellitus, Hypertension, Indonesian adult, sdLDL-C

Hypertriglyceridemia contributes significantly to high prevalence of small dense LDL-cholesterol in patients with type 2 diabetes, even when LDL-C targets are achieved.

Small-dense (sd)LDL-cholesterol (C) is a potent risk factor for atherosclerotic cardiovascular disease (ASCVD) beyond LDL-C, and 35mg/dL has been proposed as a cut-off value for high-sdLDL-C. sdLDL-C levels are strongly regulated by triglycerides (TG) and LDL-C levels. LDL-C has detailed targets for the prevention of ASCVD, while TG is only defined as abnormal at ≥ 150mg/dL. We investigated the effect of hypertriglyceridemia on the prevalence of high-sdLDL-C in patients with type 2 diabetes and explored the optimal TG levels that would suppress high-sdLDL-C. Fasting plasma was obtained from 1569 patients with type 2 diabetes who were enrolled in the regional cohort study. sdLDL-C concentrations were measured by the homogeneous assay established by us. High-sdLDL-C was defined as ≤ 35mg/dL according to the Hisayama Study. Hypertriglyceridemia was defined as ≥ 150mg/dL. All lipid parameters except HDL-C were higher in the high-sdLDL-C group than in the normal-sdLDL-C group. The receiver operating characteristic (ROC) curves revealed that high sdLDL-C was identified sensitively by TG and LDL-C, with cut-off values of 115mg/dL for TG and 110mg/dL for LDL-C. The presence of hypertriglyceridemia increased the prevalence of high-sdLDL-C sixfold more than the normotriglyceridemic counterpart, regardless of statin use. This substantial influence of hypertriglyceridemia was found even within the control target of LDL-C levels (70-120mg/dL) for diabetic subjects. The TG cut-off for high-sdLDL-C was well below 150mg/dL in a diabetic population. Amelioration of hypertriglyceridemia is needed even when LDL-C targets for diabetes are achieved.

Discordance between lipoprotein (a) and LDL-cholesterol levels in cardiovascular risk assessment in apparently healthy subjects

Background and aimsLipoprotein(a) is a recognized independent cardiovascular risk factor and apolipoprotein B (apoB) level better reflects the risk than LDL-cholesterol. Despite this cardiovascular prediction mostly relies on traditional risk factors. We evaluated the association between Lp(a) and lipid biomarkers of cardiovascular risk in relation to age and sex in apparently healthy individuals. Methods and results422 presumably healthy subjects aged 19–84 were included. Lipid profile, Lp(a), apoB and small dense low-density lipoprotein cholesterol (sdLDL-C) were assayed. Subjects were divided at desirable cut-points of apoB and LDL-C. A group with elevated apoB (≥100 mg/dL) at low LDL-C (≤115 mg/dL) was appointed as high-risk and a group with low apoB but elevated LDL-C as low-risk. Significantly elevated triglycerides, TG/HDL-C and sdLDL-C were found in high risk group, but Lp(a) levels were comparable. TG/HDL-C was the best predictor of high risk with a very good diagnostic accuracy (AUC = 0.85), whereas Lp(a) had no discriminatory power. Women aged ≤40 with low LDL-C ≤ 100 mg/dL and elevated Lp(a) ≥ 40 mg/dL had higher levels of apoB and sdLDL-C (p = 0.002; p = 0.07) than those with Lp(a) < 40 mg/dL, which was not observed in men. In young females increase of LDL-C and apoB significantly raised the risk of elevated Lp(a). ConclusionsWomen younger than 40 with low LDL-C may be at increased cardiovascular risk associated with elevated Lp(a) and apolipoprotein B levels. Inclusion of Lp(a) and apoB in the routine lipid testing providing information on an individual level may improve the prediction of cardiovascular risk in primary prevention.

Hepatitis C virus eradication by direct-acting antivirals causes a simultaneous increase in the prevalence of fatty liver and hyper low-density lipoprotein cholesterolemia without an increase in body weight.

Hepatitis C virus (HCV) infection has been reported to cause liver steatosis. Thus, eradicating HCV with direct-acting antivirals (DAAs) is expected to reduce liver steatosis. We aimed to clarify long-term changes in the prevalence of fatty liver and hyper-low-density lipoprotein (LDL) cholesterolemia and their associations in patients who achieve successful HCV eradication using DAAs. This retrospective study included patients with HCV who achieved sustained virologic response after interferon-free DAA and analyzed the changes in the prevalence of fatty liver diagnosed with controlled attenuation parameter (CAP), hyper-LDL cholesterolemia, and their relationships at baseline (n=100) and 24weeks (SVR24, n=100), 96weeks (SVR96, n=100), and 144weeks (SVR144, n=90) after DAA. In 100 participants, the prevalence of fatty liver (19% vs. 32%, p=0.0349) and hyper-LDL cholesterolemia (6% vs. 15%, p=0.0379) significantly increased without changes in body weight at SVR96. Median total cholesterol, low-density lipoprotein cholesterol (LDL-C), and small-dense-LDL (sdLDL) levels and CAP values were significantly greater at SVR24, SVR96, and SVR144 than at baseline. Baseline CAP values and changes in CAP values were significantly negatively correlated at every observation point: r=-0.5305, p<0.0001 at SVR24; r=-0.3617, p=0.0005 at SVR96; and r=-0.4735, p<0.0001 at SVR144. A similar relationship was observed in cholesterol levels. Unlike at baseline, CAP values were significantly positively correlated with LDL-C and sdLDL-C levels at all observation points after DAAs. Direct-acting antivirals may cause an increased prevalence of fatty liver accompanying hyper-LDL cholesterolemia without increased body weight. As post-SVR liver steatosis could cause HCC, careful follow-up may be required.

Serum bilirubin levels are negatively associated with atherogenic lipids in Saudi subjects with type 2 diabetes: A pilot study

&lt;b&gt;Background: &lt;/b&gt;Recent research has demonstrated the possible relevance of bilirubin in metabolic and cardiovascular disorders. Lipid abnormalities are a major problem that is related with an increased risk of cardiovascular disease in diabetics. This study examined the relationship between serum bilirubin and direct bilirubin concentrations and atherogenic lipids in patients with type 2 diabetes (T2DM).&lt;br /&gt; &lt;b&gt;Methods&lt;/b&gt;: This cross-sectional included 67 patients with type 2 diabetes and 39 matched healthy control. The lipid profile, including total cholesterol, HDL-C, and TG levels, fasting blood glucose, total bilirubin, direct bilirubin, ALT, AST, and ALP were measured using a dimension EXL clinical chemistry analyzer (Siemens Healthcare Diagnostics). Cholesterol in VLDL, LDL, and sdLDL were calculated from standard lipid assay results by the equations of Sampson et al.&lt;br /&gt; &lt;b&gt;Results&lt;/b&gt;: Serum bilirubin was lower in non T2DM subjects nearly significant (p=0.0.51) whereas direct bilirubin concentrations were lower in T2DM (p=0.008). ALT, AST, and ALP levels were higher in T2DM groups. The mean values of LDL-C, sdLDL-C, non HDL-C and VLDL-C were significantly increased in T2DM group and lower HDL-C. An inverse relationship could be observed with increase in serum total bilirubin and serum levels of LDL-C (r&lt;sup&gt;2&lt;/sup&gt;=0.139, p&amp;lt;0.005), sdLDL-C (r&lt;sup&gt;2&lt;/sup&gt;=0.137, p&amp;lt;0.005), VLDL-C (r&lt;sup&gt;2&lt;/sup&gt;=0.074, p&amp;lt;0.044), and non HDL-C (r&lt;sup&gt;2&lt;/sup&gt;=0.166, p&amp;lt;0.002) in T2DM group. The same inverse relationship was observed with serum direct bilirubin and serum levels of LDL-C (r&lt;sup&gt;2&lt;/sup&gt;=0.133, p&amp;lt;0.006), sdLDL-C (r&lt;sup&gt;2&lt;/sup&gt;=0.172, p&amp;lt;0.001), VLDL-C (r&lt;sup&gt;2&lt;/sup&gt;=0.118, p&amp;lt;0.01), and non HDL-C (r&lt;sup&gt;2&lt;/sup&gt;=0.182, p&amp;lt;0.001) in T2DM group.&lt;br /&gt; &lt;b&gt;Conclusions&lt;/b&gt;: A significant negative association was found between serum bilirubin levels and direct serum bilirubin with atherogenic lipids, suggesting that serum bilirubin may protect T2DM patients from development of cardiovascular disease. These findings indicate the need for additional research in a large cohort.

Glycative Stress, Glycated Hemoglobin, and Atherogenic Dyslipidemia in Patients with Hyperlipidemia.

(1) Background: Diabetes mellitus (DM) is a significant health problem and is associated with dyslipidemia; however, the association between glycative stress, in terms of glycated hemoglobin (HbA1c), and atherogenic dyslipidemia in hyperlipidemic patients with and without DM has rarely been reported. (2) Methods: We prospectively recruited 949 hyperlipidemic patients from the Lipid Clinic of the National Taiwan University Hospital. HbA1c and fasting serum lipids, including total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), small dense LDL-C (sdLDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, and advanced glycation end-products (AGEs), were measured. After fasting for 10-14 h, all subjects except those with DM underwent a standard oral glucose tolerance test (OGTT) with 75 g of glucose loading. All subjects were asked to discontinue the use of lipid-lowering agents for 8 weeks before recruitment. (3) Results: Patients with DM had a higher prevalence of hypertension and higher levels of triglyceride, TC/HDL-C ratio, AGEs, VLDL-C, and sdLDL-C. Among patients with higher HbA1c, the serum VLDL-C, AGEs, and TC/HDL-C ratio were significantly higher than those with lower HbA1c. After adjustment for covariates, multiple logistic regression analyses revealed different groups of dysglycemia with higher HbA1c had a higher odds ratio for TC/HDL-C ≥ 5, sdLDL-C ≥ 75th percentile, VLDL-C ≥ 75th percentile and AGEs ≥ 75th percentile. (4) Conclusions: A higher HbA1c was associated with a significant increase in the risk of atherogenic dyslipidemia and AGEs levels in patients with hyperlipidemia. The findings can be very promising in clinical application.

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.

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.

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.