Direct LDL-C Research Articles

Comparison of low-density lipoprotein cholesterol level calculated using the modified Martin/Hopkins estimation or the Friedewald formula with direct homogeneous assay measured low-density lipoprotein cholesterol.

IntroductionLow-density lipoprotein cholesterol (LDL-C) represents the primary lipoprotein target for reducing cardiovascular risk (CV). The aim of our study is to compare the direct and the calculated LDL-C levels in the range below 1.8 mmol/l and 2.6 mmol/l depending on triglycerides, and to evaluate the variation in remnant lipoprotein cholesterol.Material and methodsWe investigated 14 906 lipid profiles from fasting blood samples of Hungarian individuals with triglycerides < 4.5 mmol/l. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and direct LDL-C were measured by the enzymatic assay. We calculated LDL-C by Friedewald’s formula (F-LDL-C) and by using the new Martin/Hopkins estimation (MH-LDL-C).ResultsFor F-LDL-C below 1.8 mmol/l, MH-LDL-C was 58% between 1.8 and 2.59 mmol/l when TG was in the range 2.3–4.5 mmol/l. For F-LDL-C below 2.6 mmol/l, the MH-LDL-C concordance was 73% in the same TG range (2.3–4.5 mmol/l. If MH-LDL-C was less than 1.8 mmol/l or between 1.8 and 2.59 mmol/l, the difference between non-HDL-C (TC – HDL-C = AC: atherogenic cholesterol) and (MH)LDL-C was less than 0.8 mmol/l in the TG range below 2.3 mmol/l. The remnant lipoprotein cholesterol values were on average 0.5 mmol/l lower by the Martin/Hopkins estimation compared to the Friedewald’s calculation if the TG was above 2.3 mmol/l.ConclusionsThe Friedewald equation tends to underestimate LDL-C levels in very high and high-risk settings. Our analysis supports the conclusion that in Hungarian patients, LDL-C estimation using the Martin/Hopkins formula, which is validated by the beta-quantification method, yields a more accurate LDL-C value than that calculated by the Friedewald formula.

Dose-Response Effects of Strawberries on Atherogenic Lipoproteins: A Randomized Controlled Crossover Trial

Abstract Objectives Previous research indicates that consumption of strawberries may provide benefits for reduction of atherogenic lipoproteins but has not identified an optimal dose. Our objective was to evaluate effects of 2 doses of strawberry powder, approximately equivalent to 1 and 3 servings of strawberries per day, on serum lipoprotein concentrations. Methods Middle-aged adults (n = 40, age 49 ± 1 year) with elevated LDL-C (140 ± 4 mg/dL) and elevated BMI (29.4 ± 0.4 kg/m2) consumed 0 g/d (control), 13 g/d (low-dose), and 40 g/d (high-dose) of freeze-dried strawberry powder in a randomized crossover design (4-week supplementation periods separated by a 2 week compliance break). Fasting blood samples were obtained on two separate days (and averaged) at study-entry baseline and following each supplementation period. Results There were significant main effects of treatment (P ≤ 0.05) for calculated LDL-C, nonHDL-C, and total cholesterol (TC). In post hoc tests, the low-dose resulted in 5% lower LDL-C vs. the high-dose (P = 0.01), 4% lower nonHDL-C vs. control (P = 0.04), and 3% lower TC for the low-dose vs. control and high-dose (P ≤ 0.04). Compared to baseline, low-dose strawberry supplementation also significantly reduced direct LDL-C (−6.8 mg/dL, P = 0.02), but there was not a main effect of treatment. Conclusions Our results suggest that low-dose supplementation with freeze dried strawberry powder, roughly equivalent to one serving of strawberries per day, was superior to high-dose supplementation for improving atherogenic lipoproteins in overweight adults. Funding Sources California Strawberry Commission.

Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression.

Aim: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan.Methods: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression.Results: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C < 100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend = 0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population.Conclusions: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

P5332Magic mirror on the wall, can we reach our LDL-C goal? Comparison of calculated LDL-C and direct measured LDL-C levels in atherogenic dyslipidemia condition

Abstract Background LDL-C represents the primary lipoprotein target for reducing cardiovascular risk. LDL-C can either be calculated or measured directly. Friedewald equation has certain limitations especially with high triglyceride and low LDL-C levels. Although a number of automated direct LDL-C assays are commercially available, non of them is considered to be equivalent to the “gold standard” of direct LDL-C, beta quantitation, a complex and expensive process that is unavailable in routine clinical practice. In atherogenic dyslipidemia condition (ADC) (triglycerides≥2.3 mmol/L and HDL-C&lt;1.0 mmol/L) non-HDL-C and remnant cholesterol are proven additional risk factors. Purpose We compared one of the direct homogeneous assays with the widely used Friedewald's and the new Martin/Hopkins methods of estimation of LDL-C to see the differences in average LDL-C, remnant cholesterol and non-HDL-C levels and in availability of less than 1.8 mmol/L of LDL-C in atherogenic dyslipidemia condition. Methods We investigated 14 906 lipid profiles from fasting blood samples of Hungarian individuals with triglycerides &lt;4.5 mmol/L. Total cholesterol (TC), HDL-C, triglycerides (TG) and direct LDL-C (D-LDL-C) were measured directly by the enzimatic assays. We also estimated calculated LDL-C by the Friedewald's formula (F-LDL-C) and by using the new Martin/Hopkins estimation (MH-LDL-C). We have now prepared first a variant of Martin/Hopkins table in mmol/L, in which the modified adjustable factors of 2.2 are included. We determined also non-HDL-C and remnant cholesterol (RC) as a difference of non-HDL-C and F-LDL-C (F-RC), MH-LDL-C (MH-RC), D-LDL-C (D-RC). Results In the investigated population 19.25% was F-LDL-C, 15.48% MH-LDL-C and 7.92% D-LDL-C below 1.8 mmol/L. ADC occurred at 8.12%. For ADC, when F-LDL-C&lt;1.8 mmol/L (A), mean values for F-LDL-C, MH-LDL-C, D-LDL-C and non-HDL-C were 1.23±0.4; 1.65±0.39; 2.06±0.4 and 2.46±0.5 mmol/L respectively. These mean levels were 1.01±0.36; 1.4±0.3; 1.83±0.3 and 2.15±0.34 mmol/L for MH-LDL-C&lt;1.8 mmol/L (B). For D-LDL-C&lt;1.8 mmol/L (C), mean values were 0.79±0.35; 1.13±0.26; 1.54±0.19 and 1.83±0.25 mmol/L respectively. The average RC values (in mmol/L) for A were F-RC: 1.23±0.36; MH-RC: 0.81±0.18; D-RC: 0.4±0.17, for B 1.14±0.33; 0.74±0.14; 0.32±0.13, and for C 1.04±0.27; 0.70±0.1; 0.29±0.12 respectively. Conclusions The Friedewald equation tends to underestimate and the homogeneous enzimatic direct LDL-C assays to overestimate the LDL-C levels compared to the new, accurate, calculated LDL-C values in atherogenic dyslipidemia condition. Based on the data presented in our investigation we should like to propose that more realistic vasculo-protective lipid status can be attained if we calculate LDL-C using the Martin/Hopkins estimation.

Developing a Modified Low-Density Lipoprotein (M-LDL-C) Friedewald's Equation as a Substitute for Direct LDL-C Measure in a Ghanaian Population: A Comparative Study.

Despite the availability of several homogenous LDL-C assays, calculated Friedewald's LDL-C equation remains the widely used formula in clinical practice. Several novel formulas developed in different populations have been reported to outperform the Friedewald formula. This study validated the existing LDL-C formulas and derived a modified LDL-C formula specific to a Ghanaian population. In this comparative study, we recruited 1518 participants, derived a new modified Friedewald's LDL-C (M-LDL-C) equation, evaluated LDL-C by Friedewald's formula (F-LDL-C), Martin's formula (N-LDL-C), Anandaraja's formula (A-LDL-C), and compared them to direct measurement of LDL-C (D-LDL-C). The mean D-LDL-C (2.47±0.71 mmol/L) was significantly lower compared to F-LDL-C (2.76±1.05 mmol/L), N-LDL-C (2.74±1.04 mmol/L), A-LDL-C (2.99±1.02 mmol/L), and M-LDL-C (2.97±1.08 mmol/L) p < 0.001. There was a significantly positive correlation between D-LDL-C and A-LDL-C (r=0.658, p<0.0001), N-LDL-C (r=0.693, p<0.0001), and M-LDL-C (r=0.693, p<0.0001). M-LDL-c yielded a better diagnostic performance [(area under the curve (AUC)=0.81; sensitivity (SE) (60%) and specificity (SP) (88%)] followed by N-LDL-C [(AUC=0.81; SE (63%) and SP (85%)], F-LDL-C [(AUC=0.80; SE (63%) and SP (84%)], and A-LDL-C (AUC=0.77; SE (68%) and SP (78%)] using D-LDL-C as gold standard. Bland–Altman plots showed a definite agreement between means and differences of D-LDL-C and the calculated formulas with 95% of values lying within ±0.50 SD limits. The modified LDL-C (M-LDL-C) formula derived by this study yielded a better diagnostic accuracy compared to A-LDL-C and F-LDL-C equations and thus could serve as a substitute for D-LDL-C and F-LDL-C equations in the Ghanaian population.

ANALYSIS OF LDL-C MEASUREMENT USING DIRECT AND FRIEDEWALD FORMULA IN TYPE 2 DIABETES MELLITUS PATIENTS

LDL-C is important to evaluate the risk of cardiovascular disease. LDL-C can be measured directly or by using the Friedewald equation. Type 2 Diabetes Mellitus (DM) patients have tighter LDL-C target compared with normal population. This research is aimed to analyze the difference of LDL-C level measured by direct test and Friedewald equation in DM and non-DM. This research was a cross-sectional study using LDL-C data of 208 patients who were tested in Laboratory of Clinical Pathology, Hasanuddin University Hospital from a period of August 2015 to January 2016. LDL-C and other lipid were measured using ABX Pentra 400 meanwhile Friedewald LDL-C was calculated with equation LDLC= Total Cholesterol-HDL-C-(1/5 Triglycerides). Type 2 DM patients were diagnosed by ADA 2015 criteria or who had previous DM history. Friedewald LDL-C estimates lower than direct method (139.07+50.60 mg/dL vs 155.33+51.74 mg/dL, p=0.000). Delta of direct LDL-C and Friedewald equation measurement is higher in DM than non-DM patients (11.97+11.52% vs 8.49+11.27%, p=0.030) Fridewald LDL-C estimates LDL-C lower than direct method and the difference is wider in DM than non-DM. It is suggested to measure LDL-C directly in DM type 2 to reach the actual LDL-C target.

Validation of the Friedewald formula for the estimation of low density lipoprotein cholesterol in a sub-Saharan African population

BackgroundLow density lipoprotein cholesterol (LDL-C) levels are used to estimate cardiovascular disease (CVD) risk and to guide prescriptions. To circumvent the challenges of direct LDL-C measurement, guidelines recommend the use of Friedewald formula derived LDL-C levels. Despite reported limitations of this formula, its validity in sub-Saharan Africans has not been adequately investigated. ObjectiveTo assess the validity of the Friedewald formula derived against directly (homogeneous) measured LDL-C in adult Cameroonians. MethodsWe reviewed the fasting lipid profiles of 2500 patients, performed between March 2012 and January 2016 using enzymatic colorimetric method (reference), at the Douala General Hospital laboratory. The Friedewald formula was used to calculate LDL-C from total cholesterol, high density lipoprotein cholesterol and triglyceride levels. Calculated LDL-C values were compared to the reference values, and clinical significance of differences between the two methods was assessed using total error allowable (TEa). ResultsThe difference between means of calculated and the reference LDL-C values was neither statistically nor clinically significant (3.33±1.51 vs. 3.33±1.25mmol/l; p=0.704). The calculated LDL-C correlated positively with the measured LDL-C value (r=0.749) and both methods showed a good agreement on Bland-Altman plot. Conversely, there was only moderate agreement (kappa=0.478, 95% CI: 0.455–0.502) between the two values in the stratification of cardiovascular risk according to the National Cholesterol Education Program/Adult Treatment Panel III. Consequently, 40.6% of the participants were misclassified. ConclusionFriedewald formula is technically accurate but has a modest clinical accuracy which can translate into a substantial misclassification of patients' cardiovascular risk and subsequent inappropriate therapeutic decisions.

LDL-cholesterol measurement in diabetic type 2 patients: a comparison between direct assay and popular equations

BackgroundLow density lipoprotein –Cholesterol (LDL-C) is one of the main factors for assessment of cardiovascular disease risk and it is more important in diabetic patients. Various methods are currently used for LDL-C measurements which are compared in this study.MethodsThis study was conducted in Diabetes Research Center based on laboratory results of 1721 diabetic patients who referred to laboratory for regular follow-up of lipid profile. LDL-C was measured directly and also estimated according to Friedwald, Anandraja and Chen formulas.ResultsResults of direct LDL-C measurements were lower than all calculations at triglycerides (TG) levels less than 150 mg/dL while in higher TG levels direct measurement values were higher than Friedwald and Anandraja formula. Friedwald and Chen formula results had better correlation(r) with direct measurement than Anandraja in different levels of TG and also were able to define LDL-C > 100 mg/dL more accurately.ConclusionsAlthough we observed excellent correlation between the studied formulas with direct measurement, using the formula can misclassified diabetic patients with LDL-C values near threshold (100 mg/dL). However calculated LDL-C based on Chen and Friedwald formula can be a suitable alternative for direct measurement especially in regions with limited resources.

Risk of misclassification with a non-fasting lipid profile in secondary cardiovascular prevention

AimsRoutinely fasting is not necessary for measuring the lipid profile according to the latest European consensus. However, LDL-C tends to be lower in the non-fasting state with risk of misclassification. The extent of misclassification in secondary cardiovascular prevention with a non-fasting lipid profile was investigated. Methods and results329 patients on lipid lowering therapy for secondary cardiovascular prevention measured a fasting and non-fasting lipid profile. Cut-off values for LDL-C, non-HDL-C and apolipoprotein B were set at <1.8mmol/l, <2.6mmol/l and <0.8g/l, respectively. Study outcomes were net misclassification with non-fasting LDL-C (calculated using the Friedewald formula), direct LDL-C, non-HDL-C and apolipoprotein B. Net misclassification <10% was considered clinically irrelevant. Mean age was 68.3±8.5years and the majority were men (79%). Non-fasting measurements resulted in lower LDL-C (−0.2±0.4mmol/l, P<0.001), direct LDL-C (−0.1±0.2mmol/l, P=0.001), non-HDL-C (−0.1±0.4mmol/l, P=0.004) and apolipoprotein B (−0.02±0.10g/l, P=0.004). 36.0% of the patients reached a fasting LDL-C target of <1.8mmol/l with a significant net misclassification of 10.7% (95% CI 6.4–15.0%) in the non-fasting state. In the non-fasting state net misclassification with direct LDL-C was 5.7% (95% CI 2.1–9.2%), 4.0% (95% CI 1.0–7.4%) with non-HDL-C and 4.1% (95% CI 1.1–9.1%) with apolipoprotein B. ConclusionUse of non-fasting LDL-C as treatment target in secondary cardiovascular prevention resulted in significant misclassification with subsequent risk of undertreatment, whereas non-fasting direct LDL-C, non-HDL-C and apolipoprotein B are reliable parameters.

Current Understanding in the Measurement of Low Density Lipoprotein Cholesterol: A Comparison of Direct Measurement by Homogenous Assays versus Calculations

Background: To compare the results obtained by direct homogenous assay for LDL-C to those obtained by Friedwalds and Anandrajas formulas with the assumption that the results obtained by direct assay are most accurate. This was a comparative study for the estimation of LDL-C using two different types of calculation formulas and direct estimation of LDL-C by homogenous method. Method: Serum Lipids and lipoproteins were measured in 505 fasting samples. Serum Total cholesterol was measured using CHOD-PAP method first described by Stadman on Siemens Dimensions Clinical Chemistry RXL Analyzer. Triglycerides were measured by Glycerol Phosphate peroxidase - PAP method. Direct LDL-C was measured by a homogenous assay by siemens diagnostics. A- HDL was measured by a homogenous method which uses PEG- cholesterol esterase using kit from siemens diagnostics. This was a comparative study for the estimation of LDL-C using two different types of calculation formulas and direct estimation of LDL-C by homogenous method. Results: A good correlation was found between D-LDL as compared to both F-LDL and A-LDL. Pearsons coefficient of correlation between F-LDL & D-LDL was 0.891 (p

An assessment of oxidized LDL in the lipid profiles of patients with obstructive sleep apnea and its association with both hypertension and dyslipidemia, and the impact of treatment with CPAP.

Obstructive sleep apnea (OSA) has been linked to increased oxidative stress, lipid peroxidation and worsening atherosclerosis. This study investigated oxidized low-density lipoprotein (oxLDL) as a marker of lipid peroxidation, and total LDL cholesterol (direct LDL-C), as a marker of the lipid profile among individuals with OSA, and its association with hypertension (HYP) and dyslipidemia (DYS). The impact of one year of continuous positive airway pressure (CPAP) was also assessed. Blood was collected after 12h of fasting from 99 consecutive patients who were diagnosed with OSA via polysomnography, and were also diagnosed with both HYP and DYS via clinical and laboratory studies. The patients were classified into the following three groups: GI [OSA with comorbidities (HYP or DYS)], GII [OSA without comorbidities], and GIII [control]. Thirty-five patients with an apnea/hypopnea index >20 per hour of sleep were randomized to groups that received either Sham-CPAP or CPAP treatments over 12 months. In a binary regression controlled for sex, age, body mass index, and glycemia, model 1 which analyzed direct LDL-C, demonstrated significant levels of risk in the setting of DYS but not in the settings of HYP and OSA. In model 2, which analyzed oxLDL, DYS (p=0.01), HYP (p=0.032), and OSA (p=0.039) were statistically significant. Significant alterations were observed in only the sleep parameters following one year of CPAP. Based on the statistical regression model, only the presence of DYS (p=0.001) was associated with the levels of direct LDL-C. The remaining comorbidities (OSA and HYP) were not significantly related to the levels of direct LDL-C. Regarding oxLDL, OSA, HYP and DYS each added significant score values to the levels of oxLDL. These findings are suggestive of the importance of assessing oxLDL among patients presenting with OSA, both with and without comorbidities.

Clinical impact of direct HDLc and LDLc method bias in hypertriglyceridemia. A simulation study of the EAS-EFLM Collaborative Project Group

BackgroundDespite international standardization programs for LDLc and HDLc measurements, results vary significantly with methods from different manufacturers. We aimed to simulate the impact of analytical error and hypertriglyceridemia on HDLc- and LDLc-based cardiovascular risk classification. MethodsFrom the Dutch National EQA-2012 external quality assessment of 200 clinical laboratories, we examined data from normotriglyceridemic (∼1 mmol/l) and hypertriglyceridemic (∼7 mmol/l) serum pools with lipid target values assigned by the Lipid Reference Laboratory in Rotterdam. HDLc and LDLc were measured using direct methods of Abbott, Beckman, Siemens, Roche, Olympus, or Ortho Clinical Diagnostics. We simulated risk reclassification using HDL- and sex-specific SCORE multipliers considering two fictitious moderate-risk patients with initial SCORE 4% (man) and 3% (woman). Classification into high-risk treatment groups (LDLc >2.50 mmol/l) was compared between calculated LDLc and direct LDLc methods. ResultsOverall HDLc measurements in hypertriglyceridemic serum showed negative mean bias of −15%. HDL-multipliers falsely reclassified 70% of women and 43% of men to a high-risk (SCORE >5%) in hypertriglyceridemic serum (P < 0.0001 vs. normotriglyceridemic serum) with method-dependent risk reclassifications. Direct LDLc in hypertriglyceridemic serum showed positive mean bias with Abbott (+16%) and Beckman (+14%) and negative mean bias with Roche (−7%). In hypertriglyceridemic serum, 57% of direct LDLc measurements were above high-risk treatment goal (2.50 mmol/l) vs. 29% of direct LDLc (33% of calculated LDLc) in normotriglyceridemic sera. ConclusionLDLc and HDLc measurements are unreliable in severe hypertriglyceridemia, and should be applied with caution in SCORE risk classification and therapeutic strategies.

Assessment of apoB dyslipoproteinemia in Korean population

ObjectivesThere is sparse data on apoB dyslipoproteinemia in Asian population. The purpose of this study was to assess apoB dyslipoproteinemia and to compare the LDL-C, non-HDL and apoB for risk assessment with percentile equivalent cut off in Korean population. MethodsWith 1193 Korean adult subjects, the prevalence and characteristics of different types of dyslipoproteinemias were analyzed in each age and gender group. The percentile values of direct LDL-C, calculated LDL-C, non HDL-C, HDL-C, apoAI, apoB and apoB/apoAI ratio were estimated. ResultsThe prevalences of normoapoB–hyperTG, hyperapoB–normoTG and hyperapoB–hyperTG dyslipoproteinemia were 6.9, 8.9 and 10.9% in men and 3.7, 6.4 and 2.8% in women. The 40th percentile of direct LDL-C, calculated LDL-C, non-HDL-C and apo B were 108, 104.2, 126 and 85mg/dl, respectively. The individual above optimal cut off was significantly underestimated with LDL-C than with non-HDL and apoB, in groups with adverse risk factors. ConclusionsThis study firstly shows the prevalence of various types of dyslipoproteinemias in Asian population. The percentile values of Korean population were similar to those of NHANES. Integration of lipid markers is needed for making clinical decisions and further research involving various populations and methodologies should be performed.

Small Dense Low-Density Lipoproteins Cholesterol can Predict Incident Cardiovascular Disease in an Urban Japanese Cohort: The Suita Study

Several lines of evidence indicate that small dense low-density lipoproteins (sd-LDL) are more atherogenic than large buoyant LDL; however, few prospective studies have addressed the role of sd-LDL in cardiovascular disease (CVD). We therefore examined the association between sd-LDL cholesterol (sd-LDL-C) and CVD in a Japanese cohort. An 11.7-year prospective study was performed using a general population aged 30-79 without a history of cardiovascular disease. Direct LDL-C and sd-LDL-C were measured in samples from 2034 participants (968 men and 1066 women). During the follow-up period, there were 116 incident cases of CVD. The multivariable-adjusted hazard ratios (HRs) of sd-LDL-C for CVD were calculated using a proportional hazards regression model after adjusting for age, hypertension, diabetes, use of lipid-lowering drugs, body mass index, and current smoking and alcohol drinking, and found that increasing quartiles of sd-LDL-C were associated with increased risk of CVD. We also determined that age and sex-adjusted HRs per 10 mg/dL of sd-LDL-C and HRs for CVD, stroke, cerebral infarction, and coronary artery disease were 1.21 (95% CI: 1.12-1.31), 1.17 (95% CI: 1.05-1.30), 1.15 (95% CI: 1.00-1.33), and 1.29 (95% CI: 1.14-1.45), respectively. It was demonstrated that sd-LDL-C was significantly associated with CVD in a Japanese population, providing evidence of sd-LDL-C as an important biomarker to predict CVD.

Serum small-dense LDL abnormalities in chronic renal disease patients

ABSTRACTCardiovascular disease (CVD) is the principal cause of mortality in chronic kidney disease (CKD) patients. Dyslipoproteinaemia is a common metabolic derangement in CKD and a traditional risk factor for CVD. This study investigates serum lipoprotein, especially small-dense low-density lipoprotein (sd-LDL), abnormalities in CKD patients. A total of 131 CKD patients (age: 59±12 years, male=64) diagnosed according to Kidney Disease: Improving Global Outcomes, 2004 (KDIGO) and 121 age-and gender-matched control subjects (age: 58±6 years, male=62) were recruited from Hong Kong and Macau. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and direct LDL-C were assayed enzymatically. In addition, sd-LDL, together with very low density and intermediate-density lipoproteins (VLDL and IDL) were measured by US Food and Drug Administration (FDA)-approved polyacrylamide gradient gel electrophoresis. Compared to controls, CKD patients showed significantly decreased TC, LDL-C, normal-size LDL and HDL-C with increased TG, VLDL, IDL and sd-LDL (all P<0.01). The increased sd-LDL and decreased normal-size LDL fractions resulted in a significantly elevated sd-LDL:LDL ratio in CKD (P<0.005). In contrast to the low TC and LDL-C, sd-LDL and sd-LDL:LDL ratio were significantly elevated in CKD. Thus, sd-LDL will be used increasingly for CVD risk assessment in CKD and other diseases that show lipoprotein derangement.

Type 2 diabetes with good glycemic control have improved insulin response and lower non-esterified fatty acid level after a meal challenge

Background: Pathogenesis of type 2 diabetes (T2DM) involves defects in β-cell function with impaired first and second phase insulin response, and reduced insulin sensitivity. Diabetic dyslipidemia is an important and common risk factor for coronary heart disease (CHD). Aims: This study examined the effect of glycemic control on post prandial insulin and lipid parameters in response to a standardised meal challenge among Type 2 diabetes patients with good and poor glycemic control. Methods: We cross-sectionally studied 31 T2DM patients with good glycemic control and 32 T2DM patients with poor glycemic control. Subjects were given, after minimum 10 hours of fasting, a standard meal containing 58% fat. Fasting and serial postprandial blood samples were taken over 8 hours to determine levels of triglyceride, direct LDL-C, apoB lipoprotein, non-esterified-fatty-acid, insulin and blood glucose. Results: Post prandial NEFA was significantly higher in poor controlled diabetes patients compared to good control diabetes patients (p = 0.019), and post-hoc analysis showed significant difference from 3 hours post prandial to 4 hours post prandial, where p= 0.021. Although the difference in insulin between the 2 groups did not reach statistical significance (p =0.058), post-hoc analysis showed significant difference between the 2 groups from fasting to 1 hour post prandial (p = 0.034) despite postprandial glucose being significantly higher in poor controlled diabetes patients (p < 0.001), throughout the postprandial period. Conclusion: T2DM patients with good glycemic control have improved insulin response with lower non-esterified fatty acid.

Analytical performances of sentinel and vitros direct LDL-C assay methods, and classification of hyperlipidemia

Analytical performances of sentinel and vitros direct LDL-C assay methods, and classification of hyperlipidemia

Method of LDL Cholesterol Measurement Influences Classification of LDL Cholesterol Treatment Goals

BackgroundLow-density lipoprotein cholesterol (LDL-C) has been clearly associated with the risk of developing coronary heart disease. The best and most convenient method for determining LDL-C has come under increased scrutiny...

Atherogenic dyslipidemia as evidenced by the lipid triad: prevalence and associated risk in statin-treated patients in ambulatory care

Objective:The prevalence of atherogenic dyslipidaemia (AD) can be assessed using the lipid triad (low high-density lipoprotein cholesterol [HDL-C] <35 mg/dl, high triglyceride (TG) levels (≥200 mg/dl) and a high total cholesterol HDL-C ratio (TC/HDL-C>5). The aim of the present analysis was (1) to describe the prevalence of the lipid triad, (2) to quantify the associated cardiovascular risk on the basis of the PROCAM score, and (3) to calculate the additional risk reduction that can be obtained by adding nicotinic acid (NA) to a pre-existing statin therapy (model based on the outcomes of a previous randomized controlled study).Methods:Descriptive post-hoc analysis of the German 4E registry in 24,500 patients receiving statins for primary cardiovascular prevention in ambulatory care.Results:The sample comprised 24,500 patients in primary prevention, who had an overall 10-year risk of 16.2%. The prevalence of patients with lipid triad was 24.0%. The mean estimated risk reduction in the total sample (calculated on the basis of a mean LDL-C decrease by 24.3% and other lipid parameter changes) achieved after 6-week statin treatment was 46.6%, the estimated additional relative risk reduction by NA 45.1% (total effect compared to baseline about 70%). In the lipid triad group, the additional relative risk reduction by NA treatment was 42.9%. Relative treatment effects were consistent, irrespective of age and gender. Limitations of this analysis include the use of the TC/HDL-C ratio instead of the direct small dense LDL-C measurements, and the unknown variations of effect size of NA induced lipid reduction when used in combination with statins.Conclusions:Our model calculations indicate that the residual risk which persists after statin treatment could be substantially lowered if besides LDL-C also HDL-C and TG would be addressed, e.g. by adding NA to statin therapy. Definitive prospective studies are needed to confirm this hypothesis.

Small Dense LDL Cholesterol and Coronary Heart Disease: Results from the Framingham Offspring Study

We sought to establish reference values for a new direct assay for small dense LDL cholesterol (sdLDL-C) and to measure sdLDL-C concentrations in patients with established coronary heart disease (CHD) vs controls. Direct LDL-C and sdLDL-C were measured in samples from 3188 male and female participants of the Framingham Offspring Study, including 173 men and 74 women with CHD. Postmenopausal status and male sex were associated with higher sdLDL-C concentrations (P < 0.0001). Cholesterol-lowering medication use was more frequent (P < 0.0001) in CHD patients than in controls (46.8% vs 11.4% in men; 35.1% vs 8.8% in women). In men, mean LDL-C was lower in CHD than in controls (3.22 vs 3.51 mmol/L, P < 0.0001), whereas mean sdLDL-C concentrations were similar (0.83 vs 0.84 mmol/L, P = 0.609). In women, mean LDL-C was similar in CHD and controls (3.53 vs 3.46 mmol/L, P = 0.543), but mean sdLDL-C was higher (0.83 vs 0.68 mmol/L, P = 0.0015). The mean percentage of LDL-C as sdLDL-C was higher in both men and women with CHD than controls (P < 0.01). Increased LDL-C and sdLDL-C were found in 10.4% and 22.0% of men and in 24.3% and 27.8% of women with CHD, respectively. Despite 4-fold greater cholesterol-lowering therapy use, CHD patients had mean LDL-C concentrations above the LDL-C goal of <2.6 mmol/L (<100 mg/dL). Although women with CHD had higher sdLDL-C concentrations than controls, this difference was not seen in men. These findings may explain some of the high residual risk of future CHD events in CHD patients.