LDL-C Measurement Research Articles

Pitavastatin Use in Patients with Previous Statin Intolerance

65.3% HIV+ (P 5 .0007). HIV+/HIV2 groups had similar levels of serum triglycerides, apoB, and LDL-C. HIV+ had greater LDL-P (1719 vs. 1514 nmol/L; P 5 .04), lower HDL-C (44 vs. 58 mg/dL; P , .0001), lower HDL-P (30 vs. 35 nmol/L, P 5 .0015), and were more likely to be on a statin drug. HIV+ had an LDL-P mean 1719 vs. 1514 nmol/L for HIV2, P 5 .03. HIVhad an LDL-C mean of 100 vs. 112mg/dL for HIV+, P 5 .09. LDL-P and LDL-C were weakly correlated (r 5 0.34) for both groups. In the HIV2 group, LDL-P and LDL-Cwere negatively discordant in 18% of patients and positively discordant in 51% of patients. In contrast, HIV+ patients showed 48% negative discordance and 20% positive discordance. Conclusion: LDL-C and LDL-P were poorly correlated in both HIV2 and HIV+ groups, but the HIV+ group had a significantly greater proportion of patients with LDL-P . LDL-C. This suggests that measurement of LDL-C in this population of HIV-infected patients may underestimate atherogenic burden and risk for CVD.

Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a)

We carried out a genome-wide association study (GWAS) of LDL-c response to statin using data from participants in the Collaborative Atorvastatin Diabetes Study (CARDS; n = 1,156), the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT; n = 895), and the observational phase of ASCOT (n = 651), all of whom were prescribed atorvastatin 10 mg. Following genome-wide imputation, we combined data from the three studies in a meta-analysis. We found associations of LDL-c response to atorvastatin that reached genome-wide significance at rs10455872 (P = 6.13 × 10−9) within the LPA gene and at two single nucleotide polymorphisms (SNP) within the APOE region (rs445925; P = 2.22 × 10−16 and rs4420638; P = 1.01 × 10−11) that are proxies for the ϵ2 and ϵ4 variants, respectively, in APOE. The novel association with the LPA SNP was replicated in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial (P = 0.009). Using CARDS data, we further showed that atorvastatin therapy did not alter lipoprotein(a) [Lp(a)] and that Lp(a) levels accounted for all of the associations of SNPs in the LPA gene and the apparent LDL-c response levels. However, statin therapy had a similar effect in reducing cardiovascular disease (CVD) in patients in the top quartile for serum Lp(a) levels (HR = 0.60) compared with those in the lower three quartiles (HR = 0.66; P = 0.8 for interaction). The data emphasize that high Lp(a) levels affect the measurement of LDL-c and the clinical estimation of LDL-c response. Therefore, an apparently lower LDL-c response to statin therapy may indicate a need for measurement of Lp(a). However, statin therapy seems beneficial even in those with high Lp(a).

Biological Effect of High Energy Drink on Normal and Hyperglycemic Rats

Several studies suggest that there was relationships between energy drink consumption and problem behaviors among adolescents and adults as it increase lipolysis glycogenolysis and catecholamine secretion. This study aimed to find out the potential effects of high energy drinks recommended intake and toxic dose on normal and hyperglycemic rats. Thirty-six (36) male adult Sprague-Dawley rats weighting 145±5.3 g each were used in this investigation. Non-diabetic rats [control-ve 6 rats feed on basal diet only and 12 Normal Rats (NR) divided into two groups consumed basal diet with 1 and 2 ml of High Energy Drink (HED) by gastric tube], while Diabetic Rats (DR) control+ve 6 rats received basal diet only and 12 rats divided into two groups consumed basal diet with 1 and 2 ml of HED after injected with alloxan for inducing diabetes mellitus. Body Weight Gain (BWG) and food intake were recorded weekly for 6 weeks. Blood samples were collected after 12 hours fasting at the end of experiment. Liver was removed and weighted. Blood serum was prepared for measurements of glucose, triglyceride, cholesterol, HDL-c, LDL-c, VLDL-c, AST, ALT and ALP. The BWG of NR groups received 2 ml only and DR groups received 1 and 2 ml of HED by oral injection recorded significant decrease (p<0.001) as compared to the control negative group. Blood glucose level was significantly higher (p<0.001) for DR fed on 1 and 2 ml compared with control (-). Serum AST, ALT and ALP were significantly higher (p<0.01 and p<0.001 resp.) for NR received the two doses of HED compared with normal rats control (-). As for cholesterol, triglycerides and LDLc levels were significantly higher (p<0.01) in the hyperglycemic rats group fed on 2 ml of HED compared with control (-). Also LDLc/HDLc ratio increased gradually when the level of HED increased. Oral injection by HED cause histopathological changes in the liver for NR and DR like atrophy and cell damage also changes in the chemical and morphological structure.

Abstract P225: African American LDL-C GWAS Reveals a Strong Protective SNP Association in APOE; The eMERGE Study

Several Genome-Wide Association Studies (GWAS) of LDL-C have been published in populations of European-Ancestry but only one previous GWAS of LDL-C has been published in African Americans. Using phenotype data extracted from repeated lab measurements of LDL-C in electronic medical records (EMR) and the Illumina 1M Duo array we performed a LDL-C GWAS in African Americans in the eMERGE study. Methods: African Americans from eMERGE sites Northwestern University and Vanderbilt University were included in the analysis. All available LDL-C measurements as well as information about statin and hormone prescriptions, cancer, diabetes, and hypo/hyperthyroidism were abstracted from electronic medical records. Two separate samples were created; a sample incorporating exclusions due to medication use and disease diagnoses (n = 618) and a sample without exclusions (n = 1249). After data extraction and cleaning, median LDL-C for each individual was used for both analyses. GWAS analysis of median LDL-C was conducted using PLINK, controlling for age, age2, sex, recruitment site, genotyping batch, and the first three principal components of ancestry. Results: One SNP was significantly (p &lt; 5 X 10-8) associated with LDL-C in both samples; rs7412 in the APOE gene. In the sample excluding measurements taken from those on medication or with prevalent disease, the effect size of this association was large compared to SNPs identified in previous GWAS results for LDL-C (a decrease of 19.9 mg/dl per one additional copy of the minor allele, p = 8.7 x 10 -11). The percent of LDL-C variance accounted for by rs7412 in this sample was 6.7%. The effect size of the rs7412 association was smaller in the sample without exclusions (a decrease of 12.3 mg/dl in LDL-C per allele, p = 1.6 x 10 -9) but still large compared to other LDL-C GWAS findings. Effect sizes for SNPs previously identified in the other African American GWAS of LDL-C were consistent with the earlier report, although there was not sufficient power for these associations to achieve genome-wide significance in this population. Discussion: SNP rs7412 appears to be an important common genetic variant influencing LDL-C levels. Although other signals in APOE have been detected in previous GWAS of European-Ancestry populations and African Americans and this specific SNP has been reported in several previous candidate gene studies, this association has not been identified previously in GWAS likely because rs7412 (or a good proxy) was not included on the genotyping arrays used in these studies. Our results (a) indicate that the association of rs7412 and LDL-C should be examined in other larger African American study populations, (b) further validate the use if EMR-derived traits in genetic research and (c) suggest one should be cautious in concluding that currently published GWAS have discovered all important common genetic variation contributing to certain disease traits.

Abstract 17196: An Improved Equation for Estimation of LDL Cholesterol in European and African American Adults

Introduction: The Friedewald equation (FE) has been the US standard for estimating LDL-cholesterol (LDL-C) levels when direct measures are not available, but loses accuracy at triglyceride (TG) levels ≥400 mg/dL. A new formula (Chen et al) has been shown to more accurately estimate LDL-C across the range of TG, including values ≥400 mg/dL in a Chinese population. We tested the new Chen formula (CF) and the FE against LDL-C measured by NMR spectroscopy in European (EA) and African American (AA) adults. Methods and Results: The sample consisted of 937 apparently healthy subjects ages 31 to 75 years (51.3 ± 8.1 years; 58.3% female; 47.2 EA, 52.8 % AA). Blood was obtained in fasting subjects and total cholesterol (TC), HDL cholesterol (HDL-C), and TG were measured using standard enzymatic methods; LDL-C was estimated using both the FE, [(LDL-C)=(TC)-(HDL-C)-(TG/5)], and the CF [(LDL-C)=0.9[(TC)-(HDL-C)] - 0.1(TG)]. LDL-C was also measured directly using proton NMR spectroscopy (NMR) as the reference standard. Overall mean LDL-C was 130.2 ± 40.mg/dL 1 for FE and 128.6 ± 36.5 mg/dL for CF, p=&lt;0.0001 for correlation (r2= 0.95). The % error for each the FE and CF against NMR LDL-C is plotted against TG levels (log) in the Figure. The FE underestimates NMR LDL-C as TG increases, (beta -1.6% error per 10% higher TG), whereas the CF only slightly overestimates NMR LDL-C at higher values of TG (beta 0.5% error per 10% higher TG) and remains accurate at levels ≥400 mg/dL. Conclusion: The CF more accurately estimates LDL-C compared with the FF across all TG values and remains accurate for levels ≥400 mg/dL in both races. Thus, the Chen formula may offer improved LDL-C estimation utility in African American and European American adults, particularly for TG levels ≥400 mg/dL, when direct measurement of LDL-C is not accessible or cost prohibitive. Figure: Friedewald Equation and Chen Formula Estimates of LDL-C Across TG Levels

Limitations of Direct Methods and the Reference Method for Measuring HDL and LDL Cholesterol

To the Editor: Miller and colleagues (1) compared the results obtained by direct measurements of HDL cholesterol (HDL-C) and LDL-C with those obtained with reference methods requiring ultracentrifugation. They used frozen pooled serum samples and fresh serum samples from 37 healthy controls and 138 individuals with dyslipidemia or heart disease that they had obtained from the NIH. Assay kits, calibrators, and controls were provided by 7 manufacturers. The authors reported CVs of <3.7% for HDL-C and <4.4% for LDL-C for the frozen serum pools, biases for fresh serum from the healthy controls of −5.4% to 4.4% for HDL-C and −6.8% to 1.1% for LDL-C. The biases for the patients with disease were −8.6% to 8.8% for HDL-C and −11.8% to 4.1% for LDL-C, compared with the reference method. The total error for the healthy controls ranged from −13.4% to 1.6% for HDL-C and from −13.3% to 13.5% for LDL-C. For the disease group, total errors ranged from −19.8% to 36.3% for HDL-C and from −26.6% to 31.9% for LDL-C. The authors concluded that 6 of 8 direct HDL-C …

Non–HDL Cholesterol Shows Improved Accuracy for Cardiovascular Risk Score Classification Compared to Direct or Calculated LDL Cholesterol in a Dyslipidemic Population

Our objective was to evaluate the accuracy of cardiovascular disease (CVD) risk score classification by direct LDL cholesterol (dLDL-C), calculated LDL cholesterol (cLDL-C), and non-HDL cholesterol (non-HDL-C) compared to classification by reference measurement procedures (RMPs) performed at the CDC. We examined 175 individuals, including 138 with CVD or conditions that may affect LDL-C measurement. dLDL-C measurements were performed using Denka, Kyowa, Sekisui, Serotec, Sysmex, UMA, and Wako reagents. cLDL-C was calculated by the Friedewald equation, using each manufacturer's direct HDL-C assay measurements, and total cholesterol and triglyceride measurements by Roche and Siemens (Advia) assays, respectively. For participants with triglycerides<2.26 mmol/L (<200 mg/dL), the overall misclassification rate for the CVD risk score ranged from 5% to 17% for cLDL-C methods and 8% to 26% for dLDL-C methods when compared to the RMP. Only Wako dLDL-C had fewer misclassifications than its corresponding cLDL-C method (8% vs 17%; P<0.05). Non-HDL-C assays misclassified fewer patients than dLDL-C for 4 of 8 methods (P<0.05). For participants with triglycerides≥2.26 mmol/L (≥200 mg/dL) and<4.52 mmol/L (<400 mg/dL), dLDL-C methods, in general, performed better than cLDL-C methods, and non-HDL-C methods showed better correspondence to the RMP for CVD risk score than either dLDL-C or cLDL-C methods. Except for hypertriglyceridemic individuals, 7 of 8 dLDL-C methods failed to show improved CVD risk score classification over the corresponding cLDL-C methods. Non-HDL-C showed overall the best concordance with the RMP for CVD risk score classification of both normal and hypertriglyceridemic individuals.

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.

Direct assessment of plasma low density lipoprotein and high density lipoprotein cholesterol levels and coronary heart disease: Results from the Framingham Offspring Study

Background We evaluated direct low density lipoprotein (LDL) cholesterol (C) and high density lipoprotein (HDL) cholesterol (C) versus standard methods using fasting plasma samples from participants in cycle 6 of the Framingham Offspring Study. Methods Direct LDL-C and HDL-C measurements were performed on fasting plasma from male (1335 controls, 173 CHD cases) and female (1606 controls, 74 cases) participants, and compared with LDL-C, as calculated with the Friedewald formula, and HDL-C, as measured after dextran-Mg 2+ precipitation. Results Values for direct LDL-C and HDL-C correlated well with standard methods (both about r 2 = 0.94, p < 0.001) with similar absolute values. Biases of >10% were present for 7.7% of samples for LDL-C, while for HDL-C this value was 8.5%. Despite higher use of cholesterol-lowering medication in CHD cases, calculated or direct LDL-C values were still well above recommended values [<2.6 mmol/L (100 mg/dL)] in CHD cases, especially in females. Conclusions Direct assays for both LDL-C and HDL-C provide an acceptable guide for lipid treatment. In Framingham Offspring Study participants most CHD cases had LDL-C levels above the recommended target.

Determination of non-treatment with statins of high risk patients in the Netherlands

Objective:To determine in the Netherlands what proportions of high risk patients with established cardiovascular disease (CVD) or diabetes mellitus type 2 (DM2) who were not treated with statins on 1 January 2007 and which characteristics were associated with non-treatment.Methods:From the IPCI GP database patients were selected who were registered with a GP on 1 January 2007 who had a history of either CVD (CVD patients), DM2 (diabetics) or both (diabetics with CVD). The proportion of patients using statins around 1 January 2007 was determined. Associations of patient characteristics with non-treatment were quantified (CVD patients and diabetics only).Results:In all, 19 628 CVD patients, 5006 diabetics and 3767 diabetics with CVD were identified. Of these patients 71%, 54% and 45%, respectively did not use statins. These proportions were similar in the subgroups of patients with recent LDL-C measurements. Among these subgroups the vast majority of non-treated patients was eligible for statin treatment (LDL-C >2.5 mmol/l). The proportion of statin-treated patients was larger among diabetics than among CVD patients. Among CVD patients, female gender, age below 40 years, living in a deprived area, a history of CVD of less than 1 year and arrhythmia were significantly associated with non-treatment. Among diabetics, significant associations were: living in a deprived area and specialist visits in the previous year. In 2003, treatment rates among diabetics were lower, but among CVD patients they were similar. This suggests that the higher treatment rates among diabetics compared to CVD patients in 2007 may be the result of disease-management programmes introduced for diabetics in 2004.Conclusion:The majority of patients with established CVD or DM2 were not treated with statins on 1 January 2007. Eligibility for statin treatment may have been overestimated due to unavailability of cholesterol levels among many non-treated patients. Implementation of care programmes for CVD patients may increase treatment rates among eligible CVD patients.

Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis

While conventional LDL-C, HDL-C, and triglyceride measurements reflect aggregate properties of plasma lipoprotein fractions, NMR-based measurements more accurately reflect lipoprotein particle concentrations according to class (LDL, HDL, and VLDL) and particle size (small, medium, and large). The concentrations of these lipoprotein sub-fractions may be related to risk of cardiovascular disease and related metabolic disorders. We performed a genome-wide association study of 17 lipoprotein measures determined by NMR together with LDL-C, HDL-C, triglycerides, ApoA1, and ApoB in 17,296 women from the Women's Genome Health Study (WGHS). Among 36 loci with genome-wide significance (P<5×10−8) in primary and secondary analysis, ten (PCCB/STAG1 (3q22.3), GMPR/MYLIP (6p22.3), BTNL2 (6p21.32), KLF14 (7q32.2), 8p23.1, JMJD1C (10q21.3), SBF2 (11p15.4), 12q23.2, CCDC92/DNAH10/ZNF664 (12q24.31.B), and WIPI1 (17q24.2)) have not been reported in prior genome-wide association studies for plasma lipid concentration. Associations with mean lipoprotein particle size but not cholesterol content were found for LDL at four loci (7q11.23, LPL (8p21.3), 12q24.31.B, and LIPG (18q21.1)) and for HDL at one locus (GCKR (2p23.3)). In addition, genetic determinants of total IDL and total VLDL concentration were found at many loci, most strongly at LIPC (15q22.1) and APOC-APOE complex (19q13.32), respectively. Associations at seven more loci previously known for effects on conventional plasma lipid measures reveal additional genetic influences on lipoprotein profiles and bring the total number of loci to 43. Thus, genome-wide associations identified novel loci involved with lipoprotein metabolism—including loci that affect the NMR-based measures of concentration or size of LDL, HDL, and VLDL particles—all characteristics of lipoprotein profiles that may impact disease risk but are not available by conventional assay.

LDL-C reductions and goal attainment among naive statin users in the Netherlands: real life results

ABSTRACTObjective: The effectiveness of statin therapy in a real life setting may differ from that in clinical trials, as physicians make non-randomised treatment decisions for patients with less uniform and possibly different characteristics. We therefore performed a study to compare the effectiveness of different statins and doses in routine clinical practice with respect to total serum cholesterol and LDL-cholesterol (LDL-C) reduction and goal attainment according to European guidelines on the prevention of cardiovascular disease (CVD).Research design and methods: Naive statin users starting treatment in 2003 and 2004 with LDL-C measurements at baseline and between 30 and 365 days after start of treatment were extracted from the PHARMO database. During treatment with their initial statin dose LDL-C reduction and attainment of cholesterol goals were compared between different statins and doses.Results: Of 2303 identified naive patients, approximately 30% were allocated to the high CVD-risk group. Average LDL-C reductions were 48%, 42%, 39%, and 32% at mean doses of 11 mg rosuvastatin, 17 mg atorvastatin, 22 mg simvastatin and 35 mg pravastatin, respectively. The proportion of patients attaining cholesterol goals was 75% for rosuvastatin, 68% for atorvastatin, 56% for simvastatin, and 42% for pravastatin. Dose comparisons showed greater LDL-C reduction and increased goal attainment for rosuvastatin 10 mg compared to other statins at most doses (adjusted p < 0.05).Conclusions: In a real life setting, both LDL-C reduction and the proportion of patients attaining cholesterol goals appear to be significantly increased among users of rosuvastatin compared to other statins. These results confirm and extend reported clinical trial results to a real world setting.

Effects of albuminuria and renal dysfunction on development of dyslipidaemia in type 2 diabetes--the Hong Kong Diabetes Registry

It is uncertain whether albuminuria precedes the future development of high total cholesterol (TC > 6.2 mmol/l) and high LDL-C (>4.1 mmol/l) while renal dysfunction precedes the future development of low HDL-C (<0.9 mmol/l) in type 2 diabetes. A prospective cohort of 2761 type 2 diabetic patients without significant dyslipidaemia and having at least one measurement of TC, LDL-C and HDL-C during 2.8 years of follow-up was analysed. The spline Cox regression model was used to derive hazard ratio (HR) curves of the spot urinary albumin:creatinine ratio (ACR) and the estimated glomerular filtration rate (eGFR) for dyslipidaemia, followed by standard Cox models to confirm the findings from the HR curves. Seven percent of the cohort developed high TC, 4.6% developed high LDL-C and 5.7% developed low HDL-C during follow-up. In multivariate analysis, the HR of ACR for high TC and high LDL-C increased rapidly and linearly from zero with no apparent threshold. Patients with macroalbuminuria (ACR >/=25 mg/mmol) were, respectively, 1.6- and 2.4 folds more likely to develop high TC and high LDL-C than those with normoalbuminuria at baseline. The HR of eGFR for low HDL-C increased rapidly with declining eGFR at <110 ml/min/ 1.73 m(2). Subjects with eGFR <60 ml/min/1.73 m(2) and >/=60-<110 ml/min/1.73 m(2), respectively, had 3.0-fold and 1.8-fold risks of low HDL-C compared to those with eGFR >/=110-<140 ml/min/1.73 m(2). In type 2 diabetes, macroalbumninuria predicts high TC and high LDL-C, while reduced renal function, even within normal range, predicts low HDL-C.

Plant sterols added to combination statin and colesevelam hydrochloride therapy failed to lower low-density lipoprotein cholesterol concentrations

The purpose of this study was to evaluate the effects on LDL-cholesterol (LDL-C) from addition of plant sterol treatment to patients with dyslipidemia already taking a statin and colesevelam hydrochloride (HCl). Current cholesterol treatment guidelines recommend use of plant stanols/sterols to help reach LDL-C goals in patients taking other lipid-lowering therapies. Previous data demonstrate LDL-C lowering by adding stanols/sterols to statins. However, data are conflicting regarding the benefit from combination stanols/sterols with bile acid sequestrants. Fifty-five subjects on a stable dose of statin completed a 10-week, double-blind, randomized study of colesevelam HCl 3.75 g/day alone for 4 weeks, then 6 weeks of additional 2 g/day plant sterol-fortified orange juice (S-OJ) or placebo orange juice (P-OJ). Serum total cholesterol (TC), LDL-C, HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline, 4 weeks, and 10 weeks. Baseline LDL-C measurements (mean ± SD) were similar between S-OJ and P-OJ groups (122 ± 20 vs 126 ± 24 mg/dL, respectively). Four weeks of colesevelam HCl in combination with a statin significantly reduced TC, LDL-C, and ApoB (9.6%, P < 0.001; 21.9%, P < 0.001; and 8.5%, P = 0.001, respectively), and significantly increased HDL-C (6.2%, P = 0.002) and TG (18.8%, P = 0.002). However, compared to P-OJ, 10 weeks of S-OJ produced no effect on any outcome parameter beyond that of colesevelam HCl. Plant S-OJ appears to be ineffective at further reducing LDL-C when added to statin and colesevelam HCl combination therapy in patients with dyslipidemia.

Regression of hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is a lipid-lowering and antioxidant agent. It suppresses the development of hypercholesterolemic atherosclerosis in rabbits. It is however not known if SDG would produce regression of atherosclerosis. The objectives of this study were to determine (i) if SDG produces regression of atherosclerosis; (ii) if regression is associated with reduction in serum lipids, oxidative stress or both; and (iii) if the duration of treatment has an effect on regression. Rabbits were assigned to five groups: Group I, regular diet (control); Group II, 0.5% cholesterol diet for 2 months (mo); Group III, same as Group II but followed by regular diet for 2 mo; Group IV, same as Group II and followed by regular diet with SDG (20 mg·kg body wt −1·day −1 PO) for 2 mo; and Group V, same as Group IV but SDG treatment for an additional 2 mo. Blood samples were collected from rabbits before and at monthly intervals thereafter on their respective diet regimen for measurement of triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and malondialdehyde (MDA), a lipid peroxidation product. At the end of the protocol, the aorta was removed for assessment of atherosclerotic lesions, aortic MDA and aortic chemiluminescence (Aortic-CL), a measure of antioxidant reserve. MDA and Aortic-CL provide an index of oxidative stress. Increases in serum TG, TC, LDL-C, HDL-C and the risk ratio TC/HDL-C in Group II were associated with an increase in oxidative stress and development of atherosclerosis (57% of aortic intimal surface covered with lesions). Serum lipids decreased to a similar extent in Groups III–V, however atherosclerotic lesions were 84%, 63% and 44%, respectively in Groups III–V. There were more atherosclerotic lesions in Group III (+48.9%) as compared to Group II. The atherosclerotic lesions decreased by 24% and 45%, respectively in Groups IV and V compared to Group III. The reduction in atherosclerotic lesions was associated with a reduction in oxidative stress. These results suggest that (i) regular diet following a high cholesterol diet accelerates atherosclerosis in spite of a decrease in serum lipids; (ii) SDG treatment prevents the progression of atherosclerosis on a regular diet following a high cholesterol diet; (iii) prevention of progression is associated with a reduction of aortic oxidative stress and not with reductions in serum lipids; (iv) a longer duration of treatment reduces the progression of atherosclerosis to a greater extent, and tends to regress the atherosclerosis.

Comparison of Direct and Indirect Measurement of LDL-C in HIV-Infected Individuals: ACTG 5087

Background: Hypertriglyceridemia is common in HIV-infected individuals on antiretroviral therapy. Triglyceride (TG) levels >400 mg/dL interfere with the accurate determination of low-density lipoproteins (LDL-C) by the Friedewald equation, making it difficult to assess coronary heart disease risk. Objective: The objective of this study is to compare the agreement of the direct LDL-C assay and the Friedewald equation with a reference ultracentrifugation method in the estimation of LDL-C concentrations. Method: Samples from ACTG 5087 were assayed by ultracentrifugation and a direct enzymatic assay and calculated using the Friedewald equation. Results: In subjects with TG <400 mg/dL (n = 271), 90% of the direct LDL-C values and Friedewald calculations were within 30 mg/dL and 32 mg/dL of the ultracentrifugation values, respectively. With TG ⩾400 mg/dL (n = 186), 90% of the direct assay and Friedewald observations were within 68 mg/dL and 120 mg/dL of the ultracentrifugation results, respectively. Only 27% of the LDL-C values were within 15 mg/dL of the ultracentrifugation LDL-C results for direct assay and 16.3% for the Friedewald equation. Conclusion: The direct LDL-C assay and the calculated LDL-C values did not display adequate agreement with the reference ultracentrifugation method. In subjects with TG >400 mg/dL, the direct assay overestimates the actual LDL-C whereas the Friedewald calculation underestimates the actual LDL. Clinical usage of these methods may lead to misclassification of the severity of dyslipidemia, resulting in improper management.

Suppression of hypercholesterolemic atherosclerosis by pentoxifylline and its mechanism

Reactive oxygen species (ROS) have been implicated in the development of hypercholesterolemic atherosclerosis. Hypercholesterolemia increases the levels of platelet activating factor (PAF) and cytokines which are known to stimulate granulocytes and endothelial cells to produce ROS. Pentoxifylline (PTX) is an inhibitor of cytokines and PAF and would reduce the generation of ROS by granulocytes and endothelial cells. PTX therefore would be expected to reduce the development of hypercholesterolemic atherosclerosis. New Zealand white female rabbits were assigned to four groups: Group I ( n = 12), control; Group II (n = 5), PTX control (40 mg/kg body weight daily orally); Group III ( n = 13), 0.5% cholesterol; Group IV ( n = 9), 0.5% cholesterol + PTX (40 mg/kg body weight daily orally). Blood samples were collected before (0 time) and after 1 and 2 months on experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and serum malondialdehyde (MDA), a lipid peroxidation product. At the end of 2 months the aorta was removed for measurement of atherosclerotic plaques, MDA, and aortic tissue chemiluminescence (Ao-CL), a marker for antioxidant reserve. Rabbits in Group III developed atherosclerosis (56.61 ± 6.90% of the intimal surface of aorta was covered with atherosclerotic plaques) which was associated with an increase in the serum TG, TC, LDL-C, HDL-C, TC/HDL-C, MDA and aortic MDA and antioxidant reserve. PTX reduced the development of atherosclerosis by 38.1% and this was associated with decreases in serum MDA by 32%, aortic MDA by 37%, and antioxidant reserve by 17.3% without changes in the serum lipids. These results suggest that ROS generated during hypercholesterolemia via cytokines and PAF may in part contribute to the development of hypercholesterolemic atherosclerosis and that suppression of production and activity of cytokines and PAF may reduce the development of hypercholesterolemic atherosclerosis.

Improved Specificity of a New Homogeneous Assay for LDL-Cholesterol in Serum with Abnormal Lipoproteins

Although a homogeneous assay for serum LDL-cholesterol (LDL-C) has become a routine clinical procedure, problems remain in assay performance characteristics. We examined the performance of a recently developed automated homogeneous assay (New-Daiichi assay) for serum LDL-C and compared the results with those obtained by the current homogeneous method (Denka-Seiken assay) or by ultracentrifugation as a control. The New-Daiichi assay showed satisfactory basic performance characteristics such as reproducibility, linearity, and stability. There was no interference in the assay by various substances examined. The LDL-C values obtained with this method correlated well with those obtained by ultracentrifugation. In samples from patients with obstructive jaundice, both methods detected cholesterol from abnormal lipoproteins (such as lipoprotein-X and -Y), but the New-Daiichi assay was less reactive and more specific for LDL-C. The new method has improved performance for the accurate measurement of LDL-C in clinical practice.

The “Good Cholesterol”

Atherosclerosis is an insidious and dangerous disease: a progressive chemical and structural injury to the blood vessels in such critical organs as the heart, brain, and kidney. The hallmark feature of atherosclerosis is the buildup of cholesterol into lesions called plaques that can reduce the flow of blood. When the delivery of blood to heart muscle drops enough, this can result in the development of chest pain or angina. Angina indicates that the heart muscle is not receiving enough oxygen to carry out its pumping functions. Atherosclerotic plaques can also suddenly rupture, develop a blood clot on their surface, and completely choke off a portion of heart muscle. This chain of events frequently results in heart attack or sudden death without warning. Atherosclerotic disease also predisposes people to stroke, peripheral vascular disease, lower-extremity amputation, and loss of kidney function, among other devastating outcomes. Despite all that we have learned in the past 50 years, atherosclerosis remains the No. 1 killer of men and women and the chief reason for loss of quality of life in Western countries. We are, however, gaining ground. Considerable research has revealed the importance of factors that increase an individual’s risk for developing this disease. Among the most important of these risk factors are elevated blood pressure, diabetes mellitus, obesity, inactivity, smoking, and cholesterol levels. When your physician measures your cholesterol level, he or she is looking at your lipid profile, which comprises low-density lipoprotein cholesterol (LDL-C, or the “bad” cholesterol), triglycerides (blood fats), and high-density lipoprotein cholesterol (HDL-C, or the “good” cholesterol). In a general way, when it comes to measurement of your LDL-C and triglyceride values, a lower value is better because these lipids drive the development and progression of atherosclerosis. In sharp contrast, when it …