Friedewald Formula Research Articles

Estimating LDL ApoB: Infomania or Clinical Advance?

Epidemiological and clinical studies have consistently demonstrated that increased concentrations of LDL cholesterol in plasma are associated with increased risk of atherosclerotic cardiovascular disease (CVD).1 The reference method for LDL cholesterol is β-quantification, a method developed by the CDC that requires ultracentrifugation and is accordingly labor intensive, time consuming, and expensive. Thus, in routine clinical laboratory practice, LDL cholesterol is estimated by the Friedewald formula(1). This equation requires the measurement of total cholesterol, HDL cholesterol, and triglycerides, together with a calculation factor that estimates the concentration of cholesterol in very-low-density lipoprotein (VLDL). However, this formula is not valid for nonfasting patients, when plasma triglyceride concentrations are ≥4.5 mmol/L (400 mg/dL), in familial dysbetalipoproteinemia, or when there is abnormal VLDL composition. Direct measures of LDL cholesterol are available, but they are not standardized and are expensive. Apolipoprotein B (apoB), a large amphipathic glycoprotein, plays a central role in human lipoprotein metabolism(2). The APOB gene is located on chromosome 2 and produces, via a unique mRNA editing process, two forms of apoB in circulating lipoproteins, apoB-48 and apoB-100(3). ApoB-48 is the truncated form of apoB-100 consisting of the N-terminal 48% of full-length apoB-100. ApoB-48 is synthesized in the intestine and is essential for the formation and secretion of chylomicrons. ApoB-100 is synthesized in the liver and is an essential structural and functional component of VLDL and its metabolic products, intermediate-density lipoprotein (IDL) and LDL, being the ligand for the LDL receptor. Essentially all circulating apoB is associated with lipoproteins, and unlike most other apoproteins, apoB cannot exchange freely among lipoprotein particles(2)(3). VLDL, IDL, LDL, and lipoprotein each contain one molecule of apoB-100. Similarly, chylomicrons and their remnants contain a single molecule of apoB-48. Hence, plasma apoB concentrations reflect the total number of atherogenic particles present …

LDL cholesterol estimation using the Anandaraja's and Friedewald's formulas in schizophrenic patients treated with antipsychotic drugs

Objectives The use of new antipsychotic drugs is associated with an increased risk of diabetes and metabolic syndrome, and the routine monitoring of blood lipids during treatment has been recommended. Recently, a new formula for the estimation of low-density lipoprotein (LDL) cholesterol from total cholesterol and triglycerides has been proposed by Anandaraja et al. (Int J Cardiol 2005; 102: 117), and the aim of our study was its evaluation in schizophrenic patients treated with antipsychotic drugs. Materials and methods In 487 serum samples from schizophrenic patients treated with clozapine in polytherapy, the concentrations of LDL cholesterol were determined by agar gel electrophoresis and the formula of Friedewald et al. (Clin Chem 1972; 18: 499), and compared with the results of the Anandaraja's formula. Results A higher correlation and lower error of the estimate of the electrophoresis results was found with those of Friedewald ( r = 0.940, ma68 = 0.17 mmol/L) than those of Anandaraja ( r = 0.811, ma68 = 0.31 mmol/L). Similar results were obtained on making a dichotomy of the patients with and without metabolic syndrome lipid profile. A highly significant correlation was found between the high-density lipoprotein (HDL) cholesterol levels and the Anandaraja/Electrophoresis ( r = 0.817, p < 0.001) and Anandaraja/Friedewald ( r = 0.977, p < 0.001) ratios. Conclusions According to our data, Anandaraja's formula tends towards an overestimation or underestimation of LDL cholesterol levels, depending on whether the HDL cholesterol levels are high or low, which may be clinically significant. These results do not support the proposed better accuracy of the Anandaraja's than the Friedewald's formula.

Do not use the Friedewald formula to calculate LDL‐cholesterol in hypercholesterolaemic rats

AbstractReputable calculations such as the Friedewald formula are used extensively to determine LDL‐cholesterol (LDL‐C) values from known total cholesterol, triacylglycerol and HDL‐cholesterol (HDL‐C) levels. To the best of our knowledge, however, the validity of this equation has not yet been confirmed in rats. The aim of the present study is to give some insights as to why this formula must be used carefully in rats, and to find cut‐off points below which this formula can be considered reliable. Sera of 54 rats with different cholesterol, triacylglycerol and HDL‐C levels were tested. LDL was isolated by ultracentrifugation and LDL‐C measured by an enzymatic colorimetric method and compared against LDL‐C obtained by the formula. In rats whose serum cholesterol was &lt;100 mg/dL, or whose HDL‐C constituted ≥75% of total cholesterol, or whose cholesterol/phospholipids ratio was &lt;1, or whose serum did not contain β‐VLDL, LDL‐C obtained by both methods did not significantly differ. Under other conditions, however, and particularly in hypercholesterolaemic rats who did present β‐VLDL, the results clearly show that the Friedewald formula overestimates LDL‐C levels. In conclusion, (VLDL + LDL)‐C instead of VLDL‐C and LDL‐C must be used when ultracentrifugation or other alternative methods are not available to measure LDL‐C in hypercholesterolaemic rats.

Associations of alcohol drinking and cigarette smoking with serum lipid levels in healthy middle-aged men

The aim of this study is to determine whether influences of drinking alcohol on serum lipid levels are different in smokers and non-smokers. Subjects were 25,689 healthy male workers aged 40 to 59 years. Serum total and HDL cholesterol and triglyceride concentrations were measured and LDL cholesterol concentrations were estimated by using the Friedewald formula. The subjects were divided into three groups by average daily consumption of cigarettes (non-smokers; light smokers, less than 20 cigarettes per day; heavy smokers, 20 or more cigarettes per day) and by average daily alcohol consumption (non-drinkers; light drinkers, less than 30 g of ethanol per day; heavy drinkers, 30 g or more of ethanol per day). In overall subjects, serum HDL, LDL and total cholesterol were significantly lower and triglyceride was significantly higher in heavy smokers than in non-smokers. In the smoker groups, serum total cholesterol was significantly lower in heavy drinkers than in non-drinkers, while no difference in total cholesterol was observed in non- and heavy drinkers of the non-smoker group. Both in the smoker and non-smoker groups, HDL cholesterol was higher and LDL cholesterol was lower in drinkers than in non-drinkers. The difference in LDL cholesterol between non-drinkers and drinkers was more prominent in smokers than in non-smokers. The above associations were not altered after the adjustment for age, body weight and alcohol intake. The results suggest that smoking increases the lowering effect of alcohol drinking on LDL cholesterol, but does not affect the relationship of alcohol drinking with HDL cholesterol.

LDL-cholesterol concentrations: a genome-wide association study

SummaryBackgroundLDL cholesterol has a causal role in the development of cardiovascular disease. Improved understanding of the biological mechanisms that underlie the metabolism and regulation of LDL cholesterol might help to identify novel therapeutic targets. We therefore did a genome-wide association study of LDL-cholesterol concentrations.MethodsWe used genome-wide association data from up to 11 685 participants with measures of circulating LDL-cholesterol concentrations across five studies, including data for 293 461 autosomal single nucleotide polymorphisms (SNPs) with a minor allele frequency of 5% or more that passed our quality control criteria. We also used data from a second genome-wide array in up to 4337 participants from three of these five studies, with data for 290 140 SNPs. We did replication studies in two independent populations consisting of up to 4979 participants. Statistical approaches, including meta-analysis and linkage disequilibrium plots, were used to refine association signals; we analysed pooled data from all seven populations to determine the effect of each SNP on variations in circulating LDL-cholesterol concentrations.FindingsIn our initial scan, we found two SNPs (rs599839 [p=1·7×10−15] and rs4970834 [p=3·0×10−11]) that showed genome-wide statistical association with LDL cholesterol at chromosomal locus 1p13.3. The second genome screen found a third statistically associated SNP at the same locus (rs646776 [p=4·3×10−9]). Meta-analysis of data from all studies showed an association of SNPs rs599839 (combined p=1·2×10−33) and rs646776 (p=4·8×10−20) with LDL-cholesterol concentrations. SNPs rs599839 and rs646776 both explained around 1% of the variation in circulating LDL-cholesterol concentrations and were associated with about 15% of an SD change in LDL cholesterol per allele, assuming an SD of 1 mmol/L.InterpretationWe found evidence for a novel locus for LDL cholesterol on chromosome 1p13.3. These results potentially provide insight into the biological mechanisms that underlie the regulation of LDL cholesterol and might help in the discovery of novel therapeutic targets for cardiovascular disease.

Serum paraoxonase activity, high-sensitivity C-reactive protein, and lipoprotein disturbances in end-stage renal disease patients on long-term hemodialysis

Hemodialysis patients are at high risk for atherosclerotic events. Enhanced oxidant stress, dyslipidemia, and inflammation may have a major role in this risk. In this work, we assessed lipoprotein status, total homocysteine, high-sensitivity C-reactive protein (hs-CRP), and paraoxonase activity in hemodialysis patients to determine the correlations among these parameters and to compare these values with those measured in normal control subjects. We enrolled 109 end-stage renal disease patients on long-term hemodialysis and 100 age- and gender-matched healthy subjects. Total cholesterol, triglycerides, and high-density lipoprotein cholesterol levels were evaluated using colorimetric methods. Low-density lipoprotein (LDL) cholesterol was calculated according to the Friedewald formula. Serum levels of hs-CRP, apolipoproteins (Apo) AI, B, E, and lipoprotein(a) were measured by nephelometry. Lipoprotein particle (Lp) A-I and LpA-I:A-II were determined by immunoelectrophoresis. Total homocysteine levels were evaluated by the fluorescence polarization immunoassay method. Paraoxonase activity was determined using the paraoxon-like substrate. Compared with controls, hemodialysis patients had more frequent atherogenic dyslipidemia, hyperhomocysteinemia, and elevated hs-CRP levels. These latter findings inversely correlate with ApoA-I and LpA-I:A-II and positively with ApoB, lipoprotein(a), and ApoB/ApoA-I ratio. Homocysteine levels correlated positively with age. Paraoxonase activity was decreased in hemodialysis patients, especially in elderly patients. This enzyme activity positively correlated with LpA-I:A-II, and inversely with hs-CRP, LDL-cholesterol, and ApoE levels. The present study demonstrated an abnormal lipoprotein profile associated with increased hs-CRP and decreased paraoxonase activity in hemodialysis patients. Hence, inflammation, dyslipidemia, and increased oxidant stress linked to uremia may be contributors to increased cardiovascular risk in this population.

Effects of total cholesterol and triglyceride on the percentage difference between the low-density lipoprotein cholesterol concentration measured directly and calculated using the Friedewald formula

We elucidate how the triglyceride (TG) and total cholesterol (TC) concentrations affect the percentage difference (%DeltaLDL) between the low-density lipoprotein cholesterol (LDL-C) concentration evaluated by direct measurement (DLDL-C) and calculated using the Friedewald formula (FLDL-C), under conditions allowing the calculation. Serum concentrations of TC, TG, high-density lipoprotein cholesterol (HDL-C), and DLDL-C were measured and the FLDL-C and %DeltaLDL were calculated for 38,243 Koreans who had TG values <4.52 mmol/L. The DLDL-C was measured using the homogeneous Kyowa Medex assay (Kyowa, Tokyo, Japan). The %DeltaLDL was calculated using the equation: [(FLDL-C-DLDL-C)/DLDL-C]x100. The mean %DeltaLDL-C was -9.1+/-6.4%. The %DeltaLDL differed by more than +/-5% in 75.4% of the subjects, and the FLDL-C was lower than the DLDL-C in 96.3%. The mean %DeltaLDL-C for the group with the highest TG and lowest TC was 11.8-fold that for the group with the lowest TG and highest TC. Under conditions satisfying the requirements of the Friedewald formula, the DLDL-C and FLDL-C differed significantly over the concentration ranges of both TC and TG. In an evaluation of patients with hyperlipidemia, the Friedewald calculation may underestimate the risk for coronary heart disease.

A More Atherogenic Serum Lipoprotein Profile Is Present in Women with Polycystic Ovary Syndrome: A Case-Control Study

Polycystic ovary syndrome (PCOS) is associated with a higher frequency of cardiovascular risk factors. Apolipoprotein (apo) A-I and apoB are potent markers for cardiovascular risk. Data on apo levels in women with PCOS are scarce and contradictory. Our objective was to identify changes in lipid metabolism in women with PCOS, and the relative impact of obesity, insulin resistance, and hyperandrogenism on lipid parameters. This was a case-control study. The study was performed at a single referral center. PCOS was diagnosed according to the 2003 Rotterdam criteria. Healthy mothers with regular menstrual cycles served as controls. Fasting insulin, triglycerides (TGs), cholesterol, high-density lipoprotein (HDL)-cholesterol, apoA-I, and apoB were determined. Low-density lipoprotein (LDL)-cholesterol was calculated using the Friedewald formula. We included 557 women with PCOS and 295 controls. After correction for age and body mass index, PCOS women had higher median levels of insulin (10.1 vs. 6.9 mU/liter), TGs (95 vs. 81 mg/dl), cholesterol (196 vs. 178 mg/dl), and LDL-cholesterol (125 vs. 106 mg/dl) in combination with lower levels of HDL-cholesterol (46 vs. 55 mg/dl) and apoA-I (118 vs. 146 mg/dl) compared with controls (all P values < or = 0.01). apoB levels were similar in cases and controls. Free androgen index, body mass index, SHBG, and estradiol were independent predictors of apoA-I levels in women with PCOS. PCOS is associated with a more pronounced atherogenic lipid profile. Furthermore, obesity and hyperandrogenism contribute to an adverse lipid profile. Finally, PCOS seems to constitute an additional risk factor for an atherogenic lipid profile.

Proinflammatory Lipids in Sickle Cell Disease-Associated Pulmonary Hypertension.

Introduction: Pulmonary hypertension (PHT) occurs commonly in patients with sickle cell disease (SCD). The pathogenesis of PHT in this setting is likely multifactorial. There is an abundance of evidence suggesting that SCD is characterized by a chronic inflammatory state. In addition, we have recently reported that SCD patients with PHT exhibit higher levels of inflammatory markers compared to those SCD patients without PHT. The purpose of this study is to determine whether proinflammatory lipids are associated with PHT in SCD.Methods: A cohort of patients followed at the Sickle Cell Clinic at UNC-Chapel Hill was evaluated in this cross-sectional study. Doppler echocardiography was used to determine the pulmonary artery systolic pressure (PASP). Pulmonary hypertension was subsequently defined using an age-, sex- and BMI-adjusted reference range. Lipid profiles, including total cholesterol, triglyceride and high-density lipoprotein (HDL) were measured, and low-density lipoprotein (LDL) levels were calculated using the Friedewald formula (LDL = Total cholesterol - Triglyceride/5 - HDL) in all SCD patients and controls subjects without SCD. To determine the levels of proinflammatory HDL, we measured the rates of fluorescence intensity of dichlorofluorescein (DCF) over 2 hours following its addition to an HDL aliquot. Nonparametric tests (α = 0.05) were used to compare median values in SCD patients with (PHT) and without PHT (no PHT) as well as control individuals.Results: Seventy-one patients with SCD, 24 of whom had PHT (33.8%), and 12 healthy, control subjects (African-Americans and Caucasians) were evaluated. Compared with controls, both SCD patients with and without PHT had lower total cholesterol levels (PHT 96.8 mg/dL, no PHT 106.3 mg/dL, control 133.4 mg/dL; p = 0.004) and LDL levels (PHT 34.6 mg/dL, no PHT 43.6 mg/dL, control 63.6; p = 0.009). In addition, SCD patients with and without PHT had higher levels of proinflammatory HDL (presented as slopes of the increase in DCF fluorescence over time) than control subjects (PHT 4.06 FU, no PHT 3.41 FU, control 2.37 FU; p = 0.0001). However, no significant differences in HDL or triglyceride levels were observed when all three groups were compared. Finally, when SCD patients with PHT were compared only to SCD patients without PHT, median levels of proinflammatory HDL were higher (p = 0.03), although the difference was only of borderline statistical significance when corrected for multiple comparisons (α = 0.05/3 = 0.0167). No significant differences in the other measured variables were observed when only SCD patients with and without PHT were compared.Conclusion: Although patients with SCD have lower levels of total cholesterol and LDL compared to healthy control subjects, they exhibit higher levels of proinflammatory HDL. Furthermore, median levels of inflammatory lipids appear to be higher in SCD patients with PHT compared to those patients without this complication. These findings confirm the inflammatory nature of SCD and further suggest a contribution of inflammation to the pathogenesis of PHT in these patients. While proinflammatory HDL is hypothesized to predispose to atherosclerosis in the general population, the occurrence of this complication is thought to be low in SCD patients. Further studies are required to determine the significance of increased inflammatory lipids in SCD and their contribution to the pathogenesis of PHT in SCD.

Association between erythrocyte Na+K+-ATPase activity and some blood lipids in type 1 diabetic patients from Lagos, Nigeria

BackgroundAltered levels of erythrocyte Na+K+-ATPase, atherogenic and anti-atherogenic lipid metabolites have been implicated in diabetic complications but their pattern of interactions remains poorly understood.This study evaluated this relationship in Nigerian patients with Type 1 diabetes mellitus.MethodsA total of 34 consented Type 1 diabetic patients and age -matched 27 non-diabetic controls were enrolled. Fasting plasma levels of total cholesterol, triglycerides and HDL-cholesterol were determined spectrophotometrically and LDL-cholesterol estimated using Friedewald formula. Total protein content and Na+K+-ATPase activity were also determined spectrophotometrically from ghost erythrocyte membrane prepared by osmotic lysis.ResultsResults indicate significant (P < 0.05) reduction in Na+K+-ATPase activity in the Type 1 diabetic patients (0.38 ± 0.08 vs. 0.59 ± 0.07 uM Pi/mgprotein/h) compared to the control but with greater reduction in the diabetic subgroup with poor glycemic control (n = 20) and in whom cases of hypercholesterolemia (8.8%), hypertriglyceridemia (2.9%) and elevated LDL-cholesterol (5.9% each) were found. Correlation analyses further revealed significant (P < 0.05) inverse correlations [r = -(0.708-0.797] between all the atherogenic lipid metabolites measured and Na+K+-ATPase in this subgroup contrary to group with good glycemic control or non-diabetic subjects in which significant (P < 0.05) Na+K+-ATPase and HDL-C association were found (r = 0.427 - 0.489). The Na+K+-ATPase from the diabetic patients also exhibited increased sensitivity to digoxin and alterations in kinetic constants Vmax and Km determined by glycemic status of the patients.ConclusionIt can be concluded that poor glycemic control evokes greater reduction in erythrocyte Na+K+-ATPase activity and promote enzyme-blood atherogenic lipid relationships in Type 1 diabetic Nigerian patients.

A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study.

BackgroundBlood lipid levels including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are highly heritable. Genome-wide association is a promising approach to map genetic loci related to these heritable phenotypes.MethodsIn 1087 Framingham Heart Study Offspring cohort participants (mean age 47 years, 52% women), we conducted genome-wide analyses (Affymetrix 100K GeneChip) for fasting blood lipid traits. Total cholesterol, HDL-C, and TG were measured by standard enzymatic methods and LDL-C was calculated using the Friedewald formula. The long-term averages of up to seven measurements of LDL-C, HDL-C, and TG over a ~30 year span were the primary phenotypes. We used generalized estimating equations (GEE), family-based association tests (FBAT) and variance components linkage to investigate the relationships between SNPs (on autosomes, with minor allele frequency ≥10%, genotypic call rate ≥80%, and Hardy-Weinberg equilibrium p ≥ 0.001) and multivariable-adjusted residuals. We pursued a three-stage replication strategy of the GEE association results with 287 SNPs (P < 0.001 in Stage I) tested in Stage II (n ~1450 individuals) and 40 SNPs (P < 0.001 in joint analysis of Stages I and II) tested in Stage III (n~6650 individuals).ResultsLong-term averages of LDL-C, HDL-C, and TG were highly heritable (h2 = 0.66, 0.69, 0.58, respectively; each P < 0.0001). Of 70,987 tests for each of the phenotypes, two SNPs had p < 10-5 in GEE results for LDL-C, four for HDL-C, and one for TG. For each multivariable-adjusted phenotype, the number of SNPs with association p < 10-4 ranged from 13 to 18 and with p < 10-3, from 94 to 149. Some results confirmed previously reported associations with candidate genes including variation in the lipoprotein lipase gene (LPL) and HDL-C and TG (rs7007797; P = 0.0005 for HDL-C and 0.002 for TG). The full set of GEE, FBAT and linkage results are posted at the database of Genotype and Phenotype (dbGaP). After three stages of replication, there was no convincing statistical evidence for association (i.e., combined P < 10-5 across all three stages) between any of the tested SNPs and lipid phenotypes.ConclusionUsing a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.

Colesterol não-HDL em escolares de 7 a 17 anos de idade em um município brasileiro

To describe the levels of non-HDL cholesterol and correlated factors in a group of Brazilian male and female children and adolescents. From March to October 2002 we evaluated 2,029 schoolchildren from 7 to 17 years old in the town of Maracaí, São Paulo, Brazil. The biochemical determinations of triglycerides, total cholesterol, and high-density lipoprotein (HDL) cholesterol were carried out using enzymatic reactions and the Vitros 750 analyzer. Low-density lipoprotein (LDL) cholesterol levels were calculated using the Friedewald formula: LDL cholesterol = total cholesterol-HDL cholesterol-(triglycerides/5). Non-HDL cholesterol was calculated by subtracting HDL cholesterol from total cholesterol. The correlation between non-HDL cholesterol levels and LDL cholesterol levels was 0.971 (P < 0.001). Non-HDL cholesterol had a stronger correlation than did LDL cholesterol with all the variables under study: total cholesterol, triglycerides, HDL cholesterol, very low-density lipoproteins, body mass index, and waist circumference. The non-HDL cutpoints identified as corresponding to the four cutpoints of LDL cholesterol (110, 130, 160, and 190 mg/dL) indicating the need to treat dyslipidemia in children and adolescents were, respectively: 127.8, 149.2, 181.2, and 213.2 mg/dL. Our findings contribute toward estimating non-HDL levels in Brazilian children and adolescents. The results also indicate that non-HDL cholesterol is a reliable and less costly method for researching the presence of dyslipidemias in this age group.

Serum lipid and lipoprotein profile of Asian tortoise (Agrionemys horsfieldi) in prehibernation state

The Asian tortoise (Agrionemys horsfieldi), which now has a worldwide distribution, originates from Iran, Pakistan, West China, Kazakstan, Turkmenia, and Russia. Because of the increasing popularity of this animal as a domestic pet and its presence in many zoological gardens, knowledge of its physiological characteristics at different stages of life is important. In this regard, serum lipid and lipoprotein profiles of Asian tortoise were measured just before hibernation. Blood samples were collected from the jugular vein of 16 tortoises of both sexes. Total cholesterol (TC), phospholipid (PL), high-density lipoprotein cholesterol (HDL-C) were measured chemically, very-low-density lipoprotein cholesterol (VLDL-C) was calculated as an estimation of one fifth of triglyceride (TG), low-density lipoprotein cholesterol was determined on the basis of Friedewald's formula, and total lipid was calculated from the summation of TG, TC, and PL. PL and TC comprised 79 and 21% of total lipid in the male and 85 and 14% in the female, respectively. TG level was low in both sexes. Moreover, approximately 86 and 12% of TC were carried through LDL and HDL, respectively. Before hibernation, PL and LDL-C are the major lipid and cholesterol fractions of serum, respectively.

Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events

The relationship between autoantibodies to oxidized low density lipoprotein (OxLDL) and coronary artery disease (CAD) remains controversial. IgM and IgG OxLDL autoantibodies to malondialdehyde (MDA)-modified LDL, copper oxidized low density lipoprotein (CuOxLDL), and oxidized cholesterol linoleate (OxCL), as well as apolipoprotein B-100 immune complexes (apoB-ICs), were measured in 504 patients undergoing clinically indicated coronary angiography. Patients were followed for cardiovascular events for a median of 4 years. In univariate analysis, IgM OxLDL autoantibodies and IgM apoB-ICs were inversely associated with the presence of angiographically determined CAD, whereas IgG OxLDL autoantibodies and IgG apoB-ICs were positively associated. In logistic regression analysis, compared with the first quartile, patients in the fourth quartile of IgM OxLDL autoantibodies and apoB-ICs showed a lower probability of angiographically determined CAD (>50% diameter stenosis). Odds ratios and (95% confidence intervals) were as follows: MDA-LDL, 0.51 (0.32-0.82; P = 0.005); CuOxLDL, 0.63 (0.39-1.01; P = 0.05); OxCL, 0.63 (0.39-1.01; P = 0.05); and apoB-IC, 0.55 (0.34-0.88; P = 0.013). These relationships were accentuated in the setting of hypercholesterolemia, with the highest IgM levels showing the lowest risk of CAD for the same level of hypercholesterolemia. Multivariable analysis revealed that neither IgM or IgG OxLDL autoantibodies nor apoB-ICs were independently associated with angiographically determined CAD or cardiovascular events. In conclusion, IgG and IgM OxLDL biomarkers have divergent associations with CAD in univariate analysis but are not independent predictors of CAD or clinical events.

Response to: Low-density lipoprotein cholesterol estimation by a new formula — Confirmation

Gasko et al. in their study of over 10,000 patients have confirmed the utility of the new formula derived by us [ [1] Anandaraja S. Narang R. Godeswar R. Laksmy R. Talwar K.K. Low-density lipoprotein cholesterol estimation by a new formula in Indian population. Int J Cardiol. 2005; 102: 117-120 Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar ] for the indirect estimation of low-density lipoprotein cholesterol. Our formula had better correlation than the conventional Friedewald formula as compared to direct method of estimation of low-density lipoprotein cholesterol. The validation was conducted in a mix of urban and rural population of Brazil. The mean low-density lipoprotein cholesterol level calculated by direct method and that estimated by the indirect Friedewald method were similar to our population (116±22 mg/dl vs 116±41.5 mg/dl and 120±24 mg/dl vs 119±46 mg/dl, respectively). It is heartening to find that the utility of the formula derived from Indians is equally effective to a different ethnic group, indicating that the new formula is applicable for a wider range of population. The ratio of triglycerides to very low-density lipoprotein cholesterol varies with the population studied [ 2 Hata Y. Nakajima K. Application of Friedenwald LDL-cholesterol estimation formula to serum lipids in the Japanese population. Jpn Circ J. 1986; 50: 1191 Crossref PubMed Scopus (32) Google Scholar , 3 Fujimoto W.Y. Friedenwald's LDL-cholesterol estimation formula in a Japanese American population. Jpn Circ J. 1988; 52: 604-606 Crossref PubMed Scopus (11) Google Scholar ] and hence application of the Friedewald formula for low-density lipoprotein cholesterol estimation in different populations may lead to varying accuracies. Our formula is solely based on regression analysis and hence may have a wider utility as reported by Gasko et al. in their present study.

The lipid-lowering effect of ezetimibe in pure vegetarians

Results of previous studies have shown that ezetimibe (10 mg/day) reduces LDL cholesterol in patients with mild hypercholesterolemia on a normal-cholesterol diet (dietary intake of 200-500 mg/day) by 16-22%. However, the LDL cholesterol-lowering effect of ezetimibe in subjects with an extremely low dietary cholesterol intake (vegetarians) has not been studied. We conducted a randomized, double-blind, placebo-controlled, two-phase crossover study in 18 healthy pure vegetarians to assess the effect of ezetimibe (10 mg/day) on plasma lipids, cholesterol absorption, and its synthesis. Treatment periods lasted 2 weeks each, with an intervening 2 week washout period. Fractional cholesterol absorption was determined using the continuous dual stable isotope feeding method. Mean dietary cholesterol intake in the pure vegetarians was extremely low and averaged 29.4 +/- 16.8 and 31.4 +/- 14.4 mg/day during the placebo and ezetimibe administration phases, respectively. Fractional cholesterol absorption during the placebo phase was 48.2 +/- 8.2% and was decreased by 58% during ezetimibe treatment to 20.2 +/- 6.2% (P < 0.001). This change in intestinal cholesterol absorption was followed by a significant reduction in LDL cholesterol of 17.3%. In individuals with extremely low dietary cholesterol intake, treatment with ezetimibe (10 mg/day) leads to a significant reduction of cholesterol absorption and a clinically relevant decrease of plasma LDL cholesterol, comparable to that of subjects with a normal dietary cholesterol intake. Thus, the lipid-lowering effect of ezetimibe is mediated mainly through a reduction of the absorption of endogenous (biliary) cholesterol.

Falsely Low LDL Cholesterol Results and Cholestasis

LDL cholesterol (LDL-C) is commonly measured for evaluation and management of hypercholesterolemia. The Friedewald formula [LDL-C = (total cholesterol)—(HDL cholesterol)—triglycerides/2.2 for mmol/L] is commonly used to determine LDL-C, but this method has some well-established shortcomings and may not meet the National Cholesterol Education Program criteria of total error <12% (1)(2)(3). Another approach is the use of homogeneous methods for direct quantification of LDL-C. In our laboratory, we use the Kyowa Medex® method 2nd-generation assay on a Roche Cobas Integra 800® analyzer (1)(3)(4). We report a case of falsely low LDL-C results in a man 69 years of age with type IIa dyslipidemia according to the Frederickson classification. The patient was admitted to the hospital for coronary heart disease and weight loss of 8 kg over a 3-week period. On admission, we performed a lipid evaluation on the Cobas Integra 800. The results revealed a discrepancy between the total cholesterol (TC; 9.18 mmol/L), and the sum of direct LDL-C (3.55 mmol/L) …

Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol

We studied the relationship of apolipoprotein E (apoE) isoforms and coronary artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing diagnostic coronary angiography. The presence of CAD was defined as >50% stenosis in at least one artery. ApoE allele frequencies were 0.12, 0.62, and 0.26 for epsilon 2, epsilon 3, and epsilon 4, respectively, in African Americans and 0.08, 0.78, and 0.14 for epsilon 2, epsilon 3, and epsilon 4, respectively, in Caucasians. Among African Americans, CAD was present in 9 of 34 epsilon 2 carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39 of 82 epsilon 3 carriers and 43 of 92 epsilon 4 carriers (48% and 47%, respectively), suggesting a protective effect of the epsilon 2 allele. No such difference was seen in Caucasians. In African Americans but not Caucasians, LDL cholesterol was lower in epsilon 2 carriers than in epsilon 3 and epsilon 4 carriers (106 vs. 127 and 134 mg/dl, respectively; P < 0.005). After adjusting for lipid levels, the association between apoE2 and CAD was no longer significant. Thus, the protective effect of apoE2 seen in African Americans could be explained by a favorable lipid profile in epsilon 2 carriers, whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 on the lipid profile.

LDL-cholesterol calculation formulas in patients with or without the metabolic syndrome

The present study compares the low-density lipoprotein cholesterol (LDL-C) values obtained by the Friedewald formula (LDL-F) with those derived from a new equation that uses only the concentrations of total cholesterol and triglycerides (LDL-A) in patients with the metabolic syndrome (MS) (n = 118) and in age- and sex-matched controls (n = 112). According to our results, LDL-A was correlated with LDL-F in the MS as well as in the control group (p for both < 0.001). However, LDL-A slightly overestimated the LDL-C levels compared with LDL-F in the control group, possible due to the higher high-density lipoprotein cholesterol (HDL-C) levels in these individuals. Importantly, no difference was observed between the two equations in the MS group. LDL-A may be useful for the calculation of LDL-C levels when HDL-C level are not easily available.

Cord blood lipoprotein profile after magnesium sulphate treatment in pre‐eclamptic patients

To determine lipoprotein metabolism alterations in magnesium-exposed neonates of women with pre-eclampsia. The study group comprised seven singleton neonates of women with pre-eclampsia at term and treated with magnesium sulphate. Controls were 26 neonates of uncomplicated pregnancies of term delivery. Total serum magnesium concentrations were analysed by the photometric colour method. Total serum cholesterol, triglycerides and high-density lipoprotein cholesterol (HDL-C) levels were determined by enzymatic colour methods, while apoprotein (apo) A-I and apo B values were measured by immunoturbidimetry. Low-density lipoprotein cholesterol (LDL-C) levels were calculated by Friedewald's formula. Very-low-density lipoprotein cholesterol levels, total cholesterol/ HDL-C, apo B/apo A-I, LDL-C/apo B, LDL-C/HDL-C, and HDL-C/apo A-I ratios were determined by calculation. Magnesium levels of magnesium-exposed neonates were found to be 1.6 times higher than those of controls. Magnesium-exposed neonates had lower serum apo A-I levels, and they had higher apo B/apo A-I and HDL-C/apo A-I ratios when compared to controls. The lipoprotein profile became more atherogenic in magnesium-exposed neonates as it may be a potential risk factor of cardiovascular heart disease.