Safety profile of atorvastatin-treated patients with low LDL-cholesterol levels

Data pooled from 21 atorvastatin clinical trials have been analyzed to establish the safety of reducing low density lipoprotein cholesterol (LDL-C) levels below currently recommended minimum targets in hypercholesterolemic patients. Safety data for atorvastatin-treated patients with at least one LDL-C value < or =80 mg/dl (2.1 mmol/l) (n = 319) during treatment (mean LDL-C level throughout treatment was 91 mg/dl [2.4 mmol/l]) were compared to those from all atorvastatin-treated patients (n = 2502) and patients treated with lovastatin, simvastatin or pravastatin (n = 742). The frequency of treatment-associated adverse events (AEs) in the atorvastatin LDL-C < or =80 mg/dl (2.1 mmol/l) subgroup (24%) was comparable to the frequencies observed for all atorvastatin-treated patients (20%) and for patients receiving the other statins (24%). Patient withdrawals due to treatment-associated AEs (constipation, dyspepsia and flatulence being the most common) were consistent and low across treatment groups. No treatment-associated deaths occurred in any group. Safety data for 21 atorvastatin-treated patients with LDL-C < or =50 mg/dl (1.3 mmol/l) were also analyzed and found to be similar to all atorvastatin-treated patients and patients treated with the other statins. While recognizing the short-term nature of the data (all patients who received atorvastatin were treated for < or =1 year and approximately 30% were treated for < or =6 months), this analysis suggests that reducing LDL-C levels below 80 (2.1 mmol/l) or 50 mg/dl (1.3 mmol/l) with atorvastatin does not alter its safety profile, as measured by frequency of AEs, which remains similar to those of other statins.     

Analytical performance of a direct assay for LDL-cholesterol: a comparative assessment versus Friedewald's formula.

OBJECTIVE: Because low density lipoprotein-cholesterol (LDL-C) is a modifiable risk factor for coronary artery disease (CAD), its routine measurement is recommended in the evaluation and management of hypercholesterolemia. Concentrations of LDL-C are commonly monitored by means of the Friedewald formula (FF), which provides a relative estimation of LDL-C concentration when the triglyceride (TGs) concentration is <200 mg/dl and there are no abnormal lipids. Because of the limitations of the Friedewald calculation, direct methods for an accurate quantification of LDL-C are needed. METHODS: We critically examined an immunoseparation method for direct assay of LDL-C in a comparison with FF. 1) We measured intraassay and interassay precision using quality-control sera and patient serum pools. Accuracy was evaluated from total error analyses. Sample stability was examined over 2 months. 2) The LDL-C levels obtained with direct assay were compared with those calculated by the FF in 47 randomly chosen patient samples. The samples were classified as group 1 (patients with TGs 60-308 mg/dl, n=25) and group 2 (patients with TGs 320-695 mg/dl, n=22). RESULTS: The direct immunoseparation assay displayed an excellent precision (total coefficient of variance (CV)<2.5%, intraassay CV<1.5% and interassay CV<1.5%). Mean total error was 4.34%. The direct assay met the current National Cholesterol Education Program (NCEP) requirements for LDL-C testing for precision and accuracy. The results of direct method (x) and the FF (y) were highly correlated (r=0.9908, y=1.030 x -0.289, n=25) in group 1, but the results of two methods disagreed (r=0.716, y=0.956 x -24.869, n=22) in group 2 (patients with TGs 320-695 mg/dl). CONCLUSION: The direct immunoseparation assay meets the currently established analytical performance goals and may be useful for the diagnosis and management of hyperlipidemic patients.     

血清低密度脂蛋白胆固醇直接测定与公式计算结果相关性的研究

目的 :分析匀相测定法测定的血清低密度脂蛋白胆固醇 (LDL C)值与Friedewald公式 (F公式 )计算结果 ,对比二法LDL C值的差异 ,评价二种方法在大规模流行病调查和临床应用方面的适用条件及影响LDL C值的因素。方法 :对北京市自然人群采取分层随机抽样的方法进行心血管病危险因素调查 ,测定其血脂 (TC、TG、HDL C、LDL C等 )水平 ,数据完整用于分析的为 2 5～ 6 4岁的男女共计 12 18人。结果 :1 TG≤ 4 5 2mmol L时F公式法与匀相测定法的相关性 (r=0 831)好于TG >4 5 2mmol L时 (r=0 6 2 0 )。 2 比较二种方法差值的绝对值 ,在TG >4 5 2mmol L组其差值较大 ,与其它各组差值的差异均有显著性 (P <0 0 0 1)。 3 总胆固醇 (TC)水平对LDL C结果也有影响 :TG≤ 4 5 2mmol L时 ,TC <6 2 1mmol L组二种结果的相关性好于TC≥ 6 2 1mmol L组 ;而当TG >4 5 2mmol L时 ,TC <6 2 1mmol L组二种结果的差异最大 (r=0 2 19)。结论 :Friedewald公式在TG水平≤ 4 5 2mmol L时与匀相测定法相关性较好 ,且TC <6 2 1mmol L时的相关性好于TC≥ 6 2 1mmol L时。在确保TC、TG、HDL C结果准确可靠的情况下 ,可以用Friedewald公式计算的LDL C值作为参考     

Inverse correlation between plasma oxysterol and LDL-cholesterol levels in hepatitis C virus-infected patients

BackgroundHepatitis C virus infection is characterised by enhanced oxidative stress, which can be measured quantitatively by plasma oxysterol concentration. These molecules may affect lipid metabolism through the activation of Liver X Receptors. Hepatitis C virus exploits host lipid metabolism to facilitate its replication and diffusion. In our study we aimed to evaluate and highlight the potential pathogenetic role of oxysterols, 7-ketocholesterol and 7-β-hydroxycholesterol, in hepatitis C virus-related lipid dysmetabolism.MethodsThe study was performed in 42 patients with chronic hepatitis C (93% genotype 1b) and 38 non-alcoholic fatty liver disease patients. Plasma oxysterols 7-ketocholesterol and 7-β-hydroxycholesterol were determined by isotope dilution gas chromatography/mass spectrometry.ResultsGas chromatography/mass spectrometry revealed higher 7-ketocholesterol (71.2 ± 77.3 vs 30.4 ± 14.5; p < 0.005) and 7-β-hydroxycholesterol (23.7 ± 20.6 vs 11.5 ± 4.9; p < 0.001) plasma levels in hepatitis C virus patients. Furthermore, multivariate regression analysis highlighted an inverse independent correlation between high oxysterol levels and low low-density lipoprotein cholesterol (p = 0.01 for 7-β-hydroxycholesterol; p = 0.02 for 7-ketocholesterol) in the hepatitis C virus group; in contrast, the non-alcoholic fatty liver disease group showed a direct correlation between oxysterol levels and low-density lipoprotein-cholesterol (p < 0.001 for 7-β-hydroxycholesterol; p = 0.002 for 7-ketocholesterol).ConclusionThese different correlations reveal profound differences in lipid dysmetabolism between chronic hepatitis C and non-alcoholic fatty liver disease patients.     

Application of Friedewald's LDL-cholesterol estimation formula to serum lipids in the Japanese population

When direct measurement of serum low density lipoprotein cholesterol (LDL-c) is not available, it can be estimated from total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-c) by using the formula proposed by Friedewald: LDL-c = TC-[HDL-c + TG/k], k = 5 This formula assumes the triglyceride/cholesterol ratio in VLDL to be 5:1. However, it is changeable with serum triglyceride levels, and averaged as 4 among Japanese with triglycerides less than 400 mg/dl. The formula provides a better fit for Japanese people, when k = 4, rather than original k = 5. In addition, a better estimation is gained, if k is rotated according to the triglyceride levels of individual subjects; i.e. 3 for those with triglycerides less than 150 mg/dl, 4 for those with triglycerides from 150 to 299 mg/dl, 5 for those with triglycerides from 300 to 400 mg/dl. The percent error of estimation is less than 5% when k = 4, and about 1% when variable k is employed for populations of about 1,000 subjects in number.     

Antibody elutions in Thai patients with a positive direct antiglobulin test

Background

The direct antiglobulin test is performed to determine whether an anaemic patient with evidence of haemolysis has autoimmune or alloimmune haemolytic anaemia.

Materials and methods

We determined the antibody specificity of eluted IgG antibodies from patients’ blood samples with a positive direct antiglobulin test. Overall, 134 Thai patients were included in this study. EDTA blood samples were obtained from recently transfused patients, patients with unexplained anaemia and patients who had serum antibodies detected during routine pre-transfusion tests from different hospital blood banks. These complicated samples were sent to the National Blood Centre of the Thai Red Cross Society for investigation and to find compatible blood components. Each blood sample underwent a direct antiglobulin test with the gel technique using polyspecific antihuman globulin and mononospecific anti-IgG and anti-C3d. Acid eluates were prepared from the samples for which the direct antiglobulin test was positive and the specificities of the eluted antibodies were determined by the gel technique.

Results

Of the samples tested, 101 showed a positive direct antiglobulin test result (75.4%) using polyspecific antihuman globulin sera whereas only 95 samples (70.9%) were positive with anti-IgG or anti-IgG and anti-C3d. Moreover, 54 of 95 eluates (56.8%) were positive for antibody screening and tested with the reagent panel cells. Twenty-one eluates had specific alloantibodies, which were concordant with the findings in the patients’ sera and all patients had a history of blood transfusion. Additionally, 33 eluates contained pan-agglutinins. Interestingly, alloantibodies could be determined using titration studies in 5 of 26 eluates with pan-agglutinins.

Conclusion

Although the direct antiglobulin test is not routinely performed in pre-transfusion screening, this test and elution studies would be useful in patients with a history of previous transfusions, and in those for whom compatible blood cannot be found.     

Application of the Sampson equation to estimate LDL-C in children: Comparison with LDL direct measurement and Friedewald equation in the BLIP study

Background and aimsIn epidemiological trials and in clinical practices, it is relevant to have affordable and reliable methods to measure the main lipid cardiovascular risk factors, and in particular low-density lipoprotein cholesterol (LDL-C) plasma level. In this context, we aimed to compare the reliability of the Friedewald's (LDL-Cf) and Sampson's (LDL-Cs) equations with the LDL-value dosed by a validated dosage method (LDL-Cd) in a large cohort of children.Methods and resultsWe considered the lipid values of 145 infants, 278 preschoolers, 810 scholar children, and 1372 adolescents (Total N. 2605, 1291 males, 1314 females), with mean total cholesterol (TC) = 169.8 ± 39.7 mg/dL, HDL-Cholesterol = 50.8 ± 12.7 mg/dL, non HDL-Cholesterol = 118.9 ± 35.9 mg/dL, Triglycerides (TG) = 90.3 ± 77.9 mg/dL, LDL-Cd = 106.2 ± 29.9 mg/dL, LDL-Cf = 100.9 ± 33.8 mg/dL, and LDL-Cs = 102.2 ± 33.4 mg/dL. Comparing the distance to the LDL-Cd, Friedewald's equation mildly but significantly underestimated in infants (3.4 ± 5.3 mg/dL), preschoolers (1.5 ± 7.1 mg/dL). Children (1.2 ± 2.2 mg/dL) and adolescents (1.1 ± 5.9 mg/dL) compared to Sampson's equation (all comparisons, p < 0.001).ConclusionsOur analysis, being carried out on a large population sample, shows that Sampson's equation is more reliable than Friedewald's one at each considered age class and even for extreme TG values.     

Intima-media thickness after pravastatin stabilizes also in patients with moderate to no reduction in LDL-cholesterol levels: the carotid atherosclerosis Italian ultrasound study

The Carotid Atherosclerosis Italian Ultrasound study (CAIUS), a multicenter, double-blind clinical trial, performed in 305 asymptomatic, moderately hypercholesterolemic patients, clearly demonstrated beneficial effects of pravastatin on the carotid intima-media thickness (IMT) progression. The database of the CAIUS study was examined in order to investigate the presence of a relationship, if any, between the activity of pravastatin on IMT progression rate and its hypocholesterolemic effect. Quantitative B-mode ultrasound imaging was used to quantify the individual mean maximum IMT progression rate in 3 years. In the overall group of patients (placebo and pravastatin) covariance analysis showed that while the variable 'treatment' (0 = placebo, 1 = pravastatin) was significantly related to the reduction of IMT progression (F= 6.6, P = 0.01), the IMT progression did not correlate with the extent of LDL-C lowering (F= 0.00, P = 0.98). To further investigate this issue. the pravastatin treated group was stratified into quartiles of LDL-C reduction. In contrast to what was observed in the placebo group, in which a positive mean IMT progression rate was observed, independent of the extent of LDL-C reduction, no IMT progressionwas observed in any subgroup treated with pravastatin. No significant difference was found among quartiles and no trend could be identified. In conclusion, the effect of pravastatin treatment on carotid IMT progression rate is beneficial; however the CAIUS study demonstrated that lowering LDL-C by itself, does not explain the variability of beneficial changes in IMT.     

健脾清热活血方与美沙拉嗪治疗溃疡性结肠炎的对比研究

[目的]评价健脾清热活血方辨治溃疡性结肠炎的疗效。[方法]采用非劣效试验设计,应用随机对照设计,将120例符合诊断标准、纳入标准的溃疡性结肠炎患者随机分为2组,治疗组60例,对照组60例。治疗组予中药复方健脾清热活血方干预12周,对照组予美沙拉嗪干预12周。详细记录治疗前、后患者肠镜及症状变化。[结果]治疗前、后肠镜病变疗效判定,治疗组总有效率为66．66％,对照组总有效率为63．33％,在促进溃疡愈合方面,2组疗效无差异（P〉0．05）;治疗前、后症状积分判定疗效,治疗组总有效率为78．33％,对照组总有效率为61．66％,在改善临床症状方面,治疗组疗效优于对照组（P〈0.05）。[结论]健脾清热活血方具有提高溃疡性结肠炎愈合质量、缓解其临床症状的功效,值得临床推广应用。     

Influence of apolipoprotein E genotype on the reliability of the Friedewald formula in the estimation of low-density lipoprotein cholesterol concentrations

Lipoprotein data and apolipoprotein (apo) E genotype from 1302 participants, covering a wide range of total plasma cholesterol levels, were used to examine the impact of apo E genotype on the estimation of low-density lipoprotein cholesterol (LDL-C0 concentrations by the Friedewald formula using high-density lipoprotein cholesterol and triglyceride (TG) concentrations as compared with the beta -quantification reference procedure. The results showed that participants with apo E2/E2 genotype had significantly higher very low-density lipoprotein cholesterol (VLDL-C) concentrations and VLDL-C/TG ratio as well as lower LDL-C concentrations than participants with other apo E genotypes. Heterozygous carriers of the epsilon 2 allele had significantly higher VLDL-C than participants with apo E3/E3 and E4/E3 genotypes. The mean absolute error and the mean percentage of bias in calculated LDL-C according to all apo E genotypes, except E2/E2 genotype, were less than 0.16 mmol/L and 4.4%, respectively. Indeed, the mean error and the mean percentage of bias associated with the LDL-C calculated by the Friedewald formula in the apo E2/E2 group were 0.93 mmol/L and 40.6%, respectively. However, participants with the apo E2/E2 genotype and a type III phenotype showed a mean error and a mean percentage of bias reaching 1.53 mmol/L and 63.5%, respectively, whereas E2/E2 participants with a non-type III phenotype had a mean error and a mean percentage of bias of 0.18 mmol/L and 11.0%, respectively. Moreover, 41.9% to 57.1% of the participants had an absolute bias higher than 5% according to the apo E genotype, except for the apo E2/E2 genotypic group where 88.6% of the participants had an absolute bias higher than 5%. Stepwise multiple linear regression analyses revealed that the apo E genotype contributed to 39.0% of the VLDL-C/TG ratio variance, whereas sex, age, and high-density lipoprotein cholesterol explained between 0.5% and 3.2% of the variance. These results indicate that the apo E genotype exerts a significant influence on the estimation of LDL-C concentrations by the Friedewald formula as compared with the beta-quantification.     

Comparison of direct methods and HPLC for the measurement of HDL- and LDL-cholesterol with ultracentrifugation

Although ultracentrifugation is the gold standard for lipoprotein analysis, inexpensive and easy direct methods for HDL- and LDL-cholesterol (C) have recently been developed. In this study, we compared representative methods of lipoprotein analysis, namely, ultracentrifugation, direct assay methods, and HPLC, to measure LDL- and HDL-C. A good correlation was observed between HDL-C by ultracentrifugation and HDL-C by direct methods or HPLC. A good correlation was also observed between LDL-C (d1.006-1.063) by ultracentrifugation and LDL-C by direct methods or HPLC. Although the correlation between LDL-C (d1.019-1.063) by ultracentrifugation and LDL-C by direct methods was also good, the correlation coefficient was significantly decreased, suggesting that 'LDL-C' by direct methods correlates better with LDL-C (d1.006-1.063) than LDL-C (d1.019-1.063) by ultracentrifugation. Although the correlation between IDL-C (d1.006-1.019) by ultracentrifugation and the difference in LDL-C by direct methods and LDL-C (d1.019-1.063) by ultracentrifugation was investigated, no significant correlation was observed. The IDL-C contained in LDL-C (d1.006-1.063) varied from 2-28%. In homozygous CETP-deficient and LCAT-deficient subjects, the dissociation was marked. It is crucial to understand that 'LDL-C' in the Guidelines for the Diagnosis and Treatment of Hyperlipidemias in Adults by the Japanese Atherosclerosis Society should be considered to be LDL-C (d1.006-1.063) and that 'LDL-C' by direct assay methods means LDL-C (d1.006-1.063) by ultracentrifugation.     

Prevalence of low LDL-cholesterol levels and elevated high-sensitivity C-reactive protein levels in apparently healthy Korean adults

Background and aimsThe Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) reported reduced cardiovascular and all-cause mortality in patients with elevated C-reactive protein (CRP) and low LDL-cholesterol (LDL-C) levels treated with statins. The aims of this study were to determine the proportion of “JUPITER-eligible” Korean adults and to describe their characteristics.Methods and resultsAs many as 15,154 subjects with serum LDL-C levels <130 mg/dL were selected among 28,851 middle-aged participants (men ≥ 50 years, women ≥ 60 years) who participated in a routine health check-up program. Among the participants with LDL-C less than 130 mg/dL, only 15% had CRP levels ≥2.0 mg/L (7.9% of original participants). Subjects were divided into four groups according to CRP levels (<0.5, ≥0.5 ? <1.0, ≥1.0 ? <2.0, and ≥2.0 mg/L). Mean HDL-C and apolipoprotein A1 levels decreased significantly as the mean CRP values increased. The insulin and homeostasis model of insulin resistance was significantly different according to CRP quartile. The number of subjects with metabolic syndrome and its components increased significantly as the mean CRP values increased.ConclusionIn this Asian population, few individuals with low LDL-C levels had CRP levels ≥2.0 mg/L. Elevated CRP levels were associated with components of atherogenic dyslipidemia and insulin resistance. Additional clinical trials should be designed and performed in different ethnic groups, as different CRP cut-off levels may be required in different ethnic groups.     

Clinical study of Thai patients with ankylosing spondylitis

Summary Sixty-one Thai patients with ankylosing spondylitis (AS), diagnosed in accordance with Rome and New York criteria for AS, were studied. The cases includes idiopathic AS (46 cases), Reiter's syndrome AS (8 cases) and psoriatic spondylitis (7 cases). The vast majority of patients were male (MaleFemale = 11.21), and in over three-fourths the age of onset was between 10 and 39. Low back pain and peripheral arthritis as the initial manifestations were observed in 78.68 and 55.73% of patients respectively. Peripheral arthritis was evident during the course of illness in 72.13 % of cases, oligoarticular arthritis being predominant (68.97%). Heel pain, tendonitis and plantar pain were noted in 19.67, 4.92 and 3.28% respectively. Most patients had lumbosacral and thoracic spine involvements, and only 49.18% showed involvement of the cervical spine. Bilateral sacroiliitis was noted in 98.36%. Uveitis was evident in 11.47% while evidence of aortic insufficiency was noted in 3.28%. An association with HLA-B27 was encountered in 91.07% of all cases. In general, the clinical features of AS in Thai patients are similar to those reported elsewhere, but an association with inflammatory bowel disease and Behcet's disease are notably absent.     

Comparative study on the diagnostic value of direct and indirect cholangiography

The examinations contain the findings of the endoscopic retrograde cholangiopancreaticography in 600 patients, the date of a controlled comparative study intravenous cholangiotomography versus endoscopic retrograde cholangiography in 45 patients undergoing endoscopic retrograde cholangiopancreaticography and the results of the percutaneous transhepatic cholangiography in 54 patients. In anicteric patients and after subsidence of the clinical symptoms the optimum use of the intravenous cholegraphy with tomography is to be demanded. It is able multiply to clarify the diagnosis. The terminal part of the choledochus deserves particular consideration. In obstructive jaundice the percutaneous transhepatic cholangiography is essentially more successful and simpler than the endoscopic retrograde cholangiography.     

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.     

LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study.

We read with great interest the article entitled ‘LDL-cholesterolpredicts negative coronary artery remodelling in diabetic patients:an intravascular ultrasound study’.¹ A major finding ofthis study is the high frequency (72%) of negative remodelling(i.e. a