Compatibility between an overnight fasting and random cholesterol tests in Asians.

Recent Western guidelines recommend non-fasting lipid profiles to manage dyslipidaemia. We explored its applicability to an Asian population. We determined the differences between an overnight fasting and non-fasting cholesterol profiles of patients with type-2 diabetes mellitus (T2DM) in Singapore. We studied 470 multi-ethnic Asian adult patients with T2DM and dyslipidaemia from 2 primary care clinics in Singapore. Non-fasting blood specimens were collected within 6 h after their last meal and within 14 days of a fasting specimen. The intraclass correlation coefficient (ICC) was used to compare the intraindividual lipid profiles. An ICC value > 0.75 implies good correlation. The mean age and T2DM duration of the study population were 62.5 years and 9.8 years respectively. Their mean non-fasting period was 2.46 h. The mean differences between non-fasting and fasting total cholesterol (TC), high-density lipoprotein (HDL-C), triglyceride (TG), low-density lipoprotein (LDL-C), and non HDL-C were + 0.04 mmol/l, - 0.001 mmol/l, + 0.48 mmol/l, - 0.15 mmol/l, and - 0.05 mmol/l respectively. The ICC (95% CI) for TC, HDL-C, TG, LDL-C and non-HDL-C were 0.820 (0.788-0.847), 0.873 (0.850-0.893), 0.579 (0.516-0.636), 0.764 (0.723-0.799), and 0.825 (0.794-0.852) respectively. The fasting and non-fasting lipid profiles were similar in our local Asian patients with T2DM taking statin. Their non-fasting lipid profile can be used to assess their cholesterol treatment status.

Standardization of Sandwich-Structured Cu-Glass Substrates Embedded in a Flexible Diode Laser-Plasma Interface for the Detection of Cholesterol.

This study introduced sandwich-structured copper-glass substrates for standardization of laser desorption and plasma ionization. For standardized quantitative analysis, cavities were constructed which allow better reproducibility in droplet deposition and for laser application. Applying the diode laser, molten substrate material is incorporated into the glass, being trapped inside. Therefore, this method can be separated from laser ablation, achieving high ion signals without ablating material from the surface. Flexible microtube plasma (FµTP) was selected as the ionization source, this being the first time that laser desorption and FµTP ionization are coupled. This laser-plasma interface was applied to the detection of cholesterol, which showed a significantly improved limit of detection of 0.46 ng and linear dynamic range of 3 orders of magnitude in positive ion mode compared to other (ambient air mass spectrometry) methods. The main reason was the change of phase on the copper surface. The dehydrated molecule [M-H2O+H]+ was the base peak of the spectrum and no further dissociation or fragmentation was observed. Blood plasma was spiked with cholesterol. In a 1:100 chloroform dilution, the presence of the plasma was neglectable and led to the same detection limits and linear dynamic range as in the cholesterol standard. No sample preparation or internal standards were needed for calibration. The physical effects of the surface modification were investigated, including the calculation of the laser beam waist to simplify the comparison and reproducibility of results.

Evolution of reference materials for the determination of organic nutrients in food and dietary supplements-a critical review.

For over 40 years, food-matrix certified reference materials (CRMs) have been available for determination of trace element content, and a wide variety of materials are available from most producers of CRMs. However, the availability of food-matrix CRMs for organic nutrients has been more limited. The European Commission (EC) Bureau Communautaire de Référence (BCR) and the National Institute of Standards and Technology (NIST) introduced food-matrix CRMs with values assigned for vitamins and other organic nutrients such as fatty acids and carotenoids in the 1990s. The number of organic nutrients for which values were assigned has increased significantly in the past decade, and the approach and analytical methods used for assignment of the certified values have also evolved. Recently, dietary supplement-matrix CRMs such as multivitamin tablets with values assigned for vitamins and carotenoids, and fish and plant oils with values assigned for fatty acids have appeared. The development, evolution, and improvement of food- and dietary supplement-matrix CRMs for determination of vitamins, carotenoids, and fatty acids are described, with emphasis on CRMs made available in the past 10 years. Recent food and dietary supplement CRMs for the determination of organic nutrients include infant formula, multivitamin tablets, milk and egg powders, breakfast cereal, meat homogenate, blueberries, soy flour, fish and plant oils, dry cat food, and protein drink powder. Many of these food- and supplement-matrix CRMs have values assigned for over 80 organic and inorganic nutrients, toxic elements, proximates, and contaminants. The review provides a critical assessment of the challenges and evolving improvements in the production and the analytical methods used for value assignment of these CRMs. The current status and future needs for additional food- and dietary supplement-matrix CRMs for organic nutrients are also discussed. Graphical abstract Food Composition Triangle with currently-available food-matrix certified reference materials (CRMs) for the determination of organic nutrients positioned according to fat, protein, and carbohydrate composition.

International descriptive and interventional survey for oxycholesterol determination by gas- and liquid-chromatographic methods.

Increasing numbers of laboratories develop new methods based on gas-liquid and high-performance liquid chromatography to determine serum concentrations of oxygenated cholesterol metabolites such as 7α-, 24(S)-, and 27-hydroxycholesterol. We initiated a first international descriptive oxycholesterol (OCS) survey in 2013 and a second interventional survey 2014 in order to compare levels of OCS reported by different laboratories and to define possible sources of analytical errors. In 2013 a set of two lyophilized serum pools (A and B) was sent to nine laboratories in different countries for OCS measurement utilizing their own standard stock solutions. In 2014 eleven laboratories were requested to determine OCS concentrations in lyophilized pooled sera (C and D) utilizing the same provided standard stock solutions of OCS. The participating laboratories submitted results obtained after capillary gas-liquid chromatography-mass selective detection with either epicoprostanol or deuterium labelled sterols as internal standards and high-performance liquid chromatography with mass selective detection and deuterated OCS as internal standard. Each participant received a clear overview of the results in form of Youden-Plots and basic statistical evaluation in its used unit. The coefficients of variation of the concentrations obtained by all laboratories using their individual methods were 58.5-73.3% (survey 1), 56.8-60.3% (survey 2); 36.2-35.8% (survey 1), 56.6-59.8, (survey 2); 61.1-197.7% (survey 1), 47.2-74.2% (survey 2) for 24(S)-, 27-, and 7α-hydroxycholesterol, respectively. We are surprised by the very great differences between the laboratories, even under conditions when the same standards were used. The values of OCS's must be evaluated in relation to the analytical technique used, the efficiency of the ample separation and the nature of the internal standard used. Quantification of the calibration solution and inappropriate internal standards could be identified as major causes for the high variance in the reported results from the different laboratories. A harmonisation of analytical standard methods is highly needed.

Pediatric reference intervals for calculated LDL cholesterol, non-HDL cholesterol, and remnant cholesterol in the healthy CALIPER cohort.

OBJECTIVES: Increased prevalence of pediatric obesity and associated co-morbidities has heightened the concern for cardiovascular disease (CVD) risk later in life. Although the fasting lipid profile is traditionally used to assess CVD risk, the non-fasting lipid profile may simplify lipid testing and better predict CVD risk. Unfortunately, non-fasting lipid reference values are limited, particularly for children. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has recruited thousands of healthy pediatric subjects to develop a pediatric reference interval database. Here, CALIPER reports pediatric reference intervals for non-fasting calculated low-density lipoprotein cholesterol (LDLc), non-high-density lipoprotein cholesterol (non-HDLc) and remnant cholesterol. METHODS: Non-fasting serum samples from the CALIPER cohort of community children and adolescents were previously analyzed for HDLc, total cholesterol, and triglycerides. These values were used to calculate LDLc, non-HDLc, and remnant cholesterol and subsequently establish reference intervals with corresponding 90% confidence intervals according to CLSI EP28-A3c guidelines. Reference intervals were also calculated using alternative statistical methods highlighted in recent literature. RESULTS: All three lipid parameters required an age partition at 1 year due to wider reference intervals in the first year of life. LDLc and non-HDLc required sex partitioning for subjects 1-<10 years. Non-HDLc upper reference limit was higher than the 2011 National Heart, Lung, and Blood Institute (NHLBII) pediatric recommended cut-offs, suggesting elevated atherogenic lipoproteins in a proportion of apparently healthy pediatric subjects. The LDLc upper reference limit (10-<19 year partition) was the same as the NHLBI cut-off, potentially due to lower calculated LDLc values in the non-fasting state. CONCLUSIONS: With the increased use of non-fasting lipid profiles, age- and sex-specific reference intervals and appropriate clinical decision limits are necessary for pediatric lipid monitoring. Our data supports the notion that appropriate decision limits, rather than reference intervals, should be used to interpret lipid levels in children as there is a high prevalence of hyperlipidemia in the apparently healthy pediatric population.

Sources and performance criteria of uncertainty of reference measurement procedures.

OBJECTIVE: This article wants to focus on the today available Reference Measurement Procedures (RMPs) for the determination of various analytes in Laboratory Medicine and the possible tools to evaluate their performance in the laboratories who are currently using them. METHODS: A brief review on the RMPs has been performed by investigating the Joint Committee for Traceability in Laboratory Medicine (JCTLM) database. In order to evaluate their performances, we have checked the organization of three international ring trials, i.e. those regularly performed by the IFCC External Quality assessment scheme for Reference Laboratories in Laboratory Medicine (RELA), by the Center for Disease Control and Prevention (CDC) cholesterol network and by the IFCC Network for HbA1c. RESULTS: Several RMPs are available through the JCTLM database, but the best way to collect information about the RMPs and their uncertainties is to look at the reference measurement service providers (RMS). This part of the database and the background on how to listed in the database is very helpful for the assessment of expanded uncertainty (MU) and performance in general of RMPs. Worldwide, 17 RMS are listed in the database, and for most of the measurands more than one RMS is able to run the relative RMPs, with similar expanded uncertainties. As an example, for a-amylase, 4 SP offer their services with MU between 1.6 and 3.3%. In other cases (such as total cholesterol, the U may span over a broader range, i.e. from 0.02 to 3.6%). With regard to the performance evaluation, the approach is often heterogenous, and it is difficult to compare the performance of laboratories running the same RMP for the same measurand if involved in more than one EQAS. CONCLUSIONS: The reference measurement services have been created to help laboratory professionals and manufacturers to implement the correct metrological traceability, and the JCTLM database is the only correct way to retrieve all the necessary important information to this end.

Electrochemical nonenzymatic sensor for cholesterol determination in food.

The treatment of some inborn metabolism errors requires cholesterol substitution therapy. Cholesterol plays a vital role in the human body. Therefore, the majority of cholesterol determination techniques are targeted to blood and blood serum. Nevertheless, cholesterol determination in food is important as well. In this paper, cholesterol determination using differential pulse voltammetry (DPV) in dairy products (e.g., milk, clotted cream, yogurt, butter, etc.) is reported with a novel nonenzymatic sensor based on diphosphonic acid of 1,4-diacetylglycoluril (DPADGU) as an electrode surface modifier. Stable anodic response was obtained from cholesterol on the modified carbon-based electrode. The sensor has high stability, sensitivity (20 µA mol L-1 cm-2), and a wide linear range from 1 up to 200 µM. The LOD and LOQ values are 1.5 and 5.1 µM, respectively. The developed methods were successfully applied to the above mentioned dairy products. Graphical abstract ᅟ.

Breaking the Barriers in Resident Education: A Quality Improvement Initiative.

INTRODUCTION: In 2013, the American College of Cardiology and American Heart Association updated the cholesterol guideline. Despite strong evidence supporting the recommendations, a discernible gap exists in the number of residents who practice them. Our study aimed to identify barriers hindering residents from guideline implementation. METHODS: Twenty eight residents were administered a preintervention and postintervention questionnaire to identify barriers in guideline application. The questionnaire was categorized into three barriers: knowledge, attitude, and behavior. A multifaceted educational intervention consisting of directed teaching sessions and supervised patient encounters was conducted. RESULTS: Our analysis showed that our residents lacked awareness, familiarity, and self-efficacy in using the cholesterol guideline. The intervention led to significant improvements in awareness (79% vs. 43%, p = .0129), familiarity (61% vs. 29%, p = .0306), and self-efficacy (65% vs. 16%, p = .0018) and achieved a 31% increase in knowledge (p = .0001), 38% in attitude (p = .0001), and 20% in behavior (p = .019). The overall improvement in scores averaged 30% (p = .0001). CONCLUSION: Our quality improvement initiative successfully improved our resident's comprehension and applicability of the 2013 ACC/AHA cholesterol guideline. We recommend a multifaceted educational approach tailored toward addressing specific barriers to improve the practice of evidence-based medicine.

Something important is missing in the ACC/AHA cholesterol treatment guidelines.

OBJECTIVE: To discuss factors surrounding development of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and reasons they have not yet been adopted by clinicians. SUMMARY: The new ACC/AHA cholesterol guidelines were released in November 2013. The guidelines are based on randomized controlled trial evidence and, if fully implemented, are likely to result in a reduction of atherosclerotic cardiovascular disease (ASCVD) in Americans. Despite this, the guidelines have not been adopted by clinicians. This is because the guidelines are missing something very important-guidance for the clinician and the public. Guidelines are supposed to give guidance to clinicians on how to manage the various clinical presentations encountered in daily practice and to help them translate science into practice. Guidelines are also supposed to help the public define dyslipidemias in a way they can understand and thus seek treatment and actively follow the progress of their treatment. CONCLUSION: The National Lipid Association (NLA) stepped in to help fill the void in the ACC/AHA cholesterol guidelines and offered recommendations for treating individual patients who have increased risk of ASCVD. The NLA recommendations give clinicians the expert guidance and LDL-C goal rudder they need to successfully manage their patient's cholesterol.

The new pooled cohort equations risk calculator.

In the National Cholesterol Education Program Adult Treatment Panel III guidelines published in 2001, estimation of cardiovascular risk was recommended based on the Framingham score for 10-year risk of myocardial infarction and the Canadian Cardiovascular Society currently recommends the Framingham total cardiovascular risk score. During development of joint guidelines released in 2013 by the American College of Cardiology (ACC) and American Heart Association (AHA), the decision was taken to develop a new risk score. This resulted in the ACC/AHA Pooled Cohort Equations Risk Calculator. This risk calculator, based on major National Heart, Lung, and Blood Institute-funded cohort studies, is designed to predict 10-year risk of 'hard' atherosclerotic cardiovascular disease (ASCVD) events, namely, nonfatal myocardial infarction, fatal coronary heart disease, nonfatal, or fatal stroke. Considerable strengths are its inclusion of stroke as an end point and race as a characteristic, which allows better risk prediction especially in African-American individuals, plus provision of lifetime ASCVD risk estimates for adults aged 20-59 years. Notable omissions from the risk factors include chronic kidney disease and any measure of social deprivation. An early criticism of the Pooled Cohort Equations Risk Calculator has been its alleged overestimation of ASCVD risk which, if confirmed in the general population, is likely to result in statin therapy being prescribed to many individuals at lower risk than the intended 7.5% 10-year ASCVD risk threshold for treatment in the joint ACC/AHA cholesterol guidelines. In this review we discuss the development of the new risk calculator, its strengths and weaknesses, and potential implications for its routine use.

Chicago Healthy Aging Study: objectives and design.

Investigators in the Chicago Healthy Aging Study (CHAS) reexamined 1,395 surviving participants aged 65-84 years (28% women) from the Chicago Heart Association Detection Project in Industry (CHA) 1967-1973 cohort whose cardiovascular disease (CVD) risk profiles were originally ascertained at ages 25-44 years. CHAS investigators reexamined 421 participants who were low-risk (LR) at baseline and 974 participants who were non-LR at baseline. LR was defined as having favorable levels of 4 major CVD risk factors: serum total cholesterol level <200 mg/dL and no use of cholesterol-lowering medication; blood pressure 120/≤80 mm Hg and no use of antihypertensive medication; no current smoking; and no history of diabetes or heart attack. While the potential of LR status in overcoming the CVD epidemic is being recognized, the long-term association of LR with objectively measured health in older age has not been examined. It is hypothesized that persons who were LR in 1967-1973 and have survived to older age will have less clinical and subclinical CVD, lower levels of inflammatory markers, and better physical performance/functioning and sleep quality. Here we describe the rationale, objectives, design, and implementation of this longitudinal epidemiologic study, compare baseline and follow-up characteristics of participants and nonparticipants, and highlight the feasibility of reexamining study participants after an extended period postbaseline with minimal interim contact.

Investigation of cholesterol bias due to a matrix effect of external quality assurance samples: how true is your cholesterol method?

BACKGROUND: Comparability of cholesterol measurement is clinically required and external quality assurance (EQA) programmes are important to verify the trueness of routine methods. METHODS: We developed a gas chromatography-isotope dilution mass spectrometry (GC-IDMS) total cholesterol assay to investigate the cause of a suspected matrix-related negative bias with the Beckman Coulter enzymatic method discovered in an EQA programme. The GC-IDMS method was calibrated with certified reference material and verified against a secondary reference method. Bias between the GC-IDMS and Beckman Coulter methods was estimated according to Clinical and Laboratory Standards Institute (CLSI) protocol EP9-A2 with 40 clinical samples. RESULTS: At clinically important decision levels, no significant bias was demonstrated on patients' samples (all results within a ±3% limit). A matrix effect confined to the EQA material that affected the Beckman Coulter total cholesterol method was confirmed. CONCLUSIONS: The GC-IDMS method is suitable as a higher order total cholesterol method in a routine clinical laboratory. Matrix effects defeat the objectives of EQA schemes by preventing the verification of trueness. Given the importance of obtaining a true cholesterol result without systematic error, we recommend that EQA material without matrix effects should be used.

Study on the reference values of serum lipids in children aged 3-18 years old in Beijing, China.

BACKGROUND: The present study was designed to explore the reference values of serum lipids in children in Beijing. METHODS: A total of 1071 healthy children from Beijing between 3 and 18 years of age were enrolled and divided into four groups: A, 3-5-year-old group; B, 6-9-year-old group; C, 10-14-year-old group; and D, 15-18-year-old group. Blood samples were obtained from the cubital veins of the participants under a fasting condition. A Hitachi 7600 Automatic Biochemistry Analyzer was used to determine the serum levels. The cut-off points of reference values were the 75th and 95th percentiles for total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) while the 25th and 5th percentiles were used for high-density lipoprotein cholesterol (HDL-C) concentrations. RESULTS: The highest 95th percentiles of TC among the four groups were 5.34 mmol/L for boys and 5.11 mmol/L for girls. Compared with those of boys, female TG levels were obviously higher in the 10-14-year-old group (P < 0.05) and HDL-C levels were significantly higher in the 15-18-year-old group (P < 0.05). The serum TC, HDL-C, and LDL-C all peaked during the 6-9-year-old period and then declined during the adolescent stage. Also, the serum TG continuously increased with a relative plateau during the 6-14-year-old period. Obese and overweight children had higher TG and LDL-C levels but lower HDL-C levels. CONCLUSION: This study showed a picture of the serum lipids distribution in Chinese children and found that their TC levels were lower than those of children in Japan, Iran, and France, but were higher than those of Italian children.

Measurement performance of reagent manufacturers by Centers for Disease Control and Prevention/Cholesterol Reference Method Laboratory Network lipid standardization specified for metabolic syndrome-focused health checkups program in Japan.

AIM: This study was designed to clarify the current measurement performance of 7 reagent manufacturers for high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and triglycerides (TG) specified for the metabolic syndrome (MetS)-focused health checkups program in Japan. METHODS: Twenty HDLC, 21 LDLC and 9 TG analytical reagent/instrument/calibrator systems (system), and combinations of reagent lots, instrument models and calibrator lots, underwent Centers for Disease Control and Prevention (CDC)/Cholesterol Reference Method Laboratory Network (CRMLN) lipid standardization. Eighty and 100% systems were requested to achieve an accuracy of within +/-1% and +/-2% of the reference value, so that a clinical laboratory can meet the CDC criteria. RESULTS: The CDC performance criteria of HDLC, LDLC and TG require an accuracy of within +/-5%, +/-4% and +/-5%, respectively. For HDLC, all 20 systems met the criteria. Fourteen (70.0%) and 18 (90.0%) systems were within +/-1% and +/-2%, respectively. For LDLC, 14 (66.7%) of 21 systems met the criteria, but 7 (33.3%) failed. Five (23.8%) and 17 (81.0%) systems were within +/-1% and +/-2%, respectively. For TG, 8 of 9 systems met the criteria. Two (22.2%) and 4 (44.4%) systems were within +/-1% and +/-2%, respectively. The minimum and maximum differences of a specified sample among manufacturers were 1.6 and 11.0 mg/dL for HDLC, 7.8 and 33.0 mg/dL for LDLC, and 2.8 and 27.4 mg/dL for TG, respectively. CONCLUSION: Homogeneous HDLC methods are acceptable for MetS, but further accuracy improvement of homogeneous LDLC and TG methods will be needed because of their poor performance.