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This review evaluates the status of standardization of lipids and lipoproteins. Prerequisites and some basic principles for standardization are provided. The reference systems for cholesterol, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-I (apoA-l), apolipoprotein B (apoB), and lipoprotein(a) measurements of lipids and lipoproteins. Our intention is that clinical laboratory (Lp[a]) are described. Brief descriptions of the standardization programs available for each of these analytes are also provided. Finally, the review addresses some of the challenges in standardizing these markers of cardiovascular disease (CVD).The standardization programs described have contributed to improvements in laboratory measurements of lipids and lipoproteins. Our intention is that clinical laboratory professionals and manufacturers of in vitro diagnostics will use these resources to standardize lipid and lipoprotein measurements. Manufacturers must take the initiative to thoroughly evaluate their products and ensure traceability to the reference systems. [ABSTRACT FROM AUTHOR]

The National Bone Health Alliance (NBHA) recommends standardized sample handling and patient preparation for C-terminal telopeptide of type I collagen (CTX-I) and N-terminal propeptide of type I procollagen (PINP) measurements to reduce pre-analytical variability. Controllable and uncontrollable patient-related factors are reviewed to facilitate interpretation and minimize pre-analytical variability., Introduction: The IOF and the International Federation of Clinical Chemistry (IFCC) Bone Marker Standards Working Group have identified PINP and CTX-I in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA Bone Turnover Marker Project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation., Methods: Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection., Results: Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation., Conclusion: Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.

Nonpharmacologic approaches to preserve or increase bone mineral density (BMD) include whole-body vibration (WBV), but its efficacy in elderly persons is not clear. Therefore, we conducted the Vibration to Improve Bone in Elderly Subjects (VIBES) trial, a randomized, placebo-controlled trial of 10 minutes of daily WBV (0.3g at 37 Hz) in seniors recruited from 16 independent living communities. The primary outcomes were volumetric BMD of the hip and spine measured by quantitative computed tomography (QCT) and biochemical markers of bone turnover. We randomized 174 men and women (89 active, 85 placebo) with T-scores -1 to -2.5 who were not taking bone active drugs and had no diseases affecting the skeleton (mean age 82 ± 7 years, range 65 to 102). Participants received daily calcium (1000 mg) and vitamin D (800 IU). Study platforms were activated using radio frequency ID cards providing electronic adherence monitoring; placebo platforms resembled the active platforms. In total, 61% of participants in the active arm and 73% in the placebo arm completed 24 months. The primary outcomes, median percent changes (interquartile range [IQR]) in total volumetric femoral trabecular BMD (active group (2.2% [-0.8%, 5.2%]) versus placebo 0.4% [-4.8%, 5.0%]) and in mid-vertebral trabecular BMD of L1 and L2 (active group (5.3% [-6.9%, 13.3%]) versus placebo (2.4% [-4.4%, 11.1%]), did not differ between groups (all p values > 0.1). Changes in biochemical markers of bone turnover (P1NP and sCTX) also were not different between groups (p = 0.19 and p = 0.97, respectively). In conclusion, this placebo-controlled randomized trial of daily WBV in older adults did not demonstrate evidence of significant beneficial effects on volumetric BMD or bone biomarkers; however, the high variability in vBMD changes limited our power to detect small treatment effects. The beneficial effects of WBV observed in previous studies of younger women may not occur to the same extent in elderly individuals., (© 2015 American Society for Bone and Mineral Research.)

Estimation of low-density lipoprotein cholesterol (LDL-C) using the Friedewald (FR) formula is often inaccurate when triglycerides are elevated or VLDL particle composition is altered. We hypothesized that LDL-C estimation by the FR formula and other measurement methods might also be inaccurate in individuals treated with a cholesteryl ester transfer protein (CETP) inhibitor. An assay comparison study was conducted using pre and posttreatment serum samples from 280 of the 811 patients treated with the CETP inhibitor anacetrapib in the DEFINE study (determining the efficacy and tolerability of CETP inhibition with anacetrapib). After 24 weeks of treatment with anacetrapib, mean LDL-C values by FR formula, Roche direct method (RDM) and Genzyme direct method (GDM) deviated from that measured by the β-quantification (BQ) reference method by -12.2 ± 7.5, -10.2 ± 6.6, -10.8 ± 8.8 mg/dl, respectively. After treatment with anacetrapib, the FR formula and detergent-based direct methods provided lower LDL-C values than those obtained by the BQ reference method. The bias by the FR formula appeared to be due to an overestimation of VLDL-C by the TG/5 component of the formula. Evaluation of the clinical significance of these findings awaits comprehensive lipid and cardiovascular outcome data from ongoing Phase III clinical studies of anacetrapib.

Objective: To assess and validate the application of a non-radioactive assay for cholesteryl ester transfer protein (CETP) activity in clinical samples., Design and Methods: In this Phase 0 study, CETP activity was measured following addition of the CETP inhibitor JNJ-28545595 to plasma samples from normolipidemic and three subgroups of dyslipidemic subjects with differing lipid profiles., Results: CETP activity was elevated in plasma samples from dyslipidemic subjects compared to normolipidemic subjects. Increased triglyceride levels correlated with decreased CETP inhibition. The assay was found to have good analytical precision and high throughput potential as required for clinical trial sample analysis., Conclusions: The results demonstrate that pharmacological inhibition of CETP is affected by the dyslipidemic nature of plasma samples. In addition, since the optimal degree of CETP inhibition for maximal cardiovascular benefit in patients is not known, this assay may be used to help define optimal dosing of CETP inhibitors.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Background: Methods from 7 manufacturers and 1 distributor for directly measuring HDL cholesterol (C) and LDL-C were evaluated for imprecision, trueness, total error, and specificity in nonfrozen serum samples., Methods: We performed each direct method according to the manufacturer's instructions, using a Roche/Hitachi 917 analyzer, and compared the results with those obtained with reference measurement procedures for HDL-C and LDL-C. Imprecision was estimated for 35 runs performed with frozen pooled serum specimens and triplicate measurements on each individual sample. Sera from 37 individuals without disease and 138 with disease (primarily dyslipidemic and cardiovascular) were measured by each method. Trueness and total error were evaluated from the difference between the direct methods and reference measurement procedures. Specificity was evaluated from the dispersion in differences observed., Results: Imprecision data based on 4 frozen serum pools showed total CVs <3.7% for HDL-C and <4.4% for LDL-C. Bias for the nondiseased group ranged from -5.4% to 4.8% for HDL-C and from -6.8% to 1.1% for LDL-C, and for the diseased group from -8.6% to 8.8% for HDL-C and from -11.8% to 4.1% for LDL-C. Total error for the nondiseased group ranged from -13.4% to 13.6% for HDL-C and from -13.3% to 13.5% for LDL-C, and for the diseased group from -19.8% to 36.3% for HDL-C and from -26.6% to 31.9% for LDL-C., Conclusions: Six of 8 HDL-C and 5 of 8 LDL-C direct methods met the National Cholesterol Education Program total error goals for nondiseased individuals. All the methods failed to meet these goals for diseased individuals, however, because of lack of specificity toward abnormal lipoproteins.

Background: Fasting hypertriglyceridaemia has been reported to occur commonly in cigarette smokers and is thought to increase cardiovascular disease (CVD) risk in these individuals. More recently, it has been suggested that an increase in non-fasting triglycerides, rather than fasting hypertriglyceridaemia, is an independent CVD risk factor., Methods: In this study, we divided 24 smokers into insulin-resistant (IR) and insulin-sensitive (IS) groups by determining their steady-state plasma glucose concentrations during the insulin suppression test and compared fasting and daylong postprandial accumulation of total triglycerides and remnant lipoprotein (RLP) concentrations, before and after 3 months of pioglitazone (PIO) administration., Results: The two groups were similar in age, body mass index, race and gender distribution, but differed dramatically in insulin sensitivity. Baseline fasting and postprandial triglyceride, RLP cholesterol and RLP triglyceride concentrations were significantly higher in the IR smokers (p=0.01 to <0.01). Insulin resistance [corrected] and both fasting and postprandial triglyceride and RLP triglyceride levels decreased significantly (p=0.05 to 0.01) [corrected] in PIO-treated IR smokers, without any significant increase in weight instead of insulin sensitivity and both fasting and postprandial triglyceride and RLP triglyceride levels decreased significantly (p = 0.05 to, 0.01) in PIO-treated IR smokers, without any significant increase in weight. [corrected], Conclusions: The postprandial accumulation of RLP particles is increased in the IR subset of smokers and is likely to contribute to the increased CVD risk in these individuals. Furthermore, PIO administration provides a possible therapeutic approach to decreasing postprandial lipaemia and CVD risk in IR smokers who are unwilling or unable to stop smoking.

Context: In preclinical models, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase have been shown to positively affect bone remodeling balance. Observational studies and secondary analyses from lipid-lowering trials have yielded inconsistent results regarding the effect of these agents on bone mineral density and fracture risk., Objective: Our objective was to determine whether clinically significant skeletal benefits result from hydroxymethylglutaryl-coenzyme A reductase inhibition in postmenopausal women., Design and Setting: We conducted a prospective, randomized, double-blind, placebo-controlled, dose-ranging comparative clinical trial at 62 sites in the United States., Participants: Participants included 626 postmenopausal women with low-density lipoprotein cholesterol levels of at least 130 mg/dl (3.4 mmol/liter) and less than 190 mg/dl (4.9 mmol/liter), and lumbar (L1-L4) spine bone mineral density T-score between 0.0 and -2.5., Intervention: Once-daily placebo or 10, 20, 40, or 80 mg atorvastatin was administered., Main Outcome Measures: We assessed percent change from baseline in lumbar (L1-L4) spine bone mineral density with each dose of atorvastatin compared with placebo., Results: At 52 wk, there was no significant difference between each atorvastatin and placebo group or change from baseline at any tested dose of atorvastatin or placebo in lumbar (L1-L4) spine bone mineral density. Nor did atorvastatin produce a significant change in bone mineral density at any other site. Changes in biochemical markers of bone turnover did not differ significantly between each atorvastatin and placebo group. All doses of atorvastatin were generally well tolerated, with similar incidences of adverse events across all dose groups and placebo., Conclusions: Clinically relevant doses of atorvastatin that lower lipid levels had no effect on bone mineral density or biochemical indices of bone metabolism in this study, suggesting that such oral agents are not useful in the prevention or treatment of osteoporosis.

In light of the conflicting results of the recent United Kingdom Prospective Study (UKPDS), where diabetic patients on metformin monotherapy had lower all-cause mortality and the addition of metformin in sulfonylurea-treated patients was associated with an increased risk of diabetes-related death, we sought to compare the effects on cardiovascular disease (CVD) risk factors of metformin monotherapy with metformin treatment when added to a sulfonylurea compound in patients with type 2 diabetes. Thirty-one volunteers with type 2 diabetes mellitus, 16 on dietary therapy and 15 on sulfonylurea monotherapy (SU), were treated with metformin for 12 weeks. Measurements were made of (1) fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), lipid, remnant lipoprotein cholesterol (RLP-C) levels, and low-density lipoprotein (LDL) particle size; (2) daylong plasma glucose, insulin, free fatty acid (FFA), triglyceride (TG), and RLP-C concentrations; and (3) fasting levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin). Fasting plasma glucose concentrations decreased to a similar degree after treatment with metformin in both the metformin monotherapy group (12.45 +/- 0.48 v 9.46 +/- 0.47 mmol/L, P <.001) and the combined SU and metformin therapy group (14.09 +/- 0.51 v 10.57 +/- 0.85 mmol/L, P =.001). Fasting plasma lipid concentrations and LDL particle size did not significantly change in either treatment group, whereas fasting RLP-C concentrations were significantly lower in the metformin monotherapy group (0.43 +/- 0.09 v 0.34 +/- 0.07 mmol/L, P =.02). Daylong concentrations of plasma glucose, FFA, TG, and RLP-C were lower to a similar degree in both treatment groups, whereas daylong plasma insulin concentrations were unchanged. Fasting plasma sVCAM-1 levels were significantly lower in both the metformin monotherapy group (484 +/- 19 v 446 +/- 18 ng/mL, P =.02) and the combined SU and metformin therapy group (496 +/- 29 v 456 +/- 31 ng/mL, P =.05), whereas fasting plasma sICAM-1 and sE-selectin levels were essentially unchanged. Administration of metformin, either as monotherapy or in combination with a sulfonylurea drug, improved glycemic control and led to a decrease in several CVD risk factors in patients with type 2 diabetes.

Aims: To compare lipoprotein risk factors for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) treated with a sulphonylurea (SU) compound only, metformin (MET) only, or combined SU + MET., Methods: The study population consisted of 62 patients with type 2 DM, whose antihyperglycaemic treatment program had been stable for at least 3 months, divided into three groups: 26 patients in the SU group, 17 patients in the MET group and 19 patients in the SU + MET group. None of the patients were taking lipid-lowering drugs. Fasting venous blood samples were taken to measure concentrations of glucose, total cholesterol, triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and remnant lipoprotein-cholesterol (RLP-C) as well as for determination of LDL particle diameter., Results: The three groups were similar in terms of age, gender, body mass index and fasting plasma glucose concentrations. Total cholesterol concentrations were significantly lower (p < 0.05 for trend) in those treated with SU + MET as compared with the other two groups. However, there were no significant differences between the three groups in their plasma concentrations of TG, LDL-C, HDL-C or RLP-C; furthermore, the proportion of individuals within each treatment group with small LDL particle diameter was also not different., Conclusions: The lipoprotein profile of patients with type 2 DM, matched for level of fasting hyperglycaemia, was similar irrespective of treatment with SU alone, MET alone or SU + MET. Thus, we could not identify any changes in lipoprotein metabolism that could account for differences in risk of CVD as a function of treatment.

Potentially atherogenic triglyceride-rich lipoprotein (TRL) remnants can be isolated and quantitated as remnant-like particles (RLP), using an immunoaffinity gel containing specific anti-human apolipoprotein A-I (apoA-I) and apoB-100 monoclonal antibodies. The aim of the present study was to determine the relationship between postprandial changes in RLP levels and changes in total serum triglyceride (TG) in patients with different forms of hypertriglyceridemia (HTG). Three groups of patients were selected, having similarly elevated serum TG levels: a) HTG with TRL remnant accumulation (i.e., type III patients, n = 15, TG: 3.8 +/- 0.2 mm), b) HTG with increased LDL (i.e., type IIb patients, n = 15, TG: 3.7 +/- 0.2 mm), and c) HTG without evidence of remnant or LDL accumulation (i.e., type IV patients, n = 15, TG: 3.9 +/- 0.3 mm). Ingestion of a 45-g fat meal caused a significant increase in serum TG (30;-50%) in all patients. Mean serum TG levels of the three groups were not significantly different at 4 or 6 h after the meal. RLP cholesterol (C) and TG levels increased after the meal in all patients, but these postprandial increases were also not significantly different among groups. Type III patients had significantly higher (P < 0.01) levels of RLP-C and RLP-apoE in the fasted and fed state, and also had significantly higher RLP-C-to-serum TG ratios (P < 0.001) compared with the other groups. These results indicate that 1) RLP-C and RLP-TG levels are significantly increased in the fed versus fasted state in patients with elevated fasting TG levels; 2) patients with different forms of HTG, but similar TG levels, have similar postprandial increases in RLP-C and RLP-TG; and 3) type III patients have significantly elevated levels of RLP-C and RLP-apoE in both the fed and fasted state.

Background: Familial type III hyperlipoproteinemia (HLP) is characterized by the presence of beta-migrating VLDL (beta-VLDL) and increased risk of cardiovascular disease. Assessment of plasma beta-VLDL is achieved by measuring the ratio of VLDL-cholesterol (VLDL-C) to total plasma triglycerides (TGs) or by detecting beta-VLDL in total VLDL. The objective of this study was to compare the clinical utility of the ratio of remnant-like particle-cholesterol (RLP-C) to total TGs with that of the current methods for diagnosing type III HLP., Methods: Detection of beta-VLDL by electrophoresis of VLDL was used to define type III HLP. Twenty-eight patients with type III HLP and 43 subjects lacking beta-VLDL were investigated. Fasting TG concentrations were >2.26 mmol/L in all subjects. Subjects were separated into three groups: group 1, serum total cholesterol 5.18 mmol/L and TGs between 2.26 and 9.04 mmol/L (n = 51); and group 3, TGs >9.04 mmol/L (n = 9)., Results: In group 2, a RLP-C-to-total TG molar ratio >/=0.23 (>/=0.10 when using mg/dL) and a VLDL-C-to-total TG molar ratio >/=0.69 (>/=0.30 when using mg/dL) correctly classified 94% and 90% of the subjects, respectively. The utility of the RLP-C-to-total TG ratio in diagnosing type III HLP decreased in patients in the other two groups., Conclusion: When used in an appropriate target population, the RLP-C-to-total TG ratio is a convenient and effective alternative to ultracentrifugal and electrophoretic methods for diagnosing type III HLP.

Background: Accurate and precise HDL-cholesterol (HDL-C) measurements are essential for effective application of National Cholesterol Education Program treatment guidelines. The Cholesterol Reference Method Laboratory Network (CRMLN) assists manufacturers of in vitro diagnostic products to establish traceability to the accuracy base. CRMLN sought to implement a designated comparison method (DCM) that overcomes the impracticalities of the expensive and labor-intensive reference method for HDL-C., Methods: CRMLN evaluated candidate DCMs and selected one that uses 50-kDa dextran sulfate with magnesium ions as the precipitation reagent followed by measurement of cholesterol by the CDC reference method. After validating the method, we transferred it to all CRMLN laboratories and successfully standardized it using CDC frozen serum reference materials. CRMLN laboratories participate in monthly performance evaluations., Results: CRMLN laboratories were able to meet a precision goal, as indicated by SD, of /=1.09 mmol/L (42 mg/dL) 95.6% of the time. CRMLN is working to further improve its performance by implementing a bias criterion of 0.03 mmol/L (1 mg/dL) for all HDL-C concentrations., Conclusions: CRMLN selected, validated, standardized, and implemented a DCM for HDL-C that is accurate, robust, transferable, and practical. The DCM is being used to assist manufacturers in calibrating their products so that ultimately, clinical laboratories using the products will more accurately measure HDL-C.

Substantial evidence indicates that triglyceride-rich lipoprotein remnants are atherogenic. Additional research has, however, been limited by available methods for separation and quantification of remnants. We have evaluated an immunoseparation assay developed to measure cholesterol in remnant-like particles (RLP-C). This method uses monoclonal antibodies to human apolipoproteins B-100 and A-I to remove most of the apolipoprotein B-100-containing lipoproteins (namely LDL and nascent VLDL) and apolipoprotein A-I-containing lipoproteins (namely chylomicrons and HDL), leaving behind a fraction of triglyceride-rich lipoproteins, including chylomicron and VLDL remnants, both of which are enriched in apolipoprotein E. Cholesterol in the unbound fraction is measured with a sensitive enzymatic assay. The RLP-C concentration was highly correlated with total triglyceride-rich lipoproteins (sum of VLDL-cholesterol and IDL-cholesterol) separated by ultracentrifugation and by polyacrylamide gel electrophoresis (r = 0.86 and 0.76, respectively). The within-run and run-to-run imprecision (CV) of the assay was approximately 6% and 10%, respectively. The assay was not affected by hemoglobin up to 5000 mg/L (500 mg/dL), bilirubin up to 342 mmol/L (20 mg/dL), glucose up to 67 mmol/L (1200 mg/dL), or ascorbic acid up to 170 mmol/L (3.0 mg/dL). In 726 subjects (men, n = 364; women, n = 362) in the US, the 75th percentiles of RLP-C concentration were 0.17 mmol/L (6.6 mg/dL) and 0.23 mmol/L (8.8 mg/dL) in sera obtained after overnight fasting or randomly, respectively. A group of 151 patients from nine US centers and one Canadian center with coronary artery atherosclerosis established by angiography had higher median RLP-C concentrations than 302 gender- and age-matched controls (P <0.05). We conclude that the RLP-C assay compares favorably to ultracentrifugation and electrophoresis and provides a convenient and economical approach to measure triglyceride-rich lipoprotein remnants in routine clinical laboratories.

Cholesterol and triglyceride standardization procedures have been used extensively and continuously since the 1950s. Definitive and Reference Methods, as well as primary and secondary standards, have been developed and maintained as the basis for evaluating the accuracy of results by various methods in many laboratories. But, although standardization efforts for apolipoprotein A-I and B measurements have been reported in detail in the scientific literature, much less has been reported in the area of total and lipoprotein cholesterol and triglyceride standardization efforts. Standardized cholesterol and triglyceride concentrations, determined in multiple large epidemiological and clinical studies, have been instrumental to the National Cholesterol Education Program panels that have assessed the lipoprotein values associated with risk of coronary disease, and have determined the cutpoints that are now used extensively by physicians to guide diagnosis and treatment of individual patients.

The Women's Health Trial: Feasibility Study in Minority Populations (WHT:FSMP), a randomized trial of 2208 women, was conducted to investigate three questions. First, can women from minority and low-socioeconomic-status populations be recruited in numbers sufficient to evaluate a dietary intervention designed to lower fat intake. Second, the efficacy of a low fat, increased fruit/vegetable/ grain product intervention for reducing fat consumption. Third, will participation in the intervention lower plasma cholesterol and estradiol levels relative to the controls. The baseline results showed that an adequate number of minority and low SES women could be recruited to test the study hypotheses. A diverse study population of postmenopausal women consuming a high fat diet was recruited: 28% of participants were Black, 16% were Hispanic, 11% had less than a high school level of education, and 15.5% had household incomes of < $15,000.

Background: In order to assess accuracy of a newly developed, noninstrumented, self-administered fingerstick test that measures cholesterol levels in whole blood, the AccuMeter Cholesterol Self-Test was evaluated for home-use by untrained consumers in a multicenter study., Methods: A total of 486 untrained adult volunteers of varying age, occupation, and educational background were recruited at four sites. Participants received written instructions provided in the kit, access to a telephone "800" number for additional help, and, if necessary, a short instructional video available to consumers on request. Fingerstick cholesterol results obtained by untrained volunteers were compared with paired venous serum results obtained by the Abell-Kendall cholesterol reference method. After application of exclusion criteria, 79.0% (384/486) of subjects had AccuMeter fingerstick results available for comparison with the reference method., Results: Results obtained with the AccuMeter test correlated well with the Abell-Kendall results (r = 0.91). There was a mean overall bias for the AccuMeter of -0.116 +/- 0.528 mmol/liter (-2.2%), with a mean absolute bias of 0.398 +/- 0.367 mmol/liter (7.6%). Biases at the National Cholesterol Education Program cutpoints of 5.20 and 6.20 mmol/liter were -2.2 and -2.5%, respectively. Subjects with high-risk total cholesterol values (> or = 6.20 mmol/liter) were correctly classified 80.0% of the time, with an additional 18.8% placed in the borderline category (5.20-6.20 mmol/liter); 1.2% were inappropriately placed in the desirable category. No subjects were placed in the high-risk category by the AccuMeter test if they had a desirable cholesterol value by the reference method, while 9.8% were placed in this category if they were in fact borderline., Conclusions: This test appears to be a useful addition to available options in the effort to increase awareness of cholesterol as a heart disease risk factor. A large portion of untrained consumers were able to perform the AccuMeter Cholesterol Self-Test and obtain comparable results to the reference method. This test for the first time allows consumers to determine their own cholesterol values, with a reasonably good degree of accuracy.

Clinical laboratories currently estimate low-density lipoprotein cholesterol using the Friedewald formula, which requires fasting specimens and is subject to error with increasing triglyceride levels. We describe a rapid method for isolating low-density lipoproteins using the Direct LDL Immunoseparation Reagent for subsequent measurement of cholesterol by conventional assay. This method meets current guidelines for precision with within-run and run-to-run coefficients of variation of less than 3%. Results are in good agreement with the beta quantification reference method (Direct LDL-C = 1.03 [beta quantification] -0.06 mmol/L, [2.4 mg/dL] r = 0.980), there is minimal bias associated with increasing triglycerides or high-density lipoprotein cholesterol, and patient fasting is not required for accurate analysis. The Direct LDL Immunoseparation Reagent overcomes drawbacks of the Friedewald formula and appears to be suitable for accurate quantitation of low-density lipoprotein cholesterol in the routine laboratory.

Current interest in coronary heart disease and cholesterol has led to the development of a new generation of compact analysis systems designed for fingerstick whole blood measurement. Since reliable classification of patients based on national cut-points for serum cholesterol concentration requires accurate results, the question whether results from fingerstick capillary specimens are equivalent to those from conventional venous-derived serum specimens, the basis for the national cut-points, is germane. Earlier studies in the literature are contradictory, with fingerstick differences ranging from 9% low to 6% high. We developed guidelines for reliable fingerstick collection and, following these guidelines, achieved results that were comparable to results derived from concurrently collected venous serum specimens. Results measured either by an accurate, standardized enzymatic assay or by the AccuMeter, a new noninstrumented device, were in close agreement with serum results, ie, within 1% and 1.7%, respectively, suggesting that fingerstick measurements are appropriate for identifying individuals with elevated cholesterol levels and monitoring their treatment.

Although dextran-Mg2+ precipitation produces accurate and precise results for high-density lipoprotein (HDL) cholesterol in fresh plasma and serum, precipitation of frozen specimens with triglycerides > 2.26 mmol/L (> 200 mg/dL) is difficult. We developed a modification that dilutes thawed samples by 35% and increases dextran-Mg2+ reagent to 15% of sample volume. Standard precipitations were performed on 62 fresh EDTA-treated plasma specimens; supernatant solutions were analyzed fresh and after freezing. Standard and modified methods were also performed on thawed, paired plasmas. In specimens with triglycerides < or = 2.26 mmol/L, HDL cholesterol results for all methods were similar. For triglycerides > 2.26 mmol/L, however, bias and precision were significantly affected by freezing, and 38.5% of samples with standard precipitation required additional procedures to produce clear supernatant solutions. HDL cholesterol concentrations for thawed samples with standard precipitation were significantly greater than for fresh samples (P < 0.02), but those for the modified method were not different from fresh samples, and only one specimen required additional steps to produce a clear supernate.

We have conducted a voluntary, community blood-gas proficiency testing program, with use of tonometered human blood, for 32 analyzers located in 16 laboratories. Instruments initially showed inaccuracies as large as -30.8 to +17.3% for po(2), and -14.0 to +42.9% for pco(2), but inaccuracy and imprecision decreased in most laboratories during the program. For a typical 15-week period, mean group precision (CV) was 4.3 To 5.1% for po(2) from 6.92 to 33.3 Pa (52 to 250 mmHg), and 4.0 to 6.9% for pco(2) from 2.0 to 6.8 Pa (15 to 51 mmHg). This program can detect increasing imprecision or inaccuracy caused by analyzer deterioration, and can identify interlaboratory or interinstrument bias and problems not detected by participant quality-control programs. Participants have used the proficiency information in discussing data quality with clinicians, promoting internal control and maintenance programs, and justifying instrument purchases. We believe that proficiency-testing documentation of variability in blood-gas analysis may help to establish realistic patient-care protocols.

We have used equilibrated human blood for blood-gas quality control since 1970. In blood equilibrated 24 h after shedding, gas tensions are stable for 4 to 6 h at 0 to 4 degrees C; each control specimen is analyzed several times during that period to resolve malfunctions, etc. Three-fourths of all errors in gas-tension measurement detected with equilibrated blood were detected with the highest-tension controls. Equilibrated blood controls signal about one error every 14 d on each instrument. For more complete quality control, we supplement analysis of equilibrated blood with other sorts of controls, comparing results obtained by assaying each patient's specimen on two instruments being our most effective adjunct. Such comparisons have identified erroneous assays in 3.9% of the specimens tested. The magnitude of interinstrument discrepancies (random errors) have ranged from 9 to 100% of the appropriate determinations. We use control data derived from equilibrated blood analysis for special management purposes (evaluating instruments, quantitating micro- vs. macro-sampling discrepancies, and decreasing instrument-repair costs).

We compared three commercially supplied blood-gas quality control solutions ("contrIL," "G.A.S.," and "Quantra") and tonometered whole blood under research and service conditions in four hospital laboratories. In some situations Quantra and tonometered blood were comparably sensitive to problems with blood-gas instrument malfunctions (e.g., hydraulics or temperature control) but the aqueous buffer-based materials were less sensitive. Within-day precision for all control materials was similar. The precision of pCO2 determinations in long-term studies was also similar for all control materials, as were pH determinations on commercial controls. For pO2 (especially at O2 < 50 mmHg), sample handling technique influenced the precision and accuracy of Quantra more than the other materials. The variability in pO2 determination with Quantra seems primarily to result from sensitivity in incubation temperature (3% change per degree C at 145 mmHg and 7% change per degree C at 43 mmHg). This study identifies some of the limitations of blood-gas control materials per se and some limitations related to specific blood-gas instruments that affect interpretation of results from them.