Should quality goals be defined for multicenter laboratory testing? Lessons learned from a pilot survey on a national surveillance program for diabetes.

QUALITY PROBLEM: Robust laboratory protocols and stringent quality control (QC) procedures are essential for meaningful collection of data from multiple sites in large-scale population-based studies. Failure to design and implement an effective QC program not only adversely affects the scientific outcome, but also affects public confidence in the acceptability of the data. INITIAL ASSESSMENT: A pilot survey was conducted to assess the analytical performance of multicenter plasma glucose measurements in a national surveillance program for diabetes in China. CHOICE OF SOLUTION: Quality goals of the imprecision in terms of coefficient of variation (CV) and total analytical error (TEa) were defined based on the Clinical Laboratory Improvement Amendments (CLIA) criteria for acceptable performance of proficiency testing (PT) for plasma glucose using commercial QC preparations. IMPLEMENTATION: A web-based internal QC (IQC) program was established to monitor the analytical performance of the 302 centers participating in the survey. EVALUATION: The participation rate was 96% (289/302). Statistical analysis showed that the percentage of centers meeting the acceptable specifications of CV ≤5.0% and TEa ≤10% using the CLIA PT criteria was 91.7% while 76.4% of laboratories achieved the goals for desirable performance of CV ≤2.9% and TEa ≤6.9%, as proposed by the Laboratory Medicine Practice Guidelines for the management of diabetes mellitus based on biological criteria. LESSONS LEARNED: Communications and training are important in ensuring the data integrity of multicenter population-based studies. Performance verification and IQC programs should be implemented to help identify centers that can fulfill the eligibility criteria to perform laboratory analyses.

Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians.

OBJECTIVE: The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. METHODS: We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. RESULTS: The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. CONCLUSION: Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians.

[Designing and implementation of a web-based quality monitoring system for plasma glucose measurement in multicenter population study].

OBJECTIVE: The aim of this paper is to describe the designing and implementation of a web-based plasma glucose measurement quality monitoring system to assess the analytical quality of plasma glucose measurements in multicenter population study and provide evidence for the future studies. METHODS: In the chronic non-communicable disease and related factor surveillance in China, a web based quality monitoring system for plasma glucose measurement was established to conduct evaluation on plasma glucose monitoring quality and effectiveness in 302 surveillance centers, including quality control data entry, transmission and feedback. RESULTS: The majority of the surveillance centers met the quality requirements and passed the evaluation of reproducibility and precision of plasma glucose measurement, only a few centers required intensive training and re-assessment. CONCLUSION: In order to ensure the completeness and reliability of plasma glucose measurement in the surveillance centers, the establishment of web-based plasma glucose measurement quality control system can facilitate the identification of the qualified surveillance centers and evaluation of plasma glucose measurement quality in different regions. Communication and training are important in ensuring plasma glucose measurement quality. It is necessary to further improve this web-based plasma glucose measurement quality monitoring system in the future to reduce the method specific plasma glucose measurement bias.

Age-related distributions of nine fasting plasma free fatty acids in a population of Chinese adults.

BACKGROUND: Free fatty acids (FFAs) play important roles in health and disease. We investigated the distributions of nine plasma FFAs in a population of Chinese adults. METHOD: Three hundred and ninety-nine healthy individuals aged 18-104 years were divided into 4 groups: 18-39 years; 40-59 years; 60-79 years; and 80-104 years. Nine plasma FFAs, including C12:0, C14:0, C16:0, C16:1, C18:0, C18:1 C18:2, C20:4 and C20:5 were determined using a validated HPLC method. RESULTS: There were significant differences among the 4 age groups in the plasma total FFA (TFA), saturated fatty acid (SFA), unsaturated fatty acid (UFA), and eight specific FFA concentrations, and the ratios of SFA to UFA, SFA to TFA, and UFA to TFA as well (all P<0.05), except for FFA C16:1. However, no significant difference was found between males and females. The 4 most abundant FFAs, C16:0, C18:0, C18:1 and C18:2 account for >90% of plasma total FFA. Reference intervals for individual FFAs are set at the 10th-90th percentile. CONCLUSIONS: Significant differences in eight specific plasma FFAs among various age groups were found in a population of Chinese adults. C16:0, C18:0, C18:1 and C18:2 are the most abundant FFAs in the fasting plasma. Reference intervals are established for the local Chinese community.

High density lipoprotein-cholesterol levels increase with age in American women but not in Hong Kong Chinese women.

OBJECTIVES: High-density lipoprotein (HDL) cholesterol is a powerful cardiovascular risk factor. Important gender and ethnic differences in plasma HDL levels exist and warrant investigation. DESIGN: Cross-sectional survey in two different general populations. Patients 7700 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2002 and 1944 participants of the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2) 2000-2004. MEASUREMENTS: Plasma HDL levels. RESULTS: Plasma HDL levels were higher in women than in men in both populations. In the United States women, it increased with age, whereas in Chinese women, it declined with age and converged with male HDL levels. In the United States, 37.1 +/- 1.2% men and 38.9 +/- 1.1% women had low HDL levels. In Hong Kong, 34.3 +/- 1.6% men and 34.5 +/- 1.5% women had low HDL levels. In Americans, the independent predictors of low HDL levels were lower age, being non-Mexican Hispanic, waist circumference, triglycerides and not drinking alcohol in men, and lower age, being Hispanic, waist circumference, triglycerides, current smoking and not drinking alcohol in women. In Hong Kong Chinese, the independent predictors of low HDL levels were body mass index, triglycerides, current smoking and not drinking alcohol in men, and lower age, waist circumference, triglycerides, diabetes and former smoking in women. CONCLUSIONS: The decline in plasma HDL with age in Chinese women is opposite to that seen in American women. The increased cardiovascular risk in elderly Chinese women requires further study.

Plasma lipid, lipoprotein and apolipoprotein levels in a random population sample of 2875 Hong Kong Chinese adults and their implications (NCEP ATP-III, 2001 guidelines) on cardiovascular risk assessment.

The age- and sex-related levels of plasma lipids, lipoproteins and apolipoproteins in a random population sample of 2875 Hong Kong Chinese Adults (1397 men and 1478 women aged 25-74) and their implications on cardiovascular risk assessment are reported. Total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides increased with age in both sexes. Postmenopausal women had the worst profiles. They also showed higher triglyceride and non-high density lipoprotein (non-HDL)-cholesterol and had higher percentage of values greater than the desirable limits, compared with men of the same age groups. Overall 39% of men and 29% of women had non-HDL cholesterol of 4.2 mmol/L or greater. Apolipoproteins A-I and B followed the same trends as HDL-cholesterol and LDL-cholesterol, respectively. Apolipoprotein E (apo E) allele frequencies were: epsilon2 8.7, epsilon3 80.4 and epsilon4 10.9% with the genotype having a significant effect on plasma apo E concentration (p < 0.001). Carriers of the epsilon2 allele had higher apo E values than those homozygous for E3. Lipoprotein(a) levels were higher in women than men (geometric mean 152 versus 102 mg/L, p < 0.05) and in women with FSH above versus below 40 IU/L (185 versus 136 mg/L, p < 0.05). With respect to the NCEP ATP-III 2001 guidelines, the prevalence of hyperlipidemia in the Hong Kong population approached those in high CHD prevalence Caucasian communities. Local management guidelines and community-wide programs to reduce fat intake, increase regular moderate exercise and reduce the prevalence of overweight and obesity are urgently required, and hormone replacement therapy for postmenopausal women might be warranted.

Novel use of the Friedewald formula to tackle anomalous HDL-C results in two cases of paraproteinaemia.

OBJECTIVES: We report here two cases of paraproteinaemia with one falsely low and the other dubiously high HDL-cholesterol (HDL-C) results. The spurious results seemed to be related to the nature (IgG or IgM) as well as the concentration of the paraproteins. DESIGN AND METHODS: We have been using an alternative approach to estimate the HDL-C concentration by incorporating into it the LDL-cholesterol (LDL-C) value obtained by direct measurements and by back-calculation based on the time-honored Friedewald equation in these atypical specimens as an interim measure, pending optimization of the Roche direct HDL-C plus assay currently in use in our laboratory. RESULTS: This approach is convenient and does not require sophisticated instrumentation. What we are suggesting is to tackle this analytical problems on HDL-C assay due to paraprotein interference by back-calculating the HDL-C values from the measured LDL-C and triglyceride values using the Friedewald formula and is to be regarded as an alternative way to circumvent the interference issue without the need for more elaborative laboratory procedures. We do not intend to advocate screening every single HDL-C value obtained by the direct method for possible analytical errors using this approach. CONCLUSIONS: The back-calculation for HDL-C based on the Friedewald formula is conceived by the authors as an alternative and relatively simple way to estimate the HDL-C value in the presence of paraprotein interference, in particular when there is a minus HDL-C value or when the result is dubiously high. By the same token, when the measured HDL-C and the calculated HDL-C do not match further investigations would be warranted to safeguard the validity of the reported result. It is also, to the best of our knowledge, the first time extra bands due to the IgM and IgG paraproteins were demonstrated in the lipoprotein electrophoresis plate.