A Novel Method for Estimating Low-Density Lipoprotein (LDL) Levels: Total Cholesterol and Non-High-Density Lipoprotein (HDL) Can Be Used to Predict Abnormal LDL Level in an Apparently Healthy Population.

BACKGROUND We aimed to predict the abnormal LDL level by using TG, TC, HDL, and non-HDL in this study. MATERIAL AND METHODS Triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) data were obtained from the Laboratory Information System (LIS) for 4 years (Oct 1, 2013 to Sept 30, 2017) from among 34 270 healthy Chinese patients at Shuyang People's Hospital. TG, TC, HDL, and LDL (direct clearance method) were measured using a TBA2000FR biochemical analyzer. The non-HDL was calculated as TC minus HDL. Correlations between TG, TC, non-HDL, and LDL were analyzed using Spearman's rank correlation. Receiver operating characteristics (ROC) curve analysis was used to evaluate the predictive utility of TG, TC, and non-HDL for the abnormal LDL level (<130 mg/dL). RESULTS Both TC (r=0.870) and non-HDL (r=0.893) were significantly positively correlated with LDL. The area under curve of TC and non-HDL can be used to predict abnormal LDL levels. Optimal thresholds were 182.5 mg/Dl (4.72 mmol/L) for TC and 135.3 mg/Dl (3.50 mmol/L) for non-HDL. Based on these optimal thresholds, less than 0.5% and 0.4% of tests with elevated LDL were missed using TC and non-HDL, respectively, but the value of these missed LDL levels was not very high (<147.3 mg/dL). CONCLUSIONS If the value of non-HDL is less than 135.3 mg/Dl (3.50 mmol/L) and/or TC is less than 182.5 mg/Dl (4.72 mmol/L) for the apparently healthy populations, the LDL level will be less than 130 mg/Dl (3.36 mmol/L). TC and non-HDL can be used to predict the abnormal LDL level in apparently healthy populations.

Reference intervals of carbohydrate antigen 19-9 in the apparently healthy adult population.

BACKGROUND: To establish reference intervals of carbohydrate antigen 19-9(CA 19-9) according to the CLSI CA28-A3 guideline and to evaluate age- and gender-related variations. METHODS: Serum CA 19-9 values of 10 149 healthy subjects (from 20 years old to 60 years old) were measured from location health checkups. The relationship between CA 19-9 and age was analyzed using Spearman's approach. The reference intervals of CA19-9 were established using Q2.5 and Q97.5 , and the 90% confidence intervals of upper limits were calculated. RESULTS: The reference intervals of CA 19-9 were 1.98-25.12 U/mL for males (1.97-25.06 U/mL for 20-50 years old and 2.31-26.13 U/mL for 50-60 years old) and 2.36-29.29 U/mL for adult (20-60 years old) females. The upper limit of reference intervals for all individuals was 26.45 U/mL; the level of CA 19-9 is higher in females than males. Carbohydrate antigen (CA) 19-9 is significantly associated with aging in adult males(r = .0930, P < .0001), but not in females (P = .4734). CONCLUSIONS: Establishing reference intervals for CA19-9 and giving age-related reference intervals of CA19-9 using a big data of healthy adult, we first discovered that CA19-9 tends to increase with age in adult males but not in females.

Limiting the testing of urea: Urea along with every plasma creatinine test?

BACKGROUND: We found that it is not necessary to simultaneously detect both creatinine (CREA) and urea until the concentration of CREA is lower than the certain level. To reduce urea testing, we suggest measuring urea only when CREA or estimated glomerular filtration rate (eGFR) exceeds a predetermined limit. MATERIALS AND METHODS: CREA and urea data were analyzed consisting of almost all of people age above 65 years old check-up (n=95441) in Shuyang countryside, and inpatients (n=101631), outpatients (n=18474) and Routine Health Check-up (n=20509) in Shuyang People's Hospital. The proportions of elevated urea were derived. The data used in this study was generated from people more than 13 years old in both outpatients and inpatients. RESULTS: When the limits for initiating urea testing were used at 85 µmol/L CREA and 120 mL/min/1.73 m2 eGFR, the percentage of unnecessary urea test are 94.5% and 64.7% (elderly health check-up), 67.9% and 84.5% (outpatients), 88.5% and 73.2% (inpatients), 92.2% and 81.7% (routine health check-up). The missing rate of urea are 1%, 2.5%, 4.6% and 9.2%, 0.1%, 0.4%, 0.9% and 1.8%, 0.4%, 0.8%, 1.4%, and 2.5%, 0.05%, 0.1%, 1.1%, and 0.8% of ureas exceeding 9.28 mmol/L and 8.3 mmol/L in above each group, respectively. If the CREA≤85 µmol/L or eGFR≥90 mL/min/1.73 m2 , there is 97.5% urea <10.1 mmol/L, the proportion of elevated urea missed is 2.5%. CONCLUSIONS: We suggest that the initiating urea testing should be based on the upper limit of Reference Intervals serum CREA of females or a 120 mL/min/1.73 m2 eGFR limit. Conservatively, the urea testing would be reduced by 65% at least.

Establishing Reference Intervals of Aspartate Aminotransferase-to-Platelet Ratio Index for Apparently Healthy Elderly.

BACKGROUND: Aspartate aminotransferase (AST) to platelet ratio index (APRI) serves as a parameter in evaluating liver fibrosis in current clinical practice. However, reference standard (reference intervals, RIs) or baseline levels of APRI have not been previously reported. The purpose of this paper is to establish the reference intervals of APRI in apparently healthy elderly people from the region of Shuyang, China. METHODS: Blood specimens were collected from local elderly residents (selected 51,263 elderly Han Shuyang Chinese from 65 to 97 years old, 32.97% males and 67.03% females) by standard procedures. Complete blood counts were determined by Sysmex XE-2100 analyzer and the AST values were measured by a TBA2000FR automatic biochemical analyzer (Toshiba Co., Ltd., Japan). The 95% reference intervals were calculated by using the non-parametric method according to the document: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline-Third Edition (C28-A3) of CLSI. RESULTS: RIs established for healthy elderly include: 0.1398-0.6266 for males and 0.1282-0.5798 for females (0.1284-0.5086 for 65-74 years old; 0.1209-0.5704 for > or = 75 years old). Ris of APRI for elderly males were higher than those of females, and values of APRI increased with increasing age for females. CONCLUSIONS: We established scientific and reasonable RIs of APRI for the healthy elderly in our region.

Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population.

BACKGROUND The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. MATERIAL AND METHODS Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. RESULTS We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31-7.89 ng/ml (males) and 1.01-7.10 ng/ml (females); CEA, 0.51-4.86 ng/ml (males) and 0.35-3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). CONCLUSIONS Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups.

Laboratory reference intervals of complete blood count for apparently healthy elderly people in Shuyang, China.

BACKGROUND: Currently, there are no appropriate RIs of blood cells available for the elderly in most clinical laboratories in China. The aim of this study is to establish the RIs of complete blood cell count for apparently healthy elderly people. METHODS: Blood specimens were collected from elderly residents by standard procedures. Complete blood counts were determined by Sysmex XE-2100 analyzer. The RIs and 95% confidence intervals were calculated by the robust method recommended by CLSI C28-A3 guideline. RESULTS: RIs established for healthy elderly include: total WBC 3.63 - 10.3 x 10(9)/L for males and 3.64 - 10.3 x 10(9)/L for females; RBC 3.74 - 5.49 x 10(12)/L for males and 3.74 - 5.53 x 10(12)/L for females; Hb 109 - 167 g/L for males and 109 - 168 g/L for females; HCT 36.0 - 51.8% for males and 35.7 - 51.8% for females; MCV 86.0 - 105 fL for males and 86.2 - 106 fL for females; MCH 26.4 - 33.6 pg for males and 26.4 - 33.8 pg for females; MCHC 293 - 333 g/L for males and 291 - 335 g/L for females; RDW-SD 39.3 - 53.7 fL for males and 39.6 - 54.5 fL for females; RDW-CV 11.7 - 15.1% for males and 11.7 - 15.2% for females; PLT 122 - 355 x 10(9)/L for males and 122 - 350 x 10(9)/L for females; PCT 14.1 - 37.6 x 10(-1) mL/L for males and 13.9 - 37.9 x 10(-1) mL/L for females; MPV 11.3 - 15.5 fL for males and 11.3 - 15.5 fL for females; PDW 9.74 - 17.0% for males and 9.72 - 17.0% for females; platelet-LCR (P-LCR) 21.3 - 51.2% for males and 21.1 - 51.4% for females. CONCLUSIONS: We established scientific and reasonable RIs of blood cell analysis for the healthy elderly in our region.

Reference intervals for total bilirubin, ALT, AST and creatinine in healthy Chinese elderly.

BACKGROUND: The aim of this study was to establish the reference intervals (RIs) of total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate transaminase (AST), and creatinine (CREA) for apparently healthy elderly (Han ethnicity) in Shuyang, China. MATERIAL AND METHODS: A total of 54 912 blood specimens from elderly residents age 65-104 years were collected by standard procedures in Shuyang county of Jiangsu province. TBIL, ALT, AST, and CREA for each participant were determined by automatic biochemical analyzer. Distribution and differences of TBIL, ALT, AST, and CREA were analyzed and compared between the elderly of the same age of different sexes and different ages of the same sex. RIs of TBIL, ALT, AST, and CREA were compared with the current RIs. The RIs and 95% confidence intervals were calculated using nonparametric method (2.5th-97.5th percentiles) according to the guideline of the Clinical and Laboratory Standards Institute. RESULTS: RIs established for the healthy elderly include: TBIL 7.8~30.6 µmol/L for males and 7.3~26.1 µmol/L for females; ALT 8.7~47.3 U/L for males and 8.4~45.2 U/L for females; AST 15.7~46.9 U/L for males and 15.1~46.2 U/L for females; and CREA 45.1~100.9 µmol/L for males and 38.7~85.0 µmol/L for females. Reference intervals of TBIL, ALT, AST, and CREA for male elderly were higher than those of females, and values of CREA increased with increasing age. CONCLUSIONS: We have established a panel of locally relevant RIs. It is necessary to establish scientific and reasonable RIs of TBIL, ALT, AST, and CREA for the healthy elderly in our region, which will provide a reference for clinicians and inspection officers.

Is testing of aspartate aminotransferase necessary along with every alanine aminotransferase for health check in elderly individuals?

OBJECTIVE: This study is to evaluate whether Aspartate Aminotransferase (AST) is necessary to screen for liver function in apparently healthy elderly individuals. METHODS: We derived the proportions of elevated ASTs that would not be measured based on 2018-year of paired Chinese elderly (Age ≥ 65 years old) check-up. Defined as AST > 40U/L is elevated. The relationship between alanine aminotransferase (ALT) and AST was analyzed by using Pearson's approach. Receiver operating characteristics curve analysis was used to evaluate the predictive accuracy of ALT for abnormal AST. RESULTS: 52,857 pairs of ALT and AST were analyzed. Serum AST was found to be positively correlated with serum ALT, r = 0.81, p < 0.01 for the entire cohort. The receiver operating characteristics (ROC) curve of ALT for predicting positive AST is 0.918. The optimal threshold for ALT is 28 U/L with the sensitivity of 82.6%, and specificity of 86.8%. At the threshold, below 0.7% of subjects with positive AST were missed, but approximately 83% of the AST tests were eliminated. CONCLUSION: Our study showed that tests of AST were not necessary along with every ALT test for health check in elderly individuals. An estimated 84.5% of subjects were not needed for AST tests which could have saved about CN¥ 815 million (USD$115 million or EURO$100 million) every year.

Age-Specific Reference Intervals for PT, aPTT, Fibrinogen and Thrombin Time for Parturient Women.

BACKGROUND: Parturient women are healthy individuals who require special consideration. Parturient women are considered to be in a hyper-coagulable state. For example, the fibrinogen (FIB) levels are often higher than the upper limit of normal reference intervals (RIs) in parturient women than in non-parturient healthy individuals (2-4 g/L). OBJECTIVE: The aim of this study is to establish the RIs of pro-thrombin time (PT), activated partial thromboplastin time (aPTT), FIB levels and thrombin time (TT) for parturient women. MATERIALS AND METHODS: Blood levels of PT, aPTT, FIB and TT were assayed on an ACL TOP 700 automatic coagulation analyser using plasma samples from 10,472 parturient women. Outlier results were excluded by using Tukey's test. The RIs were calculated by the Clinical and Laboratory Standards Institute C28-A3 guideline. RESULTS: The RIs of PT, aPTT, FIB and TT were 8.7 to 12.1 seconds (8.7-12.2 seconds for 16-20 years old, 8.7-12.1 second for 21-25 years old, 8.6-12.0 second for 26-30 years old, 8.7-12.0 second for 31-35 years old, 8.7-12.6 second for 36-40 years old and 8.8-12.2 second for 41 years old), 22.9 to 42.3 seconds, 1.98 to 5.82 g/L and 9.9 to 16.7 seconds, respectively. PT levels were found to be positively associated with aging. CONCLUSION: The above-established age-specific RIs, defined by using a large dataset, may assist clinicians in making accurate medical decisions. This was the first study in which the RIs of PT, aPTT, FIB and TT were established for parturient women in different age groups.

The "bad" cholesterol can predict abnormal apolipoprotein B levels in a large unselected outpatient cohort.

BACKGROUND: The significant association between total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL), and low-density lipoprotein cholesterol (LDL) has been shown to be associated with Apolipoprotein B (Apo B). The objective of this study was to assess whether abnormal levels of TC, non-HDL and LDL can be used as predictors of abnormal serum Apo B levels. RESULTS: TC (r = 0.752), non-HDL (r = 0.799), and LDL(r = 0.817) were significantly positively correlated with Apo B. Areas under the curve of TC, non-HDL, and LDL for predicting abnormal Apo B (>1.10 g/L) were 0.906, 0.918, and 0.928, respectively. The optimal thresholds of prediction of abnormal Apo B were 5.13 mmol/L for TC, 4.23 mmol/L for non-HDL, and 3.34 mmol/L for LDL. At these optimal thresholds of TC, non-HDL and LDL, less than 1.13%, 1.67%, and 0.62% of tests with abnormal Apo B results would have been missed, but approximately 69.4%, 79.7%, and 73.2% of the performed Apo B tests could have been eliminated, respectively. CONCLUSIONS: Apo B levels of unselected outpatients need be not tested (especially when LDL < 3.34 mmol/L, non-HDL < 4.23 mmol/L, and/or TC < 5.13 mmol/L). It will result in 69% reduction in number of ordered Apo B tests. LDL was significantly better than the TC and non-HDL for predicting abnormal Apo B indicating that Apo B needn't tested when LDL level is normal. METHODS: We retrospectively analyzed results of TC, HDL, LDL, and Apo B in a large cohort of unselected outpatients (n = 5486) in Shuyang People's Hospital, Shuyang, China. Non-HDL was calculated by deducting HDL from TC. Correlations between TC, non-HDL, LDL, and Apo B were analyzed by using Spearman's rho approach. Receiver operating characteristics curve analysis was used to evaluate the predictive value of TC, non-HDL, and LDL for abnormal Apo B.