Wide-range CRP versus high-sensitivity CRP on Roche analyzers: focus on low-grade inflammation ranges and high-sensitivity cardiac troponin T levels

<p>Wide-range C-reactive protein (wr-CRP) has been proposed as an economical alternative to high-sensitivity C-reactive protein (hs-CRP) for the evaluation of low-grade inflammation-associated cardiovascular risk (LGI-CVR). Concomitant values of serum hs-CRP and plasma wr-CRP ≤5 mg/L, and high-sensitivity cardiac troponin T (hs-cTnT), all assayed on Roche Diagnostics analyzers over a 1.8-year period, were extracted from a hospital laboratory database. Hs-CRP and wr-CRP values were compared (Bland–Altman method; Deming’s correlation), then separately classified into low (<1 mg/L), moderate (1–3 mg/L) and high (>3 mg/L) LGI-CVR ranges for agreement test (κ), assessed before and after Deming’s regression-based adjustment of wr-CRP (Adj-wr-CRP). Wr-CRP and hs-CRP values were strongly correlated, with linearity, whether below 5 mg/L (<i>n</i> = 744; τ = 0.933; <i>p</i> < .001) or below 1 mg/L (<i>n</i> = 283; τ = 0.823; <i>p</i> < .001). Overall, wr-CRP values were lower than hs-CRP (mean bias: –0.11 ± 0.17 mg/L). Agreement was good, with 8.1% of wr-CRP values misclassified compared to hs-CRP (κ: 0.874), and weakly improved after regression-based adjustment (7.7% reclassified values; κ: 0.881). Lowering the Adj-wr-CRP cutoff of the moderate LGI-CVR subrange from 1.0 to 0.9 mg/L resulted in an almost perfect agreement (3.2% reclassified data; κ: 0.950). Hs-cTnT concentration was positively associated with hs-CRP, wr-CRP, and Adj-wr-CRP (<i>p</i> < .001). Within each LGI-CVR subrange, hs-cTnT medians were similar regardless of the hs-CRP, wr-CRP or Adj-wr-CRP used for risk classification. Based on hs-cTnT, this study supports the use of wr-CRP as a low-cost alternative to hs-CRP for cardiovascular risk evaluation.</p

Hemolysis indexes for biochemical tests and immunoassays on Roche analyzers: Determination of allowable interference limits according to different calculation methods

<div><p></p><p><b><i>Objectives.</i></b> To determine the hemolysis interference on biochemical tests and immunoassays performed on Roche Diagnostics analyzers, according to different maximum allowable limits. <b><i>Design and methods.</i></b> Heparinized plasma and serum pools, free of interferences, were overloaded by increasing amounts of a hemoglobin-titrated hemolysate. This interference was evaluated for 45 analytes using Modular^® and Cobas^® analyzers. For each parameter, the hemolysis index (HI) corresponding to the traditional ± 10% change of concentrations from baseline (± 10%Δ) was determined, as well as those corresponding to the analytical change limit (ACL), and to the reference change value (RCV). Then, the relative frequencies distribution (% RFD) of hemolyzed tests performed in a hospital laboratory over a 25-day period were established for each HI as allowable limit. <b><i>Results.</i></b> Considering the ± 10%Δ, the analyte concentrations enhanced by hemolysis were: Lactate dehydrogenase (LDH), aspartate aminotransferase (AST), folate, potassium, creatine kinase, phosphorus, iron, alanine aminotransferase, lipase, magnesium and triglycerides, decreasingly. The analyte concentrations decreased by hemolysis were: Haptoglobin, high-sensitive troponin T and alkaline phosphatase. Over the 25-day period, the % RFD of tests impacted more than 10%Δ by hemolysis were < 7% for LDH; < 5% for AST, folates and iron; and < 1% for the other analytes. Considering the ACL, HI were lower, giving % RFD substantially increased for many analytes, whereas only four analytes remain sensitive to hemolysis when considering RCV. <b><i>Conclusion.</i></b> This study proposes new HI based on different allowable limits, and can therefore serve as a starting point for future harmonization of hemolysis interference evaluation needed in routine laboratory practice.</p></div

Comparison of Area under the Receiver Operating Characteristics Curves (AUROC) for survival endpoints, between FibroTest, ActiTest, ALT, viral load, Pugh score and APRI index. N = 978.

f<p>FibroTest AUROC greater than that with ActiTest (p = 0.001), ALT (p<0.001), Viral Load (p<0.001), Pugh classification (p = 0.0025), APRI Index (p<0.001).</p>g<p>FibroTest AUROC greater than that with ActiTest (p = 0.0016), ALT (p<0.001), Viral Load (p<0.001), Pugh classification (p = 0.005), APRI Index (p<0.001).</p>h<p>FibroTest AUROC greater than that with ActiTest (p<0.001), ALT (p<0.001), Viral Load (p<0.001), Pugh classification (p = 0.002), APRI Index (p<0.001).</p

Comparison of Area under the Receiver Operating Characteristics Curves (AUROC) for survival endpoints, between FibroTest, ActiTest, ALT and viral load. N = 1074.

c<p>FibroTest AUROC greater than that with ActiTest (p<0.001), ALT (p<0.001), Viral load (p<0.001).</p>d<p>FibroTest AUROC greater than that with ActiTest (p = 0.0009), ALT (p = <0.001), Viral load (p<0.001).</p>e<p>FibroTest AUROC greater than that with ActiTest (p<0.001), ALT (p<0.001), Viral load (p<0.001).</p

4-year survival according to baseline FibroTest, viral load ALT values and treatment.

§<p>Survival of the severe fibrosis group was significantly lower than the two other groups (P<0.001).</p>§§<p>Overall survival of the severe fibrosis group, treated or not, was significantly lower than that of paired controls (p<0.05).</p>*<p>Overall survival of the 1074 HBV patients, was significantly lower than that of paired controls (p<0.05).</p>$<p>P = 0.03 vs treated.</p>£<p>P = 0.047 vs treated.</p>***<p>Survivals of the treated patients were similar to those of the non –treated in different groups of viral load (p>0.05).</p>****<p>Overall survival of the group with high viral load was lower than that of paired controls (p<0.05).</p>$*<p>Overall survival of the group with elevated ALT was lower than that of paired controls (p<0.05).</p><p>We used the manufacturers' definitions of normal FT (< = 0.27), normal AT (< = 0.29) and 3 classes for viral load in IU/ml.</p

Comparison of Area under the Receiver Operating Characteristics Curves (AUROC) for survival endpoints, between FibroTest and simultaneous histology. N = 97.

a<p>FibroTest AUROC was similar to that with fibrosis staging.</p>b<p>NP, not performed because the number of events was too low.</p

Survival according to definition of inactive carrier based on FibroTest-ActiTest normal values in untreated patients.

*<p>Both normal values: FibroTest < = 0.27 and ActiTest < = 0.29.</p>**<p>Survivals of patients with abnormal FibroTest and ActiTest were lower than those of normal FibroTest and ActiTest (p<0.005).</p>***<p>Survivals of patients with or without one coinfection (HVI, HCV, Delta) were not significantly different (p>0.05).</p>****<p>Overall survivals of patients with abnormal FibroTest and ActiTest were lower to those in paired controls (p<0.005).</p>$<p>Inactive carrier: anti HBe, normal ALT, viral load <2,000 IU/ml, no coinfection HCV, HIV, or Delta.</p

Causes of death and complications during the 4-year follow-up.

<p>Causes of death and complications during the 4-year follow-up.</p

Prognostic factors associated with survival without HBV complications or death in 1074 patients.

<p>Prognostic factors associated with survival without HBV complications or death in 1074 patients.</p

Characteristics of included patients.

<p>NP = Not performed.</p