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

Isometric active force normalized for cross—sectional area in control (n = 25), fatty (n = 10) rats and diabetic fatty (n = 11) rats, at baseline and after 12 hours of mechanical ventilation.

<p>Values are expressed as mean percent of baseline ± SD.*: <i>P</i> < 0.05 versus baseline.</p

General characteristics and main mechanical variables at baseline and after 12h of mechanical ventilation of Zucker control, fatty, and diabetic fatty rats.

<p>General characteristics and main mechanical variables at baseline and after 12h of mechanical ventilation of Zucker control, fatty, and diabetic fatty rats.</p

Evolution of isometric active force (AF, panel A) normalized for cross—sectional area and maximum shortening velocity (V_max, panel B) after salbutamol in control (n = 11), fatty (n = 6) rats and diabetic fatty (n = 4) rats and of AF (panel C) normalized for cross—sectional area and V_max (panel D) during fatigue and early recovery phase of fatigue in control (n = 14), fatty (n = 4) rats and diabetic fatty (n = 7) rats.

<p>Values are expressed as mean percent of baseline ± SD.*: <i>P</i> < 0.05 versus baseline. NS = not significant. The y axis in graphs 2A and 2B does not start at zero. ¹The differences are not significant between groups.</p

Morphometric study of diaphragm in control (n = 5), fatty (n = 5) and diabetic fatty (n = 5) rats at rest.

<p><b>Panel A: Histological characterization of diaphragm using Oil red O, hematein/eosin (bar = 20 μm) and Myosin Heavy Chain (MyHC) isoforms (bar = 50 μm) stainings. Zoom-in of Oil red O stainings are presented in lower panels. Panel B: fiber type composition (%). Panel C: fiber type area (μm²). Panel D: MyHC2A fiber distribution by cross sectional area. Panel E: MyHC2X fiber distribution by cross sectional area.</b> Values are expressed as mean ± SD or percentages ± SD. *: <i>P</i> < 0.05 versus control; **: <i>P</i> < 0.05 versus diabetic fatty. HE = hematoxylin-eosin coloration.</p

Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy - Fig 3

<p><b>Representative western blot and densitometric data reflecting protein expressions of β1-adrenoceptor (Panel A) and β3-adrenoceptor (Panel B) in left ventricles homogenates of healthy or diabetic rats, treated or not by atorvastatin (50 mg kg-1.day-1) during 15 days.</b> Western blot experiments were normalized using proteins using Ponceau S solution. Data are means ± SD (n = 4 to 9). *: <i>p</i><0.05 versus healthy untreated rats; †: <i>p</i><0.05 diabetic statin versus diabetic untreated rats.</p

General characteristics of healthy and diabetic treated (<i>atorvastatin</i>, 50 mg. kg^-1.day^-1) and control rats.

<p>General characteristics of healthy and diabetic treated (<i>atorvastatin</i>, 50 mg. kg^-1.day^-1) and control rats.</p

Representative Western Blot and densitometric data reflecting protein expressions of multidrug resistance protein 4 (MRP4) in left ventricles homogenates of healthy or diabetic rats, treated or not by atorvastatin (50 mg kg-1.day-1) during 15 days.

<p>Western blot experiments were normalized using GAPDH (37kDa). Data are means ± SD (n = 6). *: <i>p</i><0.05 versus healthy untreated rats; †: <i>p</i><0.05 diabetic statin versus diabetic untreated rats.</p

Effects of atorvastatin on the transcriptome of left ventricles of healthy or diabetic rats.

<p>Panel A-B Heat Map of RNA expression profiles in diabetic versus healthy left ventricles (Panel A) or in statin diabetic versus untreated diabetic left ventricles (Panel B); Color scale indicate relative expression ratio for each gene in diabetic versus healthy left ventricle (Panel A) or in statin versus untreated diabetic left ventricle. Panel C-D Volcano Plot for the modification of genes expression by diabetes in heart ventricle (Panel C) and by atorvastatin in diabetic left ventricle (Panel D). The vertical axis represents the <i>p</i> value (-log¹⁰ <i>p</i> value) and the horizontal axis range the fold change (log² ratio) between diabetic and healthy left ventricles (Panel C) or statin diabetic versus untreated diabetic left ventricles (Panel D) (by t-test). Genes in the area delimited in red have a fold change greater than 1.5 with a <i>p</i> value < 0.05. Genes in the area delimited in green have a fold change greater than -1.5 (ratio <0.67) with a <i>p</i> value < 0.05. Panel E Venn diagram representing the differently expressed genes in diabetic versus healthy left ventricles in blue and in statin diabetic versus untreated diabetic left ventricles in red (<i>p</i><0.05). D is for down-regulation in diabetic versus healthy left ventricles, U for up-regulation. The overlapping part represents the genes modified by diabetes as well as statin, with up- or down-regulation for each comparison.</p

Active force (% of baseline value) variation of left ventricle papillary muscle exposed to isoproterenol in diabetic rats pretreated with statin (atorvastatin, 50 mg kg-1 day-1) during 15 days (8 rats per group) with or without L-NAME administration.

<p>Control refers to diabetic rats not receiving statin. AF/s = active force normalized per cross-sectional area during isometric contraction. Data are expressed as mean ± SD. NS: non-significant.</p