Changes of coronary plaque composition correlate with C-reactive protein levels in patients with ST-elevation myocardial infarction following high-intensity statin therapy.

OBJECTIVES Levels of inflammatory biomarkers associate with changes of coronary atheroma burden in statin-treated patients with stable coronary artery disease. This study sought to determine changes of plaque composition in vivo in relation to high-sensitivity C-reactive protein (hs-CRP) levels in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin therapy. METHODS The IBIS-4 study performed serial (baseline and 13-month), 2-vessel intravascular ultrasound (IVUS) and radiofrequency-IVUS of the non-infarct-related arteries in patients with STEMI treated with high-intensity statin therapy. The present analysis included 44 patients (80 arteries) with serial measurements of hs-CRP. RESULTS At follow-up, median low-density lipoprotein cholesterol (LDL-C) levels decreased from 126 to 77 mg/dl, HDL-C increased from 44 to 47 mg/dl, and hs-CRP decreased from 1.6 to 0.7 mg/L. Regression of percent atheroma volume (-0.99%, 95% CI -1.84 to -0.14, p = 0.024) was accompanied by reduction of percent fibro-fatty (p = 0.04) and fibrous tissue (p < 0.001), and increase in percent necrotic core (p = 0.006) and dense calcium (p < 0.001). Follow-up levels of hs-CRP, but not LDL-C, correlated with changes in percent necrotic core (p = 0.001) and inversely with percent fibrous tissue volume (p = 0.008). Similarly, baseline-to-follow-up change of hs-CRP correlated with the change in percent necrotic core volume (p = 0.02). CONCLUSIONS In STEMI patients receiving high-intensity statin therapy, stabilization of VH-IVUS-defined necrotic core was confined to patients with lowest on-treatment levels and greatest reduction of hs-CRP. Elevated CRP levels at follow-up may identify progression of high-risk coronary plaque composition despite intensive statin therapy and overall regression of atheroma volume.

CHARACTERIZATION AND COMPARISON OF SUBHUMAN PRIMATE AND HUMAN TYPE C RETROVIRAL GENE PRODUCTS

The viral specific precursor polyproteins of simian sarcoma/simian associated virus (SiSV/SiAV), baboon endogenous viruses (BaEV), and three human isolate retroviruses, have been analyzed by radioimmunoprecipitation and tryptic peptide mapping. Cells infected with the BaEV isolates are characterized by identical precursor polyproteins: gPr80-85('env), Pr70-71('gag), and Pr65-67('gag). By tryptic digest mapping, m7-BaEV and 455K-BaEV were shown to be highly related. By comparison, mapping studies showed that BILN-BaEV was less highly related to m7-BaEV than was 455K-BaEV. Chase-incubated cells infected with BaEV also contained a stable, p28-related polyprotein termed P72('gag). This polyprotein appeared to arise by posttranslational modification of Pr70-71('gag). Tryptic digest mapping of BaEV and HL23V precursor polyproteins suggested that the BaEV-like component of HL23V was more closely related to m7-BaEV than to 455K-BaEV or BILN-BaEV.^ The intracellular precursor polyproteins of SiSV(SiAV) and gibbon ape leukemia virus (GaLV) were compared to the intracellular proteins of the human retrovirus isolates, HL23V, HEL12V, and A1476V. Cells infected with SiSV(SiAV) were characterized by polyproteins Pr200('gag-pol), gPr80('env), Pr80('gag), pr60('gag), and Pr40('gag). We have found that the human isolates are identical to true SiAV with regard to the size and structure of their precursor polyproteins. Both gPr80('env) and Pr60('gag) of SiAV were identical by tryptic peptide mapping to the respective proteins from the three human retroviral isolates examined. We have also shown that these viruses differ significantly from each of the GaLV isolates studied. Since SiAV differs substantially from any known GaLV isolate, we feel that it is unlikely that SiAV is a subtype of GaLV which exists today in the gibbon gene pool. The experimental evidence suggests that SiAV may be an exogenous human retrovirus that was transmitted originally into the human gene pool in the distant past by cross-species infection with GaLV(,SF) or with the GaLV(,SF) progenitor virus. It is, therefore, quite possible that SiAV expression in the pet woolly monkey arose from a recent infection of that monkey with SiAV from humans.^