Prevalence of intimal heat shock protein 60 homologues in unstable angina and correlation with anti-heat shock protein antibody titers.

Heat shock proteins (HSPs) are among the most highly conserved and immunogenic proteins shared by microbial agents and mammals. Human (h) HSP60 is upregulated under stress conditions and serves as a target for cross-reactive cytotoxic HSP-serum-antibodies. The present study evaluates the expressions of hHSP60 and its homologue chlamydial (c) HSP60 in advanced human coronary lesions and correlates intimal tissue-bound HSP expressions with circulating HSP-antibodies. Coronary atherectomy specimens retrieved from 100 primary target lesions of patients with unstable angina (UA; n = 40) or stable angina (SA; n = 60) were assessed immunohistochemically for the presence of hHSP60 and cHSP60. In a subgroup (n = 40), blood samples were tested for anti-Chl. pn.-IgG/IgA-titers and anti-HSP65-antibody titers. Coronary plaques revealed immunoreactive hHSP60 in 55% and cHSP60 in 45% of the lesions. Expression of both HSP homologues was significantly (each p < 0.001) higher in UA lesions compared with SA lesions (7.4 vs. 1.2% and 6.0 vs. 1.1%). HSP homologues showed positive correlations both in UA- and SA-lesions (r = 0.41, 0.33; p < 0.05). cHSP60 showed no association with anti-Chl. pn.-IgG/IgA-titers, whereas expressions of both homologues correlated positive with anti-HSP65-Ab titers (r = 0.42, p < 0.05; r = 0.50, p < 0.01). Intimal amounts of HSP60 homologues were associated with increased expressions of C-reactive protein, Toll-like receptor-4 and tissue factor. Human and chlamydial HSP60 colocalize within coronary atheroma, most prevalent in lesions associated with UA. Our data demonstrate a significant correlation between the intimal expressions of HSP60 homologues and serum HSP65 antibodies, thereby suggesting that humoral immune reactions may play an important role in coronary atherosclerosis and plaque instability.

Increased expression of C-reactive protein and tissue factor in acute coronary syndrome lesions: Correlation with serum C-reactive protein, angioscopic findings, and modification by statins.

BACKGROUND: Serum C-reactive protein (CRP) is a strong risk predictor of cardiovascular events, and tissue factor (TF) plays a central role in thrombus formation of advanced atherosclerotic plaques. Aim of the present study was to quantify in situ CRP and TF in coronary atherectomy specimens associated with acute coronary syndromes (ACS) or stable angina (SA). In addition, the effect of statin treatment on both intimal determinants was analyzed. METHODS AND RESULTS: Serial sections from atherectomy probes retrieved from coronary primary target lesions of 42 ACS and 70 SA patients were examined for CRP and TF expression using immunostaining. CRP and TF intimal expression was consistently higher in ACS lesions and a positive correlation between both determinants was detected. In both subgroups intimal staining intensity of CRP but not TF was strongly associated with serum CRP levels. Using angioscopy, complex plaques revealed a higher intimal CRP and TF expression than white/yellow plaques. Both CRP and TF were consistently lower expressed in target lesions of patients with pre-existing statin treatment. CONCLUSIONS: CRP and TF expression is markedly increased in plaques derived from patients with ACS as compared to SA patients. Statin treatment appears to reduce vascular expression of CRP and TF.

Inefficacy of different strategies to improve guideline awareness - 5-year follow-up of the hypertension evaluation project (HEP).

BACKGROUND: In spite of numerous guidelines for evidence based diagnostic and therapy adequate knowledge of current recommendations is disappointingly low. In the Hypertension Evaluation Project (HEP I) we showed that awareness of national hypertension guidelines under German practitioners was less than 25% in the year 2000. This indicates the need for efficient strategies to relevantly improve guideline awareness. METHODS: To asses different tools for amending guideline knowledge we used three strategies (guideline in print, interactive guideline, expert seminars) to train 8325 randomised physicians, who had participated in the HEP I trial. Guideline knowledge of the trained physicians was again tested with the HEP questionnaire and compared to a control group of HEP I physicians. RESULTS: The return rate of questionnaires was 57.9% without a significant distinction between the groups. Overall guideline awareness was still low but remarkably improved compared to the results of HEP I (37.1% vs. 23.7%, p < 0.0001). There was no difference between the trained physicians and the control group (35.8% and 35.9% vs. 39.7%, p = n.s.). CONCLUSION: We investigated the influence of different strategies to improve guideline awareness among German physicians. None of our interventions (guideline in print, interactive guideline, expert seminars) brought a notable benefit compared to control group. However, overall knowledge of guideline contents increased from 23.7% to 37.1% over five years. Therefore, other probably multimodal interventions are necessary to significantly improve guideline awareness beyond spontaneous advancement. TRIAL REGISTRATION: ISRCTN53383289.

Compliance of a cobalt chromium coronary stent alloy--the COVIS trial.

BACKGROUND: Cobalt chromium coronary stents are increasingly being used in percutaneous coronary interventions. There are, however, no reliable data about the characteristics of unfolding and visibility of this stent alloy in vivo. The aim of this study is to compare cobalt chromium coronary stents with conventional stainless steel stents using intracoronary ultrasound. METHODS: Twenty de novo native coronary stenoses < or = 20 mm in length (target vessel reference diameter > or = 2.5 and < or = 4.0 mm) received under sequential intracoronary ultrasound either a cobalt chromium stent (Multi-Link Vision; n = 10) or a stainless steel stent (Multi-Link Zeta; n = 10). RESULTS: For optimal unfolding, the cobalt chromium stent requires a higher balloon deployment pressure (13.90 +/- 2.03 atm) than the stainless steel stent (11.50 +/- 2.12 atm). Furthermore, the achieved target vessel diameter of the cobalt chromium stent (Visibility-Index QCA/IVUS Multi-Link Vision 1.13 / Multi-Link Zeta 1.04) is more easily overrated by Quantitative Coronary Analysis. CONCLUSION: These data indicate that stent material-specific recommendations for optimal implantation pressure and different stent material with an equal design should both be considered in interpreting QCA-analysis.

Randomized comparison of mounted versus unmounted stents: the multicenter COMUS trial.

BACKGROUND: Although the use of premounted stents on a delivery balloon has almost completely eliminated the initially used hand-crimping procedure, no data are available that prove the superiority of one or the other approach on a randomized basis. Therefore, this study was designed to examine whether the use of premounted stents is comparable with the hand-crimping procedure. METHODS: A total of 123 patients (64 treated with unmounted stents, 59 treated with premounted stents) were examined in a multicenter, randomized, prospective study. There were no significant differences in patient characteristics between groups. RESULTS: Primary end points (acute, postinterventional [within 72 hours], and late complications related to the stenting procedure) were reached in 1 patient treated with an unmounted stent versus 2 patients with mounted stents (P = not significant). In patients with angiographic follow up (n = 84, mean follow-up period 6 +/- 1 months), the total rate of restenosis was 27% (unmounted 12, mounted 11, P = not significant). Secondary end points were procedural success of stenting and maximal balloon inflation pressure needed for optimal stenting results by use of angiography. There were no differences in secondary end points for both techniques. The mean balloon pressure was 12.56 +/- 2.1 atmospheres (unmounted) and 12.12 +/- 1.92 atmospheres (mounted, P = not significant). CONCLUSION: Stenting with premounted devices was demonstrated to have a similar clinical and angiographic outcome as the hand-crimping approach for maximal inflation pressure, procedural success, major cardiac events, and rate of restenosis after 6 months of follow up. Thus, the more convenient use of a premounted stent provides procedural safety and efficacy comparable with a hand-crimped system.

Metoprolol treatment to prevent restenosis following percutaneous transluminal coronary angioplasty.

This study tested the hypothesis that metoprolol reduces the restenosis rate after percutaneous transluminal coronary angioplasty (PTCA) in native coronary arteries as compared to placebo. Apart from prognostic clinical effects in the treatment of patients with coronary heart disease, several in vivo and ex vivo studies have demonstrated antiproliferative and antiatherogenic effects of beta-blockers. In the present study, 192 male patients were randomized in a double-blind fashion to metoprolol sustained-release treatment or placebo starting at least 1 day before angioplasty. Lesion diameters and restenosis rates were evaluated using automatic edge detection systems. The study endpoint was the angiographic restenosis rate 4 months after PTCA. Ninety-seven randomized patients had a control angiography a mean of 4.5 months after PTCA. Dropouts were evenly distributed between the metoprolol and placebo groups. Lumen loss in the target lesion was 0.36 mm in the metoprolol group and 0.32 mm in the placebo group. Restenosis rates averaged 57.5% in the metoprolol group and 44.2% in the placebo group using conventional restenosis criteria. Taking metoprolol serum levels above 50 mmol/l as an indication of definite compliance with the metoprolol treatment, the restenosis rate was 58.3%. In conclusion, 95 mg of sustained-release metoprolol failed to reduce the restenosis rate following angioplasty in native coronary arteries.