Franz Weidinger

Neopterin, CD4+CD28− lymphocytes and the extent and severity of coronary artery disease

OBJECTIVES Macrophages and pro-inflammatory CD3+CD4+CD28- T lymphocytes are involved in atherosclerotic plaque destabilization. Whether neopterin, a macrophage-specific activation-marker, and circulating CD3+CD4+CD28- cells are also related to the severity and extent of coronary artery disease (CAD) in stable patients is still unclear. METHODS Coronary angiograms of 30 patients with stable angina pectoris were graded using the Gensini severity and an extent score. Patients were grouped according to the median of each score. Lymphocyte subsets were determined by FACS analysis and neopterin by radioimmunoassay. Peripheral endothelial function of the brachial artery (FMD) shown to correlate with cardiovascular risk factors was evaluated using high-resolution ultrasound. RESULTS More extensive CAD was associated with increased neopterin levels (8.3 +/- 3.3 vs. 5.5 +/- 1.2 nmol/L, p < 0.001) and increased CD3+CD4+CD28- cells (3.1 +/- 1.6 vs. 2.0 +/- 1.2%, p < 0.05). A high Gensini severity score was associated with increased neopterin levels (7.8 +/- 2.7 vs. 6.3 +/- 1.7 nmol/L, p < 0.05), but not with CD3+CD4+CD28- cells. Neopterin correlated with both the extent (r = 0.59, p < 0.001) and the Gensini score (r = 0.57, p < 0.003). FMD was not correlated with both scores. CONCLUSIONS Neopterin and CD3+CD4+CD28- lymphocytes are associated with CAD extent in stable patients, thereby emphasizing the inherent role of inflammation in atherogenesis itself beyond plaque destabilization. Neopterins correlation with CAD severity might be additionally useful in identifying patients eligible for revascularization procedures.

Is there a relation between non-calcifying coronary plaques and acute coronary syndromes? A retrospective study using multislice computed tomography.

Objectives: The purpose of this study was to assess whether different coronary plaque types as classified by multislice computed tomography (CT) are retrospectively correlated with acute coronary syndromes (ACS) in an unselected study population. Methods: Sixty-three consecutive patients were examined with 16-slice CT coronary angiography. Coronary plaque types were classified as calcifying type 1, mixed (calcifying > non-calcifying) type 2, mixed (non-calcifying > calcifying) type 3, and non-calcifying type 4. Patients who had an ACS within 17 days were included. All patients underwent invasive coronary angiography. Results: Fifty-eight patients (92%) had coronary plaques evaluated by CT: 18 type 1 (31%), 10 type 2 (17%), 16 type 3 (28%) and 14 type 4 (24%). The presence of a non-calcifying plaque component (types 2–4; 40 of 63 patients, 63%) was correlated with ACS (n = 15; 24%) (p < 0.001). Only type 3 was significantly correlated with ACS (p = 0.01), but plaque types 2 and 4 were not. The diagnostic accuracy of CT for detection of stenosis >50% in proximal segments was: sensitivity 98%, specificity 90%, negative predictive value 97%, positive predictive value 97% per patient. Conclusions: Mixed calcifying/non-calcifying plaques with a predominantly non-calcifying component (type 3) as classified by multislice CT are retrospectively correlated with ACS.

Effect of atorvastatin on peripheral endothelial function and systemic inflammatory markers in patients with stable coronary artery disease

ZusammenfassungGRUNDLAGEN: Eine endotheliale Dysfunktion, messbar an einer verminderten Fluss-vermittelten Vasodilatation (FMD) der Brachialarterie, geht mit erhöhten Konzentrationen systemischer Entzündungsparameter, wie man es bei Patienten mit koronarer Herzkrankheit (KHK) findet, einher. Therapeutische Interventionen wie etwa eine Lipidsenkung mit Statinen, verbessern die FMD und vermindern systemische Entzündungsparameter wie zum Beispiel das lösliche E-Selectin (sE-selectin), das lösliche interzelluläre Ahäsionsmolekül-1 (sICAM-1) oder des hochsensitive C-reaktive Protein (hsCRP). Die Wirkung einer Behandlung mit Atorvastatin sowohl auf die FMD als auch auf diese zirkulierenden Entzündungsstoffe in Patienten mit stabiler KHK wurde bisher noch nicht eingehend untersucht. METHODIK: Dreißig hypercholesterinämische Patienten mit einer angiographisch dokumentierten KHK und stabiler Angina pectoris wurden für 3 Monate doppelblind randomisiert zu Plazebo oder Atorvastatin (20 mg täglich). Die FMD der Brachialarterie wurde mittels hochauflösendem Ultraschall (13 MHz; Acuson Sequioa C256) bestimmt. Das hochsensitive C-reaktive Protein wurde mit einem Latex-Agglutinations-Test und das sE-Selectin sowie das sICAM-1 wurden mit einem ELISA gemessen. ERGEBNISSE: Die Patientencharakteristik zu Beginn war in beiden Gruppen gleich. Die FMD verbesserte sich in den mit Atorvastatin behandelten Patienten (6,7 ± 3,8 % to 8,5 ± 4,4 %; p < 0,01), blieb aber unverändert in den zu Plazebo randomisierten Patienten (8,2 ± 3,3 % to 8,9 ± 5,1 %; p = NS). Die Therapie mit Atorvastatin ging einher mit einer Reduktion des sICAM-1 (von 274,2 ± 92,2 auf 197,9 ± 70,0 ng/ml; p < 0,01) und des hsCRP (von 0,57 ± 0,45 auf 0,18 ± 0,15 mg/dl; p < 0,01), wohingegen Plazebo auf diese Entzündungsparameter keinen Einfluss hatte. sE-Selectin wurde weder durch Atorvastatin noch durch Plazebo beeinflusst. Darüber hinaus fand sich keine Korrelation zwischen den Veränderungen der FMD, der Lipide und der systemischen Entzündungsparameter. SCHLUSSFOLGERUNGEN: Eine Therapie mit Atorvastatin verbessert die periphere Endothelfunktion und reduziert systemische Entzündungsparameter in Patienten mit stabiler koronarer Herzkrankheit. Die fehlende Korrelation zwischen der Veränderung der Endothelfunktion und der Entzündungsparameter unterstützt das Konzept der pleiotropen Effekte von Statinen in Menschen.SummaryBACKGROUND: Endothelial dysfunction, detectable by an impaired flow-mediated vasodilation (FMD) of the brachial artery, has been shown to be associated with increased levels of circulating proinflammatory markers. Therapeutic interventions such as lipid-lowering with statins increase FMD and decrease inflammatory markers, like soluble (s) E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) or high-sensitivity Creactive protein (hsCRP). The effect of atorvastatin therapy on both FMD and inflammatory markers in patients with stable coronary artery disease (CAD) has not been investigated. METHODS: Thirty hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. FMD was assessed using highresolution ultrasound (13 MHz, Acuson Sequoia, C256). High-sensitivity CRP was measured with Latex agglutination assay, sE-selectin and sICAM-1 were determined with ELISA. RESULTS: Baseline characteristics were not different between groups. FMD improved in patients on atorvastatin (6.7 ± 3.8 % to 8.5 ± 4.4 %; p < 0.01), but remained unchanged in placebo-treated patients (8.2 ± 3.3 % to 8.9 ± 5.1 %; p = NS). Atorvastatin treatment was associated with decreases of sICAM-1 (from 274.2 ± 92.2 to 197.9 ± 70.0 ng/ml; p < 0.01) and hsCRP (from 0.57 ± 0.45 to 0.18 ± 0.15 mg/dl; p < 0.01), whereas placebo treatment had no effect on these markers. sE-selectin levels were not influenced by either treatment. No correlations were found between changes in FMD, lipids and inflammatory markers. CONCLUSIONS: Treatment with atorvastatin leads to an improvement in endothelial function and a reduction in inflammatory markers in patients with stable CAD. The lack of correlation between changes in FMD and inflammatory markers may support the concept of pleiotropic effects of statins in humans.