Systemic Low-Grade Inflammation and Risk of Coronary Heart Disease: Results from the MONICA/KORA Augsburg Cohort Studies

Zusammenfassung

Die Atherosklerose weist wesentliche Charakteristika einer lokalen Inflammation auf und ist von einer geringgradigen systemischen inflammatorischen Antwort begleitet. Zahlreiche prospektive Studien bei initial gesunden Personen, aber auch bei Patienten mit bereits klinisch manifester Atherosklerose zeigen eine starke, unabhängige Beziehung zwischen nur geringgradig erhöhten Konzentrationen verschiedener systemischer Inflammationsmarker (Plasmaviskosität, C-reaktives Protein [CRP] oder anderen Akute-Phase-Reaktanten) und verschiedenen kardiovaskulären Endpunkten. Derzeit liegen die umfangreichsten und konsistentesten Daten für CRP vor. Erste Ergebnisse zeigen, dass CRP in der Lage ist, die im Framingham-Risiko-Score enthaltene Information zu modifizieren und unlängst veröffentlichte Richtlinien von AHA/CDC empfehlen die Bestimmung von CRP bei asymptomatischen Personen mit mittlerem Risiko (10-Jahresrisiko zwischen 10 und 20 %) und bei ausgewählten Patienten nach einem akuten Koronarsyndrom. Derzeit wird in einer großen randomisierten Therapiestudie der Frage nachgegangen, ob erhöhte CRP-Spiegel eventuell ein zusätzliches Kriterium zur Statin-Behandlung von Personen mit normalem LDL-Cholesterin darstellen. Forschungsergebnisse der letzten Jahre legen nahe, dass CRP möglicherweise nicht nur ein kardiovaskulärer Risikomarker ist, sondern direkt in den Prozess der Atherogenese involviert ist. Letztlich wird derzeit eine Fülle weiterer inflammatorischer Biomarker daraufhin untersucht, ob sie die Prädiktion kardiovaskulärer Ereignisse bei verschiedenen Personengruppen verbessern können. Wir haben im Rahmen der MONICA/KORA-Studien die Assoziation einer Reihe derartiger Biomarker mit klassischen kardiovaskulären Risikofaktoren und mit koronaren Ereignissen untersucht.

Abstract

Atherosclerosis is characterised by a non-specific local inflammatory process accompanied by a systemic response. A number of prospective studies in initially healthy subjects and in patients with manifest atherosclerosis have now convincingly demonstrated a strong and independent association between even slightly elevated concentrations of various systemic markers of inflammation (plasma viscosity, C-reactive protein [CRP], and other acute phase reactants) and a number of cardiovascular endpoints. Presently, CRP, the classical acute phase protein, seems to be the marker of choice for the clinical situation. Initial evidence suggests that measurement of CRP adds to global risk assessment based on the Framingham risk score. The recent AHA/CDC consensus report recommends the measurement of CRP in asymptomatic subjects at intermediate risk for future coronary events (10-year risk of 10 - 20 %) and in selected patients after an acute coronary syndrome. Whether CRP shall alter treatment strategies in subjects without clinically manifest atherosclerosis is presently being tested in a large randomised clinical trial. In addition, recent research has suggested that CRP may not only be a risk marker, but may be directly involved in the pathogenesis of atherothrombosis. However, there are other emerging biomarkers. Lipoprotein-associated phospholipase A₂ (Lp-PLA₂), an enzyme produced by monocytes/macrophages, T-cells and mast cells was found to generate proinflammatory and proatherogenic molecules from oxidised LDL. We tested the association of these new biomarkers with traditional risk factors and their ability to predict incident coronary events, using the MONICA/KORA database.

Schlüsselwörter

Inflammation - Biomarker - koronare Ereignisse - Querschnittsstudien - prospektive Studien

Key words

Inflammation - biomarkers - coronary events - cross-sectional studies - prospective studies

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