¹³N-ammonia rest/stress PET

Summary

Aim: Hyperhomocysteinaemia (Hhcy) is known to be an independent risk factor for vascular disease. Coronary flow reserve (CFR) measured by positron emission tomography (PET) is a sensitive method to monitor the effects of pharmacologic interventions in Hhcy. We assessed coronary vascular reactivity by PET in patients with coronary artery disease (CAD) dependent on their homocysteine (Hcy) levels before and under high dose folic acid supplementation therapy (FAST). Patients, methods: Twelve patients with CAD underwent rest/adenosine 13N-ammonia PET for quantification of myocardial blood flow (MBF) and CFR before and after nine weeks FAST (10 mg/day). Results: Folate levels increased from 21 ± 6 to 210 ± 34 μg/l (+900%, p <0.0001) while Hcy levels decreased from 12.1 ± 3.6 to 9.1 ± 3.1 μmol/l (–25%; p <0.01). Global resting MBF remained nearly unchanged after FAST, while stress MBF (from 2.61 ± 0.93 to 3.25 ± 1.15 ml/ g/min; p = 0.05) and CFR (from 3.00 ± 0.76 to 3.72 ± 0.93 ml/g/min; p <0.05; +24%) significantly increased in patients with normal and elevated Hcy levels (cut off 12 μmol/l). An inverse relation was found between Hcy and CFR (R = –0.53; p = 0.08) and between Hcy and MBF at rest (R = –0.62; p < 0.05) at baseline conditions, not persisting after FAST. Conclusion: Coronary vascular reactivity can be improved by FAST in patients with CAD and normal or elevated Hcy levels. FAST might lower an increased cardiovascular risk in CAD patients possibly by mechanisms that are not related to Hcy.

Zusammenfassung

Ziel: Hyperhomocysteinämie (Hhcy) ist ein bekannter Risikofaktor für vaskuläre Erkrankungen. Die Bestimmung der koronaren Flussreserve (KFR) mittels Positronenemissionstomographie (PET) ist eine sensitive Methode um die Effektivität pharmakologischer Interventionen bei Hhcy zu überwachen. Wir untersuchten die koronare Gefäßreaktivität mittels PET in Abhängikeit der Homocystein(Hcy)-Konzentration bei Patienten mit koronarer Herzkrankheit (KHK) vor und unter hoch dosierter Folsäure-Substitutionstherapie (FAST). Patienten, Methoden: Bei zwölf Patienten mit KHK erfolgten eine Ruhe/Adenosin-13N-Ammoniak-PETUntersuchung zur Quantifizierung des myokardialen Blutflusses (MBF) und der KFR vor und neun Wochen nach FAST (10 mg/Tag). Ergebnisse: Die Folsäurekonzentrationen stiegen von 21 ± 6 auf 210 ± 34 μg/l (+900%, p <0.0001) während die Hcy-Spiegel von 12.1 ± 3.6 auf 9.1 ± 3.1 μmol/l (–25%; p <0.01) fielen. Der globale Ruhe-MBF blieb unter FAST unverändert, während der Stress-MBF (von 2.61 ± 0.93 auf 3.25 ± 1.15 ml/ g/min; p = 0.05) und die KFR (von 3.00 ± 0.76 auf 3.72 ± 0.93 ml/g/min; p <0.05; +24%) sowohl bei Patienten mit normalen als auch bei jenen mit erhöhter Hcy-Konzentration (Grenzwert: 12 μmol/l) signifikant stiegen. Initial fand sich eine inverse Relation zwischen Hcy und KFR (R = –0.53; p = 0.08) sowie zwischen Hcy und Ruhe MBF (R = –0.62; p <0.05), welche nach FAST nicht mehr vorhanden war. Schlussfolgerung: Die koronare Gefäßreaktivität kann durch FAST bei KHK-Patienten mit normaler oder erhöhter Homocysteinkonzentration verbessert werden. Es ist denkbar, dass bei KHK-Patienten durch FAST ein erhöhtes kardiovaskuläres Risiko gesenkt werden kann, dies möglicherweise durch Mechanismen, die nicht in direktem Zusammenhang mit Homocystein stehen.

Keywords

Homocysteine - coronary flow reserve - coronary artery disease - positron emission tomography

Schlüsselwörter

Homocystein - koronare Flussreseve - koronare Herzkrankheit - PET

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