Author + information
- Received September 26, 2004
- Revision received January 19, 2005
- Accepted January 25, 2005
- Published online May 3, 2005.
- Thomas H. Schindler, MD⁎,†,⁎ (, )
- Egbert U. Nitzsche, MD‡,
- Heinrich R. Schelbert, MD, PhD⁎,
- Manfred Olschewski, MSc†,
- James Sayre, PhD⁎,
- Michael Mix, MSc, PhD†,
- Ingo Brink, MD†,
- Xiao-Li Zhang, MD, PhD⁎,
- Michael Kreissl, MD⁎,
- Nobuhisa Magosaki, MD†,
- Hanjoerg Just, MD† and
- Ulrich Solzbach, MD†
- ↵⁎Reprint requests and correspondence:
Dr. Thomas H. Schindler, Department of Pharmacology, David Geffen School of Medicine at UCLA, B2-045J CHS, Box 956948, Los Angeles, California 90095-6948.
Objectives We sought to assess prospectively whether patients with normal coronary angiograms but with impaired myocardial blood flow (MBF) increases to cold pressor testing (CPT) are at increased risk for cardiovascular events.
Background Invasive angiographic assessments of coronary vasomotor function have demonstrated an impairment of endothelium-related coronary flow increases to independently predict future cardiovascular events. It is unknown whether noninvasive positron emission tomography (PET)-measured MBF alterations to sympathetic stimulation with CPT are associated with the risk of developing cardiovascular events.
Methods A total of 72 patients (44 men, 28 women, age 58 ± 8 years) referred for diagnostic cardiac catheterization were studied. Myocardial blood flow was measured in absolute units with 13N-ammonia using PET, at baseline and during CPT in each patient. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 66 ± 8 months. Patients were assigned to three groups: group 1, patients with ≥40% increase in MBF (%ΔMBF), n = 22; group 2, patients with >0 and <40% increases in MBF, n = 32; and group 3, patients with decreases in MBF (≤0%), n = 18.
Results During follow-up, one of the group 1 patients developed a cerebral stroke. In group 2, 15 cardiovascular events occurred in 9 patients and in group 3, 7 patients experienced 9 cardiovascular events (p ≤ 0.0001, univariate by log-rank test). Impaired MBF increases in group 2 and group 3 were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis (p = 0.033, log-rank test). After adjusting for known coronary risk factors, MBF responses to CPT revealed a nonsignificant trend to be independently associated with a higher incidence for cardiovascular events (p = 0.065, multivariate by Cox regression model).
Conclusions Noninvasive PET-measured impaired MBF increases to sympathetic stimulation are associated with the risk of developing cardiovascular events.
This work was supported by grants from the German Research Foundation (So 241/2-2) and Baden-Württemberg (Projekt: Sch-A1/A2) and by grant HL 331777, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
- Received September 26, 2004.
- Revision received January 19, 2005.
- Accepted January 25, 2005.
- American College of Cardiology Foundation