CLINICAL STUDIES
Association of endotoxemia with carotid atherosclerosis and cardiovascular disease
Prospective results from the bruneck study
Christian J. Wiedermann, MD*,
Stefan Kiechl, MD ,
Stefan Dunzendorfer, MD*,
Peter Schratzberger, MD*,
Georg Egger, MD ,
Friedrich Oberhollenzer, MD and
Johann Willeit, MD
* Department of Internal Medicine, Medical Faculty, University of Innsbruck, Innsbruck, Austria
Department of Neurology, Medical Faculty, University of Innsbruck, Innsbruck, Austria
Department of Internal Medicine, Federal Hospital, Bruneck, Italy
Manuscript received January 15, 1999;
revised manuscript received May 5, 1999,
accepted August 27, 1999.
Reprint requests and correspondence: Dr. Christian J. Wiedermann, Department of Internal Medicine, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
christian.wiedermann{at}uibk.ac.at
OBJECTIVES
Focus of the current study was on the significance of bacterial endotoxin, which shows a variety of pro-atherogenic properties and may occur at high concentration in the circulation of infected subjects.
BACKGROUND
The possibility of an infectious risk factor in atherogenesis and cardiovascular disease has stimulated research interest, but the nature of such process remains obscure.
METHODS
We measured plasma endotoxin levels (LAL assay) in a random population of 516 men and women 50 to 79 years old at the 1990 baseline evaluation (Bruneck Study). End points of this prospective survey were incident (early) atherosclerosis in the carotid arteries as assessed with high-resolution Duplex ultrasound (five-year follow-up rate, 98%) and incident cardiovascular disease (follow-up rate, 100%).
RESULTS
Median endotoxin concentration amounted to 14.3 pg/ml (range, 6.0 to 209.2 pg/ml). Subjects with levels beyond 50 pg/ml (90th percentile) faced a threefold risk of incident atherosclerosis (odds ratio [95% confidence interval] 2.9 [1.4–6.3]; p < 0.01). The risk associated with high endotoxin was most pronounced in subjects with chronic infections and in current and ex-smokers. Notably, smokers with low endotoxin levels and nonsmokers did not differ in their atherosclerosis risk, whereas smokers with high levels almost invariably developed new lesions. All findings emerged as independent of vascular risk factors. Similar results were obtained for incident cardiovascular disease.
CONCLUSIONS
The current study yields first epidemiologic evidence that endotoxemia constitutes a strong risk factor of early atherogenesis in subjects with chronic or recurrent bacterial infections and a link in the association between cigarette smoking and atherosclerotic disease.
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Abbreviations and Acronyms
| | CV | = coefficient of variation | | ETX | = endotoxin | | HDL | = high-density lipoprotein | | LAL | = Limulus amebocyte lysate | | LDL | = low-density lipoprotein | | ln | = log-normalized |
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