Association of endotoxemia with carotid atherosclerosis and cardiovasculardisease - Prospective results from the Bruneck Study

OBJECTIVES Focus of the current study was on the significance of bacterial endotoxin, which shows a variety of pro-atherogenic properties and map occu r at high concentration in the circulation of infected subjects. BACKGROUND The possibility of an infectious risk factor in atherogenesis an d cardiovascular disease has stimulated research interest, but the nature o f such process remains obscure. METHODS We measured plasma endotoxin levels (LAL assay) in a random populat ion 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 (earl y) atherosclerosis in the carotid arteries as assessed with high-resolution Duplex ultrasound (five-year follow-up rate, 98%) and incident cardiovascu lar disease (follow-up rate, 100%). RESULTS Median endotoxin concentration amounted to 14.3 pg/ml (range, 6.0 t o 209.2 pg/ml). Subjects with levels beyond 50 pg/ml (90th percentile) face d 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 independen t of vascular risk factors. Similar results were obtained for incident card iovascular disease. CONCLUSIONS The current study yields first epidemiologic evidence that endo toxemia constitutes a strong risk factor of early atherogenesis in subjects with chronic or recurrent bacterial infections and a link in the associati on between cigarette smoking and atherosclerotic disease. (C) 1999 by the A merican College of Cardiology.