Active and passive smoking, chronic infections, and the risk of carotid atherosclerosis: prospective results from the Bruneck Study.
OBJECTIVE
Susceptibility of the vasculature to the injurious effects of smoking varies substantially, with some smokers developing severe premature atherosclerosis and others remaining free of advanced atheroma until high ages. The present study sought to estimate the contribution of chronic infections to the variability of atherosclerosis severity among smokers.


METHODS
In the community-based Bruneck Study, 5-year changes in carotid atherosclerosis were assessed by high-resolution ultrasound. Early atherogenesis was defined by the development of nonstenotic plaques and advanced atherogenesis by the development/progression of vessel stenosis >40%.


RESULTS
The risk of early atherogenesis strongly relied on lifetime smoking exposure and remained elevated long-term after cessation of smoking. Remarkably, current and ex-smokers faced an increased atherosclerosis risk only in the presence of chronic infections (odds ratios [95% CIs], 3.3 [1.8 to 6.2] and 3.4 [1.8 to 6.3]; P<0.001 each), whereas current, past, and nonsmokers without infections did not differ substantially in their estimated risk burden (odds ratios [95% CIs], 1.4 [0.8 to 2.4], 0.9 [0.6 to 1.6], and 1.0 [reference group]). In analogy to first-hand smoking, subjects exposed to environmental tobacco smoke were found to be vulnerable to the manifestation of chronic infection, and only those infected experienced a high atherosclerosis risk. The risk of advanced atherogenesis showed a dose-response relation with the number of daily cigarettes, returned to normal shortly after cessation of smoking, and emerged as independent of infectious illness.


CONCLUSIONS
Our study provides the first epidemiological evidence that the proatherogenic effects of cigarette smoking are mediated in part by the chronic infections found in smokers. A better understanding of the vascular pathogenetic mechanisms of smoking may offer novel clues for disease prevention supplementary to the primary goal of achieving long-term abstinence.
Kiechl
Stefan
S
Department of Neurology, Innsbruck University Hospital, Innsbruck, Austria. Stefan.Kiechl@uibk.ac.at
Werner
Philipp
P
Egger
Georg
G
Oberhollenzer
Friedrich
F
Mayr
Manuel
M
Xu
Qingbo
Q
Poewe
Werner
W
Willeit
Johann
J
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000209:etiology*; D002908:Chronic Disease; D015331:Cohort Studies; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007239:Infections / Q000453:epidemiology*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D015995:Prevalence; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology; D012042:Registries / Q000706:statistics & numerical data; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology*; D016540:Smoking Cessation / Q000706:statistics & numerical data; D014028:Tobacco Smoke Pollution / Q000009:adverse effects* / Q000706:statistics & numerical data; D014463:Ultrasonography
D014028:Tobacco Smoke Pollution; D002097:C-Reactive Protein