Smokers’ Infections Increase Risk Of Early Atherosclerosis

DALLAS, Sept. 6 – Cigarette smoking turns the entire body into a breeding ground for infection, which may allow artery-clogging plaque to take hold, according to a study reported in the September issue of Stroke: Journal of the American Heart Association. Chronic infection may explain why some smokers prematurely develop the artery-clogging process that causes most heart attacks and strokes, while other smokers remain free of arterial plaque buildup until they are older.

Current and ex-smokers who had common chronic infections – such as bronchitis, ulcers, urinary tract infections and even gum disease – were more than three times as likely to develop early atherosclerosis than people without such infections. Early atherosclerosis was defined as new plaques in previously normal arteries.

"This study provides the first epidemiological evidence that the atherosclerotic effects of smoking are mediated in part by chronic infectious illnesses in smokers," says lead researcher Stefan Kiechl, M.D., professor of neurology at Austria's Innsbruck University Hospital.

Previous research has shown that smoking is linked to respiratory infections, gum infections and chronic ulcer infections. The study by Austrian, Italian and British researchers considered how smoking and exposure to secondhand smoke influences the development of arterial plaques, and the effects of smoking cessation, in patients with and without evidence of chronic infection.

"Active and passive smoking represents one of the most severe risks for atherosclerosis," Kiechl notes. "Smokers are at significantly higher risk of developing severe early atherosclerosis, but we found the risk falls to that of nonsmokers soon after they quit, unless there is a history of chronic infection."

Researchers used ultrasound scans to examine changes in the carotid arteries (the main vessels supplying blood to the brain) of 826 men and women ages 40 to 79. The participants were part of the Bruneck Study, a prospective, population-based survey in Bruneck, Italy, designed to identify factors contributing to atherosclerosis.

Over the five-year study period, 332 men and women developed new carotid plaques.

The risk of developing atherosclerosis was closely associated with the number of years and quantity of cigarettes smoked (pack years), regardless of gender, but chronic infection also had a role in plaque development, notes Kiechl.

"Remarkably, in both analyses, increased risk of atherosclerosis was observed only in smokers and ex-smokers with clinical signs of chronic infection. The risk burden in people without evidence of infection did not differ from that in nonsmokers."

Nonsmokers with chronic infection had 1.8 times the risk of premature atherosclerosis as nonsmokers free of infection. Among former smokers with infection, the risk was 1.9 times higher, while current smokers with infection had 2.9 times the risk for premature atherosclerosis as infection-free nonsmokers.

In ex-smokers with chronic infection, the risk of early atherosclerosis remained elevated even 10 years after they quit, while ex-smokers without infection showed a gradual decrease in risk over time, Kiechl says.

"We found that the ongoing risk after quitting is probably the result of chronic infections that develop during the active smoking period, especially respiratory infections, such as smokers bronchitis or chronic obstructive pulmonary disease," he says.

The group of passive smokers with chronic infection in the study also faced an increased risk of early artery disease. Researchers hypothesize that secondhand smoke renders individuals susceptible to respiratory infection and that infection increases the risk of artery disease.

Smokers should be made aware of the findings and should be advised to seek treatment for their chronic infections, he adds.

Co-authors are Philipp Werner, M.D.; Werner Poewe, M.D.; Johann Willeit, M.D.; Georg Egger, M.D.; Friedrich Oberhollenzer, M.D.; Manuel Mayr; and Qingbo Xu, M.D., Ph.D.

Note: This story has been adapted from a news release issued by American Heart Association for journalists and other members of the public. If you wish to quote from any part of this story, please credit American Heart Association as the original source. You may also wish to include the following link in any citation:

Original Contributions

Active and Passive Smoking, Chronic Infections, and the Risk of Carotid Atherosclerosis

Prospective Results From the Bruneck Study

Stefan Kiechl, MD; Philipp Werner, MD; Georg Egger, MD; Friedrich Oberhollenzer, MD; Manuel Mayr, MD; Qingbo Xu, MD, PhD; Werner Poewe, MD; Johann Willeit, MD

From the Department of Neurology, Innsbruck University Hospital, Innsbruck, Austria (S.K., P.W., W.P., J.W.); Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy (G.E., F.O.); and Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK (M.M., Q.X.).

Correspondence to Dr Stefan Kiechl, Department of Neurology, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria. E-mail Stefan.Kiechl@uibk.ac.at

Background and Purpose— Susceptibility of the vasculatureto the injurious effects of smoking varies substantially, withsome smokers developing severe premature atherosclerosis andothers remaining free of advanced atheroma until high ages.The present study sought to estimate the contribution of chronicinfections to the variability of atherosclerosis severity amongsmokers.

Methods— In the community-based Bruneck Study, 5-yearchanges in carotid atherosclerosis were assessed by high-resolutionultrasound. Early atherogenesis was defined by the developmentof nonstenotic plaques and advanced atherogenesis by the development/progressionof vessel stenosis >40%.

Results— The risk of early atherogenesis strongly reliedon lifetime smoking exposure and remained elevated long-termafter cessation of smoking. Remarkably, current and ex-smokersfaced an increased atherosclerosis risk only in the presenceof 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 substantiallyin their estimated risk burden (odds ratios [95% CIs], 1.4 [0.8to 2.4], 0.9 [0.6 to 1.6], and 1.0 [reference group]). In analogyto first-hand smoking, subjects exposed to environmental tobaccosmoke were found to be vulnerable to the manifestation of chronicinfection, and only those infected experienced a high atherosclerosisrisk. The risk of advanced atherogenesis showed a dose-responserelation with the number of daily cigarettes, returned to normalshortly after cessation of smoking, and emerged as independentof infectious illness.

Conclusions— Our study provides the first epidemiologicalevidence that the proatherogenic effects of cigarette smokingare mediated in part by the chronic infections found in smokers.A better understanding of the vascular pathogenetic mechanismsof smoking may offer novel clues for disease prevention supplementaryto the primary goal of achieving long-term abstinence.

Key Words: atherosclerosis • cigarette smoking • infection • inflammation

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