Cigarette Smoking Is Related to Endothelial Dysfunction of Resistance, but Not Conduit Arteries in the General Population-Results From the Gutenberg Health Study.

Omar Hahad,Matthias Michal,Andreas Daiber,Andreas Schulz,John F Keaney,Thomas Münzel,Manfred Beutel,Irene Schmidtmann,Jürgen H Prochaska,Norbert Pfeiffer,Natalie Arnold,Philipp S Wild,Karl J Lackner,Marina Panova-Noeva

doi:10.3389/fcvm.2021.674622

Abstract

Aims: Cigarette smoking is one of the most complex and least understood cardiovascular risk factors. Importantly, differences in the tobacco-related pathophysiology of endothelial dysfunction, an early event in atherogenesis, between circulatory beds remain elusive. Therefore, this study evaluated how smoking impacts endothelial function of conduit and resistance arteries in a large population-based cohort.Methods and results: 15,010 participants (aged 35–74 years) of the Gutenberg Health Study were examined at baseline from 2007 to 2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a computer-assisted interview. Endothelial function of conduit and resistance arteries was determined by flow-mediated dilation (FMD) of the brachial artery, reactive hyperemia index (RHI) using peripheral arterial tonometry, as well as by reflection index (RI) derived from digital photoplethysmography, respectively. Among all subjects, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Mean cumulative smoking exposure was 22.1 ± 18.1 pack-years in current smokers and mean years since quitting was 18.9 ± 12.7 in former smokers. In multivariable linear regression models adjusted for typical confounders, smoking status, pack-years of smoking, and years since quitting smoking were independently associated with RHI and RI, while no association was found for FMD. Overall, no clear dose-dependent associations were observed between variables, whereby higher exposure tended to be associated with pronounced resistance artery endothelial dysfunction.Conclusions: Cigarette smoking is associated with altered endothelial function of resistance, but not conduit arteries. The present results suggest that smoking-induced endothelial dysfunction in different circulatory beds may exhibit a differential picture.

Highlights

In 2015, smoking was ranked second as a leading cause of premature death and disability worldwide [1]
Individuals with a positive history of smoking were more likely to be male, had a lower socioeconomic status, and higher prevalence of depression as well as alcohol consumption above tolerable limit compared to never smokers
The relevance of NOX-2 for smoking associated cardiovascular complications in humans is so far not supported by associations of NADPH oxidase centered inactivating polymorphisms, there is clinical evidence that NOX-2 activation plays a pathophysiological role in smoking

Summary

Introduction

In 2015, smoking was ranked second as a leading cause of premature death and disability worldwide [1]. Smoking directly affects the health of others (mostly children) via the harmful effects of second-hand smoke [5]. Cigarette smoking is a major reversible risk factor for development and progression of cardiovascular disease (CVD) and ranks among the leading causes of coronary artery disease, ischemic stroke, and peripheral artery disease [6]. Even worse, smoking can exert additive adverse health effects with other life style drugs such as alcohol [7, 8] and probably with common environmental stressors such as traffic noise or air pollution [9]

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