## 4 Discussion  
In our large population-based study of young and healthy adults, we found significantly lower hs-cTnI concentrations in current smokers compared to that in never smokers. A large difference was observed in participants with a high life-time consumption of cigarettes and a high smoking intensity. Past smokers had similar hs-cTnI levels to never smokers. The absolute between-group differences in hs-cTnI concentrations were small. Our findings are in line with and expand previously published data showing lower levels of hs-cTnI in smokers compared to those in never smokers in the general population [7]. Previous research on hs-cTnI levels in smokers showed results with similar small deviations between smoking groups aged 19 to 94 exhibiting significantly lower levels of cTnI than never smokers and former smokers [6]. However, data in stable CAD from smokers compared to non-smokers presented significantly lower hs-cTnI but not hs-cTnI concentrations [4]. Compared to the existing literature investigating hs-cTnI across a wide range of age groups, our results demonstrate lower hs-cTnI levels in adults aged 25 to 41 who currently smoke. Analyzing hs-cTnI in this narrow young age group minimizes the risk of unmeasured confounding or survival bias and also lowers the risk of undetected CAD. Our study also adds to the existing literature by showing the intensity dose-response relationship by the used Fagerstrom score. Like previous studies [4; 6; 7], we evaluated hs-cTnI concentrations in different smoking groups (current, past, and never) and showed lower hs-cTnI levels in current smokers compared to those in never smokers. We also calculated pack-years to measure the lifetime exposure to smoking and found a strong trend across pre-specified groups of pack-yearssmoked. Smoking intensity as measured by the validated Fagerstrom score [13] was also inversely associated with troponin levels. Our results, therefore, provide evidence of a dose-response relationship, suggesting that the observed associations may be causal. Our study further confirms the results of prior studies showing smoking as one of the main cardiovascular risk factors associated with lower hs-cTnI levels [6; 7]. Our results underline these findings for a group of young (25-41 years old) and healthy adults from the general population The level of cardiac troponin hs-cTnI is low in the studied population of smokers, and there are no significant differences in troponin values between the compared groups. These findings are somewhat paradoxical since smoking is a strong cardiovascular risk factor and higher troponin levels are also associated with a worse cardiovascular risk profile and worse cardiovascular outcomes [1; 18]. However, given the known adverse health effects of smoking, it is very unlikely that this association reflects a protective effect. More likely, negative feedback mechanisms produced by smoking could be a mechanistic for the perception of low hs-cTnI levels in circulation that induce an increase in its production at the level of myocardium, causing damage to the myocardial cell. Additionally, other mechanisms could be involved that will need more clarification in future investigations. Whether the small differences observed between groups should lead to different reference value ranges of hs-cTn concentrations is currently unclear and should be evaluated in future studies [19; 20; 21]. Given the small differences and the fact that most routine laboratories cannot detect these troponin levels, we expect a small clinical impact. The strengths of our study are the large sample size of well-characterized young and healthy adults with a relatively short life-time exposure to environmental confounders within a population-based study design. The potential limitations of our dataset include its cross-sectional design, the fact that most of the study population was white, and the fact that all smoking information was self-reported. These hamper the widespread generalizability of our results.