Impact of smoking on premature vascular aging in a cohort of healthy men with erectile dysfunction

Background Vascular aging in smokers is a multi-factorial process, driven by traditional cardiovascular risk factors that mostly rely on cumulative tobacco exposure. While this is standard clinical practice, it may fail to identify early subclinical signs suggesting early-onset vascular decay. This study aimed to evaluate premature functional and structural markers that can predict vascular dysregulation at earlier stages than classic risk-factor assessment, before structural remodeling appears. Methods A total of 386 active healthy smokers (mean age: 52±14 years) with ultrasonographically documented vasculogenic erectile dysfunction (ED), without known cardiovascular disease underwent a multi-modal vascular assessment, which included carotid Intima-Media Thickness (IMT) measurements to evaluate structural remodeling, carotid-femoral Pulse Wave Velocity (PWV) values as an indicator of arterial stiffness, and brachial Flow-Mediated Dilation (FMD) metrics to estimate endothelial dysfunction. Results Participants were further subdivided into two groups based on carotid IMT values: Normal wall thickness (IMT ≤ 0.9 mm, N = 224) and increased IMT (IMT > 0.9 mm, N = 162). Compared to smokers with normal carotid wall thickness, smokers with increased IMT exhibited substantially worse vascular profiles, regarding impaired endothelial function (2.44 ± 1.29% vs. 3.41 ± 1.58%, p < .001) and higher arterial stiffness (9.53 ± 1.47 vs. 8.54 ± 1.44 m/s, p < .001). Notably, even smokers with normal carotid IMT exhibited impaired FMD (mean value of 3.41%), suggesting that a significant endothelial impairment precedes overt structural atherosclerosis. In correlation analysis, FMD and PWV demonstrated a significant inverse correlation (r = -0.261, p < .001), and when tailored to pack-years, no apparent linear relationship with FMD or PWV was observed, indicating a dose-independent outcome (figure). The above-mentioned associations remained statistically significant after adjusting for age, body mass index, lipid profile and mean arterial pressure (aR2 = 0.237, p < .001). Conclusion Vascular decay in smokers appears to follow a worsening trajectory that, however, can be identified in earlier stages using the vascular function biomarkers. While IMT is a later-stage indicator of vascular remodeling, FMD and PWV can detect changes in functional properties of normally structured arteries before macroscopic changes emerge. These findings suggest that relying solely on smoking history or structural imaging may underestimate early functional impairment of the vasculature. Clinicians should consider functional assessments (FMD/PWV) to better capture the total cardiovascular burden in smokers. It is also evident that, despite accumulated tobacco exposure, cigarette smoking—even at any extent—is sufficient to initiate a premature process of vascular aging.