Cumulative tobacco consumption has a dose-dependent effect on atheromatosis burden and improves severe atheromatosis prediction in asymptomatic middle-aged individuals: The ILERVAS study

Atherosclerotic cardiovascular disease (ASCVD) is a progressive condition where atheroma plaques develop in the artery walls, and it is usually widely extended when an adverse event occurs. The association of the atheroma plaque with future cardiovascular events has been extensively confirmed [1]. Thus, early detection of subclinical atheromatosis is of paramount importance to prevent cardiovascular events.

Vascular ultrasound is a non-invasive imaging technique that can detect the presence and estimate the burden of ASCVD. Atheroma plaque detection improves cardiovascular risk assessment in asymptomatic individuals. Indeed, the 2021 European Society of Cardiology guidelines recommend vascular ultrasounds as a tool to improve risk classification in patients at intermediate risk [2]. Carotid and femoral arteries are the most commonly explored vascular beds by vascular ultrasound. Strikingly, multiterritorial vascular ultrasound assessment determining the number of vascular territories with atheroma plaques, improves ASCVD risk assessment, since it is a strong predictor of future cardiovascular events [3] and cardiovascular mortality [4].

Cigarette smoking is still the first preventable cause of death worldwide, and is a well-known risk factor for cardiovascular events [5]. Although ASCVD is clearly involved in the pathophysiology of smoking-induced cardiovascular diseases [6], the mechanism accounting for these associations has not been fully elucidated. Smoking is associated with carotid intima-media thickness [7,8], coronary atherosclerosis [9], carotid and femoral atherosclerosis [[10], [11], [12]], peripheral artery disease [13], and increases the risk of intermittent claudication by 3- to 10-fold [14].

Cardiovascular mortality remains higher in females than in males [15]. Continued smoking is significantly more deleterious for females [16,17], and increases their risk up to 7-fold [18]. However, there is no information regarding the sex-specific impact of tobacco on atheromatosis burden. Thus, sex-stratified analyses are urgently required.

Current European guidelines on cardiovascular prevention use smoking habit (non-smoker vs smoker) as a clinical predictor to stratify ASCVD risk, but they omit information regarding the cumulative tobacco consumption (CTC) [2]. Therefore, the aims of current study are (i) to evaluate the sex-specific impact of CTC on atheromatosis localization and burden (number of vascular territories and total plaque area); and, (ii) to assess whether addition of CTC data improves severe atheromatosis (SA) risk prediction.

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