Research Article|Articles in Press

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


      • CTC provokes a higher risk of atheromatosis in femoral arteries than in carotids.
      • CTC had a dose-dependent effect on atheromatosis burden similar in both sexes.
      • Addition of CTC to the SCORE2 model improved severe atheromatosis (SA) prediction.
      • Age and CTC were the most important clinical predictors of SA in both sexes.


      Background and aims

      Sex-specific impact of cumulative tobacco consumption (CTC) on atheromatosis extension and total plaque area remains unknown. We aimed to determine the impact of CTC in atheromatosis localization and burden.


      We performed a cross-sectional analysis in 8330 asymptomatic middle-aged individuals. 12-territory vascular ultrasounds in carotid and femoral arteries were performed to detect atheromatous plaque presence and to measure total plaque area. Adjusted regressions and conditional predictions by smoking habit or CTC (stratified in terciles as low (≤13.53), medium (13.54–29.3), and high (>29.3 packs-year)) were calculated. Severe atheromatosis (SA, ≥3 territories with atheroma plaque) was predicted with the Systematic COronary Risk Evaluation 2 (SCORE2) model. The improvement of SA prediction after adding CTC was evaluated.


      CTC was associated with an increased risk of atheromatosis, stronger in femoral than in carotid artery, but similar in both sexes. A dose-dependent effect of CTC on the number of territories with atheroma plaque and total plaque area was observed. Addition of CTC to the SCORE2 showed a higher sensitivity, accuracy, and negative predictive value in males, and a higher specificity and positive predictive value in females. In both sexes, the new SCORE2-CTC model showed a significant increase in AUC (males: 0.033, females: 0.038), and in the integrated discrimination index (males: 0.072; females: 0.058, p < 0.001). Age and CTC were the most important clinical predictors of SA in both sexes.


      CTC shows a dose-dependent association with atheromatosis burden, impacts more strongly in femoral arteries, and improves SA prediction.

      : NCT03228459.

      Graphical abstract


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