Cardiovascular
Although diabetes remains a predictor of major limb amputation in chronic limb-threatening ischemia patients, smoking history may need to be more carefully considered Sydney Browder* Sydney Browder Teresa Filipowicz Nicole Kelly Katharine McGinigle
Objective:
Smoking and diabetes are clear risk factors for peripheral artery disease and its worst form, chronic limb-threatening ischemia (CLTI). Although the co-occurrence of smoking and diabetes increases poor outcomes in general, the combined effect of these factors on the risk of major limb amputation has yet to be quantified in a CLTI population.
Methods:
This was a secondary data analysis of PREVENT III, a randomized controlled trial of CLTI patients undergoing bypass surgery from 2001-2003. Smoking status was defined as never, former, or current and history of diabetes was binary. Interaction between smoking and diabetes was assessed using a likelihood ratio test (LRT; α=0.05). We used crude generalized linear models to estimate stratum specific risks of limb amputation at 1 year and calculate RRs.
Results:
The 1,421 participants were mean age 68±12 years, 27% non-White, 36% female, 74% former or current smokers, and 64% had diabetes. Within 1 year, 31% had a limb amputation. There was no significant interaction between smoking and diabetes (LRT=1.84; p=0.175). Current smokers without diabetes were the least likely to have an amputation (15%) and never smokers with diabetes were the most likely (44%) [Diff (95%CI) = 29% (21%, 36%), p<0.001]. Diabetics were more likely to have an amputation compared to non-diabetics, regardless of smoking status, while ever smokers were less likely to have an amputation compared to never smokers (Figure 1).
Conclusions:
Ever smokers had a lower risk of amputation compared to never smokers which was not originally hypothesized. We considered two explanations: 1) never smokers are less likely to develop CLTI than ever smokers; therefore, never smokers who develop CLTI may have more aggressive/extensive disease and 2) ever smokers are less likely to survive to experience a major amputation than never smokers (survivor bias). Covariate selection should be carefully considered when studying CLTI and other advanced, chronic diseases.
