Smoker’s pseudoparadox: Age difference explains benefit of smoking in AMI

Controlling for patient age eliminates the often-observed association between smoking and better clinical outcomes in acute myocardial infarction (AMI), according to a recent Singapore study.

“[W]e found that smokers seemingly had better clinical outcomes (30-day and 1-year mortalities) after ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI),” the researchers said. “However, upon adjustment, the seemingly beneficial effects of smoking on mortality disappeared and the risk of recurrent MI within 1-year was significant higher in … smokers, confirming the presence of a smokers’ pseudoparadox.”

Drawing from the Singapore Myocardial Infarction Registry (SMIR), the researchers retrieved de-identified data of 21,261 AMI patients, of whom 12,307 had STEMI and 8,954 had NSTEMI. All participants were treated with percutaneous coronary intervention (PCI). Study outcomes included all-cause mortality and first MI episode within a year after PCI.

Majority of the participants were either current (n=6,055) or former (n=1,703) smokers; 4,549 never smokers were also included. At baseline, never and former smokers were of comparable median ages, but current smokers were significantly younger by approximately 8 years. [Sci Rep 2021;11:6466]

Unadjusted Cox regression analysis revealed that in STEMI patients, current smokers were 50-percent less likely to die within 30 days (hazard ratio [HR], 0.50, 95 percent confidence interval [CI], 0.43–0.59) or 1 year (HR, 0.50, 95 percent CI, 0.44–0.57) as compared with never smokers.

A similar and stronger effect was reported in the NSTEMI subgroup, where the risk of death within 30 days dropped by nearly 70 percent (HR, 0.32, 95 percent CI, 0.22–0.48), and death within 1 year by over 50 percent (HR, 0.45, 95 percent CI, 0.37–0.56), in current vs never smokers. The risk of recurrent MI within a year was also suppressed among current smokers (HR, 0.68, 95 percent CI, 0.56–0.81).

However, upon multivariable adjustment, the protective effect of smoking disappeared in both patient subgroups.

Among STEMI patients, for example, adjusted HRs for death within 30 days and 1 year were 0.84 (95 percent CI, 0.64–1.10) and 1.00 (95 percent CI, 0.80–1.24), respectively. Notably, taking confounders into account also revealed that recurrent MI within a year was almost 40 percent more likely among current vs never smokers (adjusted HR, 1.39, 95 percent CI, 1.06–1.81).

A similar effect was found in NSTEMI patients, with adjusted HRs for 30-day and 1-year death and 1-year recurrent MI of 0.78 (95 percent CI, 0.45–1.35), 1.00 (95 percent CI, 0.74–1.35), and 1.46 (95 percent CI, 1.13–1.89), respectively.

“The role of cigarette smoking on the outcomes of STEMI and NSTEMI patients remains controversial and has implications on public health,” the researchers said, noting that current findings do not support the often-observed smoker’s paradox among AMI patients, and instead point to a pseudoparadox, suggesting that age has been an under-appreciated confounder in this population.

Nevertheless, important limitations need consideration, they added. “[T]he SMIR database does not contain information on the duration of smoking and the number of cigarettes the smokers consume. Additionally, the SMIR does not include the information on how long it has been after the former smokers quit their smoking behavior,” limiting the generalizability of the present findings.