Childhood appendectomy, tonsillectomy, and risk for premature acute myocardial infarction--a nationwide population-based cohort study

Abstract

Although inflammation contributes to cardiovascular disease, the associations of appendectomy and tonsillectomy, which remove mucosa-associated lymphoid tissue, with risk of acute myocardial infarction (AMI) are unknown. Our aim was to assess the association between these operations performed in childhood and AMI risk later in life. We conducted a prospective matched cohort study among all Swedish residents born between 1955 and 1970. A national register identified all appendectomies and tonsillectomies. For each patient undergoing appendectomy or tonsillectomy, we randomly selected five controls without the history of the respective operation, matched on sex, age, and county of residence. Participants were followed for fatal and non-fatal AMI for an average of 23.5 years. Because appendiceal and tonsillar tissues have reduced function after adolescence, our primary analyses were restricted to individuals below age 20 at the time of surgery (54 449 appendectomies and 27 284 tonsillectomies). We derived hazard ratios (HRs) from proportional hazard models adjusted for parental occupation and parental history of AMI. Operations before 20 years of age were associated with an increased risk for AMI (417 and 216 events in the appendectomy and tonsillectomy datasets, respectively), with adjusted HRs of 1.33 [95% confidence interval (CI), 1.05–1.70] for appendectomy and 1.44 (95% CI, 1.04–2.01) for tonsillectomy. This association was graded, with the highest risk among those undergoing both procedures, and generally similar among both males and females. Appendectomy and tonsillectomy performed at or above 20 years of age were not associated with the risk of AMI. We found a higher risk of AMI related to surgical removal of the tonsils and appendix before age 20. These results are consistent with the hypothesis that subtle alterations in immune function following these operations may alter the subsequent cardiovascular risk, but further studies are needed to confirm these findings and to explore possible mechanisms.