Antidepressant Use and Risk of Myocardial Infarction: A Longitudinal Investigation of Sex-Specific Associations in the HUNT Study

Abstract

Objective: Antidepressants are thought to affect the risk of cardiovascular disease, although the nature of the association is unclear. Men and women have unique cardiovascular risk factors, and sex differences in depression as well as the efficacy of antidepressants are important to consider. We examined whether antidepressant use was associated with risk of having a myocardial infarction (MI) and whether this association was sex-specific. Methods: Data from The Trøndelag Health Study were used, gathered from a population in Norway (N = 31,765), collected from 1995 to 2008. These data were combined with the Norwegian Cause of Death Registry and the Norwegian Prescription Database. We performed logistic regression models to examine the association of antidepressant use on risk of having a fatal or nonfatal MI, adjusting for depression, anxiety, diabetes, systolic blood pressure, cholesterol, waist-hip ratio, smoking, age, and sex. Results are presented as odds ratios (ORs) and 95% confidence intervals in parentheses. Results: The results indicated that antidepressant use was associated with a reduced risk of having MI at a later date (OR = 0.49 [0.38-0.64]). Although this association was somewhat stronger for women (OR = 0.46 [0.31-0.68]) compared with men (OR = 0.53 [0.37-0.75]), analysis did not identify a sex-specific association of antidepressant use on MI. Follow-up analyses on different subtypes of antidepressants showed that both selective serotonin reuptake inhibitor and tricyclic antidepressant were associated with a reduced risk of MI. Conclusions: In this population study, the use of antidepressants was associated with a reduced risk of MI. This association was stronger for women, although we detected no interaction between sex and antidepressant use in terms of reduced risk of MI. Although limitations apply regarding causality, especially concerning a dose-response relationship, the results suggest that antidepressant use might reduce the risk of MI among both men and women.

Serotonergic Modulation of Neurovascular Transmission: A Focus on Prejunctional 5-HT Receptors/Mechanisms

“…This effect is clearly dependent on SERT function, as SERT knock-out mice are less prone to the chronic 5-HT-induced drop in blood pressure [134]. Interestingly, some clinical studies have shown that chronic inhibition of 5-HT reuptake by SERT inhibitors reduced the risk of a myocardial infarction [135], but an increase in blood pressure was recorded at night [136]. In this regard, in dogs, chronic oral treatment with fluoxetine does not affect mean arterial blood pressure (measured at diurnal time), but the capsaicin-induced trigeminal CGRP release (resulting in vasodilatation) is diminished at the craniovascular (external carotid) level [137]; this finding may help explain the mechanism of action of some SERT inhibitors to treat migraine.…”

Examining Antidepressant Use and Myocardial Infarction Risk in the HUNT Study

“…We read with great interest the article by Karlsen et al (1) that investigated the association between antidepressant use and risk of myocardial infarction (MI) in a Norwegian population ( N = 31,765) from the Trøndelag HUNT studies between 1995 and 2008. We appreciate the authors’ investigation and would like to offer further points of discussion, which we have done hereinafter.…”