Influence of Low-Density Lipoprotein Cholesterol Levels on NSAID-Associated Cardiovascular Risks After Myocardial Infarction: A Population-Based Cohort Study

Abstract

Aim

To examine whether low-density lipoprotein cholesterol (LDL-C) levels influence the cardiovascular risk associated with non-aspirin non-steroidal anti-inflammatory drug (NSAID) use after myocardial infarction (MI).

Methods

Using Danish health registries, we conducted a population-based cohort study of all adult patients with first-time MI during 2010–2020 with an LDL-C value before discharge. Based on the latest LDL-C value, we categorized patients into a low and a high LDL-C group (<3.0 vs ≥3.0 mmol/L). We used time varying Cox regression to compute hazard ratios (HRs) with 95% confidence intervals of the association between NSAID use and a major adverse cardiovascular event (MACE: recurrent MI, ischemic stroke, and all-cause death).

Results

We followed 50,573 patients for a median of 3.1 years. While exposed, 521 patients experienced a MACE: 312 in the low LDL-C group and 209 in the high LDL-C group. The HRs for MACE comparing NSAID use with non-use were 1.21 (1.11–1.32) overall, 1.19 (1.06–1.33) in the low LDL-C group, and 1.23 (1.07–1.41) in the high LDL-group. The HRs for recurrent MI and ischemic stroke were comparable between the LDL-C subgroups. The HRs for all-cause death were 1.22 (1.07–1.39) in the low LDL-C group and 1.54 (1.30–1.83) in the high LDL-C group. Changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L showed consistent results.

Conclusion

In patients with MI, LDL-C levels did not influence the increased risk of MACE associated with NSAID use, but might influence the association between NSAID use and all-cause death.

Graphical Abstract

Keywords:

• cardiovascular disease
• non-steroidal anti-inflammatory drugs
• cholesterol
• low-density lipoprotein cholesterol
• myocardial infarction
• effect modification

Data Sharing Statement

Not allowed. No new data were generated in support of this research.

Ethical Approval

The use of data from the national registers was approved by the Danish Data Protection Agency through institutional registration (record number 2016-051-000001, Aarhus University record number 2016-051-000001-810). Ethical approval is not required for registry-based studies in Denmark.

Acknowledgments

This paper has been uploaded to Authorea as a preprint: https://www.authorea.com/doi/full/10.22541/au.169105324.49649214/v1. Department of Clinical Epidemiology, Aarhus University, receives funding for other studies in the form of institutional research grants to (and administered by) Aarhus University. None of these studies has any relation to the present study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

The project was supported by the Novo Nordisk Foundation (grant NNF19OC0054908). The funding organization did not have any role in the design and conduct of the study; in the collection, management, and analysis of the data; or in the preparation, review and approval of the manuscript.