Incident Hypertension Associated With Continuous NSAID Use in Ankylosing Spondylitis

Knee osteoarthritis linked to risk of hypertension
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Researchers investigated the association of NSAID use with the development of incident hypertension in a cohort of patients with ankylosing spondylitis.

The continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with the development of incident hypertension in patients with ankylosing spondylitis (AS), compared with patients with AS who reported noncontinuous or no NSAID use, according to research results published in Arthritis Care and Research.

Researchers investigated the link between NSAID use and the development of incident hypertension in a prospective, observational cohort of patients with AS. Longitudinal data from the Prospective Study of Outcomes in AS (PSOAS) were included, with patients who were aged ≥18 years and met the modified New York criteria for AS recruited from investigators’ clinics, patient support groups, and community rheumatologists.

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Overall, 834 patients with AS from the PSOAS cohort, with at least 1 year of follow-up, were included. After excluding the data of patients with missing NSAID index and baseline hypertension, the final cohort included 628 patients. The mean age at study entry was 39±13 years; 72% of patients were men, and 80% were white. At study entry, the mean symptom duration was 16±12 years and mean AS Disease Activity Score (DAS) was 2.0±0.9. A total of 43% of patients were being treated with biologic medications (primarily tumor necrosis factor inhibitors [TNFis]), and 7% were being treated with glucocorticoids.

Of the 628 patients, 200 reported continuous NSAID use on the NSAID index, and 428 reported low dose or no NSAID use. Patients who received NSAIDs at baseline had significantly higher disease activity and elevated C-reactive protein levels. Compared with number of patients in the continuous NSAID use group, a greater number of patients in the  noncontinuous or no NSAID use group were being treated with biologic therapies (33% vs 47%; P <.001).

Over a median of 7 years of follow-up (interquartile range, 5.2), a new diagnosis of hypertension was reported in 129 patients. Of these patients, 52 (40%) reported continuous NSAID use at baseline, 60 (47%) were receiving TNFis, and 21 (16%) were receiving both continuous NSAIDs and TNFis.

After adjusting for study site, age, sex, race, body mass index (BMI), TNFi use, and ASDAS, investigators indicated that continuous NSAID use was associated with an increased risk for incident hypertension, compared with noncontinuous or no NSAID use (hazard ratio [HR], 1.12; 95% CI, 1.04-1.20). Other significant predictors of incident hypertension included baseline age and a BMI indicative of obesity (HRs, 1.07 and 3.24; 95% CI, 1.06-1.09 and 1.86-5.63, respectively). In subgroups defined by age, BMI, disease activity, or TNFi use, the association did not differ.

Similar results were found across multiple sensitivity analyses. All models found that both continuous NSAID use and greater age at study entry were significant predictors of incident hypertension. However, the researchers noted that both TNFi use and disease activity were statistically significant predictors of incident hypertension in the complete case analysis (HRs, 1.08 and 1.09; 95% CI, 1.01-1.17 and 1.04-1.14, respectively).

Overall, compared with noncontinuous or no NSAID use, continuous NSAID use was linked to an increased risk by 12% for the development of incident hypertension in ankylosing spondylitis.

Study limitations included a limited ability to make causal inferences due to the observational nature of the study, potential residual confounding, missing study data, and the prospective cohort study design.

“This study highlights the potential negative [cardiovascular] effects of first-line pharmacological therapy for AS,” the researchers concluded. “Due to the paucity of available data, current guidelines do not specifically address the prevention or management of [cardiovascular disease] in individuals with AS. There is an unmet need to clarify how treatment choices…impact [cardiovascular] risk factors…and events in AS.” They added that further studies focusing on precision medicine and risk and benefit prediction are needed.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Liew JW, Ward MM, Reveille JD, et al. Nonsteroidal anti-inflammatory drug use is associated with incident hypertension in ankylosing spondylitis [published online September 17, 2019]. Arthritis Care Res. doi:10.1002/acr.24070