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NSAID Use Linked With Hypertension in Ankylosing Spondylitis

Continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) among patients with ankylosing spondylitis (AS) was associated with the development of incident hypertension, a prospective cohort study found.

After adjustment for factors including age, sex, race, body mass index, concurrent use of tumor necrosis factor (TNF) inhibitors, and disease activity, continuous NSAID use was associated with a modest 12% increase in risk of incident hypertension compared with noncontinuous or no NSAID use (HR 1.12, 95% CI 1.04-1.20, P<0.01), according to Jean W. Liew, MD, of the University of Washington in Seattle, and colleagues.

Other factors that predicted the development of hypertension included baseline age (HR 1.07 per year, 95% CI 1.06-1.09, P<0.01) and obesity (HR 3.24, 95% CI 1.86-5.63, P<0.01), the researchers reported online in Arthritis Care & Research.

Patients with AS are at increased risk for cardiovascular disease and mortality, and they have high rates of risk factors for these outcomes, including hypertension, which has a reported prevalence of 11-44%.

Current guidelines recommend NSAIDs as first-line therapy for AS, but these drugs are recognized as increasing the risk for hypertension. "Conversely, population-level data suggest that NSAID use in AS may be cardioprotective, possibly via their modulation of the chronic inflammatory state," the researchers wrote. "Better control of AS disease activity, in turn, may lead to increases in physical activity and improvements in CV risk parameters."

Therefore, to more fully examine the effects of NSAID use on hypertension, the investigators analyzed longitudinal data from the Prospective Study of Outcomes in AS cohort, which enrolled patients from 2002 to 2018 from five centers in the U.S. and Australia.

Patients were seen every 4 to 6 months, with assessments including disease activity and function, medications and dosages, and measurements of blood pressure and C-reactive protein levels.

NSAID use was quantified according to the NSAID index, in which a patient taking the full recommended dosage of an individual NSAID for the previous 6 months was given a score of 100, and a patient not taking any NSAIDs during that period had a score of zero. A score of 50 was used as the cutoff between high/continuous and low/nonuse.

The analysis included 628 patients without hypertension at baseline. Patients' mean age was 39, and most were white men. Mean duration of symptoms at baseline was 16 years, and mean AS Disease Activity Score was 2. Biologics (mostly TNF inhibitors) were being used by 43% of patients and glucocorticoids by 7%. Continuous NSAID use was reported by 200 patients, and noncontinuous or no use by 428.

Those who were taking continuous NSAIDs had higher disease activity and more often had elevated C reactive protein, while more patients with noncontinuous or no NSAID use were receiving biologics (47% vs 33%, P<0.001).

During a median follow-up of 7 years, 129 patients developed hypertension. A total of 40% of those patients had been taking continuous NSAIDs at baseline, 47% were using TNF inhibitors, and 16% were receiving both continuous NSAIDs and TNF inhibitors.

In contrast to continuous NSAID use, age, and obesity, factors that were not associated with incident hypertension included sex, race, disease activity score, and TNF inhibitor use.

While TNF inhibitor use did not reach statistical significance in that primary analysis (HR 1.07, 95% CI 0.99-1.16, P=0.09), sensitivity analyses found a significant association with hypertension, which was not what had been expected based on previous data showing a reduction in cardiovascular risk with greater suppression of inflammation. "The association of TNF inhibitor use and incident hypertension requires further clarification in future studies," which may require specialized statistical approaches such as with inverse probability of treatment weighting, the authors explained.

"The association of NSAIDs and incident hypertension remains particularly concerning, as the early development of hypertension may portend a higher risk of premature cardiovascular events due to cumulative exposure," they stated.

Further research should more fully explore the relationships between treatment choices and cardiovascular risk factors and events in patients with AS, and hopefully provide data for revision of treatment guidelines incorporating risks and benefits of medications used, they concluded.

Limitations of the study, Liew and co-authors said, included its reliance on observational data and the possibility of residual confounding by factors such as extra-articular disease manifestations.

The authors reported financial relationships with the National Institutes of Health, the Assessment of Spondyloarthritis Society, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Galapagos, AbbVie, Amgen, and the Spondylitis Association of America.

The author has no conflicts of interest to disclose related to this subject

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