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Although the adverse effects of systemic glucocorticosteroids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, MSc, a researcher at the Center for Epidemiology Versus Arthritis in the Center for Musculoskeletal Research at the University of Manchester, United Kingdom, conclude that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Costello and colleagues' study were published June 27 in Rheumatology.

"While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed," Costello told Medscape Medical News.

To better understand the possible association, Costello and colleagues identified 17,760 patients who were newly diagnosed withRA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the UK population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7421 (41.8%) were prescribed GCs during post-diagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1000 person-years (95% CI, 62.5 65.7). There were 6243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1321 patients developed hypertension, for an IR of 87.6 per 1000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10 1.24).

The researchers note that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. "Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease," they write.

They note that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

"There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don't currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease," said Costello.

"Glucocorticoids increase fluid retention and promote obesity and hypertension," said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. "So patients need to be monitored for these risk factors," he told Medscape Medical News.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, "That specific link has been difficult to tease out since RA patients are often on multiple medications."

In regard to the role of dosage, Bhatt said that hypertension risk increases with higher GC doses, as the UK study indicates, and usually subsides when patients stop using GCs.

"Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses," Costello added.

In regard to using drugs that are less cardiotoxic than CGs, Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. "All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible," he said.

Costello and colleagues note that their results are consonant with earlier research, including a single-center cross-sectional study in which less than 6 months' use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published this week found that even short-term courses of a few days' duration entail risks for serious adverse events.

Costello's group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Center for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Center. Coauthor Dixon has received consultancy fees from Google and Beyer unrelated to this study. Bhatt has disclosed no relevant financial relationships.

Rheumatol. Published online June 27, 2020. Full text

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Steroids Linked to Increased Hypertension in RA - Medscape

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