Wednesday, 24 Apr 2019

You are here

Resistant Hypertension Common in SLE

Rates of resistant hypertension were doubled among patients with systemic lupus erythematosus (SLE), significantly increasing their mortality risks, a retrospective single-center study found.

Among patients with SLE, the prevalence of resistant hypertension was 10.2% compared with 5.3% among controls (OR 2.02, 95% CI 1.60-2.55, P<0.0001), according to Cecilia P. Chung, MD, and colleagues from Vanderbilt University in Nashville.

And after adjustment for age, sex, race, creatinine, and the presence of baseline end-stage renal disease (ESRD), the hazard ratio for mortality was 2.91 (95% CI 1.60-5.29, P<0.001), the researchers reported online in Arthritis Care & Research.

Patients with SLE have a five-fold greater prevalence of cardiovascular events compared with the general population, which is not fully attributable to conventional cardiovascular risk factors such as smoking and obesity. A novel risk factor could be resistant hypertension, which has been associated with an increase of >40% in coronary artery disease and an almost 60% increased rate of stroke in the overall population.

"Despite the recognition that resistant hypertension increases cardiovascular risk substantially in the general population, there is no information regarding the incidence, prevalence, and associated factors in patients with SLE or its consequences in routine clinical practice," Chung and colleagues wrote.

Accordingly, they reviewed the electronic health records of patients seen at Vanderbilt University Medical Center from 1989 to 2017, identifying 1,044 patients with SLE and 5,241 age-, sex-, and race-matched controls.

Resistant hypertension was defined as blood pressure uncontrolled on three antihypertensive medications after at least 1 month of treatment, or requiring four or more antihypertensives to attain control.

Compared with controls, patients with SLE had higher levels of creatinine, lower estimated glomerular filtration (EGFR) rates, and more often had hypertension at baseline. They also had lower HDL cholesterol and higher triglycerides, whereas controls had higher total cholesterol and LDL cholesterol levels.

Among SLE patients, 40% had used azathioprine, 32% had been treated with mycophenolate mofetil (CellCept), and 10% had been given cyclophosphamide.

There were 63 incident cases of resistant hypertension among SLE patients during 6,200 patient-years of follow-up and 207 during 33,686 person-years of follow-up among controls. The incidence rates were 10.1 versus 6.2 per 1,000 person-years among cases and controls, respectively, for a hazard ratio of 1.67 (95% CI 1.26-2.21, P=0.0004), which remained significant after adjustment for calendar year, ESRD at baseline, and creatinine (HR 1.72, 95% CI 1.28-2.30, P<0.001).

The researchers then compared 106 SLE patients who had resistant hypertension at any time with 938 SLE patients who never developed resistant hypertension, finding that those who did were older (47 vs 41) and more often were black (45.3% vs 21%, P<0.001). They also were more likely to have been treated with prednisone (83% vs 72.2%, P=0.017) or a calcineurin inhibitor (16% vs 6.8%, P<0.001), and to have higher creatinine, total cholesterol, and triglycerides, but lower EGFR rate.

In a further analysis, these factors were associated with incident resistant hypertension:

  • Black race: HR 3.43 (95% CI 2.66-4.42, P<0.0001)
  • Older age: HR 1.05 (95% CI 1.04-1.06, P<0.0001)
  • Creatinine: HR 1.15 (95% CI 1.07-1.23, P=0.0001)

"These findings indicate that resistant hypertension may be an important and previously unrecognized cardiovascular risk factor in SLE patients," Chung and colleagues wrote.

The observation that black patients were more likely to develop resistant hypertension could relate to the greater frequency of nephritis and ESRD in this group, and also their increased risks of obesity, salt sensitivity, and high stress levels.

The pathogenesis of resistant hypertension in SLE has not been examined, but might relate to inflammation and the consequent use of prednisone and calcineurin inhibitors, which can worsen hypertension, the researchers explained.

"Our findings support the notion that both primary care and specialty physicians need to recognize resistant hypertension in SLE as a predictor of increased mortality, which warrants close monitoring and potentially aggressive management," they concluded.

A limitation of the study was the unavailability of information about medication adherence, which often is poor in SLE.

The study was supported by the Rheumatology Research Foundation, the Vanderbilt University School of Medicine's Research Immersion Program, the Vanderbilt Institute for Clinical and Translational Research, the Vanderbilt University Medical Center's Synthetic Derivative, the NIH, the Lupus Research Alliance, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Chung and co-authors disclosed no relevant relationships with industry.

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

Add new comment

More Like This

Improved Survival in Lupus

A longitudinal study of systemic lupus erythematosus (SLE) from the Toronto Lupus Clinic has shown that mortality has decreased over time.

The cohort incuded 1732 SLE patients followed between 1971 and 2013. The cause of death was gleaned from death certificates, autopsy reports, hospital records or the records of the family physicians.  

EULAR 2019 Update to Lupus Management

The goal of SLE treatment is remission or low disease activity and flare prevention. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. Glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent). Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can be tailored to the clinical scenarios and may allow for tapering or discontinuation of GC.

Mortality Risk Factors in Systemic Sclerosis

A French cohort study of 625 systemic sclerosis (SStc) patients has found a significantly increased mortality risk that can be predicted by common clinical variables.

In addition to a multicenter prospective study, investigators performed a metanalysis on SSc standarized mortality ratios (SMR) and hazard ratios of prognosis factors.

Better Tests Ahead in Lupus

The advent of "big data" and "-omics" technologies offers hope that clinicians will soon have better diagnostics for systemic lupus erythematosus, rheumatologists here were told.

GCA Relapse Risk High with Steroids

Prior to the introduction of tocilizumab to manage giant cell arteritis (GCA), glucocorticoids (GC) have been the mainstay of therapy, but has been limited by relapses in disease. A recent metanalysis shows that relapses occur in nearly half of patients and are related to the duration of therapy rather than the initial dose of GC.

A literature review found 34 studies (2,505 patients) from 8 RCTs of GCA patients only treated with GC.