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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.