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Cardiovascular Autonomic Neuropathy Associated with Impaired Quality of Life in Patients with Lupus

Patients with systemic lupus erythematosus presented more cardiovascular autonomic neuropathy, along with impaired health-related quality of life and parasympathetic function, when compared with a control cohort.

Cardiovascular autonomic neuropathy (CAN) was frequently self-reported in patients with systemic lupus erythematosus (SLE) and associated with impaired health-related quality of life (HRQoL), according to a study published in BMJ Journals.1 Further, this patient population showed impaired parasympathetic function, even without CAN, when compared with a control cohort.

“Dysfunction of the autonomic nervous system (ANS) is increasingly studied in rheumatic diseases, including SLE,” stated investigators. “Dysfunction of the ANS may present as impaired cardiovascular regulation, denoted as CAN.”

In this cross-sectional, controlled study, CAN, which is assessed by heart rate variability (HRV) measures and cardiovascular autonomic reflex tests (CARTs), was measured in a group of patients with SLE and a group of healthy controls (HCs). Investigators used 5-minute HRV and 3 CARTs to understand parasympathetic and mixed sympathetic-parasympathetic function in these cohorts. HRQoL was determined by the self-reported Short Form 12 (SF-12) and split into a mental health component score with weighted scorings of 12 individual items. CAN was split up into 3 categories: no, early, or definitive.

A total of 111 patients were recruited from the Prospective Lupus Study on Cardiovascular Risk Factors (PLUSheart) between October 2018 and March 2019. Data from 100 control subjects were used for matching the SLE cohort. After exclusion criteria was applied, including cardiac arrythmias, and considering sex and age, 55 patients were matched in each cohort. These patients tended to be older, with a higher BMI, and a lower hip/waist ratio.

During the passive HRV test, patients relaxed for 5 minutes while the pattern of changes in R-peaks (RR intervals) and normal heart beats (NN intervals) were analyzed. Afterwards, 3 CARTs were performed, determining the response to standing (RS) ration, expiration inspiration (EI) ration, and Valsalva maneuver (VM) ration. CAN scoring was utilized in patients who completed >2 CARTs, with 2 or more abnormal CARTs being classified as definitive CAN and 1 abnormal CART signifying early CAN.

Within the 2 cohorts, CAN was present in 24.1% of patients with SLE and 1.9% of HCs. HRV and CART scores were lower in patients with SLE controls (RS ratio: 14.3%, EI ratio: 5.7% and VM ratio: 11.1%.

Autonomic modulation was more prevalent in patients with SLE and no CAN when compared with the control group. Definitive CAN was reported in 24.8% of patients with SLE, and 57.8% had either definitive or early CAN.

When comparing patients with SLE and definitive CAN with patients without CAN, ANS was similarly associated with impaired modulation of parasympathetic nervous system (PNS) activity as well as mixed sympathetic nervous system (SNS)-PNS activity. The PNS and SNS-PNS were significantly lower in the group of patients with SLE and no CAN. Patients in the SLE cohort with definitive CAN presented signs of mixed sympathetic-parasympathetic dysfunction, while those without CAN and impaired parasympathetic activity. These dysfunctions were also linked to low physical SF-12 component scores.

The cross-sectional design limits the study by being unable to determine the natural of the course of autonomic dysfunction of SLE as well as the relationship of dysfunction and HRQoL. Additionally, sympathetic function measures, such as blood pressure CARTs, were not included in the study. However, this was the first study to show how ANS dysfunction can influence the physical symptoms of SLE, which may be a clinically useful way to show poor HRQoL that is not easily explained by traditional disease characteristics of this condition.

“We found that compared with controls, patients with SLE presented more frequently with CAN characterized by mixed parasympathetic/sympathetic impairment,” concluded investigators. “Furthermore, even in patients without clinical signs of CAN, we demonstrated impaired parasympathetic function. These impairments were in patients with SLE associated with self-report of poor physical quality of life.”


Zinglersen AH, Iversen KK, Leffers HCB, Laugesen E, Fleischer J, Jacobsen S. Characteristics of cardiovascular autonomic dysfunction and association with quality of life in patients with systemic lupus erythematosus. Lupus Sci Med. 2021;8(1):e000507. doi:10.1136/lupus-2021-000507