Testing for cardiovascular autonomic neuropathy (CAN), which manifests in patients with schizophrenia, may ease detecting early stages of cardiovascular disease (CVD) in these patients, according to research published in the Nordic Journal of Psychiatry.

The researchers conducted a cross-sectional study at the Department of Cardiology at Aalborg University Hospital in Denmark, collaborating with Psychiatry-Aalborg University Hospital, from December 2015 to May 2017.

The researchers included 46 adult patients who had had schizophrenia for more than 10 years from an ongoing observational study whom they age-matched (within 5 years) and sex-matched to controls who did not have psychiatric disease or diabetes.

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The researchers conducted CAN assessments with the hand-held VagusTM device, which records single lead electrocardiogram (ECG) traces that calculate heart rate variability (HRV). They asked participants to stop smoking, eating, and drinking caffeinated liquids at least 2 hours prior to their recording ECG in 3 cardiac reflex tests (CARTs). The tests they conducted were response-to-standing (RS) after lying still for 5 minutes, expiration-to-inspiration (EI) after resting for 5 minutes and taking 6 deep breaths, and Valsalva maneuver (VM), which involved forcibly exhaling into a manometer at a pressure of 40 mmHG for 15 seconds.

HRV was defined as the ratio of the longest interval to the shortest interval between heartbeats and adjusted for age. The researchers obtained CAN scores (no, early, and manifest) through scoring the results of CARTS.

Comparing the baseline data of each group, vastly more patients with schizophrenia were active smokers (87%) than were the control group members (29%). More patients with schizophrenia had obesity (38%) and were in treatment for diabetes (17%) compared with the control group (11%, 0% respectively) (P =.005, P =.003, respectively).

Patients with schizophrenia had significantly higher manifest CAN (39%) and early CAN (22%) than the group of healthy controls (6%, 9%, respectively, P <.0001 for both sets of results).

In the sensitivity analysis, researchers compared patients with schizophrenia who were not diagnosed with diabetes with the healthy controls and found similar results (37% vs. 5% for controls, P <.0001).

Limitations of the study included that the number of incomplete CARTs was higher in the schizophrenia group and that the control sample was not truly generalizable.

“CAN is common in patients with schizophrenia irrespective of diabetes status,” the researchers wrote. “Testing for CAN is feasible and might be a new clinically tool for detecting early stages of CVD in patients with schizophrenia.”

Disclosure: One researcher is a co-inventor of the medical device VagusTM and declared affiliation with Medicus Engineering. Two other researchers declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Omar M, Wieben ES, Polcwiartek C, et al. Cardiovascular autonomic neuropathy in patients with schizophrenia. Nordic J of Psychiatry. Published online April 7, 2021. doi:10.1080/08039488.2021.1902566