Reduced 24-hour heart rate variability in neurosyphilis: a retrospective case-control study

Neurosyphilis may involve central or peripheral autonomic pathways, but its association with cardiac autonomic regulation has not been systematically evaluated. We compared 24-h heart rate variability (HRV) between patients with neurosyphilis and controls without known neurologic disease and examined daytime-to-nighttime changes and associated clinical factors.

This single-center retrospective case-control study included 98 patients with neurosyphilis and 53 controls, all of whom underwent 24-h Holter monitoring. The primary endpoint was the standard deviation of all normal-to-normal intervals over 24 h (SDNN). Log-transformed HRV measures were analyzed using multivariable linear regression adjusted for demographic characteristics, vascular and metabolic risk factors, smoking status, and renal function. Multiple comparisons across secondary endpoints were controlled using the Benjamini-Hochberg procedure. Linear mixed-effects models evaluated daytime-to-nighttime changes, and exploratory analyses examined neurologic involvement and disability in patients with neurosyphilis.

Median 24-h SDNN was 112.5 ms in the neurosyphilis group and 128.0 ms in controls. After multivariable adjustment, SDNN was 15.3% lower in the neurosyphilis group [geometric mean ratio (GMR), 0.847; 95% confidence interval (CI), 0.773-0.928; p < 0.001]. Five of seven secondary time and frequency-domain endpoints were also lower after correction for multiple comparisons, whereas the ratio of low-frequency to high-frequency power did not differ significantly between groups. The nighttime increase in the root mean square of successive differences (RMSSD) was smaller in the neurosyphilis group (group-by-period interaction GMR, 0.854; 95% CI, 0.747-0.975; false discovery rate-adjusted p = 0.030). Among patients with neurosyphilis, each 1-point higher admission modified Rankin Scale score was associated with an 8.2% lower SDNN (GMR, 0.918; 95% CI, 0.881-0.956; p < 0.001). The primary estimate was similar after additional adjustment for mean heart rate and sleep quality, inverse probability of treatment weighting, and exclusion of participants with diabetes or patients with major neurologic involvement.

Neurosyphilis was associated with lower values across several time and frequency-domain measures of 24-h HRV. Lower RMSSD and high-frequency power and a smaller nighttime increase in RMSSD were consistent with attenuation of vagally mediated short-term HRV.