Haemodynamic uniformity in orthostatic hypotension: questioning the clinical relevance of aetiological subtypes

We read with great interest the study by Johansson et al.¹ which investigated the haemodynamic profiles of neurogenic (nOH), non-neurogenic (non-nOH), and mixed orthostatic hypotension (OH) using tilt table testing. The authors reported no significant differences in mean arterial pressure (MAP), heart rate, stroke volume, or total peripheral resistance responses among the three groups, challenging the clinical utility of OH subtyping. While this retrospective analysis provides valuable insights, several points merit further discussion.

First, the study underscores the complexity of OH pathophysiology. The high prevalence of mixed aetiology (50%) aligns with emerging evidence suggesting that autonomic dysfunction often coexists with cardiovascular comorbidities.^2,3 However, the absence of haemodynamic distinctions between subgroups raises critical questions. For instance, the log-ratio method, while innovative, may lack sensitivity to detect subtle autonomic variances, such as impaired baroreflex-mediated vasoconstriction in nOH.⁴ Future studies incorporating direct sympathetic activity measurements (e.g. microneurography) could clarify these mechanisms.

Second, the retrospective classification of OH aetiology based on clinical records introduces potential bias. Neurogenic causes, particularly secondary forms (e.g. diabetic neuropathy), often overlap with non-nOH factors (e.g. antihypertensive medications), complicating definitive categorization. A prospective design with standardized diagnostic criteria, as proposed by Fedorowski et al.⁵ would strengthen causal inferences.

Third, the small sample size (n = 52) limits statistical power. Larger cohorts are needed to validate the findings, especially given trends toward greater MAP reduction in nOH (−0.10 vs. −0.06 in mixed OH). Additionally, the tertiary care setting may over represent severe cases, limiting generalizability to community-based populations.⁶

In conclusion, Johansson et al. highlight the need to reconsider traditional OH classification. Their findings align with recent arguments that autonomic failure underpins most OH cases, regardless of aetiology.² However, refining diagnostic tools and adopting a multidimensional assessment framework—integrating clinical, haemodynamic, and neurophysiological data—remains essential for personalized management.