Fig. 4: Histochemical analysis of skin from hypertensive patients and clinical correlates.

Panel a bars show mean ± 95% CI, with individual points (overlay); Na⁺ and K⁺ concentrations and water content in the epidermis/superficial dermis (ESD) and deep dermis (DD) layers, reflecting different architecture and cellularity. Panel b skin Na⁺ + K⁺ concentration in ESD and DD; red X = automatically detected outliers (ROUT, Q = 1%); in virtually no patient, including n = 3 cases with primary aldosteronism, did [Na⁺ + K⁺] exceed physiological values (grey). Panel c correlations of histochemical parameters in ESD and DD; Pearson ρ and statistical significance are colour coded as per legend. Panel d association of ESD water, [Na⁺] and [K⁺] with age, reflecting the development of oedema and the shift in ECV/ICV ratio; red X = automatically detected outlier; bottom: representative pictures of age-related reduction in skin cellularity; immunofluorescence, DAPI staining; scale bars (bottom right) = 200 μm. Panel e relationships between skin histochemical parameters, age, BMI, Na intake and pulse pressure (PP), plasma NT-proBNP and transepidermal water loss (TEWL), by skin layer. Data are presented as standardised B regression coefficients (95% CI); for skin histochemical parameters, coefficients for all patients are visualised in black, for males in blue, for females in pink. PP and NT-proBNP positive associations with ESD water accumulation were mostly driven by females; the association with Na⁺/K⁺ ratio was overall generalised to both layers and sexes. No significant associations were observed with TEWL, making relative local water deficit an unlikely explanation for any Na⁺ hypertonic excess. All panels refer to n = 76 samples from independent subjects; missing data due to technical issues or unavailable samples were ≤8 for all variables/correlations; source data are provided as a Source Data file.