Abstract Body (Do not enter title and authors here): Background:
Hypertension-mediated organ damage (HMOD) can develop concurrently in the heart, the brain, the kidneys and the vasculature, yet most research still relies on counting the number of affected systems or recording the presence versus absence of multi-organ damage, approaches that overlook the complex, multisystem nature of HMOD.
Objective:
To identify HMOD profiles in adults with hypertension and to quantify sex-specific differences.
Methods:
We analyzed 4,787 UK Biobank participants with physician-diagnosed or self-reported hypertension (mean ± SD age 57.4 ± 6.8 years; 41.6 % women). Twenty-two continuous indicators, assessed at baseline or first follow-up and spanning cardiac structure and function, vascular stiffness, brain integrity (white-matter hyperintensity volume and fractional anisotropy), and renal function, were log-transformed and entered into latent profile analysis (LPA). Sex differences in profile membership were subsequently examined.
Results:
A four-profile solution (entropy = 0.86) best balanced statistical fit with clinical interpretability. The largest profile, comprising 38.0% participants, showed modest arterial stiffness and mild concentric left-ventricular remodeling with largely preserved cerebral and renal integrity; males were more common in this group (17% females vs 53.2% males, p < 0.001). A second profile (37.6%) was marked by heightened autonomic tone, micro-albuminuria and subtle micro-structural brain changes without overt cardiac dysfunction (65.4% females vs 17.6% males, p < 0.001). The third profile (22.1 %) combined QRS prolongation, elevated cystatin-C and albumin-creatinine ratio, and a higher burden of white-matter hyperintensities, indicating a cardio-neuro-renal stress pattern (15.3% females vs 27.1% males, p < 0.001). The smallest profile (2.2 %) exhibited pronounced ventricular dilatation, reduced ejection fraction, rapid ventricular rate and marked QRS widening, consistent with cardiac overload and dysfunction; (2.4 % females vs 2.0% males).
Conclusion:
LPA identifies four biologically coherent HMOD profiles. Most males fall into a mild vascular–cardiac strain profile, underscoring the need for optimized blood pressure control and arterial stiffness monitoring. Most females cluster in an autonomic–renal–cerebral stress profile with preserved cardiac function, indicating that early renal and neurovascular surveillance should be prioritized for them even when conventional cardiac indices appear normal.