Long-term multisystem organ damage following hypertensive disorders of pregnancy across clinical risk subgroups: a UK Biobank study

Background Hypertensive disorders of pregnancy (HDP) are associated with increased long-term cardiovascular, cerebrovascular, and renal risk, yet pathways linking HDP to later organ damage remain poorly understood. Persistent vascular dysfunction after HDP and subsequent cardiovascular risk factors may contribute to long-term hypertension-mediated organ damage (HMOD). We evaluated associations between HDP and long-term cerebral, cardiac, vascular, and renal HMOD across clinically relevant risk subgroups. Methods In this UK Biobank matched cohort study, parous females with a history of HDP were matched 1:4 to females without HDP by age at first delivery and parity. HMOD was assessed using white matter hyperintensity volume, left ventricular ejection fraction, pulse wave arterial stiffness index, and urine albumin-to-creatinine ratio. Multivariate linear regression models adjusted for cardiovascular risk factors assessed associations between HDP and each HMOD marker. Analyses were stratified by subsequent hypertension, menopausal status, age ≥50 years, antihypertensive medication use, and time since HDP ≥10 years. Results Among participants (mean age 50 ± 7 years), HDP was not associated with white matter hyperintensity volume ( β = −0.31, 95% CI −1.04 to 0.41, p = 0.401), left ventricular ejection fraction ( β = 0.76, 95% CI −0.38 to 1.90, p = 0.193), pulse wave arterial stiffness index ( β = 0.14, 95% CI −0.36 to 0.64, p = 0.595), or urine albumin-to-creatinine ratio ( β = −0.12, 95% CI −0.51 to 0.26, p = 0.535) after multivariate adjustment. Subgroup analyses revealed an isolated significant adjusted association with lower log-transformed white matter hyperintensity volume among participants with subsequent hypertension ( β = −0.41, 95% CI −0.79 to −0.03, p = 0.033), while other associations were not consistently significant. Discussion HDP was not consistently associated with selected measures of long-term subclinical HMOD across clinically relevant subgroups. Established long-term cardiovascular and renal risks following HDP may not be uniformly reflected by HMOD markers assessed at a single time point later in life. Future longitudinal studies using repeated assessments are needed to identify which HMOD phenotypes emerge following HDP and whether they predict or mediate subsequent cardiovascular, cerebrovascular, and renal outcomes.