Renin-to-Aldosterone Ratio Is Associated with Ambulatory Blood Pressure Levels and Control in Treated Hypertensive Patients with Overweight or Obesity

Introduction: Combination therapy, including a renin-angiotensin system inhibitor (RASi) and a thiazide diuretic (TZD) or a calcium channel blocker (CCB), is the first-line approach in hypertension management and modulates circulating markers of the Renin-Angiotensin-Aldosterone System (RAAS). Excess adiposity may induce renin-aldosterone axis dysregulation and contribute to blood pressure variability and treatment resistance. This study aimed to evaluate the association between the renin-to-aldosterone ratio (RAR) and ambulatory blood pressure monitoring (ABPM) in treated hypertensive patients with central overweight (OW) or obesity (OB). Methods: In a cross-sectional design, 97 adults with essential hypertension and OW/OB on stable RASi + TZD and/or CCB therapy were matched with 97 normal-weight hypertensive controls. All participants underwent 24-hour ABPM and orthostatic direct renin concentration (DRC) and plasma aldosterone concentration (PAC) measurements. RAR was calculated as the ratio between DRC and PAC. For the analyses values were normalized using natural logarithm (Ln). Results: LnRAR and LnDRC were inversely associated with 24-hour, daytime, and night-time ABP levels in controls, but not in OW/OB patients. However, higher LnRAR and LnDRC values were linked to greater odds of achieving ABP control in both OW/OB and normal-weight for 24h [LnRAR OR 1.74 (1.25-2.42), p=0.001 in OW/OB], daytime, and night-time periods, whereas LnPAC showed no significant associations. Two-way ANOVA confirmed that patients with controlled ABP had higher median LnRAR and LnDRC values than those with uncontrolled ABP, regardless of weight status (p for interaction >0.05). Conclusion: RAR, primarily driven by higher DRC levels and likely linked to a pharmacologic response to RAS inhibition, shows a mechanism-based association with ABP control in treated hypertension, regardless of the presence of visceral obesity.