The renin‐angiotensin‐aldosterone system and salt sensitivity of blood pressure offer new insights in obesity phenotypes

Objective Individuals who have metabolically healthy overweight/obesity (MHOO) do not have cardiometabolic complications despite an elevated BMI. Renin‐angiotensin‐aldosterone system (RAAS) activation and salt sensitivity of blood pressure (SSBP) are cardiovascular disease (CVD) risks, which are increased in individuals with higher BMI values. Little is known about the differences in RAAS activation and SSBP between MHOO and metabolically unhealthy overweight/obesity (MUOO) phenotypes. Methods We studied 1430 adults on controlled dietary sodium. Individuals in the MHOO group had BMI ≥ 25 kg/m 2 without comorbidities (e.g., diabetes, dyslipidemia, hypertension, CVD), whereas individuals in the MUOO group had BMI ≥ 25 kg/m 2 and at least one comorbidity. The control group included healthy individuals (BMI 18.5–24.9 kg/m 2 ). Results BMI was similar between the MHOO (28.9 kg/m 2 ) and MUOO groups (29.3 kg/m 2 ; p = 0.317). On liberal sodium, the MUOO group had activated RAAS compared with the MHOO group, including higher plasma aldosterone concentration (mean [SD], 1.11 [0.48] ng/dL; p = 0.020), plasma angiotensin II levels (4.11 [2.0] pg/mL; p = 0.040), and percentage of individuals with plasma renin activity ≥ 1.0 ng/mL/h (+3.6%; p = 0.017). The MUOO group had higher SSBP than the MHOO group (6.0 [1.9] mm Hg; p = 0.002). Applying a zero‐to‐six‐point metabolic health score found that a worse score was associated with higher measurements of RAAS activity and SSBP ( p < 0.001). Conclusions Compared to the MHOO group, the MUOO group was characterized by an increase in the following two CVD risk factors: higher RAAS activity and SSBP on controlled sodium diets. Therapeutic interventions targeting the effects of angiotensin II and/or aldosterone may offer cardiometabolic protection for individuals with the MUOO phenotype.