Circulating Levels of Angiotensinogen, Sex, and Hormone Therapy - The Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundAngiotensinogen, the unique precursor of all angiotensin hormones of the Renin-Angiotensin-Aldosterone System (RAAS), is now a potential target in a novel pharmacological approach to hypertension. Investigating the factors that influence angiotensinogen levels, including sex hormones, may have important therapeutic implications. MethodsPlasma angiotensinogen and sex hormones levels were measured in 5,171 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Linear models were employed to determine the associations of angiotensinogen with sex hormones, and mediation analysis was performed to evaluate the effect of HT on blood pressure (BP) and hypertension through angiotensinogen. ResultsAngiotensinogen levels were significantly higher in postmenopausal women receiving HT (n=760) compared to women not receiving HRT (n=1,675) and in men (n=2,736). A positive association was present between angiotensinogen and estrogen levels that differed in magnitude between sexes and by HT status among postmenopausal women (women on HT: r=0.44, p< 0.0001; women not on HT: r=0.09, p=0.0002; and men: r= 0.07, p=0.0003). The type of HT formulation (estrogen or estrogen/progesterone) and its duration of use did not significantly affect angiotensinogen levels. HT indirectly increased systolic BP ({beta}=1.24) and the odds of hypertension (OR=1.065) through its effect of increasing angiotensinogen. ConclusionsA positive association was present between angiotensinogen and estrogen levels that differed by HT status. HT impacts systolic BP and hypertension indirectly by increasing angiotensinogen. This study underscores the role of angiotensinogen in hypertension, and the complex relationship between HT and hypertension.