Abstract 75: Sex Differences in the Renin-angiotensin System In Middle Aged Adults at Risk for Stroke
Background/Objective: Angiotensinogen is the substrate for renin, which then converts angiotensinogen to angiotensin I. Sex differences in multiple components of the renin angiotensin system (RAS) have been described. We examined sex differences in angiotensinogen (Aogen) and renin activity in middle aged men and women at risk for stroke, accounting for sex hormone binding globulin and use of RAS-influencing drugs.
Methods: The Sex Age and Variation in Vascular functionalitY (SAVVY) study measured sex differences in subclinical vascular disease and biomarkers in men and women aged 45 to 64 with at least one stroke risk factor, but free of cardiovascular events using a cross-sectional design. Women were oversampled to assess pre- and post-menopausal time points. Aogen, renin activity, and sex hormone binding globulin (SHBG) were performed using commercial ELISAs/RIAs. We compared biomarker levels by sex using parametric statistical tests, and multiple linear regression models were developed to determine if sex, SHBG, and other RAS-related factors were associated with Aogen level and renin activity.
Results: In total, 113 subjects (78 women, 35 men) were included. Men (mean 55 y; std 5.3 y) and women (56.6 y; std 5.8 y) were similar in age; Black race (9% in men and 14% in women) and risk factors: hypertension (men 63% vs. women 58%), diabetes (20% vs 18%), hyperlipidemia (80% vs. 76%), and smoking (6% vs. 10%). Systolic and diastolic blood pressures were similar. Women had significantly higher levels of Aogen (mean 35,123 ng/ml; std 12,557) than men (mean 26,601 ng/ml; std 4578; p<.0001), whereas men had higher renin activity (median 2.4 ng/ml/hr; IQR 0.9, 5.0) vs women (median 1.0; IQR 0.6, 2.6; p=0.058). Multiple regression modeling showed that Aogen levels were positively associated with female sex (p=0.018) and SHBG levels (p<.001) after adjustment for hypertension, and concurrent ACE-I/ ARB use. Renin levels were associated with ARB (p=0.008) and ACE-I (p=0.001) use but not sex (p=0.103).
Conclusions: Aogen, but not renin, is influenced by female sex after accounting for SHBG, hypertension, and use of RAS-influencing drugs. This suggests that potentially different mechanisms may contribute to the identified risk factors for stroke in men and women.
Author Disclosures: C. Bushnell: Research Grant; Significant; World Federation of Neurology support for the International Maternal Newborn Stroke Registry. G. Evans: None. D. Diz: None. K. Brosnihan: None.
- © 2015 by American Heart Association, Inc.