Normally, AGT levels are relatively stable, rising only during pregnancy (up to 2–3-fold),78 and decreasing significantly during huge renin upregulation, like in subjects with heart failure.35,79 Women display higher AGT levels than men, but this is counterbalanced by their lower renin levels.80,81 Similarly, the AGT M235T polymorphism-related changes in plasma AGT (carriers of the T allele displaying 5% to 10% higher AGT levels) are neutralized by inverse changes in renin (ie, carriers of the T allele displaying 5% to 10% lower renin levels),82 leaving plasma renin activity unaltered. Here, REN is linked to heart failure.