The sex-based subgroup analysis in the PARAGON-HF study testing the efficacy of angiotensin receptor–neprilysin inhibitors (ARNi; sacubitril-valsartan, Novartis) for patients with HFpEF identified a more favourable treatment effect in women compared with men.7,8 Considering the mechanism of action for ARNi as cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) activation, the cGMP-PKG pathway might be specifically involved in the pathophysiology of heart failure in women following menopause. The gene discussed is PRKG1; the disease is heart failure.