REN and cardiac hypertrophy: In HF, reduced cardiac output lowers renal blood flow, triggering compensatory activation of the renin–angiotensin–aldosterone system (RAAS).168 Renin, which is secreted by juxtaglomerular cells that sense hypoperfusion, catalyzes angiotensin II synthesis, inducing afferent arteriolar vasoconstriction, increasing systemic blood pressure, and promoting sodium–water retention via aldosterone.169 Initially, adaptive, chronic RAAS overactivation drives myocardial hypertrophy, interstitial fibrosis, and ventricular remodeling, exacerbating HF.