In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial, major CV protection was derived from inhibition of the renin-angiotensin-aldosterone system, despite the UA-lowering effect of Losartan explaining 29% of the positive effect on the primary composite end points of cardiovascular death, myocardial infarction, and stroke [31]. The gene discussed is REN; the disease is Stroke.