This evidence is indirect, hence diminishing the certainty of the bene ts and strength of recommendation of targeting SBP <120 mm Hg. Low diastolic blood pressure. Numerous observational including those that examine data from RCTs in a post hoc observational manner,128 although not all studies, have suggested a J-shaped curve with very low DBP being associated with an increased risk of CVevents, particularly MI among patients with pre-existing coronary artery disease.94 The validity of these observations is supported by biological plausibility, as low DBP in the setting of coronary stenosis could lead to impaired subendocardial blood ow during diastole. However, this association is heavily confounded, as patients with very low DBP inherently have high CV risks. Beddhu et al. recently showed that in SPRINT participants, baseline DBP indeed bore a U-shaped relationship with mor- tality. However, the CV-protective bene ts of intensive SBP lowering were independent of baseline DBP, including the lowest DBP quintile at baseline with a mean DBP of 61  Whether this bene cial effect of SBP lowering persists at even lower DBP levels (e.g., <45 mm Hg) cannot be determined from these data. Kidney outcomes. Rate of decline in GFR. The effects of intensive BP lowering on GFR are often complicated by an exaggerated early acute GFR decline that is also seen with inhibitors of the renin-angiotensin system (RAS) and the sodium glucose cotransporter-2 (SGLT2) system. This acute eGFR decrease with BP lowering may be mediated, at least in part, by intrarenal hemodynamic changes. 