acute kidney failure. Statistical Analyses We computed the mean follow-up BP for each study participant by averaging the SBP or DBP measurements from month 3 to the last available reading. We used boxplots to display the mean follow-up SBP and DBP within the intensive and standard groups by tertile of baseline DBP. A total of 75 participants (2.8%; 28 in the intensive group and 47 in the standard group) had missing BP measurements after month 2 and were not included in this descriptive portion of the analysis. Our analysis is on the basis of information provided in the SPRINT public access Biological Specimen and Data Repository Information Coordinating Center database. It includes events that occurred on or before the trial was stopped on August 20, 2015 and were recognized with the use of a data freeze date of October 14, 2015. Associations of Baseline DBP with Outcomes. We calculated the incidence per 100 person-years of the primary composite end point, all-cause death, and adverse events by tertile of baseline DBP for descriptive purposes. We related baseline DBP to these outcomes by fitting separate Cox regression models with baseline DBP as a cubic spline with knot points at the 25th, 50th, and 75th percentiles, with adjustment for the randomized SBP intervention, age, sex, and race as covariates. In sensitivity analyses, we repeated the above models with additional covariate adjustment for history of cardiovascular disease, Framingham 10-year Standard Intensive < 69 Middle tertile, DBP 70 - 79 Highest tertile, DBP ≥ 80 Hazard ratio for primary composite endpoint (intensive vs standard) 0.25 0.5 1.0 2.0 B Cohort HR (95% Cl) 0.72 (0.53, 0.99) 0.74 (0.46, 1.18) 0.83 (0.48, 1.44) 0.61 (0.33, 1.12) Entire CKD By DBP tertiles Lowest tertile, DBP < 69 Middle tertile, DBP 70 - 79 Highest tertile, DBP ≥ 80 Hazard ratio for all-cause death (intensive vs standard) 0.25 0.5 1.0 2.0 Figure 4. | The effect of intensive SBP lowering on outcomes by tertile of baseline DBP, hazard ratios for the SBP intervention for the primary composite end point and all-cause death were similar. Forest plots showing hazard ratios (HRs) and 95% CIs for the effect of the randomized SBP intervention on the primary composite end point (A) and all-cause death (B) for the entire CKD cohort and by baseline DBP tertile. Likelihood ratio tests comparing HR for the SBP intervention among baseline DBP tertiles were nonsignificant (primary composite end point interaction P50.85; all-cause death interaction P50.75). Models are unadjusted. 372 KIDNEY360 Adverse Events The incidence of any serious adverse event was higher in the lowest tertiles of baseline DBP in both the intensive and standard SBP lowering arms (Table 2). The effect of intensive versus standard SBP lowering on adverse events did not differ by tertiles of baseline DBP. Discussion On-treatment observational studies have shown associations among lower DBP and higher rates of adverse cardiac ischemic events, particularly in populations with established coronary artery disease (1–4,12). For example, a secondary observational reanalysis of 22,576 patients with hypertension and coronary artery disease enrolled in the International Verapamil-Trandolapril study showed that patients with an achieved mean DBP of ,60 mm Hg had a higher incidence of cardiovascular events and death compared with their counterparts who had a higher mean achieved DBP (12). An observational reanalysis of the Treating to New Targets trial in which patients with clinically evident coronary artery disease were treated with higher or lower doses of atorvastatin again showed that an achieved DBP ,80 mm Hg was associated with higher rates of fatal and nonfatal cardiovascular events (2). Given the associations among lower DBP and cardiovascular events in these observational studies, concerns about DBP lowering could be even more pronounced in patients with CKD. Interventions aimed at lowering SBP will generally reduce DBP as well and could theoretically lead to underperfusion and ischemia of vital organs. Patients with CKD also have a high prevalence of hypertension and left ventricular hypertrophy, which impair coronary blood flow autoregulation, wherein more intensive BP lowering could lead to more marked declines in coronary perfusion pressures (13). In this study of SPRINT participants with CKD, we found that an observational analysis yielded the expected association between lower baseline DBP and higher rates of the primary outcome and all-cause mortality. However, in randomized comparisons of the two treatment groups, we found no indication that the beneficial effect of the intensive SBP intervention in SPRINT participants with CKD on the primary composite end point and all-cause death differed by baseline level of DBP. Therefore, although lower baseline DBP may serve as a marker of poor vascular health and/or other conditions that signal higher risk of cardiovascular and other adverse events, more intensive BP treatment in participants with lower DBP and CKD still proved beneficial. Table 2. Incidence rates (per 100 person-years [N of event per follow-up year]) for intensive and standard treatment groups, hazard ratios, and 95% confidence intervals for the effect of the intensive versus standard systolic BP intervention on serious adverse events in the Systolic Blood Pressure Intervention Trial