Due to the similarity of the study design and study population, we combined data from the SPRINT and ACCORD-BP trials. To avoid potential bias by combining data from 2 different studies, we also analyzed data from the 2 trials separately. Patients with achieved SBP of less than 130 mm Hg were selected and divided into subgroups on the basis of their mean achieved DBP at the following cutoffs: less than 60, 60 to less than 70, 70 to less than 80, and at least 80 mm Hg, with 70 to less than 80 mm Hg as the reference (ie, hazard ratio [HR] considered 1). Groups were tested for differences using 1-way analysis of variance for continuous data and the χ2 test for categorical data. HRs for all outcomes were analyzed by DBP category and tested for differences using Cox regression, adjusting for study, study group (intensive vs standard BP control; intensive vs standard glycemic control), and baseline patient characteristics (ie, age, sex, tobacco use, education, heart rate, body mass index [BMI, calculated as weight in kilograms divided by height in meters squared], renal function, serum level of low density lipoprotein cholesterol [LDL-C] and glucose, history of hypertension, history of cardiovascular disease, family history of cardiovascular disease, and concomitant medications). History of cardiovascular disease was defined as history of myocardial infarction, stroke, acute coronary syndrome, coronary artery bypass grafting or percutaneous coronary intervention, other revascularization (ie, carotid, peripheral, abdominal aortic aneurysm repair), left ventricular hypertrophy, ankle brachial index of 0.9 or less, and at least 50% stenosis of artery. The association between mean achieved DBP and DBP changes from baseline as continuous variables with SBP of less than 130 mm Hg was also analyzed with restricted cubic splines that allow exploration of nonlinear associations.24 Likelihood-ratio test was used to assess whether the association was really nonlinear. To avoid potential reverse associations, we excluded patients with any primary or secondary events within 30 days after randomization. In addition, sensitivity analyses were conducted by excluding patients with mean achieved SBP of less than 110 mm Hg, by additional adjustment of baseline PP as a categorical variable (≥60 mm Hg or not) and baseline DBP in the Cox regression model, and by additional adjustment of baseline PP (≥60 mm Hg or not), baseline SBP, and achieved SBP in the Cox regression model. We also analyzed the association of intensive vs standard BP control with cardiovascular and mortality outcomes in a subgroup of patients with baseline DBP of less than 60 mm Hg in the ACCORD-BP and SPRINT trials separately. All analyses were done with SPSS statistical software version 20.0 (IBM Corp) and RStudio version 1.2.5033 (survival and rms packages; R Project for Statistical Computing). A 2-tailed P < .05 was considered statistically significant.

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