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The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated the benefit of lowering systolic blood pressure (SBP) to 120 mm Hg, yet other trials, such as Heart Outcomes Prevention Evaluation–3 (HOPE-3), did not find consistent benefit. How to incorporate these results into the treatment of those with elevated SBP in the general population is not clear.To assess the representativeness of SPRINT and HOPE-3 relative to patients in the United States and to explore the cardiovascular disease (CVD) risk profiles of various populations with elevated SBP.The study examined data from nonpregnant adults aged 20 to 79 years participating in the 2007-2012 National Health and Nutrition Examination Survey (NHANES) who had complete data available (n = 14 142), representing 206.9 million US adults. The study was performed from October 1, 2015, to August 2, 2016.The study estimated the number and characteristics of adults with SBP of 120 mm Hg or higher, including SPRINT and HOPE-3 eligibility, and estimated who may have newly required treatment initiation or intensification if various trial or risk-based criteria were applied.NHANES included completed clinical evaluations from mobile examination centers on 15 974 adults aged 20 to 79 years (mean [SD] age, 45.9 [15.5] years). The study excluded 182 pregnant women and 1650 adults in whom CVD risk data were unavailable, leaving a final study population of 14 142 (50.5% women [95% CI, 49.6%-51.3%] and 49.5% men [95% CI, 48.6%-50.4%]). An estimated 53.3 million untreated and 19.8 million treated US adults have an SBP in the diagnostic and treatment gray zone (120-139 mm Hg), a small proportion of whom would have been eligible for SPRINT (5.4% untreated, 13.9% treated) or HOPE-3 (13.9% treated, 1.7% untreated). Even among those with prior CVD or high risk of CVD and elevated SBP (120-139 mm Hg), only a few would have qualified for SPRINT (27.0% and 21.9% of untreated and treated patients, respectively) or HOPE-3 (10.6% and 2.1% of untreated and treated, respectively). If blood pressure treatment recommendations were extended to adults with an SBP between 120 and 139 mm Hg, as well as prior CVD or CVD risk of 15% or higher, then 5.8 million untreated adults would be reclassified as treatment eligible; furthermore, 8.5 million treated patients would require medication intensification.Millions of US adults have elevated SBP and high CVD risk, most of whom would not have been eligible for SPRINT. Until more definitive evidence becomes available, clinicians should consider a management paradigm based on CVD risk in addition to blood pressure measurements.