KM, Still CH, Supiano MA, Snyder JK, Wadley VG, Walker J, Weiner DE, Whelton PK, Wilson VM, Woolard N, Wright JT Jr., Wright CB; SPRINT MIND Investigators for the SPRINT Research Group: Effect of intensive vs standard blood pressure control on probable dementia: A randomized clinical trial. JAMA 321: 553–561, 2019 11. Johnson KC, Whelton PK, Cushman WC, Cutler JA, Evans GW, Snyder JK, Ambrosius WT, Beddhu S, Cheung AK, Fine LJ, Lewis CE, Rahman M, Reboussin DM, Rocco MV, Oparil S, Wright JT Jr.; SPRINT Research Group: Blood pressure measurement in sprint (systolic blood pressure intervention trial). Hypertension 71: 848–857, 2018 12. Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A, Kolloch R, Benetos A, Pepine CJ: Dogma disputed: Can aggressively lowering blood pressure in hypertensive patients with coronary a SPRINT Protocol Executive Summary The Systolic Blood Pressure Intervention Trial (SPRINT) is a 2-arm, multicenter, randomized clinical trial designed to test whether a treatment program aimed at reducing systolic blood pressure (SBP) to a lower goal than currently recommended will reduce cardiovascular disease (CVD) risk. About 9250 participants with SBP ≥ 130 mm Hg and at least one additional CVD risk factor will be recruited at approximately 90 clinics within 5 clinical center networks (CCNs) over a 2-year period, and will be followed for 4-6 years. Approximately 4300 participants will have chronic kidney disease (CKD), and 3250 will be aged 75 or older. The primary outcome is the first occurrence of a myocardial infarction (MI), acute coronary syndrome (ACS), stroke, heart failure (HF), or CVD death. Secondary outcomes include all-cause mortality, decline in renal function or development of end stage renal disease (ESRD), dementia, decline in cognitive function, and small vessel cerebral ischemic disease. Design SPRINT will randomize about 9250 participants aged ≥ 50 years with SBP ≥130 mm Hg and at least one additional CVD risk factor. The trial will compare the effects of randomization to a treatment program of an intensive SBP goal with randomization to a treatment program of a standard goal. Target SBP goals are 60 years. Two-thirds of those over age 60 have HTN, and the prevalence has increased in recent decades (Chobanian and others, 2003;Cutler and others, 2008;Hajjar and Kotchen, 2003;Ong and others, 2007;World Health Organization, 2002). By age 50 years, isolated systolic hypertension (ISH) is the most common form of HTN, and is associated with greatest risk of target organ damage and adverse health outcomes (Franklin, 1999;Franklin and others, 2001). 1.1.2 Hypertension as a cardiovascular risk factor The importance of BP, especially SBP, as an independent risk factor for coronary events, stroke, chronic heart failure (CHF), and ESRD is well documented (Vasan and others, 2001;Collins and others, 1990;Macmahon and others, 1990;Sacco and others, 2001;Jackson, 2000;Staessen and others, 1997;Hsu and others, 2005;Chobanian and others, 2003;Gillum, 1991;Prospective Studies Collaboration, 2002;Levy and others, 1996). There is also substantial epidemiologic and clinical trial evidence supporting a role for hypertension therapy in reducing risk for age-related dementia, including vascular dementia and Alzheimer's dementia (Forette and others, 1998;Luchsinger and Version 4.0 4 November 1, 2012 Mayeux, 2004;Reitz and others, 2007;Skoog and Gustafson, 2003;Skoog and others, 2005;Skoog and Gustafson, 2006;Tzourio and others, 2003). Clinical trial data have shown reductions in CVD outcomes, including incident stroke (35% to 40%), MI (15% to 25%), and CHF (up to 50%) (Chobanian and others, 2003;Psaty and others, 1997;Neal, Macmahon, and Chapman, 2000). However, optimal targets for BP lowering are not established. 1.1.3 Support for current target In addition to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) (Chobanian and others, 2003), most recent practice guidelines recommend a target SBP 140 mm Hg. 1.1.4 Risk of SBP above normal but below current target The World Health Organization estimates that about two-thirds of the cerebrovascular disease burden and one-half of the coronary heart disease (CHD) burden on a worldwide basis is attributable to SBP >115 mm Hg (World Health Organization, 2002). Further, SBP > 115 mm Hg has been estimated to account for 7.6 million premature deaths (13.5% of the global total), 92 million disability-adjusted life years (6.0% of the global total), 54% of stroke, and 47% of ischemic heart disease. About half of this burden is in persons with a SBP1.5 mg/dL, which are prevalent in the US population and associated with high CV risk. (v) the glycemia arm of the ACCORD trial was stopped early because of an excess in total mortality and the possibility of interaction between these two interventions is still under investigation. The safety and benefit of intensive BP reduction in patients > age 75 remain to be tested. Thus, it is imperative that the potential benefits and harms of intense SBP-lowering be examined definitively in this and other high-risk populations, e.g. those with chronic kidney disease (CKD) or underlying CVD. Version 4.0 7 November 1, 2012 1.1.6 Possible harm from treatment of SBP to 3