drug classes were required for the intensive SBP goal group to achieve a SBP average of 119 mm Hg, compared with 2 classes in the standard SBP goal group with a mean SBP achieved of 134 mm Hg (The ACCORD Study Group, 2010). In addition to being more costly and having greater potential for drug-related adverse events, even 1-2 more medications per day may contribute to reduced adherence to other evidence-based drug treatment (e.g., statins or aspirin). Patients may choose to not take medications without more evidence for safety and benefit. In addition to being more costly, burdensome, and potentially risky, a 20-mm Hg lower SBP goal (and/or a 10 mm Hg lower DBP goal) would likely mean that up to 70-80 million Americans now considered "prehypertensive" may require drug therapy for a condition that has not been proven to be benefited by treatment (Greenlund, Croft, and Mensah, 2004). Finally, all medications carry an intrinsic risk of side effects which may adversely affect clinical outcomes and quality of life, and lead to drug interactions, especially in older persons who may need to take a variety of medications. 1.1.7 Conclusion If the SPRINT results are positive and support a SBP goal 130 mm Hg who either have or are at high risk for CVD. SPRINT will focus on three high risk groups: individuals with clinical CVD other than stroke, individuals with CKD (estimated glomerular filtration rate [eGFR] 20-59 ml/min/1.73 m2 ), and individuals without clinical CVD who have high estimated CVD risk based on factors such as smoking, low levels of HDL, high levels of LDL or age. Three other groups will be excluded: patients with diabetes, patients with polycystic kidney disease (PKD), and patients who have had a stroke. Patients with diabetes have been studied in the ACCORD trial; patients with prior stroke and PKD are part of other ongoing trials. 1.2.1 Chronic Kidney Disease (CKD) An important and under-studied high-risk group for CVD is the population with CKD (Coca and others, 2006). In the U.S., the number of persons with Stage 3 CKD (eGFR between 30 and 60 ml/min/1.73 m2 ) has recently been estimated to be 7.7% of the adult population, or 15.5 million (Coresh and others, 2007). Patients with prevalent CVD have a high prevalence of CKD, with reported ranges of 30-60% (Keeley and others, 2003;Levey and others, 1998;Shlipak and others, 2002). Individuals with CKD are at high risk for CVD events (Shlipak and others, 2009;Go and others, 2004;Rahman and others, 2006;Weiner and others, 2004;Foster and others, 2007;McCullough and others, 2007;Rashidi and others, 2008;Fried and others, 2009). A meta-analysis of reported data from prospective studies in Western populations demonstrated that people with an eGFR of 60 ml/min/1.73m2 (Di Angelantonio and others, 2007). The relative risk increases as eGFR declines (Go and others, 2004). Pooled data from the ARIC and CHS cohorts demonstrated that participants with CKD were also at increased risk for stroke (Weiner and others, 2007), and CKD was a risk factor for CVD and all-cause mortality independent of traditional CVD risk factors (Weiner and others, 2004). In ALLHAT, despite exclusion criteria designed to exclude participants with significant GFR impairment, about 18% of participants had an eGFR 30-60 ml/min/1.73m2 . In that CKD subgroup, CHD was 38% higher and combined CVD 35% higher than in those with an eGFR >90 ml/min/1.73m2 (Rahman and others, 2006). Version 4.0 9 November 1, 2012 The effect of BP control on the development of CVD in the CKD population is far less clear (Berl and others, 2005). A strategy of treating to a lower BP goal may reduce the progression of kidney disease. The risk of CKD increases progressively beginning with pre-HTN levels of BP through the various stages of HTN (Haroun and others, 2003). Several observational studies have suggested that achievement of lower BP is associated with lower risk of adverse kidney outcomes (Bakris and others, 2000;Klag and others, 1996;Schaeffner and others, 2008). However, two randomized clinical trials, AASK and the Modification of Diet in Renal Disease Study (MDRD) that examined lower-than-usual BP goals failed to show an overall significant beneficial long-term effect of lower BP on decline in kidney function (Klahr and others, 1994;Wright, Jr. and others, 2002b) Both studies enrolled participants with non-diabetic CKD and randomized them to a mean arterial pressure (MAP) goal of 300 mg/day who were randomized to the lower goal (Appel and others, 2008). Among 585 non-diabetic participants with Stage 3/4 CKD in MDRD, 24% had PKD and only 53 were African American (Klahr and others, 1994). Mean baseline proteinuria was 2.2 g/d, and a beneficial effect of the lower BP goal on GFR was observed in the subgroup with urinary protein > 1 g/d (Peterson and others, 1995;Sarnak and others, 2005). In addition to the inherent problems associated with subgroup analysis, major caveats of these results from the MDRD Study were that the number of patients in the heavy proteinuric subgroups was small and the results were confounded by the use of angiotensin converting enzyme (ACE) inhibitors. Together, these studies fail to show convincing renoprotective effects for the lower BP goal; however their results have led to clinical recommendations that patients with high levels of proteinuria should