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CLINICAL STATEMENTS AND GUIDELINES September 16, 2025 Circulation. 2025;152:e114–e218. DOI: 10.1161/CIR.0000000000001356 e168 ICH) showed a significantly lower rate of recurrent stroke in patients with an achieved SBP of <130 mg Hg.3 It should be noted that in subgroups of 2 large meta-analyses, the greatest benefit of tighter BP control was noted in patients with ICH as an index event.3,5 3 The recommended threshold BP of >130/80 mm Hg for starting antihypertensive medications is informed by the baseline BPs of patients with cerebrovascular disease studied in trials of BP treatment. Among the 4 RCTs comparing intensive and standard BP targets in patients with prior cerebrovascular disease, the RESPECT,5 PAST-BP,6 and PODCAST7 trials included patients with baseline SBPs as low as 125 mm Hg. In PAST-BP,6 approximately 50% of patients had base line SBP <140 mm Hg. Similarly, in the PROFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial of >20 000 patients with ischemic stroke, approximately 33% of patients had baseline SBP <135 mm Hg.19 The large number of subjects with prior stroke and SBP <140 mm Hg included in these trials supports the safety and efficacy of the use of antihypertensive medications in patients with SBP ≥130 mm Hg. 5.3.9.4 Mild Cognitive Impairment and Dementia Recommendation for Prevention of Mild Cognitive Impairment and Dementia Referenced studies that support the recommendation are summarized in the Evidence Table. COR LOE Recommendation 1 A 1 In adults with hypertension, a goal of <130 mm Hg SBP is recommended to prevent mild cognitive impairment and dementia.1–5 Synopsis Dementia affects the memory and other cognitive func tions, behavioral functioning, and social abilities, im pairing daily life and resulting in most nursing home placements. Prior studies estimate that more than 9 million Americans could have dementia by 2030 and nearly 12 million by 2040.6 The prevalence of mild cognitive impairment, a transitional state between nor mal cognitive aging and dementia, is also expected to markedly increase.7 Interventions that produce a 5-year delay in onset of dementia would likely decrease the number of cases of incident dementia and accompany ing institutionalizations by about 50% after several de cades.8 Hypertension has been identified as a prevalent modifiable risk factor for cognitive decline and demen tia.9–12 Cerebrovascular disease, a complication of hy pertension, is commonly present in Alzheimer disease and related forms of dementia, where it frequently cooccurs with beta-amyloid and tau neuropathology.12,13 Hypertension is the primary risk factor for small-vessel ischemic disease and cortical white matter abnor malities14–16 in the brain, which are highly predictive of cognitive decline and dementia.17 Most observational studies and clinical trials have suggested that better control of SBP reduces Alzheimer disease and related dementias, with the strongest association for BP lower ing in middle age.18,19 These data support intensive BP treatment as an important strategy for the prevention of cognitive impairment and suggest some degree of persistent benefit on the development of cognitive im pairment from even a few years of intensive treatment. Recommendation-Specific Supportive Text 1 Meta-analyses of RCTs, excluding the 2 most recent large trials, have strongly supported a beneficial effect of BP reduction on dementia risk.2,20,21 Of the 7 large trials finding a lower risk for demen tia, the trials showing a reduction in dementia achieved relative SBP reductions of 7 to 21 mm Hg. The largest meta-analysis and 2 large recent BP-lowering trials each demonstrated a 12% to 19% reduction in dementia incidence; however, the reduction in SPRINT was not significant.19,20,22 Early cognitive decline was reduced in participants without adjudicated incident dementia in the 2 largest RCTs (SPRINT and CRHCP [China Rural Hypertension Control Project]), each with a treat ment goal of 120 mm Hg SBP.20,22 New results from the SPRINT-MIND legacy follow-up show that unlike mortality, significant benefit in reducing the risk of incident mild cognitive impairment alone with or without dementia continued for at least 7 years.4 A nonstatistically significant reduction in dementia risk remained, with each of these findings a result of only 3.5 years of intensive BP treatment. Other work has shown that the 12-mm Hg SBP reduction achieved in SPRINT rapidly dissipated after the trial was stopped.23 Importantly, no RCT of BP lowering has demonstrated an adverse impact on dementia incidence or cognitive function, nor have the 2 large RCTs of BP lowering demonstrated harm, such as increase in overall adverse events, falls, fall-related fractures, or kidney failure, even at an SBP treat ment goal of 120 mm Hg.24 5.3.10 Peripheral Artery Disease Synopsis Hypertension is present in 35% to 55% of patients at the time of their PAD diagnosis1 and is the most common risk factor for PAD. Hypertension is associated with a longitudinal decline in ankle brachial index in adults >65 years of age.2 Treatment of hypertension to a goal BP of <130/80 mm Hg in adults with PAD is optimal to re duce the risk of MACE, including stroke, MI, HF, and car diovascular death. Historically, some concern has been Downloaded from http://ahajournals.org by on October 7, 2026