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CLINICAL STATEMENTS AND GUIDELINES

September 16, 2025 Circulation. 2025;152:e114–e218. DOI: 10.1161/CIR.0000000000001356 e148

of individual-level participant data from the Blood Pressure Lowering Treatment Trialists reported a prerandomization average DBP of 84 mm Hg from 48 RCTs among 157 728 patients with previous CVD who demonstrated benefit with initiation of antihypertensive therapy for BP lowering.3

5 Among individuals without clinical CVD but at

increased CVD risk, initiation of antihyperten­ sive therapy at an SBP threshold of ≥130 mm Hg reduces CVD events.3,7,8,10–12 Three groups of individuals were identified at increased CVD risk without clinical CVD: 1) individuals with diabetes; 2) individuals with CKD; 3) individuals aged 30 to 79 years without CVD, diabetes, or CKD who have a 10-year estimated CVD risk of ≥7.5% with PREVENT. In the SPRINT trial, increased predicted risk of CVD of ≥15% based on the Framingham risk score was an inclusion criterion, and 76% of enrolled participants had a Framingham 10-year estimated CVD risk ≥15%.7,8 In the STEP trial, 65% of participants had a Framingham 10-year esti­ mated CVD risk ≥15%, and this group (but not those at lower predicted risk) benefited from BP lower­ ing. The level of risk estimated by Framingham risk ≥15% is roughly equivalent to 10-year estimated CVD risk ≥7.5% with PREVENT and 10-year esti­ mated ASCVD risk ≥10% with PCEs.7,17 Predicted CVD risk ≥15% based on Framingham and ≥7.5% based on PREVENT also represent the age- and sex-specific 75th percentile among US adults with untreated SBP 130 to 139 mm Hg, which has been a threshold used in other prevention guide­ lines.18 Initiation of antihypertensive treatment for adults aged ≥80 years (for whom estimated risk models are limited) is recommended at ≥130/80 mm Hg when clinical judgment suggests benefits will outweigh harms and when aligned with the patient’s goals of care. In the SPRINT trial, 12.5% of participants were aged ≥80 years, and there was no difference in benefit by age. Observational data also suggest a similar relative risk reduction of BP lowering across age categories, including those aged ≥85 years.9

6 Among individuals without clinical CVD but at

increased CVD risk, initiation of antihypertensive therapy at an average DBP threshold of ≥80 mm Hg reduces CVD events.3,7,8,10–12 While elevated DBP ≥80 mm Hg was included as an entry cri­ terion in the ABCD trial that enrolled adults with diabetes and hypertension (with or without CVD), clinical trials have not exclusively enrolled indi­ viduals with elevated DBP ≥80 mm Hg. A metaanalysis of individual-level participant data from the Blood Pressure Lowering Treatment Trialists reported a prerandomization average DBP of 89 mm Hg from 48 RCTs among 186 988 patients without previous CVD who demonstrated benefit with initiation of antihypertensive therapy for BP lowering.3

7 In adults without clinical CVD who are at lower

10-year predicted CVD risk based on PREVENT (<7.5%), there are limited data about the net ben­ efit of initiation of antihypertensive therapy at a lower threshold with an average SBP ≥130 mm Hg. Therefore, lifestyle interventions should be encouraged first to lower BP (Section 5.1, “Lifestyle and Psychosocial Approaches”). However, lifestyle interventions may not be successful at lowering SBP, and even when successful initially, it can be difficult to sustain optimal SBP levels. Therefore, if average SBP is ≥130 mm Hg after a 3- to 6-month trial, initiation of antihypertensive therapy is advised as an adjunct to lifestyle interventions. This is sup­ ported by the PREVER-Prevention (Hypertension Prevention in Pre-Hypertensive Individuals) trial, which demonstrated lower rates of progression to stage 2 hypertension (≥140/90 mm Hg) and end-organ damage (left ventricular mass) follow­ ing a 3-month lifestyle intervention among partici­ pants with elevated BP (120 to 139/80 to 89 mm Hg) who were subsequently randomized to diuretic treatment compared with placebo in adults aged 30 to 70 years.19 For those adults age <30 years for whom models estimate risk is limited, initiation of antihypertensive therapy could be considered at an average SBP ≥130 mm Hg after a trial of life­ style modification, but data are limited. In addition, BP should continue to be monitored (Section 5.2.7, “BP Goal for Patients With Hypertension”) as BP tends to increase over time,20 and greater cumula­ tive BP exposure is associated with higher risk of clinical CVD.21,22 Data from observational cohorts of younger adults demonstrate lower risk of sub­ clinical CVD among those with BP <130/80 mm Hg.23,24 Other modalities for risk assessment, such as imaging (eg, echocardiography) or biomark­ ers (eg, BNP, hs-cTn) or applying the long-term 30-year risk estimation with PREVENT, may be useful to guide clinician-patient discussions.25,26 Having a history of hypertensive disorders of preg­ nancy may also identify individuals who have higher long-term predicted risk and may benefit from ear­ lier initiation of antihypertensive therapy.27

8 In adults without clinical CVD and at lower 10-year

predicted CVD risk based on PREVENT (<7.5%), there are limited data about the net benefit of initia­ tion of antihypertensive therapy at a lower thresh­ old with an average DBP ≥80 mm Hg. Therefore, lifestyle interventions should be encouraged first to lower BP (Section 5.1, “Lifestyle and Psychosocial Approaches”). However, lifestyle interventions may not be successful at lowering DBP, and even when

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