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CLINICAL STATEMENTS AND GUIDELINES

September 16, 2025 Circulation. 2025;152:e114–e218. DOI: 10.1161/CIR.0000000000001356 e186

3 well-performed meta-analyses.15,21,31 The first 2 of

these meta-analyses called into question the strength of evidence for benefit of BB, while raising concerns about harms related to hypotension and stroke.21,31 A more recent review confirmed earlier meta-analytic results while assessing that the certainty of evidence was low given biases and heterogeneity among the studies reviewed; each of these meta-analyses results were driven in part by the large POISE (Perioperative Ischemic Evaluation)29 sample size.

7 EVIDENCE GAPS AND FUTURE

DIRECTIONS

Since the 2017 high BP guideline was published, there have been numerous advancements in high BP manage­ ment. However, key questions on the awareness of high BP and optimal management of high BP remain, and these knowledge gaps suggest areas for future research as described in this section. Among adults with hypertension in the United States, most are not controlled to <130/80 mm Hg. More than 50% are unaware that they have hypertension. Population management strategies are just beginning to utilize the EHR and consider community-engaged strategies to iden­ tify those with undiagnosed or uncontrolled hypertension to focus resources. There is a need for research regarding effective screening methods and for more effective imple­ mentation strategies within and outside the health care system to control BP and reduce CVD risk. Observational data demonstrate increased risk of CVD among younger adults with stage 1 hypertension, and ele­ vated BP can be associated with evidence of target organ damage. There is a need to clarify those areas where current clinical trial evidence is sufficient on which to base our treat­ ment decisions for younger adults, and where the needs for additional research are greatest. There is a lack of evidence to support BP targets for diastolic hypertension, which is more common in younger adults who have low short-term CVD risk but have a longer time horizon to consider for prevention. Research related to this issue should include detection of CVD endpoints organized outside academic centers, such as by pragmatic trial designs, to allow financial feasibility, use of surrogate endpoints such as left ventricular hypertrophy, which are not widely measured clinically, and evaluations for target organ damage performed at baseline and during longitudinal follow-up. Accurate BP measurement remains a major challenge. Trials are needed that compare measurements taken by attended AOBP and unattended AOBP methods. Contin­ ued studies are needed in the realm of alternative meth­ ods for measurements, including accurate wearable and cuffless devices to provide near-continuous monitoring, HBPM, ABPM, and other novel approaches to measuring or estimating BP load. Additional studies comparing home and ambulatory BP measurements in estimating CVD risk are greatly needed to reduce treatment disparities due to lack of availability of ABPM to all populations. There is a need for studies utilizing HBPM combined with inter­ ventions to effectively achieve and maintain BP control utilizing health technology and to minimize nonadherence.

Further studies are needed at the intersection of BP, race/ethnicity, and SDOH, which includes those who are underinsured or uninsured to allow more precise predic­ tions of needs and better focused prevention and man­ agement. To ensure optimal application of guidelines and evidence-based approaches that are effective and equitable for all groups, the BP treatment thresholds and treatment targets for different subpopulations need to be further clarified. With these efforts, there will be a need for additional data monitoring to evaluate new approaches and their effects on BP control and CVD outcomes across differences in sex/gender, race/ethnicity, socioeconomic status, education level, and access to medical care. Further studies are needed to help us understand the role of genetic and epigenetic factors in BP. Using risk estimates that consider the influence of environmental and behavioral factors on genetic risk may add clarity to the areas of great­ est need and potential benefit. Overall, further studies of envi­ ronmental and lifestyle issues are needed, including nutrition, physical activity, and especially obesity and the role of emerg­ ing interventions for weight management in persons living with obesity and hypertension. We need additional studies of patients with white-coat hypertension to determine whether this condition carries additional long-term risk. Using risk estimates that incorporate genetic risk, but that also consider the influence of environmental and behavioral factors on this risk, may add clarity to areas of greatest need and potential benefit. In the realm of treatment approaches, there is prior evi­ dence to support the contribution of sleep apnea to hyperten­ sion and resistant hypertension, but evidence of BP lowering from sleep apnea treatment is limited. This is an area ripe for research, particularly as sleep apnea treatment includes serial monitoring, which could incorporate BP tracking. Early studies using stress management techniques have shown promise but need to be tested across a greater breadth of patients with adverse SDOH. We need additional trials comparing combinations of medications, dosed as separate agents and using SPCs to improve adherence and therefore effectiveness while monitoring for patient tolerance. While pregnancy is an area where different concepts apply and decisions must account for optimal manage­ ment of both the pregnant individual and the fetus, pregnancy planning and management have important implications for women with or at risk for high BP. Among women with preexisting hypertension or at risk for hyper­ tension, safety and effectiveness of antihypertensive therapies should be considered, along with counseling on appropriate contraction options and recommendations for prophylactic aspirin therapy among those at greatest risk for acute onset or worsening of prior hypertension.

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