In 2017 the American College of Cardiology (ACC) and the American Heart Association (AHA) lowered the definition of hypertension to ≥130/80 mm Hg,¹ whereas the 2023 European Society of Hypertension (ESH) and the 2024 European Society of Cardiology (ESC) guidelines use a definition of ≥140/90 mm Hg.^2,3 However, the European guidelines generally recommend a treatment goal of <130/80 mm Hg for most adults,² making these different guideline treatment recommendations more similar than dissimilar.

Although there is still debate regarding the definition of hypertension and whether the systolic blood pressure (SBP) goal of <130 mm Hg should apply to all individuals, growing evidence demonstrates that an even lower SBP of <120 mm Hg significantly reduces atherosclerotic cardiovascular disease (ASCVD) risk for patients at high risk.⁴

The first trial to investigate a SBP goal of <120 mm Hg was the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, published in 2008.⁵ It employed a factorial design testing the interventions of hemoglobin A1c (HbA1c) concentration <6% versus 7-7.9% and SBP <120 versus <140 mm Hg among patients with type 2 diabetes mellitus who had established cardiovascular disease (CVD) or additional CVD risk factors.⁵ Neither the HbA1c intervention (hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.78-1.04) nor the SBP lowering intervention (HR, 0.88; 95% CI, 0.73-1) significantly reduced the risk of ASCVD. However, among the participants in the standard-glycemic group treated to goal SBP <120 mm Hg, there was a significantly lower risk of ASCVD (HR, 0.71; 95% CI, 0.56-0.95).⁵ Moreover, in the ACCORDION (Action to Control Cardiovascular Risk in Diabetes Follow-On) study, which followed participants for an additional 3.5 years (9 years total), a significant interaction between the treatment groups was observed and participants in the standard-glycemic group treated to goal SBP <120 mm Hg had a 21% lower risk of ASCVD (HR, 0.79; 95% CI, 0.65-0.96).⁶

The SPRINT (Systolic Blood Pressure Intervention Trial) tested treatment to SBP <120 mm Hg among patients at an increased CVD risk without diabetes mellitus or stroke.⁷ The trial was stopped early at 3.3 years because of the 25% lower risk of major adverse cardiovascular events (MACE; HR, 0.75; 95% CI, 0.64-0.89) and all-cause mortality (HR, 0.73; 95% CI, 0.6-0.9).⁷ At the end of study, the mean SBP was 120 mm Hg in the intensive-treatment group and 133.9 mm Hg in the standard-treatment group.⁷ There was no significant difference (p = 0.23) in overall serious adverse events (SAE), although there was a higher risk of hypotension, electrolyte abnormalities, and acute kidney injury.⁷

The RESPECT (Recurrent Stroke Prevention Clinical Outcome) trial examined treatment to SBP <120 mm Hg and found no significant difference between treatment groups (HR, 0.73; 95% CI, 0.49-1.11).⁸ This nonsignificant finding may be explained in part by the relatively small mean difference in SBP of 6.5 mm Hg (126 vs. 133 mm Hg) and the lower-than-expected event rate that led to insufficient power.

Subsequently, the ESPRIT (Effects of Intensive Blood Pressure Lowering Treatment in Reducing Risk of Cardiovascular Events) trial evaluated a SBP target of <120 mm Hg among Chinese patients with increased CVD risk.⁹ During a median 3.4 year of follow-up, the mean achieved SBP was 119 versus 135 mm Hg and those in the intensive-treatment group had a 12% reduction in the risk of MACE (HR, 0.88; 95% CI, 0.78-0.99), with no significant difference seen when the results were stratified by patients with diabetes mellitus or prior stroke nor a significant difference in overall SAE (p = 0.78).⁹

Most recently, the BPROAD (Blood Pressure Control Target in Diabetes) trial examined a SBP goal of <120 mm Hg in patients with type 2 diabetes mellitus with elevated CVD risk.¹⁰ At the end of the study, the mean achieved SBP was 122 versus 133 mm Hg and participants in the intensive-SBP group had a 21% reduction in the risk of MACE (HR, 0.79; 95% CI, 0.69-0.9), with no significant difference in overall SAE (p = 0.96).¹⁰

Of particular relevance for guideline-writing groups considering whether a SBP goal even lower than the current 130 mm Hg should be recommended, the achieved SBPs in the aforementioned trials were generally in the low 120s mm Hg versus the low 130s mm Hg. The 20-25% ASCVD risk reduction observed in many of these trials is a clinically meaningful risk reduction with a number needed to treat ranging from 52 to 75, and there was no significant difference in overall SAE for the SPRINT, ESPIRT, or BPROAD populations.^7,9,10 Treating to goal SBP <120 mm Hg generally required one additional medication for a mean of two or three blood pressure (BP) medications that were mostly thiazide-type diuretics, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and calcium channel blockers. The use of combination pill therapy to help facilitate intensive BP control, as recommended by the ACC/AHA, ESH, and 2023 European guidelines can help achieve these lower BP goals without additional pill burden.^1-3

The results from these trials highlight that, among persons at increased CVD risk (e.g., prior CVD event, diabetes mellitus, or high 10-year estimated ASCVD risk), treatment to SBP goal <120 mm Hg has a degree ASCVD risk reduction comparable to many other treatments with Class 1a guideline recommendations. Although there remains concern regarding the potential for SAE, the overall SAE event rate was similar between treatment groups in these trials. These are compelling data to support a SBP goal of <120 mm Hg among individuals at high ASCVD risk (Table 1), which should strongly be considered by future BP guideline groups.

Table 1: Summary of Trials Treating to SBP <120 vs. <140 mm Hg

^a 2 x 2: SBP <120 versus <140 mm Hg and HbA1c concentration <6% versus 7-7.9%
^b For combined outcomes of worsening kidney function, hemodialysis, syncope, dehydration, and abnormal electrolytes
ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACS = acute coronary syndrome; ADHF = acute decompensated heart failure; ASCVD = atherosclerotic cardiovascular disease; BPROAD = Blood Pressure Control Target in Diabetes; CI = confidence interval; CVD = cardiovascular disease; ESPRIT = Effects of Intensive Systolic Blood Pressure Lower Treatment in Reducing Risk of Vascular Events; HF = heart failure; HbA1c = hemoglobin A1c; HR = hazard ratio; MI = myocardial infarction; NNT = number needed to treat; RCT = randomized controlled trial; RESPECT = Recurrent Stroke Prevention Clinical Outcome; RR = risk ratio; SAE = serious adverse event; SBP = systolic blood pressure; SPRINT = Systolic Blood Pressure Intervention Trial; T2DM = type 2 diabetes mellitus.

References

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