A newer tool used to assess cardiovascular disease risk comes with both answers…and some questions.

In a study published in the Journal of the American College of Cardiology, investigators used data from the SPRINT trial to see how patients were most likely to benefit from intensive blood pressure lowering vs standard therapy based on their 10-year risk for cardiovascular disease as calculated using the newer Predicting Risk of Cardiovascular Disease Events (PREVENT) equations. They discovered that although intensive treatment reduced cardiovascular events across all risk groups, the absolute benefit was higher for those with a higher predicted risk.

“These results were not surprising to us,” investigators Adam Bress, PharmD, MS, and Catherine Derington, PharmD, MS, told Medscape Medical News. “They reinforce how PREVENT can help clinicians quantify who stands to gain the most in absolute terms, allowing more targeted and efficient use of intensive blood pressure treatment where it can have the greatest impact. We also conducted this study before the release of the 2025 AHA/ACC [American Heart Association/American College of Cardiology] high blood pressure guidelines, which now place the PREVENT equations at the center of treatment decision-making.”

The SPRINT trial, published in 2015, demonstrated the benefits of intensive blood pressure-lowering therapy in participants with high cardiovascular risk. The findings contributed to the 2017 ACC/AHA hypertension guidelines recommending intensive therapy for patients with stage 1 hypertension who have a high risk for cardiovascular disease based on the pooled cohort equations.

The pooled cohort equations calculator has been used since 2013 to estimate the 10-year risk for cardiovascular disease in adults without the condition. Criteria include age, sex, and race, as well as current medical conditions. The newer PREVENT model excludes race and includes additional metabolic factors, like BMI and kidney function, as compared with the pooled cohort equations.

Intensive Therapy Beneficial Across PREVENT Risk Categories

The SPRINT trial enrolled adults aged 50 years or older with systolic blood pressure ranging from 130 mm Hg to 180 mm Hg who had an increased risk for cardiovascular disease. Those with diabetes, prior stroke, or heart failure were excluded.

In this post hoc analysis of 6554 SPRINT participants, the median 10-year risk for total cardiovascular disease using the PREVENT calculator was 13%. A breakdown of the data showed 16% of participants were classified as low- or borderline-risk, 62% were classified as intermediate-risk, and 22% were classified as high-risk.

During a median follow-up of 3.86 years, the relative benefit of intensive therapy compared with standard therapy was consistent across risk categories. However, the 4-year absolute risk differences varied, ranging from 0.2% in the low- or borderline-risk group to 2.4% in the high-risk group.

The investigators noted similar relative risks for serious adverse events related to treatment with intensive vs standard blood pressure-lowering therapy across PREVENT total cardiovascular disease risk categories, but absolute risk differences also increased with increasing risk category, according to the data.

Notably, the PREVENT model reclassified a large proportion of SPRINT participants — particularly those the pooled cohort equations labeled as high-risk — moving them into lower-risk categories. Investigators attributed reclassification to several factors, including the removal of race as a criterion, inclusion of heart failure, and the use of larger and newer datasets, among other reasons.

Lingering Questions

In an accompanying editorial, Cian P. McCarthy, MBBCH, BAO, SM; John W. McEvoy, MBBCH, BAO, MHS, PHD; and Jenifer M. Brown, MD, placed this post hoc analysis in the context of the new ACC/AHA blood pressure guidelines. 

In light of the study’s findings, they discussed treatment for stage 1 hypertension for patients with PREVENT scores of 7.5% or higher, as recommended by the 2025 guidelines. This threshold was chosen in part because it matched older cardiovascular disease risk thresholds used for inclusion in the SPRINT trial. But given that a large proportion of SPRINT participants were reclassified to lower risk categories using PREVENT and still benefited from intensive therapy raises some questions. 

They also noted that if side effects from treatment are considered equally as serious as cardiovascular outcomes, then lowering blood pressure might not seem worthwhile for most people who haven’t yet developed cardiovascular disease. However, they said research shows that patients think major events like stroke and heart attack are much worse than treatment-related side effects such as kidney injury, fainting, or low blood pressure. 

“Consequently, modeling a risk threshold to determine the net benefit for blood pressure-lowering treatment has been challenging, as all outcomes cannot be considered equal,” McCarthy and colleagues wrote.

Furthermore, the commentary observed that the new 2025 ACC/AHA high blood pressure guideline has expanded pharmacologic treatment to low-risk individuals with stage 1 hypertension if their blood pressure remains uncontrolled despite lifestyle interventions. In doing so, the guideline in essence has shifted away from a black-and-white recommendation based on a cardiovascular risk threshold alone.

As a result, shared decision-making between patient and healthcare provider, particularly for low-risk individuals, is more crucial than ever, with possible treatment options at times on the more conservative side, they added.

In an interview, McCarthy elaborated: “For instance, for a patient with frailty or symptomatic orthostatic hypotension, if you are starting blood pressure-lowering therapy, you might start with monotherapy instead of a single-pill combination. Or if the patient is not tolerating intensive blood pressure targets (eg, targeting a systolic blood pressure of 120 mm Hg), you might just lower the blood pressure to as low as that individual can tolerate without side effects, but not necessarily that low.”

Bress reported receiving grants from the National Institute on Aging and from the National Heart, Lung, and Blood Institute. Derington reported having no conflicts of interest. McCarthy reported receiving support from the National Heart, Lung, and Blood Institute and consulting fees or honoraria from Abbott Laboratories, Alnylam Pharmaceuticals, Corcept Therapeutics, Cleerly Health, Heartflow, NewAmsterdam Pharma, and Roche Diagnostics. Brown reported receiving support from the National Heart, Lung, and Blood Institute and consulting fees from Recordati Rare Diseases Inc. and AstraZeneca. 

Lois Anzelowitz Levine is a medical writer who has written for Dermatology Times, Infection Control Today, and Contemporary Pediatrics, among other journals. She is based in Dallas.