Biomarker Levels ID Patients With Most to Gain From Intensive BP Lowering

Intensive lowering of blood pressure improves clinical outcomes across a broad swath of patients, although the absolute benefits are magnified in those with elevated levels of biomarkers that have been associated with risks of death and heart failure (HF), a post hoc analysis of the SPRINT trial shows.

Trial participants with higher levels of high-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) had both greater risks of those adverse outcomes and the most to gain from intensive treatment, Jarett Berry, MD (UT Southwestern Medical Center, Dallas, TX), and colleagues report in a study published online in JAMA Cardiology.

Though the results also show that the relative benefits of aggressive treatment were consistent regardless of biomarker levels, they nevertheless raise the possibility of using a more-individualized approach for intensive BP control, Berry told TCTMD.

“I already measure these markers as a guide to help me think about applying intensive blood pressure control in the same way that I use coronary calcium as a guide to identify who might be a candidate for statin therapy,” he explained.

“The field has mixed opinions on this,” he acknowledged. “You have the guideline-based approach, the trial-based approach, and I think you also have some of these observations that have not been formally tested in trials and that are not present in the guidelines that I think are nuanced. And I think that it provides an opportunity for personalized medicine. The conclusion of the paper probably goes further than just: ‘We should use this to encourage patients to take their blood pressure medicine.’ I think there’s an opportunity here, but I think the flip side is if someone has squeaky clean, normal biomarkers, our data would suggest that the benefit of [intensive] treatment is pretty minimal.”

The results are “pretty persuasive,” Berry stressed, “but I think for most physicians and I think for the guidelines we’re going to need to see a prospective trial that’s based on this concept.”

Seeing a greater impact of intensive treatment in the highest-risk patients “is not something really unexpected” because that’s typically been seen with other interventions, commented Salim Hayek, MD (University of Michigan, Ann Arbor).

Thus, even though the idea was to identify a group of patients who might warrant special attention when it comes to delivering intensive BP lowering, the study shouldn’t change management approaches, “because even the patients with the low biomarker levels still derive benefit from aggressive blood pressure reduction,” he told TCTMD. That “essentially means that there is no reason to specifically select the higher-risk patients.”

Groups Most at Risk

To evaluate the influence of biomarker levels on the impact of intensive BP lowering, the investigators turned to the SPRINT trial. The main results showed that treating systolic BP to a goal of less than 120 mm Hg versus a goal of less than 140 mm Hg reduced adverse clinical outcomes, including all-cause mortality and HF, in nondiabetic patients with hypertension and a high cardiovascular risk.

This post hoc analysis defined an elevated high-sensitivity troponin T level as 14 ng/L or more and an elevated NT-proBNP level as 125 pg/mL or more. Overall, 25.6% and 38.2%, respectively, had increased levels of those biomarkers, with median concentrations of 9.4 ng/L and 86 pg/mL.

I already measure these markers as a guide to help me think about applying intensive blood pressure control in the same way that I use coronary calcium as a guide to identify who might be a candidate for statin therapy. Jarett Berry

As expected, patients with increased biomarker levels had worse clinical outcomes, including a greater risk of a composite of all-cause mortality and HF—that went for troponin T (HR 1.60; 95% CI 1.26-2.04) and NT-proBNP (HR 2.26; 95% CI 1.76-2.89). Patients with elevations in both biomarkers had the highest risk (HR 4.75; 95% CI 3.48-6.81) compared with those with normal levels of both.

For the outcome of death/HF through 4 years of follow-up, intensive BP lowering led to a greater absolute reduction in patients with versus without elevated levels of troponin (4.9% vs 1.7%) and with versus without increased NT-proBNP concentrations (4.6% vs 1.8%). The disparity in risk reduction was greatest for patients with higher levels of both biomarkers (7.8% vs 1.7%).

However, “no significant treatment group by biomarker category interactions were seen,” the researchers report, indicating that the relative benefits of intensive treatment were consistent regardless of biomarker levels.

Implications at Multiple Levels

These findings “could have implications for population health programs,” Berry et al say, noting that implementing intensive BP control across the population would be difficult and would come with increases in syncope, hypotension, or both.

“Our data suggest the hypothesis that integrating widely available biomarker tests with these types of systems-level interventions could represent an efficient and effective approach to identifying patients at the highest risk for CVD,” Berry et al write, acknowledging that additional research is needed to test this.

Researchers say the results could be useful when it comes to discussing potential management plans with patients, especially those reluctant to take additional medications. They stress, however, that “these data do not support the use of low biomarker levels to defer intensive blood pressure control.”

Still, for Berry, there’s room for nuanced decision-making. “I do think that there is an opportunity to identify that subgroup of patients who are going to benefit most and I think it allows us to . . . personalize our recommendations a little bit more armed with this information,” he said, citing the example of a patient with a systolic BP in the high 130s who doesn’t tolerate intensive therapy and has normal biomarker levels as someone who may not need to be treated as aggressively. “On the flip side, if those biomarkers are elevated, I think it would suggest we really need to get serious about hitting these lower targets, because you’re really going to benefit from this. So I think it provides an opportunity, but I think it’s the first chapter in a longer story that needs to be written.”

Hayek said “the findings here do not justify us using biomarkers as a guide to target blood pressure reduction.” He added, however, that the study “doesn’t invalidate the use of biomarkers in general. It just says that in this specific satiation, [patients with either] high biomarkers and low biomarkers derive some benefit.”

Future clinical trials, he said, “should incorporate biomarkers of risk to always identify the population which would derive the most benefit from a treatment. So this is a great example of how it could potentially be used. It didn’t pan out here in the sense that all groups did benefit, but perhaps for other therapies we could find differences between groups.”