Incorporation of biomarkers into risk assessment for allocation of antihypertensive medication according to the 2017 ACC/AHA high blood pressure guideline: a pooled cohort analysis

Authors: Ambarish Pandey, Kershaw V. Patel, Wanpen Vongpatanasin, Colby Ayers, Jarett D. Berry, Robert J. Mentz, Michael J. Blaha, John W. McEvoy, Paul Muntner, Muthiah Vaduganathan, Adolfo Correa, Javed Butler, Daichi Shimbo, Vijay Nambi, Christopher deFilippi, Stephen L. Seliger, Christie M. Ballantyne, Elizabeth Selvin, James A. de Lemos, Parag H. Joshi


Study Questions: Can blood-based biomarkers improve the risk stratification of patients with stage 1 hypertension but otherwise no indication for antihypertensive therapy?

Methods: The authors measured high-sensitivity troponin T (hs-TnT) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels in 12,987 participants included from three population-based cohorts in the Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis. Participants with known cardiovascular disease (CVD) or on antihypertensive therapy were excluded. The authors examined the association between biomarker levels and a composite of CV events (nonfatal myocardial infarction, nonfatal stroke, CV death, or heart failure [HF]), stratified by blood pressure groups defined according to the latest American College of Cardiology/American Heart Association (ACC/AHA) high blood pressure guideline and atherosclerotic CVD (ASCVD) risk.

Results: Overall, the combined cohort consisted of 55% women, with a mean age of 55 years, of whom 22% had elevated hs-TnT (>6 ng/L) and 18% had elevated NT-proBNP (>100 pg/ml). Participants with elevated biomarkers were more likely to be older and have CV risk factors. Across all blood pressure-defined subgroups and subset without left ventricular hypertrophy, participants with higher biomarker levels had a higher incidence of CV events including incident HF. Notably, participants with stage 1 hypertension but no indication for antihypertensives and high biomarker levels had a 11% incidence of CV events at 10 years compared to 4.6% in those with low levels. Using effect size derivations from the SPRINT trial for that subgroup, the authors estimated a number needed to treat of 36 to prevent one event within 10 years, compared to 85 for those with high biomarker levels.

Conclusions: High hs-TnT and NT-proBNP levels are associated with higher risk of CV events even in patients with stage 1 hypertension and no indication for antihypertensive therapy.

Perspective: The study highlights two important points: 1) a substantial proportion of participants with stage 1 hypertension who are otherwise not recommended antihypertensive therapy have high levels of hs-TnT and NT-proBNP, and 2) these biomarkers can further risk-stratify a subgroup of hypertensives otherwise deemed as low risk. What is assumed by the authors but, however, not shown in the study itself, is that antihypertensive therapy in this subgroup of patients with high biomarker levels may lead to improved outcomes. This remains an assumption, as treatment with antihypertensives may not mitigate the increased risk associated with high hs-TnT and NT-proBNP levels. Clinical trials should incorporate biomarker measurements to identify subgroups that would maximally derive benefit from treatments.

Source: Circulation, 2019