21st European Meeting on Hypertension and Cardiovascular Prevention

Adding baseline N-terminal brain natriuretic peptide (NT-BNP) values to standard cardiovascular (CV) risk models improved risk prediction in patients with hypertension and no history of cardiovascular disease (CVD), according to a retrospective analysis from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Professor Peter S. Sever, Imperial College, London, UK, presented findings from the study.

Previous reports from the landmark ASCOT demonstrated the benefits of primary prevention with intensive blood pressure control and lipid-lowering therapy in patients with hypertension [Sever PS. Lancet 2003; Dahlöf B. Lancet 2005]. The ASCOT Biomarker Programme was designed to evaluate the prognostic value of baseline NT-BNP and plasma renin activity (PRA) measures using nested case-control studies. Baseline measures in patients who developed CV events (‘cases’) during ASCOT were compared to those of matched participants who did not develop CV events (‘controls’).

In a multivariate analysis, baseline NT-BNP significantly predicted future CV events. Baseline NT-BNP was prognostic when measured as a continuous variable (p <0.0001) and when the highest-risk tertile was compared with the lowest risk tertile (OR, 1.70; p = 0.0007).

To understand the implications of adding NT-BNP to current risk models, investigators calculated the net reclassification of individuals (NRI), a statistical measure that estimates the usefulness of novel biomarkers. For the 483 patients who experienced an event, adding NT-BNP to the Framingham risk model increased the estimated probability of an event in 229 and decreased the estimated probability in 212, resulting in a net gain in reclassification of 3.5%. Among 1364 controls, adding NT-BNP increased the estimated probability in 563 and decreased in 676, for a net gain in reclassification for the model with NT-BNP over the model without NT-BNP of 8.3%. Overall, adding NT-BNP to the risk model improved the ability of the Framingham risk score to predict future CV events 11.8% (p = 0.02).

In contrast to NT-BNP, baseline PRA measurements did not correspond with CV events or all-cause mortality in this patient population. However, baseline PRA identified patients with worsening renal function over 5.5 years of follow-up (p=0.04). After adjusting for other baseline variables including antihypertensive therapy, patients in the highest-risk quartile (PRA >2.5 ng/mL/hr) were nearly 4 times as likely to develop renal impairment as those in the lowest-risk quartile (PRA <0.78 ng/mL/hr; OR, 3.89; p=0.02).

In this retrospective analysis of patients with hypertension and no history of CV events, baseline NT-BNP and PRA measures enhanced the assessment of CV and renal risk, respectively. The true value of these measures in evaluating risk and guiding therapy must be evaluated in prospective clinical trials.

Further Reading:

Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895-906.

Sever PS, Dahlöf P, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003;361:1149-1158.