Elevated NT-ProBNP Identifies Subjects at High CV Risk
<ѻý class="dek">—These data provide evidence that increased levels of NT-proBNP in patients without cardiovascular disease are associated with increased risk for cardiovascular events.ѻý>Elevated levels of NT-proBNP among individuals with mildly elevated blood pressure may identify those at higher risk for heart failure, ischemic stroke, and cardiovascular and all-cause mortality, as well as those who might benefit from intensive blood pressure goals, recent study findings suggest.1
“Hypertension management is crucial in the prevention of all types of cardiovascular diseases,” Aliza Hussain, MD, of Baylor College of Medicine in Houston, Texas, told ѻý. “However, clinically it can also be very challenging. We know that as systolic blood pressure increases above 115 mmHg cardiovascular risk increases but treatment has its own side effects.”
The recent American College of Cardiology/American Heart Association hypertension guidelines established new cutoffs for diagnosing hypertension and recommended more intensive goals for blood pressure based on 10-year cardiovascular risk estimated using the pooled cohort equation.2 Notably, this equation does not include heart failure as a predicted outcome.
“Biomarkers such as NT-proBNP and high-sensitivity troponins can detect subclinical disease and identify those at risk of developing cardiovascular disease,” noted Hussain. “Therefore, we wanted to evaluate whether NT-proBNP could help identify individuals at the highest risk for cardiovascular disease, and hence, help identify those who may, in theory, benefit most from intensive blood pressure control.”
Elevated NT-proBNP is associated with cardiovascular outcomes
The population-based ARIC study included 15,792 men and women (41.7% men; 21.5% black) aged 45 to 64 years from 4 communities in the US between 1987 and 1989. Among 11,656 participants who attended ARIC visit 4 in 1996 to 1998, 9309 participants without CVD were included. Participants with higher baseline levels of NT-proBNP were more likely to be older, White, women, and smokers; to have hypertension or diabetes; and to use antihypertensive medications.
Over a median of 16.3 years of follow-up, 25.9% of participants experienced a cardiovascular event, including 1359 incidents of congestive heart disease, 500 incidents of ischemic stroke, and 1328 heart failure hospitalizations. Overall, 52% of participants with baseline NT-proBNP of 300 pg/mL or higher experienced a cardiovascular disease event during follow-up.
Increasing NT-proBNP levels (≥100 pg/mL) were associated with higher risk of cardiovascular disease events, cardiovascular mortality, and all-cause mortality, independent of systolic blood pressure.
“Patients with systolic blood pressure between 120 and 139 mm Hg (stage 1 hypertension) but with elevated NT-proBNP (>100 pg/mL) had a higher risk for cardiovascular disease, particularly heart failure and cardiovascular mortality, compared with those with a higher systolic blood pressure of 140-149 mmHg (stage 2 hypertension) but NT-proBNP <100 pg/mL,” Hussain noted.
Similar associations were observed for incident congestive heart disease, ischemic stroke, and heart failure hospitalization. Increasing NT-proBNP levels had consistently higher event rates and significantly increased risk of each cardiovascular event across all diastolic blood pressure categories.
“Although it is not surprising that NT-proBNP predicted all cardiovascular events, including incident stroke, we were surprised with the strength of association with stroke across blood pressure categories,” Hussain said. “In prior studies, another well-studied biomarker, high-sensitivity cardiac troponin T, has shown at best a modest association with ischemic stroke.”
Conclusions
“NT-proBNP is traditionally considered to be a prognostic marker in heart failure,” Hussain said. “However, our data provide strong evidence that increased levels of NT-proBNP in patients without cardiovascular disease are associated with increased risk for cardiovascular events, including heart failure and cardiovascular mortality, across narrow categories of systolic blood pressure, diastolic blood pressure, and pulse pressure.”
The main limitation of this study is the observational design, requiring randomized prospective clinical trials to establish whether biomarker-based strategies for intensive blood pressure management can improve outcomes compared to the traditional approach.
“Biomarkers that identify subclinical cardiovascular injury/disease and reflect the downstream consequences of cardiac risk factors are well suited to help identify patients in whom the risk-benefit will be most favorable,” Hussain concluded.
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