Brain Natriuretic Peptide Measurement in Rheumatoid Arthritis Save

Cardiovascular (CV) risk and adverse cardiac outcomes are common in rheumatoid arthritis (RA). It has been presumed that chronic systemic inflammation has a deleterious effect on the myocardium and vasculature, thereby leading to higher rates of MI, CHF and CV death. These assertions are supported by numerous studies showing that chronic use of either methotrexate or TNF inhibitors improves survival and lowers CV event rates and CV death, especially in those who are treated for greater than 18 months.

For the last 15 years, brain natriuretic peptide (BNP) has become an often used biomarker for the assessment of heart failure (CHF) especially in urgent or emergent evaluations. Finding a normal BNP can easily rule out heart failure or significant left ventricular (LV) dysfunction. BNP is produced by the ventricles in response to distention of the myocytes. There are several kinds of natriuretic peptides secreted by the heart: atrial (ANP) and brain (BNP). BNP has a longer half-life than does ANP and N-terminal fragment of BNP (NT-proBNP) has an even longer half-life and is more sensitive than does BNP, making it a better assay for cardiac status. Both BNP and NT-pro-BNP can be assayed, with higher levels found in patients with CHF. Most authors agree that a cutoff level of 100 ng/L of BNP has a strong negative predictive value, ruling out a diagnosis of heart failure. BNP levels may be affected by underlying conditions such as renal failure or chronic pulmonary disease (increased levels), obesity (falsely low levels), insulin resistance in RA (higher level) and high titers of RF (lowers by up to 21%).

Several studies have assessed the utility of BNP measurements in either screening for CV risk or monitoring response to therapy in those with heart failure or CV risk. BNP is strongly correlated with NY State Cardiac status and BNP level is a strong predictor of risk of death and cardiovascular events in patients previously diagnosed with heart failure or cardiac dysfunction. The value of BNP for monitoring therapeutic success can be questioned for trials that demonstrate clinical benefit without statistically significant decreases in biomarker levels. NT-pro-BNP levels have been shown to have predictive value in both at-risk populations and the general population; where higher levels are associated with higher CV event rates (2, 3).

BNP testing may also predict death and cardiovascular events in patients without a previous heart disease diagnosis. There are studies that assess the prognostic value of BNP in asymptomatic populations. In the two largest studies, the relative risk of death during the four to five have years of follow-up approximately doubled in patients with a BNP value higher than relatively low cutoff levels (17.9 to 23.3 pg per mL [17.9 to 23.3 ng per L]).

BNP levels have been studied in the early inflammatory arthritis (IP) patients in the Norfolk RA registry (4). In their 960 early IP subjects, 17% had prior CVD history, 39% patients had a baseline NT-pro-BNP levels ≥ 100 pg/ml. NT-pro-BNP was correlated with age, female gender, HAQ score, CRP, current smoking, history of hypertension, prior CVD and the presence of carotid plaque. Ten percent of these IP subjects died including 31 (3%) from CVD. In an age and gender adjusted analysis, having a raised NT-pro-BNP level (≥ 100 pg/ml) was associated with both all-cause and CVD mortality (adjusted HR (95% CI) 2.36 (1.42 to 3.94) and 3.40 (1.28 to 9.03), respectively). These authors suggested that NT-pro-BNP may have may play a role in a screening strategy to identify IP patients who may benefit from a more aggressive risk management strategy for CVD. Nevertheless they called for a better understanding of the relationship between NT-pro-BNP and cardiac/vascular outcomes in patients with inflammatory disease to establish its predictive utility.

Crowson et al studied RA patients without a history of CVD and compared 231 RA and 1,730 non-RA subjects. They and others have found that RA patients may have higher BNP levels than controls (16% versus 9%; P 0.001). They found BNP was significantly higher in subjects with moderate/severe LV dysfunction (by ECHO) compared to those with no or mild LVD (P = 0.02 for RA and P 0.001 for non-RA subjects). However the positive predictive value (25% in RA and 18% in non-RA subjects) and sensitivity (40% in RA and 26% in non-RA subjects) were both similarly low and the specificity was significantly lower in RA than in non-RA subjects (89% versus 94%; P = 0.02). They suggested that BNP may be less effective as a screening tool in RA, especially when compared to the general population (5).

There are no current recommendations calling for the use of BNP screening in the general population. BNP or NT-proBNP screening is not appropriate for low-risk, asymptomatic patients. Screening may have value in certain at-risk populations. But if the goal is to assess LV function, echocardiography is still the study of choice.

As a significant number of RA patients may be at risk for LV dysfunction and future CV events, further research is needed to define if one time or annual screening of BNP is appropriate and sufficiently predictive.

References

1. http://emedicine.medscape.com/article/761722-overview#a7

2. N Engl J Med. 2005 Feb 17;352(7):666-75.

3. Eur Heart J. 2010 Jan;31(1):120-7.

4. Ann Rheum Dis. 2014 Apr;73(4):684-90.

5. Arthritis Care Res (Hoboken). 2011 May;63(5):729-34.