Amino-terminal fragment of the prohormone brain-type natriuretic peptide in rheumatoid arthritis

Abstract

Objective: Increased concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality, but little is known about their relationship to chronic inflammation. Patients with rheumatoid arthritis (RA) have chronic inflammation, increased arterial stiffness, and accelerated coronary atherosclerosis. This study was undertaken to test the hypothesis that NT-proBNP concentrations are elevated in patients with RA and are associated with coronary artery calcification and markers of inflammation.

Methods: In 159 patients with RA (90 with early RA and 69 with longstanding RA) without heart failure and 88 control subjects, serum concentrations of NT-proBNP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha) were measured and coronary calcification was assessed. Associations between NT-proBNP levels and the other parameters were investigated.

Results: NT-proBNP concentrations were elevated in patients with longstanding RA (median 142.8 pg/ml [interquartile range 54.8-270.5]) and those with early RA (median 58.1 pg/ml [interquartile range 19.4-157.6]) compared with controls (18.1 [3.2-46.0]) (P < 0.001). In patients with RA, NT-proBNP concentrations were associated with age (rho = 0.35, P < 0.001), levels of IL-6 (rho = 0.33, P < 0.001), TNFalpha (rho = 0.23, P = 0.003), and C-reactive protein (CRP) (rho = 0.21, P = 0.01), coronary calcium score (rho = 0.30, P < 0.001), systolic blood pressure (rho = 0.30, P < 0.001), and disease activity (rho = 0.29, P < 0.001). After adjustment for age, race, and sex, the associations between NT-proBNP concentrations and disease activity, TNFalpha, IL-6, and CRP remained significant, but those with systolic blood pressure and coronary calcium score were attenuated.

Conclusion: NT-proBNP concentrations are increased in patients with RA without clinical heart failure and may indicate subclinical cardiovascular disease and a chronic inflammatory state.

Figure 1. Serum Concentrations of NT-proBNP in patients with early RA, long-term RA, and controls

PANEL A: Concentrations of NT-proBNP in patients with early and late RA and control subjects. The box represents the 25^th –75^th percentile. The median is shown as a line across the box. The whiskers represent the lower quartile minus 1.5 times the interquartile range, or the upper quartile plus 1.5 times the interquartile range. Concentrations were higher in patients with early and late RA than control subjects, (P<0.001) for both comparisons after adjustment for age, race and sex. PANEL B: Model predicted concentrations of NT-proBNP after adjustment for age, sex, homocysteine, HDL and LDL cholesterol, triglycerides, lipoprotein (a), hypertension, BMI, diabetes, smoking, creatinine, family history of coronary heart disease, and past history of cardiovascular disease. Adjusted means and 95% confidence intervals are represented.