Serum Bone Morphogenic Protein-4 Contributes to Discriminating Coronary Artery Disease Severity

Bone morphogenic protein 4 (BMP-4) is a known pro-inflammatory and pro-atherogenic cytokine. Here, we investigated whether the serum BMP-4 level predicts coronary artery disease (CAD) severity in humans. We measured serum BMP-4 concentrations in 1044 consecutive patients who underwent elective coronary angiography and percutaneous coronary intervention. CAD severity was estimated by the number of diseased vessels showing ≥50% diameter stenosis. Among males, the serum BMP-4 level was significantly lower in patients with multivessel disease (MVD) compared with those with single-vessel disease (SVD) (16.3 ± 22.6 vs. 22.0 ± 28.4 pg/mL, P < 0.01). After adjustment for other cardiovascular risk factors, a high serum BMP-4 level was an independent predictor for a decreased risk of MVD (odds ratio, 0.992; 95% confidence interval [CI], 0.985–0.998; P = 0.01) and patients in the lower tertile were 1.55-fold more likely to have MVD compared with upper tertile patients. Receiver-operating characteristic curve analysis demonstrated that the serum BMP-4 level had a 54% sensitivity and 54% specificity for predicting MVD (area under the curve [AUC], 56.5%; 95% CI, 51.9–61.0%; P < 0.01). Serum BMP-4 improved the predictive capability of risk factors for MVD (AUC with and without BMP-4: 64.9 and 63.6%, respectively). Considering the likelihood ratio and number of parameters, adding the serum BMP-4 level provided a better-fit model for predicting MVD compared with the model consisting of conventional risk factors (likelihood ratio χ(2) = 6.20, P = 0.01). However, an association between serum BMP-4 and CAD was not observed in females. Serum BMP-4 levels are independently associated with CAD severity and contribute to discriminating CAD severity in males.