Elevated Outpatient C-Reactive Protein Independently Predicts Stroke and Gastrointestinal Bleeding in LVAD Patients

Y. Brailovsky, A. Javaid, G. M. Mondellini, L. Braghieri, M. Tiburcio, N. Uriel, G. T. Sayer, V. K. Topkara, K. Takeda, Y. Naka, R. T. Demmer, M. Yuzefpolskaya, P. C. Colombo

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Abstract

PURPOSE: Inflammation and congestion may contribute to stroke and gastrointestinal bleeding (GIB) in LVAD pts. C-Reactive Protein (CRP), erythrocyte sedimentation rate (ESR), and N-terminal-pro B-type natriuretic peptide (NT-proBNP) are established biomarkers of inflammation and congestion. We aimed to investigate the association of these biomarkers with stroke and GIB in LVAD pts who survived to their first outpt visit. METHODS: Serum CRP, ESR and NT-proBNP were prospectively measured in consecutive LVAD pts at outpt visits. Pts with stroke or GIB prior to their first visit were excluded from the respective analysis. Biomarker levels were averaged to the date of the outcome of interest. ROC curves were constructed to identify the optimal biomarkers cut off points to predict stroke and GIB. Multivariable Cox proportional hazard models were built to assess the association of CRP with stroke and GIB after adjusting for age, gender, BMI, diabetes, INTERMACS profile, and NT-proBNP. RESULTS: 228 LVAD pts (105 HMII and 105 HM3, 18 others) were enrolled. 216 pts met inclusion for the GIB analysis (Cohort 1) and 223 for the stroke analysis (Cohort 2). The median follow-up was 829 [408-1196] and 857 [464-1209]d, respectively. 35 pts had a GIB and 24 had a stroke at a median follow up of 223 [120-695] and 415 [164-768]d. Median CRP, ESR and NT-proBNP were 14.6 [7.27-30.7] mg/L, 38.3 [25.8-55.5] mm/hr, and 1144 [655-2314] pg/mL in Cohort 1, and 22 [6.14-30.5] mg/L, 41.7 [25.1-53.0] mm/hr, and 1157 [662-2366] pg/mL in Cohort 2. The ROC curves identified significant cut offs only for CRP: 15.5 mg/L (AUC 0.66, p<0.01) for stroke (Fig 1a), and 8 mg/L (AUC 0.61, p<0.05) for GIB (Fig 1b). Multivariable Cox proportional Hazard models demonstrated that CRP >15.5 mg/L was an independent predictor of stroke (HR 4.2 95% CI 1.6-11.1, p=0.004) and CRP>8 mg/L was an independent predictor of GIB (HR 3.0 95% CI 1.0-8.6, p=0.04) CONCLUSION: Elevated outpt CRP is an independent predictor of stroke and GIB in LVAD recipients.

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