Evaluation of Plasma Fibrillin-1 Fragment Levels in Patients Without Aortic Pathology

Abstract

Fibrillin-1 is a structural component muscular arteries, and plasma fibrillin-1 fragment levels (PFFLSs) are detectable in patients with aortic dissections and thoracic aortic aneurysms. However, little is known regarding PFFLSs in patients without aortic pathology or in patients with other cardiovascular conditions, thereby limiting its use as a biomarker for aortic pathology. We sought to determine the detectability and concentration of PFFLSs in patients without aortic pathology who present with acute chest pain of cardiac and noncardiac origin. Three hundred patients older than 18 years presenting to the emergency department with chief complaint of chest pain were prospectively enrolled. Patients with aortic pathology, malignancy, or postoperative pain were excluded from analysis. Demographic data, medical comorbidities, and the determined cause of chest pain was determined from the electronic medical record. PFFLSs were determined using a modified sandwich enzyme-linked immunosorbent assay with biotinylated capture antibodies and alkaline phosphatase-conjugated detector antibodies. Patients were categorized into three groups based on the cause of chest pain: group 1, ischemic cardiac chest pain (ICCP), group 2, non-ICCP (NICCP), and group 3, noncardiac chest pain (NCCP). The ICCP group consisted of patients presenting with myocardial infarction or angina. The NCCP included patients presenting with arrhythmia, heart failure, hypertensive urgency, and pericarditis/myocarditis/endocarditis. Differences in categorical variable were assessed using Fisher’s exact test and differences in continuous variables were assessed using Kruskal-Wallis test and Wilcoxon rank-sum test as appropriate. Two hundred sixty-five patients (135 men and 130 women) were included in the analysis. The cause of chest pain was determined to be ICCP in 30 patients, NICCP in 39 patients, and NCP in 196 patients. Detectable PFFLSs were found in 192 (72%) patients and detectability did not differ between genders or diagnosis groups (P = .74). Mean PFFLSs are lower in the ICCP group compared to the NICCP and NCCP groups (0.19, 0.38, and 0.56 μg/mL, respectively; P < .013). PPFLs were lower in ICCP patients with diabetes and there was a trend toward lower PPFLs in men in the ICCP group (Tables I and II). PFFLS are detectible in the majority of all patients presenting with chest pain. PFFLS are lower in patients presenting with ICCP. In patients presenting with chest pain of cardiac origin (ICCP and NICCP), PFFLSs are lower in men and patients with diabetes. Further characterization of PFFLs in patients with and without cardiovascular disease and risk factors has the potential to lead to biomarker development and mechanistic insights into cardiovascular disease development.Table IMean and interquartile values of plasma fibrillin-1 fragment levels by diagnosis groupPFFL (μg/mL)ICCP (n = 30)NICCP (n = 39)NCCP (n = 196)25th percentile00050th percentile0.020.060.0875th percentile0.060.160.23Mean0.19a0.380.56Standard deviation0.830.961.9ICCP, Ischemic cardiac chest pain; NCCP, noncardiac chest pain; NICCP, nonischemic cardiac chest pain; PFFL, plasma fibrillin-1 fragment level.aP < .013. Open table in a new tab Table IIMedian and interquartile plasma fibrillin-1 fragment levels categorized by diagnosis group, gender and presence of diabetes mellitus (DM)PPFL (μg/mL)ICCP (n = 30)NICCP (n = 39)NCCP (n = 196)DM 25th percentile0.0100.03 50th percentile0.030.040.13 75th percentile0.070.380.36 Mean0.04a0.160.55 SD0.040.221.2No DM 25th percentile000 50th percentile0.010.040.07 75th percentile0.040.380.21 Mean0.290.160.57 SD1.10.222.0Male 25th percentile000 50th percentile0.020.060.08 75th percentile0.080.160.22 Mean0.05b0.240.47 SD0.070.381.7Female 25th percentile000 50th percentile0.010.030.07 75th percentile0.040.080.23 Mean0.520.570.4 SD1.51.32.0ICCP, Ischemic cardiac chest pain; NCCP, noncardiac chest pain; NICCP, nonischemic cardiac chest pain; PFFL, plasma fibrillin-1 fragment level; SD, standard deviation.aP < .05 compared to patients with DM in the NICCP and NCCP groups.bP < .07 compared to patients with men in the NICCP and NCCP groups. Open table in a new tab