Haptoglobin and other biomarkers of coronary artery disease in young adults with hypertension and acute myocardial infarction

Abstract

Acute myocardial infraction (AMI) is the most common clinical manifestation of coronary artery disease (CAD). Young age is no longer considered a protective factor since the incidence of young adults with AMI is increasing. Hypertension is an important risk factor for CAD in young adults. Prehypertension without proper management is also associated with an increased risk of CAD. Hence, the identification of CAD biomarkers in young hypertensive and prehypertensive adults is necessary to improve risk stratification of premature AMI in these cohorts. The main objective of this study was to compare protein expression profiles of young adults with AMI to control subjects for the identification of proteins (candidate biomarkers) that are differentially expressed in AMI patients. This study also aimed to determine the plasma concentrations of the candidate biomarkers in young adults with normotension, prehypertension, hypertension and AMI and evaluate the relationship between AMI and potential CAD biomarker/s in young hypertensive and prehypertensive subjects. This study comprised of two phases; discovery and verification. In the discovery phase, proteins in the pooled plasma samples from young male adults (10 AMI patients and 10 controls) aged 18 to 45 years were separated by two-dimensional gel electrophoresis (2-DE). The protein spots that were differentially expressed in AMI patients relative to the controls were identified via matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry. In the verification phase, the plasma concentrations of the identified proteins were measured using enzyme-linked immunosorbent assay (ELISA) in 40 plasma samples of control, prehypertensive, hypertensive and AMI groups. In the discovery phase, haptoglobin (Hp), apolipoprotein AI (Apo AI) and apolipoprotein AIV (Apo IV) were significantly upregulated in AMI patients in comparison to the controls (p < 0.05). Meanwhile in the verification phase, the plasma concentration of Hp was significantly higher in AMI patients in comparison to the control, prehypertensive and hypertensive subjects (290.63±99.90 vs. 170.02±108.11 vs. 175.05±108.11 and vs. 208.47±112.97 ng/ml, p < 0.006) respectively. The plasma concentrations of Apo AI and Apo AIV were also elevated in AMI patients, yet the increases were not significant compared to the other groups (p > 0.05). Plasma concentration of Hp was significantly associated with young AMI (OR: 1.019, 95% CI: 1.006-1.033, p = 0.003) after adjusting for other known CAD risk factors. There was also a significant association between AMI and plasma concentration of Hp in hypertensive and prehypertensive subjects (OR: 0.985, 95% CI: 0.973-0.997, p = 0.017 and OR: 0.981, 95% CI: 0.969-0.993, p = 0.002) respectively, independent of other known CAD risk factors. Plasma Hp concentration was significantly correlated with high sensitivity C-reactive protein hs-CRP (r = 0.370, p < 0.001). In Conclusion, consistent upregulation of Hp in discovery and verification phases reflect its potential role as a biomarker of CAD in young adults. Hp is also a potential CAD biomarker that could be utilized as AMI predictor in young adults with hypertension and prehypertension.The significant correlation between Hp and hs-CRP indicates the potential role of these proteins as inflammatory markers in the establishment of CAD in young adults.