Abstract
Introduction: Women are frequently present with questionable angina . Lack of specificity and sensitivity in imaging procedures and absence of a blood-based biomarker that can detect myocardial ischemia earlier than cell death, may contribute to women being under-investigated and under-treated, with worse outcomes. The blood-based biomarkers, Nourin protein and its regulatory miRNAs (miR-137 and miR-106b) are elevated in the setting of myocardial ischemia before it progresses to infarction . Hypothesis: Unlike hs-TnI, Nourin-dependent miR-137 and miR-106b can identify or exclude myocardial ischemia in patients suspected of having CAD, as proven by stress test results. Methods: Serum levels of Nourin miRNAs (qPCR) and plasma hs-TnI were measured blindly in: 1) chest pain patients suspected of having CAD (n=12) both before stress ECHO/ECG test (pre-test) and 30 minutes after test completion (post-test); 2) STEMI patients (n=16); and 3) healthy subjects (n=16). Results: 1) very low baseline levels of Nourin miRNAs in healthy (range: 1.38 to 1.43) and CAD negative (range: 1.84 to 4.53); 2) significant upregulation of miR-137 (2,156 pre and 2,574 post) and miR-106b (423 pre and 521 post) in CAD positive (n=5) compared to CAD negative (n=7) (range: 1.84 to 4.53) pre-test (continuous release in response to chronic myocardial ischemia) and post-test; 3) higher levels in STEMI (4,509 (miR-137) and 950 (miR-106b) pre) compared to CAD (2,156 and 423 pre); 4) over 86% sensitivity and 100% specificity that can “rule out” myocardial ischemia, just as NT-proBNP for heart failure and D-dimer for deep vein thrombosis; and 5) hs-TnI was elevated only in STEMI, but not in CAD patients, pre & post. Conclusions: Assessment of Nourin miRNAs enables the identification of a population of patients with ischemia, but without injury or infarction , and exclusion of myocardial ischemia, based on its strong negative predictive value, thus potentially improving the treatment algorithms for women .
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