Cyclin dependent kinase inhibitor 1 C is a female-specific marker of left ventricular function after acute myocardial infarction. (1st January 2019)

• Record Type: Journal Article
• Authors: Lalem, Torkia; Zhang, Lu; Scholz, Markus; Burkhardt, Ralph; Saccheti, Victoria; Teren, Andrej; Thiery, Joachim; Devaux, Yvan
• Is Part Of: International journal of cardiology. Volume 274(2019)
• Page Start: 319
• Page End: 325
• Publication Date: 2019-01-01
• Subjects: AMI acute myocardial infarction -- CDKN1C cyclin dependent kinase inhibitor 1C -- CPK creatine phosphokinase -- cTn cardiac troponins -- EF ejection fraction -- HF heart failure -- KCNQ1OT1 KQT-like subfamily, member 1 opposite strand/antisense transcript 1 -- LV left ventricular -- Nt-proBNP N-terminal pro brain natriuretic peptide -- STEMI ST-segment elevation myocardial infarction -- NSTEMI non-ST-segment elevation myocardial infarction; Myocardial infarction -- Left ventricular function -- Gender -- Biomarkers -- Gene expression; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2018.07.042
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: A significant proportion of patients develop left ventricular (LV) remodeling leading to heart failure after acute myocardial infarction (AMI). Being able to identify these patients would represent a step forward towards personalized medicine. The present study aimed to determine the ability of cyclin dependent kinase inhibitor 1C (CDKN1C) to risk stratify AMI patients, in a sex-specific manner. Methods: CDKN1C expression was measured in blood samples obtained at admission in a test cohort of 447 AMI patients and a validation cohort of 294 patients. The study end-point was LV function assessed by the ejection fraction (EF) at follow-up. Results: In the test cohort, CDKN1C was lower in patients with a reduced EF (<40%) compared to patients with preserved EF (≥50%). This observation was specific to women. CDKN1C was a significant univariate predictor of LV function in women only. In multivariable analysis including demographic and clinical parameters, CDKN1C predicted LV function in women (odds ratio [95% confidence interval] 0.44 [0.23–0.82]) but not in men (0.90 [0.70–1.16]). Addition of CDKN1C to a multivariable clinical model reduced the Akaike information criterion, attesting for an incremental predictive value, in women ( p = 0.006) but not in men ( p = 0.41). Bootstrap internal validation confirmed the added value of CDKN1C in women. The female-specific predictive value of CDKN1C was validated in the independent cohort. Conclusion: CDKN1C is a novel female-specific biomarker of LV function after AMI. Highlights: Predicting outcome after myocardial infarction would allow personalizing healthcare. Current prediction strategies lack accuracy and are not sex-specific. The CDKN1C gene predicts outcome after myocardial infarction, specifically in women. This finding was validated in two independent patient cohorts. CDKN1C is a novel female-specific prognostic biomarker after myocardial infarction.