Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock

Abstract

Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5–10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p < 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1–3.0), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2–3.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.

miR-21 in Human Cardiomyopathies

“…In other cases, various cardiomyopathies, including dilated cardiomyopathy, left ventricular ejection fraction, and ischemic cardiomyopathy, upregulated miR-21 expression levels were shown in heart tissue and circulation (53,54,58,65). In addition, increased miR-21 level was suggested as a new biomarker of cardiovascular disease-related premature death to predict patients at great risk of adverse outcomes (66,67). However, unchanged expression miR-21 level was also reported in patients with hypertrophic cardiomyopathy (53).…”

Diagnostic and prognostic significance of miR-320a-3p in patients with chronic heart failure

“…Among many miRNAs, the focus of this study is miR-320a-3p, a well-known miRNA, which is abnormally expressed in many cancers, such as lung cancer [17], breast cancer [18]. Previous studies have shown that miR-320a-3p levels in circulating plasma at baseline in non-survivors of cardiogenic shock are elevated and correlated with markers of hypoperfusion [19]. Second, Burns et al found in a study on adverse drug reactions that miR-320a-3p was enhanced in the serum of patients with clozapine-induced cardiotoxicity [20].…”

Trimethylamine n-Oxide (TMAO) Modulates the Expression of Cardiovascular Disease-Related microRNAs and Their Targets

“…miR-21 has been extensively studied in cancerous processes and has recently been linked to CVDs and inflammation [ 14 , 15 ]. It has been shown that circulating levels of miR-21 are increased in subjects with a higher risk of CVD death, with atherosclerosis [ 16 ], and with cardiogenic shock [ 45 ], suggesting its potential as a biomarker to assess CVD risk. Indeed, consumption of the Mediterranean diet with extra virgin olive oil seems to reduce circulating miR-21 [ 46 ].…”