Improved risk stratification in prevention by use of a panel of selected circulating microRNAs

Abstract

Risk stratification is crucial in prevention. Circulating microRNAs have been proposed as biomarkers in cardiovascular disease. Here a miR panel consisting of miRs related to different cardiovascular pathophysiologies, was evaluated to predict outcome in the context of prevention. MiR-34a, miR-223, miR-378, miR-499 and miR-133 were determined from peripheral blood by qPCR and combined to a risk panel. As derivation cohort, 178 individuals of the DETECT study, and as validation cohort, 129 individuals of the SHIP study were used in a case-control approach. Overall mortality and cardiovascular events were outcome measures. The Framingham Risk Score(FRS) and the SCORE system were applied as risk classification systems. The identified miR panel was significantly associated with mortality given by a hazard ratio(HR) of 3.0 (95% (CI): 1.09–8.43; p = 0.034) and of 2.9 (95% CI: 1.32–6.33; p = 0.008) after adjusting for the FRS in the derivation cohort. In a validation cohort the miR-panel had a HR of 1.31 (95% CI: 1.03–1.66; p = 0.03) and of 1.29 (95% CI: 1.02–1.64; p = 0.03) in a FRS/SCORE adjusted-model. A FRS/SCORE risk model was significantly improved to predict mortality by the miR panel with continuous net reclassification index of 0.42/0.49 (p = 0.014/0.005). The present miR panel of 5 circulating miRs is able to improve risk stratification in prevention with respect to mortality beyond the FRS or SCORE.

The Potential Role of Platelet-Related microRNAs in the Development of Cardiovascular Events in High-Risk Populations, Including Diabetic Patients: A Review

“…To date, three studies analyzed the association of miR-223 with clinical endpoints ( 37 – 39 ). Schulte evaluated 873 individuals and revealed that elevated miR-223 levels reliably predicted future cardiovascular deaths [HR 2.23 per one SD increase (1.20; 4.14), P = 0.011, C-index 0.80], as 2.1% ( n = 18) of the subject experienced cardiovascular death over a median follow-up time of 4 years ( 37 ).…”

“…More recently, Keller et al analyzed a panel of miRNAs to predict outcome in the context of cardiovascular disease prevention. They determined that all-cause 5-year mortality was associated with lower miR-223 levels (HR: 0.30; 95% CI: 0.08–1.07; P = 0.063) ( 39 ). The presented results show that miR-223 may not only serve as a biomarker of platelet activation, but could also be exploited as a prognostic marker.…”

Circulating miR-26a, miR-106b, miR-107 and miR-133b stratify hepatocellular carcinoma patients according to their response to transarterial chemoembolization

“…A growing evidence elucidates the role of microRNAs (miRs) in development and progression of HCC. Since miRs are released to the circulating blood, their potential value as diagnostic and prognostic markers in HCC have gained more attention [9][10][11][12][13][14]. There is an increasing interest in understanding the association of miR expression in HCC cells with their chemo-and radiosensitivity to increase the efficacy of the treatment modality in HCC patients.…”

Strategies for the prevention of chronic non-communicable diseases: a modern look at the problem

“…Одним из многообещающих способов улучшения стандартных шкал риска FRS (Framingham Risk Score) -Фрамингемская шкала риска, и SCORE (Systematic COronary Risk Evaluation) -Систематическая оценка коронарного риска, в дополнение к описанным ранее [44], является панель циркулирующих микроРНК -биомаркеров ССЗ, характеризующих различные патофизиологические механизмы, которые играют важную роль в развитии и прогрессировании патологии [45][46][47][48]. Эта работа продемонстрировала, что анализ отдельных микроРНК не обладает прогностической ценностью в отношении смертности от ССЗ, тогда как вся панель способна значительно улучшить существующую стратификацию риска [45].…”