Objective: To study the role of long noncoding RNAs as potential biomarkers in heart disease. Methods and Results: Global transcriptomic analyses were done in plasma RNA from patients with or without left ventricular remodeling after myocardial infarction. Regulated candidates were validated in 3 independent patient cohorts developing cardiac remodeling and heart failure (788 patients). The mitochondrial long noncoding RNA uc022bqs.1 (LIPCAR) was downregulated early after myocardial infarction but upregulated during later stages. LIPCAR levels identified patients developing cardiac remodeling and were independently to other risk markers associated with future cardiovascular deaths. Key Words: cardiac biomarkers ■ cardiac remodeling ■ circulating lncRNA ■ heart failure ■ mitochondria ■ myocardial infarction ■ RNA, long noncoding Conclusions: LIPCAR isOriginal received March 10, 2014; revision received March 20, 2014; accepted March 24, 2014. In February 2014, the average time from submission to first decision for all original research papers submitted to Circulation Research was 13.8 days.Brief UltraRapid Communications are designed to be a format for manuscripts that are of outstanding interest to the readership, report definitive observations, but have a relatively narrow scope. Less comprehensive than Regular Articles but still scientifically rigorous, BURCs present seminal findings that have the potential to open up new avenues of research. A decision on BURCs is rendered within 7 days of submission.From the Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx (R.K., I.V., J.F., A.H., T.T.) and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Hannover, Germany; Inserm, U744, University Lille Nord de France, Lille, France (C.B., F.M., G.L., P.d.G., F.P.); Institut Pasteur de Lille, Lille, France (C.B., F.M., G.L., P.d.G., F.P.); Centre Hospitalier Régional et Universitaire de Lille, Lille, France (C.B., G.L., P.d.G., F.P.); Faculté de Médecine de Lille, Lille, France (C.B., G.L.); and National Heart and Lung Institute, Imperial College London, London, United Kingdom (T.T. Methods Populations of Patients With HFThe strategy of lncRNA screening and validation is depicted in Figure 1A. A potential association between detectable lncRNAs in EDTA-plasma and presence of future LV remodeling post MI was analyzed in the REmodelage VEntriculaire (REVE)-2 cohort. This prospective multicenter study was designed to analyze the association between circulating biomarkers and LV remodeling. 15 A total of 246 patients with a first anterior wall Q-wave MI have been enrolled from February 2006 to September 2008. Inclusion criteria were hospitalization within 24 hours after symptom onset and ≥3 akinetic LV segments in the infarct zone at the predischarge echocardiography. Exclusion criteria were inadequate echocardiographic image quality, life-limiting noncardiac disease, significant valvular disease, or prior Q-wave MI. The protocol required serial echographic studies at hospital discharge ...

Effective prevention of Alzheimer’s disease (AD) requires the development of risk prediction tools permitting preclinical intervention. We constructed a genetic risk score (GRS) comprising common genetic variants associated with AD, evaluated its association with incident AD and assessed its capacity to improve risk prediction over traditional models based on age, sex, education, and APOE ε4. In eight prospective cohorts included in the International Genomics of Alzheimer’s Project (IGAP), we derived weighted sum of risk alleles from the 19 top SNPs reported by the IGAP GWAS in participants aged 65 and older without prevalent dementia. Hazard ratios (HR) of incident AD were estimated in Cox models. Improvement in risk prediction was measured by the difference in C-index (Δ–C), the integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI>0). Overall, 19,687 participants at risk were included, of whom 2,782 developed AD. The GRS was associated with a 17% increase in AD risk (pooled HR = 1.17; 95%CI = [1.13–1.21] per standard deviation increase in GRS; p-value = 2.86 × 10−16). This association was stronger among persons with at least one APOE ε4 allele (HRGRS = 1.24; 95%CI = [1.15–1.34]) than in others (HRGRS = 1.13; 95%CI = [1.08–1.18]; pinteraction = 3.45 × 10−2). Risk prediction after seven years of follow-up showed a small improvement when adding the GRS to age, sex, APOE ε4, and education (Δ–Cindex = 0.0043 [0.0019–0.0067]). Similar patterns were observed for IDI and NRI>0. In conclusion, a risk score incorporating common genetic variation outside the APOE ε4 locus improved AD risk prediction and may facilitate risk stratification for prevention trials.