SISANews

Nuovi marcatori per la cardiopatia ischemica

Ancora metabolomica. Si sono messi insieme svedesi, americani ed inglesi per studiare con cromatografia liquida e spettrometria di massa il metaboloma, cioè l'insieme dei metaboliti necessari alle reazioni biochimiche e prodotti da esse, al fine di identificare quelli associati al rischio di malattia coronarica. Sono stati studiati 3.668 soggetti che facevano parte di tre studi di popolazione e sono stati trovati quattro metaboliti (lisofosfatidilcolina 18:1, lisofosfatidilcolina 18:2, monogliceride 18:2 e sfingomielina 28:1) che mostravano una significativa associazione con la malattia coronarica, indipendentemente dai tradizionali fattori di rischio. Anche in questo studio, al pari di quanto emerso in quello illustrato in precedenza in questa rubrica (23.12.2014), l'aggiunta di questi nuovi biomarcatori ai fattori di rischio tradizionali porta solo ad un miglioramento marginale della stratificazione del rischio.

Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease.

Ganna A, Salihovic S, Sundström J, Broeckling CD, Hedman ÅK, Magnusson PKE, Pedersen NL,
Larsson A, Siegbahn A, Zilmer M, Prenni J, Ärnlöv J, Lind L, Fall T, Ingelsson E

PLOS Genet 2014;10:e1004801

Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18:1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18:2 (HR = 0.81, P-value<0.001), monoglyceride 18:2 (MG 18:2; HR = 1.18, P-value = 0.011) and sphingomyelin 28:1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18:2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18:2. MG 18:2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18:2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.

PLOS Genet 2014;10:e1004801