Details

Autor(en) / Beteiligte

• Shah, Svati H., MD, MHS
• Sun, Jie-Lena, MS
• Stevens, Robert D., PhD
• Bain, James R., PhD
• Muehlbauer, Michael J., PhD
• Pieper, Karen S., MS
• Haynes, Carol, BS
• Hauser, Elizabeth R., PhD
• Kraus, William E., MD
• Granger, Christopher B., MD
• Newgard, Christopher B., PhD
• Califf, Robert M., MD
• Newby, L. Kristin, MD, MHS

Titel

Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease

Ist Teil von

• The American heart journal, 2012-05, Vol.163 (5), p.844-850.e1

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Background Cardiovascular risk models remain incomplete. Small-molecule metabolites may reflect underlying disease and, as such, serve as novel biomarkers of cardiovascular risk. Methods We studied 2,023 consecutive patients undergoing cardiac catheterization. Mass spectrometry profiling of 69 metabolites and lipid assessments were performed in fasting plasma. Principal component analysis reduced metabolites to a smaller number of uncorrelated factors. Independent relationships between factors and time-to-clinical events were assessed using Cox modeling. Clinical and metabolomic models were compared using log-likelihood and reclassification analyses. Results At median follow-up of 3.1 years, there were 232 deaths and 294 death/myocardial infarction (MI) events. Five of 13 metabolite factors were independently associated with mortality: factor 1 (medium-chain acylcarnitines: hazard ratio [HR] 1.12 [95% CI, 1.04-1.21], P = .005), factor 2 (short-chain dicarboxylacylcarnitines: HR 1.17 [1.05-1.31], P = .005), factor 3 (long-chain dicarboxylacylcarnitines: HR 1.14 [1.05-1.25], P = .002); factor 6 (branched-chain amino acids: HR 0.86 [0.75-0.99], P = .03), and factor 12 (fatty acids: HR 1.19 [1.06-1.35], P = .004). Three factors independently predicted death/MI: factor 2 (HR 1.11 [1.01-1.23], P = .04), factor 3 (HR 1.13 [1.04-1.22], P = .005), and factor 12 (HR 1.18 [1.05-1.32], P = .004). For mortality, 27% of intermediate-risk patients were correctly reclassified (net reclassification improvement 8.8%, integrated discrimination index 0.017); for death/MI model, 11% were correctly reclassified (net reclassification improvement 3.9%, integrated discrimination index 0.012). Conclusions Metabolic profiles predict cardiovascular events independently of standard predictors.