Mass spectrometry in medicine: a technology for the future?

Mass spectrometry in medicine: a technology for the future

In reply: Response to letter to the editor ‘Predictive Value of NT-proBNP in Patients with Acute Myocardial Infarction’; Regarding Article ‘Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction"

In reply: Response to letter to the editor ‘Predictive Value of NT-proBNP in Patients with Acute Myocardial Infarction’; Regarding Article ‘Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction

Advances in quadrupole and time-of-flight mass spectrometry for peptide MRM based translational research analysis

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The application of unit resolution tandem quadrupole and high-resolution orthogonal acceleration ToF mass spectrometers for the quantitation and translational analysis of proteolytic peptides is described. The MS platforms were contrasted in terms of sensitivity and linear response. Moreover, the selectivity of the platforms was investigated and the effect on quantitative precision studied. Chromatographic LC conditions, including gradient length and configuration, were investigated with respect to speed/throughput, while minimizing isobaric interferences, thereby providing information with regard to practical sample cohort size limitations of LC-MS for large cohort experiments. In addition to these fundamental analytical performance metrics, precision and linear dynamic ranges were also studied. An LC-MS configuration that encompasses the best combination of throughput and analytical accuracy for translational studies was chosen, despite the MS platforms giving similar quantitative performance, and instances were identified where alternative combinations were found to be beneficial. This configuration was utilized to demonstrate that proteolytically digested nondepleted samples from heart failure patients could be classified with good discriminative power using a subset of proteins previously suggested as candidate biomarkers for cardiovascular diseases

Trimethylamine N-oxide and risk stratification after acute myocardial infarction

© 2016 American Association for Clinical Chemistry. BACKGROUND: Risk stratification in acute myocardial infarction (MI) remains a clinical challenge. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, was investigated for its ability to assist in risk stratification for acute MI hospitalizations. METHODS: TMAO was analyzed in 1079 acute MI patients. Associations with adverse outcome of all-cause mortality or reinfarction (death/MI) for shorter (6-month) and longer (2-year) terms were assessed and compared to other cohort-specific biomarkers. Added value in risk stratification by combined use with the Global Registry of Acute Coronary Events (GRACE) score was also investigated. RESULTS: TMAO independently predicted death/MI at 2 years [292 events, hazard ratio 1.21 (95% CI, 1.03-1.43), P = 0.023], but was not able to predict death/MI at 6 months (161 events, P = 0.119). For death/MI at 2 years, TMAO retained independent prediction of risk (P = 0.034) and improved stratification even after addition of multiple alternative and contemporary biomarkers previously shown to provide added prognostic value in this cohort. From these contemporary biomarkers, TMAO remained the only significant predictor of outcome. Further, TMAO improved risk stratification for death/MI at 6 months by down-classifying risk in patients with GRACE score > 119 and plasmaTMAOconcentration ≤3.7 μmol/L. CONCLUSIONS: TMAO levels showed association with poor prognosis (death/MI) at 2 years and superiority over contemporary biomarkers for patients hospitalized due to acute MI. Furthermore, when used with the GRACE score for calculating risk at 6 months, TMAO reidentified patients at lower risk after initial categorization into a higher-risk group and showed usefulness as a secondary risk stratification biomarker

Trimethylamine N-oxide and risk stratification after acute myocardial infarction (vol 63, pg 420, 2017) [Correction]

Trimethylamine N-oxide and risk stratification after acute myocardial infarction (vol 63, pg 420, 2017) [Correction

Pro-substance p for evaluation of risk in acute myocardial infarction.

Background Pro-substance P (ProSP) is a stable surrogate marker for labile substance P, which has pro-inflammatory effects, increases platelet aggregation and clot strength, and reduces fibrinolysis. Objectives This study assessed whether ProSP was associated with poor prognosis after acute myocardial infarction (AMI) to identify novel pathophysiological mechanisms. Methods ProSP was measured in 1,148 AMI patients (825 men, mean age 66.2 ± 12.8 years). Endpoints were major adverse cardiac events (composite of death, reinfarction, and heart failure [HF] hospitalization), death/reinfarction, and death/HF. GRACE (Global Registry of Acute Coronary Events) scores were compared with ProSP for death and/or reinfarction at 6 months. Results During 2-year follow-up, there were 140 deaths, 112 HF hospitalizations, and 149 re-AMI. ProSP levels were highest on the first 2 days after admission and related to estimated glomerular filtration rate, age, history of diabetes, ischemic heart disease or hypertension, Killip class, left ventricular wall motion index, and sex. Multivariate Cox regression models showed ProSP level was a predictor of major adverse events (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 1.10 to 1.54; p < 0.002), death and/or AMI (HR: 1.42; 95% CI: 1.20 to 1.68; p < 0.0005), death and/or HF (HR: 1.38; 95% CI: 1.14 to 1.67; p < 0.001). ProSP levels with GRACE scores were independent predictors of 6-month death and/or reinfarction (p < 0.0005 for both). ProSP-adjusted GRACE scores reclassified patients significantly (overall category-free net reclassification improvement of 31.6 (95% CI: 14.3 to 49.0; p < 0.0005) mainly by down-classifying those without endpoints. Conclusions ProSP levels post-AMI are prognostic for death, recurrent AMI, or HF, and they improve risk prediction of GRACE scores, predominantly by down-classifying risk in those without events