Red blood cell fatty acid levels improve GRACE score prediction of 2-yr mortality in patients with myocardial infarction

Abstract

Background: Blood omega-3 and omega-6 fatty acid levels have been associated with reduced risk for total mortality in patients with stable coronary heart disease (CHD), but their relationships with mortality in the setting of myocardial infarction (MI) are unknown.

Objective: To determine the association between red blood cell (RBC) fatty acid levels measured at admission and 2-year mortality in MI patients, independent of the GRACE risk score, a traditional mode of risk stratification.

Design: Admission RBC fatty acid levels were measured in patients enrolled in a prospective, 24-center MI registry (TRIUMPH). Two-year mortality was modeled with Cox proportional hazards regression to assess the extent to which the inclusion of fatty acid levels would improve, over and above the GRACE score, risk stratification for 2-year mortality.

Results: RBC fatty acid data were available from 1144 patients who did not report taking fish oil supplements after discharge. Two RBC fatty acids [eicosapentaenoic acid (EPA) and docosapentaenoic n-6 (DPA)] were univariate predictors of total mortality. The combined fatty acid c-statistic (0.60, p<0.001) improved the c-statistic of the GRACE score alone from 0.747 (p<0.001) to 0.768 (p<0.05 vs. GRACE alone). The net reclassification index improved by 31% (95% CI, 15% to 48%) and the relative incremental discrimination index improved by 19.8% (7.5% to 35.7%).

Conclusion: RBC EPA and DPA n-6 levels improved the prediction of 2-yr mortality over and above the GRACE score in MI patients.

Keywords: CAD; CHD; CV; DHA; DPA; Docosapentaenoic acid; EDTA; EPA; Eicosapentaenoic acid; GRACE; GRACE score; Global Registry of Acute Coronary Events; MI; Mortality; Omega-3 fatty acids; RBC; TRIUMPH; Translational Research Investigating Underlying disparities in recovery from acute Myocardial infarction; US; United States; cardiovascular; coronary artery disease; coronary heart disease; docosahexaenoic acid; docosapentaenoic acid; eicosapentaenoic acid; ethylenediaminetetraacetic acid; myocardial infarction; red blood cells.

Figure 1

The Martingale residual plots show the difference between the observed and predicted (by GRACE score) 2-year mortality as a function of two RBC fatty levels: A) eicosapentaenoic acid (EPA) and B) n-6 docosapentaenoic acid (both expressed as a % of total RBC fatty acids). Values above 0 represent more deaths than predicted, and those below, fewer deaths than predicted. The relationship between EPA and risk was non-linear, therefore cut points (vertical lines) were selected to estimate high (<0.25%), intermediate (0.25% and 0.8%) and low risk categories (>0.8%). Therefore, EPA was modeled as a categorical variable. Relationships with DPA were relatively linear, therefore this fatty acid was modeled as a continuous variable.

Figure 1

The Martingale residual plots show the difference between the observed and predicted (by GRACE score) 2-year mortality as a function of two RBC fatty levels: A) eicosapentaenoic acid (EPA) and B) n-6 docosapentaenoic acid (both expressed as a % of total RBC fatty acids). Values above 0 represent more deaths than predicted, and those below, fewer deaths than predicted. The relationship between EPA and risk was non-linear, therefore cut points (vertical lines) were selected to estimate high (<0.25%), intermediate (0.25% and 0.8%) and low risk categories (>0.8%). Therefore, EPA was modeled as a categorical variable. Relationships with DPA were relatively linear, therefore this fatty acid was modeled as a continuous variable.

Figure 2

Kaplan-Meier curves describing the unadjusted mortality by A) RBC EPA cutpoints (log rank p<0.001), and B) RBC DPA tertiles (log rank p=0.018).

Figure 2

Kaplan-Meier curves describing the unadjusted mortality by A) RBC EPA cutpoints (log rank p<0.001), and B) RBC DPA tertiles (log rank p=0.018).