The ratio of serum n-3 to n-6 polyunsaturated fatty acids is associated with diabetes mellitus in patients with prior myocardial infarction: a multicenter cross-sectional study

Abstract

Background: In prior myocardial infarction (PMI) patients, diabetes mellitus (DM), dyslipidemia, and hypertension increase the risk of secondary cardiovascular events. Although a decreased ratio of serum eicosapentaenoic acid (EPA) to arachidonic acid (AA; EPA/AA) has been shown to significantly correlate with the onset of acute coronary syndrome, the associations between polyunsaturated fatty acid (PUFA) levels and coronary risk factors in PMI patients have not been evaluated thoroughly. This study aimed to assess the associations between PUFAs levels and the risk factors in PMI patients.

Methods: We enrolled 1733 patients with known PUFA levels who were treated in five divisions of cardiology in a metropolitan area of Japan, including 303 patients with PMI. EPA/AA and docosahexaenoic acid (DHA) to AA level ratio (DHA/AA) in patients with and without PMI were analyzed according to presence of coronary risk factors.

Results: Diabetes patients with PMI had significantly lower EPA/AA and DHA/AA than diabetes patients without PMI (EPA/AA: P <0.01; DHA/AA: P =0.003), with no such differences in dyslipidemia and hypertension patients. In DM patients with high high-sensitivity C-reactive protein (hs-CRP) levels (>0.1 mg/dL), EPA/AA was low in individuals who also had PMI, whereas DHA/AA was not (EPA/AA, with PMI: 0.43 ± 0.24; without PMI: 0.53 ± 0.30, P < 0.05). Moreover, patients on statins had significantly lower DHA/AA ratios, whereas the EPA/AA ratio did not depend on statin use. Multiple regression analysis revealed that statin use in DM patients was associated with low DHA/AA but not EPA/AA.

Conclusion: PMI patients with DM have low EPA/AA and DHA/AA. EPA/AA and DHA/AA are differently related to hs-CRP level in DM patients with PMI. Statin use can potentially affect DHA/AA but not EPA/AA, and therefore EPA/AA ratio is a better marker of assessment for cardiovascular events.

Keywords: Diabetes mellitus (DM); Eicosapentaenoic acid (EPA); High-sensitivity C-reactive protein (hs-CRP); Inflammation; Polyunsaturated fatty acids (PUFAs); Prior myocardial infarction (PMI); Statin.

Fig. 1

Comparison of ratios of eicosapentaenoic acid (EPA) to arachidonic acid (AA) levels (EPA/AA) and docosahexaenoic acid (DHA) to arachidonic acid (AA) levels (DHA/AA) between the patients with and without prior myocardial infarction (PMI). Analysis for all patients (a) and patients with hypertension (HTN; b), dyslipidemia (DL; c), and diabetes mellitus (DM; d). A statistically significant difference in EPA/AA ratios was only present for the patients with DM, whereas that in DHA/AA ratios was present for all and DM patients

Fig. 2

Eicosapentaenoic acid to arachidonic acid (EPA/AA, panel a) and docosahexaenoic acid to AA (DHA/AA, panel b) ratios were categorized according to high-sensitivity C-reactive protein (hs-CRP) levels (the threshold between low and high hs-CRP levels was set to 0.1 mg/dL) in all, hypertension, dyslipidemia, and diabetes mellitus (DM) patients with or without prior myocardial infarction (PMI). ^* P < 0.05 (with vs. without PMI); ^# P < 0.01 (with vs. without PMI)

Fig. 3

Ratios of n-3 PUFA to AA levels plotted against levels of hemoglobin A1c (HbA1c). The ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA, EPA/AA) was significantly correlated with HbA1c levels in diabetes mellitus (DM) patients with prior myocardial infarction (PMI) (N = 117, R = 0.18, P = 0.049, panel a) and in patients with PMI (N = 245, R = 0.16, P = 0.015, panel b), but not in the entire cohort (N = 1103, panel c). The ratio of docosahexaenoic acid (DHA) to AA (DHA/AA) was significantly correlated with HbA1c levels in DM patients with PMI (N = 117, R = 0.21, P = 0.020, panel d) and in patients with PMI (N = 245, R = 0.17, P = 0.008, panel e), but not in the entire cohort (N = 1103, panel f)