Sphingosine-1-phosphate: A mediator of the ARB-MI paradox?

BACKGROUND

Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are important in the prevention of cardiovascular disease. The "ARB-MI paradox" implies that no risk reduction of myocardial infarction (MI) was found in ARB-treated patients despite target blood pressure control. Sphingosine-1-phosphate (S1P) is a cardioprotective sphingolipid which is released by platelets during activation. In this study we aimed to investigate differences of S1P homeostasis mediated by bradykinin and sphingosine kinases during ACEI/ARB treatment.

METHODS

In this hypothesis generating pilot study, we investigated S1P plasma concentrations in 34 patients before and 3 months after ARB/ACEI medication. S1P levels were measured via liquid chromatography-tandem mass spectrometry. Bradykinin levels were measured by an enzyme-linked immunosorbent assay.

RESULTS

Patient characteristics were not different between the ACEI and ARB group. Baseline S1P plasma concentrations were similar before ARB and ACEI treatment (7.4 SD 1.9 pmol vs. 7.8 SD 2.7 pmol, p = 0.54). After 3 months, S1P plasma levels were significantly higher in ACEI (9.3 SD 2.2 pmol) as compared to ARB treated patients (7.4 SD 2.4 pmol, p = 0.001). Pearson correlation showed no significant association between bradykinin and S1P levels before (r = -0.219; 95% CI [-0.54-0.15]; p = 0.245) or after three months of treatment with ACEI or ARB (r = -0.015; 95% CI [-0.48-0.45]; p = 0.95).

CONCLUSIONS

S1P plasma concentrations are higher in ACE treated patients as compared to ARB treatment. This leads to the hypothesis, that differences in S1P metabolism might partially explain the ARB-MI paradox. This needs to be tested in clinical trials.