Sulfido-peptide leukotrienes in coronary heart disease - relationship with disease instability and myocardial ischaemia

P>Background Urinary excretion of leukotriene (LT) E-4 is an index of LTC4 biosynthesis and platelet-neutrophil interactions, which may occur in coronary heart disease and contribute to myocardial ischaemia. Enhanced LTC4 biosynthesis may be a consequence of myocardial ischaemia or be linked to its pathogenetic substrate. Methods and results Overnight urine collections were obtained from 17 patients with chronic stable angina, three patients with Prinzmetal's angina, 16 patients with non ST-elevation acute coronary syndromes (NSTE-ACS) and six patients with acute ST-elevation myocardial infarction (STEMI). LTE4 excretion was measured by enzyme immunoassay after HPLC separation. Compared with healthy controls (51 center dot 1 +/- 21 center dot 3 pg mg-1 creatinine, mean +/- SD, n = 11) and with non-coronary cardiac controls (36 center dot 6 +/- 9 center dot 8 pg mg-1 creatinine, n = 9), LTE4 excretion was unchanged in stable angina (40 center dot 5 +/- 25 center dot 8 pg mg-1 creatinine), but significantly (P < 0 center dot 01) increased in NSTE-ACS (122 center dot 7 +/- 137 center dot 2 pg mg-1 creatinine) and STEMI (213 center dot 4 +/- 172 center dot 4 pg mg-1 creatinine). In these patients, LTE4 excretion rapidly dropped after day 1, consistent with effective coronary reperfusion. In patients with NSTE-ACS, the increase in LTE4 excretion was entirely restricted to patients with recent (< 48 h) spontaneous anginal episodes. Myocardial ischaemia elicited by a positive exercise stress test was not accompanied by any detectable increase in LTE4 excretion, while a significant (P < 0 center dot 01) increase was detected after a single-vessel percutaneous coronary interventions (PCI) procedure (n = 10), as compared with diagnostic angiography (n = 9). Conclusions In coronary heart disease, increased LTC4 biosynthesis is restricted to ACS and not linked to myocardial ischaemia per se, but likely to the occurrence of plaque disruption.