Lo Presti R

Persistence of high plasma elastase level in young subjects with acute myocardial infarction.

Activated granulocytes release several proteins and among these elastase plays a key-role in the development and progression of coronary heart disease (CHD). In subjects with angiographically diagnosed coronary lesions, plasma elastase was significantly increased in comparison with normal controls and also distinguished subjects with coronary complex atheromatous plaque from those with simple plaque (1,2). In the Edinburgh Artery Study (3) the group of subjects with baseline angina, during more than 5-year follow-up, showed a positive association between elastase level and risk for fatal or nonfatal cardiovascular events. Other authors (4) had previously observed an increase of peptide Bβ30-43 (a specific human granulocyte elastase-derived peptide) in subjects with unstable angina and acute myocardial infarction (AMI). Elastase was evaluated during and after cardiopulmonary resuscitation in a group of subjects with cardiac arrest subdivided according to the return or not to spontaneous circulation (5). This proteolytic enzyme, measured after arrival at the emergency department and after 30 minutes, 60 minutes, 6 hours, and 24 hours, was increased in the survivors and also at the first points of observation in the nonsurvivors. In the survivor group, elastase reached the peak after 6 and 24 hours and this trend is similar to that observed by other authors (6). Our group (7) recently evaluated plasma elastase, employing an enzyme-linked immunosorbent assay method, in a group of 49 young subjects with AMI (46 men and 3 women; mean age 38.8 ± 6.8 years; range 19–45 years). Regarding risk factors, 49% had family history of CHD, 61% were cigarette smokers, and 16% exsmokers; hypercholesterolemia was present in 26%, diabetes mellitus in 14%, and essential hypertension in 10%. Two of the three women were taking oral contraceptives. The time interval between AMI onset and the first examination (T1) was 13 ± 7 days and all the patients were reexamined three months after the first evaluation (T2). All the patients were treated with angiotensin-converting enzyme (ACE) inhibitors, statins, and platelet antiaggregation agents (aspirin or ticlopidine or clopidogrel). In this group of AMI patients, the elastase level was raised compared to control subjects, both at T1 (AMI patients: 101.60 ± 41.90 ng/mL; control subjects: 59.73 ± 17.60 ng/mL; P < .001) and at T2 (AMI patients: 91.65 ± 36.50 ng/mL; P < .001 vs control subjects). In control subjects and in AMI patients, both at T1 and T2, no relationship was found between plasma elastase and granulocyte count. These data confirm our previous findings regarding other aspects of granulocyte function in subjects with recent AMI (8). We in fact observed an abnormality in granulocyte membrane fluidity and cytosolic Ca2+ content (in particular after in vitro activation) that was still present after 12 months. An antielastase action has been observed for some calcium channel blockers (9,10), but their employment in AMI patients has not been evaluated from this point of view and is controversial because of collateral effects. In experimental models of myocardial ischemia, administration of elastase inhibitors was followed by a decrease in tissue damage (11,12).