Abstract
Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 ± 60% in S10 and decreased by −6 ± 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 ± 145% (WS), 22 ± 117% (S20), 16 ± 61% (S40) and −2% ± 88% (S80) (p = 0.001). In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.
Highlights
Regardless of acute phase glycaemia, the residual risk of death in patients with myocardial infarction (MI) remains high
There were no significant differences between simvastatin groups regarding sex, gender, clinical characteristics upon admission, or anthropometric characteristics
The differences in Delta insulin sensitivity index (ISi) between simvastatin groups were confirmed by both Student’s t-test (p = 0.04) and Analysis of covariance (ANCOVA) adjusted for sex, age, and ISi at D2 (p = 0.025)
Summary
Regardless of acute phase glycaemia, the residual risk of death in patients with MI remains high Mitigation of this residual risk has been attempted through the inclusion of high dose of potent statins in the early treatment of acute coronary syndromes (ACS), a rationale that was largely based on a broad range of potentially beneficial mechanisms[9], even though evidence from clinical trials does not fully support this practice[10,11]. It can be hypothesized that statin treatment initiated in the acute phase of MI may favor hyperglycaemia during the acute phase If this is so, such negative effect may restrict or even surpass a spectrum of beneficial mechanisms related to the use of these drugs during ACS9. Euglycemic hyperinsulinemic clamps (EHC) were used for being the gold standard method in a small group of patients and the Homeostasis Model Assessment (HOMA) was used for being a fast and accessible index feasible to be applied in a larger group of STEMI patients allowing us to confirm the findings and investigate interactions
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