Hyperglycemia Drives Stent Restenosis in STEMI Patients

ST-elevation myocardial infarction (STEMI) is one of the leading causes of death and hospitalization worldwide (1). Hyperglycemia (HG) has been shown to adversely affect STEMI clinical outcomes, leading to higher mortality and severe complications (1,2).

The aim of our study was to investigate the impact of HG at hospital admission on the risk of restenosis after primary percutaneous coronary intervention (PCI) for STEMI, comparing normoglycemic subjects (NG group), patients without diabetes mellitus (DM) but with HG (HG-non-DM group), and patients with both HG and DM (HG-DM group). HG was defined by glycemia >140 mg/dL, according to the guidelines of the American Diabetes Association (3). We evaluated STEMI patients referred to the Division of Cardiology of “Antonio Cardarelli” Hospital from February 2008 to February 2016. Inclusion criteria were age >18 years and first STEMI. Exclusion criteria were left ventricular ejection fraction <25% and prior coronary artery bypass grafting. Routine blood analysis, including HbA_1c, was obtained at admission. The STEMI culprit lesion was identified and treated via primary PCI, crossed with an angioplasty guidewire followed by stent implantation. All patients were contacted 1 year after the procedure. The sample size was calculated via GPower software. Research was carried out according to the Declaration of Helsinki, and every patient signed an informed consent; the Institutional Review Board of the University of Campania approved the protocol.

The three groups (NG, HG-non-DM, and HG-DM) were matched using a propensity score-matching algorithm developed according to the predictive probabilities of a multivariable logistic regression model. We calculated Kaplan-Meier product limit estimates and compared curves, from admission to 365 days, using the log-rank test. Furthermore, we performed a multivariate Cox regression analysis to calculate hazard ratio, CI, and P value, evaluating whether age, systolic and diastolic blood pressure, heart rate, glycemia, BMI, total and LDL cholesterol, creatinine, use of statins, and HbA_1c could affect the risk of restenosis. Rehospitalization for restenosis was defined as readmission to the hospital for acute coronary syndrome, which was confirmed to be due to restenosis of a previously successfully treated lesion, as determined by quantitative coronary angiography (2). All calculations were computed using SPSS 26.

A total of 336 propensity score-matched patients were included in the study: 112 NG, 112 HG-non-DM, and 112 HG-DM. We used bare metal stents or 2nd-generation drug-eluting stents (DES), detecting no significant differences among our three groups in terms of the type of stent implanted (percentage of 2nd-generation DES: NG 76.8%, HG-non-DM 76%, HG-DM 77%).

At 1 year follow-up, 6.5% of NG, 14.0% of HG-non-DM, and 18.5% of HG-DM patients had been rehospitalized for restenosis; Kaplan-Meier curves (P = 0.009) are depicted in Fig. 1A.

Interestingly, the significant association between restenosis and glycemia at hospital admission in HG-non-DM patients was confirmed in a Cox proportional hazards regression model after adjusting for other potential risk factors for restenosis, including cholesterol (total and LDL), creatinine, BMI, systolic and diastolic blood pressure, heart rate, age, use of statins, and HbA_1c values (Fig. 1B).

HG triggers endothelial dysfunction, an established mechanism underlying restenosis (4), leading to vascular damage and microvascular obstruction(s), and is also known to increase oxidative stress, inflammation, and platelet aggregation (1,4). Of note, HG may also be a marker for disease severity (5). During the year following the PCI, other factors, including blood pressure control, HbA_1c, and lipid levels, all could have affected the risk of restenosis (6); however, in our regression analysis the association between restenosis and glycemia in HG-non-DM patients remained significant even after accounting for an expanded set of potential risk factors.

To the best of our knowledge, the impact of HG on restenosis has not been assessed in patients without DM. The current study is the first to evaluate the effects of HG on the risk of restenosis in STEMI patients without DM, comparing the results to both HG-DM and NG subjects. Taken together, our data indicate that HG is associated with adverse outcomes in STEMI patients independent of DM.