Acute Hyperglycemia Worsens Post-AMI Prognosis

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Patients with acute myocardial infarction (AMI) have poorer short-term outcomes if they develop acute hyperglycemia, according to a registry study published online September 26, 2014, ahead of print in the American Journal of Cardiology. However, the adverse impact of acutely elevated glucose levels is neutralized by a history of hyperglycemia.

Methods
Investigators led by Masaharu Ishihara, MD, of the Hyogo College of Medicine (Nishinomiya, Japan), analyzed data from 696 AMI patients who presented to the National Cerebral and Cardiovascular Center of Japan within 48 hours of onset and were enrolled in its registry between January 2007 and June 2012. Overall, 652 patients (94%) underwent emergency angiography and 606 (87%) received primary PCI. Grade 3 final TIMI flow was achieved in 91% of the PCI cohort.

 

 Patients with acute hyperglycemia (defined as admission plasma glucose 200 mg/dL; 23%) had higher plasma glucose levels on admission and higher HbA1c values (reflecting average glucose levels over about 2 months) than those without acute hyperglycemia (both P < .001). Acute hyperglycemia patients also had more diabetes, chronic kidney disease, and Killip class of at least 2 as well as higher mean BMI.

Patients with chronic hyperglycemia (defined as an HbA1c 6.5%; 30%) had higher admission plasma glucose and HbA1c (both P < .001) as well as more diabetes and dyslipidemia compared with those with euglycemia.

Peak creatine kinase levels and in-hospital mortality were higher for patients with acute hyperglycemia than those without the condition, while these outcomes were similar between patients with vs without chronic hyperglycemia (tables 1 and 2).

Table 1. Short-term Outcomes by Acute Hyperglycemia Status

 

With

(n = 163)

Without

(n = 533)

P Value

Peak Creatine Kinase, IU/L

4,094 ± 4,594

2.526 ± 2,227

< .001

In-Hospital Mortality

9.8%

1.6%

< .001

  

 Table 2. Short-term Outcomes by Chronic Hyperglycemia Status

 

With

(n = 212)

Without

(n = 484)

P Value

Peak Creatine Kinase, IU/L

2,803 ± 2,661

2,940 ± 3,181

.59

In-Hospital Mortality

3.3%

3.7%

.79

 

On multivariate analysis, acute hyperglycemia was associated with a more than 6-fold increased risk of in-hospital mortality (OR 6.35; 95% CI 2.29-18.9; P < .001), while chronic hyperglycemia showed no such link (P = .16). Similarly, analyzed as a continuous variable, plasma glucose predicted in-hospital mortality (OR 1.21; 95% CI 1.09-1.35; P < .001), but HbA1c did not (P = .36).

Interestingly, among patients with acute hyperglycemia, a concomitant history of chronic hyperglycemia was associated with smaller peak creatine kinase (3,221 ± 3,001 vs 5,904 ± 6,473 IU/L; P < .001) and lower in-hospital mortality (5.5% vs 18.9%; P = .01).

How Acute Hyperglycemia Harms Vessels

Acute hyperglycemia is common in AMI patients regardless of diabetic status, the authors note. Experimental and clinical studies have shown that the increase in plasma glucose causes a host of harmful effects, including oxidative stress, inflammation, apoptosis, endothelial dysfunction, and hypercoagulation. Moreover, in patients undergoing primary PCI, no-reflow is predicted by acute hyperglycemia but not by a history of diabetes or by HbA1c level (Iwakura K, et al. J Am Coll Cardiol. 2003;41:1-7). In addition, the study authors previously reported that acute hyperglycemia abolishes any positive effect of ischemic preconditioning.

Together, these factors promote myocardial damage and worse outcomes after AMI, Dr. Ishihara and colleagues say.

The investigators also offer several possible reasons why chronic hyperglycemia may attenuate the adverse effects of acute hyperglycemia in patients with both conditions. The magnitude of acute glucose elevation in patients with chronic hyperglycemia may be relatively small because baseline levels are likely already high, they say. Moreover, “[e]xperimental studies have suggested that [the] diabetic heart is paradoxically more resistant to ischemic insults,” they observe, adding that decreased glucose utilization in diabetic cells may be beneficial in the setting of high plasma glucose.

Results of previous studies investigating the hypothesis that continuous insulin infusion to normalize glucose levels can improve AMI outcomes have been inconsistent, the authors observe. However, they suggest, inclusion of patients with concomitant acute and chronic hyperglycemia may have diluted any positive effects of the treatment.

‘Skillful’ Insulin Infusion May Be Beneficial

In a telephone interview with TCTMD, Paul S. Jellinger, MD, of the University of Miami Miller School of Medicine (Miami, FL), said that while “there is a lot of experimental evidence that a sudden sharp rise in glucose is harmful to already damaged [myocardial] tissue, the idea that patients with chronic hyperglycemia don’t seem to be as vulnerable is a new twist.” Adaptive mechanisms may be at work, he said, although that is speculative.

Dr. Jellinger suggested that the mixed results of studies testing insulin infusion to counter acute hyperglycemia may be due in part to the fact that most were performed by cardiologists, who are not as experienced in controlling blood sugar as endocrinologists or diabetologists. “I think there is something to be said for reasonably tight glucose control by way of an insulin infusion at the time of acute MI as long as it is done skillfully and blood sugar is not allowed to deteriorate to hypoglycemia,” he observed.

The current study, Dr. Jellinger added, is “a bit of a wake-up call to cardiologists managing AMI patients to reevaluate their targets for glucose control, which have slacked off in the past few years out of concern for some studies showing that it might not be so helpful.”

 

Source:

Fujino M, Ishihara M, Honda S, et al. Impact of acute and chronic hyperglycemia on in-hospital outcomes of patients with acute myocardial infarction. Am J Cardiol. 2014;Epub ahead of print.

  • The paper contains no statement regarding conflicts of interest for Dr. Ishihara.
  • Dr. Jellinger reports no relevant conflicts of interest.

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Disclosures
  • The study was supported by the Intramural Research Fund for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center of Japan.

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