Elevated admission glucose is associated with increased long-term mortality in myocardial infarction patients, irrespective of the initially applied reperfusion strategy

doi:10.1016/j.ahj.2010.06.047

American Heart Journal

Volume 160, Issue 3, September 2010, Pages 412-419

https://doi.org/10.1016/j.ahj.2010.06.047 Get rights and content

Background

It is uncertain if elevated admission plasma glucose (APG) remains an independent determinant of longer-term mortality in myocardial infarction (MI) patients with early restoration of coronary reperfusion by primary percutaneous coronary intervention. The objective of the study was to describe the relation between elevated APG and long-term mortality in MI patients undergoing invasive management.

Methods

We studied 1,185 consecutive MI patients treated in the Medical Center Alkmaar in the separate years 1996 and 1999 (preinvasive era) and 2003 and 2006 (invasive era). In both eras, APG was derived according to a standard protocol. A multivariate Cox regression model was created to study the relation between APG, reperfusion era, and 5-year mortality.

Results

During a median follow-up of 63 months, 261 patients had died. Mortality was lower in the invasive (19%) than in the preinvasive era (28%). Increased APG was associated with increased mortality, irrespective of the initial reperfusion strategy, although the relation was more pronounced in the preinvasive era (P value for heterogeneity of effects < .001). Each millimole-per-liter APG increase corresponded to a 7% increased mortality (adjusted hazard ratio 1.07, 95% CI 1.04-1.10). Patients with an APG >11 mmol/L had nearly 2-fold higher mortality (hazard ratio 1.9, 95% CI 1.3-2.7) than those with lower values.

Conclusion

Elevated APG remains a determinant of long-term mortality in MI patients, irrespective of the advances that have been made in reperfusion therapy.

Section snippets

Regional situation

The Medical Center Alkmaar (MCA) is a large teaching hospital with an adherence region of approximately 350,000 inhabitants, mainly white. Since 2002, off-site PCI service has been offered 24 hours per day and 7 days per week by 3 experienced interventional cardiologists. Surgical backup is provided by a nearby (45 km) university hospital. Currently, all patients with (suspected) MI in the larger Alkmaar area are transported to our hospital by the ambulance service to undergo immediate CAG and

Patient characteristics

The study cohort consisted of 1,185 MI patients, with a mean age of 66 ± 11 years. Most patients (72%) were men. There were some differences in baseline characteristics between the 612 patients who were treated in the years 1996 or 1999 (preinvasive era) and the 573 patients who were treated in 2003 or 2006 (invasive era) (Table I). In the invasive era, significantly more patients had known hypertension (38% vs 32%), hypercholesterolemia (58 vs 39%), a family history of MI (42% vs 28%), and

Discussion

Myocardial infarction patients who were treated during 1996-2006 in the MCA, a dedicated regional center for MI treatment, and who had elevated APG had higher 5-year mortality than their counterparts with normal glucose levels. Interestingly, high blood glucose remained associated with increased mortality in the current era of invasive management. Although at lower mortality risk than those receiving non–PCI-based treatment, apparently, patients are not protected against the negative effects of

Conclusion

Elevated APG remains a prognostic predictor of long-term outcome in the era of invasive MI treatment in patients with or without previously documented DM. Five-year mortality increases by 7% for every millimole-per-liter increase in admission glucose; the excess mortality emerged in the first month after admission. However, controversy on the optimal glucose management strategy still exists.

Acknowledgements

We would like to thank Annet Schaap for her contribution in data collection

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Citation Excerpt :
Elevated glucose levels are often seen in MI patients, even without diabetes mellitus [27]. In non-diabetic hyperglycemic MI patients, our study groups has previously found a significant association with admission glucose levels and mortality [40]. An elevated glucose level at admission is often thought of as a parameter of temporary physical stress but could also be a sign of an impaired glucose metabolism [41].
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At six months follow-up 143 (6.96%) reached the composite endpoint. Nine variables were included in the final LR model: GRACE score, urea, sodium, potassium, alkaline phosphatase, LDL cholesterol, glucose, hemoglobin and C-reactive protein. This extended GRACE score model showed improved discrimination (C-statistic 0.76 vs 0.70, p = <0.001) and classification (continuous net reclassification index 0.49, p < 0.001) compared with the GRACE score only.
The ability of the GRACE score for detecting MI patients at high risk for mortality or MI within 6 months, was significantly improved by adding several biomarkers measured routinely at admission.
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Studies differed in the determination of the threshold for stress hyperglycemia, Capes et al. [11] used the value of 110 mg/dL as the threshold for hyperglycemia in non-diabetic patients and Marfella et al. [12] used the value of 126 mg/dL. While others like Maarten de Mulder et al. [13] took the value of 140 mg/dL as the threshold. Goldberg et al. [14] supposed that instead of threshold, multiple glucose results must be analyzed; several measurements exist, such as mean glucose level, time averaged glucose level, hyperglycemia index and patient day glucose level.
Our aim was to determine the association between admission glucose level and short-term outcome and extent of coronary artery occlusion in non-diabetic patients with ST segment elevation myocardial infarction (STEMI).
250 consecutive patients were included in this study without known diabetes mellitus admitted with STEMI. Both glucose and HbA1c were measured on admission. All included patients had hemoglobin A (1c) less than 6.5%. In-hospital and 3 months' major cardiac events MACE (mortality, heart failure, arrhythmias, cardiogenic shock and recurrent ischemia) were documented. They were classified into two groups according to the admission mean glucose level (group A with glucose level ≥ 160 ± 52 mg/dl and group B included those glucose level < 160 ± 52 mg/dl).
Cardiac events were significantly higher in group A versus group-B (P < 0.001). In-hospital and 3-month mortality was higher in group-A than group-B patients (p < 0.01). Elevated admission glucose was associated with larger infarct size (P < 0.002). The prevalence of coronary lesions and the multi-vessels disease was significantly higher in group-A versus group-B patients (P < 0.01). After multivariate analysis, glucose level was independently associated with short-term mortality, and MACE (OR = 6.9; P < 0.03 and 2.4; P < 0.02, respectively). ROC analysis showed that the admission blood glucose level of 160 mg/dl is an independent cut-off value (AUC = 0.68; p < 0.001) in prediction of outcome of non-diabetic patients presented with STEMI.
In non-diabetic patients presented with STEMI, elevated admission glucose level was associated with adverse outcome and more severe multi-vessel coronary lesions. The cut-off value was > 160 mg/dl and was considered an independent factor in prediction of outcome of non-diabetics presented with SEMI. Measurement of admission blood glucose level enables identification of this high-risk group for aggressive secondary risk prevention.
Prediabetes and coronary artery disease: Outcome after revascularization procedures
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Determinar si la prediabetes, a largo plazo, se asocia a un mayor riesgo de eventos cardiovasculares en pacientes con cardiopatía isquémica y revascularización coronaria percutánea.
Cohortes retrospectivo. De los procedimientos de revascularización realizados durante 2010 se seleccionaron aquellos sin diagnóstico de diabetes y con determinación de hemoglobina glucosilada. Se constituyeron 2 grupos: prediabetes (5,7-6,5%) y control (< 5,7%). Se registraron variables demográficas, clínicas e intervencionistas. Los objetivos de estudio fueron mortalidad, ingresos hospitalarios, infarto de miocardio (IM) y procedimientos de revascularización.
Los sujetos de estudio fueron 132 (hombres 82,6%; edad 65,26 ± 12,46). No se encontraron diferencias significativas en las variables demográficas, clínicas ni intervencionistas. La prevalencia de prediabetes fue 40,2%. El 64,1% de los casos de revascularización se debieron a IM con elevación de ST. Tras un seguimiento de 42,3 ± 3,6 meses no se encontraron diferencias entre prediabetes y control en mortalidad total: 5,4% vs 1,9% (riesgo relativo [RR]: 2,86, intervalo de confianza del 95% [IC 95%]): 0,27-30,44, p = 0,56), mortalidad no cardiovascular: 2,7% vs 1,9% (RR: 1,43, IC 95%: 0,93-22,18, p = 0,79), ingresos de cualquier causa: 19% vs 25% (RR: 1,13, IC 95%: 0,73-1,73, p = 0,57), IM: 3% vs 1% (RR: 4,28, IC 95%: 0,46-39,52; p = 0,30) ni revascularización de la lesión tratada: 3% vs 6% (RR: 0,70, IC 95%: 0,18-2,61, p = 0,72).
En pacientes sometidos a revascularización coronaria la presencia de prediabetes, definida según valores de hemoglobina glucosilada, no se asocia a un incremento de eventos cardiovasculares a largo plazo.
To assess the long-term association between prediabetes and an increased risk of cardiovascular events in patients with coronary artery disease and percutaneous coronary intervention (PCI).
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Relation of admission glucose levels, short- and long-term (20-year) mortality after acute myocardial infarction
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Citation Excerpt :
Our results expand the current knowledge on the relation between admission glucose and outcomes over the past decades in patients hospitalized with acute MI. Previous studies reported an association between elevated glucose on admission and short-term mortality in patients with acute MI during limited calendar periods.2–6,10,11 Similar to our findings, most of these studies also noted that this association is not dependent on diabetic status.4,5,10,11
We examined temporal trends in mortality after myocardial infarction from 1985 to 2008 depending on admission glucose levels. We included 11,324 consecutive patients admitted to our intensive coronary care unit for myocardial infarction from 1985 to 2008. Patients were categorized into normal, mild, and severe hyperglycemia groups (admission glucose levels <140, 140 to 200, and ≥200 mg/dl, respectively). Temporal trends were determined using 3 groups: 1985 to 1990, 1990 to 2000, and 2000 to 2008. The prevalence of hyperglycemia increased from 26% in the 1980s to 49% in the 2000s. The prevalence of hyperglycemia primarily increased in patients without diabetes. Kaplan-Meier mortality was 4%, 8%, and 17% at 30 days and 64%, 71%, and 82% at 20 years in patients with normal, mild, and severe hyperglycemia, respectively. Compared with normal admission glucose level, adjusted 30-day mortality was 3.6-fold greater (95% confidence interval 2.9 to 4.3) in patients with severe hyperglycemia. This association was not dependent on diabetic status (p for interaction = 0.43) but was dependent on the decade of hospitalization with a stronger association from 2000 to 2008 (adjusted odds ratio 7.7, 95% confidence interval 5.4 to 11, p for interaction <0.001). Compared with diabetes, hyperglycemia was a better discriminator for 30-day mortality. Mortality at 30 days decreased from 1985 to 2008, however, it decreased less in patients with hyperglycemia compared with those with normoglycemia. In conclusion, elevated admission glucose levels are common in patients with myocardial infarction and are strongly associated with increased mortality. Mortality decreased less from 1985 to 2008 in patients with hyperglycemia compared with those with normoglycemia. Efforts that establish optimal treatment for these patients remain warranted.
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Clinical InvestigationAcute Ischemic Heart DiseaseElevated admission glucose is associated with increased long-term mortality in myocardial infarction patients, irrespective of the initially applied reperfusion strategy

Background

Methods

Results

Conclusion

Section snippets

Regional situation

Patient characteristics

Discussion

Conclusion

Acknowledgements

Int J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

Admission plasma glucose. Independent risk factor for long-term prognosis after myocardial infarction even in nondiabetic patients

Diabetes Care

Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus

Arch Intern Med

Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction

N Engl J Med

Tailored thrombolytic therapy. A perspective

Circulation

‘Expected infarct size without thrombolysis’, a concept that predicts immediate and long-term benefit from thrombolysis for evolving myocardial infarction

Eur Heart J

An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators

N Engl J Med

Effect of hyperglycemia and insulin in acute coronary syndromes

Am J Cardiol

Clinical Investigation
Acute Ischemic Heart Disease
Elevated admission glucose is associated with increased long-term mortality in myocardial infarction patients, irrespective of the initially applied reperfusion strategy