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Chronic Glycemic Ratio at Admission in Acute Myocardial Infarction

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Chronic Glycemic Ratio at Admission in Acute Myocardial Infarction Diabetes Care Volume 41, April 2018 847 Giancarlo Marenzi,1 Nicola Cosentino,1 Prognostic Value of the Acute-to- Valentina Milazzo,1 Monica De Metrio,1 Milena Cecere,1 Susanna Mosca,1 Chronic Glycemic Ratio at Mara Rubino,1 Jeness Campodonico,1 Marco Moltrasio,1 Ivana Marana,1 Admission in Acute Myocardial Marco Grazi,1 Gianfranco Lauri,1 Alice Bonomi,1 Fabrizio Veglia,1 Infarction: A Prospective Study Roberto Manfrini,1 and 1,2 Diabetes Care 2018;41:847–853 | https://doi.org/10.2337/dc17-1732 Antonio L. Bartorelli OBJECTIVE Acute hyperglycemia is a powerful predictor of poor prognosis in acute myocardial infarction (AMI), particularly in patients without diabetes. This emphasizes the im- portance of an acute glycemic rise rather than glycemia level at admission alone. We investigated in AMI whether the combined evaluation of acute and chronic glycemic levels, as compared with admission glycemia alone, may have a better prognostic value. RESEARCH DESIGN AND METHODS We prospectively measured admission glycemia and estimated average chronic glucose levels (mg/dL) by the following formula: [(28.7 3 glycosylated hemoglobin %) 2 46.7], and calculated the acute-to-chronic (A/C) glycemic ratio in 1,553 consecutive AMI patients (mean 6 SD age 67 6 13 years). The primary end point was the combination of in-hospital mortality, acute pulmonary edema, and cardiogenic shock. RESULTS CARDIOVASCULAR AND METABOLIC RISK The primary end point rate increased in parallel with A/C glycemic ratio tertiles (5%, 8%, and 20%, respectively; P for trend <0.0001). A parallel increase was observed in troponin I peak value (15 6 34 ng/mL, 34 6 66 ng/mL, and 68 6 131 ng/mL; P < 0.0001). At multivariable analysis, A/C glycemic ratio remained an independent pre- dictor of the primary end point and of troponin I peak value, even after adjustment for major confounders. At reclassification analyses, A/C glycemic ratio showed the best prognostic power in predicting the primary end point as compared with glycemia at 1Centro Cardiologico Monzino, Istituto di Rico- admission in the entire population (net reclassification improvement 12% [95% CI 4–20]; P = vero e Cura a Carattere Scientifico, Milan, Italy 2 0.003) and, particularly, in patients with diabetes (27% [95% CI 14–40]; P < 0.0001). Department of Biomedical and Clinical Sciences “Luigi Sacco,” University of Milan, Milan, Italy CONCLUSIONS Corresponding author: Giancarlo Marenzi, giancarlo In AMI patients with diabetes, A/C glycemic ratio is a better predictor of in-hospital [email protected]. morbidity and mortality than glycemia at admission. Received 18 August 2017 and accepted 19 December 2017. This article contains Supplementary Data online Elevated levels of plasma glucose at hospital admission (acute hyperglycemia) are at http://care.diabetesjournals.org/lookup/ common among patients with acute myocardial infarction (AMI) (1,2). Acute hyper- suppl/doi:10.2337/dc17-1732/-/DC1. glycemia has been recognized as an independent determinant of adverse outcomes, © 2018 by the American Diabetes Association. both in patients with and in patients without diabetes (3,4). Acute hyperglycemia Readers may use this article as long as the work fl is properly cited, the use is educational and not results in a prothrombotic state, modulates in ammatory response and oxidative for profit, and the work is not altered. More infor- stress, and is the cause of endothelial dysfunction and impaired microcirculatory func- mation is available at http://www.diabetesjournals tion (5–7), leading to larger infarct size (8,9). These phenomena may explain the .org/content/license. 848 Acute Hyperglycemia and AMI Diabetes Care Volume 41, April 2018 association between elevated plasma glu- with a history of hemoglobinopathy were with echocardiography in all patients cose and poor prognosis in AMI. Indeed, excluded. The study complied with the within 24 h from hospital admission. patients with acute hyperglycemia typi- Declaration of Helsinki, and the ethics The TIMI (Thrombolysis In Myocardial In- cally have a more complicated in-hospital committee of Centro Cardiologico Monzino farction) risk score was calculated in clinical course, including a higher incidence approved the research protocol (no. STEMI and NSTEMI patients. of heart failure, cardiogenic shock, and R520-CCM549). Written informed con- death (1–9). sent was obtained from all participants. Study End Points In AMI, patients with diabetes have a No extramural funding was used to sup- The primary end point of the study was worse outcome than those without dia- port this work. the combination of in-hospital mortality, betes (10,11). However, acute hypergly- nonfatal acute pulmonary edema, and cemia has been shown to be a powerful Study Protocol cardiogenic shock. Acute pulmonary predictor of poor prognosis, particularly Blood glucose and HbA1c levels were edema was defined as severe respiratory in patients without diabetes (12–14). measured in all patients at hospital ad- distress, tachypnea, and orthopnea with This emphasizes the role of an acute rise mission. A diagnosis of diabetes was rales over the lung fields and arterial ox- of glucose level, as compared with a made if this disease or antidiabetes treat- ygen saturation ,90% on room air prior chronic elevation, in predisposing patients ment, including oral agents or insulin, was to treatment with oxygen. Cardiogenic toward a worse prognosis. Chronic eleva- recorded in the admission history. A di- shock was defined as prolonged hypoten- tion of glucose levels cannot be deter- agnosis of unknown diabetes was made sion (systolic blood pressure #85 mmHg) minedinpatientsadmittedwithAMI, when patients had $6.5% (48 mmol/mol) with evidence of decreased organ perfu- but it can be estimated by assessing the HbA1c despite no previous history of the sion caused by severe left ventricular dys- glycosylated hemoglobin (HbA1c)value disease (16). These patients were consid- function, right ventricular infarction, or (15). Therefore, in AMI patients, the com- ered to have diabetes. Acute hyperglyce- mechanical complications of infarction re- bined information provided by acute mia was defined as a blood glucose at quiring intra-aortic balloon pump and/or (measured at hospital admission) and admission .198 mg/dL (.11 mmol/L) inotropic agents. Infarct size, estimated chronic (estimated by HbA1c) glycemic according to the definition used in previ- by troponin I peak value, was the second- value assessment may be a better prog- ous studies (17). As currently no uniform ary end point of the study. nostic predictor than glycemic value at definition of acute hyperglycemia in admission or diabetes status alone. Indeed, the setting of AMI exists, we also con- Statistical Analysis it represents the “true” acute glycemic in- sidered a cutoff value of .144 mg/dL A sample size of 1,500 patients was cal- crease. This may be particularly relevant (18). Average chronic glucose levels culated under the following assumptions: in patients with diabetes, in whom ele- 10% overall incidence of the primary end were estimated by HbA1c, expressed as vated glucose levels at admission do not percent value, according to the following point, with an expected 7% and 14% in- necessarily indicate the occurrence of formula (15): cidence in patients with the lowest and acute hyperglycemia. the highest A/C glycemic ratio tertile, re- Thus, the purpose of our study was to Estimated chronic glucose levels ðmg=dLÞ spectively (odds ratio [OR] 2.16). This investigate the possible association be- sample size allowed a 95% statistical 5½ð28:7 3 HbA1c %Þ 2 46:7 tween the ratio of acute to chronic (A/C) power in assessing a significant difference glycemic values and in-hospital outcomes (a error of 0.05) of the combined end in an unselected cohort of consecutive The A/C glycemic ratio was calculated in point between the three A/C glycemic ra- AMI patients. In particular, we hypothe- all patients with measurement of blood tio tertiles. sized that A/C glycemic ratio, as compared glucose at admission and estimation of Continuous variables are presented as with admission glycemic value, is more chronic glucose levels. mean 6 SD. Variables with a skewed dis- closelyassociatedwithinfarctsizeandthe Study patients received standard med- tribution are presented as median and most clinically relevant hemodynamic con- ical treatment and coronary revasculari- interquartile ranges. Categorical data are sequences of AMI, such as acute pulmonary zation at the discretion of the attending presented as n (%). Trends across A/C edema, cardiogenic shock, and death. physician based on the current standards glycemic ratio tertiles were assessed by of care recommended by published ANCOVA and by Mantel-Haenszel x2 as guidelines. In all patients with diabetes, appropriate. The association between A/C RESEARCH DESIGN AND METHODS antidiabetes medications were withheld glycemic ratio tertiles and the primary This was a prospective, observational study. at hospital admission. In patients with end point and troponin I peak value (be- We enrolled all consecutive patients with acute hyperglycemia (.198 mg/dL), insu- low or above the median value) was as- AMI, both ST-elevation myocardial infarc- lin was administered, with a glucose level sessed by logistic regression analysis. tion (STEMI) and non–ST-elevation myo- target range of 140–180 mg/dL (19). Analyses were adjusted for the baseline cardial infarction (NSTEMI), admitted Demographical, clinical, biochemical, risk profile of the patient, as assessed by to the Intensive Cardiac Care Unit of echocardiographic, and angiographic the TIMI risk score, and for a model in- Centro Cardiologico Monzino in Milan data were obtained. Troponin I (Beckman cluding independent predictors of both between 1 June 2010 and 29 June 2016. Coulter, Fullerton, CA) was measured ev- the primary end point and troponin I peak Patients experiencing AMI as a complica- ery 6 h from hospital admission to 24 h value, identified by performing a logistic tion of elective percutaneous coronary in- after it reached peak value.
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