Prevalence of new alterations of glycemia in acute coronary syndrome
STELLA M. MACÍN, MARÍA L. CORONEL, EDUARDO R. PERNA,
BILDA GONZÁLEZ ARJOL, OMAR LARROSA MARIELA ONOCKO,
FACUNDO FALCÓN, GASTÓN POZZI, FERNANDA MEDINA, MÓNICA BRIZUELA
Instituto de Cardiología “JF Cabral”.
Facultad de Medicina UNNE.
(W3400CDS) Corrientes, Argentina. E-mail
Recibido 31-OCT-2018 – ACEPTADO después de revisión el 04-DICIEMBRE-2018
There are no conflicts of interest to disclose.
Introduction: The presence of diabetes is associated with adverse outcomes. The importance of glycosylated hemoglobin in patients with ACS is poorly known. Objectives: To evaluate new cases of glycemic alterations in patients hospitalized for acute coronary syndrome and its relationship with events. Materials and Methods: From January 1, 2014 to December 31, 2014, 92 patients were included with acute coronary syndrome. Glycemia and glycosylated hemoglobin were dosed at admission. According to the definition of the ADA by Glycosylated Hb ≥6.5%, plasma glucose ≥200 mg/dl, fasting plasma glucose ≥126 mg/dl the population was separated into three groups: Group I: non-diabetic 41% (44.6), Group II: new DBT 24 (26.1%) and Group III: known DBT: 27 (29.3%). New DBT were considered to be those with glycosylated Hb ≥ 6.5% or blood glucose ≥200 mg/dl. Results: The average age of the population was 64.4 ± 15 years, 19% were women. No baseline differences were observed between groups I, II and III with respect to sex: 63.8% (28 pts) vs 58.3% (14 pts) vs 77.8% (21 pts) p = 0.32; dyslipidemia 39% (16 pts) vs 62% (15 pts) vs 63% (17 pts), p = 0.07; obesity 12.2% (5 pts) 33.3% (9 pts) 12.5% (3 pts), p = 0.06; smoking 43.9% (3 pts) vs 40.7% (11 pts) vs 23.7% (9 pts), p = 0.94; hypothyroidism 7.3% (3 pts) 7.4% (2 pts) 4.2% (1 pts), p = 0.86, respectively, except in HTN: 67.5% (27 pts) vs 67.5% (27 pts) vs 81.5% (22 pts), p = 0.02. The correlation of the composite endpoint of heart failure, cardiogenic shock, re-infarction and death in "non-diabetic patients" with respect to glycemia ≥200 and <200 mg / dl and glycosylated hemoglobin ≥6.5 was 3 vs 13 and with glycosylated Hb <6.5 it was 8 vs 41 events (p = ns); and in "diabetic patients" with glycemia ≥200 and <200 mg / dl and glycosylated hemoglobin ≥6.5 it was 9 vs 11 and with glycosylated Hb <6.5 it was 0 vs 7 events (p = 0.04).
Eight new cases of diabetes were detected by ≥200 mg/dl (8.7%) and 16 by glycosylated Hb ≥6.5% (17.4%) and there were 27 cases of diabetes already diagnosed (29.3%), with 41 cases of patients without diabetes, Kappa coefficient 0.50, p <0.001. Conclusions: Glycosylated hemoglobin >6.5 in non-diabetic subjects and/or glycemia greater than or equal to 200 mg/dl. They identified 17.4% and 8.7% of prevalence of new subjects with metabolic disorders, respectively, and they were associated with a higher prevalence of events in hospital patients for acute coronary syndrome.
Key words: Hyperglycaemia. Acute coronary syndrome. Prognosis. New diabetes.
Diabetes mellitus is well known to be associated to a higher risk of mortality, resulting from an advanced state of systemic and cardiovascular atherosclerosis [1,2]. It increases the risk of cardiovascular disease two or three times, and it often precedes metabolic syndrome, with its prevalence drastically increasing in Europe and Western countries in the last 20 years . The pathophysiological links between diabetes and its history, on one hand; and cardiovascular disease on the other, are complex and entail hyperglycemia, resistance to insulin, beta-cell dysfunction, and a grouping of risk factors for atherosclerosis [1,4,5].
Approximately, one third of patients admitted due to acute myocardial infarction have preexisting diabetes mellitus. In spite of its high prevalence in the population of patients with myocardial infarction, the diagnosis has traditionally been transferred to ambulatory configuration [1,6]. This is mainly due to the very well-known deregulation of glucose metabolism during infarction, which makes hyperglycemia to be common, thus affecting the accuracy of diabetes diagnosis if only using glucose levels in plasma [1,7,8]. Previous studies, with tests of tolerance to glucose, a highly sensitive method to detect metabolic anomalies, have estimated that 1 in every 4 patients with coronary artery disease but with no previously established diabetes, have not been diagnosed as having diabetes [1,3,9].
In 2010, the American Diabetes Association (ADA) adopted glycosylated hemoglobin as a reliable measure for the chronic evaluation of glycemia to help diagnosis ; regardless of glycemia levels in blood, and this has been suggested in patients with infarction and hyperglycemia but with no history of diabetes to identify those that may benefit from starting an evaluation of the lifestyle or hypoglycemic therapy [1,3,11].
Hyperglycemia in admission due to an acute coronary syndrome is associated to a less favorable result in patients with or without known diabetes and has been considered an acute response to stress .
The hypothesis of this paper is that the presence of undiagnosed new cases of diabetes in admission worsen the evolution of patients with acute coronary syndrome.
To evaluate new cases of glycemia alterations in patients admitted due to acute coronary syndrome and their links to events.
MATERIALS AND METHODS Study protocol
Observational, prospective study, where 92 patients with ACS (acute coronary syndrome) were studied consecutively, admitted into the Instituto de Cardiología de Corrientes, from January 1st to December 31st, 2014. According to the ADA’s definition by glycosylated Hb ≥6.5%, plasma glycemia at random ≥200 mg/dl, plasma glycemia in a fasting state ≥126 mg/dl, the population was divided into three groups: Group I: non-diabetic patients 41% (44.6), Group II: new DBT 24 (26.1%) and Group III: known DBT 27 (29.3%). Patients were considered to present new DBT when presenting glycosylated Hb 6.5% or glycemia at random ≥200 mg/dl.
It was constituted by patients older than 18 years, admitted into the Coronary Unit of the Instituto de Cardiología de Corrientes, from January 1st to December 31st, 2014, with diagnosis of acute coronary syndrome.
Patients admitted by ACS within 24 hours after the onset of symptoms older than 18 years, who gave their informed consent to participate in the study.
Patients with diagnosis of secondary acute coronary syndrome (anemia, tachyarrhythmia, hyperthyroidism, sepsis, trauma), dilated cardiomyopathy, myocarditis, cardiogenic shock, acute pulmonary edema, pulmonary thromboembolism, congenital diseases, hypertrophic heart disease, severe or pericardial valve disease, who refused to give their informed consent and younger than 18 years.
Definitions Acute coronary syndrome (ACS): defined by the presence of precordial pain lasting more than 15 minutes, functional class IV, associated to ECG changes (ST segment elevation, ST depression, negative T waves, pseudo-normalization, or no changes). If Troponin T values were within the normal range (<0.02 ng/dl), patients were defined as having unstable angina and if greater than 0.02 ng/dl they were considered to have infarction .
The final diagnosis of infarction was based on the 3rd universal definition of infarction, requiring an increase or decrease in cardiac biomarkers values, with at least one value above the 99th percentile upper reference and with at least one of the following: ischemia symptoms, new significant ST-T segment changes or new His bundle left bundle branch block, appearance of pathological Q waves in ECG, imaging tests of new loss of viable myocardium or new regional anomalies in the wall movement, identification of intracoronary thrombus in angiography or autopsy .
Diabetes: defined based on diagnostic criteria proposed by the American Diabetes Association (ADA) 2016 .
Glucose in a fasting state ≥126 mg/dl (no having had caloric ingestion over the last 8 hours) or
Plasma glucose at 2 hours ≥200 mg/dl during an oral test of tolerance to glucose. The test should be made with a load of 75 grams of anhydroglucose dissolved in water, or
Glycosylated hemoglobin (A1C) ≥6.5%. This test should be made in certified labs according to A1C standards of the DCCT.
All patients were admitted into the Coronary Unit and the complete clinical history was made, as well as physical examination, 12-lead ECG upon admission, chest X-ray upon admission, lab tests including chemical tests, hematology, high-sensitivity troponin T (detection limit of 14 ng/dl), NT-proBNP (assessed by electrochemiluminescence Elecsys 2010), high-sensitivity C-reactive protein, glycemia and glycosylated hemoglobin.
The patients were followed by institutional registries over 1 year.
The study protocol was designed according to the Helsinki declaration, and the committee of institutional ethics approved the study. All participants expressed their wish to participate and granted their written informed consent before being included in the study.
A data base was built with the SPSS 21.0 software, including the information of the patients (clinical characteristics, risk factors, complications, lab data, and additional tests).
Qualitative variables were expressed in percentages, and compared through the chi-square test. Quantitative variables were expressed in means with standard deviation, and analyzed by the T-test, or with nonparametric tests as it corresponded.
The differences were considered statistically significant when p<0.05. The kappa coefficient of Cohen was used. The data obtained were analyzed by the SPSS 21.0 software.
RESULTS From January 1st to December 31st, 2014, there were 92 consecutive patients included with acute coronary syndrome. Glycemia and glycosylated hemoglobin were measured upon admission. According to the ADA definition by glycosylated Hb ≥6.5%, plasma glycemia at random ≥200 mg/dl, plasma glycemia in a fasting state ≥126 mg/dl, the population was divided into three groups: Group I: non-diabetic patients 41%; Group II: new DBT 24 (26.1%) and Group III: known DBT: 27 (29.3%). Figure 1.
The mean age was 64.4±12 years, 19% were women.
In Table 1, we can observe the characteristics of the population, where we show that there were no differences between groups, but for a higher prevalence of hypertension in group II.
Glycosylated hemoglobin >6.5% in nondiabetic individuals and/or glycemia greater or equal to 200 mg/dl, identified 17.4% and 8.7% of prevalence of new individuals with metabolic alterations respectively, and were associated to a greater prevalence of events in patients admitted due to acute coronary syndrome.
Significance of hyperglycemia upon admission
The fundamental alteration triggered by hyperglycemia occurs in the vascular endothelium [1,9,14]. Endothelial dysfunction translates into vasoconstriction, hyperplasia of the vascular media layer, inflammation and prothrombotic state by alteration in fibrinolysis and platelet function, increase in cytokines activation, increase in lipolysis and levels of free fatty acids, decrease in glycolysis and glucose oxidation, increase in oxidative stress, apoptosis, microcirculation function alteration, “no-reflow” phenomenon, ischemic preconditioning, insulin secretion alteration, and glucose uptake stimulated by insulin . Also, an accumulation of metalloproteinases is generated, leading to atherosclerotic platelet rupture [14,16]. Chronic hyperglycemia perpetuates the process, so that vascular alteration worsens progressively and a close and damaging relationship sets between hyperglycemia, coronary events in the mid and/or long term, and time of evolution of diabetes [14,17].
Acute hyperglycemia or stress have a facilitating role in the development of acute coronary syndrome and accentuates the consequences of cell damage produced by acute myocardial ischemia . The increase of oxidative stress interferes with nitric oxide, vasodilation and generates a reduction in coronary blood flow at microvascular level [18,19]. In individuals with ST-segment elevation infarctions, acute hyperglycemia is associated to TIMI 3 flow, reduced before the intervention, in comparison to euglycemia, and it is the most important predictor of events .
The main hypothesis on why hyperglycemia predicts higher mortality in patients with acute coronary syndrome is due to different mechanisms; first, elevated glycemia in blood could be a physiological response to hormones, such as epinephrine or cortisol, which are released under high systemic stress [2,15]; and therefore, it may indicate more general severity of the disease, as well as those individuals with larger areas of ischemia or myocardial necrosis and left ventricular function impairment, a function that could have a stronger sympathetic activation, leading to higher glycose levels .
Second, hyperglycemia could be an indicator of systemic metabolism and specific organ deregulation, particularly deficient insulin signaling; and in this regard, insulin resistance does not just cause hyperglycemia, but may also lead to a reduction in energy production in the heart and other organs, producing less tolerance to hypoperfusion [14,21].
Third, acute hyperglycemia is implicated in the activation of other pathological processes that may contribute to cell and tissue lesions, such as increasing the formation of free radicals and oxidative stress and inducing prothrombotic stress and endothelial function worsening [14,20].
New cases of diabetes
As we have seen, approximately one third of hospitalized patients due to acute myocardial infarction have preexisting diabetes mellitus. In spite of its high prevalence in a scenario of infarction, diagnosis has been traditionally transferred to an ambulatory field [1,21-23].
Arnold et al, found in 2854 patients with acute myocardial infarction with no known diabetes upon admission, that 287 patients (10%) met the criteria for type 2 diabetes, defined by a central laboratory test of glycated hemoglobin of ≥6.5% . They discovered that 2 out of 3 patients with recently diagnosed diabetes were not identified by the attending physicians, who did not receive an education on diabetes, anti-diabetic medication upon discharge, or documents on diabetes .
Based only on glycosylated hemoglobin tests, it is possible to detect diabetes and pre-diabetes in high risk, in approximately 1 in each 10 patients with diabetes [6,24]. Previous studies that investigated the prevalence of undiagnosed type 2 diabetes using glucose tolerance curve during admission, in patients with acute coronary syndrome, or after discharge, found this pathology in around 20-30% of individuals [24,25].
Moreover, the incidence of prediabetes and diabetes were not different between patients with different degrees of severity of acute coronary syndrome . This is supported by previous studies that showed in stable patients, with unstable CAD, cerebral and peripheral vascular disease, which have approximately the same proportion of previously unknown diabetes [25,26].
Snir et al, found in an observational multicenter trial with 1743 patients with acute coronary syndrome, that just 41% of patients with diabetes had glycosylated hemoglobin measured in the hospital. There was a great variation in the practice in different centers, from 7.7 to 87.6% [15,27].
In this study, 8.7% new cases of diabetes were diagnosed by hyperglycemia greater or equal to 200 mg/dl in a fasting state and 17.4% by glycosylated hemoglobin measured upon admission, which increases by 26% the new cases of diabetes, very important to perform a proper therapy and for prevention in the initial stages. Thus, already in the first stages of glycometabolic impairment, coronary plaques are affected [2,28].
Both hyperglycemia and insulin resistance promote the release of inflammatory cytokines as tumor necrosis factor α, interleukin-6, plasminogen activator inhibitor, and angiotensin [1,14]. This leads to a proinflammatory state with accelerated atherosclerosis, vascular inflammation, and endothelial dysfunction. Further, hyperinsulinemia and daily glucose fluctuations have been associated to coronary plaque vulnerability [15,29].
Amano et al, investigated coronary lesions causing CAD and found plaques with more volume of lipid content in patients with diabetes and prediabetes [14,18]. Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients, and comparable between prediabetic and diabetic patients [29,30]. Mild or moderate disorders in the metabolism of glucose as in prediabetes, could be a risk factor of cardiovascular disease, as diabetes per se.
Likewise, Kurihara et al, showed a higher degree of vulnerable plaques in patients with prediabetes and diabetes using coronary optical coherence tomography [29,30].
Hospitalization by infarction is frequently, the first opportunity to identify and treat previously unknown diabetes, particularly for patients with little to no routine health care before the event [1,23]. As a result, identifying the presence of underlying diabetes during infarction may represent a unique chance for a better identification and earlier treatment for diabetes, with implications for the chronic management of education, as well as initiation and titration of anti-diabetic therapy and information on the care of CAD, included revascularization options, platelet antiaggregation therapy and choice of antihypertensive medications [1,17,30].
Elevated glycemia as a prognostic marker
The finding of hyperglycemia upon hospital admission due to acute coronary syndrome is quite common, and should be considered an important marker for adverse clinical results associated to a greater mortality in patients with and without history of diabetes .
In spite of most studies having focused particularly on the prognostic value of glycemia upon admission, it is just a measure in time and does not reflect the total exposition of hyperglycemia during hospitalization [23,25]. In the study by Monteiro et al, the magnitude of glycemia variation during hospitalization was an independent predictor of subsequent endpoints upon discharge after acute coronary syndrome in nondiabetic patients .
Suleiman et al, showed a gradual relation between elevated glycemia in a fasting state, glycemia upon admission and mortality at 30 days in nondiabetic patients with infarction, suggesting that glycemia in a fasting state is a significant predictor of mortality at 30 days, more than glucose upon admission [30,31]. Patients with elevated glycemia upon admission and elevated glucose in a fasting state on the following day had thrice the mortality . Likewise, the failure to normalize an elevated level of glucose within 24 hours after admission is associated to a worse prognosis. Persistent hyperglycemia is a good discriminator for mortality; probably better than glucose upon admission in patients hospitalized by infarction .
In the nondiabetic population under study, an important association was found between the high levels of glycosylated hemoglobin and glycemia in a fasting state greater than 200 mg/dl with in-hospital events; i.e. heart failure, cardiogenic shock, reinfarction and death.
Current evidence suggests that hyperglycemia is a mediator of worse prognosis, directly exacerbating myocardial impairment and necrosis [23,24]. Higher levels of glucose in patients with infarction have been associated to greater concentrations of free fatty acids, insulin resistance and glucose consumption deterioration in the myocardium, thus increasing oxygen consumption and worsening ischemia .
The most significant limitations of this study are the small number of patients and the fact that it was conducted in a single center.
This study has significant clinical implications, as it is estimated that by 2025 there will be 300 million diabetic patients in the world, from whom 90% will have type 2 diabetes mellitus [3,4]. So it is very useful to detect this entity in the presence of acute coronary syndrome, and it would be much more so preventing the development of it, when glycemia levels are between 100 and 126 mg/dl [1,23,30].
Nondiabetic patients may present hyperglycemia induced by stress during the acute phase of the coronary event due to increased levels of counterregulatory insulin mediators, such as proinflammatory cytokines, epinephrine, cortisol and tumor necrosis factor alpha [1,14-16].
The early diagnosis of new cases of diabetes would facilitate performing the treatment to a larger number of individuals with this pathology much earlier, minimizing the complications that this disease entails [1,8,33].
The optimal strategy for the identification of individuals with glycemic alterations in a scenario of myocardial infarction is not fully defined [25,28]. However, glycemic monitoring, glycosylated hemoglobin measuring and glycemia greater than 200 mg/dl, could be useful tools to guide the therapy in hospitalized patients and post-infarction, and thus preventing a significant number of individuals that may evolve into necrotic ischemic dilated cardiomyopathy, heart failure with preserved systolic function and progression into atherosclerotic disease with wide costs for public health [25,33]. Future trials with a greater number of individuals would enable improving this scenario and implementing the results in guidelines [25,34].
The determination of glycosylated hemoglobin ≥6.5% in nondiabetic individuals and/or glycemia ≥200 mg/dl, identified the prevalence of new individuals with metabolic alterations in 17.4% and 8.7% respectively; which was associated to a higher incidence of events in hospitalized patients with acute coronary syndrome.
Arnold SV, Stolker JM, Lipska KJ, et al. Recognition of incident diabetes mellitus during an acute myocardial infarction. Circ Cardiovasc Qual Outcomes 2015; 8: 260-67.
De Caterina R, Madonna R, Sourij H, Wascher T. Glycaemic control in acute coronary syndromes: prognostic value and therapeutic options. Eur Heart J 2010; 31: 1557-64.
Curós Abadal A, Serra Flores J. Relevancia de la hiperglucemia en el síndrome coronario agudo. Rev Esp Cardiol 2008; 61: 447-50.
López de Sá E. La hiperglucemia en el síndrome coronario agudo: ¿objetivo terapéutico o espectador que confiere un mayor riesgo?. Rev Clin Esp 2011; 211 (6): 298-300.
Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction). Study Group. BMJ 1997; 314: 1512-15.
Marfella R, Di Filippo C, Portoghese M, et al. Tight glycemic control reduces heart inflammation and remodeling during acute myocardial infarction in hyperglycemic patients. J Am Coll Cardiol 2009; 53: 1425-36.
Cabrerizo-García JL, Gimeno-Orna J, Zalba-Etayo B, Pérez-Calvo J. La hiperglucemia como factor de mal pronóstico en el síndrome coronario agudo. Rev Clin Esp 2011; 211: 275-82.
Monteiro S, Monteiro P, Goncalves F, et al. Hyperglycaemia at admission in acute coronary syndrome patients: prognostic value in diabetics and non-diabetics. Eur J Cardiovasc Prev Rehabil 2010; 17: 155-59.
Datey KK, Nanda NC. Hyperglycemia after acute myocardial infarction. Its relation to diabetes mellitus. N Engl J Med 1967; 276: 262-5.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33 (Suppl. 1): S62–S69.
Wei CH, Litwin SE. Hyperglycemia and Adverse Outcomes in Acute Coronary Syndromes: Is Serum Glucose the Provocateur or Innocent Bystander?. Diabetes 2014; 63: 2209-12.
Gomez-Arbelaeza D, Sánchez-Vallejo G, Pereze M, et al. Hiperglucemia se asocia a mayor número de desenlaces adversos en individuos latinoamericanos con infarto agudo de miocardio. Clin Investig Arterioscler 2016; 28 (1): 9-18
Ceriello A. Acute hyperglycaemia: a ‘new’ risk factor during myocardial infarction. Eur Heart J 2005; 26: 328-31.
Thygesen K, Alpert JS, Jaffe AS, et al: the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction Eur Heart J 2012; 33: 2551-67.
Macín Stella Maris. Hyperglycemia and insulin in myocardial infarction: the controversy continues. Med Clin 2008; 130: 613-14.
Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360: 1283-97.
Gómez-Arbeláez D, López-Jaramillo P. Mechanisms of acute coronary syndromes. N Engl J Med 2013; 369: 882.
Silvia Monteiro, Francisco Goncalves,a Pedro Monteiro, Mario Freitas,a,b and Luis A. Providencia. The Magnitude of the Variation in Glycemia: A New Parameter for Risk Assessment in Acute Coronary Syndrome? Rev Esp Cardiol 2009; 62: 1099-108.
Weston C, Walker L, Birkhead J. Early impact of insulin treatment on mortality for hyperglycaemic patients without known diabetes who present with an acute coronary syndrome. Heart 2007; 93: 1542-46.
Kosiborod M, Inzucchi SE, Krumholz HM, et al. Glucose normalization and outcomes in patients with acute myocardial infarction. Arch Intern Med 2009; 169: 438-46.
Sinnaeve PR, Steg PG, Fox KA, et al. Association of elevated fasting glucose with increased short-term and 6-month mortality in ST-segment elevation and non-ST-segment elevation acute coronary syndromes: the Global Registry of Acute Coronary Events. Arch Intern Med 2009; 169: 402-09.
Macín SM, Perna ER, Coronel ML, et al. Influencia de la concentración de glucemia en el momento del ingreso en la evolución a largo plazo de los pacientes con síndrome coronario agudo. Rev Esp Cardiol 2006; 59: 1268-75.
Lugg ST, May CJJ, Nightingale P, et al. HbA1c screening for new onset diabetes following acute coronary syndrome: is it a worthwhile test in clinical practice? J Diabetes Metab Disord 2017; 16: 14.
Schunkert R, Schunkert H. Diabetics with acute coronary syndrome: advances, challenges, and uncertainties Peter W. Eurn Heart J 2010; 31, 2971-73.
Gyberg V, De Bacquer D, Kotseva K, et al. Screening for dysglycaemia in patients with coronary artery disease as reflected by fasting glucose, oral glucose tolerance test, and HbA1c: a report from EUROASPIRE IV-a survey from the European Society of Cardiology. Eur Heart J.2015; 36: 1171-77.
Snir A, Dabin B, Hyun K, et al. HbA1c Assessment in diabetic patients with acute coronary syndromes. Intern Med J 2016; 46: 574-82.
Okosieme OE, Peter R, Usman M, et al. Can admission and fasting glucose reliably identify undiagnosed diabetes in patients with acute coronary syndrome? Diabetes Care 2008; 31: 1955-59.
Kurihara O, Takano M, Yamamoto M, et al. Impact of Prediabetic Status on Coronary Atherosclerosis. Diabetes Care 2013; 36:729-33.
Farhan S, Redfors B, Maehara A, et al. Impact of pre-diabetes on coronary plaque composition and clinical outcome in patients with acute coronary syndromes. An analysis from the PROSPECT study. J Am Coll Cardiol Img 2017: S1936-878X; 30806-9.
Donahoe SM, Stewart GC, McCabe CH; et al Diabetes and Mortality Following Acute Coronary Syndromes. JAMA 2007; 298: 765-75.
Karamat MA, Raja UY, Manley SE, et al. Prevalence of undiagnosed type 2 diabetes in patients admitted with acute coronary syndrome: the utility of easily reproducible screening methods. Karamat et al. BMC Endocrine Disorders 2017; 17: 3.
De Mulder M, Oemrawsingh RM, Stam F, et al. Comparison of diagnostic criteria to detect undiagnosed diabetes in hyperglycaemic patients with acute coronary syndrome. Heart 2012; 98: 37-41.
McCune C, Maynard S, McClements B, Lindsay JR. HbA1c for diabetes screening in acute coronary syndrome: time for a reappraisal of the guidelines?. Ulster Med J. 2015; 84: 154-56.