Relation of hemoglobin A1c to rate of major adverse cardiac events in nondiabetic patients undergoing percutaneous coronary revascularization

doi:10.1016/j.amjcard.2003.08.008

The American Journal of Cardiology

Volume 92, Issue 11, 1 December 2003, Pages 1282-1286

https://doi.org/10.1016/j.amjcard.2003.08.008 Get rights and content

Abstract

Abnormalities in plasma glucose below the “diabetic range” of glycemia are associated with increased cardiovascular morbidity and mortality in patients without diabetes mellitus. The purpose of this study was to investigate the relation between ambient glycemic levels as measured by hemoglobin A1c and outcome after elective percutaneous coronary intervention (PCI). Baseline laboratory studies, including hemoglobin A1c, were drawn in 500 consecutive patients before elective PCI. Nondiabetic patients were defined as those without a history of diet or pharmacologically controlled diabetes mellitus and a hemoglobin A1c level <7.0%. Of the 500 patients studied, 291 (59%) were nondiabetic patients. Abnormal hemoglobin A1c levels (6% to 7%) were found in 30% of nondiabetic patients. Nondiabetic patients with an abnormal hemoglobin A1c level had a significantly higher rate of major adverse cardiac events (33% vs 22%, p = 0.04), target vessel revascularization (31% vs 19%, p = 0.02), and cardiovascular mortality (4.6% vs 0.5%, p = 0.03) compared with nondiabetic patients with hemoglobin A1c levels <6%. Multivariate analysis disclosed that a hemoglobin A1c level of 6% to 7% was a significant independent predictor of major adverse cardiac events, target vessel revascularization, and cardiovascular mortality 12 months after PCI in nondiabetic patients. These data demonstrate that an abnormal hemoglobin A1c level may have prognostic significance in nondiabetic patients who undergo PCI.

Section snippets

Study design

From August 2000 to October 2000, all patients who underwent elective PCI of a single-vessel de novo coronary artery narrowing had baseline laboratory studies, including hemoglobin A1c levels, drawn before cardiac catheterization. Coronary intervention was performed using standard techniques, including percutaneous transluminal coronary angioplasty, intracoronary stenting, and/or mechanical rotational atherectomy. All patients were treated with aspirin. After intracoronary stent implantation,

Results

From August 2000 to October 2000, a total of 898 patients underwent percutaneous coronary revascularization at this institution. Of these patients, 602 met entry criteria for this study. Five hundred patients (83%) consented to participate in the study.

Discussion

We have demonstrated that an abnormal hemoglobin A1c level (defined as a hemoglobin A1c level of 6% to 7%) is associated with a significantly higher risk of MACEs, TVR, and cardiovascular mortality after elective PCI in nondiabetic patients. Furthermore, nondiabetics with a hemoglobin A1c level of 6% to 7% had similar outcomes compared with diabetic patients. These results indicate that an abnormal hemoglobin A1c level may have prognostic significance in nondiabetic patients who undergo PCI.

The

Acknowledgements

The investigators wish to acknowledge Julie Madison, RN, and Gwen Williams-Hennesey, RT, for their tireless efforts in the collection and organization of data for this study. The investigators also wish to thank Judith A. Boura, MS, for her statistical expertise and Sue Tomaszycki, BS, for her graphical support in the preparation of the manuscript.

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Baseline high-sensitivity C-reactive protein and glycosylated hemoglobinA1c predict adverse outcomes in patients with chronic coronary syndromes undergoing percutaneous coronary intervention
2024, Heliyon
This study explored the ability of high-sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin A1c (HbA1c) to predict adverse cardiac and cerebrovascular outcomes in patients with chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI).
In total, 4083 consecutive patients with CCS undergoing PCI were investigated throughout 2013 at a single center. The primary endpoint was all-cause death at the 5-year follow-up. Hs-CRP and HbA1c data were collected on admission.
The highest quartile of hs-CRP had a significantly increased the risk of all-cause death, with an adjusted HR of 1.747 (95 % CI 1.066–2.863), while, there was no difference in all-cause death among the groups of HbA1c after adjustment, with an adjusted HR of 1.383 (95 % CI 0.716–2.674). The highest quartiles for hs-CRP and HbA1c in the study population had a significantly increased risk of major adverse cardiac and cerebrovascular events (MACCE), with an adjusted hazard ratios (HR) of 1.263 (95 % confidence intervals [CI] 1.032–1.545) for hs-CRP and an adjusted HR of 1.417 (95 % CI 1.091–1.840) for HbA1c. Remarkably, the incidence of all-cause death and that of MACCE were significantly increased when both hs-CRP and HbA1c were elevated (HR 1.971, 95 % CI 1.079–3.601, P = 0.027 and HR 1.560, 95 % CI 1.191–2.042), P = 0.001, respectively). Addition of hs-CRP and HbA1c to conventional risk factors significantly improved prediction of the risk of all cause death (net reclassification index 0.492, P < 0.001; integrated discrimination improvement 0.007, P = 0.011) and MACCE (net reclassification index 0.160, P < 0.001; integrated discrimination improvement 0.006, P < 0.001).
Hs-CRP and HbA1c can serve as independent predictors of MACCE in patients with CCS undergoing PCI. Furthermore, a combination of hs-CRP and HbA1c could predict all cause death and MACCE better than each component individually.
Effects of prediabetes on long-term clinical outcomes of patients with acute myocardial infarction who underwent PCI using new-generation drug-eluting stents
2020, Diabetes Research and Clinical Practice
We investigated the 2-year clinical outcomes of patients with acute myocardial infarction (AMI) and prediabetes after new-generation drug-eluting stents implantation.
A total of 11,962 patients with AMI were classified into normoglycemia (group A; 3,080), prediabetes (group B; 3,709), and diabetes (group C; 5,173) groups. The primary outcomes were the patient-oriented composite outcomes (POCOs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization. Secondary outcomes were the individual components of POCOs and stent thrombosis (ST).
POCOs in groups B and C were significantly higher than those in group A. Cardiac death (adjusted hazard ratio [aHR]: 1.957, 95% confidence interval [CI]: 1.126–3.402; p = 0.017) and any repeat revascularization (aHR: 1.597, 95% CI: 1.052–2.424; p = 0.028) rates were significantly higher in group B than in group A. Re-MI (aHR: 1.884, 95% CI: 1.201–2.954; p = 0.006) and death or MI (aHR: 1.438, 95% CI: 1.098–1.884; p = 0.008) were significantly higher in group C than in group B.
In this study, prediabetes showed bad clinical outcomes post AMI. However, larger randomized controlled studies including ethnically diverse population are needed to confirm these harmful cardiovascular effects of prediabetes in the future.
HbA1c: High in acute cerebral infarction and low in brain trauma
2019, Progress in Molecular Biology and Translational Science
Citation Excerpt :
Selvin et al. indicated that increased HbA1c levels are better predictor of microangiopathy than the fasting blood glucose.24 In recent years, the correlation between the increased HbA1c levels and cardiovascular and brain-related diseases has been confirmed by several independent studies.25–29 It has also been reported that elevated HbA1c levels are closely associated with increased risk of cancers.30–40
HbA1c is a glycated hemoglobin. The ≥ 6.5% HbA1c in total hemoglobins has been used in diagnosing and guiding therapy for patients with diabetes since 1970s. Increased HbA1c levels are observed in other nondiabetic conditions, such as cancers, uremia, macro- and microvascular diseases. However, a systematic comparison of the HbA1c levels in different types of human diseases has not been reported. In current study, 48,183 clinical lab test results of HbA1c levels from healthy individuals and patients with 36 different types of diseases during the past 5 years in our hospital were retrieved and analyzed. Based on the mean (SD), median, and p (− Log₁₀ p) values, we found that patients suffering type 2 diabetes, acute cerebral infarction, nephrotic syndrome, endometrial cancer, cerebral ischemia, leukemia, bladder cancer, chronic obstructive pulmonary disease plus other 27 diseases had significantly (p < 0.05, − Log₁₀ p > 1.30) increased HbA1c levels, whereas patients suffering brain trauma had significantly decreased HbA1c levels compared to that of healthy controls. Moreover, the highest − Log₁₀ p values were observed in type 2 diabetes, acute cerebral infarction, coronary heart disease, cerebrovascular disease, healthy controls > 65 years old, and diabetic nephropathy, indicating the increased HbA1c levels were associated with aging and aging-related diseases. Unexpectedly, 29/36 diseases had both mean and median HbA1c levels ≥ 6.5%. These data suggested that the increased HbA1c levels were a common feature of nondiabetic diseases. Revealing the molecular mechanisms underlying the data presented in current study might help better understand the meaning of glycemic control.
“Silent” Diabetes and Clinical Outcome After Treatment With Contemporary Drug-Eluting Stents: The BIO-RESORT Silent Diabetes Study
2018, JACC: Cardiovascular Interventions
This study sought to assess the prevalence and clinical impact of silent diabetes and pre-diabetes in “nondiabetic” percutaneous coronary intervention (PCI) all-comers.
Patients with undetected and thus untreated (silent) diabetes may have higher event risks after PCI with contemporary drug-eluting stents (DES).
The BIO-RESORT Silent Diabetes study, performed at Thoraxcentrum Twente, is a substudy of the randomized multicenter BIO-RESORT (BIOdegradable Polymer and DuRable Polymer Drug-eluting Stents in an All COmeRs PopulaTion) trial (NCT01674803). Patients underwent oral glucose tolerance testing (OGTT), and assessment of glycosylated hemoglobin with fasting plasma glucose. Primary endpoint was a composite of cardiac death, target vessel–related myocardial infarction, or target vessel revascularization at 1 year.
Of the 988 participants, OGTT detected silent diabetes in 68 (6.9%), pre-diabetes in 133 (13.3%), and normal glucose metabolism in 788 (79.8%). Patients with silent diabetes had higher primary endpoint rates (13.2% vs. 7.6% vs. 4.8%; p < 0.001; silent diabetes vs. normal: hazard ratio: 4.2; 95% confidence interval: 1.9 to 9.2). Differences were driven by myocardial infarction (p < 0.001) which occurred mostly <48 h. Based on glycosylated hemoglobin and fasting plasma glucose, silent diabetes was found in 33 (3.3%) patients, pre-diabetes in 217 (22.0%) patients, and normal glucose metabolism in 738 (74.7%) patients; primary endpoint rates were similar to OGTT-based analyses (12.1% vs. 5.5% vs. 3.1%; p = 0.01). Multivariate analyses demonstrated that abnormal glucose metabolism by either diagnostic approach, present in 330 (33.4%) patients, independently predicted adverse event risk (hazard ratio: 2.2; 95% confidence interval: 1.2 to 4.2).
Abnormal glucose metabolism was detected in 1 of 3 “nondiabetic” PCI patients and was independently associated with up to 4-fold higher event risks. Future intervention trials should determine whether meaningful benefits accrue from routine glycemia testing in such patients.
Relationship of non-cardiac biomarkers with periprocedural myocardial injury in patients undergoing percutaneous coronary intervention
2016, International Journal of Cardiology
Citation Excerpt :
Studies had contributed compelling evidence that glucose levels, regardless of diabetic status, are associated with risk of cardiovascular events in patients with CAD and AMI [77,78]. Glycosylated hemoglobin (HbA1c), reflecting on the control of chronic glucose, have been associated to a poor prognosis after PCI in non-diabetic and diabetic patients [79,80]. The disadvantages of hyperglycemia might be attributable to inducing inflammation, platelet hyper reactivity and endothelial dysfunction [81].
percutaneous coronary intervention (PCI) is one of the dominant methods for revascularization in patient with coronary artery disease (CAD), which accompanied with high incidence of periprocedural myocardial injury (PMI) evaluated by postprocedural cardiac biomarker elevation. For the convenience of risk stratification of PMI following PCI, the aim of present review provides a unique opportunity to summarize the relationship of non-cardiac biomarkers with PMI by extensively searching in the MEDLINE to identify all the relevant studies. In conclusion, we found that PCI related PMI might be correlated positively to those non-cardiac biomarkers such as low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, total cholesterol, triglyceride, the ratios of LDL-C to high-density lipoprotein cholesterol (HDL-C), the ratios of HDL-C to apolipoprotein A-I, the ratio of eicosapentaenoic acid to arachidonic acid, lectin-like oxidized low-density lipoprotein receptor-1, C-reactive protein, high on-treatment platelet reactivity, platelet-monocyte aggregates, N-term pro-B-type natriuretic peptide, hemoglobin and albuminuria. Inversely, no relationships of PMI with those non-cardiac biomarkers such as mean platelet volume, platelet distribution width, platelet-larger cell ratio, uric acid, eosinophils count and the genetic variant of methylenetetrahydrofolate reductase (MTHFR) 677 C > T polymorphism. Moreover, there were controversial associations between PMI and those non-cardiac biomarkers such as high-density lipoprotein cholesterol, glycosylated hemoglobin, homocysteine and the polymorphism Leu33Pro of platelet glycoprotein IIbIIIa. However, almost all studies failed to provide definite mechanism of its findings, and further reaches are needed to focus on the potential mechanisms of association between non-cardiac biomarkers and PMI related to PCI.
Glycosylated hemoglobin and the risk of periprocedural myocardial infarction in non-diabetic patients
2015, Journal of Diabetes and its Complications
Alterations of glucose homeostasis have been reported to occur even in non-diabetic patients, thus increasing the risk of cardiovascular events and worsening the outcome after an acute myocardial infarction (AMI). Still debated is the role of impaired glucose control in patients undergoing percutaneous coronary intervention (PCI), as hyperglycemia, represents an important pro-thrombotic stimulus, increasing platelet reactivity and potentially procedural complications. Therefore, the aim of our study was to assess the association between glycosylated hemoglobin and periprocedural myocardial infarction (PMI) in non-diabetic patients undergoing PCI.
We included patients without history of diabetes undergoing elective PCI. PMI was defined as creatine kinase-MB increase by 3 times the upper limit normal or by 50% of an elevated baseline value, whereas periprocedural myonecrosis as Troponin I increase by 3 × ULN or 50% of baseline.
Our population is represented by 1199 patients, who were divided according to tertile values of glycosylated hemoglobin (HbA1c). Higher HbA1c was associated with ageing (p < 0.001), hypertension (p = 0.005), previous myocardial infarction (p = 0.009), PCI (p < 0.001) or CABG (p = 0.001), treatment with diuretics (p < 0.001), higher levels of glycemia (p < 0.001) and white blood cells (p = 0.02), multivessel coronary artery disease (p = 0.03), higher rate of instent restenosis (p = 0.02).
HbA1c did not impact on periprocedural myocardial infarction (p = 0.85; adjusted OR [95% CI] = 0.91 [0.74–1.12], p = 0.38) or myonecrosis (p = 0.69; adjusted OR [95% CI] = 0.95 [0.80–1.13], p = 0.56). Similar results were obtained fasting glycemia for PMI (p = 0.82, adjusted OR [95% CI] = 0.90 [0.71–1.14], p = 0.37) and myonecrosis (p = 0.21, adjusted OR [95% CI] = 1.02 [0.84–1.24], p = 0.84) and confirmed in high-risk subsets of patients.
In non-diabetic patients undergoing elective PCI, neither glycosylated hemoglobin levels nor fasting glycemia are associated with the risk of periprocedural myocardial infarction and necrosis.

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Coronary artery diseaseRelation of hemoglobin A1c to rate of major adverse cardiac events in nondiabetic patients undergoing percutaneous coronary revascularization

Abstract

Section snippets

Study design

Results

Discussion

Acknowledgements

Am Heart J

J Clin Epidemiol

Sex differences in fasting glycemia as a risk factor for ischemic heart disease

Am J Epidemiol

Glucose tolerance and cardiovascular mortality

Cardiovasc Rev Rep

Risk factors for myocardial infarction and death in newly detected NIDDMthe Diabetes Intervention Study, 11 year follow-up

Diabetologia

Coronary artery disease
Relation of hemoglobin A1c to rate of major adverse cardiac events in nondiabetic patients undergoing percutaneous coronary revascularization