Author + information
- Published online February 14, 2018.
- Michael E. Farkouh, MD, MSc∗ ()
- Peter Munk Cardiac Centre, Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto, Toronto, Ontario, Canada
- ↵∗Address for correspondence:
Dr. Michael E. Farkouh, Toronto General Hospital, 585 University Avenue, 4N474, Toronto, Ontario, Canada M5G 2N2.
If the interventional cardiology community is to make the greatest impact on the lives of our patients with coronary artery disease, they must focus on a coordinated approach to optimizing medical management post-percutaneous coronary intervention (PCI). A great deal of emphasis has been placed on lipid management and antiplatelet regimens, but this also includes a better understanding of the role of short- and long-term glycemic control in all of our patients whether or not they are known to have type 2 diabetes mellitus (T2DM). More than a decade ago, the DECODE study (Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe) established the association between the pre-diabetes (PDM) state of impaired glucose tolerance as a marker of increased cardiovascular (CV) risk (1). For interventional cardiologists, the role of screening for dysglycemia has been proposed as an important marker of outcomes after PCI, but it is not a routine part of clinical guidelines (2).
The American Diabetes Association defines T2DM on the basis of a number of criteria including as plasma glucose criteria a 2-h post–75-g oral glucose tolerance test (OGTT) plasma glucose (PG) ≥200 mg/dl OR fasting plasma glucose (FPG) of ≥126 mg/dl OR a glycosylated hemoglobin (HbA1c) level ≥6.5% (3). The CV community has largely accepted the HbA1c criterion as the primary method of diagnosis due to standardized measurement and practicality. PDM is defined by a 2-h post OGTT PG of 140 to 199 mg/dl OR FPG 100 to 125 mg/dl OR a HbA1c level between 5.7% and 6.4%. For the purposes of screening for PDM, the 2-h OGTT and HbA1c criteria are considered equal. For the purposes of this editorial, all 3 criteria define patients with some degree of dysglycemia. Finally, in recent years, the combination of an impaired FPG and HbA1c below 6.5% has been shown to be highly predictive of impaired glucose tolerance as diagnosed by the OGTT (4). This has led many to use this metric over the OGTT.
Before moving onto the importance of screening for T2DM and PDM in a PCI population, it is important to emphasize the role of elevated plasma glucose in predicting events in PCI patients without known T2DM treated for an acute coronary syndrome (5). There is clear evidence that admission hyperglycemia, particularly when >200 mg/dl, is a potent predictor of mortality post-acute coronary syndrome (6). The mechanism by which this risk is conferred is likely multifactorial and includes impaired myocardial energy metabolism, increased oxidative stress, and impaired platelet function, to name a few. But the role of stress hyperglycemia on outcomes post-PCI must be clearly distinguished from the diagnosis of T2DM or PDM. The challenges of finding short-term interventions to affect major adverse CV events (MACE) outcomes makes the treatment of the hyperglycemic patient complicated. For example, there is no role for the administration of glucose-insulin-potassium infusions in patients with non–ST-segment myocardial infarction (MI) (2).
In this edition of JACC: Cardiovascular Interventions, von Birgelen et al. (7) report on the outcomes of PCI patients with silent T2DM and PDM from the BIO-RESORT (Comparison of BIOdegradable Polymer and DuRablE Polymer Drug-eluting Stents in an All COmeRs PopulaTion) Silent Diabetes study. This analysis addresses 2 questions that have been in play for over a decade: first, what is the prevalence of silent T2DM and PDM in a contemporary PCI population; and second, what are the related CV outcomes. The authors find that up to one-third of patients have established dysglycemia and that the risk of worse CV outcomes is more than 2-fold greater than those without dysglycemia. The 1-year event rates are largely driven by differences in the rate of any MI (periprocedural and target vessel MI and non–ST-segment MI) and target vessel failure despite a robust prescription of background medical therapy.
These findings are largely confirmatory. A recent meta-analysis involving over 22,000 patients in 20 studies showed no association of elevated HbA1c with an excess of short-term deaths (8). However, in the long term, there was an association of elevated HbA1c and excess risk of mortality and MI. This confirms that the risk of dysglycemia as measured by HbA1c or OGTT is predictive of long-term CV events and holds the promise of a modifiable course.
Some important take-home messages resonate from this paper. The proportion of all-comer patients undergoing PCI that have dysglycemia, either silent T2DM or PDM, is incredibly high. This creates a perfect storm for a quality initiative to better characterize our PCI patients because screening is an opportunity to risk stratify our patients. Because FPG and HbA1c are as effective as OGTT in categorizing patients, it would be important to inform the guidelines to routinely check these indices at the index PCI. This will allow for patients to be managed with optimal medical therapy for the long term.
Another important theme emerging from these data is the increased risk of MACE in patients with dysglycemia. There is a graded risk of MACE from normal glycemia to PDM to T2D. There is a tremendous public health opportunity to potentially prevent PDM patients from progressing to full-blown T2DM. Adherence to optimal medical therapy including statins, antiplatelet drugs, and lifestyle modification will undoubtedly lead to fewer cases of transformation from PDM to T2DM. The real limitation of this analysis is the lack of reporting of success in achieving medical risk factor targets including low-density lipoprotein cholesterol levels and systolic blood pressure determinations, given the fact that both T2DM and PDM must be considered with the complete risk factor profile in mind. The interventional community needs to work in concert with the community physicians and general cardiologists to ensure that all patients with dysglycemia reach the pertinent target for all of these risk factors. The advent of newer antidiabetic drugs such as the sodium-dependent glucose cotransporter-2 (SGLT2) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists classes that have been shown to reduce MACE events in large outcomes trials will alter the course for many of our post-PCI patients with dysglycemia (9,10).
It is refreshing to observe the interest of the interventional community to better characterize their patients and to provide more individualized care. The silent dysglycemia patient should be identified as early as possible to prevent the serious microvascular and macrovascular complications of diabetes. The optimal revascularization strategy for these patients is also a topic of great debate. As the PDM population grows, the cardiology community will need to actively prevent future CV events through comprehensive, multispecialty models of long-term care. The guidelines for post-PCI patients must adopt these new metrics by routinely screening all PCI patients with a fasting plasma glucose level and a HbA1c.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Farkouh has reported that he has no relationships relevant to the contents of this paper to disclose.
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