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Canadian Pharmacists Association
Canadian Pharmacists Association
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Chapter 23: Screening for the Presence of Coronary Artery Disease

Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada

Cardiovascular Disease in Diabetes
  • The majority (65% to 80%) of people with diabetes will die from heart disease, many with no prior signs and symptoms. Compared to people without diabetes, people with diabetes (especially women) are at higher risk of developing heart disease, and at an earlier age.
  • People with diabetes have a high prevalence of silent myocardial ischemia, and almost one-third of myocardial infarctions (MIs) occur without recognized or typical symptoms (silent MIs).
  • The goals of screening are to improve life expectancy and quality of life by preventing MI and heart failure through the early detection of coronary artery disease (CAD).
Role of Stress Testing
  • People with diabetes should undergo investigation for CAD by exercise ECG stress testing as the initial test [Grade D, Consensus] in the presence of the following:
    • Typical or atypical cardiac symptoms (e.g. unexplained dyspnea, chest discomfort) [Grade C, Level 3]
    • Signs or symptoms of associated diseases
      • Peripheral arterial disease (abnormal ankle-brachial index) [Grade D, Level 4]
      • Carotid bruits (the sound of turbulent flow heard over the carotid artery, caused by abnormal narrowing of the vessel. Narrowing can be due to cholesterol or plaque buildup in the artery) [Grade D, Consensus]

      • Transient ischemic attack [Grade D, Consensus]
      • Stroke [Grade D, Consensus]
    • Resting abnormalities on ECG (e.g. Q waves) [Grade D, Consensus]
  • A baseline resting ECG should be performed in individuals with any of the following [Grade D, Consensus]:
    • Age >40 years
    • Duration of diabetes >15 years and age >30 years
    • End organ damage (microvascular, macrovascular)
    • Cardiac risk factors
  • A repeat resting ECG should be performed every 2 years in patients with diabetes [Grade D, Consensus].
  • There is evidence that early screening and intervention in people with diabetes and with silent ischemia is beneficial and may improve long-term survival.
    • Silent ischemia is most likely to occur in individuals with diabetes who are older (mean age 65 years) and have elevated total cholesterol and proteinuria.
    • An ECG with ST-T abnormalities at rest is the most predictive for silent ischemia and is the only significant predictor of silent ischemia in women.
  • Silent MI is common (40%) in older asymptomatic people with type 2 diabetes, but is more frequent (65%) in those with diabetes who also have microalbuminuria.
  • People with diabetes and silent ischemia have an annual event rate for CAD of 6.2% (50% of events were new-onset angina and 50% were cardiac death or MIs). Thus, silent MI is a prelude not only to symptomatic ischemia, but also to potentially fatal events.
  • Exercise capacity is frequently impaired in people with diabetes due to the high prevalence of obesity, sedentary lifestyle, peripheral neuropathy (both sensory and motor), and vascular disease in this population.
    • Individuals with diabetes who demonstrate ischemia at low exercise capacity (<5 metabolic equivalents) on stress testing should be referred to a cardiac specialist [Grade D, Consensus].
    • Individuals who are unable to perform an exercise ECG stress test are required to complete pharmacologic stress imaging using dipyridamole, adenosine, or dobutamine
CVD in Type 1 Diabetes

Incidence and prevalence of CVD

  • CVD complications are important causes of morbidity and mortality among individuals with type 1 diabetes that may have been under-recognized in the past. Reported prevalence rates of CVD in type 1 diabetes vary between 3% and 12.4%. It is important to emphasize that the cardiovascular risk burden and profile of patients with type 1 diabetes differs from type 2 diabetes.
    • The Diabetes UK longitudinal cohort study reported that type 1 diabetes is associated with markedly increased adjusted hazard ratio for major CAD events in men (HR 3.6) and women (HR 9.6). These risks are comparable to those observed in patients with type 2 diabetes.
    • Gender and race/ethnicity are important features of increased risk of CVD; male gender and African-Americans have higher rates of CVD compared to Europeans.

Differences from type 2 diabetes

  • The risk of CAD mortality is comparable in women and men with type 1 diabetes
  • There is a high prevalence of silent CAD in young adults with type 1 diabetes, which may be related to cardiac autonomic neuropathy.
  • The disease process seems to be more severe in type 1 diabetes. Compared with nondiabetic controls, patients with type 1 diabetes are more likely to have severe coronary stenosis, involvement of all 3 major coronary arteries and distal segment disease, resulting in major cardiovascular events with poor outcome and/or early development of heart failure.

Coronary artery disease and cerebrovascular disease

  • CAD appears more common than stroke. For the most part, studies report incidences around 15%. Mortality rates from CAD are reported between 6 and 8%, are likely higher in men than women, and in those >40 years of age.
  • Stroke is still an important outcome in type 1 diabetes; the cumulative incidence of stroke was 3.3% over 6 years among African-Americans, 5.9% over 20 years in the WESDR (Wisconsin Epidemiologic Study of Diabetic Retinopathy), and 0.74% per year in the EURODIAB Study. Also, prevalence of silent brain infarcts or leukoaraiosis is extremely high (34.5%) in type 1 diabetes.
Peripheral Vascular Disease
  • Peripheral vascular disease (PVD) is an important vascular complication of type 1 diabetes. Incidence rates of lower extremity amputation vary by age from 3.6 per 1000 person-years among individuals 25 to 44 years of age to as high as 7.2%.
  • By age 65, the cumulative probability of PVD is 11% in women and 20.7% in men. Compared to the general population, the rate of PVD among those with type 1 diabetes may be very high.
  • In addition to the clinical endpoints of CAD, stroke and PVD, subclinical carotid disease may be commonly associated with type 1 diabetes.
  • Compared to age-/sex-matched healthy controls, greater carotid intima-media thickness (IMT) has been observed in studies of children with type 1 diabetes with a mean age as young as 11 years.
Time course of events
  • Although CAD rarely presents within the first 20 years of diagnosis, by age 30 years, many individuals will have had type 1 diabetes for 20 years and rates of CVD begin to approach the considered “high-risk” category.
  • The recent decline in diabetic kidney disease has not been accompanied by a corresponding fall in CAD rates.
  • The well-recognized increase in CVD risk associated with proteinuria explains only a portion of the CVD risk.
  •  In the DCCT study, the treatment group effect of intensive treatment therapy on CVD risk persisted after adjustment for microalbuminuria (hazard ratio [HR] 0.62) and albuminuria (HR 0.58), suggesting that, although diabetic kidney disease is important, differences in mean A1C are clearly significant drivers.
Effect of gender
  • Compared to women without diabetes, women with type 1 diabetes had a 3.5 times higher risk of having coronary artery calcifications.
  • While standardized mortality rates from ischemic heart disease were higher in men than women at all ages in the general population, there was no difference in mortality from ischemic heart disease in men and women with type 1 diabetes <40 years of age.
  • Men with type 1 diabetes age ≥40 years had a higher mortality rate from CVD than women with type 1 diabetes. The presence of type 1 diabetes (as well as in type 2 diabetes) seems to dramatically increase the risk for CVD, particularly in women.
Testing for CVD in type 1 diabetes
  • Considering that risk scores are accurate in type 1 diabetes, the following patients with type 1 diabetes should have additional testing for CAD:
    • Those with symptoms suggestive of CAD
    • Those with an abnormal resting ECG or clustering of cardiac risk factors, yielding to an intermediate or high global risk estimate
  • For patients able to walk on a treadmill without significant baseline ST segment abnormality, exercise treadmill testing remains the first-line diagnostic test due to the high cost efficacy and widespread availability.
    • Sometimes treadmill testing may not be possible due to the burden of peripheral neuropathy, foot pathology, lower extremity amputation and ECG abnormalities as left ventricular hypertrophy in the patient population with type 1 diabetes.
    • Individuals who require stress testing and are unable to exercise should undergo pharmacological stress echocardiography or nuclear imaging [Grade C, Level 3]. In addition, pharmacological stress echocardiography or nuclear imaging should be used in individuals with diabetes in whom resting ECG abnormalities preclude the use of exercise ECG stress testing (e.g. left bundle branch block or ST-T abnormalities) [Grade D, Consensus].
  • Coronary artery calcium, assessed by CT imaging, is common and more frequent in patients with type 1 diabetes than in those without diabetes. Progression of coronary artery calcium is reduced by intensive glycemic control.
  • The presence of coronary artery calcium is independently associated with increased prevalence of CAD, even after adjustment for traditional risk factors, and test performance in patients with type 1 diabetes is comparable to that of the general population.

For definitions of the levels of evidence cited in this chapter, please refer to the Guideline Recommendations: Levels of Evidence.

If you would like more details on this topic, please visit the Canadian Diabetes Association Clinical Practice Guidelines: Chapter 23.