Should adults with type 2 diabetes be screened for atherosclerotic cardiovascular disease?

Coronary artery calcium screening

CAC assesses the extent of calcified atherosclerotic plaques in the coronary arteries and is exquisitely sensitive for detection of atherosclerosis¹⁴. CAC scanning has emerged as the most powerful tool for refining risk assessment on top of global risk assessment in asymptomatic individuals¹⁵. In those subjects with DM, a CAC score of 0 is associated with ASCVD event rates as low as or lower than those of many persons without DM and increasing CAC scores are associated with progressively higher ASCVD event rates; those with DM who have CAC scores of at least 400 have 10-fold greater event rates (CHD incidence of 4% per year) than those with CAC of 0 (38% of our DM subjects)¹¹. Subjects who undergo scanning for CAC also appear to have improved outcomes in terms of improved risk factor control, including blood pressure, low-density lipoprotein cholesterol, and waist circumference, compared with those not scanned¹⁶. This observation may be explained by greater adherence to lifestyle modifications and medical therapy on the basis of visualizing their disease^17–20. Also, CAC screening has been noted to be more cost-effective than myocardial perfusion imaging (MPI); it was estimated that CAC scanning can prevent one event at a cost of $71,249, about a third of the cost of MPI and half that of no screening (treating everyone)²¹.

Most guidelines have suggested that CAC be considered for screening and risk stratification of patients with DM. Both the 2010 AHA risk assessment guidelines (level IIa) and the 2014 position statement of the Brazilian Diabetes Society (level A) recommend CAC scanning for those who are at intermediate risk or who have diabetes^22,23. The 2012 American Association of Clinical Endocrinology (AACE) Lipid Management Guideline also stated that CAC can be used in those with DM to refine risk stratification and the need for more aggressive preventive strategies²⁴. Most recently, the ACC/AHA guideline on the assessment of cardiovascular risk²⁵ identifies CAC screening (as well as family history of premature ASCVD, ankle brachial index, and high-sensitivity C-reactive protein) as a tool that can be used when, after quantitative risk assessment, a risk-based treatment decision is uncertain. Although current guidelines recommend that all DM patients who are 40 or over be on statin therapy, the intensity of therapy (or possible consideration of therapy in those younger than 40 years of age) may be guided by the use of such testing.

Stress myocardial perfusion imaging

Observational investigations of MPI have shown high sensitivity (86%) in those with DM and even higher sensitivity among those at higher risk (94%)^26,27. However, the Detection of Ischemia in Asymptomatic Diabetics (DIAD) randomized clinical trial demonstrated that screening patients with DM does not improve clinical outcomes²⁸, even when ischemia is present upon repeat testing (at 3 years)²⁹. The negative result may be due to the low prevalence of CAD and thus a low incidence of coronary events. Although some guidelines have advocated screening for silent myocardial ischemia in high-risk asymptomatic patients with DM²², it is no longer routinely recommended in current guidelines^5,23.

Coronary computed tomography angiography

Coronary computed tomography angiography (CCTA) allows the evaluation of the full spectrum of CAD from totally normal arteries to non-obstructive disease to significant coronary stenosis and total occlusion. It also allows plaque characterization, including calcified and non-calcified plaque, spotty calcification, positive remodeling, and the napkin ring sign³⁰. Some of these features are associated with a higher likelihood of near-term major adverse cardiovascular events. Several studies have shown the prognostic value of CCTA findings in subjects with asymptomatic DM^31,32. Whether clinical outcomes can be impacted by CCTA screening, however, was only recently reported by the FACTOR-64 randomized clinical trial, which enrolled 900 asymptomatic patients with diabetes; while showing a 20% reduced risk of subsequent adverse cardiovascular events in those screened with CCTA, the findings were not statistically significant and this was due in part to the fairly low event rates³³. Due to a lack of sufficient supportive evidence, CCTA is not conventionally recommended for screening asymptomatic individuals with DM in current guidelines^34–36.

Carotid intima-media thickness

CIMT is an indicator of atherosclerosis in the carotid artery, measuring the combined thickness of the intima and media with B-mode ultrasound. Although CIMT is related to higher CVD event risk³⁷, the meaning of measuring CIMT alone has recently been questioned, as meta-analysis and pooled cohort studies showed that the addition of common CIMT to traditional risk models was associated with only a modest improvement and is unlikely to be of clinical importance^38,39. Similar findings in a cohort of 4,220 patients with DM demonstrated that common CIMT did not add predictive value to the FRS during a median follow-up of 8.7 years⁴⁰. However, if combined with CAC, ankle brachial index, high-sensitivity C-reactive protein, and family history, the predictive ability for future CHD events may supersede the traditional FRS and UKPDS risk engine⁴¹. Importantly, the presence of carotid plaques alone and in combination with CIMT does add to risk prediction beyond FRS, as demonstrated by Nambi and colleagues⁴², although this question was not specifically evaluated in those with DM in that study.