Table 8.

Screening Tests for Asymptomatic CAD in Patients With Diabetes Mellitus

Test	Description	Key Results	Inclusion in a Recent AHA Guideline?
ECG	Resting electric activity through the cardiac cycle	In the UKPDS study, 1 in 6 patients with newly diagnosed type 2 diabetes mellitus had evidence of silent MI on the baseline surface ECG.211 Prevalence of ECG abnormalities in patients with diabetes mellitus and no known CAD was even higher in older studies, approaching 20%.212 UKPDS data indicate that an abnormal ECG is an independent risk factor for all-cause mortality and fatal MI in patients with diabetes mellitus.211 Specific ECG abnormalities associated with increased risk of CVD events in cohort studies include pathological Q waves, LVH (particularly if accompanied by repolarization abnormalities), QRS prolongation, ST-segment depressions, and pathological T-wave inversions.213 Abnormal ECG findings have been demonstrated to predict inducible ischemia.214	Class IIa: A resting ECG is reasonable for cardiovascular risk assessment in asymptomatic adults with hypertension or diabetes mellitus (Level of Evidence C).213
ABI	Ratio of systolic blood pressure at the ankle and arm. Used as an indicator of underlying peripheral arterial disease	A systematic review of ABI as a predictor of future CVD events demonstrated high specificity (≈93%) but very low sensitivity (16%),215 thus limiting its utility as a screening test for CAD.	Class IIa: Measurement of ABI is reasonable for cardiovascular risk assessment in asymptomatic adults at intermediate risk (Level of Evidence B).213
Stress MPI	Radioactive tracer (eg, thallium-201, Tc99m sestamibi, or Tc99m tetrofosmin) uptake within the myocardium is assessed before and after stress with scintigraphy. Option for pharmacological stress (dipyridamole, adenosine, or regadenoson) in those not able to exercise	MiSAD216: A total of 925 asymptomatic patients with type 2 diabetes mellitus underwent an ECG stress testing, which, if positive or equivocal, led to stress thallium MPI. Silent CAD prevalence 12.5% for abnormal exercise ECG and 6.4% for both abnormal ECG and MPI. Abnormal scintigraphy predicted cardiac events at 5 y (HR, 5.5; 95% CI, 2.4–12.3; P<0.001). DIAD217,219: In total, 1123 patients with type 2 diabetes mellitus were enrolled from multiple centers (mean duration of diabetes mellitus, 8.5 y); 522 patients were randomized to adenosine sestamibi SPECT MPI, and 561 served as the control group and were randomized to follow-up alone. Silent ischemia prevalence=21.5%. At 5 y of follow-up, there was no difference in the primary end point, nonfatal MI and cardiac death, between the screened and unscreened cohorts (overall annual rate, 0.6%; 15 vs 17 events; HR, 0.88; 95% CI, 0.44–1.80; P=0.73). No differences in any secondary end points (unstable angina, heart failure, stroke, coronary revascularization). DYNAMIT trial218: Prospective, randomized, double-blind, multicenter study conducted in France. In total, 631 patients were randomized to either CAD screening with either a stress ETT or dipyridamole SPECT MPI vs follow-up only (without screening). Study was stopped prematurely; no difference in cardiac outcomes was seen between screened and unscreened groups (HR, 1.00; 95% CI, 0.59–1.71).	Class IIb: Stress MPI may be considered for advanced cardiovascular risk assessment in asymptomatic adults with diabetes mellitus or asymptomatic adults with a strong family history of CHD or when previous risk assessment testing suggests a high risk of CHD (eg, a CAC score of ≥400) (Level of Evidence C).213 Class III: No benefit. Stress MPI is not indicated for cardiovascular risk assessment in low- or intermediate-risk asymptomatic adults (Level of Evidence C).213
CAC scoring	Quantitative assessment of calcium deposited within the coronary arteries (as a marker of atherosclerosis) via EBCT or multidetector CT, stratified by Agatston units, yielding CAC scores of <100 (low risk), 100–400 (moderate risk), and >400 (high risk)	Linear relationship between CAC and clinical CHD events among individuals with and without diabetes mellitus.220–225 Patients with diabetes mellitus have a greater prevalence and extent of CAC than those without diabetes mellitus.225–228 Prognostic significance of elevated CAC in predicting adverse events is greater in patients with diabetes mellitus than in those without diabetes mellitus.229 No dedicated randomized trials have suggested that the detection of subclinical CAD by CAC leads to improvement in clinical events. This represents an important area of future research.	In asymptomatic adults with diabetes mellitus ≥40 y of age, measurement of CAC is reasonable for cardiovascular risk assessment (Level of Evidence B).213

ABI indicates ankle-brachial index; AHA, American Heart Association; CAC, coronary artery calcium; CAD, coronary artery disease; CHD, coronary heart disease; CI, confidence interval; CT, computed tomography; CVD, cardiovascular disease; DIAD, Detection of Ischemia in Asymptomatic Diabetics; DYNAMIT, Do You Need to Assess Myocardial Ischemia in Type 2 Diabetes; EBCT, electron-beam computed tomography; ETT, exercise tolerance testing; HR, hazard ratio; LVH, left ventricular hypertrophy; MI, myocardial infarction; MiSAD, Milan Study on Atherosclerosis and Diabetes; MPI, myocardial perfusion imaging; SPECT, single-photon emission computed tomography; and UKPDS, United Kingdom Prospective Diabetes Study.