1. Description of index tests.

Test	Description	Advantages	Disadvantages	Type of result	Presence of cut‐off values
Screening tests
MPS Stress Exercise dipyridamole dobutamine Radionucleotide thallium‐201 or Tc‐99m sestamibi radionucleotide agents	This compares perfusion of myocardium at rest and after a ‘stress’ such as exercise or drugs (e.g. dipyridamole). When coronary arteries are normal, ‘stress’ results in vasodilatation and increased coronary blood flow. However, diseased coronary arteries cannot dilate because they are already maximally dilated and there is no increase in blood flow after a stress. MPS reveals these areas as regions of decreased perfusion. A reversible perfusion defect is a sign of ischaemia. A fixed defect (when there is decreased perfusion before, during and after the stress) is an indicator of infarction. Pharmacological agents overcome limitations of exercise testing in patients with kidney disease	Non‐invasive Provides information regarding functional status of myocardium under stress conditions	Neither 100% sensitive nor specific Radiation dose Results subject to interpretation and reader bias False positives due to increase in attenuation artefacts caused by left ventricular hypertrophy False negatives due to balanced ischaemia (e.g. triple vessel disease) More expensive than exercise ECG	Dichotomous (i.e. stress test positive or stress test negative)	None. However, whether a stress test is interpreted as positive or negative depends largely on observer interpretation
DSE Stress Exercise dobutamine	Stress echocardiography compares the regional wall motion and thickness of myocardium both at rest and after stress. Regional systolic dysfunction is usually caused by CAD. Pharmacological stress agent overcomes limitations of exercise testing in patients with kidney disease	Non‐invasive No radiation dose Provides information regarding functional status of myocardium under stress conditions Provides assessment of ventricular size and function	Neither 100% sensitive nor specific Results subject to interpretation and reader bias Operator dependent Acoustic windows not possible in up to 20% of subjects Hypertensive response to stress agent possible Cardiomyopathies may also show regional variation in function	Dichotomous (i.e. stress test positive or stress test negative)	None. However, whether a stress test is interpreted as positive or negative depends largely on observer interpretation
Exercise ECG Bruce protocol stress ECG	Patient exercises on a treadmill while connected to an ECG. The level of exercise is increased in progressive stages. The patient's symptoms and blood pressure response are checked repeatedly. Ischaemic ECG changes or angina symptoms brought on by exercise are highly suggestive of underlying CAD	Non‐invasive Provides information regarding functional status of myocardium under stress conditions	Neither 100% sensitive nor specific Results subject to interpretation and reader bias Often limited by the inability of CKD patients to achieve an adequate peak exercise workload, development of exercise‐induced hypotension High proportion have abnormal baseline ECG (left ventricular hypertrophy)	Dichotomous (i.e. stress test positive or stress test negative)	No. However, whether a stress test is interpreted as positive or negative depends largely on observer interpretation
Coronary artery calcium score EBCT Multidetector computed tomography	Cardiac calcium scoring is a non‐invasive test that uses computed tomography to detect the presence of calcium in plaque on the walls of the arteries of the heart (coronary arteries). A calcium score is then derived, calculated as a summation of all calcified lesions in the coronary arteries. The calcium score is then compared with a reference range appropriate to a patient's age and sex. High calcium scores are associated with higher risks of cardiovascular events	Non‐invasive	Neither 100% sensitive nor specific Radiation dose	Continuous	There is no uniformly agreed cut‐off value at which patients are considered at high risk of CAD. We planned to analyse results by combining data from studies which share identical cut‐off values
Echocardiography Trans‐thoracic Trans‐oesophageal	An ultrasound of the heart that enables assessment of structure and function. Impairment in systolic function can result from pre‐existing CAD	Provides information regarding myocardial function and regional wall abnormalities, which may suggest pre‐existing ischaemia or MI Enables assessment of structure	Neither highly sensitive nor specific Does not provide any information of reversible ischaemia Results subject to interpretation and reader bias	Dichotomous (e.g. presence or absence of resting wall motion abnormality)	None
CT coronary angiography	Specialised form of CT that enables imaging of the heart and computerised reconstruction of coronary arteries, permitting assessment of the lumen and vessel walls	Non‐invasive Enables diagnosis of precise location and severity of each lesion as opposed to vascular territory affected, as is the case for most functional tests. Assesses not only the lumen of the vessel but also the wall. It can also demonstrate soft atheromatous plaques, which cannot be demonstrated on conventional coronary angiography	Radiation dose Contrast nephropathy Inability to provide opportunity for immediate intervention (as opposed to coronary angiography)	Dichotomous (i.e. presence or absence of significant CAD)	Yes (i.e. ≥ 50% stenosis or ≥ 70% stenosis) We planned to manage the issue of different cut points by involving an analysis that included: All studies regardless of threshold of CAD on coronary angiography (these will include both studies which have ≥ 50% stenosis and ≥ 70% stenosis Only studies which had ≥ 70% stenosis threshold
Cardiac magnetic resonance imaging	MRI of the heart that enables evaluation of its structure and function	Non‐invasive No radiation dose Enables assessment of structure of myocardium High spatial resolution means low inter‐observer variability	Neither highly sensitive nor specific	Dichotomous (e.g. presence or absence of left ventricular systolic dysfunction)	None
Resting ECG	Transthoracic interpretation of the electrical activity of the heart over time captured and externally recorded by skin electrodes	Provides information regarding the electrical function of the myocardium, which may suggest pre‐existing ischaemia, left ventricular hypertrophy or arrhythmias	Neither sensitive nor specific Does not provide any information of reversible ischaemia	Dichotomous (i.e. presence or absence of certain ECG features)	None
CIMT	Measurement of the thickness of artery walls, usually by external ultrasound, to detect both the presence and to track the progression of atherosclerotic disease in humans. Used as a surrogate marker for atherosclerosis	Non‐invasive	Neither highly sensitive nor specific Does not provide any information on cardiac function	Continuous	Yes. This will vary depending on the institution (e.g. 0.75 mm)
Cardiopulmonary exercise testing	Evaluates both cardiac and pulmonary function. Cardiac function is evaluated in terms of aerobic capacity and respiratory function. The subject is exercised on a bicycle ergometer or treadmill. The test enables calculation of maximal aerobic capacity and the point during exercise where anaerobic metabolism is used to supplement aerobic metabolism as a source of energy. These can be measured via gas exchange data	Non‐invasive measurement of ventricular function, respiratory function and cellular function via measurement of gas exchange, as well as detection of myocardial ischaemia Excellent method of evaluating fitness and operative fitness	Not commonly performed	Dichotomous (e.g. stress ECG positive or stress ECG negative; presence or absence of cardiac failure) and Continuous (e.g. measurement of the maximum aerobic capacity and anaerobic threshold)	Yes, although these will vary for different variables and for different institutions
DSF	Used to detect coronary artery calcification. Digital subtraction improves resolution of conventional fluoroscopic methods	Non‐invasive Non exercise	Not commonly used Radiation dose	Dichotomous (i.e. presence or absence of calcification)	None
Exercise radionucleotide ventriculography	Technique for a combined assessment of exercise capacity and an evaluation of ventricular size and performance		Not commonly used Radiation dose	Dichotomous (i.e. stress test positive or stress test negative)	None. However, whether a stress test is interpreted as positive or negative depends largely on observer interpretation
Reference standard
Coronary angiography	Coronary catheterisation is an invasive procedure to access the coronary circulation and blood filled chambers of the heart using a catheter. It can be performed for both diagnostic and interventional (treatment) purposes. It assesses the diameter of coronary artery lumens, heart chamber size and heart muscle contraction performance	Gold standard for detecting CAD. Enables diagnosis of precise location and severity of each lesion Intervention (PTCA) possible during procedure	High cost Lack of sensitivity to intramural coronary atherosclerosis Risk of complications Intravenous contrast media may worsen kidney function Little information on function Radiation dose Results subject to interpretation and reader bias, although to a lesser extent than functional tests	Dichotomous (i.e. presence or absence of significant CAD)	Yes (i.e. ≥ 50% stenosis or ≥ 70% stenosis). We managed the issue of different cut points by involving an analysis which included: All studies regardless of threshold of CAD on coronary angiography (these will include both studies which have ≥ 50% stenosis and ≥ 70% stenosis Only studies which had ≥ 70% stenosis threshold

CAD: coronary artery disease; CIMT: carotid intimal medial thickness; CT: computed tomography; ECG: electrocardiograph; MPS: myocardial perfusion scintigraphy; MRI: magnetic resonance imaging; PTAC: percutaneous transluminal coronary angioplasty