History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include smoking, hypertension, hyperlipidaemia, isolated low HDL cholesterol, diabetes, inactivity, obesity, family history of coronary heart disease, male sex, and illicit drug use.

typical angina symptoms

Typical angina is: 1) chest pressure or squeezing lasting several minutes, 2) provoked by exercise or emotional stress, and 3) relieved by rest or glyceryl trinitrate. This symptom complex is most consistently associated with coronary disease.[66][67]

atypical angina symptoms

Atypical angina is defined as chest discomfort with only two characteristics of typical angina. It is less predictive of coronary disease than typical angina, but may be more frequent in women, people with diabetes, or older people.[107][108][109][110]​ Some guidelines avoid the term 'atypical' and instead suggest ‘cardiac’, ‘possibly cardiac’, and ‘non-cardiac’ pain, although symptoms alone can not determine the cause of chest pain. 

symptoms of low-risk unstable angina

Features of low-risk unstable angina include pain from exertion lasting less than 20 minutes, pain not rapidly increasing, and normal/unchanged ECG.

normal examination

Typically, normal in chronic stable angina.

Other diagnostic factors

common

known medical history of exacerbating factor

As anginal pain results from an imbalance between myocardial oxygen supply and myocardial oxygen demand, patient history should also be evaluated for problems that may exacerbate this imbalance. Thyroid disease, anaemia, hyperviscosity syndrome, arteriovenous fistula, and underlying lung disease are known exacerbating factors.

non-anginal chest pain

Non-anginal chest pain is defined as chest discomfort with only one or none of the characteristics of typical angina. It is less predictive of coronary disease than typical or atypical angina, but should be evaluated with consideration of the patient's age and other risk factors.[66][70]

uncommon

epigastric discomfort

An alternate location for anginal discomfort, more commonly in women, people with diabetes, or older people.

jaw pain

An alternate location for anginal discomfort.

arm pain

An alternate location for anginal discomfort, more commonly the left arm.

dyspnoea on exertion

This may suggest exercise-induced left ventricular dysfunction; coronary disease should be considered among the differential diagnosis in this setting. It may be an anginal equivalent (e.g., in patients with diabetes). Additionally, dyspnoea may suggest underlying lung disease or anaemia that can contribute to anginal symptoms.

nausea/vomiting

May be associated with angina.

perspiration (diaphoresis)

This may be associated with angina, but should also raise suspicion for illicit drug use (cocaine) or thyrotoxicosis.

fatigue

May be associated with angina, but should also raise suspicion for anaemia.

hypoxia

Hypoxia may exacerbate anginal symptoms as a result of poor oxygen delivery to ischaemic myocardium. Evaluation for underlying pulmonary processes should be considered.

tachycardia

Tachycardia should raise suspicion for alternative or exacerbating causes of angina, including thyrotoxicosis, anaemia, sympathomimetic drug use, arteriovenous fistula, or primary atrial or ventricular tachycardia.

S3

If present in the setting of chest discomfort, this suggests ischaemia-induced left ventricular dysfunction and high-risk coronary disease.[71]

mitral regurgitation murmur

If present in the setting of chest discomfort, this suggests ischaemia-induced papillary muscle dysfunction.[71]

bibasilar rales

If present in the setting of chest discomfort, this suggests ischaemia-induced left ventricular dysfunction and high-risk coronary disease.

aortic outflow murmur

This suggests aortic stenosis or hypertrophic cardiomyopathy as an alternative aetiology of anginal pain.[24]​​

carotid bruit

Presence of peripheral vascular disease increases the likelihood of atherosclerotic coronary disease.[73]

diminished peripheral pulses

Presence of peripheral vascular disease increases the likelihood of atherosclerotic coronary disease.

signs of abdominal aortic aneurysm

Presence of peripheral vascular disease increases the likelihood of atherosclerotic coronary disease.

retinopathy seen on fundoscopic examination

Presence of increased light reflexes and arteriovenous nicking provide evidence of hypertension and associated risk of coronary disease.

xanthomas or xanthelasma

Presence of xanthomas or xanthelasma suggests severe hypercholesterolaemia.

Risk factors

strong

age and sex

Advancing age is the single most powerful risk factor for coronary disease in both men and women. Those older than age 70 years are often at very high-risk even without other risk factors.[33]​ There is a male predominance. In female patients risk rises more slowly before the menopause and more rapidly thereafter.[9]

smoking

Aside from age, cigarette smoking is the most important risk factor for coronary disease. In the case-control INTERHEART study, smoking accounted for 36% of global risk for myocardial infarction. Risk was dose-dependent and started at as little as 1 to 5 cigarettes per day.[34] Risks of other combustible and non-combustible nicotine products are less clearly defined.

hypertension

Hypertension is an important risk factor for cardiovascular disease (CVD) and a common comorbidity in patients with CCD. There is robust observational evidence of a linear association between systolic and diastolic blood pressure and coronary disease mortality.[35] Randomised controlled trials support the benefit of blood pressure control in reducing ischaemic heart disease outcomes.[36][37]

dyslipidaemia

Numerous lipid measures are predictive of cardiovascular risk. Low-density lipoprotein (LDL) cholesterol is a key risk factor in the causal pathway for atherosclerosis. Alternative measures (e.g., non-high-density lipoprotein (HDL) cholesterol) or specific lipoproteins (e.g., apolipoprotein B, lipoprotein(a)) may provide additional and overlapping prognostic information.[33]​ Other traditional lipid measures associated with risk of coronary disease include low HDL cholesterol and high triglycerides, although it is not clear these factors are in the causal pathway nor key targets for pharmacotherapy.

diabetes

Individuals with diabetes mellitus have a 2- to 4-fold increased risk for CCD.[38][39]​​ CCD and diabetes are common comorbidities, and both are associated with obesity, dyslipidaemia, and hypertension. Coronary artery disease is the leading cause of morbidity and mortality in people with type 2 diabetes mellitus.[40]

inactivity

Observational studies have demonstrated a strong association between levels of physical activity and rates of CVD.[34][41]

diet

Diets low in fresh fruits and vegetables are associated with coronary disease.[26][34]

race, ethnicity, geography

Risks of coronary disease vary between and within racial and ethnic groups. Prevalence of ischaemic heart disease varies both between and within countries.[4][11][12]​​ The differences are likely mediated largely by environmental and behavioural factors including social determinants of health.

psychosocial factors and social determinants of health

A psychosocial index including depression, stress, life events, and sense of control is predictive of coronary events.[34]​ Additional relevant social determinants of coronary health include education, access to care, and social vulnerability.[26]

chronic kidney disease (CKD)

CKD is a risk factor for CVD, independent of comorbidities such as diabetes, hypertension, and dyslipidaemia. Worsening kidney function (lower glomerular filtration rate (GFR), increased albuminuria) is associated with progressively increased risk of coronary disease.[42] A new concept of cardiovascular-kidney-metabolic (CKM) syndrome reflects the connections between CVD, kidney disease, and metabolic disease (obesity, diabetes, metabolic syndrome), as well as the social determinants of health that often underlie them.[43]

inflammatory and other diseases

HIV and other inflammatory disease (e.g., rheumatoid arthritis, psoriasis) are risk factors for coronary disease.[33][44]​ Cancer and coronary disease are commonly comorbid conditions, and a cancer diagnosis is associated with a worse prognosis in patients with coronary disease.[45]​ Cancer treatments such as chest radiation and selected cancer chemotherapies also increase risk.[46][47]

obesity

Body mass index (BMI) and waist circumference (a measure of central adiposity) are associated with coronary disease. It is unclear the extent to which risk associated with overweight and obesity are independent or reflective of factors such as blood pressure, lipids, insulin resistance, physical activity, and diet. BMI in particular has known limits in predicting individual risk and may need to be applied in the context of demographic factors including, age, sex, gender, race, and ethnicity.[48][49][50]

substance misuse

Use of sympathomimetic agents (e.g., cocaine, amfetamines) contributes to coronary disease.[51][52]​ Current evidence is not consistent with a putative protective role for alcohol in coronary disease.[26]

family history of coronary disease

Family history is a risk factor for coronary disease but adds little prognostic information when combined with other common risk factors.[34] This finding suggests that whether through genes or shared lifestyle, much of the effect of family history is mediated through known risk factors including hyperlipidaemia, hypertension, diabetes, obesity, smoking, and diet.

pollution

Particulate air pollution is associated with increased coronary disease prevalence, events, and death.[53][54][55][56][57]​ Exposure to toxic metal pollutants, such as mercury, lead, arsenic, and cadmium has also been associated with an increased risk of cardiovascular disease.[55]

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