Cardiovascular disease causes half of all deaths in Europe

Cardiovascular disease (CVD) is a disease of the coronary arteries- the blood vessels supplying the heart with oxygen and nutrients. Changes in blood vessels, for example deposits of fat, build up over several years resulting in a narrowing of arteries (stenosis) in the heart, neck and legs. This in turn leads to a lack of blood supply (ischaemia) to the organs. This process can occur to a greater extent in some people who therefore have an increased risk of angina and heart attack. If the blockage is not cleared within 12 hours, it will result in cell death (necrosis) in the effected area. When this process occurs in the heart it is called a heart attack or myocardial infarction (MI). Symptoms include chest pain, shortness of breath, palpitations and nausea. In patients with diabetes, it is not unusual for myocardial ischaemia to be silent, that is, to occur without any chest pain due to associated nerve damage. There is an abundance of risk factors for CVD including high blood pressure, elevated cholesterol, diabetes, smoking, obesity and family history. CVD causes nearly half of all deaths in Europe and estimated to cause the EU economy €169 billion every year.

The common markers for CVD are CK-MB, myoglobin and troponin, with additional markers now available. In the past, the World Health Organisation (WHO) developed a general consensus for the detection of MI. This was defined by a combination of two of three characteristics: typical symptoms, typical enzyme changes and a typical ECG pattern. The advent of sensitive and specific serological markers and the results of epidemiological studies and clinical trials have necessitated the re-evaluation of this. For example, patients who present with chest pain and positive troponin T or I levels within the first 24 hours have an increased mortality that can be reduced with appropriate treatment.

The following biochemical indicators are commonly used for the detection of cardiac cell death:

• Maximal concentration of troponin T or I exceeding the decision limit (99th percentile of the values for a reference control group) on at least one occasion during the first 24 hours after the index clinical event.
• Maximal value of CK-MB isoenzyme (preferably CK-MB mass) exceeding the 99th percentile of the values for a reference control group on two successive samples, or maximal values exceeding twice the upper limit of normal for the specific institution on one occasion during the first hours after the index clinical event.
• Values for CK-MB should rise and fall; values that remain elevated without change are almost never due to a myocardial infarction.
• In the absence of availability of a troponin or CK-MB assay, total CK (greater than two times the upper reference limit) or the B fraction of CK may be employed, but these last two markers are considerably less satisfactory than CK-MB.

There is no longer a role for lactate dehydrogenase and its isoenzymes in the diagnosis of CVD.

The triage of patients with chest pain is difficult. The admission of patients with a low probability of acute CVD often leads to misdiagnosis resulting in excessive costs and potential associated litigation. For most patients, blood should be obtained for testing on hospital admission, at 6 to 9 hours and again at 12 to 24 hours if the earlier samples are negative and the clinical index of suspicion is high. For patients in need of an early diagnosis, a rapidly appearing marker (commonly myoglobin or rarely CK-MB isoforms are used for this purpose), plus a marker that rises later (such as cardiac specific troponin), is recommended for confirmation of the diagnosis. In unstable angina, the CK and CK-MB remain within the normal reference range while troponin I and T may be elevated. As those patients who are positive for troponin have such a poor prognosis, the measurement of troponin is essential to any assessment of acute chest pain.

In acute MI patients with diagnostic ECGs, biochemical marker testing at a reduced frequency of blood collection (for example, twice per day) is valuable for confirmation of diagnosis, to qualitatively estimate the size of the infarction, and to detect the presence of complications such as re-infarction. The role of high sensitivity C-Reactive Protein is evolving in acute ischaemic heart disease (IHD) and is frequently employed as a prognostic marker. All patients with acute IHD should be investigated for risk factors.

Further reading:

• Joint British recommendations on prevention of coronary heart disease in clinical practice Heart 1998 Volume 2 Supplement 2
• National Academy of Clinical Biochemistry Standards of Laboratory Practice: Recommendations for the use of Cardiac Markers in Coronary Heart Diseases. Clinical Chemistry 1999,45:7; 1104-1121.
• Myocardial Infarction Redefined-A Consensus Document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Journal of the American College of Cardiology 2000, 36:3; 959-969