These are the key indicator for heart health in the medical laboratory.
Cardiac markers are essential biomolecules used in the diagnosis, risk stratification, and management of cardiovascular diseases, particularly acute coronary syndromes (ACS) and heart failure. These biomarkers, detectable in blood, provide critical insights into heart health and aid in timely clinical decision-making. Over the years, advancements in cardiac marker testing have revolutionized cardiovascular medicine, offering higher accuracy and earlier detection of heart-related conditions.
Cardiac markers fit into roughly three distinct categories:
Markers of acute cardiac injury
Markers of heart failure (chronic conditions)
Markers of systemic inflammation
Cardiac markers are essential diagnostic tools used to evaluate myocardial injury, assess heart function, and determine cardiovascular risk. In the laboratory setting, several key markers are routinely tested to aid in the diagnosis and management of cardiac conditions along with other testing such as EKGs (electrocardiograms).
MARKERS OF ACUTE CARDIAC INJURY
One of the most important markers is troponin, particularly the subtypes Troponin I and Troponin T. These proteins are highly specific and sensitive indicators of cardiac muscle injury, making them the gold standard for diagnosing myocardial infarction. High-sensitivity troponin assays have further enhanced the ability to detect myocardial damage earlier, often within hours of symptom onset. Another marker frequently analyzed is creatine kinase-MB (CK-MB), a cardiac-specific isoenzyme of creatine kinase. While its use has diminished due to the higher accuracy of troponins, CK-MB remains valuable in detecting reinfarction and in certain cases where troponins are inconclusive. Myoglobin is another early marker of myocardial injury, although it lacks specificity to cardiac tissue, limiting its standalone diagnostic utility.
MARKERS OF HEART FAILURE (CHRONIC)
For assessing heart failure, B-type natriuretic peptide (BNP) and its more stable precursor, NT-proBNP, are commonly tested. These peptides are released by the ventricles in response to wall stress and volume overload, providing crucial information for diagnosing and monitoring heart failure. They also offer prognostic insights, as elevated levels are associated with worse outcomes in patients with cardiac conditions.
MARKERS OF SYSTEMIC INFLAMMATION
Inflammation also plays a significant role in cardiovascular diseases, and markers such as C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) are important for evaluating systemic inflammation. While CRP is an acute-phase reactant useful in detecting inflammatory states, hs-CRP is particularly valuable for assessing cardiovascular risk in asymptomatic individuals. Elevated hs-CRP levels are strongly associated with an increased risk of myocardial infarction, stroke, and other adverse cardiovascular events.
LOOKING AHEAD
In addition to these traditional markers, emerging biomarkers are gaining clinical attention. Copeptin, a stable surrogate marker for arginine vasopressin, is increasingly used alongside troponins to rule out myocardial infarction early in its course. Heart-type fatty acid binding protein (H-FABP) shows promise as an early and sensitive marker of myocardial damage, while ischemia-modified albumin (IMA) provides insights into early ischemic changes. Although lactate dehydrogenase (LDH) was historically used as a marker for myocardial infarction, its role has declined with the advent of more specific biomarkers.
The choice of cardiac markers for testing depends on the clinical context. For patients presenting with acute coronary syndromes, troponins are the primary focus, sometimes supplemented by CK-MB or myoglobin. In cases of suspected heart failure, BNP or NT-proBNP testing is critical. For cardiovascular risk assessment in asymptomatic individuals, hs-CRP is particularly useful, while emergent conditions may require additional markers like copeptin or IMA for early ischemia detection.
Through accurate testing and interpretation of these biomarkers, laboratories play a pivotal role in improving the diagnosis, treatment, and prognosis of cardiovascular diseases.
Typical Reference Ranges for Cardia Markers
The reference ranges for cardiac markers vary depending on the laboratory, assay manufacturer, and patient-specific factors such as age, sex, and clinical condition. It is always important to refer to the assay-specific documentation provided by the manufacturer and the laboratory’s established reference intervals.
For Troponin I (cTnI), the typical reference range is less than 0.04 ng/mL, with values above this level often indicating myocardial injury. High-sensitivity Troponin I assays may have lower thresholds, with upper limits often specified separately for males and females. Troponin T (cTnT) has a typical reference range of less than 0.01 ng/mL, and elevations are indicative of myocardial damage.
For high-sensitivity Troponin T (hs-cTnT), the upper reference limits are typically around 22 ng/L for males and 14 ng/L for females. High-sensitivity Troponin I (hs-cTnI) assays commonly report upper reference limits of less than 20 ng/L for males and less than 10 ng/L for females, with values above the 99th percentile considered significant for myocardial injury.
Creatine Kinase (CK) levels typically range between 50 and 200 U/L for males and 30 to 150 U/L for females. Elevated CK levels indicate muscle damage but are not specific to cardiac tissue. For CK-MB, the absolute concentration is usually less than 7 ng/mL, and CK-MB as a percentage of total CK is less than 6 percent. Higher values are suggestive of cardiac injury.
Myoglobin, an early marker of muscle injury, typically has a reference range of 10 to 95 ng/mL for males and 10 to 65 ng/mL for females. Although elevations in myoglobin can occur in both cardiac and skeletal muscle injury, it is not specific to cardiac events.
B-Type Natriuretic Peptide (BNP) is commonly used to assess heart failure. The normal reference range is less than 100 pg/mL. Levels below 100 pg/mL are considered normal, while levels between 100 and 400 pg/mL are indeterminate and require further evaluation. Levels above 400 pg/mL are suggestive of heart failure.
For NT-proBNP, the typical reference range depends on age. In individuals under 50 years, the upper limit is 450 pg/mL. For those aged 50 to 75 years, it is 900 pg/mL, and for individuals over 75 years, the upper limit is 1800 pg/mL. Elevated NT-proBNP levels indicate ventricular stress or heart failure.
C-Reactive Protein (CRP) levels also serve as a marker of inflammation. Standard CRP levels are generally less than 10 mg/L. High-sensitivity CRP (hs-CRP) is used for cardiovascular risk assessment, with levels below 1 mg/L indicating low risk, levels between 1 and 3 mg/L indicating moderate risk, and levels above 3 mg/L associated with high risk or significant inflammation.
These ranges are meant to serve as general guidelines. Each laboratory must validate its own reference intervals to ensure accuracy based on its specific methodologies and patient populations.