Cardiovascular disease stands as the leading cause of death globally, responsible for 17.9 million deaths annually. Its prevalence underscores the critical need for proactive approaches in risk assessment, followed by early detection and intervention in at-risk individuals. Among the various tools identified as prognostic indicators for cardiovascular health, troponin and NT-proBNP emerge as key indicators in cardiology diagnostics. This article delves into the significance of these biomarkers, exploring their utility in identifying cardiac muscle injury and assessing heart failure risk. Understanding when to utilize troponin and NT-proBNP tests is paramount in advancing early detection strategies, ultimately contributing to more effective cardiovascular healthcare. 

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Understanding Cardiac Risk and Its Indicators

Atherosclerotic cardiovascular disease (ASCVD), caused by plaque buildup within the arterial walls (atherosclerosis), refers to conditions that include coronary heart disease, cerebrovascular disease, peripheral artery disease, and aortic atherosclerotic disease. ASCVD-related conditions remain the leading cause of morbidity and mortality globally. Calculating cardiovascular risk is crucial for early identification and intervention, allowing healthcare professionals to implement targeted measures to prevent heart-related events. It provides a comprehensive assessment of an individual's likelihood of developing atherosclerosis, coronary artery disease, heart attack, heart failure, or stroke and guides the intensity of interventions based on the assessed risk level. This proactive approach helps reduce the incidence of heart-related issues and improve overall cardiovascular health.

Cardiovascular risk is the likelihood of an individual developing an ASCVD event over a specific period of time, taking into account risk factors. The level of intervention needed corresponds to the assessed risk, with higher risk prompting more intense interventions. The European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) guidelines employ the Systematic Coronary Risk Estimation (SCORE) system to calculate cardiovascular risk and categorize it into four groups: very high, high, moderate, and low risk. Calculating cardiovascular risk is recommended for apparently healthy people without documented ASCVD carrying multiple risk factors that increase their total risk for CVD. (9) 

The American College of Cardiology (ACC) Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator is a tool designed to estimate an individual's (age 40-79) 10-year risk of developing heart disease by considering age, gender, race, cholesterol levels, blood pressures, diabetes status, and smoking history. For individuals at moderate risk, other biomarkers, including apolipoprotein B (ApoB), lipoprotein(a) (Lp[a]), the number and size of lipid-carrying particles, high-sensitivity C-reactive protein (hs-CRP), and a coronary artery calcium (CAC) score, can help in better stratifying risk.  

Troponin Test in Cardiac Assessment

Troponin is a protein found in certain types of muscle. Under normal circumstances, troponin exists mainly in muscle cells, with only small amounts circulating in the bloodstream. However, damage to muscle cells allows troponin to escape into the blood, leading to elevations detectable in a blood test. Three troponin proteins are specific to the heart: troponin C (TnC), troponin I (TnI), and troponin T (TnT). Troponin C binds calcium and transports troponin I so cardiac muscles can contract. Troponin T binds troponin proteins to muscle fibers. Following heart injury, troponins I and T are released from heart muscles and leak into the bloodstream. (35, 38) 

A troponin blood test helps detect heart muscle injury. It is most commonly indicated to confirm or rule out a heart attack. Troponin levels increase within 3-12 hours and peak 24 hours after a heart attack, where they then remain elevated for up to 14 days. Because of this, troponin is now considered standard in diagnosing recent heart attacks. (35, 36) 

Symptoms of a heart attack include:

• Chest pain or discomfort that radiates to the neck, back, arm, or jaw
• Shortness of breath
• Lightheadedness or dizziness
• Nausea or vomiting
• Heartburn or indigestion
• Sweating
• Fatigue

Any kind of damage to the heart can cause troponin release into the bloodstream. Aside from heart attacks, conditions that can increase troponin include congestive heart failure, heart surgery, chemotherapy-induced heart damage, myocarditis, heart valve disease, arrhythmia, sepsis, and extreme physical or emotional strain (e.g., strenuous exercise, stress). Conditions originating from other parts of the body, like chronic kidney disease (CKD), pulmonary embolism, and chronic obstructive pulmonary disease (COPD), may also cause troponin levels to rise. (34, 35)

NT-proBNP Test in Heart Failure Evaluation

B‐type natriuretic peptide (BNP) is a protein synthesized by the heart that helps regulate blood circulation throughout the body. BNP is synthesized as a prehormone called proBNP that is then cleaved into BNP and N-terminal pro-B-type natriuretic peptide (NT-proBNP) once it is in circulation. Increased stretching of the heart muscle cells, especially within the left ventricle, augments the release of BNP and NT-proBNP into the bloodstream.

A BNP or NT-proBNP test can detect heart failure by measuring the respective amount of protein in the bloodstream. High levels of BNP or NT-proBNP are a sign of heart failure, in which the heart is unable to perform to meet the body's needs. Therefore, these tests are commonly ordered as part of a cardiology workup for patients with symptoms like shortness of breath, fatigue, and edema to distinguish between cardiac and non-cardiac causes of the symptoms and rule in the diagnosis of heart failure. (4)

Numerous studies provide compelling evidence supporting the use of NT-proBNP in heart failure risk assessment, encouraging its incorporation into the primary prevention of CVD. Its predictive value is evident in various investigations, showing that elevated baseline levels are strongly associated with a higher risk of adverse outcomes, including cardiovascular events, hospitalizations, and mortality. NT-proBNP significantly contributes to risk stratification, helping categorize patients into different risk groups and guiding clinicians in tailoring management strategies. Moreover, studies consistently demonstrate its ability to monitor treatment response, with changes in NT-proBNP levels correlating with improved cardiac function and better outcomes. (29)

Interpreting Troponin and NT-proBNP Test Results

Troponin levels are typically undetectable in the blood of healthy individuals. The diagnostic threshold for a heart attack is often set based on the 99th percentile of a healthy population. Having normal troponin levels 12 hours after the onset of chest pain indicates that a heart attack is improbable. Elevated troponin levels, especially if there is a rising pattern in serial measurements over 24 hours, strongly suggest a heart attack. A false negative troponin result may occur if the measurement is taken too early during a cardiac event. However, advancements in laboratory testing have introduced a high-sensitivity version of the troponin test, approved in 2017. This upgraded version can detect elevated troponin levels at an earlier stage compared to its predecessors. For instance, the high-sensitivity cardiac troponin I (hs-cTnI) test can identify over 90% of heart attacks within a timeframe as short as three hours, allowing for more prompt and accurate diagnosis in clinical settings. (36, 38)

The reference values of BNP and NT-proBNP are different to exclude or confirm a diagnosis of heart failure. They tend to be higher in female and elderly populations. Normal findings for BNP and NT-proBNP are < 100 pg/mL and < 300 pg/mL, respectively. Values under these cutoff points make a diagnosis of heart failure extremely unlikely in an acutely dyspneic patient (breathing with difficulty). However, it's important to note an exception to this rule in the case of obese patients, as increased adiposity is associated with falsely low BNP and NT-proBNP levels. Elevated levels indicate increased cardiac stress and are strongly predictive of heart failure, distinguishing between heart failure and non-cardiac causes of symptoms like shortness of breath. However, it's important to recognize that NT-proBNP can elevate in the presence of other conditions, such as renal dysfunction and pulmonary disease, so results should be interpreted with clinical findings and other diagnostic tests. (25, 28) 

Integrating Biomarker Tests in Overall Cardiac Care

So far, we've established that troponin and NT-proBNP play integral roles in cardiac care and risk assessment, especially for heart attack and heart failure. These biomarkers can effectively expedite the diagnosis of each heart condition, guide immediate medical interventions, and monitor the patient's response to treatment responses. These markers are especially valuable in emergency settings, where cost, accessibility, and time are limiting factors to utilizing more advanced diagnostic techniques.  

However, these tests are most effective when integrated with other diagnostic tools. Combining troponin and NT-proBNP results with other diagnostic techniques, such as electrocardiograms (ECG) and echocardiograms, provides a comprehensive understanding of cardiac health. 

ECG is a noninvasive test that records the heart's electrical signals to detect heart problems. 

Current guidelines published by the National Institute for Health and Clinical Excellence (NICE) recommend that patients with suspected heart attack (myocardial infarction) have both an ECG and high-sensitivity troponin test upon hospital arrival. For patients without the typical ST elevation on ECG, characteristic of an ST-elevation myocardial infarction (STEMI), a repeat high-sensitivity troponin three hours later can confirm or rule out non-ST elevation myocardial infarction. (6) 

There is also strong evidence to support the integrated use of echocardiograms and BNPs in diagnosing and managing CVD. Echocardiography uses ultrasound imaging techniques to evaluate the structure and function of your heart. Using echocardiography to measure the ejection fraction (the percent of the blood in the left ventricle pumped out of the heart with each heartbeat) helps classify heart failure. Elevations in NT-proBNP or BNP can enhance the effectiveness of echocardiography in screening for asymptomatic left ventricular dysfunction. Conversely, echocardiography improves diagnostic accuracy for heart failure in cases with intermediate BNP or NT-proBNP levels. (37) 

Challenges and Considerations in Biomarker Testing

Navigating biomarker testing in assessing CVD risk presents certain challenges and considerations. One notable challenge is the timing of testing, as obtaining accurate results hinges on the optimal window post-symptom onset. Additionally, interpretation complexities may arise, especially when elevated levels are not exclusive to cardiac issues. Strategies to address these challenges include refining the timing protocols for troponin and NT-proBNP tests, considering individual patient factors, and integrating the results with other diagnostic tools (as discussed above) for a more comprehensive assessment. 

Moreover, the development and integration of artificial intelligence (AI) into mainstream cardiology practice emerge as a promising avenue to overcoming challenges related to stratifying and diagnosing cardiovascular risk and diseases. AI can enhance the precision of risk assessment, aiding in timely diagnosis and treatment decisions. Its ability to analyze vast datasets and recognize subtle patterns may contribute to overcoming timing challenges and refining interpretation complexities associated with biomarker testing. By embracing these strategies and leveraging AI, clinicians can ensure more accurate assessments, leading to effective patient care and improved outcomes in cardiovascular disease.

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Troponin and NT-proBNP Testing Interpretation: Final Thoughts

Troponin and NT-proBNP are valuable biomarkers for detecting cardiac muscle injury and assessing heart failure risk. These tests provide crucial information for timely diagnosis, risk stratification, and effective treatment plans. Emphasizing the significance of a comprehensive approach in cardiac care, integrating troponin and NT-proBNP tests with other diagnostic tools ensures a more holistic evaluation of cardiovascular health.