What is the role of cardiac biomarkers (Troponins I & T, Creatine Kinase (CK) & Isoenzymes, Myoglobin, Brain Natriuretic Peptide (BNP) / Pro-BNP, Atrial Natriuretic Peptide (ANP)) and lipid profiles (Total Cholesterol, High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL)) in diagnosing and managing cardiovascular diseases?

Role of Cardiac Biomarkers and Lipid Profiles in Cardiovascular Disease

Cardiac biomarkers and lipid profiles are essential diagnostic and prognostic tools that significantly improve the management of cardiovascular diseases by providing critical information about disease severity, progression, and response to treatment. 1

Cardiac Biomarkers

Natriuretic Peptides (BNP/NT-proBNP)

• BNP and NT-proBNP are the most established biomarkers for heart failure diagnosis, with primary utility in confirming or refuting the diagnosis of heart failure and stratifying long-term risk profiles 1
• BNP/NT-proBNP levels increase in response to ventricular wall tension due to pressure and volume overload, making them reliable indicators of cardiac dysfunction 1
• Diagnostic cutoff values differ between acute and chronic settings; values <100 pg/mL for BNP effectively exclude heart failure in acute settings 1
• Serial measurements can track changes in risk profiles and clinical status among heart failure patients when additional risk stratification is required 1
• BNP/NT-proBNP testing is not a stand-alone test and must be interpreted within the larger clinical context, with confounding factors considered 1

Troponins I & T

• Cardiac troponins are the preferred biomarkers for diagnosing acute myocardial infarction 2
• High-sensitivity troponin assays can detect small elevations above reference intervals, showing a gradient of risk across the reference range even in healthy individuals 3
• Troponin testing can identify heart failure patients at increased risk beyond the setting of acute coronary syndromes 1
• Troponin levels typically decrease gradually during hospitalization for acute heart failure, with persistently elevated or rising values associated with greater risk 1

Creatine Kinase (CK) & Isoenzymes

• CK and its cardiac-specific isoenzyme CK-MB were historically used for myocardial injury detection but have been largely replaced by troponins due to their superior cardiac specificity 4
• CK-MB can still provide complementary information in specific scenarios such as reinfarction assessment or when troponin results are unavailable 5

Myoglobin

• Myoglobin is an early marker of myocardial injury that rises within 1-3 hours after myocardial damage 2
• Limited specificity (also found in skeletal muscle) has reduced its clinical utility as a standalone marker 5
• May be used as part of a multi-marker strategy for early detection of myocardial injury 2

ANP (Atrial Natriuretic Peptide)

• ANP is released primarily from atrial tissue in response to atrial stretch 1
• Mid-regional pro-A-type natriuretic peptide has emerged as a potential biomarker in heart failure assessment 1
• Less commonly used clinically than BNP/NT-proBNP due to shorter half-life and less robust clinical evidence 1

Lipid Profile Components

Total Cholesterol, HDL, and LDL

• Lipid profiles are fundamental for cardiovascular risk assessment and management decisions 3
• LDL cholesterol is the primary target for lipid-lowering therapy to reduce cardiovascular risk 3
• HDL cholesterol levels are inversely associated with cardiovascular risk, though interventions specifically targeting HDL have not shown consistent benefits 3
• Non-HDL cholesterol (total cholesterol minus HDL) provides additional risk information, especially in patients with elevated triglycerides 3

Clinical Applications

Diagnosis

• BNP/NT-proBNP testing is particularly valuable in the emergency department when the cause of dyspnea is unclear 1
• Troponins are the gold standard for diagnosing acute myocardial infarction 2
• Lipid profiles help identify patients at risk for atherosclerotic cardiovascular disease 3

Risk Stratification

• Elevated BNP/NT-proBNP levels in heart failure patients correlate with increased mortality and hospitalization risk 1
• Troponin elevation in heart failure, even without acute coronary syndrome, indicates increased risk 1
• Changes in BNP/NT-proBNP levels during treatment correlate with differences in long-term clinical outcomes 1

Treatment Guidance

• Serial BNP/NT-proBNP measurements can help track treatment response, with successful treatment resulting in measurable decreases in levels 6
• Persistent elevation or rising BNP/NT-proBNP levels may indicate inadequate treatment 6
• BNP/NT-proBNP-guided therapy may be beneficial in specialized heart failure centers with structured disease management programs 1

Clinical Trial Applications

• BNP and NT-proBNP have been increasingly used in randomized clinical trials to confirm a clinical diagnosis of heart failure for trial entry criteria 1
• Biomarkers have been successfully used for clinical trial risk enhancement, allowing enrollment of higher-risk patients 1

Important Considerations and Limitations

• Natriuretic peptide levels may be affected by age, race, sex, body mass index, and comorbidities such as atrial fibrillation 1
• Obesity may lead to relatively lower BNP levels despite cardiac dysfunction 6
• Some medications (including ACE inhibitors, ARBs, beta-blockers) can reduce BNP levels, potentially masking elevated levels in treated patients 6
• Neprilysin inhibitors (sacubitril) increase BNP levels but not NT-proBNP levels, making NT-proBNP the preferred biomarker for monitoring patients on these medications 1
• Troponin assay sensitivity varies widely, affecting diagnostic thresholds and interpretation 5

Emerging Biomarkers

• Soluble suppressor of tumorigenicity 2 (sST2), galectin-3, and growth differentiation factor 15 (GDF-15) are emerging biomarkers for heart failure assessment 1
• High-sensitivity C-reactive protein (hsCRP) and other inflammatory markers may provide additional risk stratification in cardiovascular disease 1
• Mid-regional pro-adrenomedullin and copeptin are being evaluated as markers of systemic stress in heart failure 5