Newer Cardiac Biomarkers in Myocardial Injury and Their Interpretation

High-sensitivity cardiac troponin (hs-cTn) I and T is the gold standard biomarker of myocardial injury and the cornerstone of ACS diagnosis.

Myocardial injury is defined by a troponin value above the 99th percentile upper reference limit. It becomes acute when there is a rise and/or fall on serial testing.

Myocardial infarction requires evidence of injury plus clinical evidence of ischaemia — symptoms, ECG change, imaging evidence, or thrombus on angiography.

Troponin elevation is not synonymous with myocardial infarction — this is the single most important interpretive principle.

Type 1 MI — plaque rupture or erosion with coronary thrombosis. This is atherothrombotic.

Type 2 MI — oxygen supply–demand mismatch without plaque rupture; the myocardium is starved rather than blocked.

Common causes of Type 2 MI in older people are sepsis, hypotension, tachyarrhythmias, anaemia, hypoxaemia, and organ dysfunction.

Older people are far more likely to have raised hs-troponin from Type 2 MI than younger individuals, because of demand-supply mismatch causing non-atherosclerotic myonecrosis.

Type 2 MI carries a poor prognosis — mortality up to 63% at 3 years — but the deaths are driven by comorbidities rather than myocardial damage, and PCI is unlikely to help.

Types 3, 4 and 5 cover sudden cardiac death before biomarker sampling, PCI-related MI, and CABG-related MI respectively.

Chronic troponin elevation without a rise-and-fall pattern occurs in chronic kidney disease, heart failure, left ventricular hypertrophy, amyloidosis, and advanced age itself.

Other non-ischaemic causes: myocarditis, pulmonary embolism, stroke and subarachnoid haemorrhage, cardiac contusion, cardioversion, ablation, and chemotherapy-related cardiotoxicity.

In old age, elevated troponin combined with non-specific symptoms and age-related baseline ECG changes (Q waves, bundle branch block) can lead to a false diagnosis of ACS.

BNP and NT-proBNP are markers of myocardial wall stress, not injury, and are the primary rule-out test for heart failure.

ESC thresholds for further investigation: BNP >35 pg/ml and NT-proBNP >125 pg/ml in the non-acute setting. Normal levels make heart failure unlikely.

They are equally predictive in HFrEF and HFpEF and carry independent prognostic information.

Levels rise with age and with renal impairment, and fall with obesity — all must be factored into interpretation.

Cardiac myosin-binding protein C (cMyC) is the most promising competitor to troponin — it is released earlier and is currently the leading candidate for very early rule-out.

Copeptin, the C-terminal fragment of provasopressin, is a marker of endogenous stress; combined with troponin it allows a dual-marker single-draw rule-out, but it lacks cardiac specificity.

GDF-15, sST2, galectin-3, and hs-CRP are prognostic rather than diagnostic — they reflect oxidative stress, fibrosis, and inflammation, and predict mortality and hospitalisation.

GDF-15 and hs-cTnT are components of the ABC bleeding risk score in atrial fibrillation, illustrating the biomarker-based risk-scoring approach.

Adding NT-proBNP, hs-cTnT, and hs-CRP to the pooled cohort equation improved 4-year cardiovascular risk prediction in adults aged 69–88 years (ARIC study).