Table 1.

Overview of novel biomarkers of subclinical cardiac dysfunction in the general population

Biomarker	Accepted values	Proposed mechanism	Clinical utility	At-risk populations
hs-cTnT	Abnormal range: 0.014 ng/mL–unknown upper limit of detection	Troponin T present in cardiac muscles bound to myofilaments is continuously released during chronic myocardial injury	Chronically elevated cardiac troponins in the general population is associated with all-cause mortality and HF Temporal increases were strongly associated with incident HF	High-risk phenotypes, including patients with subclinical HF and left ventricular hypertrophy
NT-proBNP	Abnormal range: 300 pg/mL–unknown upper limit of detection	Family of proteins involved in maintenance of cardio-renal homeostasis through natriuretic, vasodilatory, and diuretic effects	Independent prognostic value for death and heart failure Predictive value for all-cause mortality was even stronger when combined with detectable troponin T	Patients with hypertension and/or diabetes have twice odds of diastolic or systolic dysfunction on echo Chronic renal insufficiency showed higher rates of HF
ST-2	Radix Biosolutions Range of detection: 0.40 to 200 μg/L Median: 1.3 μg/L Critical Diagnostics Prestige Normal range: 1.75–34.3 U/mL Median: 25.7 U/mL Values above the median approach abnormal	Interleukin-33 binding, dummy receptor is released and sequesters cytokines to limit cytokine toxicity to myocardium	Good sensitivity and specificity (73.5 and 79.6%) for diagnosis of HF. Predicts adverse outcomes in HF including death	African Americans have twice the prevalence of elevated ST2 compared with other race/ethnic groups in the population
Heart type fatty acid binding protein	Range of detection: 0.5–24 ng/mL Median: 5.0 ng/mL Values above the median approach abnormal	Myocardial cytosolic protein involved in transport of long-chain fatty acids across the cell and mitochondrial membrane is released during periods of chronic myocardial injury	Initially used as an indicator of myocardial ischemia alongside troponin I. Incremental risk shown when elevated with BNP. Raises the specificity of BNP in the diagnosis of HF	Acute coronary syndrome patients. Predicts outcomes in HF with reduced and preserved ejection fraction
Rho-kinase and myosin light chain phosphatase 1 activity MYPT1-P/T	Range of detection: unknown however activity levels reported 4.3–44 (no units) range in diseased individuals Normal mean value: 1.2 ± 0.2 (no units)	The two enzymes are involved in activity of myosin molecules during contraction and relaxation. Mechanism is poorly understood	Elevated leukocyte Rho-kinase activity correlated with clinical and echocardiographic indices of HF risk	Potentially identifies hypertensive patients at risk for HF
GDF-15	Range of detection: 90–13,790 ng/L Median value: 1109 ng/L Values above the median approach abnormal	Considered a marker of inflammatory stress that is a mediator of myocardial fibrosis	Elevated during disease exacerbation. Inflammatory marker that supplements NT-proBNP disease prognosis	Risk stratification after myocardial infarction, atrial fibrillation, prognostication of heart failure, and prediction of bleeding events when on anticoagulation
Galectin 3	Range of detection: 2.4–950 ng/mL Median value: 17.8 ng/mL Values above the median approach abnormal	Paracrine molecule related to aldosterone signaling. Member of galactoside lectin binding family involved in the development of myocardial fibrosis	Elevated concentrations associated with adverse clinical outcomes of HF associated hospitalization and death	Galectin-3 concentrations are prognostic in HF and associated with a 2-fold to 3-fold increase in death and hospitalization in patients presenting with HF
Osteoprotogerin (OPG)	Range of detection: 15–2211 ng/L Median value: 1164 ng/L Values above the median approach abnormal	Dysregulation of OPG and RANK/RANKL signaling leads to progression of coronary plaque and stimulates MMP-related cardiomyocyte extracellular matrix degradation leading to myocardial injury	Elevated concentrations associated with adverse clinical outcomes including HF-associated hospitalization and death Incremental risk shown when elevated with NT-proBNP	Post-myocardial infarction predictor of infarct size, HF hospitalization, and cardiovascular death
IGF B-7	Range of detection: 0.10–79.80 ng/mL Median value: 50.30 ng/mL Values above the median approach abnormal	IGF B-7 binds to IGF-1 blocking its pro-survival action on cardiac myocytes and promotes cell death	Elevated concentrations associated with adverse cardiovascular events Good correlation with echo-derived measurements for diastolic HF (E/A, E/E′, LA volume index, RVSP)	Potential significance in the aging population given trend to lower IGF-1 in elderly

HF heart failure, LA left atrial, RVSP right ventricular systolic pressure