Method Sensitivity/biomarker efficiency Confirmatory diagnosis References Coronary CT angiography Highly sensitive Cardiac characterization with contrast studies, pressure measurement, and O2 saturation. Detect valvular heart disease and intracardiac problems, biomarkers in acute coronary syndrome [62 , 63 ] Spectral analysis of electrocardiography Highly sensitive Flow of blood across valves or septal defects are determined [63 ] Aortic wave reflection and pulse pressure amplification Moderately Heart rate, rhythm, volume, and accessing synchronicity of heart beats, [64 ] ECG Highly sensitive Cardiac arrhythmias and conduction abnormalities, LVH defects, mitral stenosis, pulmonary embolism, confirming ischaemic heart disease, and myocardial infarction CXR Moderately sensitive Identify cardiac enlargement and cardiac chamber defects Imaging biomarkers Hemorrhagic complications, acute stroke [65 ] Palpography and elastography/thermography Moderately sensitive Demonstrate increased temperature at the site of inflamed, vulnerable plaques, and strain of fibrous caps Perfusion imaging Moderately sensitive 31 P magnetic resonance spectroscopyHighly sensitive Intramyocellular lipid content, stroke, and characterization of adipose tissue Magnetic resonance imaging (MRI) Highly sensitive Coronary artery disease hypertrophic cardiomyopathy and heart wall motion abnormalities Framingham risk score Highly sensitive [66 ] Intraplaque neovascularization Moderately sensitive Carotid atherosclerosis [67 ] Ultrasound (US) and computed tomography (CT) Moderately sensitive Stenoses, coronary calcification Bioluminescence, single-photon emission computed tomography (SPECT) Highly sensitive To estimate the 10-year risk of developing coronary heart disease Positron emission tomography (PET) Highly sensitive Oedema, inflammation, fibrosis, and IIM [68 , 69 ] Cardiac magnetic resonance Highly sensitive Left atrial volume and function [70 ] Unstable carotid plaque High-risk for stroke patients [71 ] Pulse wave velocity Aortic wall material/stiffness Various cardiovascular pathologies [72 ] Transthoracic echocardiography/MRI Highly sensitive Atherosclerosis in the aorta and carotid arteries Coronary angiography Moderately sensitive Obstructive coronary artery disease Intravascular ultrasound (IVUS) Highly sensitive Optical coherence tomography Highly sensitive Degree of inflammatory activity within plaque, measures the thickness of the fibrous cap MRI-visible perivascular spaces Highly sensitive Cerebral small vessel disease [73 ] Electroanatomic, fluoroscopy Highly sensitive Aging and cerebral small vessel disease [73 ] Electroanatomic mapping Highly sensitive Display catheter positions and stored electrograms jointly with anatomic information of the target heart chamber generated through other imaging modalities [74 ] Static FLAIR anatomical images Highly sensitive WM integrity [75 ] Visible retinal lesions Highly sensitive Dot-blot hemorrhages, retinal neovascularization [76 ] DM-AA score Moderately sensitive Development of CVD [77 ] Epicardial adipose/epicardial fat determination Moderately sensitive Coronary artery disease, atherogenic and inflammatory cytokines [78 ] Infantile hemangiography Moderately sensitive Capillaries blockage [79 ] Cerebral amyloid angiopathy Moderately sensitive Spontaneous intracerebral haemorrhage (ICH)
[27 ] Serum biomarkers β 7 integrin (LPAM-1) and its ligand, mucosal addressin cell adhesion molecule (MAdCAM-1), focal adhesion kinase (FAK) and MAPK/ERK1/2 in macrophage Triglyceride to HDL cholesterol ration Lipid abnormalities Total cholesterol (TC) to HDL-C ratio Low to high cholesterol levels provide appropriate information about risks of cardiovascular diseases [80 ] Fasting and nonfasting triglyceride levels Mixed dyslipidemic patterns PON1 activity/HDL-C ratio Endothelial dysfunctions [81 ] HDL, LDL, triglycerides and total cholesterol levels Type 2 diabetes mellitus (T2DM) Cholesterol, LDL-C, ApoB, Lp(a), and ApoA1/ApoB ratio Endothelial dysfunctions, atherosclerosis [80 ] Lipid-lipoprotein ratio Oxidized forms of LDL Severe cardiovascular risks, atherogenic lipid particles Levels of ApoB and ApoAI or ratio of ApoB : ApoAI Myocardial infarction Statin Slowing progression of coronary atherosclerosis [82 ] Lp-PLA2 Lp-PLA2 is platelet-activating factor (PAF) acetylhydrolase ACAT acetyl cholesterol transferase Fatty acid metabolism, synthesis and degradation of ketone bodies [83 ] HDL protein HDL particles remove fats and cholesterol from cells, including within artery wall atheroma, and transport it back to the liver for excretion or reutilization [84 ] M-FABPs Atherosclerosis [85 ] Sterol regulatory DNA elements and binding with proteins AT, CVD, and lipid homeostasis [86 ] Specific mRNA level Rapid utilization of fatty acids [87 ] Enzyme acyl CoA: transferase Increase and decrease in cholesterol level HDLs and apolipoproteins level Non-high-density lipoprotein and low-density lipoprotein cholesterol Cardiovascular diseases [88 , 89 ] Postprandial lipid profiles in combination with ApoB Heterozygous familial hypercholesterolemia, familial combined hyperlipidemia, and familial hypertriglyceridemia [90 ] Sphingolipids Sphingomyelin(SM) and sphingosine 1-phosphate (Sph-1-P) Atherosclerotic disorders [91 ] Lipid transfer particles as biomarkers Different types of LTPs Transcytosis, transport, and signaling for lipid metabolism [92 ] Blood pressure (BP), height, weight, lipid profiles, blood glucose (BG), body mass index (BMI), fasting insulin (FINS), serum uric acid (SUA), and the urinary albumin/creatinine ratio (UACR) Moderately sensitive Metabolic disorders in nondiabetic elderly patients [93 ] Plasma levels of high-density lipoprotein cholesterol Coronary artery [66 ] Framingham risk score (FRS) Coronary artery [66 ] Immunohistochemical markers MDM2 overexpression; MFAP4 in serum Cardiovascular conditions [94 , 95 ] N-cadherin and connexin-43 Arrhythmogenic right ventricular cardiomyopathy (ARVC) [96 ] ARVC plakoglobin Intravascular papillary endothelial hyperplasia Hyperplastic endothelial cells [97 ] Localization of lipid binding proteins Become good markers for CVDs [98 ] StarD5 cholesterol binding proteins lipid transport in health and disease, steroidogenic acute regulatory protein- (StAR-) related lipid-3 transfer (START) domain family [99 ] Rho, Rho-kinase 1, and ROCK2 Regulating the shape and movement of cells by acting on the cytoskeleton [100 ] Sterol regulatory element binding protein-2 Activated SREBPs t bind to specific sterol regulatory element DNA sequences. Indicating cellular cholesterol levels [101 ] Endothelial markers CD31 Myocardial ischemia [100 ] Oxidative stress-related biomarkers [102 ] Advanced oxidation protein products (AOPPs, circulating OGN and NGAL/MMP9 complex) Increased OS [103 ] TBARS, MetS Oxidative stress, oxidative PTM [104 , 105 ] Reactive oxygen/nitrogen species/superoxide production Neurodegeneration [104 ] F2-IsoPs and F4-NPs Neurodegenerative diseases [106 ] Inflammatory biomarkers Level of chemokines and number of its receptors, and inflammatory lipids CAD, atherosclerotic vascular disease, mainly chronic inflammation in the case of atherosclerosis [107 , 108 ] Thrombotic disease [109 ] Interleukin-1 receptor-like 1 (ST2) and interleukin-33, and interleukin-1 receptor family Cardiovascular risk, cardiovascular diseases
[28 , 110 ] IL1R1 and its ligand, IL1 Cardiovascular disease, obesity, and infection, activating platelets and megakaryocytes to promote atherothrombosis. Cardiovascular risk factors [111 , 112 ] Complement C3 Cardiometabolic risk in psoriasis [113 ] CCR5, chemokine expression of CCL2, CCL3, CCL5 and CXCL10, and RAGE and FABP4 Prognostic biomarker for plaque stability [114 –116 ] Acute inflammation VCAM-1, ICAM-1 MCP-1, VCAM-1, ICAM-1, IL-1, and TNF-α Inflammation, arteriosclerosis, and lipid peroxidation problems [117 ] C-reactive protein Inflammation [118 ] Myeloperoxidase MPO Leukocyte-derived prooxidant enzyme [119 ] PAF-AH Inflammatory markers, oxidation of phospholipids [119 ] Accumulation of free radicals Posttraumatic stress disorder (PTSD) Interleukin-33, copeptin Heart failure [120 , 121 ] ST2 as CVD markers Transmembrane receptor (ST2L) Endothelial intima thickness [122 ] ST2 and galectin-3 (Gal-3) Heart failure [123 ] ST2, GDF-15, and hsTnI Atrial fibrillation [124 , 125 ] Copeptin, MR-proADM, abd MR- proANP CV death and HF [126 ] Physiological markers Enzyme indoleamine 2,3-dioxygenase (IDO) Cellular immune response, ROS production by activated immune effector cells like macrophages [127 ] RAAS Development and progression of CVD, cardiovascular and renal diseases, and inflammation [128 ] Highly toxic peroxynitrite (ONOO(−), superoxide anion (O2 (−)) Vascular inflammation [128 ] Neopterin and kynurenine to tryptophan ratio Robust markers of immune activation in vitro , IDO enzyme activity [127 ] (ACE)/angiotensin II (Ang II)/AT1 Vasoconstriction, cell proliferation, and fibrosis [129 ] Erbin Inhibitor of pathological cardiac hypertrophy [130 ] Endothelial MPs, E-selectin; CD51; CD105 Potential biomarkers for COPD [131 ] Serum concentrations of factor I–XII, platelet count Evaluate hemostasis in pregnancy [132 ] STIM1 Normal cardiac function, regulation of ER, and mitochondrial function [133 ] Blood pressure, fasting glucose, HDL, LDL, or C-reactive protein levels, insulin, triglyceride, and cholesterol Higher risk of CVD Vitamin D status Cardiometabolic problems [62 ] Anatomical markers Left ventricular hypertrophy High risk of CVD, left ventricular systolic dysfunction [134 ] Galectin-3/plasma galectin-3 levels Outflow tract tachycardias, hypertrophied hearts [135 , 136 ] Omega-3 Index as biomarker (eicosapentaenoic acid + docosahexaenoic acid) content in red blood cell membranes Acute coronary [137 ] n-3 PUFA Plasma phospholipid and dietary alpha linolenic acid, DHA Increasing n-3 LC-PUFA in RBC and plasma lipids, improving cardiovascular health, and significantly decreasing plasma triglyceride levels [138 –140 ] n-3 fatty acid α -linolenic acid Cardiometabolic risk factors, congestive heart failure [141 ] Omega-3 fatty acids Positive effects on weight, systolic blood pressure, lipid profile, and markers of inflammation and autoimmunity [142 , 143 ] Genetic markers Rare genetic variants Lipid related morbidities, genes [144 ] Mutations causing low LDL-cholesterol and ApoB CVD progression, lipid metabolism [145 ] Mutations in ApoB, proprotein convertase subtilisin/kexin type 9 MTP genes, and ANGPTL3 gene Familial combined hypolipidemia [145 ] Sterol response element-binding protein LDL-cholesterol (LDL-C) uptake [146 ] Analysis of polymorphism of genes Coronary heart disease, ApoB; ApoC111; ApoE; X2 of ApoB; and S2 of ApoCIII [147 ] Human ApoE gene e2, e3, and e4 Impaired lipid metabolism [148 ] MicroRNAs Diagnostic and prognostic biomarkers in atherosclerosis [149 ] Missense mutation in MED30 gene; MED1, MED13, MED14, MED15, MED23, MED25, and CDK8 CVD-related metabolic disorders, progressive cardiomyopathy [150 ] DNA based diagnostics Genetic variants in known lipid genes Severe dyslipidemias [151 ] Lipid metabolomics Metabolomics Study design and data analysis in diabetes, CVDs, HF, and obesity research LC-MS/MS-based metabololipidomics Resolvin (Rv) D1, RvD2, protectin (PD) 1, and lipoxin (LX) A4 Lipid disorders, genetic variance and intermediate metabolic phenotypes, peripheral vascular disease, PD1, and 17-HDHA levels [152 ] by LDLRAP1, ApoA5, ANGPLT3/4, and PCSK9 Modulators or adaptor proteins [153 ] Functional mutations in ApoB Long elevated LDL levels, risk of heart disease [154 ] MicroRNAs HFpEF versus HFrEF markers [155 ] Therapeutic markers Hs-cTnI Multiple analysis, troponin I [70 ] NT-proBNP and sST2 Cardiac death (SCD) risk, ICD therapy implantable cardioverter defibrillator [156 ] Standard lipid-lowering therapies Age-related vascular disorders [157 ] Adiponectin, Local coronary circulation Antiatherosclerotic properties [158 ] Multiple high-resolution molecular imaging modalities Abdominal aortic aneurysm disease
[68 ] Hormone therapy Biochemical and ultrasound markers of endothelial function, improving DSD patients [159 ] VE-cadherin, E-selectin, thrombomodulin, and vWf Improve endothelial functions [159 ] PLA2G2E Act as metabolic coordinators [160 ] Flippase, ATP13A2 Local lipid dynamics during vesicle formation and membrane fusion events [161 ] Consumption index of various fatty acids Coronary heart diseases [162 ] Docosahexaenoic acid (DHA) Therapeutic marker, reduce the risk of cardiovascular disease [163 ] Omega-3 Index Emerging as a risk factor for fatal and nonfatal cardiovascular events, therapeutic markers [164 ]
