Conceptualization of Heterogeneity of Chronic Diseases and Atherosclerosis as a Pathway to Precision Medicine: Endophenotype, Endotype, and Residual Cardiovascular Risk

Table 1

Summary of the main endotypes of atherosclerosis [36, 37, 42, 61, 62, 70, 84, 93, 99–105].

Endotype	Genetics	Biomarkers	Clinical features and comorbid conditions
LDL	LDLR, PCSK9, APOE, APOB-100, SORT1, and ANGPTL3	Total cholesterol, LDL-C, ApoB, ApoВ-100, ox-LDLs, modified LDL, sdLDL, and PCSK9	Alzheimer’s disease, breast cancer, colon cancer, and prostate cancer
Lp (a)	LPA	LP(а) and apo(a) isoforms	Aortic stenosis and venous thromboembolism
Hypertension	ADAMTS7, THBS2, CFDP1, NOX4, EDNRA, PHACTR1, GUCY1A3, CNNM2, CYP17A1, FGF5, and NOS3	Endothelin, angiotensin, adrenomedullin, natriuretic peptides, von Willebrand factor, cell adhesion molecules, endothelial progenitor cells, endothelial microparticles, NO, and asymmetric dimethylarginine	Hemorrhagic stroke, chronic kidney disease, atrial fibrillation, vascular dementia, and left ventricular hypertrophy
Inflammation	MCP-1, M-CSF, VCAM-1, IL-6R, PECAM1, SH2B3, CXCL12, SMAD3, and TLRs-genes	TNF, IL-1b, IL-6, IL-12, IL-18, IL-23, IFN-g+IL-17+IL-22+TH17 cells, hsCRP, pentraxin-3, sCD40L, VCAM, and ICAM	Rheumatoid arthritis, inflammatory bowel disease, solid tumors, and psychiatric disorders
Metabolic	HNF1A, SH2B3, PPP1R3B, and CTRB1/2	Blood glucose, blood insulin, C-peptide, glycated hemoglobin, and glycated albumin	Diabetes mellitus, maturity onset diabetes of the young, hepatic adenoma, psoriasis, Alzheimer’s disease, affective disorders, breast cancer, colorectal cancer, and pancreatic cancer

Comments: EDNRA=endothelin receptor type A; PHACTR1=phosphatase and actin regulator 1; GUCY1A3=guanylate cyclase 1 soluble subunit alpha 1; CNNM2=cyclin and CBS domain divalent metal cation transport mediator 2; CYP17A1=cytochrome P450 family 17 subfamily A member 1; SORT1=sortilin 1; FGF5=fibroblast growth factor 5; HNF1A=hepatocyte nuclear factor 1 homeobox A; SH2B3=SH2B adaptor protein 3; PECAM1=platelet endothelial cell adhesion molecule 1; CXCL12=C-X-C motif ligand 12; ANGPTL3=angiopoietin-like protein 3; PPP1R3B=protein phosphatase 1 regulatory subunit 3B; CTRB1/2=chymotrypsinogen B1; SMAD3=mothers against decapentaplegic homolog 3; NOS3=nitric oxide synthase 3; LDLR=low-density lipoprotein receptor; PCSK9=proprotein convertase subtilisin/kexin type 9; APOB=apolipoprotein B; sdLDL=small dense low-density lipoproteins; ADAMTS=a disintegrin and metalloproteinase with thrombospondin motifs; THBS2=thrombospondin-2; CFDP1=craniofacial development protein 1; NOX4=NADPH oxidase 4; MCP-1=monocyte chemoattractant protein 1; M-CSF=macrophage colony-stimulating factor; VCAM-1=vascular cell adhesion molecule 1; IL-6R=interleukin-6 receptor; HNF1A=hepatocyte nuclear factor 1 homeobox A; TNF=tumor necrosis factor; IL=interleukin; hsCRP=high-sensitivity C-reactive protein; sCD40L=soluble CD40 ligand.