# From polygenic risk to digital twins: the future of personalised cardiovascular medicine

**Authors:** Ibrahim Antoun, Alkassem Alkhayer, Ahmed Abdelrazik, Mahmoud Eldesouky, Kaung Myat Thu, Mokhtar Ibrahim, Harshil Dhutia, Riyaz Somani, G. Andre Ng

PMC · DOI: 10.3389/fcvm.2026.1735094 · Frontiers in Cardiovascular Medicine · 2026-02-09

## TL;DR

This review explores how personalized cardiovascular medicine is evolving through genomics, digital tools, and AI to improve individualized care and outcomes.

## Contribution

The paper synthesizes recent advances and challenges in precision cardiology, emphasizing the need for equitable implementation and multidisciplinary collaboration.

## Key findings

- Polygenic risk scores and multi-omics data improve cardiovascular risk stratification and understanding of disease mechanisms.
- AI and machine learning enhance predictive models using imaging, health records, and wearable data.
- Digital twins and CRISPR-based technologies offer new frontiers in personalized cardiovascular care.

## Abstract

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. Traditional risk assessment and treatment approaches often follow generalised strategies that inadequately capture individual variability in disease susceptibility, progression, and therapeutic response. Precision cardiology seeks to overcome these limitations by leveraging genomic, molecular, and computational innovations to enable more individualised care. Advances in polygenic risk scores have improved our ability to stratify cardiovascular risk at a population level, though challenges remain in ensuring clinical utility across diverse populations. Integrating multi-omics platforms, including transcriptomics, proteomics, and metabolomics, offers a more comprehensive understanding of CVD pathophysiology and potential diagnostic or prognostic biomarkers. Pharmacogenomic insights increasingly guide the selection and dosing of cardiovascular therapies such as statins and antiplatelets, supporting the shift toward personalised pharmacologic strategies. Applying artificial intelligence and machine learning to cardiovascular imaging, electronic health records, and wearable data enables more accurate, scalable predictive models. Emerging technologies, including CRISPR-based gene editing, single-cell sequencing, and digital twin modelling, further expand the frontiers of personalised cardiovascular medicine. However, real-world implementation remains limited by regulatory uncertainty, data integration challenges, cost, and concerns about equity and access. This review synthesises advances across genomic, omics, digital, and therapeutic domains in cardiovascular precision medicine, discusses key translational gaps, and highlights ethical and implementation challenges. We emphasise the need for multidisciplinary collaboration, robust validation frameworks, and equitable infrastructure to ensure these innovations lead to meaningful clinical impact. Personalised cardiology is poised to redefine prevention, diagnosis, and treatment paradigms as the field matures, moving from reactive care to proactive, patient-specific strategies.

## Linked entities

- **Diseases:** cardiovascular disease (MONDO:0004995)

## Full-text entities

- **Genes:** JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, CYP2C9 (cytochrome P450 family 2 subfamily C member 9) [NCBI Gene 1559] {aka CPC9, CYP2C, CYP2C10, CYPIIC9, P450-2C9, P450IIC9}, MYH7 (myosin heavy chain 7) [NCBI Gene 4625] {aka CMD1S, CMH1, CMYO7A, CMYO7B, CMYP7A, CMYP7B}, VKORC1 (vitamin K epoxide reductase complex subunit 1) [NCBI Gene 79001] {aka EDTP308, MST134, MST576, VKCFD2, VKOR}, SCN5A (sodium voltage-gated channel alpha subunit 5) [NCBI Gene 6331] {aka CDCD2, CMD1E, CMPD2, HB1, HB2, HBBD}, SLCO1B1 (solute carrier organic anion transporter family member 1B1) [NCBI Gene 10599] {aka HBLRR, LST-1, OATP-C, OATP1B1, OATP2, OATPC}, PCSK9 (proprotein convertase subtilisin/kexin type 9) [NCBI Gene 255738] {aka FH3, FHCL3, HCHOLA3, LDLCQ1, NARC-1, NARC1}, PKP2 (plakophilin 2) [NCBI Gene 5318] {aka ARVD9}, ASXL1 (ASXL transcriptional regulator 1) [NCBI Gene 171023] {aka BOPS, MDS}, KCNQ1 (potassium voltage-gated channel subfamily Q member 1) [NCBI Gene 3784] {aka ATFB1, ATFB3, JLNS1, KCNA8, KCNA9, KVLQT1}, TTN (titin) [NCBI Gene 7273] {aka CMD1G, CMH9, CMPD4, CMYO5, CMYP5, EOMFC}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, TTR (transthyretin) [NCBI Gene 7276] {aka AMYLD1, ATTR, CTS, CTS1, HEL111, HsT2651}, LPA (lipoprotein(a)) [NCBI Gene 4018] {aka AK38, APOA, LP}, LDLR (low density lipoprotein receptor) [NCBI Gene 3949] {aka LDLCQ2}, ANGPTL3 (angiopoietin like 3) [NCBI Gene 27329] {aka ANG-5, ANGPT5, ANL3, FHBL2}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, DSP (desmoplakin) [NCBI Gene 1832] {aka DCWHKTA, DP}, MYBPC3 (myosin binding protein C3) [NCBI Gene 4607] {aka CMD1MM, CMH4, FHC, LVNC10, MYBP-C, cMyBP-C}, TET2 (tet methylcytosine dioxygenase 2) [NCBI Gene 54790] {aka IMD75, KIAA1546, MDS}, CYP2D6 (cytochrome P450 family 2 subfamily D member 6 (gene/pseudogene)) [NCBI Gene 1565] {aka CPD6, CYP2D, CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2}, ADRB1 (adrenoceptor beta 1) [NCBI Gene 153] {aka ADRB1R, B1AR, BETA1AR, FNSS2, RHR}, CYP2C19 (cytochrome P450 family 2 subfamily C member 19) [NCBI Gene 1557] {aka CPCJ, CYP2C, CYPIIC17, CYPIIC19, P450C2C, P450IIC19}
- **Diseases:** CAD (MESH:D003324), myalgia (MESH:D063806), heart disease (MESH:D006331), HCM (MESH:D002312), myopathy (MESH:D009135), cardiac remodelling (MESH:D020257), Heart failure (MESH:D006333), high-cholesterol disorder (MESH:D006937), ARVC (MESH:D019571), TTR amyloidosis (MESH:D000686), HFpEF (MESH:D054144), Transthyretin amyloidosis (MESH:C567782), VT (MESH:D017180), long QT syndrome (MESH:D008133), lipid disorders (MESH:D011017), Mendelian cardiovascular disorders (MESH:D018376), atherogenic (MESH:D050197), hypertension (MESH:D006973), microvascular dysfunction (MESH:D017566), stent thrombosis (MESH:D013927), protein-misfolding disease (MESH:D057165), toxicity (MESH:D064420), FH (MESH:D006938), atrial fibrillation (MESH:D001281), myocardial infarction (MESH:D009203), dilated cardiomyopathies (MESH:D002311), CVD (MESH:D002318), myocarditis (MESH:D009205), stroke (MESH:D020521), cardiomyopathies (MESH:D009202), arrhythmia (MESH:D001145), bleeding (MESH:D006470), aortic stenosis (MESH:D001024), AI (MESH:C538142), arrhythmic (OMIM:212500), luminal stenosis (MESH:D003251), acute coronary syndrome (MESH:D054058), coronary disease (MESH:D003327), atrial remodelling (MESH:D064752), fibrosis (MESH:D005355), hyperlipidemias (MESH:D006949), cardiometabolic derangements (MESH:D024821), cardiomyocyte injury (MESH:D014947), shock (MESH:D012769), Conditions (MESH:D020763), inflammation (MESH:D007249), channelopathies (MESH:D053447), diabetes (MESH:D003920), ischemic (MESH:D002545), cancer (MESH:D009369)
- **Chemicals:** lipid (MESH:D008055), calcium (MESH:D002118), rosuvastatin (MESH:D000068718), simvastatin (MESH:D019821), Warfarin (MESH:D014859), ticagrelor (MESH:D000077486), DOACs (-), Clopidogrel (MESH:D000077144), pravastatin (MESH:D017035), vitamin K (MESH:D014812), ceramide (MESH:D002518), nitric oxide (MESH:D009569), cholesterol (MESH:D002784), branched-chain amino acids (MESH:D000597), TMAO (MESH:C005855), bucindolol (MESH:C024307), prasugrel (MESH:D000068799), triglycerides (MESH:D014280), hydralazine-isosorbide dinitrate (MESH:C431665)
- **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227], gut metagenome (species) [taxon 749906], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** c.521T > C, Arg389Arg, Arg389Gly

## Full text

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## Figures

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## References

86 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926492/full.md

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Source: https://tomesphere.com/paper/PMC12926492