Clonal Haematopoiesis: A Hidden Risk Factor for Heart Disease

Synopsis

Clonal Haematopoiesis is an age-related blood condition where a mutated stem cell gradually takes over, driving chronic inflammation that raises heart disease risk even when cholesterol and blood pressure look normal.

Key takeaways:

CHIP mutation raises cardiovascular risk.
The driver is vascular inflammation, not blood cancer; most people with CHIP never develop leukaemia or lymphoma.
Detection is a simple, non-invasive blood test using next-generation sequencing.
A positive result means closer monitoring and more intensive attention to modifiable risk factors.
Targeted anti-inflammatory treatments for CHIP, including colchicine and NLRP3 inhibitors, are in active clinical trials but not yet standard of care.

A New Risk Factor Hidden in Your Blood

When we think about heart disease risk, most of us picture the usual suspects: high cholesterol, high blood pressure, smoking, diabetes, obesity. These are real and important. But a growing body of research is revealing a significant risk factor that most people have never heard of.

It's called Clonal Haematopoiesis, or CH. And it may help explain why some people develop cardiovascular disease even when their traditional risk factors look perfectly normal.

What Is Clonal Haematopoiesis?

Your blood is continuously replenished by haematopoietic stem cells — specialised cells in the bone marrow that produce billions of red blood cells, white blood cells, and platelets every single day.

Over a lifetime, these stem cells can accumulate random genetic mutations. Most of these mutations are harmless and have no consequences. But occasionally, a mutation gives one stem cell a competitive advantage, causing it to divide more rapidly than its neighbours. Over time its descendants — all carrying the same mutation — make up an increasingly large fraction of your blood cells.

This process is called clonal expansion, and these mutations could indicate a precursor to blood cancer, but in the vast majority of people, they never progress to leukaemia or lymphoma.

What researchers didn't anticipate — and what has since become one of the most important discoveries in cardiovascular medicine — is what these mutations do to the heart.

How Common Is It?

Very common, and becoming more so with age.

CH affects more than 10% of individuals over the age of 70.¹ It is rarely seen under the age of 40, but its prevalence climbs steeply through midlife and beyond.

The Surprising Link to Heart Disease

Here is where the story takes an unexpected turn.

Researchers studying large population cohorts noticed something striking: people with clonal hematopoiesis of indeterminate potential (CHIP) mutations had an elevated risk of coronary heart disease and all-cause mortality — even after accounting for every conventional cardiovascular risk factor. The increased risk was comparable in magnitude to having type 2 diabetes.¹

This was not a small effect. Certain mutations were associated with even more dramatic elevations in risk, up to a 12-fold increased risk of coronary heart disease.²

The critical question was: why?

Inflammation — The Hidden Mechanism

The answer lies in inflammation.

Mutated blood cells behave differently from normal immune cells. When they enter the walls of blood vessels and fatty deposits (atherosclerotic plaques), they trigger exaggerated inflammatory responses that accelerate the formation and destabilisation of plaques.^2,3 They stoke a chronic, low-grade inflammatory fire inside blood vessel walls. This is the same inflammatory pathway implicated in heart attacks, strokes, and progressive heart failure.⁴

This discovery is significant because it offers not just an explanation for unexplained cardiovascular events, but a potential therapeutic target.

How Is It Detected?

CHIP is detected through Next-Generation Sequencing (NGS) of a standard peripheral blood sample — a sophisticated form of genetic testing that can identify mutations even when they are present at low frequencies in the blood.⁵

This is a non-invasive, relatively straightforward test. No bone marrow biopsy is required for most cases.

What Happens After a Positive Test?

A positive CHIP result does not mean you will develop leukaemia or that heart disease is inevitable.

What a positive result does mean is that you carry a risk-modifying factor that should inform your cardiovascular prevention strategy.

Haematologic Surveillance

For most individuals with low-risk mutations simple monitoring with a full blood count every 6–12 months is appropriate.⁶ If blood counts become abnormal, further haematological evaluation is indicated.

Cardiovascular Risk Reduction — Where the Real Opportunity Lies

Individuals with high-risk CHIP genotypes should be treated as having an elevated cardiovascular risk profile — one that warrants more intensive attention to every modifiable risk factor.⁴

Lipid management⁴ — optimising LDL-cholesterol and considering lipid-lowering therapy where thresholds are met
Blood pressure control⁴ — maintaining tight blood pressure targets
Metabolic health⁴ — addressing blood glucose, and weight
Lifestyle factors⁴ — smoking cessation (which creates selective pressure favouring clonal expansion), regular physical activity and dietary quality
Inflammation monitoring⁷ — tracking high-sensitivity CRP and other inflammatory markers, which may be elevated in CHIP and serve as a guide to intervention intensity

The Emerging Therapeutic Frontier

Perhaps the most exciting implication of CHIP research is the potential for targeted anti-inflammatory therapies, including colchicine (a well-established medicine) and NLRP3 inhibitors — are currently under active investigation in clinical trials.⁸

While these are not yet standard of care for CHIP, this research trajectory suggests that in the near future, knowing your CHIP status may guide not just lifestyle and conventional preventive therapies, but also more targeted anti-inflammatory strategies.

The Bigger Picture

Clonal Haematopoiesis represents a paradigm shift in how we think about ageing, inflammation, and cardiovascular disease.

For decades, heart disease prevention has focused on lipids, blood pressure, and blood glucose. These remain essential. But CHIP research reminds us that the immune system — and the inflammatory signals it generates — plays an equally central role in cardiovascular ageing.

Many people who suffer heart attacks and strokes "out of nowhere" — with seemingly normal cholesterol and blood pressure — may in fact be carrying clonal mutations silently amplifying their cardiovascular risk for years or decades beforehand.

Testing for CHIP won't be right for every patient. But for individuals with unexplained cardiovascular events, a strong family history, or those seeking a genuinely comprehensive picture of their long-term health risks, it represents one of the most significant advances in preventive medicine of the last decade.

Dr Tim Trodd

Family Medicine, Functional Medicine, General Practice

MBBS (London)
DCH (London)
DRCOG (UK)
MRCGP (UK)
FHKAM (Family Medicine)

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References

Wu, H. et al. (2026) Clonal hematopoiesis of indeterminate potential and cardiovascular disease: mechanistic insights, clinical implications, and the dawn of precision cardio-hematology. Front. Cardiovasc. Med. https://doi.org/10.3389/fcvm.2026.1796328
Cacic, A.M. et al. (2023) Molecular and clinical aspects relevant for counseling individuals with clonal hematopoiesis of indeterminate potential. Front. Oncol. https://doi.org/10.3389/fonc.2023.1303785
Dorsheimer, L. et al. (2019) Association of mutations contributing to clonal hematopoiesis with prognosis in chronic ischemic heart failure. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2018.3965
Oren, O. et al. (2026) Clonal hematopoiesis of indeterminate potential and heart disease: what every internist needs to know. CCJM. https://doi.org/10.3949/ccjm.93a.26003
Cho, Y.U. (2024) The role of next-generation sequencing in hematologic malignancies. Blood Research. https://doi.org/10.1007/s44313-024-00010-0
Vanner, R.J. et al. (2026) Clinical decisions in clonal hematopoiesis: a contemporary review for clinicians. Haematologica. https://doi.org/10.3324/haematol.2025.287422
Libby, P, et al. (2019). Clonal Hematopoiesis: Crossroads of Aging, Cardiovascular Disease, and Cancer: JACC Review Topic of the Week. Journal of the American College of Cardiology. 74(4), 567–577. https://doi.org/10.1016/j.jacc.2019.06.007
Oren, O. et al. (2025) Managing cardiovascular risk in clonal hematopoiesis of indeterminate potential. JACC: CardioOncology. https://doi.org/10.1016/j.jaccao.2025.05.013