Cardiovascular health

Main CVD risk factors for MPN patients

Most CVD develops from atherosclerosis which is a slow, decades long process:
– cholesterol plus inflammation builds up in artery walls;
– this causes arteries to become stiff and narrow; and
– plaques can rupture which leads to clots forming.

Some risk factors can’t be altered, such as: age; sex; genetics.
But most can be managed, such as smoking, being overweight, having an unhealthy diet, lack of physical activity, high blood pressure, high cholesterol, uncontrolled diabetes. Electrical problems of the heart should also be managed – eg  atrial fibrillation, arrythmias.

Below are the main cardiovascular risk factors that haematologists look out for and to manage in their MPN patients

1. Thrombosis (blood clot) risk

Australian haematologist Dr Cecily Forsyth presented on thrombosis (blood clots) at the MPN symposium in October 2025.
Her presentation slides and video describe specific concerns for MPN patients and how to manage them.

Myelofibrosis patients and thrombosis – MF patients need nuanced treatment in managing thrombosis and cardiovascular disease. For more information about this topic and thrombosis for MPN patients in general, see our separate webpage on this topic: recognising and preventing blood clots.

2. Heart attack and stroke risk

This risk is often caused by atherosclerosis which is a plaque build-up in blood vessels and blood vessel walls that can mainly affect the heart but can also affect the blood vessels of the brain and also the blood vessels of the legs.

Blood clots are the main cause of heart attacks and strokes in MPN patients as MPNs make the blood thicker, stickier, and more inflammatory than normal.  Importantly, in MPNs there is also higher underlying chronic inflammation which leads to faster plaque build up and higher predisposing to plaque rupture.

 Heart attack and MPN patients

A heart attack happens when a coronary artery (the vessels that feed the heart muscle) suddenly becomes blocked. The heart muscle downstream is starved of oxygen and starts to die.  In MPNs, blockages can form even without plaques from cholesterol plaques. Mechanisms include:

• High red cell mass (especially in PV) causes sluggish blood flow
• Overactive platelets (especially in ET) causes clots form too easily
• Inflammation from the malignant clone (Jak2, CALR or MPL) so vessels become more “clot-friendly”, especially the Jak2 clone.
• Microclots can cause small vessels to be blocked.

An MPN patient can have a heart attack with normal or even low cholesterol.
MPN-related heart attacks may:

• Occur younger than expected
• Be silent or atypical (fatigue, breathlessness, jaw or back pain)
• Occur despite aspirin or “good numbers”

Stroke in MPN patients

Most strokes in MPNs are ischemic strokes—a clot blocks blood flow to part of the brain.  MPN patients are at higher risk of stroke because:

• Having the Jak2 mutation – (research shows that 11% of patients with an ischemic stroke have the Jak2 mutation although not all may have an MPN).
• Platelet activation can cause clots in cerebral arteries
• High haematocrit leads to poor microcirculation in the brain
• Abnormal clot breakdown means clots persist longer
• Small-vessel disease can cause repeated tiny infarcts over time

MPNs patients are also more prone to transient ischemic attacks (TIAs or mini-strokes),  and also unusual stroke locations, including small cortical or deep brain vessels.

 Especially in MPNs, strokes may show up as:

• Visual changes
• Word-finding difficulty
• Confusion or personality change
• Balance problems
• Migraines or “weird neurological episodes” that later turn out to be TIAs

Standard risk calculators underestimate MPN risk as they do not account for clonal hematopoiesis, platelet activation, or inflammatory thrombosis, which are central in MPNs.

3. Heart failure

Heart failure arises from either:

• systolic heart failure (caused by weakening of heart muscle and impaired pumping function), or
• diastolic heart failure (stiffness of heart muscle leading to impaired filling)

Symptoms are shortness of breath, swelling of legs, or abdomen, shortness of breath when flat, when tying shoes.
Importantly, MF patients may have other reasons that cause swelling of abdomen, leg swelling etc so it’s sometimes difficult to tease these out.

Over time, as the heart is damaged, it can cause kidney failure and/or liver failure, so it is important to identify and treat heart failure early to reduce risk of other complications.

Dr Orly Leiva’s research informs us that MPN patients are at increased risk for developing heart failure compared with the general population. And ‘among patients already at risk, such as those with acute coronary syndrome (heart attacks) or arrhythmias, those with MPNs have higher rates of heart failure hospitalisations’.

Myelofibrosis patients and heart failure

Myelofibrosis (MF) patients should be evaluated from a cardiologist in these situations.

How does heart failure tie in with MF?

A retrospective study showed patients with a more advanced form of MPN are at the highest risk of heart failure – eg a high WCC, large spleen. While there are not many studies yet available, Ruxolitinib seems to be associated with lower risk of heart failure.

Dr Leiva has just published in 2026, an article in Leukemia and Lymphoma titled ‘Ruxolitinib and heart failure outcomes among patients with myelofibrosis‘. It is freely available to access.

Interestingly, the research of Dr Leiva and team has showed that if PV and ET patients whose heart failure is serious enough to see the patient hospitalised – this should be a warning flag to haematologists to look out for disease progression in their MPN.

For more detail, an article published in 2025 and of which Dr Leiva is a lead author, sheds more light on this issue. Full access is available.
Beyond Thrombosis: Pulmonary Hypertension and Heart Failure in Patients With Myeloproliferative Neoplasms: JACC: CardioOncology State-of-the-Art Review

4. Pulmonary hypertension

Pulmonary hypertension means that blood pressure in the blood vessels of the lungs is too high.  It is different from normal blood pressure as it is a specific problem with lung circulation.

In pulmonary hypertension, blood vessels in the lungs become narrow, stiff or blocked.  This makes it more difficult for blood to move through, so pressure builds up.  This means the right side of the heart has to work much harder to push blood into the lungs. And over time, that strain can cause: shortness of breath (especially on exertion), fatigue, dizziness or fainting, swollen ankles or legs, and chest discomfort.

As with congestive heart failure, pulmonary hypertension is not uncommon in MF patients

Dr Leiva’s article from late 2025, linked above, explains that pulmonary hypertension in particular has been linked to worse prognosis in patients with MPNs. And interestingly, it is also associated with increased risk for progression to either myelofibrosis or acute myeloid leukaemia.

5. Electrical system of the heart

Electricity problems include arrhythmias, atrial fibrillation (AF), heart block.
These should be evaluated by a cardiologist to determine best management.

The heart has its own built-in electrical system. If there are electrical problems and this signalling is disrupted, arrhythmias can occur. Arrhythmias are abnormal heart rhythms which can be intermittent or constant. They can be too fast (tachycardia), too slow (bradycardia) or irregular (fibrillation).

Electrical issues often overlap with pump or vessel disease in that they can reduce cardiac output; increase stroke risk (especially AF); cause sudden cardiac death; or often worsen other cardiovascular conditions.

Prevention and management of electrical issues might include: treating underlying heart disease; correcting electrolytes avoid triggers (stimulants, alcohol excess); prescribing medications to control rate or rhythm; anticoagulation when stroke risk is high; using devices (pacemaker, defibrillator) when needed.

A research article published in 2025 may be of interest to MPN patients with atrial fibrillation and the Jak2 mutation. Titled ‘Incidence, Outcomes and Risk Factors for Atrial Fibrillation in Patients With JAK2V617F-Positive Myeloproliferative Neoplasms‘ the full article is freely available from Cancer Medicine.