IPM Take
Cardiology has spent decades perfecting the familiar risk checklist: smoking, blood pressure, cholesterol, diabetes, obesity and age. Pain rarely makes the list. That may need to change. PainFACT suggests that chronic pain is not simply a quality-of-life issue parked in another specialty. It may be a marker of deeper systemic vulnerability, especially when pain, fatigue, mood disorders and cardiovascular risk cluster together. The danger is obvious: if health systems keep treating pain, mental health and cardiovascular disease in separate silos, they may keep missing the patient in front of them.
Executive Summary
The EU-funded PainFACT project has reported new findings linking chronic pain, pain sensitivity and cardiovascular disease. The project analysed health data from more than five million people in Norway and incorporated large international population resources, including UK Biobank and the Danish Blood Donor Study. Researchers integrated patient registry data, genetics, blood protein measurements, imaging and experimental models to investigate why chronic pain frequently co-occurs with fatigue, anxiety, depression, cardiovascular disease and broader multimorbidity.
PainFACT identified a strong association between chronic pain and future cardiovascular disease, particularly in conditions such as fibromyalgia. Individuals with increased pain sensitivity also showed higher cardiovascular risk, even after accounting for traditional risk factors including smoking, cholesterol and hypertension. The project also carried out a large genome-wide association study of pain sensitivity using the cold-pressor test in approximately 30,000 participants, identifying genes linked to pain tolerance, including TRPM8, which is involved in both pain perception and blood pressure regulation.
The findings are reinforced by a 2026 systematic review and meta-analysis in Pain, which found that chronic widespread pain was consistently associated with incident atherosclerotic disease. Together, the evidence suggests that chronic pain may deserve more attention in cardiovascular prevention, risk stratification and integrated care pathways.
Why it matters
- Policymakers: Chronic pain and cardiovascular disease are often managed in separate policy lanes, but emerging evidence suggests they may be connected through shared biological and social risk pathways.
- Public authorities: Prevention strategies may need to consider chronic pain populations as potentially higher-risk groups for cardiovascular assessment and follow-up.
- Clinicians: Patients with fibromyalgia, chronic widespread pain or high pain sensitivity may require more proactive cardiovascular risk evaluation, especially when fatigue, depression or metabolic risk factors are also present.
- Hospitals / providers: Pain clinics, cardiology services, primary care and mental health teams will need better referral pathways if multimorbidity is to be managed before it becomes advanced disease.
- Researchers / academia: More work is needed to establish causality, validate biomarkers, understand sex-specific mechanisms and test whether cardiovascular prevention in chronic pain populations improves outcomes.
- Patients / advocates: People living with chronic pain should not be dismissed as “complex” or “psychosomatic.” Their symptoms may reflect systemic risk that deserves structured assessment.
- Industry / innovation partners: The findings create space for biomarker, digital phenotyping and risk-stratification tools linking pain biology with cardiovascular prevention.
Chronic pain has too often been treated as a problem of suffering, not survival.
That distinction may be getting harder to defend.
A new Results in Brief article from the EU-funded PainFACT project argues that chronic pain is deeply interconnected with broader systemic health, including cardiovascular disease. The project set out to investigate why chronic pain so often travels with fatigue, anxiety, depression, cardiovascular disease and multimorbidity.
The scale matters. PainFACT analysed health data from more than five million individuals across Norway, alongside major population resources such as UK Biobank and the Danish Blood Donor Study. Researchers combined patient registries, genetics, blood protein measurements, imaging data and experimental models to look beneath the surface of disease clustering.
What they found should make cardiology uncomfortable.
PainFACT identified a strong association between chronic pain and future cardiovascular disease. The signal was particularly pronounced in conditions such as fibromyalgia, and people with increased pain sensitivity showed higher cardiovascular risk even after traditional risk factors such as smoking, cholesterol and hypertension were taken into account.
That does not mean chronic pain directly causes heart disease in every patient. But it does mean chronic pain may be more than a background condition. It may be a clinical marker of cardiovascular vulnerability that current pathways are poorly designed to capture.
The finding is especially important for women. Chronic pain disorders disproportionately affect women, and cardiovascular disease in women has long been under-recognised, under-diagnosed and sometimes misread through male-centred symptom models. If pain sensitivity and chronic pain are linked to cardiovascular risk, ignoring them could reinforce an already dangerous diagnostic gap.
The genetic findings sharpen the point.
PainFACT carried out a large genome-wide association study of pain sensitivity using the cold-pressor test, which measures tolerance to cold-induced pain. Researchers analysed approximately 30,000 participants and identified five genes associated with pain tolerance. One of the most notable was TRPM8, a gene involved in pain perception and blood pressure regulation.
Further analysis found genetic overlap between pain sensitivity, chronic pain conditions such as migraine and coronary artery disease. That overlap matters because it suggests chronic pain and cardiovascular disease may not be two separate conditions randomly colliding in the same patient. They may share biological pathways.
This is where the policy implications begin.
Cardiovascular prevention is still organised around a familiar set of measurable risks. Blood pressure can be measured. LDL cholesterol can be measured. HbA1c can be measured. Smoking can be recorded. But chronic pain sits awkwardly in health systems: common, disabling, poorly reimbursed, often stigmatised and frequently fragmented across primary care, rheumatology, neurology, pain medicine, mental health and rehabilitation.
That fragmentation is not harmless.
A 2026 systematic review and meta-analysis in Pain found that chronic widespread pain was consistently associated with incident atherosclerotic disease. The analysis included 18 studies covering more than 80,000 people with chronic widespread pain and nearly 34,000 cardiovascular events. In maximally adjusted models, chronic widespread pain remained associated with higher risk of atherosclerotic disease, while evidence for cardiovascular mortality was less conclusive.
The message is not that every patient with chronic pain should be medicalised as a cardiac patient. The message is that chronic pain populations may represent an under-recognised cardiovascular risk group, especially when pain coexists with fatigue, depression, inactivity, poor sleep, obesity, hypertension or socioeconomic disadvantage.
This also connects with wider evidence on the overlap between mental health and cardiovascular disease. A 2026 review in Nature Cardiovascular Research argues that anxiety and mood disorders share biological, behavioural, psychological and social risk mechanisms with cardiovascular disease, and that patients with both conditions may benefit from collaborative care focused on modifiable shared risk factors such as lifestyle and stress management.
For IPM, this is the real policy signal.
The patient with chronic pain is not a referral problem to be passed between specialties. They may be the model patient of modern multimorbidity: pain, fatigue, mood symptoms, cardiovascular risk, metabolic risk and social vulnerability all interacting in one body.
Health systems are not built for that patient.
They are built for single-disease pathways, short appointments, narrow reimbursement codes and specialist silos. PainFACT challenges that architecture. If chronic pain and cardiovascular disease share mechanisms, then prevention cannot remain locked inside cardiology clinics. It has to move into pain pathways, primary care, rehabilitation, women’s health and mental health services.
The next step is not to overstate the evidence. More research is needed to prove causality, validate risk markers and test whether targeted cardiovascular prevention in chronic pain populations changes outcomes.
But waiting for perfect certainty would also be a mistake.
Chronic pain affects millions, and cardiovascular disease remains the world’s leading cause of death. If the overlap between the two is real, even modest improvements in recognition, risk assessment and integrated care could matter.
The political question is whether health systems are willing to treat pain as part of systemic health, or whether they will keep pretending that the heart, brain, immune system and lived experience of the patient operate in separate departments.
