Australian researchers have uncovered extensive cardiac damage in people with lupus and rheumatoid arthritis, with the greatest excess burden seen in younger patients.
People with systemic lupus erythematosus and rheumatoid arthritis have significantly higher rates of cardiac fibrosis, inflammation, and coronary artery disease than the general population, according to a major Australian postmortem study.
The research, published in The Journal of Rheumatology, found that myocardial inflammation was almost 15 times more likely in people with systemic lupus erythematosus (SLE) and more than six times more likely in those with rheumatoid arthritis (RA), compared with controls.
“These unique data describe the pathological spectrum of cardiac disease associated with autoimmune diseases,” the researchers wrote.
“SLE and RA were characterised by large hearts with fibroinflammatory myocardial disease and accelerated atherosclerosis. Associations were strongest in younger patients and persisted after adjustment for CAD, highlighting the burden of non-ischaemic cardiac disease.
“Cardiac death, the leading cause of mortality in these diseases, was associated with cardiomegaly, myocardial fibrosis, and epicardial CAD in both SLE and RA, and microvascular disease in SLE.
“Whilst our findings are limited by a lack of antemortem data, this study near-universally demonstrated increased cardiac abnormalities in autoimmune diseases which were associated with cardiovascular death.”
Myocardial fibrosis was associated with approximately fourfold higher odds in both conditions, while coronary microvascular disease was associated with tenfold higher odds in SLE and almost sevenfold higher odds in RA.
The findings suggested that cardiovascular damage in autoimmune rheumatic diseases extended well beyond accelerated atherosclerosis, with inflammatory and fibrotic changes potentially contributing to premature cardiovascular mortality.
Researchers led by Dr Jessica Fairley from St Vincent’s Hospital Melbourne and the University of Melbourne analysed postmortem findings from 486 Australians, including 123 with SLE, 240 with RA, and 123 controls who died in motor vehicle accidents.
Using data from the National Coronial Information System between 2000 and 2025, the investigators examined cardiovascular pathology and its association with cause of death.
The median age at death was 53 years among people with SLE and 66 years among those with RA, compared with 59 years in the control group.
Cardiovascular disease accounted for 51.2% of deaths in the SLE group and 56.3% in the RA group. Sudden cardiac death was more common in SLE than RA, occurring in 46.6% and 34.8% of cases, respectively.
The researchers found substantial differences in cardiac pathology between the autoimmune disease groups and controls.
Myocardial fibrosis was identified in 75.8% of people with RA and 57.9% of those with SLE, compared with 39% of controls.
Myocardial inflammation was present in 20.2% of SLE cases and 8.8% of RA cases, compared with just 1.6% of controls.
Cardiomegaly was also substantially more common, affecting 46.6% of people with SLE and 49.6% of those with RA, compared with 18.6% of controls.
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After adjusting for age, sex, and body mass index, the odds of cardiomegaly were 5.7 times higher in SLE and 3.5 times higher in RA.
Significant coronary artery disease was identified in 59.5% of RA cases and 42.1% of SLE cases, compared with 30.4% of controls.
The adjusted odds of significant coronary artery disease were approximately 2.5 times higher in both autoimmune conditions.
Importantly, the researchers found that associations between autoimmune disease and cardiac abnormalities were generally strongest among people younger than 60 years.
In this younger group, the odds of cardiomegaly were approximately 11 times higher in SLE and ten times higher in RA compared with controls.
Myocardial fibrosis was associated with more than fivefold higher odds in younger people with SLE and almost ninefold higher odds in those with RA.
Significant coronary artery disease was also associated with approximately fourfold higher odds in both conditions among people younger than 60.
The researchers said the findings highlighted the substantial burden of premature cardiovascular pathology in autoimmune rheumatic diseases.
Of particular significance was the persistence of myocardial abnormalities after adjustment for significant coronary artery disease.
Even after accounting for coronary disease, myocardial fibrosis remained associated with almost threefold higher odds in SLE and RA, while cardiomegaly and microvascular disease also remained strongly associated with both conditions.
This suggested that mechanisms beyond obstructive coronary artery disease were contributing to cardiac damage, the researchers said.
The study also identified important differences between the two autoimmune conditions.
Myocardial inflammation, pericardial abnormalities and valvular pathology were significantly more common in SLE than RA.
Coronary microvascular disease was identified in 14.9% of people with SLE and 9.7% of those with RA, compared with 1.6% of controls.
Inflammatory coronary lesions were also more common in SLE, occurring in 8.8% of cases compared with 1.8% in RA and none of the controls.
The researchers found that several cardiac abnormalities were independently associated with cardiovascular death.
In SLE, myocardial fibrosis was associated with more than double the odds of cardiovascular death, cardiomegaly with almost fourfold higher odds and significant coronary artery disease with more than fourfold higher odds.
In RA, myocardial fibrosis was associated with 3.6-fold higher odds of cardiovascular death, cardiomegaly with 2.5-fold higher odds and significant coronary artery disease with almost 13-fold higher odds.
Microvascular disease and valvular pathology were also significantly associated with cardiovascular death in SLE, but not RA.
Significant coronary artery disease was associated with sudden cardiac death in both conditions, while myocardial fibrosis was associated with sudden cardiac death in RA even after adjustment for coronary artery disease.
The researchers said their findings provided important pathological evidence supporting the contribution of both atherosclerotic and non-ischaemic cardiac disease to mortality in SLE and RA.
They noted that myocardial fibrosis could provide a substrate for arrhythmias and contribute to heart failure, while microvascular dysfunction might represent another important mechanism of cardiovascular injury.
However, the researchers acknowledged several limitations, including potential selection bias associated with coronial autopsies and the use of motor vehicle accident deaths as controls.
The study population may have been enriched for people with severe autoimmune disease or sudden and unexplained deaths, potentially exaggerating differences between groups.
Limited information on disease activity, cardiovascular risk factors, and medication exposure also prevented the researchers from examining the contribution of individual treatments or disease characteristics to cardiac pathology.
The observational findings could not establish causation or determine whether earlier detection of cardiac abnormalities would improve outcomes.
Nevertheless, the researchers said the results highlighted the importance of recognising cardiovascular disease as a major contributor to mortality in autoimmune rheumatic conditions, particularly among younger patients.
“These unique data highlight the direct and indirect mechanisms, severity and importance of cardiac disease in autoimmune diseases,” the researchers concluded.
“Furthermore, these data underscore the need for more sensitive, non-invasive methods of risk-stratifying individuals with autoimmune disease, particularly younger individuals at risk of premature cardiovascular disease.”
