After adjusting for established cardiovascular disease (CVD) risk factors, our analysis showed a significant association between CFS/ME and CVD, demonstrating that CFS/ME may be an independent risk factor for CVD.
Nature
On 17 January 2025, Nature published a research paper titled, ‘Association between chronic fatigue syndrome/myalgic encephalomyelitis and cardiovascular disease.'
Extracts
Introduction
The relationship between CFS/ME and CVD is not fully understood. However, several mechanisms have been proposed to explain the association. Chronic inflammation has been implicated in both CFS/ME and CVD. Studies have shown that individuals with CFS/ME have higher levels of pro-inflammatory cytokines, and these are also associated with the development of atherosclerosis and CVD. Additional studies have noted that individuals with CFS/ME have reduced stroke volume, with a significant inverse relation between cardiac output and the severity of the disease. Patients with CFS/ME were observed to have a small left ventricular size and low cardiac output, with marked orthostatic intolerance.
Furthermore, autonomic dysfunction is frequently seen in individuals with CFS/ME and is associated with an increased risk of CVD. In other studies, CFS/ME was characterized by reduced blood pressure and systolic blood pressure variability. At the same time, oxidative stress, which is elevated in CFS/ME, is believed to potentially contribute to the development of CVD. These physiological changes contribute to some of the symptoms experienced by individuals with CFS/ME, including extreme fatigue.
Data source, study design, and study population
Data from the 2021–2022 national health interview survey (NHIS) was utilized for this study. The NHIS is an annual cross-sectional household survey by the national center for health statistics (NCHS) of the center for disease control and prevention (CDC).
Statistical analysis
Descriptive statistics summaries were produced for sociodemographic and cardiovascular risk factors. The differences in demographic characteristics and risk factors for cardiovascular disease (CVD) were then assessed based on cardiovascular disease (CVD) history using the chi-squared test. Multivariable logistic regression models were used to assess the association between CFS/ME and CVD, adjusting for traditional risk factors for CVD (age, sex, race, hypertension, diabetes, dyslipidemia, smoking, and BMI). The svy: command in Stata was used for all analysis to account for the sampling methods employed by the NHIS survey. A two-sided alpha (α) level of < 0.05 was used to determine the statistical significance of the results, and all statistical analyses were conducted using Stata version 17.
Results
History of Chronic Fatigue Syndrome was associated with increased odds of cardiovascular disease (OR 3.26, CI 2.85–3.72, p-value < 0.001) after adjusting for all other cardiovascular disease risk factors examined in this study.
Discussion
It is pertinent to acknowledge that while this observational study shows an association between CFS/ME and CVD, the limitations of the survey data used should be considered. The NHIS survey has limitations of recall bias among participants for diagnosis of both CFS/ME and CVS, potentially affecting the estimates from this analysis. The observed associations do not directly represent causality or reverse-causality between the two conditions. We are unable to establish temporality causation from our study based on the nature of the survey data used. Residual confounding for the association between CFS/ME and CVS is likely to further account for some of the estimates from our analysis.
Comment from Dr Charles Shepherd
This is not a subject that has attracted any serious research interest in the past.
This new research study indicates that there is an increased risk.
Previous research into cardiac function and endothelial dysfunction in ME/ CFS is summarised and referenced in section 5.5 of the Research chapter of the ME Association's ME/CFS/PVFS Clinical & Research Guide 2022 Edition (also know as the ‘purple book')
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
