Heterogeneity in the Association Between Endometriosis and Early-Onset Cardiovascular Disease by Systemic Inflammation: NHANES 1999–2006

Chidinma Oli
In: Epidemiology · 2026 · vol. 37(S2) · doi:10.1097/01.ede.0001280120.20930.d4 · W7221571668
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Analysis of NHANES data reveals that the association between endometriosis and early-onset cardiovascular disease is stronger in women with high hs-CRP or intermediate systemic immune-inflammation index levels.

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This study analyzed data from 5,309 women aged 20–54 in the NHANES survey to determine if systemic inflammation modifies the link between endometriosis and early-onset cardiovascular disease. Researchers used survey-weighted logistic regression with inverse probability weighting to adjust for confounders while assessing associations across different levels of high-sensitivity C-reactive protein and the systemic immune-inflammation index. The key finding was that endometriosis was significantly associated with higher odds of early-onset CVD only among women with high hs-CRP levels or intermediate SII tertiles, indicating heterogeneity based on inflammatory status. This paper is centrally about endometriosis — specifically examining its association with cardiovascular outcomes mediated by systemic inflammation markers.

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Background

Endometriosis is a chronic inflammatory condition associated with increased cardiovascular disease (CVD) risk, yet the role of systemic inflammation in shaping this association remains poorly understood. We examined whether systemic inflammation modifies the association between endometriosis and early-onset CVD among U.S. women.

Methods

We analyzed data from 5,309 women aged 20–54 years in the National Health and Nutrition Examination Survey (1999–2006). Endometriosis and early-onset cardiovascular disease (i.e., CVD before age 55) were based on self-reported physician diagnoses. Early-onset CVD included congestive heart failure, coronary heart disease, angina, myocardial infarction, or stroke. Systemic inflammation was characterized using high-sensitivity C-reactive protein [hs-CRP; low (3mg/L)] and the systemic immune-inflammation index (SII; tertiles). Survey-weighted logistic regression was used to assess heterogeneity across inflammation levels, with stabilized inverse probability of treatment weighting (IPTW) to adjust for confounding.

Results

Among 5,309 women, 356 (7.06%) reported an endometriosis diagnosis and 152 (3.02%) early-onset CVD. After IPTW adjustment for age, body mass index, smoking, education, age at menarche, physical activity and race/ethnicity, endometriosis was associated with higher odds of early-onset CVD among women with high hs-CRP (prevalence odds ratio [POR] = 2.37, 95% CI: 1.50–3.74), but not among those with low or moderate hs-CRP levels (p-interaction= 0.24). Across SII strata, the strongest association was observed among women in the medium SII tertile (POR = 3.09, 95% CI: 1.55–6.16), with no associations in the low or high tertiles (p-interaction = 0.16).

Conclusion

The association between endometriosis and early-onset CVD showed heterogeneity across levels of systemic inflammation, with stronger associations observed at higher hs-CRP and intermediate SII levels.

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