**Background:** Cardiovascular disease (CVD) remains the leading cause of death globally, with inflammation playing a key role in its pathogenesis. Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease affecting 0.5–1% of the global population, is known to increase CVD risk. The Mediterranean diet (MD), characterized by high intake of fish, olive oil, fruits, vegetables, whole grains, legumes, nuts, and moderate alcohol, has anti-inflammatory properties and is considered cardioprotective. Despite evidence that MD may reduce pain and improve physical function in RA patients, few studies have examined the combined effect of RA and MD on CVD risk. This study aimed to investigate the interaction between RA and MD adherence on CVD risk using NHANES data.
**Methods:** This cross-sectional study analyzed data from NHANES 2005–2010. From 4,750 middle-aged and elderly participants (≥40 years) with complete dietary data, exclusions were applied for CVD preceding RA (n=2), unavailable RA assessment (n=1,386), and extreme energy intakes (n=10), yielding 3,352 participants (385 CVD, 2,967 non-CVD). RA and CVD were defined by self-reported physician diagnosis. MD adherence was assessed using the alternate Mediterranean Diet Index (aMD), with scores <3.80 classified as low adherence (based on median). Weighted multivariate logistic regression was used, with Model 1 adjusting for age, gender, and ethnicity, and Model 2 additionally adjusting for educational level, poverty-income ratio, waist circumference, smoking, physical activity, hypertension, diabetes, dyslipidemia, family history of CVD, uric acid, eGFR, and energy. Additive interaction was evaluated using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). Multiplicative interaction was assessed via the product-term odds ratio (OR). Subgroup analyses were performed by age, gender, ethnicity, BMI, and family history of CVD.
**Key Results:** RA was significantly associated with increased CVD risk (Model 1: OR=3.98, 95% CI: 2.76–5.73; Model 2: OR=2.65, 95% CI: 1.69–4.16). Low MD adherence was also associated with higher CVD risk (Model 1: OR=1.82, 95% CI: 1.13–2.93; Model 2: OR=1.67, 95% CI: 1.01–2.77). For the combined categories (fully adjusted), compared to the non-RA & high MD reference group: RA & low MD had OR=6.42 (95% CI: 3.06–13.43), non-RA & low MD had OR=1.29 (95% CI: 0.76–2.20), and RA & high MD had OR=1.37 (95% CI: 0.74–2.56). Significant additive interaction was observed (RERI=4.76, 95% CI: 0.52–9.00; AP=0.74, 95% CI: 0.54–0.95; SI=8.21, 95% CI: 1.48–45.51). Multiplicative interaction was also significant (OR for product-term=3.63, 95% CI: 1.44–9.15; likelihood ratio test P=0.009). Subgroup analyses revealed significant multiplicative interactions among non-Hispanic White participants (OR=5.42, 95% CI: 1.69–17.37), those aged ≥60 years (OR=4.06, 95% CI: 1.42–11.62), those without a family history of CVD (OR=2.84, 95% CI: 1.07–7.50), and those with BMI 25–30 kg/m² (OR=6.09, 95% CI: 1.09–33.89). Neither additive nor multiplicative interactions were statistically significant in the subgroup with a family history of CVD (n=476).
**Clinical Implications:** This study provides the first evidence from NHANES of a synergistic interaction between RA and low MD adherence on CVD risk. The findings suggest that patients with RA who have poor dietary habits are at disproportionately higher CVD risk than would be expected from either factor alone. The synergistic effect implies that improving MD adherence in RA patients could yield greater-than-expected cardiovascular benefits. Mechanistically, shared inflammatory pathways, endothelial dysfunction, and oxidative stress may underlie this interaction, with MD's anti-inflammatory and antioxidant properties potentially counteracting RA-related CVD risk. Limitations include the cross-sectional design (precluding causal inference), reliance on self-reported RA, MD, and CVD diagnoses (recall bias), and exclusion of participants with unavailable RA assessment. Prospective studies are needed to confirm these findings and elucidate mechanisms.