DOI: 10.1177/00368504261479101 ISSN: 0036-8504

Sex-specific associations of the CALLY index with mortality in hypertension: Stronger relative protection in males but greater absolute benefit in females-a retrospective cohort study

Ying Xu, Jiping Wang, Qiaoyi Li, Likun Zhu
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Objective

Inflammation, immunity, and nutrition are established factors in hypertension, but the prognostic role of the C-reactive protein-albumin-lymphocyte (CALLY) index remains undefined. We aimed to clarify its impact on mortality.

Methods

This retrospective cohort study used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2010.We identified 9,199 adults with hypertension and linked their records to the National Death Index to obtain mortality follow-up through December 31, 2019. The association between the CALLY index and both all-cause mortality (ACM) and cardiovascular mortality (CVM) was assessed using survey-weighted Cox proportional hazards models. To evaluate potential sex-specific differences, we performed sex-stratified subgroup analyses and quantified additive interactions via the relative excess risk due to interaction (RERI) and attributable proportion (AP).

Results

Over a median follow-up of 11.2 years, 3,259 ACM (35.4%) and 1,111 CVM (12.1%) occurred. Subgroup analyses showed numerically stronger inverse associations in males than females for both ACM (male: HR = 0.82; female: HR = 0.87) and CVM (male: HR = 0.79; female: HR = 0.90), although multiplicative interaction was not significant (ACM: p = 0.13; CVM: p = 0.84). On the additive scale, a significant sex difference was observed for ACM (RERI = 0.14, 95% CI: 0.05–0.24), but not for CVM (RERI = 0.09, 95% CI: -0.07 to 0.26). Nonlinear dose-response patterns were observed for ACM ( p < 0.001) but not for CVM ( p = 0.072).

Conclusion

The CALLY index was independently associated with mortality in hypertensive adults. Although the relative protective effect was numerically stronger in males, additive interaction analysis revealed that females exhibited a significant additional absolute risk reduction associated with higher CALLY levels for ACM. These findings suggest the potential for sex-specific risk assessment using the CALLY index, though given the observational design and the lack of significant multiplicative interaction, these results should be considered hypothesis-generating and do not support therapeutic recommendations.

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