Effect Modification by Sex of the Hemoglobin Concentration on Frailty Risk in Hospitalized Older Patients

Abstract

Background

Hemoglobin concentration differs by sex, possibly affecting any association between hemoglobin and frailty. This study aimed to evaluate the potential interaction effect of hemoglobin and sex on frailty in Chinese older inpatients.

Methods

A cross-sectional study was conducted between February 2015 and November 2017 in a tertiary hospital. Frailty was defined by the Fried phenotype. Hemoglobin concentration was measured with a standard procedure. Covariates included demographics, clinical characteristics, and serum biomarkers. Logistic regression was applied to examine the association between hemoglobin concentration and frailty. The relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) were used to evaluate the additive interaction.

Results

A total of 619 older inpatients [mean age 69.26±7.44 years; 334 men, 285 women] were included. The mean hemoglobin concentration was significantly lower in the elderly who were frail (11.9 g/L in frail versus 13.1g/L in non-frail; p<0.001). In the multivariable regression models, lower hemoglobin in patients was significantly associated with frailty (adjusted odds ratio (OR) = 2.51, 95% CI:1.37, 4.60). The stratified analyses indicated that lower hemoglobin was associated with frailty among older inpatients with different characteristics. Female inpatients with lower hemoglobin had the highest risk of frailty (adjusted OR=6.43, 95%: 2.38, 17.3); there were interactions between hemoglobin and sex on the development of frailty (RERI=4.30, 95% CI=−1.41, 10.01; AP=0.67, 95% CI=0.37, 0.97;SI=4.80, 95% CI=1.22, 18.84).

Conclusions and Implications

Our study provided evidence that sex and lower hemoglobin have an interaction effect on frailty; it is suggested that clinicians may consider sex-specific strategies for the elderly to conform the concept of precision medicine.

Keywords:

• hemoglobin concentration
• frailty phenotype
• older inpatient
• interaction effect

Acknowledgments

We extend our sincere thanks to the geriatric inpatients of Xuanwu Hospital, Capital Medical University for their voluntary participation in the study, as well as the managers of the hospital for supporting the smooth completion of the study. We thank Jie Liu, PhD (Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital) and Wangping Jia, PhD (Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Chinese PLA General Hospital) for their helpful review and suggestions concerning the manuscript.

Highlights

• Frailty symptom is common in hospitalized older patients.

• Hemoglobin concentration and anemia were independently and significantly associated with frailty.

• Sex and anemia have an interaction effect on frailty.

Data Sharing Statement

Data will be made available upon reasonable request to the corresponding author.

Ethical Considerations

Participation was voluntary, and informed consent was obtained from all participants. The study was conducted in accordance with the Declaration of Helsinki, and ethical approval of this study was granted by the Institutional Review Board of Xuanwu hospital, Capital Medical University.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.