The main finding of this study was that decreased grip strength in adults was associated with an increased risk for all-cause mortality. Using four different measures of grip strength, we found similar non-linear inverse correlations. HGS (AUC = 0.714) had the best ability to predict all-cause mortality, followed by MGS (AUC = 0.712). Participants with low grip strength were at increased risk of mortality, and the HR was highest in the lowest 20% grip strength group (HR = 2.20 for men, 2.52 for women). We found no significant interaction of age, sex, and grip strength, except for low reference grip strength and gender (Pinteraction=0.013).
Our finding of inverse associations between grip strength and all-cause mortality were in agreement with previous studies. A meta-analysis conducted on 42 studies including 3,002,203 participants showed that grip strength was an independent predictor of all-cause mortality, the HRs (95% CIs) with per-5-kg decrease in grip strength was 1.16 (1.12, 1.20) for all-cause mortality[22]. These results were comparable to our findings, where we found that 5-kg lower HGS in men was associated with an HR of 1.36 in men for all-cause mortality, and an HR of 1.49 in women. Cai, Y. et al.[27] similarly found that the HR (95% CI) for all-cause mortality per 5-kg reduction in grip strength was 1.11(1.06, 1.18) in men and 1.17(1.08, 1.28) in women.
In our study, we found that after standardizing all grip strength indicators, the association of absolute grip strength indicators with the risk of all-cause mortality was stronger than that of relative grip strength indicators, with the highest being for HGS (HR = 1.81 for men and HR = 1.62 for women). Inconsistently, a study, also based on NHANES, found that compared with the sum of the maximum values of both hands (GS), GS/BMI had a stronger correlation with cardiovascular biomarkers as a relative grip strength indicator[7]. Wonjeong Jeong et al. [29] also found that HGS/BMI was more associated with risk of all-cause mortality compared with HGS, the associations persisted after adjustment for chronic diseases. Similarly, Yanan Gao et al. [9] also recommended HGS/BMI or HGS/body weight as the best choice for grip strength expression to predict the risk of CVD risk factors. However, by comparing AUC in our study, we recommend HGS or MGS as the optimal predictor of all-cause mortality risk. Meanwhile, Ho FKW et al.[12] compared different expressions of grip strength in adults with an average age of 56 years (range 37–73) based on UK Biobank and found no difference in the association between absolute and relative grip strength and all-cause mortality. They believed that the simplest method of handgrip strength measurement, i.e., the absolute unit (kg), was perfectly suitable for predicting health outcomes in clinical practice.
We found participants with low grip strength carried higher mortality risk, irrespective of which definition was used, which was in line with previous studies [20, 25, 30]. However, few studies have compared the effect of different measures of low grip strength in the same population. Our study showed that the HRs was highest when using the definition of “lowest 20% grip strength” (HR = 2.20 for men, 2.52 for women), possibly because this definition could identify participants with the worst muscle strength, and better distinguish them from people with normal grip strength.
Overall, we did not find significant modifying effect of gender and age on the association between grip strength and all-cause mortality, except for the interaction between low reference grip strength and gender, where the effect of low grip strength was only found in men, which was consistent with the previous conclusion of Strand BH et al in Tromsø database[24]. However, this was opposite to the results of a previous KORA-based study[31], which found that the association between muscular strength and all-cause mortality tended to be stronger in women. Actually, most previous studies suggested no interaction of grip strength and gender, on the risk of death[22, 24, 25].
Existing evidence stratified by age also suggested inconclusive results. A study based on UK Biobank demonstrated that the hazard ratio of grip strength with all-cause death was higher in the younger age group in both genders[25]. Similar results were also found in the China Health and Retirement Longitudinal Study (CHARLS) study in China, where the association between MGS and all-cause mortality was stronger in young men (HR = 0.29, 95% CI: 0.18–0.45) than in older men (HR = 0.49, 95% CI:0.33–0.73)[32]. Whereas Rachel et al. [26] found that the association between low grip strength and all-cause mortality was higher in people over 70 years old (HR = 1.80, 95% CI: 1.48–2.18) than those of under 60 years old (HR = 1.43, 95% CI: 1.07–1.91). Further research is needed to examine the interaction effect of age and sex.
Our study had several advantages. First, we used relatively comprehensive measures of grip strength, including absolute grip strength (HGS, MGS), relative grip strength (HGS/BMI, MGS/weight), and low grip strength, to examine and compare their associations with all-cause mortality. Meanwhile, by using the relative grip strength index, the influence of body shape factors (such as fat, weight, BMI) can be effectively excluded to some extent, so that more reliable conclusions can be obtained. Second, this study used a large representative sample from the American NHANES. The grip strength was standardized (Z score) to further study the correlation between grip strength and all-cause mortality. ROC curve was used to compare the area under the curve (AUC) to obtain the optimal index of grip strength to predict the risk of all-cause death. However, our study had some limitations. First, as the NHANES is a repeated cross-sectional study, it cannot provide data on changes in grip strength, so we could only examine the association of baseline grip strength with all-cause death. Nevertheless, previous studies have found that baseline grip strength measures are the best predictors of cardiovascular mortality[33]. Second, as an outcome variable in handgrip strength studies, the composition of all-cause mortality tends to be more complex. For example, accidental death may not be intrinsically related to grip strength, so if accidental death accounted for a substantial proportion during the study, it is likely to affect the validity of the study results. Third, we only employed two widely-used relative grip strength indicators (HGS/BMI, MGS/weight), exploring other combinations such as MGS/BMI or HGS/weight may also be of great value in the future. Finally, although we have accounted for as many confounding factors as possible, residual confounding still exists.