This cohort study demonstrates that multimorbidity has a positive association with all-cause mortality. The results from sensitivity analyses were robust. In the LTCs ≥ 2 category, the chronic disease combination that included hypertension, diabetes, CHD, COPD, and stroke had the greatest impact on mortality. In the stratified model by age and sex, absolute all-cause mortality was higher in the age group ≥ 75 years, but the relative magnitude of the effect on mortality risk was greater among those < 75 years.
The higher all-cause mortality risk among participants with 1, 2, and ≥ 3 LTCs found in this study is consistent with previous studies that have focused on older adults[26, 27]. The study of Martinez-Gomez et al. observed significant upward trends with 1 LTC (HR 1.26), 2 LTC (HR 1.78), and ≥ 3 LTC (HR 2.27) than those without LTC. Similarly, Nunes et al. conducted a meta-analysis of 26 studies and observed similar effect sizes. And we also found that LTCs combinations were most strongly associated with all-cause mortality relative to the number of multimorbidity alone, whereas previous studies mainly focused on the role of a single disease in death, such as diabetes. Moreover, the present study found that hypertension was the most frequent occurrence, with presence in 11 of the 16 different combinations, suggesting that there may be a potential link between hypertension and a variety of chronic diseases. However, a large sample of participants aged 40 to 69 years study based on 36 chronic conditions showed that conditions such as hypertension, diabetes, and asthma were at the center of common multimorbidity. These findings suggest there is a need for further research to explore the links between these diseases and their possible interactions, which is of great significance for the guidance and treatment of multimorbidity, and also provides a theoretical basis for the formulation of health management measures and allocation of medical resources for the elderly population to some extent.
A prospective population-based cohort study of England people aged 37 to 73 years shown that participants in the younger age group 37–49 years with ≥ 4 LTCs had the highest relative risk of all-cause mortality. And we found that the association on risk of all-cause mortality with an increasing number of LTCs was particularly evident among younger age groups (< 75 vs ≥ 75 years old), which not only fills in the gap of the age of participants, but also is basically consistent with the trend of previous studies. This study found that female had a higher prevalence of multimorbidity than male, which was consistent with previous findings[29, 30]. However, the observed magnitude of mortality effect size was similar for both female and male. Potential explanations for the phenomenon are that females are generally more sensitized to their health, more likely to report more conditions, and more likely to engage in preventive health behavior. These findings suggest the need for early intervention to manage and prevent chronic diseases and to reduce the prevalence of multiple diseases as much as possible.
Studies have shown that the causes of death from multimorbidity can be attributed to 4 major underlying risk factors: smoking, alcohol consumption, underweight, and physical inactivity[11, 33]. While previous studies found that smoking was a risk factor for all-cause mortality, our results found no statistically significant difference, which is possibly explained by the quitter bias (people may stop smoking because they are in poor health and may be advised not to continue). The results of the risk study on alcohol consumption were basically consistent with the results of Ortolá et al., which showed that there was no statistically significant difference in mortality between light-to-moderate alcohol consumption and no alcohol consumption among people over 60 years old. As well, we found the greater all-cause mortality risk among persons with underweight (BMI < 18.5 kg/m2) in this study, which agreed with previous studies[21, 35, 36]. In addition, this study suggests that physical activity is associated with a lower mortality risk, and the underlying mechanism behind this finding may be that physical activity delays disease progression by preventing many chronic diseases, including diabetes, cardiovascular and respiratory diseases, and some types of cancer. Therefore, once any of these chronic conditions is diagnosed, physical activity is often incorporated into treatment plans to improve quality of life and survival[26, 37, 38].
Our study has several strengths. First, the determination of chronic diseases was relatively accurate and comprehensive, including the self-reported condition of participants and the diagnosis made by the physician based on the professional comprehensive examination. Second, our study was also novel in that we explored combinations of multimorbidity that were associated with the highest risk of death. In addition, it is more convincing to assess the relationship between multimorbidity and all-cause mortality based on a large sample size. Finally, the main results remained robust after conducting sensitivity analyses. However, the study has some limitations. Since we included only seven chronic diseases registered at baseline, some other diseases associated with older people such as hyperlipidemia and arthritis could not be taken into account, which may underestimate the prevalence of many diseases in this study, and there was no way to estimate the severity of conditions as well. Another restriction is that our participants were people over 65 years, which should caution generalizing our findings to younger age groups. In addition, although we adjusted for various covariates, there is still a possibility of residual confounding, such as diet factors. Last, recall bias is unavoidable in self-reported information.