Multimorbidity Patterns and Association with Mortality in 0.5 Million Chinese Adults

Multimorbidity Patterns and Association with Mortality in 0.5 Million Chinese Adults

Multimorbidity, defined as the coexistence of two or more chronic diseases in an individual, is a growing public health concern worldwide. While the prevalence of multimorbidity increases with age, it is not limited to older adults, as more than half of individuals with multimorbidity are under 65 years old. Multimorbidity is associated with increased risks of functional decline, polypharmacy, disability, hospitalization, and mortality, placing a significant burden on healthcare systems. Understanding the patterns of multimorbidity and their association with mortality is crucial for developing effective prevention and treatment strategies. This study aimed to identify multimorbidity patterns and examine their associations with mortality risk among middle-aged and older adults in China, using data from the China Kadoorie Biobank (CKB).

The study included 512,723 participants aged 30 to 79 years from the CKB, a large prospective cohort study conducted in ten regions across China. Multimorbidity was defined as the presence of two or more of 15 chronic diseases, which were assessed through self-report, physical examination, or blood tests at baseline. The chronic diseases included hypertension, diabetes, coronary heart disease, stroke or transient ischemic attack, tuberculosis, asthma, chronic obstructive pulmonary disease (COPD), gallstone disease, peptic ulcer, cirrhosis/chronic hepatitis, chronic kidney disease, cancer, neurasthenia, psychiatric disorder, and rheumatoid arthritis. Hierarchical cluster analysis was used to identify multimorbidity patterns, and Cox regression models were employed to estimate the associations of these patterns and the number of chronic diseases with all-cause and cause-specific mortality.

The study found that 15.8% of participants had multimorbidity, with the prevalence increasing with age and being higher in urban compared to rural areas. Among participants aged less than 50 years, 6.4% had multimorbidity, while the prevalence rose to 17.0% in those aged 50 to 59 years and 31.8% in those aged 60 years and older. Urban participants had a higher prevalence of multimorbidity (18.7%) compared to rural participants (13.5%), and there was no significant difference in prevalence between men (16.3%) and women (15.5%).

Four distinct multimorbidity patterns were identified through hierarchical cluster analysis. The first pattern, cardiometabolic multimorbidity, included diabetes, coronary heart disease, stroke, and hypertension, and was observed in 6.0% of participants. The second pattern, respiratory multimorbidity, comprised tuberculosis, asthma, and COPD, and was present in 0.4% of participants. The third pattern, gastrointestinal and hepatorenal multimorbidity, included gallstone disease, chronic kidney disease, cirrhosis, peptic ulcer, and cancer, and was found in 0.8% of participants. The fourth pattern, mental and arthritis multimorbidity, consisted of neurasthenia, psychiatric disorder, and rheumatoid arthritis, and was observed in 0.2% of participants. Additionally, 0.2% of participants had more than two patterns of multimorbidity, 8.2% had no specific patterns, and 84.2% did not have multimorbidity.

Participants with cardiometabolic multimorbidity were more likely to be older, live in urban areas, and have lower levels of physical activity, higher body mass index (BMI), and larger waist circumference. Those with respiratory multimorbidity were more likely to be men, while participants with mental and arthritis multimorbidity were predominantly women. The patterns of multimorbidity varied slightly across subgroups, with differences observed between men and women, urban and rural residents, and younger and older participants.

The study also examined the observed and expected prevalence of disease pairs and their association with mortality. The most strongly associated disease pairs were psychiatric disorder and neurasthenia (observed/expected ratio = 8.00), followed by asthma and COPD (observed/expected ratio = 6.00). The disease pair with the highest mortality risk was cirrhosis and cancer (hazard ratio [HR] = 5.09), followed by diabetes and stroke (HR = 3.41).

During a median follow-up of 10.8 years, 49,371 deaths occurred, including 18,421 deaths from cardiovascular diseases (CVD), 4,652 deaths from respiratory diseases, 15,750 deaths from cancer, and 10,548 deaths from other causes. Compared to participants without multimorbidity, those with cardiometabolic multimorbidity had the highest risk of all-cause mortality (HR = 2.20), followed by respiratory multimorbidity (HR = 2.13) and gastrointestinal and hepatorenal multimorbidity (HR = 1.33). No significant increase in mortality risk was observed for participants with mental and arthritis multimorbidity (HR = 1.18), possibly due to the small number of deaths in this group. Participants with two or more patterns of multimorbidity had a two-fold increased risk of mortality (HR = 2.21), while those with no specific patterns had a 46% higher risk (HR = 1.46).

The study also found a dose-response relationship between the number of chronic diseases and mortality risk. With each additional chronic disease, the risk of mortality increased by 36% (HR = 1.36). Compared to participants without any chronic diseases, those with one, two, three, and four or more diseases had HRs of 1.59, 2.25, 2.69, and 3.19, respectively, for all-cause mortality.

In cause-specific mortality analyses, participants with cardiometabolic multimorbidity had the highest risk of death from CVD (HR = 2.98), followed by those with respiratory multimorbidity (HR = 1.34). For respiratory disease mortality, participants with respiratory multimorbidity had the highest risk (HR = 7.16), followed by those with cardiometabolic multimorbidity (HR = 1.87). For cancer mortality, participants with gastrointestinal and hepatorenal multimorbidity had the highest risk (HR = 1.74).

The findings of this study highlight the importance of addressing multimorbidity in the Chinese population, particularly cardiometabolic and respiratory multimorbidity, which pose the highest threats to mortality. The results suggest that prevention efforts should target shared risk factors and that clinical guidelines should be developed to manage patients with multiple chronic diseases. Future research should explore the underlying mechanisms of multimorbidity and its impact on health outcomes.

In conclusion, this study provides valuable insights into the patterns of multimorbidity and their association with mortality in a large cohort of Chinese adults. The identification of specific multimorbidity patterns and their varying risks of mortality underscores the need for tailored interventions to reduce the burden of multimorbidity and improve health outcomes in the population.

doi.org/10.1097/CM9.0000000000001985

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