Chronic diseases spectrum and multimorbidity in elderly inpatients based on a 12-year epidemiological survey in China

Population aging has been steadily increasing worldwide. By the end of 2022, there were 209.78 million people aged 65 or above in China, accounting for 14.9% of the total population. Meanwhile, it is estimated that in the year 2057, the number of elderly will reach a peak at 425 million, accounting for 32.9%-37.6% of the national population [1, 2]. Since aging is accompanied by a decreased reserve function of multiple organs as well as an increased prevalence of multiple chronic diseases, the elderly can be challenged to maintain good health and quality of life [3, 4].

Multimorbidity, defined as the presence of two or more long-term physical or mental health conditions, which cannot be currently cured but can be improved with multidisciplinary management, has been an increasingly prominent issue associated with population aging [5‐7]. A previous meta-analysis showed that the prevalence of multimorbidity widely varied across studies, around 20–30% when the whole population was considered but from 55 to 98% when only older persons were included [8]. The prevalence of multimorbidity increases with age and varies widely across studies. A previous systematic review revealed that there was an S-shaped curve for the association between age and prevalence of multimorbidity. Before the age of 40 years, the prevalence was about 20% or lower and then increased dramatically, which eventually reach a plateau of 75% at the age of 70 years [9]. Another study focusing on the mortality related to multimorbidity revealed that patients with multimorbidity had a 37% increased risk of death [10]. Compared to patients with a single condition, multimorbidity patients have an increased risk of functional decline, poorer quality of life, longer hospital stay, and increased healthcare costs [11, 12]. In addition, several studies on patterns of multimorbidity showed that hypertensive diseases were the most frequent condition in multimorbidity pattern, followed by diabetes mellitus and arthropathies, and the most frequent single disease conditions identified in patients with multimorbidity were hypertensive diseases, diabetes mellitus, cerebrovascular diseases, heart diseases, arthropathies, and chronic lower respiratory diseases [13].

Additionally, as the number of diseases increases, the number of drug prescriptions tends to increase. Polypharmacy, which is common among elderly patients with multimorbidity, is stated as the concurrent use of multiple medications [14]. While there is no consensus on the medication threshold, polypharmacy is often commonly defined as concomitant use of 5 or more medications [15, 16]. Previous studies have revealed that polypharmacy was associated with numerous poor health outcomes, including an increased risk of hospitalization and death, which was probably related to drug interactions and non-adherence [15, 17, 18].

Despite multimorbidity is strongly associated with premature death, higher hospitalization rate, worse health outcomes and higher healthcare costs, most guidelines on the management of patients with multimorbidity remain focusing on single diseases [19, 20]. To date, a previous study has focused on the patterns of multimorbidity to recognize associations between common diseases in a longitudinal study among Chinese community population [21]. However, the comprehensive analysis of diseases spectrum, multimorbidity, polypharmacy, organ dysfunction and mortality of elderly inpatients is relatively scarce. Therefore, it is urgent to conduct a comprehensive investigation on the profile of common diseases and multimorbidity of elderly inpatients, so as to guide the rational allocation of limited medical resources to meet the healthcare needs of the elderly.

In this study, we collected the clinical data of elderly inpatients aged ≥ 65 years in Chinese PLA General Hospital from 2008 to 2019, and further analyzed the constitution of common diseases, comorbidities, and the status of multimorbidity of the study population. In addition, we collected oral drug prescriptions and analyzed the oral medications taken by the study population to clarify the profile of polypharmacy in the elderly inpatients, ultimately aiming to provide supporting evidence for the comprehensive management of the elderly inpatients.

In this study, we retrospectively analyzed the disease composition, the status of multimorbidity and polypharmacy of the elderly inpatients aged ≥ 65 years old in Chinese PLA General Hospital from January 2008 to December 2019. The average age of the study population was 72.67 years old. We counted the constitution of common diseases and multimorbidity based on items of discharge diagnoses. The results showed that malignant tumor ranked high among the study population, followed by hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease, which were similar to the results of previous global studies on the burden of chronic diseases. A previous study pooled a total of 90,758 subjects derived from 75 articles and found that hypertension, hyperlipidemia, diabetes mellitus, heart disease, cerebrovascular disease and COPD are the most prevalent diseases in Chinese officers aged 60 years and over [23]. The fine distinction between our study and the cited article is mainly due to the difference in the study population. We focused on elderly inpatients, who are more likely to be hospitalized for malignant tumor, while administration staff are more likely to seek medical services in outpatient clinics instead of undergoing inpatient therapy for the management and follow-up of chronic diseases. It is also worth noting that hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease are most prevalent in both studies. Therefore, it is in urgent need to carry out primary or secondary prevention and early screening of cardio-cerebrovascular diseases for the elderly whether in community population or hospitalized inpatients. For elderly patients who have been diagnosed with common chronic diseases, it can be helpful to strengthen the management of these diseases, emphasizing the monitoring and controlling of blood pressure, glucose, lipid and other risk factors related to common chronic diseases. In recent years, a large number of studies have focused on life habits which are considered to be associated with cardiovascular diseases, metabolic diseases and other common chronic diseases in the elderly. Physical activity, sedentary behavior and weight control are the most concerned factors. A recent study revealed that the risk of type 2 diabetes mellitus (T2DM) could be significantly reduced with only six minutes of moderate-to-vigorous physical activity. In addition, the longer the duration of exercise, the lower the risk of T2DM [24]. As for weight control, previous studies suggested an association between the magnitude of weight loss and the incidence of cardiovascular disease in people with type 2 diabetes [25].

The proportion of malignant tumor in aged and super-aged elderly inpatients exhibited a declining trend. This finding could be due to the following reasons: Firstly, the overall survival of malignant tumor is less than other chronic diseases such as hypertension and respiratory diseases, and a large portion of elderly patients diagnosed with cancer can not survive over 80–85 years old. Secondly, aged and super-aged patients with malignant tumor are more likely to rehabilitate at home instead of being hospitalized because of poor physical condition, more and severe complications, as well as reduced willingness [26]. Additionally, we focused on the diseases of which the proportion presenting an overall upward trend in both male and female patients, including other types of heart disease and respiratory disease. In this part, the other types of heart disease referred to various types of arrhythmia, heart failure, cardiomyopathy, cardiac valvular disease, cardiac death and other heart diseases except for ischemic heart disease which has been clarified separately. Since the compensatory and reserve function of organs tends to deteriorate with age, the elderly are much more prone to develop complications due to primary diseases. Therefore, the proportions of various heart diseases, such as secondary arrhythmia, primary and secondary heart failure showed upward trends in general. When it comes to respiratory disease, we analyzed common respiratory diseases in the elderly inpatients, including chronic obstructive pulmonary disease, emphysema, bronchiectasis, asthma, bronchitis, and pneumonia. Based on the analysis of specific categories, we found that the proportion of pneumonia significantly elevated with age. It is widely acknowledged that pneumonia is one of the leading causes of morbidity and mortality in elderly patients. The increased frequency of pneumonia can be explained by the physiological changes linked to the progressive aging of the respiratory tree and the diminished immunological response [27]. Therefore, we should be vigilant about the occurrence of multiple complications, assess the risk in the early stage and take active measures to prevent complications. For example, we should pay attention to body position to avoid aspiration, and strengthen oral care to reduce the risk of pneumonia for elderly inpatients.

When it comes to the causes of hospitalization, we found that malignant tumor and ischemic heart disease still ranked high, while other diseases were not mentioned in the list of top 10 diseases, such as arthropathy, lens disease, and biliary and pancreatic disease in males, as well as arthropathy, lens disease, and injuries to hip and thigh in females. Therefore, we can infer that although the incidence of diabetes mellitus and hypertension is relatively high among the elderly inpatients, a large number of patients were admitted to hospitals with arthropathy and lens disease rather than such stable chronic diseases. The proportion of arthropathy showed a downward trend while injuries to hip and thigh presented an upward trend in female inpatients. According to previous reports, the onset of osteoarthropathy in females was most common at the age of 40 to 65, which may be related to the decline in the proportion of patients hospitalized for arthropathy with age in our study [28]. According to statistics, about 20 million elderly people in China have at least one fall every year, with direct medical costs exceeding 5 billion RMB. Meanwhile, falls have become the leading cause of injury-related death in the elderly [29, 30]. The most common injury associated with falls in the elderly is osteoporotic fracture [31]. Injuries of hip and thigh is mostly found in elderly patients aged over 72 years, with more than 90% attributable to falls, which is regarded as the leading cause of hospitalization after falls. It is worth noting that the prevalence of falls in females is significantly higher than in males. The underlying reason is osteoporosis caused by the decrease of estrogen levels in postmenopausal females, which is strongly related to an elevated incidence of falls, contributing to the increased risk of hip and thigh injuries [32]. A large number of elderly patients hospitalized for hip and thigh injuries are prone to serious complications such as pulmonary infections and deep vein thrombosis because of prolonged recumbency. Injuries of hip and thigh and related complications greatly increase the burden of diseases among elderly female inpatients.

In this study, the number of elderly inpatients with two or more chronic diseases accounted for 91.89%, which was similar to a foreign study, suggesting that the proportion of multimorbidity among the elderly could be as high as 95.1% [33]. We have found that malignant tumors have the highest burden of > 5 comorbidities, which was shown in Fig. 4. In view of the cancer statistics, lung cancer and liver cancer are the most prevalent in China [34]. According to the data of malignant tumor sites in the analysis of death causes, we can roughly guess that lung cancer and liver cancer are the most prevalent sites of malignant tumors in this study, so the proportions of patients combined with liver diseases and respiratory diseases are relatively high, while in patients with no malignant tumor, including patients with hypertension, ischemic heart disease, cerebrovascular disease and diabetes, the proportion combined with liver diseases and respiratory diseases are relatively low. Among these patients, the diseases combined are mostly cardiovascular, cerebrovascular diseases and metabolic diseases which are common in the whole elderly population, which may be one of the reasons for the high number of complications in patients with malignant tumor. Taking lung cancer patients as an example, previous studies have revealed that many patients develop respiratory diseases before the diagnosis of lung cancer, among which, COPD is the most common comorbidities of lung cancer, and it is associated with a significant increase in the incidence of lung cancer. A study indicated that the incidence of combined lung cancer and COPD is as high as 52% [35]. Besides, we believe that it can be attributed to the underlying diseases distribution of the study population, the organ injuries such as malnutrition, infection, diabetes, kidney dysfunction caused by cancer itself, adverse reactions to antitumor therapy, drug cardiotoxicity and so on.

We have analyzed the most prevalent types of multimorbidity and have noticed that the patients with combined malignant tumor and hypertension accounted for a large proportion. A previous study suggested that hypertension is the most common comorbidity in elderly patients with malignant tumor, with an incidence of 38% [36]. Besides, a cohort study in Canada indicated that among 6000 cases of survived cancer patients, 43% developed hypertension. Except for hypertension, heart failure and other cardiac conditions were associated with cancer. Studies have shown that patients with cancer have an 8.2-fold increased risk of cardiac death, and long-term cancer survival patients have a 15-fold increased risk of heart failure [37‐39]. The possible reasons were listed as follows: Firstly, cancer and hypertension are both common diseases due to the aging of the population. Secondly, with the advances in medical technology, the survival rate of cancer patients obviously elevated in recent years [40]. Thirdly, several risk factors of hypertension, such as obesity, smoking and a sedentary lifestyle, are also related to the development of cancer [41]. Additionally, previous studies have shown that cancer survivors had a substantially higher risk of hypertension and heart failure, which might be attributable to the exposure to cardiotoxic chemotherapy agents in cancer patients, such as anthracyclines,5-fluorouracil, paclitaxel, erythritol-elastic oncogene B-2 (ErbB2) and other types of chemotherapy agents, which cause injury to endothelial cells and cardiomyocytes, eventually leading to the development of hypertension, heart failure and even cardiac death [42, 43]. This might be one of the crucial reasons explaining the mechanism of cancer-related hypertension and other cardiovascular diseases. When it comes to the interactions between cancer and hypertension, both malignant tumor and hypertension are proliferative and inflammatory diseases, thus promoting each other and progressing rapidly [44]. Secondly, hemodynamic changes and the features of being prone to form thrombosis caused by hypertension accelerate tumor progression and metastasis [45]. To sum up, there is plenty of evidence supporting the high prevalence of combined malignant tumor and hypertension. In addition, it is in urgent need for oncologists and cardiologists to raise awareness of cardiovascular complications in cancer patients. A comprehensive and patient-targeted strategy might be helpful with cardiovascular health maintaining, as well as a better prognosis in cancer patients.

For elderly patients with multimorbidity, we need to pay attention to the general condition and the status of multi-system diseases. Moreover, the elderly are susceptible to various diseases because of the reduced reserve capability and compensatory function of the organism, eventually leading to multi-organ dysfunction [46]. The number of patients with heart failure complicated with renal failure ranked high, accounting for more than 50%. Firstly, a previous study showed that the number of patients with chronic kidney disease (CKD) is increasing worldwide, and CKD has been regarded as a global epidemic enhanced by increasing rates of diabetes and hypertension. In turn, hypertension and diabetes were associated with renal failure and heart failure, which has been found as a complication of advanced renal disease [47]. Data obtained from the death registration system of the National Health Commission of China revealed that circulatory, cancer, respiratory disease and diabetes caused most of the chronic disease-associated deaths. Which was partially consistent with the findings in our study. Therefore, we believe that it is crucial to pay more attention to the elderly, closely monitor the indicators of organ function, and identify high-risk patients, so as to realize timely attention, evaluation and intervention, with the ultimate goal of improving the outcome.

In terms of medication, the top 10 drugs used in the study population were antihypertensive, cholesterol-lowering drugs and antiplatelets. Calcium channel blockers are the most commonly used drugs in elderly patients with hypertension, followed by β-blockers, angiotensin receptor inhibitors, and angiotensin-converting enzyme inhibitors. Antiplatelets including aspirin and P2Y12 receptor antagonists (clopidogrel bisulfate + ticagrelor) are also commonly used in elderly inpatients. It is worth noting that the study population took an average of 5.4 kinds of drugs, and over 50 percent of patients took more than 5 kinds of medications. Polypharmacy is often defined as the long-term use of more than five kinds of prescribed drugs daily [48]. In clinical practice, polypharmacy might be reasonable and beneficial for patients with multimorbidity. However, the risk of inappropriate prescribing related to polypharmacy significantly increased, leading to adverse outcomes [18]. Therefore, it is necessary to pay attention to the adverse effects of multiple drugs, especially in patients with multimorbidity, such as the cardiotoxicity of antitumor agents, and bleeding disorder associated with antiplatelet drugs during the perioperative period, etc. Consequently, multi-disciplinary treatment (MDT) is essential for elderly patients with multimorbidity, and an individualized comprehensive therapeutic strategy should be developed, so as to avoid the risk of adverse effects caused by inappropriate prescription and eventually improve outcomes.

Our investigation should be interpreted in the context of several limitations. Firstly, our study was designed as a baseline full-sampled survey without standardized follow-up and could not provide supporting evidence on the risk of diseases, nor on causal relationships. Secondly, the data were obtained from a single center and only inpatients were enrolled in our study. Besides, we have not included data since the outbreak of COVID-19. Therefore, it would be beneficial to collect follow-up data in future study. If permitting, we are planning to get clinical data of inpatients and outpatients from multiple clinical centers, so as to make the reported results more representative and universal. Meanwhile, it would be meaningful to analyze the variations of common diseases and multimorbidity before and after COVID-19 to figure out the impact of COVID-19 on diseases spectrum. Despite the limitations listed above, it is a large-scale full-sampled survey over 12 years, including diseases spectrum, multimorbidity, polypharmacy and cause of death in the past decade, providing supporting evidence for reasonable treatment strategy in the elderly inpatients. Meanwhile, we focused on elderly inpatients, who are likely to develop more comorbidities and have a worse prognosis compared to the elderly in community or outpatient clinics, distinguished from most of the previous studies.

In this study, we analyzed the disease spectrum including common diseases and multiple organ failures, the profile of multimorbidity, death causes and oral medications among the elderly inpatients in the past decade. It is suggested that we should adopt active measures to prevent the development and progression of multiple chronic diseases in the elderly, pay attention to the comprehensive management of common chronic diseases such as malignant tumor, hypertension, ischemic heart disease and diabetes mellitus, strengthen MDT, and formulate rational drug use plan and treatment strategy for elderly patients with multimorbidity.