The Associations Between Mental Disorders and Cascade of Care in Managing Hypertension, Diabetes, Dyslipidemia, Chronic Kidney Disease in China: A Pooled Cross-Sectional Analysis

Physical non-communicable diseases (NCDs) and mental disorder are a rapidly increasing health burden in low-and middle-income countries. This study aims to examine the relationships between mental disorder and cascade of care in managing four common physical NCDs (hypertension, diabetes, dyslipidemia, chronic kidney disease) in China. We utilized two waves of nationally-representative China Health and Retirement Longitudinal Study (CHARLS 2011, 2015) of older adult population aged 45 and above. A series of multivariate mixed-effect logistic regression was applied to evaluate the association between presence of mental disorder and physical chronic disease awareness, treatment, and control. We found that the odds of dyslipidemia (AOR=2.88, 95% CI=2.21-3.74) and kidney disease awareness (AOR=4.14, 95% CI=2.95-5.81) were higher for individuals with mental chronic conditions, compared to those without mental chronic conditions. The odds of having hypertension treatment was higher for subjects with mental disorder, compared to those without (AOR=1.57, 95% CI=1.23-2.01). The odds of having physical chronic conditions controlled was not signicantly associated with having mental chronic conditions. These results indicated that adults with mental disorder have a greater likelihood of awareness of having dyslipidemia and kidney disease, and receiving treatment for hypertension. Strategies to address growing burden of physical-mental NCDs in China should include efforts to improve management of patients with comorbid health condition and improve access to continual high-quality treatment after the rst diagnosis. 24 . triglyceride (high lipoprotein mg/dl; (low density lipoprotein mg/dl; (total mg/dl; self-report 25 . as: 2 ; self-report a GFR . prevention and treatment of patients with multiple NCDs. Health care delivery need to shift away from the current vertical approach of treating single-disease models to the one that emphasize on horizontal integration that aims to provide more effectively management for patients with multiple NCDs, including co-existing physical and mental NCDs. Overall, our study provides evidence on the impact of comorbid mental health condition on the management of physical NCDs in China. Further research is required to better understand the epidemiology of co-existing mental-physical NCDs and associated impacts on management of the conditions and associated costs and health outcomes in LMIC settings.


Introduction
The co-occurrence of physical and mental non-communicable diseases (NCDs) is increasing rapidly in low-and middle-income countries 1 . China, the most populous country and the second-largest economy in the world, has seen rapid demographic and epidemiological transition over the last few decades. By 2050, the projected proportion of the older population, aged 60 years and over, will dramatically increase to 35.1% from 16.2% in 2017. 2 Findings from the China Mental Health Survey suggested that the prevalence of mental disorders was 9.3% in 2013 among Chinese adults, and most mental disorders have become more common over the last 30 years 3 . The rising prevalence of physical and mental chronic conditions is expected to post signi cant challenges to the health system in China.
The potential impact of mental disorder on the cascade of care in managing physical NCDS is an emerging area of research interest. The UK National Institute from Health and Care Excellence (NICE) guidelines on multimorbidity have emphasized the challenge of poor management of chronic conditions in adults, which could subsequently be associated with higher treatment burden and poorer QoL. 4,5 The literature on the impact of having multimorbidity on the management and control of each of the chronic conditions is scarce, with current studies largely from HICs that use qualitative methods. [6][7][8][9][10] There is also some quantitative research in the literature that have investigated how having more comorbid NCDs in uences management and control of speci c conditions, primarily hypertension. 11,12 Furthermore, a limited number of studies, mostly from HICs as well, have focused on the differential impact of concordant versus discordant conditions on the quality of chronic disease management. 5,13−17 While it may be hypothesised that concordant conditions would facilitate the management of a NCD due to the similar pathophysiology and treatment regiments, and discordant NCDs would have opposite effects, existing studies demonstrate inconsistencies on how concordant and discordant NCDs in uence the management of chronic diseases. 5,14,17 To illustrate, a retrospective cohort study in the United States on hypertensive primary care patients examined the impact of concordant versus discordant NCDs of hypertension, on hyperlipidemia management. 13 This study showed that additional discordant conditions were associated with lower odds of hyperlipidemia management compared with no discordant NCDs, and additional concordant conditions were associated with increased odds of hyperlipidemia management. 13 Another study analysed 15,000 patients from primary care practices in the United States who have multimorbidity and uncontrolled hypertension, and found that patients with more discordant NCDs to hypertension (28 conditions including arthritis and emphysema) were less likely to have their uncontrolled hypertension solved, compared to those with concordant conditions. 15 Our recent paper which also analysed WHO SAGE found that having more NCDs was associated with better odds of diagnosis but not better management and control of co-occurring NCDs. 18 Importantly, generating more research from MICs is crucial as the ndings from HICs may not able applicable, due to different health systems and access to healthcare for diagnostic testing and treatment. 6,10,14,19 In addition, impact of a broader range of NCDs needs to be investigated. 5,11,12,14,16,17 This study examines individuals in China with multimorbidity that consists of both physical and mental health chronic conditions. Speci cally, we investigate how having mental health conditions is associated with cascade of care in managing four common physical NCDs (e.g. hypertension, diabetes, dyslipidemia, chronic kidney disease) of the elder adult population in China.

Participants and sample
This study is analysed pooled cross-sectional data of the rst wave (2011) and third wave (2015) of China Health and Retirement Longitudinal Study (CHARLS). We have registered in CHARLS website and get the permission from Peking University of using this dataset. All participants of CHARLS have signed consent forms before face-to-face interview and all kinds of personal information, like ID, address, are coded as a string of numbers.
The CHARLS consists of nationally representative participants aged 45 or older from 450 randomly selected communities/villages in 28 provinces of China 20 . It collects information on demographics, family, health status and functioning, health care and insurance, income, work, and housing.
Respondents of CHARLS are followed up every two years via face-to-face computer-assisted personal interview (CAPI) 20 . Biomarkers for chronic diseases were used in each wave, while blood tests were conducted every two waves 21 . Additional information about CHARLS are available on http://charls.ccer.edu.cn/"http://charls.ccer.edu.cn/.
17,708 subjects participated the rst wave (2011) and 20,967 participated the third wave (2015). For those participants, 14,574 participated both the rst and third wave (2015). After excluding subjects with missing data on demographic characteristics, health status and functioning, insurance, biomarker and blood test result, the nal sample size in our study is 17,141, which include 8,189 observations in the rst wave and 8,952 observations in the third wave.

Variables
Chronic conditions CHARLS collected information on 14 NCDs, including hypertension, dyslipidemia, diabetes, chronic lung disease (CLD), liver disease, heart disease, stroke, kidney disease, stomach disease, emotional problem, memory problem, arthritis and asthma.
Four of the 14 NCDs, hypertension, diabetes, dyslipidemia and kidney disease were assessed via biomarkers result or blood tests. Hence this study only included these 4 NCDs to examine the outcomes on awareness, treatment, and control.
For hypertension, subjects were aware of the chronic condition if they answered a rmatively to "have you been diagnosed with hypertension by a doctor?" or "do you know if you have hypertension?", For diabetes, dyslipidemia, and kidney disease, subjects were aware of the chronic condition if they answered a rmatively to "have you been diagnosed with [chronic condition] by a doctor?" Respondents self-reported treatment if they answered a rmatively to "are you now taking any of the following treatment to treat […] or its complication?".

Predictor variables
The predictor variable in this study is having a mental disorder. Having mental disorder was de ned as the existence of any one of those following conditions (1) answer a rmatively to "have you been diagnosed with emotional, nervous, or psychiatric problem by a doctor?" (2) answered a rmatively to "have you been diagnosed with memory-related disease by a doctor?" (3) 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10) higher than 12 22 . This study only included respondents answered at least 9 items on CES-D-10, and used the average of the remaining 9 items to impute the missing item.

Outcome variables
Awareness Having awareness of the chronic condition is de ned as being diagnosed by doctors or being self-aware of their chronic conditions. For hypertension, blood pressure was measured three times for each participant and this study only included participants with at least two results on systolic blood pressure and diastolic blood pressure to minimize measurement error. This study revised WHO de nition for hypertension to meet the questionnaire design 23 . Participants with hypertension are de ned as the existence of one the following conditions: (1) average systolic blood pressure ≥ 140 mmHg; (2) average diastolic blood pressure ≥ 90 mmHg; (3) self-report hypertension diagnosed by a doctor or self-report aware of hypertension. Hypertension awareness is de ned as respondents with hypertension and their hypertension is diagnosed by doctors or they aware their hypertension condition. Diabetes is de ned as: (1) fasting blood glucose ≥ 126 mg/dl; (2) non-fasting blood glucose ≥ 200 mg/dl; (3) HbA1c concentration ≥ 6.5%; (4) self-report diabetes diagnosed by a doctor 24 . Dyslipidemia is de ned as: (1) triglyceride ≥ 200 mg/ml; (2) HDL (high density lipoprotein cholesterol) < 40 mg/dl; (3) LDL (low density lipoprotein cholesterol) ≥ 160 mg/dl; (4) TC (total cholesterol) ≥ 240 mg/dl; (5) self-report dyslipidemia diagnosed by a doctor 25 . Kidney disease is de ned as: (1) GFR (Glomerular Filtration Rate) < 90 ml/min/1.72 m 2 ; (2) with self-report kidney disease diagnosed by a doctor. GFR is calculated by using Levey's method 26 . Diabetes, dyslipidemia, kidney disease awareness was de ned as respondents with diabetes, dyslipidemia, or kidney disease and these conditions are diagnosed by doctors.

Treatment
Being treated for a NCD is de ned as respondents with self-report chronic conditions diagnosed by a doctor or aware of their chronic condition and take at least one treatment for this chronic condition. For hypertension, respondents answer a rmatively to "taking Chinese traditional medicine" or "taking western modern medicine" to the question "Are you taking any of the following treatments to treat hypertension or its complication?" are considered to be with hypertension treated. For diabetes and kidney disease, respondents choose any one of the following choices "taking Chinese traditional medicine", "taking western modern medicine" or "other treatments" to question "are you taking any of the following treatment to treat (…) or its complications?" are considered to be with hypertension/kidney disease treatment. For diabetes, respondents choose any one of those choices "taking Chinese traditional medicine" "taking western modern medicine" or "taking insulin injections" to the question "are you taking any of the following treatments to treat or control your diabetes" are considered to be with diabetes treated.

Controlled
Being controlled for a NCD is de ned as respondents with self-report chronic condition, with self-report treatment and with normal biomarker or blood test result. The clinical criteria for hypertension, dyslipidemia, diabetes, and kidney disease are mentioned in the part of awareness.

Statistical analysis
Demographic characteristics of participants for year 2011 and 2015 were calculated separately. The demographic characteristics of participants with hypertension, diabetes, dyslipidemia, and or kidney disease were calculated separately for subjects with mental disorder and without mental disorder.
We estimated the prevalence of NCD awareness, treatment, and control for subjects with and without mental problem separately. Pearson chi-square test was used to test the signi cance in the difference between subjects with mental health disorder and those without mental health disorder for their awareness, treatment, and control of physical chronic conditions. A serious of unadjusted and adjusted mixed-effects logistics regressions were used to evaluate the effect of mental health disorder on NCD awareness, treatment, and control. First, we conducted unadjusted mixed effect logistics regression with NCD awareness, treatment, or control as the outcome variable and mental problem as the predicting variable. Subsequently, we tted multivariate mixed effect logistics regression with NCD awareness, treatment, or control as the outcome variable, mental problem as exposure variable, and adjusted for the covariates mentioned above.  problem. For all of the four NCDs, the prevalence of NCD awareness is signi cantly higher for people with mental disorder than people without mental disorder (p-value <0.05).
For hypertension, dyslipidemia, and kidney disease, the prevalence of those physical conditions being treated is higher for people with mental problem than without mental disorder, while this difference is not signi cant for diabetes (P-value=0.510). Although the prevalence of physical conditions being controlled is lower for people without mental disorder than people with mental disorder, the difference is not signi cant at 5% level. We presented the rst study that investigate the associations between having mental disorder and cascade of care in managing four common physical NCDs in China among older adult population in China. Our study revealed that having mental disorder was associated with increased odds of being aware of having dyslipidemia, and kidney disease, after adjusting for covariates including frequency of outpatient visit. Additionally, having mental disorder was associated with increased odds of receiving treatment of hypertension, but not for diabetes, dyslipidemia, and kidney disease. However, having mental disorder was not associated with increased or decreased odds of being controlled for hypertension, diabetes, dyslipidemia and kidney disease.

Comparison with literature
The nding on the positive effect of having mental health conditions on better diagnosis of previously undiagnosed dyslipidemia and kidney disease is consistent with the small number of existing articles. Subjects with more comorbidities likely resulted in having more frequent visits to and interactions with multiple health providers, 5,17,[27][28][29] such as dyslipidemia, and kidney disease in this particular study.
Having more comorbidities and increased frequency of healthcare visits were likely associated with a greater tendency for patients to self-report kidney pain and test blood liquid 30,31 .
Studies examined the relationship between comorbid health condition and NCD treatment have shown con icting results which may re ect complexity of the issue 5,17,[32][33][34][35] It is worth noting that our study considered only whether subjects were taking treatment or not, and did not if treatment was adequate, in terms of adherence to medication. 5,17,36 While our study showed that subjects with mental disorder have higher odds of taking treatment, but in reality, with more co-occurring physical conditions, the odds of treatment adherence and having adequate treatment would decline. 5,17 The nding on having mental health conditions not associated with increased or decreased odds of being controlled for hypertension, diabetes, dyslipidemia and kidney disease is not consistent with the little amount of existing literature. The di culty in controlling NCDs tend to be exacerbated with having more co-occurring physical chronic conditions. 9,11,15 There has been debate in the recent literature on how co-occurring conditions in uence the management and control of NCDs. 5 England. 5,14 The study revealed that only 2 of 8 discordant NCDs to diabetes were correlated with worse quality of diabetes care, and only 4 of 7 concordant NCDs with diabetes were correlated with better quality of diabetes care. 14 Hence, this study along with our previous work and other papers, provide further evidence on the complexity of how co-occurring mental health conditions impact the management and control of NCDs, and the hypothesis that concordant comorbidities with mental illness facilitate the management of NCDs and discordant comorbidities with mental illness impede the management of NCDs may be oversimpli ed. 5,17 Strengths and limitations This is the rst study that used a large population of adults from China with multimorbidity, to investigate the association between having mental health conditions with the odds of being undiagnosed, untreated and uncontrolled for co-occurring physical chronic condition.
Self-reported diagnosis of chronic conditions may be under-reported especially among the lower socioeconomic groups in China. [37][38][39] Additionally, stigma could be a reason for under-reporting of depression in MICs. 40,41 However, our study utilized clinical measurement for all physical NCDs as well as mental disorder which can mitigate under-reporting of NCDs. 42 Additionally, this survey only asked if subjects were taking treatment (medicines, lifestyle changes), but did not measure self-reported treatment adherence (i.e. dosage, frequency, duration, etc). 17,36 Biomarkers used to assess whether chronic conditions were controlled may not be su ciently comprehensive, and supplemental assessment criteria may have been needed for better accuracy. However, this survey is one of the few existing surveys that utilised biomarkers, rather than only symptom-based assessment via questions. 5,17 Future studies could expand on this study by examining more NCDs, especially conditions with high prevalence and morbidity. 5,17,43 The study's cross-sectional design means that causality could not be determined, and studies that use cohort study designs could examine how mental health conditions lead to worse treatment and control of physical chronic diseases in subjects that are followed-up over a decade. 5,17,33 Clinical, policy, and research implications Clinical guidelines must be updated to include improved screening and treatment of physical chronic conditions that may occur in patients with mental health conditions. 5,17 Regarding poorer treatment and control of mental health conditions and physical chronic diseases associated with having more NCDs, clinical guidelines could incorporate more intentional monitoring of patients' adherence to medication and treatments by clinicians. 5,17 Also proposed in our previous work, current clinical guidelines are based on evidence from controlled trials for treating single NCDs, 5,17,[44][45][46] and treatments may no longer be effective and even have adverse effects when applying single-disease guidelines to patients with multimorbidity. 5,17,47 Hence, clinical guidelines should be tailored towards an approach to multimorbidity of co-occurring mental illness and physical chronic conditions, whereby clinicians review the effectiveness and risks of combining the medications and different treatments for mental illness and physical chronic diseases. 4,5,17,44 Healthcare systems in LMICs like China may need to implement policies that improve access to care from the primary care system for continual treatment after rst diagnosis. [48][49][50][51] Policies that prioritise NCD combinations that include mental health conditions that are more prevalent or associated with poorer management and control need be considered, such as reducing costs of medicines and clinic visits. 35,52 It is worth noting that health-care delivery in China is hospital-centered and fragmented, with little coordination among health-care providers across different tiers of the system 53 . Strong primary health care, underpinned by multidisciplinary teams lead by general practitioner, is also crucial for the improved prevention and treatment of patients with multiple NCDs. Health care delivery need to shift away from the current vertical approach of treating single-disease models to the one that emphasize on horizontal integration that aims to provide more effectively management for patients with multiple NCDs, including co-existing physical and mental NCDs. Overall, our study provides evidence on the impact of comorbid mental health condition on the management of physical NCDs in China. Further research is required to better understand the epidemiology of co-existing mental-physical NCDs and associated impacts on management of the conditions and associated costs and health outcomes in LMIC settings.