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PLOS Global Public Health logoLink to PLOS Global Public Health
. 2023 Aug 16;3(8):e0002215. doi: 10.1371/journal.pgph.0002215

Cardiometabolic multimorbidity and associated patterns of healthcare utilization and quality of life: Results from the Study on Global AGEing and Adult Health (SAGE) Wave 2 in Ghana

Peter Otieno 1,2,3,*, Gershim Asiki 1,4, Calistus Wilunda 1, Welcome Wami 3,5, Charles Agyemang 2
Editor: Nasheeta Peer6
PMCID: PMC10431646  PMID: 37585386

Abstract

Understanding the patterns of multimorbidity, defined as the co-occurrence of more than one chronic condition, is important for planning health system capacity and response. This study assessed the association of different cardiometabolic multimorbidity combinations with healthcare utilization and quality of life (QoL). Data were from the World Health Organization (WHO) study on global AGEing and adult health Wave 2 (2015) conducted in Ghana. We analysed the clustering of cardiometabolic diseases including angina, stroke, type 2 diabetes, and hypertension with unrelated conditions such as asthma, chronic lung disease, arthritis, cataract and depression. The clusters of adults with cardiometabolic multimorbidity were identified using latent class analysis and agglomerative hierarchical clustering algorithms. We used negative binomial regression to determine the association of multimorbidity combinations with outpatient visits. The association of multimorbidity clusters with hospitalization and QoL were assessed using multivariable logistic and linear regressions. Data from 3,128 adults aged over 50 years were analysed. We identified four distinct classes of multimorbidity: relatively “healthy class” with no multimorbidity (47.9%): abdominal obesity only (40.7%): cardiometabolic and arthritis class comprising participants with hypertension, type 2 diabetes, stroke, abdominal and general obesity, arthritis and cataract (5.7%); and cardiopulmonary and depression class including participants with angina, chronic lung disease, asthma, and depression (5.7%). Relative to the class with no multimorbidity, the cardiopulmonary and depression class was associated with a higher frequency of outpatient visits [β = 0.3; 95% CI 0.1 to 0.6] and higher odds of hospitalization [aOR = 1.9; 95% CI 1.0 to 3.7]. However, cardiometabolic and arthritis class was associated with a higher frequency of outpatient visits [β = 0.8; 95% CI 0.3 to 1.2] and not hospitalization [aOR = 1.1; 95% CI 0.5 to 2.9]. The mean QoL scores was lowest among participants in the cardiopulmonary and depression class [β = -4.8; 95% CI -7.3 to -2.3] followed by the cardiometabolic and arthritis class [β = -3.9; 95% CI -6.4 to -1.4]. Our findings show that cardiometabolic multimorbidity among older persons in Ghana cluster together in distinct patterns that differ in healthcare utilization. This evidence may be used in healthcare planning to optimize treatment and care.

Introduction

Sub-Saharan Africa is undergoing more rapid ageing than high-income countries [1]. This poses potential critical challenges for older persons, central among them is the burden of chronic diseases [2]. People living with chronic conditions often have multiple rather than a single condition, commonly referred to as multimorbidity [3]. In Ghana, three in every five older persons aged above 50 years live with multimorbidity [4]. Cardiometabolic diseases such as hypertension and type 2 diabetes account for the highest burden of multimorbidity in Ghana [5]. Importantly, cardiometabolic diseases often coexist with other chronic diseases with unrelated pathophysiology such as mental illnesses, chronic lung diseases and musculoskeletal disorders [68]. This phenomenon is referred to as discordant multimorbidity [9].

The management of multimorbidity is complex and demanding for healthcare systems in Ghana [10,11]. This is because the current chronic disease management guidelines were developed when having a single chronic disease was common and focused on a single disease [12,13]. The recent World Health Organization [WHO] guidelines on multimorbidity question this single-disease management approach and highlight the need for accounting for all multimorbidity when informing the patient about available treatment options [14]. However, studies conducted in Ghana show that people living with multimorbidity face several challenges such as fragmented appointments, difficulties with access to information, and a lack of coherence or coordination of care [15,16]. Furthermore, therapeutic interventions for multimorbidity are a major challenge due to polypharmacy and poor medication adherence [17]. Integrated management of multimorbidity and a shift of the treatment goals towards medical care that is less disruptive may partly lower the treatment burden [18].

Previous studies show a positive association between the number of co-existing chronic conditions and frequency of outpatient visits, longer hospital stays, and poor health-related quality of life [4,1922]. However, the multimorbidity counts or indices used in the vast majority of existing studies do not provide adequate information on specific disease clusters to guide integrated care interventions [23,24]. Although the use of disease count is important in establishing the prevalence of multimorbidity, clusters of conditions that tend to co-occur non-randomly is more useful for clinical practice and health policy. Thus, a deeper insight into the multimorbidity burden on healthcare utilization that goes beyond counting the number of coexisting chronic conditions is needed [25]. Understanding multimorbidity clusters and healthcare utilization patterns is important for planning health system capacity and response to optimise healthcare resources and accommodate patient needs.

The aim of this study was to identify classes of adults with cardiometabolic multimorbidity and determine the association of different multimorbidity combinations with healthcare utilization and quality of life (QoL).

Methods

Study design

The data for this study are from the WHO Study on Global AGEing and Adult Health (SAGE) Wave 2 survey conducted in Ghana in 2015 [26]. The WHO SAGE aims to provide reliable evidence on the health and well-being of older persons aged over 50 years in low and middle-income countries [27]. The study design is provided elsewhere [28]. In brief, a stratified multistage cluster sampling method was used to collect data from a nationally representative sample of adults aged 50 years and older. Detailed descriptions of sampling methods and data collection procedures have been previously published [2830].

The original study sample comprised 3,575 older persons aged over 50 years. Participants were included in the current analysis if they had valid data on the key variables: chronic diseases such as angina pectoris, stroke, type 2 diabetes, hypertension, obesity, arthritis, asthma, chronic lung disease, depression, and cataracts and sociodemographic characteristics comprising sex, age, and employment. Participants (n = 447) for which data on key variables were not captured or judged as invalid were excluded. Since the causes of missing information were not ascertained, we did not apply missing data techniques to avoid further uncertainty in the imputation models. Thus, the final analysis included 3,128 participants.

Data collection

Data used in the current study were collected using interviewer-administered structured questionnaires [31]. Detailed information on the study tools has been published [32]. Data were collected on socio-demographic characteristics, chronic conditions, healthcare utilization and QoL. The chronic conditions comprised cardiometabolic diseases such as angina pectoris, stroke, diabetes, obesity and hypertension, and unrelated conditions such as arthritis, asthma, chronic lung disease, depression, and cataracts.

Measurement and definition of variables

Outcome variable

The outcome variables were frequency of outpatient visits, hospitalization and QoL. The frequency of outpatient visits was measured as the number of times a participant had an outpatient visit in the preceding 12 months. Hospitalization was measured as any overnight stays in the hospital that lasted for at least one night in the past 12 months. An 8-item World Health Organization Quality of Life (WHOQOL) instrument was used to assess the QoL score [33]. The WHOQOL comprises two questions across each of the four main life domains: physical, psychological, social, and environmental [33]. Using a five-point Likert scale, ranging from very satisfied to very dissatisfied, the respondents rated their satisfaction with life domains such as health, ability to perform daily activities and meet basic needs, relationships, and environment. The composite score of QoL is the sum of the 8 items from the four domains expressed as a percentage.

Explanatory variables

The main explanatory variable was cardiometabolic multimorbidity defined as the coexistence of at least two cardiometabolic diseases including obesity, angina, stroke, type 2 diabetes, hypertension or a discordant multimorbidity comprising at least one cardiometabolic disease and an unrelated chronic disease such as asthma, chronic lung disease, arthritis, cataract and depression. The multimorbidity clusters were named based on their unique dominant chronic diseases.

Self-reported history of diagnosis by a healthcare professional was extracted for cardiometabolic diseases comprising angina, stroke, type 2 diabetes, hypertension and other conditions such as arthritis, asthma, chronic lung disease, depression, and cataract. The WHO symptomatology algorithms [3436] were used to screen for angina pectoris, arthritis, asthma, chronic lung disease, and depression. S1 Table shows the details of the symptomatology algorithms. Physical measurements comprised screening for blood pressure (BP) and anthropometrics. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or previous diagnosis of hypertension by a professional health care provider and/or being on hypertensive therapy [37]. Abdominal obesity was defined using WHO guidelines as a waist circumference ≥ 94 cm for men, or ≥ 80 cm for women [38]. General obesity was defined as a body mass index ≥30.0 kg/m2 [39].

Other explanatory variables comprised sociodemographic and health characteristics such as sex, age, education, employment, health insurance coverage, primary source of care (private, public, faith-based/charity hospital) and place of residence (urban or rural).

Data analysis

Descriptive statistics comprising frequencies, means, medians, standard deviations, interquartile range, and Pearson’s chi-squared tests were used to summarize the characteristics of the study participants while accounting for sampling weights.

Latent class analysis

Latent Class Analysis (LCA) was used to place participants in a number (K) of clinically meaningful classes of cardiometabolic multimorbidity. The number of multimorbidity classes was defined a priori using the adjusted Bayesian information criterion (BIC), a model selection method that balances fit with parsimony [40]. Five plausible LCA models were delineated, characterized by increasing numbers of chronic disease classes from one to five (S2 Table). The model with the lowest value of the BIC index was selected as the best-fitting model considering interpretability and clinical judgment [40,41]. Posterior probabilities were used to determine the likelihood of class membership. Finally, the participants were grouped into the multimorbidity classes with the highest-class probability [38].

Hierarchical cluster analysis

We identified clinically meaningful clusters of multimorbidity using agglomerative hierarchical clustering algorithms [39]. Data used in our analysis are a collection of binary objects arranged in an n×p matrix. The rows represent the (n = 3, 128) study participants and the columns represent the (p = 11) chronic diseases including abdominal obesity, hypertension, general obesity, arthritis, asthma, cataract, type 2 diabetes, angina, chronic lung disease, depression and stroke. The classical approach to the analysis of multimorbidity clusters comprises the grouping of “n” study participants into a set of clusters using the proximity index among the study respondents. This yields an “n×n” proximity matrix that reflects the degree of closeness among the study participants and describes the patterns of disease clusters. However, in the current study, we analysed the multimorbidity patterns by clustering the outcome variables i.e. multimorbidity rather than the observations. This approach is more robust than the former since it reduces the transposed “p×n” data matrix to a much smaller “p×p” proximity matrix among the chronic disease outcomes compared to a potentially large “n×n” proximity matrix [42]. First, individual chronic diseases were grouped in a single cluster. Second, the individual disease clusters were gradually merged with the most closely related clusters until a single cluster with all the elements was obtained. To accommodate the spread of the cluster, we used the average linkage method [43]. Finally, we assessed the number of clusters using a dendrogram and Jaccard similarity coefficient [39].

Regression analysis

We used negative binomial regression to determine the association of multimorbidity combinations with outpatient visits. Negative binomial regression has inbuilt parameters that account for the overdispersion problem of modelling healthcare utilization frequency [44]. The association of multimorbidity combinations with hospitalization and QoL were assessed using multivariable logistic and linear regressions. Bivariable negative binomial regression, logistic and linear regression with the frequency of outpatient visits, hospitalization, and QoL as the outcome variables, were first fitted for each of the multimorbidity classes followed by a multivariable model adjusting for socio-demographic characteristics namely age, sex, education, employment status, health insurance coverage, and place of residence. Because of the clustered design of the sample, robust variance estimates (Huber-White sandwich estimator) were used for the correction of standard errors to adjust for the correlation among responses within the same household [45]. The strength of association was interpreted using the adjusted odds ratios (aOR) and 95% confidence intervals (CI) from logistics regression and beta (β) coefficients from negative binomial and linear regressions [46,47]. P values of <0.05 were considered statistically significant.

We assessed the goodness of fit of the bivariate and multivariable models using the likelihood ratio test [48].

All statistical analyses were carried out using Stata 17.0 (StataCorp LP, Texas, USA) and accounted for the complex sampling design used in the WHO SAGE survey.

Ethics approval and consent to participate

All methods were carried out in accordance with the relevant guidelines and regulations. This study was approved by the World Health Organization’s Ethical Review Board (reference number RPC149) and the Ethical and Protocol Review Committee, College of Health Sciences, University of Ghana, Accra, Ghana. The respondents went through an informed consent process and their participation was voluntary and anonymous. Written consent was provided before participation.

Results

Characteristics of participants

The sociodemographic and health characteristics of the study participants are presented in Table 1. In total, 3,128 participants were included in the analysis. In general, most of the participants were women, aged between 50–59 years [51.2%], had no formal education [41.5%], self-employed [69.7%], lived in rural areas [52.1%], and sought care from public facilities [41.4%]. Only a quarter of the participants had health insurance coverage. The most prevalent chronic diseases were abdominal obesity [47.0%] and hypertension [37.1%]. The prevalence of abdominal and general obesity, arthritis angina and depression were significantly higher in females than males.

Table 1. Sociodemographic and health characteristics of the study participants.

  Characteristics (%) Both sexes Males Females P value
- N 3,128 1,306 1,822  
Age [Years] 0.063 
50–59 51.2 52.5 50.0
60–69 27.5 28.3 26.7  
70+ 21.3 19.2 23.3  
Education <0.001 
No formal education 41.5 29.8 52.2
Primary 28.3 28.7 27.8  
Secondary 26.5 35.9 17.9  
Tertiary 3.7 5.6 2.1  
Employment <0.001
Public 7.8 11.7 4.3  
Private 4.4 6.7 2.2  
Self-employed 69.7 64.8 74.2  
Informal employment 16.2 15.2 17.2  
Unemployed 1.9 1.7 2.0  
Place of residence 0.785
Urban 47.9 47.5 48.2  
Rural 52.1 52.5 51.8  
Primary source of care 0.013
Private facility 9.3 8.8 9.6  
Public facility 41.4 37.4 45  
Faith-based/charity hospital 4.0 4.3 3.7  
Others 3.6 3.6 3.6  
Never sought care 41.8 45.9 38.1  
Health insurance coverage  
Yes 25.4 21.6 28.9 <0.001
Chronic diseases  
Abdominal obesity 47.0 16.5 74.8 <0.001
Hypertension 37.1 36.7 37.4 0.761
General obesity 13.4 5.9 20.2 <0.001
Arthritis 20.4 17.3 23.2 0.005
Asthma 8.3 8.0 8.6 0.634
Cataract 7.2 6.4 7.9 0.201
Diabetes 2.6 2.5 2.7 0.798
Angina 8.4 5.0 11.4 <0.001
Chronic lung disease 4.5 4.1 4.8 0.343
Depression 4.5 3.1 5.7 <0.001
  Stroke 1.2 1.1 1.3 0.502

Cells are weighted percentages unless otherwise specified.

Other sources of primary care comprise local pharmacies and traditional healers.

Findings of Latent Class Analysis

The multimorbidity classes are shown in Fig 1. We compared LCA models with 1 to 5 classes (online S2 Table). The four-class model had the lowest BIC index and thus was selected as the best-fit model. Class one comprised relatively “healthy participants” with no multimorbidity [47.9%]. Class two included participants with a high probability of abdominal obesity only [40.7%]. Class three comprised participants with high probabilities of hypertension, diabetes, stroke, abdominal and general obesity, arthritis and cataract [5.7%]. Class four (cardiopulmonary diseases and depression) comprised participants with high probabilities of angina, chronic lung disease, asthma and depression [5.7%].

Fig 1.

Fig 1

Hierarchical cluster analysis findings

As a supplementary analysis, we used hierarchical cluster analysis with agglomerative algorithms to compute the multimorbidity patterns. Fig 2 shows a dendrogram with a hierarchical tree plot of the multimorbidity clusters. The dendrogram shows a graphical representation of the agglomeration schedules at which multimorbidity clusters are combined. In general, our results were consistent with those obtained using LCA. The hierarchical clustering algorithms revealed distinct groupings of multimorbidity in the study sample. Based on the proximity coefficients, the first cluster comprised angina, chronic lung disease, asthma, and depression (cardiopulmonary and depression class). The second cluster comprised participants with hypertension, abdominal and general obesity, arthritis, cataract stroke and diabetes (cardiometabolic diseases, arthritis and cataract class).

Fig 2.

Fig 2

Sociodemographic distribution of multimorbidity patterns

The sociodemographic distribution of multimorbidity classes is presented in Table 2. The majority of the participants with abdominal obesity were aged between 50 and 59 years. However, most participants with cardiometabolic and cardiopulmonary multimorbidity were older (aged 60–69 years and 70 years and above). Most participants with abdominal obesity and cardiometabolic multimorbidity resided in urban settings while a majority of those with cardiopulmonary multimorbidity resided in rural settings. In general, most of the participants with abdominal obesity and those with cardiometabolic and cardiopulmonary multimorbidity were females, self-employed, had no formal education nor insurance coverage, and sought care from public facilities.

Table 2. Distribution of multimorbidity by sociodemographic characteristics in Ghana.

Characteristics [%] Latent classes of multimorbidity
Class 1: Relatively healthy/no multimorbidity diseases Class 2: Abdominal obesity Class 3: Cardiometabolic diseases, arthritis & cataract Class 4: Cardiopulmonary diseases & depression P-value
  N  1,482  1,283  166  197  
Age [years]          
  50–59 50.1 57.6 31.0 35.5 <0.001
  60–69 28.3 24.8 41.0 26.1  
  70+ 21.7 17.6 28.0 38.4  
Sex          
  Male 76.0 18.9 22.5 41.2 <0.001
  Female 24.0 81.1 77.5 58.8  
Education          
  No formal education 40.2 42.6 33.7 52.3 0.080
  Primary 27.6 29.5 34.7 19.1  
  Secondary 28.6 23.9 26.5 28.1  
  Tertiary 3.7 4.1 5.1 0.6  
Employment          
  Public 8.4 7.1 6.9 9.0 <0.001
  Private 5.6 2.1 11.5 3.5  
  Self-employed 67.1 75.5 58.7 61.1  
  Informal employment 17.1 13.9 16.5 25.2  
  Unemployed 1.8 1.4 6.4 1.2  
Residence          
  Urban 40.8 54.7 69.6 37.8 <0.001
  Rural 59.2 45.3 30.4 62.2  
Primary source of care        
  Private facility 7.5 9.5 21.5 10.5 <0.001
  Public facility 37.9 44.2 48.5 43.8  
  Faith-based/charity hospital 5.0 2.8 1.8 5.4  
  Others 4.2 3.7 0.2 1.1  
  Never sought care 45.4 39.8 28.0 39.2  
Health insurance cover        
  Yes 23.8 26.8 28.2 26.3 0.490
  No 76.2 73.2 71.8 73.7  

Cells are weighted column percentages.

Other sources of primary care comprise local pharmacies and traditional healers.

IQR; Interquartile range.

‡The multimorbidity clusters included a relatively “healthy class” with no multimorbidity [class 1]: abdominal obesity [class 2]: cardiometabolic and arthritis class comprising participants with hypertension, abdominal and general obesity, arthritis and cataract [class 3]; and cardiopulmonary and depression class including participants with angina, chronic lung disease, asthma, and depression [class 4].

Frequency of healthcare utilization and quality of life

The patterns of healthcare utilization and QoL is presented in Table 3. In general, the participants who visited outpatient clinics frequently and those hospitalized at least once in the previous 12 months were mostly older, women, lived in urban settings, sought primary care from faith-based or charity organizations, and had cardiometabolic and cardiopulmonary multimorbidity. Other participants who visited outpatient clinics frequently mostly comprised those with tertiary-level of education and health insurance coverage and employed in public or informal settings. The QoL score was lowest among older participants, females, unemployed, those with no formal education nor health insurance coverage, living in urban settings, seeking care from faith-based or charity organizations, and participants with cardiometabolic and cardiopulmonary multimorbidity.

Table 3. Healthcare utilization and quality of life in Ghana [n = 3,128].

Characteristics Outpatient visits Hospitalized Quality of life
Median IQR P-value  Yes  P-value % SD P-value
Age [years]                
  50–59 0 1 <0.001 3.6 0.028 76.3 9.5 <0.001
  60–69 1 1   4.6   73.8 9.9  
  70+ 1 1   6.3   68.3 12.1  
Sex                
  Male 0 1 <0.001 1.9 0.192 75.5 10.9 <0.001
  Female 1 1   2.6   72.4 10.3  
Education                
  No formal education 0 1   1.7 0.826 71.3 10.2 <0.001
  Primary 0 1   1.4   74.4 10.8  
  Secondary 1 1   1.2   76.5 10.3  
  Tertiary 1 2   0.2   80.0 9.7  
Employment                
  Public 1 2 <0.001 3.1 0.035 76.9 11.0 <0.001
  Private 0 1   0.2   75.2 10.7  
  Self-employed 0 1   4.4   74.2 10.3  
  Informal employment 1 2   6.2   71.3 11.5  
  Unemployed 0 2   6.7   70.0 11.3  
Residence                
  Urban 1 2 <0.001 5.3 0.068 74.9 11.1 <0.001
  Rural 0 1   3.7   73.0 10.2  
Primary source of care                
  Private facility 1 2 <0.001 9.1 <0.001 74.6 9.6 <0.001
  Public facility 1 2   7.6   72.1 10.5  
  Faith-based/charity hospital 1 3   10.6   70.6 9.9  
  Others 1 1   1.5   70.0 12.2  
  Never sought care           76.2 10.5  
Health insurance cover                
  Yes 1 1 <0.001 6.0 0.035 73.2 10.2 0.528
  No 0 1   3.9   74.1 10.8  
Multimorbidity clusters                
Class 1: Relatively healthy class/no multimorbidity 0 1 <0.001 3.8 0.128 74.7 10.4 <0.001
Class 2: Abdominal obesity 1 1   4.6   74.5 10.2  
Class 3: Cardiometabolic diseases, arthritis & cataract 1 3   5.2   68.9 11.3  
Class 4: Cardiopulmonary diseases & depression 1 2   8.1   67.5 12.4  
Total 0 1   4.5   73.9 10.7  

Cells are weighted column percentages.

Other sources of primary care comprise local pharmacies and traditional healers.

IQR; Interquartile range.

‡The multimorbidity clusters included a relatively “healthy class” with no multimorbidity (class 1): abdominal obesity (class 2): cardiometabolic and arthritis class comprised participants with hypertension, abdominal and general obesity, arthritis and cataract (class 3); and cardiopulmonary and depression class included participants with angina, chronic lung disease, asthma, and depression (class 4).

Cardiometabolic multimorbidity classes and associated healthcare utilization patterns and QoL in Ghana

Fig 3 shows the association of different multimorbidity combinations with healthcare utilization and QoL. Relative to the class with no multimorbidity, the cardiopulmonary and depression class was associated with a higher frequency of outpatient visits [β = 0.3; 95% CI 0.1 to 0.6] and higher odds of hospitalization [aOR = 1.9; 95% CI 1.0 to 3.7]. However, cardiometabolic and arthritis class was associated with a higher frequency of outpatient visits [β = 0.8; 95% CI 0.3 to 1.2] and not hospitalization [aOR = 1.1; 95% CI 0.5 to 2.9]. The mean QoL scores was lowest among participants in the cardiopulmonary and depression class [β = -4.8; 95% CI -7.3 to -2.3] followed by the cardiometabolic and arthritis class [β = -3.9; 95% CI -6.4 to -1.4].

Fig 3.

Fig 3

Discussion

In this study, we identified classes of adults with cardiometabolic multimorbidity and assessed the association of different multimorbidity combinations with healthcare utilization and QoL. Our findings show four distinct patterns of multimorbidity: relatively “healthy class” with no multimorbidity: abdominal obesity: cardiometabolic and arthritis class comprising participants with hypertension, type 2 diabetes, stroke, abdominal and general obesity, arthritis and cataract; and cardiopulmonary and depression class including participants with angina, chronic lung disease, asthma, and depression Cardiopulmonary multimorbidity was associated with a higher frequency of outpatient visits and higher odds of hospitalization compared to those with no multimorbidity. However, multimorbidity of cardiometabolic diseases, cataracts and arthritis was associated with a higher frequency of outpatient visits and not hospitalization. Participants with cardiometabolic and cardiopulmonary multimorbidity had poorer quality of life compared to those with no multimorbidity.

The multimorbidity clusters identified in our study are similar to those in previous studies [49,50]. A systematic review of multimorbidity patterns from 39 studies conducted in 12 countries identified hypertension and arthritis as the most frequent multimorbidity combination [50]. Another study conducted in South Africa found two distinct multimorbidity clusters comprising hypertension and diabetes and cardiopulmonary diseases such as angina, asthma and chronic lung disease [49]. In our study: 47.9% of the participants were classified under a relatively “healthy class” with no multimorbidity: 40.7% under the abdominal obesity class: 5.7% under the cardiometabolic and arthritis class and 5.7% under the cardiopulmonary diseases and depression class. The mechanisms that underlie the clustering of cardiopulmonary diseases and depression are not definitive. However, there is strong evidence linking inflammatory markers to both depression and cardiovascular diseases [51], but why these links exist remains unclear.

Systematic reviews conducted by Mullerova et al. [52] and Prados-Torres et al. [53], identified inflammation, stress processes, hypoxia, and environmental risk factors such as air pollution and smoking as the leading risk factors for the clustering of cardiopulmonary diseases such as hypertension, angina, chronic lung disease and asthma [52,53]. Similarly, our previous study on the patterns of cardiometabolic multimorbidity in sub-Saharan Africa identified the clustering of physical inactivity and obesity as one of the leading risk factors for cardiometabolic multimorbidity. However, the study did not include the clustering of cardiometabolic diseases with unrelated conditions such as arthritis, cataract and chronic respiratory diseases [54]. Importantly, the discordant multimorbidity clusters without well-established pathogeneses such as cardiometabolic diseases and arthritis identified in the current study should be studied in the future to elucidate the causal pathways.

Our findings show that the multimorbidity patterns among older adults in Ghana are distinct with important differences with respect to healthcare utilization and QoL. Multimorbidity of cardiometabolic diseases, arthritis and cataract was associated with higher levels of healthcare utilization than cardiopulmonary and depression multimorbidity. However, cardiopulmonary and depression multimorbidity was associated with the highest odds of hospitalization. Nevertheless, both cardiopulmonary and cardiometabolic multimorbidity were positively associated with poor quality of life compared to participants with no multimorbidity. Although these findings are consistent with previous studies conducted in low and middle-income countries [4,20,55], it is important to note that the existing studies were based on multimorbidity counts without adequate information on specific disease clusters to guide primary care. Unlike the multimorbidity counts, where all morbidities are equally scored irrespective of their relationships, our approach provides crucial insight into the burden of specific multimorbidity clusters that goes beyond counting the number of coexisting chronic conditions. In line with previous studies [4,5658], there is a possibility that QoL may have deteriorated, partly due to the treatment burden including medication intake, drug management, self-monitoring, lifestyle changes and hospitalization. However, future studies should focus on identifying the underlying causal pathways connecting distinct cardiometabolic multimorbidity clusters, healthcare utilization patterns and QoL.

Strengths and limitations

This study has three main strengths. First, data are from a nationally representative population-based survey using a standardised WHO-SAGE protocol. Thus, the findings are generalizable to the population of persons aged 50 years and above in Ghana. Second, screening for obesity, hypertension, angina pectoris, arthritis, asthma, chronic lung disease, and depression was based on objective measures comprising direct physical measurement of anthropometrics, BP, symptomatology algorithms and self-reports. Third, the use of LCA and agglomerative hierarchical clustering algorithms in the identification of distinct cardiometabolic multimorbidity clusters provides crucial insights into the patterns of non-random co-occurrence of multimorbidity that goes beyond simple counts used in the majority of previous studies.

The current study has some limitations. First, the screening questions particularly for diabetes, stroke and cataract were based on self-reported history of diagnosis. This may have resulted in the underestimation of the true prevalence of chronic diseases. Second, the current study assessed the association of different cardiometabolic multimorbidity combinations with the frequency of outpatient visits and hospitalization in Ghana. However, the nature of outpatient visits or hospitalization such as routine care or emergencies was not explored. Furthermore, the association of multimorbidity clusters with the cost of care were not investigated. Thus future studies on the economic burden of different cardiometabolic multimorbidity combinations are needed. Third, the number of chronic diseases in the LCA was limited to those included in the SAGE survey in Ghana. This may have excluded other common chronic conditions among older persons, such as dementia, cancers chronic kidney disease, resulting in an underestimation of the multimorbidity burden. Future studies need to include more chronic diseases to increase the external validity. Fourth, the cross-sectional design of the data used in this analysis implies a lack of conclusions regarding the temporality or causation between the multimorbidity classes, healthcare utilization patterns and QoL. Further studies based on longitudinal analysis need to estimate the incidence of transitions between latent classes of cardiometabolic multimorbidity and their impact on healthcare utilization patterns and QoL. Finally, The WHO SAGE data used in this analysis were collected in 2015, and rapid changes in health and socioeconomic circumstances in Ghana are likely to have affected the burden of chronic diseases and quality of life in the last 8 years. Nevertheless, our findings are based on the most recent data we could access and act as a baseline with which to compare future studies on the burden of multimorbidity on healthcare utilization and quality of life in Ghana.

This study has two key policy implications. First, we identified distinct multimorbidity combinations comprising cardiometabolic diseases, arthritis and cataract class and cardiopulmonary and depression class. This may inform the design of multimorbidity treatment guidelines and primary care interventions for cardiometabolic diseases. Given that most of the existing guidelines for the management of chronic diseases in Ghana are single-disease-focused [13], there is a need for a policy discourse on integrated care of discordant cardiometabolic multimorbidity to enable patients to benefit from minimally disruptive care. Second, these results are useful for identifying target populations of people living with cardiometabolic diseases at high risk of outpatient visits, hospitalizations and poor QoL. This is important for planning service delivery capacity, optimization of resources and health system response.

Conclusions

Our results provide insight into the cardiometabolic multimorbidity clusters and the associated patterns of healthcare utilization and QoL. The findings of this study show that cardiometabolic multimorbidity among older persons in Ghana cluster together in distinct patterns that differ in healthcare utilization and QoL. This evidence may be used in healthcare planning and development of appropriate clinical guidelines for the management of cardiometabolic multimorbidity. Our findings form the basis for, future research on the aetiology and pathogenesis of discordant multimorbidity clusters, and improved policies to address healthcare access and QoL for older persons living with cardiometabolic multimorbidity in sub-Saharan Africa.

Supporting information

S1 Table. Symptomatology algorithms.

(PDF)

S2 Table. Comparison between latent class models.

(PDF)

Data Availability

Data from SAGE Ghana Wave 2 was used for this study. The necessary permission was obtained from the World Health Organization to use the data. All files were obtained from the World Health Organization Study on global AGEing and adult health (WHO-SAGE). Details on data can be found at http://www.who.int/healthinfo/sage/cohorts/en/. The authors confirm that they had no special access privileges to the data. Interested researchers will have to submit a licensed data request to WHO. Upon approval, the researchers will be granted access to licensed data.

Funding Statement

Financial support was provided by the US National Institute on Aging through Interagency Agreements (OGHA 04034785; YA1323-08-CN-0020;Y1-AG-1005-01) with the World Health Organization and a Research Project Grant (R01 AG034479- 64401A1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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PLOS Glob Public Health. doi: 10.1371/journal.pgph.0002215.r001

Decision Letter 0

Nasheeta Peer

27 Mar 2023

PGPH-D-23-00332

Cardiometabolic multimorbidity and associated patterns of healthcare utilization and quality of life: results from the Study on Global AGEing and Adult Health (SAGE) Wave 2 in Ghana.

PLOS Global Public Health

Dear Dr. Otieno,

Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, we feel that it has merit but does not fully meet PLOS Global Public Health’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 11 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at globalpubhealth@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pgph/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Nasheeta Peer

Academic Editor

PLOS Global Public Health

Journal Requirements:

1. Please ensure that Funding Information and Financial Disclosure Statement are matched.

2. In the Funding Information you indicated that no funding was received. Please revise the Funding Information field to reflect funding received.

3. Your manuscript is missing the following sections: Introduction. Please ensure these are present, and in the correct order, and that any references to subheadings in your main text are correct. An outline of the required sections can be consulted in our submission guidelines here:

https://journals.plos.org/globalpublichealth/s/submission-guidelines#loc-parts-of-a-submission

Additional Editor Comments (if provided):

On what basis were the non-cardiometabolic chronic conditions selected for inclusion in this study?

Why were cataracts included?

Lines 124-126: Please check if this sentence is correct. Why were participants deemed to have a condition if they were ‘screened negative’?

Please present Table 1 together with the overall data by men and women as well together with p-values for gender differences.

How do the faith-based/charity organisations differ from public healthcare facilities in terms of fees charged, etc.?

Table 2: Please define the multimorbidity clusters in the table or footnotes - what does minimal multimorbidity refer to? Tables need to be standalone without referring to the details in the main text.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does this manuscript meet PLOS Global Public Health’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

Reviewer #4: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I don't know

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS Global Public Health does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The article classified multimorbidity in older adults and assessed the association between these classes with healthcare utilization and quality of life. The results can affect planning of healthcare policies and interventions which will improve healthcare outcomes among older adults.

Even though the manuscript appears sound, the authors should clarify if the following terms refer to the same class to avoid confusion as they were used interchangeable. They should also clearly define these terms in the explanatory variables.

Minimal multimorbidity ( line 34, table 2, line 199, 214, 223,232, 324)

Minimal cardiometabolic multimorbidity (line 179, 211, 216)

The authors stated that one of their strength was screening for chronic diseases which was based on objective measures comprising direct physical measurement of BP, symptomatology algorithms and self -reports (line 249) However they also stated that one of the limitations of the study was screening for chronic diseases which were partially based on self- report.( 254). This looks contradictory

In the conclusion, the sentence on line 276 – 277 should be rephrased to make the message clear.

Reviewer #2: Thank you for the opportunity to review this compelling manuscript. This work represents a meaningful contribution in an understudied area using innovative statistical techniques to identify multimorbidity clusters of potential relevance to health services delivery in a global population.

There are a few areas of major improvements to this manuscript.

- Firstly, the data used in this study are from 2015. While SAGE Wave 3 data from 2018-2019 are still pending, it may potentially be valuable to wait to provide an update on this cluster analysis with newer data, given that the data represented are 8 years old with the prospect of a newer data set. The newer data may provide a more meaningful representation of the current status of the population’s multimorbidity and needs.

- Additionally, it is to be expected that patients with a higher disease burden would receive more outpatient and inpatient services. It would strengthen this analysis to include data on what kind of outpatient visits and inpatient hospitalizations patients who group into clusters received. For example, were there a greater degree of urgent outpatient visits recorded for non-routine reasons such as medication refills, but rather for exacerbations of pathologies? This would strengthen an understanding of what kinds of services are most needed by this population.

- The authors also posit that the clustering of cardiopulmonary diseases may be explained by sociodemographic factors such as smoking, however, data on participants’ smoking history, access to food support, etc. are not provided. Inclusion of this data would strengthen the causal connection, although it may be beyond the scope of what was collected in this study. Regardless, mentioning these variables in the analysis and discussion of why or why not it was included would be valuable.

- Additionally, hypertension is included in class 2 (hypertension and arthritis) and 3 (hypertension, angina, chronic lung disease, and asthma) of the cluster analyses. Given the dual appearance of hypertension within these clusters, it would be important to show any potential interaction between these clusters and whether there is any overlap or competing effects from cluster type and visits/hospitalizations.

Minor revisions include:

- Proofreading needs

- Authors mention the phenomenon of discordant multimorbidity but do not discuss the role of depression in relation to the multimorbid conditions mentioned. Additionally, the authors mention integrated care interventions that would benefit patients with multi morbid conditions, but the paper would be strengthened by inclusion of examples of these interventions.

Given this, I suggest a major revision with opportunity to resubmit to address the above points. Thank you again for the opportunity to review this work.

Reviewer #3: Thank you for the opportunity to review this interesting manuscript. The authors sought to identify classes of cardiometabolic multimorbidity groups among Ghanaian adults aged over 50 years and assess the association of the different multimorbidity combinations with healthcare utilization and quality of life(QoL) using data from the WHO SAGE wave 2. The study adds to the literature on multimorbidity in sub-Saharan Africa and has significant implications on health system planning and policies on integrated guidelines for management of patients with multimorbidity in Ghana. However, I have some comments.

There are several methodological issues.

1. The authors state “Detailed descriptions of sampling methods and data collection procedures have been previously published (26)”, “Data used in the current study were collected using interviewer-administered structured questionnaires (26)”. “Detailed information on the study tools has been published (28).”

The data set and study design used for the study are not available at the cited references “26. World Health Organization. STEPS Manual, STEPS Instrument. Geneva: WHO; 2011, .” and “28. Kowal P, Chatterji S, Naidoo N, Biritwum R, Fan W, Lopez Ridaura R, et al. Data resource profile: the World Health Organization Study on global AGEing and adult health (SAGE). International journal of epidemiology. 2012;41(6):1639-49.” respectively.

The WHO STEPS Manual does not provide the data set for the present study. Also the publication by Kowal P et al. seems to discuss WHO SAGE wave 0 and 1.

The authors can provide appropriate references for the stated methodology or outline them in detail in the current manuscript.

2. The data availability statement also states that data is publicly available on the microdata repository of the WHO (https://apps.who.int/healthinfo/systems/surveydata/index.php/catalog). However, the data on this repository does not include the data used for the present study. If the data is available on specific request that should rather be made known by the authors.

3. Concerning the sample size and sampling:

I am curious to know what informed the authors’ decision to exclude 2,037 of the 3,575 original study sample because they had not used outpatient care in the 12 months preceding the survey; and why 12 months in particular? My thought is that, “not having used outpatient care” is a pattern of healthcare utilization, and this idea has completely been jettisoned.

Frequency of hospitalization is independent of frequency of outpatient visit by their definition, so if persons with no outpatient visit in the preceding 12 months are excluded, essentially persons who may have been hospitalized in that period but had no outpatient visit are also excluded. If hospitalization is implied to be only after outpatient visit, then frequency of hospitalizations will be a subset of frequency of outpatient attendance. This seems to be a major flaw in sampling.

4. On the measurement and definition of variables:

The frequency of hospitalization as defined is expected to have been reported as a continuous variable. However, in Table 2, it is categorized as “greater than or equal to 3” and by inference“1 to 2” outpatient visits. What informs this categorization at cut-off of 3? And the authors must at least state this categorization in the methodology.

In the report of the results, line 186, it is interpreted as participants who visited outpatient clinic “more than three times” which is inaccurate. It should rather be stated as “three or more times”.

The frequency of hospitalization as defined is expected to have been reported as a continuous variable. However, in Table 2, it is categorized as “Yes” and by inference “No”.

In the report of the results, line 186, it is interpreted as participants who were hospitalized at least once. This is not consistent with their methodology.

The WHOQoL instrument gives results as a continuous variable(percentage between 0-100%). Can the authors explain why they categorized the results of QoL? …and in tertiles? Were the results normally distributed? Also why not as a binomial into poor and good quality of life because essentially the report lumped moderate and good quality of life as against poor quality of life in the results, lines 202-205 and discussion, lines 215-217. Can the result of QoL be reported or represented as odds of poor quality of life then.

History of medical conditions as well as screening questions for the chronic diseases were based on self-report which has been acknowledged as a major limitations of this study. Since hypertension was objectively screened for, the prevalence appears representative. Knowing that “hypertension and diabetes account for the highest burden of multimorbidity in Ghana (5) ” the prevalence of diabetes is expected to also be high, however, conditions that were not screened for like diabetes, stroke and cataract are likely to be under-reported.

5. In the analysis:

The authors did not state the level of p-values at which analysed variables were considered statistically significant.

Other minor issues:

1. The authors did not comply with using square brackets [] for citations.

2. In Table 2, † did not appear in the legend.

3. Under findings of latent class analysis:

What really is the meaning and import of “minimal cardiometabolic multimorbidity” in the present study? This should be addressed in the discussion as well. Were there any participants with no single morbidity or multimorbidity?

4. In the discussion:

Line 235 to 236_ the study by Sum G et al.(22) as the authors cite, did not look at number of comorbidity only but also elucidated clusters of multimorbidities which (hypertension + arthritis) seemed to a predominant multimorbidity.

Line 239 to 241_ can the authors explain or give some examples of the several underlying mechanisms that could explain the associations in the present study?

5. In the references:

15. …Journal of Morbidity and Comorbidity not “Journal of Multimorbidity and Multimorbidity.”

Reviewer #4: Overall, this paper is well-written. This study identified three groups of patients with varying probabilities on nine diseases using a latent class analysis. The researchers also examined the associations between the class memberships and three outcome variables (outpatient visits, hospitalization, and QoL). The topic is important, and the results are interesting. However, there are some major comments or suggestions regarding the methods and results that could be considered to improve the quality of this paper.

Major:

1. Partial list of cardiometabolic diseases or conditions was included in this study. Other important diseases or conditions such as obesity, dyslipidemia, and chronic kidney disease were not included. If data on some or all of these diseases are available, it would be helpful to add them to the analysis. If not, it is suggested to discuss this as a limitation.

2. Because LCA is the main analysis in this study to identify latent classes of participants with multiple cardiometabolic diseases and non- cardiometabolic diseases, more details of results from the LCA models could be provided to help readers to understand the relationships between the sociodemographic and health characteristics and latent classes. For example, how were the nine disease variables coded and modeled in LCA? What is the distribution of the sociodemographic health characteristics of the study participants (as listed in Table 1) in the three latent classes?

3. What is the meaning of the beta coefficients from the negative binomial regression (Line 200-201)? What is the clinical significance of these results? This information is important for readers to interpret the findings.

4. How was QoL coded and analyzed in ordinal logistic regression? For example, was QoL coded as low = 0, moderate=1, and high=2 or vice versa in the ordinal logistic regression model? It is important to indicate this information in order to understand the direction and magnitude of the associations.

Minor:

1. More details on the LCA modeling process could be added to the Method section (Line 134-142) to better assist readers in understanding how the latent classes were determined and how the participants were classified into each of the three latent classes. For example, the two sentences on Line 141-142 might be difficult to be understood by readers. What are the posterior probabilities? How are they related to the determination of class memberships?

2. Reference # 26 indicates WHO STEP Manual 2011 (Line 380). However, data from the WHO Study on Global AGEing and Adult Health (SAGE) Wave 2 were used (Line 83).

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.

For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Dr. Kwadwo Faka Gyan

Komfo Anokye Teaching Hospital

Kumasi, Ghana

Reviewer #4: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLOS Glob Public Health. doi: 10.1371/journal.pgph.0002215.r003

Decision Letter 1

Nasheeta Peer

8 Jun 2023

PGPH-D-23-00332R1

Cardiometabolic multimorbidity and associated patterns of healthcare utilization and quality of life: results from the Study on Global AGEing and Adult Health (SAGE) Wave 2 in Ghana.

PLOS Global Public Health

Dear Dr. Otieno,

Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, we feel that it has merit but does not fully meet PLOS Global Public Health’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jul 23 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at globalpubhealth@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pgph/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Nasheeta Peer

Academic Editor

PLOS Global Public Health

Journal Requirements:

1. Please amend your detailed Financial Disclosure statement. This is published with the article. It must therefore be completed in full sentences and contain the exact wording you wish to be published.

a. State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

b. If any authors received a salary from any of your funders, please state which authors and which funders.

If you did not receive any funding for this study, please simply state: “The authors received no specific funding for this work.”

Additional Editor Comments (if provided):

Lines 199-200: Was the higher prevalence of chronic lung diseases in women vs. men expected? What was this due to? Generally, in Africa, it’s higher in men because of their higher rates of smoking.

I suggest that you rephrase this sentence and only report the conditions that are significantly different between the sexes.

Line 207: Please clarify what is meant by “minimal chronic diseases’ – is it no chronic diseases?

Line 208: Does class two include abdominal obesity alone, with no other comorbidities?

Please also clarify in table on Page 11. This should be Table 2 and not 3 – line 233. Please also correct table numbering on line 236 and 245.

Table 1: I suggest presenting the column with the total (both sexes) data first followed by the male/female columns because the p-value relates to the latter columns. This will read better.

P values in all tables should be to 3 decimal places, please.

Line 298: Please add 'diseases' after 'cardiometabolic'.

Line 322: Please add: ‘particularly for diabetes’ after ‘diseases'.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

2. Does this manuscript meet PLOS Global Public Health’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I don't know

Reviewer #3: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS Global Public Health does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have addressed all the comments raised.

Reviewer #3: (No Response)

Reviewer #4: Thank you for addressing the comments and suggestions raised on the previous version. The major revisions are appropriate and adequate. Adding the abdominal obesity variable to the LCA modeling is helpful. The results from the 4-class model are more meaningful than the previous results from the 3-class model. The results on the associations between latent class memberships and the healthcare utilization patterns and QoL have more clinical significance in this 4-class model compared to the previous 3-class model. The following are some additional comments and suggestions for you to consider.

Major:

1. The results of the supplementary hierarchical cluster analysis seem to be unrelated to the objectives of the study and did not provide much support to the results of the LCA modeling either. They might cause unnecessary confusions to the readers. Suggest removing this method and the related results from the paper.

2. The labeling for latent class 3 and 4 seems not to reflect the highest probabilities of diseases within each latent class sufficiently. For example, in class 3, hypertension and abdominal obesity have the highest probabilities, followed by general obesity and arthritis. In class 4, asthma and chronic lung disease have the highest probabilities, followed by hypertension, abdominal obesity, and angina. As you show in Table 1, abdominal obesity has the highest prevalence, particularly in females. Hypertension has the second highest prevalence. Therefore, abdominal obesity and hypertension could be the two major diseases that could potentially be related to other comorbidities in this population.

3. I would suggest using the following method to simplify the labeling of the four latent classes based on the major diseases with the highest probabilities within each latent class: class 1 - no comorbidity; class 2 - abdominal obesity; class 3 - cardiometabolic comorbidities; class 4 - cardiopulmonary comorbidities.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.

For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: Yes: Dr. Kwadwo Faka Gyan

Komfo Anokye Teaching Hospital

Kumasi, Ghana

Reviewer #4: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLOS Glob Public Health. doi: 10.1371/journal.pgph.0002215.r005

Decision Letter 2

Nasheeta Peer

10 Jul 2023

Cardiometabolic multimorbidity and associated patterns of healthcare utilization and quality of life: results from the Study on Global AGEing and Adult Health (SAGE) Wave 2 in Ghana.

PGPH-D-23-00332R2

Dear Dr. Otieno,

We are pleased to inform you that your manuscript 'Cardiometabolic multimorbidity and associated patterns of healthcare utilization and quality of life: results from the Study on Global AGEing and Adult Health (SAGE) Wave 2 in Ghana.' has been provisionally accepted for publication in PLOS Global Public Health.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact globalpubhealth@plos.org.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Global Public Health.

Best regards,

Nasheeta Peer

Academic Editor

PLOS Global Public Health

***********************************************************

Lines 34-38: This is unclear; while the details have been provided in the main text, it also needs to be clear in the Abstract. Please amend the 2nd class, if correct, as “abdominal obesity only (40.7%)”; the 3rd class as “any combination of…” and for class 3 and 4, replace “and” with “or” where appropriate.

Please also make the corresponding amendments in the main text.

Reviewer Comments (if any, and for reference):

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

2. Does this manuscript meet PLOS Global Public Health’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #2: Yes

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS Global Public Health does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Thank you for submitting this updated manuscript. This version is much improved and significantly addresses this reviewer's prior concerns regarding the suitability of use of the SAGE Wave 2 data, the potential etiologies of connection between the disease states in the multimorbidity clusters, as well as need for proofreading.

There remain areas of remaining proofreading for consistency as well eliminating redundant language to reduce the overall length of the submission, however, I am pleased to recommend that this manuscript be accepted for its meaningful contributions to improving service planning and delivery.

Reviewer #4: Thank you for addressing the comments and suggestions. The revisions are appropriate and adequate.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.

For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Ramya Sampath, MD

Reviewer #4: No

**********

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Symptomatology algorithms.

    (PDF)

    S2 Table. Comparison between latent class models.

    (PDF)

    Attachment

    Submitted filename: Responses to reviewers comments.docx

    Attachment

    Submitted filename: response-to-reviewers-comments.docx

    Data Availability Statement

    Data from SAGE Ghana Wave 2 was used for this study. The necessary permission was obtained from the World Health Organization to use the data. All files were obtained from the World Health Organization Study on global AGEing and adult health (WHO-SAGE). Details on data can be found at http://www.who.int/healthinfo/sage/cohorts/en/. The authors confirm that they had no special access privileges to the data. Interested researchers will have to submit a licensed data request to WHO. Upon approval, the researchers will be granted access to licensed data.


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