Abstract
This study sought to determine patterns of multimorbidity and quantify their impact on use of primary health services in the presence and absence of anxiety and depression among a cohort of urban community-dwelling men in Australia. The analytic sample consisted of men (
Keywords
Background
Multimorbidity has recently been identified as one of the greatest challenges facing the global health system (Pearson-Stuttard et al., 2019). Estimates from the World Health Organization (WHO) demonstrate that between 40% and 60% of the adult population in developed countries have two or more chronic conditions (World Health Organization, 2016). The presence of multimorbidity has been associated with lower quality of life (Fortin et al., 2004), increased mortality (Nunes et al., 2016), and higher utilization of hospital and primary care services (McRae et al., 2013; Salisbury et al., 2011; Westert et al., 2001; Zulman et al., 2015). Despite this, the study of multimorbidity—distinct from earlier studies that focused on comorbidity (Feinstein, 1967)—is relatively new. Multimorbidity is particularly applicable to the primary care setting, where the general practitioner (GP) tends to focus on the whole care of the patient rather than one particular condition (Harrison & Siriwardena, 2018). In contrast to the United States, where a range of specialists provides primary care and for some conditions patients may only see a specialist (Jones et al., 2011), the Australian health-care system requires that the starting point and ongoing continuity of care is vested with GPs who are the gateway to other health-care services.
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Given these knowledge gaps, our study involves two main objectives. The first objective is to examine the patterns of multimorbidity of eight chronic conditions (anxiety, asthma, CVD, depression, diabetes, obesity, osteoarthritis, rheumatoid arthritis). The second objective concerns studying the impact of comorbid anxiety and depression on the utilization of GP services for urban-dwelling, middle-aged to elderly men.
Methods
Setting and Population
The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study was established in 2009 to investigate the associations of sex steroids, inflammation, and environmental and psychosocial factors with cardio-metabolic disease risk in men. The study population consisted of 2568 men aged 35–80 years at baseline from two cohort studies: all participants of the Florey Adelaide Male Ageing Study (FAMAS) and age-matched male participants of the North-West Adelaide Health Study (NWAHS). Data were collected on a number of chronic conditions as well as linked Medicare data about individual health service claims and utilization information. Medicare in Australia is a universal health insurance scheme serving all Australians for a wide range of health and hospital services. This contrasts with Medicare in the United States that primarily serves people over 65 years of age and younger disabled people and dialysis patients. All protocols were approved by the (Blinded, for review) and written, informed consent was obtained from all participants. Detailed information on recruitment and follow-up process is reported elsewhere (Grant et al., 2014). The data in the MAILES Stage 2 study contained 2039 men (FAMAS Stage 2: 2007–2010; NWAHS Stage 3: 2008–2010), representing data collected at clinics approximately 5 years after baseline visits in the two studies.
Chronic Conditions
Data on chronic disease status (CVD, diabetes, arthritis, depression, anxiety, asthma) were collected through self-report to the question “Have you ever been told by a doctor that you have any of the following conditions?” Classification of diabetes was by self-report and biomedical measures (fasting blood glucose ≥7.0 mmol/L and/or HbA1c ≥6.5; see Grant et al., 2014). Obesity was indicated by a waist circumference ≥100 cm as measured at the clinic visit. Depressive symptoms were assessed using the Beck Depression Inventory (BDI-Ia; Beck & Beck, 1972) for FAMAS men and the Center for Epidemiologic Studies-Depression Scale (CES-D; Radloff, 1977) for NWAHS men. Cutoff scores of 10 and 16 for the BDI-1a and CES-D, respectively, were employed to classify into the depression categories (Yes/No). Both the BDI-1a and CES-D show comparable specificities from the classification of major depression in residential, older men (Shafer, 2006). Anxiety symptoms were assessed using the seven-item Generalized Anxiety Disorder (GAD-7) scale (Spitzer et al., 2006). A cutoff score of 10 was used for the anxiety category (Yes/No). The GAD-7 shows good overall specificity for GAD in comparable men (Spitzer et al., 2006). The BDI, CES-D, and GAD-7 are not formal clinical diagnostic assessments for depression or anxiety. They are screening instruments for depression or anxiety for research in the general population.
Health Service Usage
Health service use was obtained from a self-reported, piloted, health service utilization questionnaire. The number of GP visits in 1 year during the follow-up period was categorized into four categories (0, 1–4, 5–9, and 10+). Information was also obtained regarding participants’ main reason for visiting the GP, their overall rating of the visit, whether other health issues were raised, and the use of other health service providers. GP and health utilization data were also verified through consented linkage into Medicare, the Australian Government’s nationwide medical services program. There were data available on specialist or allied health consultations (including services provided by psychologists and psychiatrists). However, the number of participants who reported the use of such services is relatively small (only around 3%), and thus such data were not considered in the analyses. This study focuses on GP services only.
Demographic and Lifestyle Factors
Age, marital status, household income, education and qualifications, work status, smoking, alcohol consumption, and physical activity were utilized as collected by self-reported questionnaires at MAILES Stage 2. Information about country of birth was taken from the baseline.
Statistical Analysis
The analysis of chronic conditions was conducted based on the clustering method of pairwise concordance statistics (Ng et al., 2012), which adopts the asymmetric Somers’ D statistic to quantify the degree of multimorbidity beyond chance (Ng, 2015; Ng et al., 2018). The identification of significant (nonrandom) multimorbidity between conditions, also known as “associative multimorbidity” (Prados-Torres et al., 2014), is more informative to view disease patterns for a potential sharing of risk factors of the diseases (Batstra et al., 2002; Baty et al., 2013; Ng, 2015; Ng et al., 2019). The clustering method adopts the Benjamini–Hochberg procedure to control for the false discovery rate at α = .05 (Benjamini & Hochberg, 1995).
A χ2 analysis (for categorical variables) or analysis of variance (ANOVA; for quantitative variables) was used to test for significant differences in participants’ characteristics and multimorbidity patterns between the four groups according to the number of GP visits in 1 year. A multinomial logistic regression method was adopted to assess the impact of depression and anxiety on the frequencies of GP visits via additive interaction terms, separately for obesity, CVD, and diabetes, with adjustment for participants’ demographic and lifestyle characteristics. Adjusted relative risk ratios (RRRs) of GP visits relative to the reference category of 1–4 GP visits were obtained, along with their 95% confidence intervals (CIs). Predicted probabilities of 10+ annual GP visits were calculated to illustrate the effects from either obesity, CVD, or diabetes alone as well as the impact of comorbid anxiety or depression. It is well recognized that any factor that is caused in part by the exposure (incidence of chronic condition) and is associated with outcome of interest (frequency of GP visits) should not be treated as a confounder or adjusted for in the regression analysis (Weinberg, 1993). Bias can result from adjusting for this “intermediate factor” as the estimated exposure-related risk will be markedly reduced. On the basis of literature and clinical evidence, medication was hypothesized to be part of the causal pathway between multimorbidity and GP visits; that is, multimorbidity is associated with more medications (Masnoon et al., 2017; Vogeli et al., 2007) and in turn more medications have been shown to be associated with increased health service utilization (Milton et al., 2008; Nishtala et al., 2014). Therefore, medication was not adjusted for in the multinomial logistic regression analysis.
The comparison analysis and logistic regression analysis were performed using STATA (SE 13.1; StataCorp, College Station, Texas) on the basis of 1904 participants (93.4% of 2039) with complete information on the annual frequency of GP visits. Sensitivity analyses were conducted regarding the definitions of anxiety and depression based on either assessment instruments (GAD-7 for anxiety; BDI-1a/CES-D for depression) or medications for anxiety and/or depression, compared to the self-reported questionnaire.
Results
Multimorbidity of Chronic Conditions
Prevalence rates in decreasing order of the eight chronic conditions among the MAILES Stage 2 cohort were: obesity (

Multimorbidity analysis. (a) Significant nonrandom multimorbidity between eight chronic conditions (nodal size is proportional to the number of conditions that are significantly comorbid with the condition; lines connect two conditions when their pairwise Somers’ D statistic is significant; lines will be bolded if they represent the “closest” pairs of conditions, with which the pairwise Somers’ D statistic is maximum and significant). (b) Significant comorbid chronic conditions (higher Somers’ D statistic [maximum is 1.0] represents a higher degree of nonrandom multimorbidity, where the strength of multimorbidity is measured through the number of concordant pairs indicating the presence of both conditions).
Primary Health Service Use
The demographic and lifestyle characteristics of all participants (
Among 1904 participants with GP service utilization information, 156 (8.2%) did not visit a GP in the last 12 months, 1084 (57.0%) visited 1–4 times, 416 (21.8%) visited 5–9 times, and 248 (13.0%) participants had 10 or more GP visits. The median range of GP visits was 3–4 times in a year. Participants’ characteristics among the four categories of GP visits are provided in Table 1. Those attending their GP more frequently tended to be older (there is a trend of increasing mean ages from 51.7 to 66.6 years,
Demographic and Lifestyle Characteristics of Participants in the Four Categories of GP Visits (
Differences in frequencies among the four categories were tested using χ2; differences in means were tested using ANOVA.
Significant differences among the four categories of GP visits (
Impact of Multimorbidity on Primary Health Service Use
Table 2 displays the differences in nine types of comorbid conditions (identified from Figure 1) among the four categories of GP visits. From Table 2, participants with comorbid conditions have generally more GP visits compared to those without any comorbid conditions (namely, decrease in proportions of 0 GP visit and 1–4 GP visits but increase in proportions of 5–9 or 10+ GP visits; see also supplemental Figure S1). Men with comorbid conditions that include CVD were more likely to have 10 or more annual GP visits. For those participants with neither anxiety nor depression, 54.1% of participants with CVD, obesity, and diabetes; 50.0% of participants with CVD and osteoarthritis; 43.8% of participants with CVD, obesity, and osteoarthritis; 42.9% of participants with CVD and diabetes; and 36.1% of participants with CVD and obesity had 10 or more annual GP visits. Table 2 also shows the increased proportions of participants with 10+ GP visits when symptoms of anxiety or depression were also present (e.g., from 54.1% to 85.7% and from 43.8% to 66.7% for participants, respectively, with “CVD, Obesity, and Diabetes” and “CVD, Obesity, and Osteoarthritis,” the two nonrandom multimorbidity clusters identified).
Frequency of GP Visits for Nine Types of Comorbid Conditions.
Values in bold indicate the highest-frequency category of GP visits for each pattern of comorbid conditions. CVD = cardiovascular disease.
The multimorbidity group corresponds to a multimorbidity cluster identified from Figure 1.
The results of multinomial logistic regression models assessing the impact of anxiety and/or depression (defined by the self-reported questionnaire) on the frequencies of GP visits are provided in Table 3, separately for Conditions A (obesity), B (CVD), and C (diabetes). As described in the “Methods” section, these results are based on the use of screening instruments and do not indicate formal diagnostic assessments for depression or anxiety. Besides age, household income, and work status, other demographic and lifestyle characteristics were not significant.
Multinomial Logistic Regression on the Four Categories of GP Visits.
Number of medications was not adjusted in the models; see text for details.
The presence of obesity was associated with an increase in the frequency of GP visits (adjusted RRRs: 1.4 for 5–9 GP visits and 2.3 for 10+ GP visits over 1–4 GP visits) for participants without anxiety and depression. For participants with obesity, the presence of anxiety or depression was associated with a further increase in the frequency of GP visits (adjusted RRRs: 2.2 for 5–9 GP visits and 3.8 for 10+ GP visits relative to 1–4 GP visits). The predicted probabilities of 10+ GP visits, comparing men without obesity, anxiety, or depression to those with obesity but no anxiety or depression, and to those with obesity and anxiety, depression, or both, are displayed in Figure 2(A). The corresponding predicted probabilities of 10+ GP visits for these three groups were 4.5%, 9.1%, and 22.3%, respectively. The adjusted risk ratio of 10+ GP visits for obesity alone was 2.0 = 9.1/4.5 (95% CI [1.5, 2.8]), whereas that attributed to anxiety or depression was 2.4 = 22.3/9.1 (95% CI [1.9, 3.2]).

Adjusted predictions of 10 or more annual GP visits with 95% CIs for (A) obesity, (B) CVD, and (C) diabetes conditions. CVD = cardiovascular disease.
The presence of CVD was associated with an increase in the frequency of GP visits (adjusted RRRs: 1.7 for 5–9 GP visits and 4.8 for 10+ GP visits) for participants without anxiety and depression. For participants with CVD, the presence of anxiety or depression was associated with a further increase in the frequency of GP visits (adjusted RRRs: 4.2 for 5–9 GP visits and 5.0 for 10+ GP visits relative to 1–4 GP visits). The predicted probabilities of 10+ GP visits were 5.7%, 21.0%, and 36.8% for the groups without CVD anxiety or depression, CVD without anxiety or depression, and CVD with anxiety and/or depression, respectively (Figure 2B). The adjusted risk ratio of 10+ GP visits for CVD alone was 3.7 (95% CI [2.8, 4.8]), whereas that attributed to anxiety or depression was 1.8 (95% CI [1.2, 2.5]).
The presence of diabetes was associated with an increase in the frequency of GP visits (adjusted RRRs: 1.9 for 5–9 GP visits and 3.1 for 10+ GP visits) for participants without anxiety and depression. For participants with diabetes, the presence of anxiety or depression was associated with a further increase in the chance of 10+ GP visits over 1–4 GP visits, with an adjusted RRR of 3.0. The predicted probabilities of 10+ GP visits were 5.5%, 13.5%, and 30.1% for the groups without diabetes, anxiety or depression, diabetes without anxiety and depression, and diabetes with anxiety and/or depression, respectively. The adjusted risk ratio of 10+ GP visits for diabetes alone was 2.4 (95% CI [1.9, 3.2]), whereas that attributed to anxiety or depression was 2.2 (95% CI [1.6, 3.1]) (Figure 2C).
Additional results of the sensitivity analyses on the definition of anxiety and depression based on formal clinical diagnosis (GAD-7 for anxiety; BDI-1a/CES-D for depression) or medications for anxiety and/or depression are provided in supplemental Tables S2 and S3. The results indicate the same conclusion as above that the presence of clinically diagnosed or medication-based anxiety and/or depression was significantly associated with a further increase in the chance of 10+ GP visits.
Discussion
This study presents findings about the utilization of GP services by older-aged community-dwelling men (38–85 years) in relation to their patterns of multimorbidity, where two nonrandom multimorbidity “clusters” of “CVD, Obesity, Diabetes” and “CVD, Obesity, Osteoarthritis” were identified, as well as the impact of comorbid anxiety and depression. There is a common misperception that “men don’t go to the doctors.” In 2014–2015, an estimated 7.4 million males aged ≥15 years (78%) in Australia had seen a GP at least once in the previous year; the proportion increased with age (from 80.4% at age 45–54 to 96.3% at age ≥65). In 2013–2014, expenditure on primary health-care and hospital services was 38% and 40%, respectively, of the total health funding in Australia (Australian Institute of Health and Welfare, 2015). We previously reported that >90% of men in our cohort attended their GP at least once in the preceding year (Wittert et al., 2011). The current study shows higher proportions of at least one GP visit in the previous year for men with comorbid conditions (e.g., 96% for men with diabetes and obesity; 100% for men with diabetes, obesity, and CVD). Specifically, this study revealed that men with chronic conditions comorbid with CVD are more likely to have 10 or more annual GP visits, compared to multimorbidity involving other conditions such as diabetes, obesity, arthritis, or depression and anxiety, in the absence of CVD. Primary health service use has previously been shown to be frequent in men with multimorbidity involving heart failure in older men (Robertson et al., 2012) or congenital heart disease in younger men (mean age 28.1 years; Billett et al., 2008). Our study quantified the impact of multimorbidity involving obesity, CVD, or diabetes on the relative risks of higher frequencies in annual GP visits, showing again higher impact from CVD compared to multimorbidity involving obesity or diabetes without CVD, after adjustment for demographic factors. Furthermore, there is a two to three-fold increase in the chance of having 10 or more GP services annually for Australian men with CVD alone.
Another significant driver of primary health-care service use among men is mental health disorders. Data from the FAMAS cohort (men aged 35–80) showed an adjusted odds ratio (
The prevalence of anxiety/depression is significantly higher in patients with comorbid conditions than in the general population (Husaini et al., 2004; Pearson-Sttuttard et al., 2019; Roy-Byrne et al., 2008), and the combination is associated with poorer health outcomes. These observations are generalizable across a variety of populations, including the United States (Li et al., 2019; Voinov et al., 2013). There is also, on an almost global basis, a higher prevalence of preexisting comorbidities and poorer health outcomes among men compared to women (Rovito et al., 2017; World Health Organization Regional Office for Europe, 2018). It is no longer tenable to assert that inequitable burden of poor health experienced by men is the consequence of failure to use health services (Schlichthorst et al., 2016). One possible explanation may relate to the markedly lower frequency with which depression is diagnosed in men (World Health Organization, 2019), possibly because of the failure to recognize a “male type” presentation typified by somatization of symptoms, irritability, anger, and substance abuse (Martin et al., 2013). Effective management of depression has long been shown to reduce primary care visit frequency and costs (Simon et al., 2001). It is also clear that an optimal outcome for chronic conditions occurs when comorbid depression and/or anxiety is recognized and effectively managed (Atlantis et al., 2013; Bhattacharya et al., 2016; DeJean et al., 2013; Tully & Baumeister, 2015). The implication of these data is that to reduce the disproportionate burden of poor health among men, a focus on strategies to efficiently recognize and manage multiple concurrent chronic diseases with a low threshold to consider depression and anxiety, particularly in men who are frequent users of health care, is required.
The major strength of the MAILES study is its value-added benefit of combining selected participants from two high-quality cohort studies to provide a wealth of measured and self-reported information about multiple chronic conditions, together with the data collected on a wide range of biomedical and sociodemographic variables as well as linked information about primary health service utilization from Medicare data. The MAILES study has a sound epidemiological base, a comparatively large sample of randomly selected community-dwelling men, and a high overall response rate, allowing its findings to be generalized to the broader population (Grant et al., 2014). As with most cohort studies, the key limitation of the MAILES study is its reliance on self-reported information for some lifestyle and medical factors, such as rheumatic diseases (Gill & Hill, 2017). However, De-Loyde et al. (2015) reported that the use of patient self-reported questionnaires to ascertain comorbid conditions remains a valid method for health services research, as shown in the sensitivity analyses, which indicated the same conclusion for using clinically diagnosed or medication-based anxiety and depression. Moreover, self-reports of cardiac and stroke events have been reported to be accurate (Bergmann et al., 1998; Kriegsman et al., 1996). There is accumulating evidence for a male-specific phenotype of depression (e.g., increased anger and risk-taking) that is not captured by the BDI or CES-D. The use of specific questionnaires such as the Male Depression Risk Scale-22 (MDRS-22; Rice et al., 2013, 2018) provides a better understanding depression (and anxiety) in men and associated service use in men. Another limitation of the study is the lack of information on the severity of the disease and type of treatment. Although the study participants were representative of its target population, they were also predominantly Caucasian, aged 35–80 years (at recruitment), and community-dwelling (Grant et al., 2014). Also, the BDI, CES-D, and GAD-7 are not formal clinical diagnostic assessments for depression or anxiety. This point should be considered when interpreting the results that are based on the use of screening instruments.
Conclusions
Our study strengthens the evidence-based information about the nature of multimorbidity in men and its impact on primary health services use, which is critical to inform guidelines and health management for effective and efficient care of men with multimorbidity and comorbid anxiety and/or depression. Coexisting conditions may also influence the effectiveness of therapies or modify patients’ priorities concerning their health care (Boyd et al., 2011). Effective management of this patient group thus requires effective management of other comorbid conditions as well (Boult, 2010; Caughey & Roughead, 2011), bearing on the different patterns in men’s health service use (Smith et al., 2006). More importantly, multimorbidity patterns involving CVD should be considered in the development of clinical trials and guidelines to better inform medical decision-making and provide comprehensive or collaborative care for patients with CVD and comorbid conditions including anxiety and/or depression (Assari et al., 2013; Boyd et al., 2011; Glynn et al., 2008; Morgan et al., 2009).
Supplemental Material
sj-pdf-1-jmh-10.1177_1557988320959993 – Supplemental material for The Effect of Multimorbidity Patterns and the Impact of Comorbid Anxiety and Depression on Primary Health Service Use: The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study
Supplemental material, sj-pdf-1-jmh-10.1177_1557988320959993 for The Effect of Multimorbidity Patterns and the Impact of Comorbid Anxiety and Depression on Primary Health Service Use: The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study by Shu-Kay Ng, Sean A. Martin, Robert J. Adams, Peter O’Loughlin and Gary A. Wittert in American Journal of Men's Health
Footnotes
Acknowledgements
The authors are most grateful for the generosity of the cohort participants in giving their time and effort to the study. The study team is also very appreciative of the work of the clinic, recruiting, and research support staff for their substantial contribution to the success of the study.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GW reports grants from Bayer Schering, grants from Eli Lilly, grants from Lawley Pharmaceuticals, nonfinancial support from Eli Lilly, nonfinancial support from Novo Nordisk, personal fees from Bayer Schering, personal fees from Eli Lilly, personal fees from Sanofi, personal fees from Novo Nordisk, personal fees from AstraZeneca, personal fees from I-Nova, personal fees from Elsevier, outside the submitted work. All other authors have no declarations.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded through the Australian National Health and Medical Research Council (Project Grant #627227) and The Hospital Research Foundation (Woodville, SA, Australia) Research Grant. The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.
Ethical Approval and Consent to Participate
All protocols were approved by the Royal Adelaide Hospital and the Queen Elizabeth Hospital Research Ethics Committees, with written, informed consent obtained from all participants.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
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