PPPM shifts the paradigm from reactive to proactive healthcare by providing a unique window of opportunity to prevent chronic disease [8]. Predictive medical approaches include, among other things, screening assessments to effectively predict individuals at risk of developing chronic diseases [7]. This study has demonstrated that the SHSQ-25 can accurately predict that carers are at far greater risk of developing chronic diseases than the general population, facilitating population level SHS prediction. This provides a unique window of opportunity for targeted population-level prevention. As SHS shares modifiable (behavioural) risk factors with chronic diseases, early identification will allow clinicians to prescribe personalised treatment algorithms [7]. Tailoring treatments to specific individuals will mitigate the development of chronic diseases in carers. Stratifying individuals into high (SHS) and low (optimal health) risk based on the SHS cut-off value could improve personalised medicine for chronic diseases from the perspective of PPPM.

Effective screening of chronic diseases, for example CVD and T2DM, is crucial in PPPM’s quest to mitigate chronic disease prevalence [15]. In line with the working hypothesis of PPPM, SHS is proactive in its approach by predicting a person’s predisposition to developing chronic diseases, creating a unique window of opportunity for the prevention and personalised treatment of chronic diseases, initiating the prescription of early interventions in at-risk individuals [3]. This simple, inexpensive and validated screening tool facilitates early identification of high-risk individuals, allowing for timely employment of targeted prevention and personalised treatment algorithms. This shared outcome by PPPM and SHS has the capacity to alter the course of disease trajectories, potentially preventing disease manifestations from occurring altogether [8]. These benefits extend beyond the state-of-the-art to improve quality of life outcomes and mitigate economic burden. At a time when global healthcare is overwhelmed by the perpetuity of chronic disease burden, SHS, with all its potential, should be adopted as the new gold standard in the fight against chronic diseases from the perspectives of PPPM.

For the first time to our knowledge, this study found unpaid, informal carers had a significantly higher SHS prevalence than in the general population (43.0% vs 12.7%), demonstrating carers are more susceptible to SHS than that in the general population in Australia. The median total SHS scores and IQR were statistically higher in carers compared to the general population (38.0; IQR 28.0–48.0 vs 20.0; IQR 13.0–32.0) as well as all domains, including fatigue (17.0; IQR 13.0~22.0 vs 9.0; IQR 6.0~14.0), cardiovascular (1.0; IQR 0.0–3.0 vs 1.0; IQR 0.0~1.0), digestive (3.0; IQR 1.0~4.0 vs 1.0; IQR 0.0~3.0), immune (2.0; IQR 1.0~4.0 vs 2.0; IQR 1.0–3.0) and mental health (12.0; IQR 9.0~17.0 vs 6.0; IQR 3.0~11.0), indicating carers suffer from poorer health than that in the general population. These findings mirrored psychological symptom prevalence. For example, we found that carers had a higher prevalence of depression than that in the general population (75.4% vs 32.1%), a higher prevalence of anxiety than the general population (69.0% vs 31.5%) and a higher prevalence of stress than the general population (72.9% vs 33.9%). Further, we found carers had significantly higher median depression, anxiety and stress scores than the general population, respectively (16.0; IQR 10.0~28.0 vs 4.0; IQR 2.0~12.0) (10.0; IQR 6.0~8.0 vs 4.0, IQR 0.0~8.0) (22.0; IQR 14.0~8.012.0; IQR 6.0~18.0), indicating carers suffered from more severe psychological symptoms than that in the general population. Our research shows, in the post-COVID-19 era, where unpaid carers have increased mental health conditions and are developing chronic diseases earlier, the value of identifying/predicting which carers via at risk of developing mental health conditions, and their sequelae, before their manifestation. This personalised approach, in the spirit of PPPM, allows optimal health care by predictive diagnosis and targeted prevention. In turn, this enables valuable resources to be directed to where they are most needed, with the aim of avoiding disease manifestation.

Psychological symptoms are known to contribute to the development of SHS. In this study, we explored the relationship between psychological symptoms and SHS prevalence in two populations in order to understand the influence of the caring role on SHS from the perspective of PPPM. We found that psychological symptoms were associated with SHS, and that carers with SHS experienced a higher prevalence of psychological symptoms than that in the general population with SHS. Further, SHS was significantly correlated with psychological symptoms with the Spearman correlation coefficient of 0.635 for depression, 0.713 for anxiety and 0.674 for stress symptoms, respectively. Further, the caregiving role was found to influence SHS prevalence, with carers 6.4 times more likely to suffer from SHS than the general population. This finding identifies the impact of the caregiving role on the health status in otherwise healthy carers and the urgent need under the concept of PPPM to proactively intervene in this vulnerable, disadvantaged population at a time when prevention of chronic diseases is still possible.

Against the concept of PPPM, the current biomedical model of health has been reactive in its response to managing chronic diseases, typically initiating treatments only after the clinical manifestation of disease [30]. The impact of chronic diseases is enormous, with an increase in total global costs predicted for cancer, CVD, chronic obstructive pulmonary disease, T2DM and mental illness, respectively [6]. SHS screening is proactive in its approach by predicting which individuals are at risk of developing certain chronic diseases before their onset, enabling the delivery of targeted, PPPM algorithms to prevent disease from occurring in the first place [8, 20]. From the lens of PPPM, this study found that the SHSQ-25 could accurately predict “at-risk” individuals for psychological and health problems. For example, within the general population, the median depression score among those with SHS was 12.0 (IQR 6.0–25.0), whilst the median depression score among those with optimal health was 4.0 (2.0–10.0), indicating SHS is associated with depressive symptoms. Similarly, the median anxiety score among those in the general population with SHS was 18.0 (9.0–32.0), whilst the median anxiety score among those with optimal health was 2.0 (0.0–6.0), indicating that SHS is associated with anxiety symptoms and optimal health is associated with no anxiety symptoms.

Stress is a key contributing factor in the development of SHS [8]. The human stress response is an evolutionarily conserved, dynamic process that aims to overcome a stressor (a real or perceived threat), promote survival and restore homeostasis [32]. The role of the two major components involved in the stress response—the sympatho-adrenomedullary (SAM) axis (producing catecholamines) and hypothalamic-pituitary-adrenal (HPA) axis (producing cortisol), respectively, is well documented [32, 33]. However, during times of chronic stress, that is, stress that persists over time, these processes become maladaptive [32]. In chronic stress, hypothalamic activation of the pituitary switches from CRH to vasopressin, decreasing the metabolism of cortisol [32]. Elevated cortisol levels and long-term cortisol exposure result, which are toxic to the human body and can lead to chronic disease [32]. It has been well-documented that carers experience substantial chronic stress as part of their caring role [8]. For example, a recent study by the Royal Australian College of General Practitioners found approximately 27% of primary carers had high psychological distress, almost three times higher than that in the general population [22]. Moreover, the carer well-being survey found that 48.1% of carers experienced moderate to high levels of psychological distress, almost twice as many as non-carers (25%) [27]. Our results were consistent with these findings, with the median depression score among carers with SHS being 22.0 (IQR 14.0~30.5), whilst the median depression score among the general population with SHS was 12.0 (IQR 6.0~25.0), indicating that carers with SHS suffered from more severe depression problems compared to the general population with SHS. Conversely, the median depression score among carers with optimal health was 14.0 (4.0–22.0) whereas the median depression score among the general population with optimal health was 4.0 (2.0–10.0), indicating that carers without SHS still experienced psychological symptoms, whilst the general population with optimal health experienced an absence of depressive symptoms. Further, the median anxiety score among carers with optimal health was 8.0 (4.0–12.0), whereas the median anxiety score among the general population with optimal health was 2.0 (0.0–6.0), indicating that carers without SHS still suffered from anxiety symptoms, whilst the general population with optimal health showed no anxiety symptoms.

From a personalised medicine approach, one of the three components of PPPM, our findings have particular relevance to women’s health. It is prudent to note that the overwhelming majority of participants in our study were females, with 93.1% of carers (n = 189) identifying as female and 87.9% of the general population (n = 145) identifying as female. We found female carers were more susceptible to SHS than females in the general population, with a significantly higher prevalence of 50.3% (95/189) compared to 12.4% (18/145). The medians and IQRs for total SHS scores were higher among female carers (39.0, IQR 29.0–48.5) than females in the general population (20.0, IQR 13.0–32.0) indicating female carers suffered more psychological problems than females in the general population. Depression scores were higher in female carers (18.0, IQR 10.0–28.0) than in females in the general population (4.0, IQR 2.0–12.0); anxiety scores were higher in female carers (10.0, IQR 6.0–28.0) than that of females in the general population (3.0, IQR 0.0–8.0); and stress scores were higher in female carers (22.0; IQR 14.0–28.0) than females in the general population (12.0, IQR 6.0–19.0). These findings hold great significance for women’s health considering anxiety and depression disorders were among the leading causes of total burden plaguing Australian females in 2022 [5]. For example, according to the Australian Institute of Health and Welfare’s Australian Burden of Disease Study 2022, anxiety disorders were the leading cause of total burden in females aged between 15 and 24 years, accounting for 14,300 individuals, or 10.2% of this age group [4]. Depressive disorders were the second cause of total burden, accounting for 11,400 individuals, or 8.2% [5]. In females aged between 25 and 44 years, anxiety disorders were again the leading cause of total burden, accounting for 39,300 individuals, or 8.9% of this age group [5]. Depressive disorders were the third cause of total burden, accounting for 32,600 individuals, or 7.4%. In females aged between 45 and 64 years, anxiety disorders were the fourth cause of total burden, accounting for 30,100 individuals, or 4.6% of this age group [5]. Depressive disorders were the fifth cause of total burden, accounting for 25,500 individuals, or 3.9% [5]. In our study, the majority of female carers were aged between 45 and 64 years (59.1%, n = 120) compared to 35.2% (n = 58) of the general population, with carers aged 25–44 years accounting for 36% (n = 73) compared to 53.9% (n = 89) of the general population.

The SHSQ-25 was able to accurately distinguish between females within the population who were at significantly greater risk of developing chronic diseases (in this study female carers). Importantly, these carers were otherwise healthy and free from disease. Further, this study found carers who were aged between 25 and 64 years had significantly higher DASS-21 scores than the general population (Table S6). These findings should serve to guide priority funding for future women’s health prevention strategies, especially considering primary prevention measures are proven to be highly cost-effective in healthcare practice following PPPM principles [10]. For example, an investment in collaborative care in primary care that addressed psychological stress and the risk of depression and anxiety disorders (that have been associated with T2DM and CVD) found the investment was cost saving, with a positive return on investment of $1.52 for every $1 invested after just 2 years [34]. Despite the growing body of evidence showing that millions of deaths can be avoided by focusing on prevention, with billions of dollars saved, investment in health promotion activities remains incredulously low, with only 2–4% of total health sector spending spent on prevention activities in most countries [35, 36]. Investment in the SHSQ-25 for the screening and detection of SHS in carers would offer a simple, low-cost, highly effective PPPM tool in the global fight against chronic diseases.

It is known that chronic diseases can manifest as a result of non-classical, modifiable risk factors (such as stress) and can induce behavioural changes such as poor diet, sedentary behaviour and substance abuse, and that this may adversely impact the health status of an individual [6]. Indeed, SHS has been shown not only to be associated with subjective markers (such as psychological symptoms) but has also been associated with objective biomarkers [8]. These include cardiovascular risk factors (including increased systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, triglycerides and plasma glucose) [8], increased plasma cortisol levels and GRB/GRA mRNA ratio [8], and endothelial dysfunction [8]. This underscores the importance of interventions designed specifically for carers. This is especially so considering carers are more sedentary than the general population.

For example, recent research has shown that carers are less likely to participate in sufficient physical activity compared to the general population, with the authors surmising that the age of carers, or a carers own disability, may have played a role in this observation [37]. This lack of physical activity in carers compared to non-carers was consistent with our results, with three quarters of all carers (75.4%) doing no vigorous exercise each week, compared to just over half (53.9%) of the general population. Interestingly however, we can confirm that the age of carers, or their disabilities, was not contributing factor in our study. In our results, the median age of carers and the general population were strikingly similar (46 years v 40 years), with all participants enrolled in the study free from any disability or comorbidity. We therefore hypothesise that carers are less likely to participate in sufficient exercise due to the demands of the caring role and the psychological impact that that exerts on their capacity to engage in exercise. Recent research found monitoring of carer health and morbidity, particularly of “at-risk” individuals such as female carers with asthma or diabetes, remains important [34]. Indeed, we found carers who ate no or less fruit were more susceptible to SHS (62.2%; 23/37) than the general population who ate no fruit (31.8%; 7/22), and carers who did not participate in any mild or moderate exercise were more susceptible to SHS (54.3%; 44/81) than the general population (8.1%; 3/37).

Carers are more likely to experience significant health problems than non-carers in Australia [26] with the role associated with a higher mortality rate than the general population [27]. The most common reason for taking on the role of an informal carer is a sense of family responsibility (70.1%) [7]. More recently, researchers discovered that carers have a higher prevalence of chronic conditions than the general population and are able to elucidate the specific chronic diseases involved: mental health disorders, CVD, T2DM, chronic obstructive pulmonary disease, asthma and arthritis [38]. A follow-up study from the same authors found carers had a higher prevalence of depression, anxiety, T2DM and arthritis than the general population, were more likely to report their health as being fair/poor and were more likely to have higher BMI and waist-hip ratio (WHR) than the general population [37]. Further, research has found carers have different biomedical profiles compared to the general population [37].

This study demonstrates that screening carers via the SHSQ-25, through the lens of PPPM, affords a predictive approach by identifying firstly that carers are at greater risk of developing chronic disease than the general public.

Specifically, carers were found to have significantly lower serum vitamin D and haemoglobin levels than the general population. The vitamin D finding is significant considering its role in preventing osteoporosis, especially considering post-menopausal women make up more than half of all female carers [37]. Caregiver-based studies need to become a part of mainstream biomedical research at both epidemiological and clinical levels [38]. Moreover, research has shown that COVID-19 has dramatically increased the early development of chronic diseases in unpaid carers.

Expert recommendation

Aspects presented in this article encompass the needs of unpaid carers, personalised screening assessments for SHS (via the SHSQ-25) to predict the risk of chronic disease development, and the cost-efficacy of implementing such a program in this vulnerable population. These pillars are in alignment with the paradigm change from reactive medicine to PPPM as promoted by the EPMA. Adoption of these recommendations has the capacity to decrease delayed diagnosis and intervention, reduce untargeted prevention and ineffective treatment, and ultimately improve quality of life outcomes for carers and healthcare system sustainability [7]. Recognising the SHSQ-25 and its role in screening for SHS will contribute to PPPM’s principles by going being the state of the art, shifting the paradigm from reactive to proactive medicine.

For the first time from the perspective of PPPM, we made the novel discovery that healthy carers, who are yet to experience significant health problems, are 6.4 times more likely to develop SHS than healthy members of the general population. We recommend:

1.

Identification of SHS enables targeted interventions to be initiated before the onset of clinical symptoms, delaying or changing disease trajectories, and preventing disease from occurring in the first place in the primary care setting [8].

2.

As a PPPM tool, SHS’s capacity to deliver personalised care directs valuable resources to where they are most needed, conferring both health and economic benefits to healthcare systems [8].

3.

Considering there are over 860,000 primary carers in Australia, the majority being female, and the fact that they experience a higher prevalence of health problems compared to females in the general population, our results are a sobering reminder to governments of the disadvantage faced by carers in the social determinants of health.

4.

Our research should serve to guide future policies and direct future women’s health prevention strategies. Investment in the SHSQ-25 for the screening of SHS in carers would offer a simple, low-cost, highly effective tool for the detection of SHS.

5.

Effective PPPM measures, such as SHS, that can reduce chronic disease burden by the smallest proportion and have the capacity to significantly mitigate their economic impact on health systems, warrant special attention [4]. This is especially true considering the WHO’s recent calls for evidence-based, cost-effective disease prevention strategies to alleviate the burgeoning costs and complications of chronic diseases [10].

This research evidences the SHSQ-25 as the novel PPPM tool in the fight against chronic disease in women’s health, and more specifically, unpaid female carers.