The Impact of Heatwaves on Mortality and Morbidity and the Associated Vulnerability Factors: A Systematic Review

Background: This study aims to investigate the current impacts of extreme temperature and heatwaves on human health in terms of both mortality and morbidity. This systematic review analyzed the impact of heatwaves on mortality, morbidity, and the associated vulnerability factors, focusing on the sensitivity component. Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 flow checklist. Four databases (Scopus, Web of Science, EBSCOhost, PubMed) were searched for articles published from 2012 to 2022. Those eligible were evaluated using the Navigation Guide Systematic Review framework. Results: A total of 32 articles were included in the systematic review. Heatwave events increased mortality and morbidity incidence. Sociodemographic (elderly, children, male, female, low socioeconomic, low education), medical conditions (cardiopulmonary diseases, renal disease, diabetes, mental disease), and rural areas were crucial vulnerability factors. Conclusions: While mortality and morbidity are critical aspects for measuring the impact of heatwaves on human health, the sensitivity in the context of sociodemographic, medical conditions, and locality posed a higher vulnerability to certain groups. Therefore, further research on climate change and health impacts on vulnerability may help stakeholders strategize effective plans to reduce the effect of heatwaves.


Introduction
The anthropogenic greenhouse has impacted the earth, resulting in climate change and increasing the global temperature. This is referred to as global warming and has caused extreme climate and weather events such as heatwaves, heavy rainfall, and drought [1][2][3]. The latest Intergovernmental Panel on Climate Change (IPCC) report showed that heatwaves have become more common and intense over the past 50 years [4].
The impacts of heatwaves on human health are evident, with health outcomes from mortality and morbidity reported. A heatwave event can be significant and often disastrous, as shown by excess deaths during the European heatwave of 2003 and the Central European and Russian heat wave of 2010 [5][6][7].
Given the devastating impact of extreme heat and heatwave events, many researchers have attempted to understand the vulnerability factors in the population [8][9][10][11]. Human vulnerability to climate change or variability is a complicated concept and has no universally accepted definition [12]. The study of the vulnerability of humans to climate change

Inclusion Criteria
It was formulated based on PECO [41], a tool based on three main concepts: participants (human), exposure (heatwave), comparator (mortality and morbidity), and outcomes (vulnerability factors). Included were research-based articles, peer-reviewed, English publications from 2012 to 2022 focused on heatwaves, study findings comprising both heatwave-related mortality/morbidity impact and vulnerability factors (focusing on the sensitivity component), and involved human participants.

Study Selection and Data Search
Related articles were identified by searching the Scopus, Web of Science, EBSCO host, and PubMed databases. The search string was created and generated using Boolean operators and keyword search (Supplementary Table S1). Following the removal of duplicates, two reviewers independently examined the titles and abstracts of all identified studies to select the articles based on the predetermined selection criteria.

Quality Assessment
The article's quality was determined by using the Navigation Guide Systematic Review framework [41] (Supplementary Table S2 and Figure S1). The third reviewer resolved any disagreement.

Data Extraction and Synthesis
Following the initial search, we created a standardized form to extract the following data: author and study year, study design, study location, type of climate, meteorological data, heatwave definitions, health data, statistical analysis, heatwave impact on mortality and morbidity, as well as the sensitivity component of vulnerability assessment.
Selected articles were divided into two groups based on mortality and morbidity outcomes. Sensitivity factors and statistical results from the quantitative analysis were thoroughly described using a narrative synthesis. Finally, the findings of the selected articles were merged using a narrative approach for the overall results.

Results
A total of 32 articles were selected and analyzed to identify the impact of heatwaves on mortality, morbidity, and the associated vulnerability factors (focusing on the sensitivity component) (Figure 1). Most articles involved time series studies (n = 27), and the rest were case-crossover studies (n = 5). The included articles represented most of the continents in the world: Asia, 14; Oceania, 8; Europe, 5; North America, 4; and South America, 1. In addition, the articles spanned lower, upper, middle, and high-income countries. Most of the studies were conducted in warm and temperate regions (n = 19) and cold and temperate (n = 7). The rest of the studies were conducted in the tropical region (n = 3), low and subarctic region (n = 2), and temperate region (n = 1). Fifteen articles described mortality's impacts and vulnerability factors (focusing on the sensitivity component), while another eighteen addressed morbidity. Table 1 summarises the characteristics and main findings of the studies included in this systematic review.

Heatwave Impact on Mortality
The included studies had various mortality indicators. The main mortality indicators were overall (all-cause) mortality, non-external cause of mortality, and cause-specific mortality. Most articles (n = 14) reported a significant association between heatwaves and mortality.

Sensitivity Component of Vulnerability Assessment for Mortality
The highest-ranked sensitivity of the vulnerability assessment was elderly age, with eleven articles. Here, we studied two categories of the elderly, ages > 65 years and >75 years. A study in China showed that people aged >65 years comprised a high percentage of the total non-accidental mortality data (average annual loss (AAL) = 61.3%, 95% CI: 30.6, 91.9) [33], while another by Wang et al. (2015) reported that the >75-year age group had the highest mortality (RR 1.46, 95% CI: 1.28, 1.66) [43]. The female and male gender had the second and third highest reported sensitivity of the vulnerability assessment with five and four articles, respectively. A study conducted in China reported that the female gender had a higher risk of heatwave-related cardiovascular mortality compared to males [50]. Another study in Finland reported that the female gender had a higher heatwave-related non-accidental mortality risk with 12.5% (95% CI: 9.1-16.0%) [62]. Meanwhile, a study in Australia reported that the male gender had a 1.22 times higher risk for heatwave-related non-accidental cause mortality (RR 1.22, 95% CI: 1.05, 1.42) [43]. A study in a cold temperate region also showed that the heatwave-related non-accidental mortality risk increased by 7.2% (95% CI: 3.3-12.0%) among the male gender [62]. Three articles reported that people with cardiovascular diseases had a significant mortality risk due to heatwave exposure. The study in Tehran showed that cardiovascular disease contributed about 52% of the total cause of death [27]. Two articles reported that people with respiratory diseases showed significant mortality risk due to heatwave exposure. People with respiratory disease accounted for 52% total cause of heatwave-related mortality [27].
The other essential sensitivities of the vulnerability assessment were low education level, renal disease, mental disease, diabetes, and rural area, with one article each. Tables 2  and 3 show additional information.

Heatwave Impact on Morbidity
Eighteen articles showed a significant association between heatwave exposure for the morbidity impact. In this systematic review, morbidity was classified into heat-related illness (heatstroke), hospital admission (non-specific), cardiovascular-related hospital admission (non-specific, arrhythmia), respiratory-related hospital admission (non-specific, asthma, chronic obstructive pulmonary disease), infectious-related admission, urinaryrelated admission, Alzheimer's disease-related admission, diabetes-related hospitalizations, emergency department (ED) visit, and ambulance callout. A USA study reported that excess respiratory admissions due to heatwaves would be 2 to 6 times higher from 2080 to 2099 than in 1991-2004 [42]. Meanwhile, a study in South Korea showed that heatwaves increased cardiovascular-related hospital admission by 14% [45]. Significant increment of heatwave-related urinary disease admissions by 88.3% compared to non-heatwave days [48]. Another in Australia reported an effect on hospitalization for diabetes during heatwaves (OR 1.37, 95% CI: 1.11, 1.69) [55].

Sensitivity Component of the Vulnerability Assessment for Morbidity
The highest-ranked sensitivity of the vulnerability assessment was being elderly, with 13 articles reporting similar findings. A study in Australia that measured the impact of heatwaves on hospital ED visits showed that patients aged >75 years had significant risk factors (RR = 1.28, 95% CI: 1.09, 1.50) [11]. A study in the USA showed that the elderly had a significant association with hyperthermia-related hospitalization (RR 11.4, 95% CI: 9.55, 13.25) [56].
Seven articles reported that children had a significant association with heatwaverelated morbidity. Heatwaves increased the risk of all-cause hospitalizations among children by 11% [31]. For heatwave-related ambulance callouts, children < 5 years old have a significant sensitivity in the vulnerability assessment (OR 1.36, 95% CI: 1.10, 1.68) [61]. The male gender followed this with six articles. A study in the USA showed male gender had a significant risk for heatwave-related asthma hospitalization (Odds ratio (OR) 1.12, 95% CI: 1.04, 1.22) [9] and a significant vulnerability assessment for cardiovascular-related admission by Kang et al. (2016) [45]. A study on heatwave-related ambulance callouts showed male gender as a significant sensitivity of the vulnerability assessment (RR 1.03, 95% CI: 1.02, 1.03) [54].
Heatwaves significantly impacted patients with cardiorespiratory diseases such as asthma, chronic obstructive pulmonary diseases, and pneumonia, found in this study [9,11,42,46]. In addition, a study in Australia found that respiratory and cardiovascular diseases increased emergency department visits by 2% and 1%, respectively, during heatwave days [11]. A population-based retrospective cohort study showed a significant increase in hospitalization for diabetic patients during heatwaves [55]. Five articles reported low socioeconomic status was significantly associated with heatwave-related morbidity. A study by Toloo et al. (2014) showed that low socioeconomic status was associated with increased emergency department visits by 12% compared to non-heatwave days [11]. Meanwhile, four articles reported female gender is a significant risk factor for heatwave-related morbidity. Another study in Vietnam showed that the female gender was associated with increased all-cause hospitalizations by 8.1% (95% CI: 2.6-13.9%) [46]. Tables 2 and 3 show additional information.

Heatwave Impact on Mortality and Morbidity
Included articles in this systematic review showed that exposure to heatwaves negatively impacts mortality and morbidity. However, the impact varied across studies and regions. For example, the literature included in the present study had multifactorial causes of mortality and morbidity indicators. Most of the causes of death were related to the cardiovascular and respiratory systems, which might be due to these diseases being the most common worldwide. The impact on morbidity also had varying underlying causes. However, the most common cause of heatwave-related hospitalizations was similar to that of mortality; cardiopulmonary-related diseases.

Sensitivity Component of Vulnerability Assessment
This current review adopted the sensitivity component of the vulnerability assessment proposed by a previous study [26]. It is ideal for studying all the components of vulnerability assessment for a more comprehensive finding. However, the diversity of vulnerability conceptualizations is seen in different contexts, referring to different systems being exposed to different hazards [13,66,67]. In this review, three major sensitivities of the vulnerability assessment factors were identified: sociodemographic, medical conditions, and locality characteristics.

Sociodemographic
Age was one of the critical factors for the population's vulnerability to heatwave exposure. The review shows that the impact of heatwaves on mortality and morbidity involves all age groups, the elderly group being the most vulnerable, explained by the decreased efficiency in body temperature regulation because of aging [68]. In addition, it is common for this group to live with co-morbid chronic medical illnesses such as heart disease and chronic obstructive pulmonary disease (COPD) [69]. Thus, combined risk factors of age and co-morbidity increase the susceptibility to heat-related illnesses. Additionally, children are at risk due to their underdeveloped body regulatory systems [70]. They are also vulnerable as they tend to spend more time playing outdoors [70]. People in the working-age group are also at risk from the impact of heatwaves due to their work activities [71].
In this review, the risk for heatwave impacts varies across gender, which can be influenced by factors such as pre-existing medical conditions, social support, and the type of work exposure of a particular person. For example, males may be at risk in some locations where outdoor work roles are predominantly male-dominated [28]. However, females may be at greater risk as women had a higher risk due to a high surface-to-mass ratio and greater subcutaneous fat thickness than men [72]. Low socioeconomic status has been identified as a common risk factor for any disease or health issues, including vulnerability to the impact of heatwaves [73,74]. There are reasons that make those living in low socioeconomic classes more vulnerable to the effects of heatwaves. Lower socioeconomic status is commonly associated with other medical conditions, such as malnutrition and infectious disease, which can aggravate the impact of heatwaves on health. In addition, because of their financial status, this group has less access to household amenities, such as fans, proper housing ventilation, and AC, which are essential for reducing the impact of heatwaves by cooling the body temperature. The nature of jobs commonly associated with outdoor work, such as construction and menial jobs, exposes people to high temperatures. Using fans and air conditioners reduces the risk of heat-related death [75]. These amenities are essential for faster body cooling and avoiding the harmful effects of heatwaves. This will be a problem, particularly for people in low and middle-income countries.
A lack of knowledge of heatwaves may expose a person to the negative impact of heatwaves on health. Most media sources provide vital information on heatwaves, such as their effects and preventive measures. However, better understanding requires knowledge and education levels. Thus, a person with a lower education level is subject to a more significant impact than a more educated person.

Medical Conditions
People with specific medical conditions are vulnerable to heatwaves. In the present systematic review, several medical conditions showed significant evidence of heatwave adverse effects on mortality and morbidity.
People with cardiovascular disease are affected by heatwave exposure. The underlying pathophysiologic mechanism for the relation between heat stress and cardiovascular disease, such as increased red and white cell counts in the circulation, leads to increased blood viscosity, platelet release into the bloodstream, and reduced plasma volume [76].
A similar impact is seen in people with respiratory disease. Human thermal regulation attempts to maintain a safe body temperature during heatwave exposure, resulting in increased cardiac output and hyperventilation. Consequently, the respiratory rate and tidal volume will increase, worsening respiratory diseases such as asthma and COPD and requiring hospitalization [77]. People with renal disease can be compromised during a heatwave. The underlying mechanism is that exposure to heatwaves increases dehydration risk and leads to electrolyte imbalance [78], which imposes extra stress on renal function and exacerbates pre-existing renal diseases. Autonomic neuropathy in diabetic patients makes them more vulnerable to heatwave effects [79].
In addition, heatwaves increase the risk of mental health-related outcomes. One possible explanation is exposing people to psychological trauma associated with higher frequency, intensity, and duration of climate-related disasters, including extreme heat exposure or heatwave events [80]. Identifying the population suffering from these medical conditions could help local health authorities and service providers incorporate mental health impacts into their heatwave warning systems, as well as develop public health policies and guidelines to address preventable heat-related mental health mortality and morbidity.
However, the findings of these medical conditions on mortality and morbidity varied between studies. This scenario can be explained by the variability of other factors influencing the outcome. Thus, further studies are warranted to address this uncertainty.

Locality
In rural areas, the population is at risk of the impact of heatwaves, possibly due to socioeconomic factors, medical infrastructure, and the aging population. For example, economic activities in rural areas are conducted outdoors, and a heatwave's impact during extreme heat can be amplified. Thus, evaluating this population's knowledge, perception, and adaptive behavior is crucial for an early preventive plan.
Meanwhile, urban areas are commonly associated with the urban heat island (UHI) phenomenon. The UHI effect is mainly due to human activities and construction that lead to heat accumulation [81]. The effects of UHI can be mitigated by improved energy efficiency, urban landscape optimization, green roof construction, high reflectivity material utilization, and green land cultivation. Different climatic zones also play a role in determining the population's heat sensitivity. Different climatic zones had different effects in this review. Acclimatization of the people, behavioral adaptations, medical infrastructure, availability of heat warning systems, and other factors could play a role.
Most of the literature included in this review was from developed countries. One possible explanation is that these countries have sufficient resources for studying this topic and publishing their findings. Developing and warmer countries, such as Southeast Asia, experience more frequent, long-lasting, and intense heatwaves [82]. However, there are limited publications from these countries, which may underestimate the burden of heatwaves on these particular countries.

Conclusions
Mortality and morbidity indicators, including all-cause and cause-specific, are critical for measuring heatwave impacts on human health. The sensitivity in the context of sociodemographic, medical conditions, and locality posed a higher heat vulnerability to certain groups. The impact of heatwaves on mortality and morbidity involves all age groups, especially the elderly and children. People with specific medical conditions, particularly cardiovascular and respiratory diseases, are most vulnerable to heatwave impacts of mortality and morbidity. The impact of heatwaves on mortality and morbidity and their associated vulnerability factors varies depending on the locality. These findings can help stakeholders strategize effective plans to reduce the effects of heatwaves according to their target populations and respective areas. Nevertheless, further study on the other component of vulnerability assessment, such as adaptive capacity, will provide more information on identifying vulnerable populations.
Supplementary Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/ijerph192316356/s1, Table S1: Keyword search used in the screening process; Table S2: Navigation Guide Systematic Review ratings of each study; Figure S1: Weighted bar plots.