Authors: Yash Desai, Haitham Khraishah, Barrak Alahmad
Categories: Mini-Review, CVD, Climate change, Heatwaves, Hot temperatures, cardiovascular
Doi: 10.59249/HGAL4894
Authors: Yash Desai, Haitham Khraishah, Barrak Alahmad
Globally, more people die from cardiovascular disease than any other cause. Extreme heat can have serious implications for heart health, especially in people with pre-existing cardiovascular conditions. In this review, we examined the relationship between heat and the leading causes of cardiovascular diseases as well as the proposed physiological mechanisms for the deleterious effect of heat on the heart. The body’s response to high temperatures, including dehydration, increased metabolic demand, hypercoagulability, electrolyte imbalances, and systemic inflammatory response, can place a significant strain on the heart. Epidemiological studies showed that heat can result in ischemic heart disease, stroke, heart failure, and arrhythmia. However, targeted research is needed to understand the underlying mechanisms of hot temperatures on these main causes of cardiovascular disease. Meanwhile, the absence of clinical guidance on how to manage heart diseases during heat events highlights the need for cardiologists and other health professionals to lead the charge in addressing the critical relationship between a warming climate and health.
The United Nations Intergovernmental Panel on Climate Change (IPCC), in its 2021 sixth assessment report from Working Group 1’s contribution, said that scientists were certain that the intensity and recurrence of heat events have increased globally since the last century [1]. It is incredibly rare for scientists to use language that does not express any uncertainty. Globally, by the end of the century, the average temperatures are expected to increase by 2.4°C (“moderate” climate change scenario) and 4.4°C (“extreme” climate change scenario), compared to pre-industrial times (from 1850 to 1900) [2]. This increase in average temperature will result in globally unprecedented heat in many areas around the world.
Exposure to higher than average temperatures seen over the last few decades have been associated with an increase in all-cause mortality in the United States [3]. From 2004-2018, an average of 702 deaths annually were attributed to heat [4]. A global analysis estimated that heat could be responsible for 490,000 excess deaths each year [5]. As climate change continues to worsen [6], if no adaptation is undertaken, the heat-related excess mortality is expected to almost triple between 2030 and 2050 [7]. In addition to mortality, hot weather has been associated with significant morbidities as well, such as increase in chronic respiratory disease exacerbations [8,9], increase in emergency room visits for ischemic heart disease and stroke [10], preterm deliveries [11], psychiatric illness related hospitalizations [12], and food- and water-borne infectious diseases [13].
Particularly, increasing temperature’s impact is salient for those with cardiovascular disease (CVD). Despite major advances in preventive cardiology, CVD has remained the leading cause of global mortality [14]. Additionally, since the 1990s, there has been a steady increase in disability-adjusted life years (DALYs) due to cardiovascular disease [14]. Questions remain to what extent extreme hot temperatures can affect cardiovascular health? A metanalysis showed that the risk of cardiovascular mortality increases with every 1°C increase in heat exposure [15]. Another metanalysis demonstrated a 15% increase in CVD mortality during heatwaves [16]. In a recent 2022 meta-analysis, heatwaves increased the risk of CVD related mortality by 11.7%, with even higher risk for older population (age >65) [17]. And a recent global analysis from 27 countries estimated that for every 1,000 cardiovascular deaths, two excess deaths were attributed to extreme heat [18]. In this review, we examine the relationship between heat and the leading causes of CVD as well as the proposed physiological mechanisms for the deleterious effect of heat on the heart.
Defining what are considered extreme temperatures is important to study epidemiologically the effect of temperature on CVD. Typically, extreme temperatures are defined by environmental metrics, such as, ambient temperature, or the temperature of the air exceeding a predefined threshold that is determined based on location-specific historical averages [19]. Currently, there is no certain Celsius or Fahrenheit temperature value that can be defined as extreme temperature everywhere. The impact of temperature, however, will differ based on region and time of the year. For example, an extreme temperature event, say a 40°C day (104°F), can have different implications for health depending on where and when it occurs. A 40°C temperature in Kuwait is a typical summer day, whereas a 40°C in London (seen in summer 2022) or in the Pacific Northwest (seen in summer 2021) could result in widespread and incalculable damage. Even within the same country, a 35°C (95°F) day in Vermont in the US is incomparable to a 35°C day in Texas. In the literature, the definition of extreme temperatures relied on the percentiles of the temperature distribution a particular location in a specific time frame (eg, the hottest 1%, 2.5%, or 5% of days in a given year) [20-22]. Once extreme hot days are sustained for a number of consecutive days, it is usually called a heatwave [23]. There is no consensus to define what is an extreme hot cutoff and what is a heatwave, however, common examples from the literature are shown in Table 1.
The mechanisms linking extreme hot temperatures to different cardiovascular diseases are related to dehydration, hemoconcentration, hypercoagulability, sympathetic activation, and inflammatory mediators. During extreme heat, there is an increase in skin blood flow (SkBF)to cool the body through sweating and evaporation. This physiological reaction may lead to dehydration, hemoconcentration, hypercoagulable state, and electrolyte derangements [24]. Hypercoagulable states may lead to clot formation leading to acute coronary events or stroke (Figure 1). Electrolyte derangements may trigger different types of arrhythmias. Electrolytes, such as sodium, potassium or magnesium, play a vital role in genesis of the transmembrane action potential and therefore electrolyte imbalance can alter action potentials of cardiac myocytes leading to arrhythmias [25]. Additionally, dehydration can activate the sympathetic nervous system, leading to an increase in heart rate and cardiac metabolic demands. In patients with pre-existing CVD, this can cause demand-supply mismatch triggering ischemic events and even plaque rupture, ending in stroke or heart attacks [26].
Similar mechanisms are responsible for the impact of heat on heart failure exacerbations. Additionally, data suggests that cutaneous vasodilation and sweating responsible for adjusting to extreme heat are impaired in patients with heart failure [27]. Studies demonstrate impaired heat-induced increase in SkBF in heart failure patients [28,29]. The precise mechanism behind this finding is not well understood, however, it is hypothesized that attenuated SkBF response in heart failure patients may be explained by endothelial dysfunction [30,31] and impaired nitric oxide-dependent vasodilation in these patients [31-33]. However, further studies are needed to elucidate attenuated SkBF in heart failure.
Additionally, a key component in treating heart failure is the use of diuretics such as furosemide, torsemide, or bumetanide, to promote natriuretic effect by inhibiting the sodium-chloride cotransport system in the loop of Henle [34]. This can exacerbate dehydration states and cause electrolyte imbalances.
In the event of heat stroke, dehydration and sympathetic activation redirects blood flow away from the gut; this decrease in gut blood flow leads to gut ischemic and an increase in gut epithelial membrane permeability, allowing harmful substances such as bacterial lipopolysaccharide and HMGB1 to enter the bloodstream. This triggers a systemic, overwhelming immune response through the activation of toll-like receptor 4, causing a systemic inflammatory response syndrome, or SIRS. Additionally, damaged vascular endothelium prompts microvascular clotting and multi-organ system failure, including cardiovascular dysfunction [35].
Ischemic heart disease is the most common cause of CVD mortality. The impact of cold temperatures on myocardial infarction (MI) hospitalizations has been well described in literature [36], whereas the impact of heat on acute MI has been less robust [37]. With increasing frequency of extreme heat and trajectory of global warming, the impact of heat on ischemic heart disease will become more apparent. In a recent large database study looking at a multi-country dataset from 27 countries, periods ranging from 1979-2019, extreme heat was associated with a 7% increase ischemic heart disease mortality [18]. In one of the largest meta-analyses on temperature-CVD studies, there was a positive relationship between increasing temperature and coronary heart disease with a 2.8% increased risk for every 1°C increase in temperature above reference temperatures [17]. Several other smaller studies have reported statistically significant increases in coronary artery disease-related hospitalizations and emergency department (ED) visits during heat wave exposure [38,39].
Stroke is the third leading cause of death worldwide [14]. Stroke can broadly be classified as either ischemic or hemorrhagic stroke. Hemorrhagic strokes can be further classified as subarachnoid hemorrhage or intracerebral hemorrhage. A literature review suggests a significant association between extreme temperature on the risk of any stroke. In a large meta-analysis of more than 2 million events of all types of stroke, an increase of 1°C increased the risk by 1.13% and that a decrease in 1°C increased the risk by 1.2% [40]. This risk was more pronounced in those aged ≥ 65 years. Stroke mortality was also associated with an increase of 1.5% for every 1°C increase in temperature, and an increase of 1.2% for every 1°C decrease in temperature [40]. A recent study with large database of 9,351,312 stroke (from any cause) deaths reported 1.6 additional deaths for every 1,000 stroke deaths attributed to extreme heat days [18]. Although the literature has shown more consistent relationship between hot temperature and all types of strokes, when evaluating the effects of hot temperature on subtypes of stroke, ischemic or hemorrhagic, data remain conflicting. For example, a systemic review and meta-analysis of 21 studies with total population of 476,511 patients found no significant association between hot temperature and ischemic stroke [41]. Another study [42] evaluated more than 3,000 incident cases of ischemic stroke from January 1, 2004, to December 31, 2013 in Seoul, South Korea, found that mean temperature was positively associated with ischemic stroke (relative risk, 1.006; P=0.003) [42]. A study based in China [43] evaluated the effect of heat exposure on total, ischemic, and hemorrhagic stroke mortality by performing a multi-city study of 12 cities in Jiangsu Province from 2009-2013. The study found that heat-related mortality risk was 1.54 (95% CI: 1.44 to 1.65) for total stroke, 1.63 (95% CI: 1.48 to 1.80) for ischemic stroke, and 1.36 (95% CI: 1.26 to 1.48) for hemorrhagic stroke, respectively. As more studies are emerging, our understanding of the association between heat and the etiologies of cerebrovascular incidents will be considerably enhanced. Consequently, a definitive consensus on this subject remains to be established.
Until recently, there was lack of literature data evaluating the relationship between extreme temperatures and heart failure. Heart failure presents either through defects in ventricular filling (heart failure with preserved ejection fraction, HFpEF), or through impairment in ejection of blood to the systemic circulation (heart failure with reduced ejection fraction, HFrEF). Previous studies have focused on seasonality and the rate of heart failure admissions [44], with data showing an increase in heart failure related admissions and mortality during winter months [44,45]. A recent large database study involving multi-country data with 3,673,723 heart failure deaths showed a significant impact of extreme hot temperatures on heart failure related mortality with 2.6 excess deaths for every 1,000 heart failure deaths (95% CI: 2.4-2.8) [18]. Extreme heat led to 12% increase in heart failure related death (relative risk 1.12 with 95% CI: 1.05–1.19) [18,37]. We know of no studies that evaluated the effects of heat on the two types of heart failure.
The evidence does not show a consistent relationship between extreme heat and arrhythmia related mortality or admissions. A South Korea based study using data from 31,629 arrhythmia-related ED visits found that each 1°C increase in diurnal temperature (difference between the maximum and minimum temperatures within 1 day) range was associated with an increase in the attributable risk of cardiac arrhythmias by 1.84%. Similarly, another study demonstrated that 1°C increase in the same day residence-specific temperature, the odds of having ventricular ectopy episodes was 1.10, and the odds associated with 1°C increase in central temperature was 1.05 [46].
However, in another study of 345,052 individuals admitted for arrhythmia in Ontario, Canada, there was no association seen between extreme temperatures on arrhythmias related admissions or mortality [47]. A study in London, England examined the risk of temperature on activation of implanted cardiac defibrillators (ICDs). The study demonstrated no significant increase in risk of ICDs activation during higher than average temperatures [48].
Despite the growing body of evidence suggesting that climate change is having a negative impact on global cardiovascular health, much of the research has focused on high-income countries. Low- and middle-income countries, which are often more vulnerable to the impacts of climate extremes, have been underrepresented in the scientific literature. The limited research that has been conducted in these regions has shown that populations in low-income countries are particularly vulnerable, not only to heat-related illnesses, but also water-borne diseases, malnutrition, respiratory problems, and others. The main research challenges arise from the lack of resources and infrastructure, which makes it difficult to conduct large-scale studies and track cardiovascular health impacts over time. In many countries, rich or poor, the health systems are often already overburdened, and the added strain of climate change-related health impacts can be detrimental.
Abnormal weather patterns can exacerbate the vulnerability of individuals suffering from cardiovascular disease. The lack of formal guidance or recommendations from prominent cardiology societies such as the American Heart Association (AHA) and the European Society of Cardiology (ESC) is a concerning issue. There are no official statements from these leading organizations on how healthcare providers can minimize the risks associated with extreme temperatures for those with cardiovascular disease. For example, what would be the best approach to balance heart failure patients’ diuretic medications during a heat wave? What medications can be started or halted during these extreme events? As temperatures continue to rise, it is imperative that healthcare professionals and cardiologists take a proactive approach and take ownership of the climate-health relationship and make it a priority in their field.
The relationship between heat and the heart is an area of ongoing research. The role of temperature fluctuations and its effect on the occurrence and outcome of cardiovascular disease should be a focus in future population- or community-based studies. Targeted research is needed to understand the underlying mechanisms of hot temperatures on the main causes of cardiovascular disease. Studies should also aim to assess the impact of preventive measures aimed at reducing the effect of temperature on cardiovascular disease, especially in resource-limited settings.