Cardiovascular challenges of aging in a hotter environment: A narrative review

Abstract

The increase in duration, severity, and frequency of extreme heat will have a profound detrimental impact on human health, as extreme heat is the deadliest weather-related event around the world. At the same time, the population of older (>65 yrs) adults is rapidly expanding. The exaggerated heat coupled with an aging population increase the number of people at risk during environmental extremes. During heat waves, cardiovascular events and complications secondary to elevated core temperatures are the leading cause of increased morbidity and mortality among older adults. Seminal work demonstrates an impaired cardiovascular response to elevated core and skin temperatures in older adults, resulting in an attenuated capacity to lose heat coupled with increased cardiac strain, in support of the epidemiological data. Here, we review the impact of heat stress on the aged cardiovascular system and highlight the question: “In what specific environments does an increased cardiovascular strain begin to occur in older adults?”.

Graphical Abstract

Introduction

Prolonged and severe environmental heat is the deadliest weather-related phenomenon globally [1]. As global temperatures continue to rise, the duration, severity, and intensity of heat waves have increased [2]. Billions of people are currently exposed to prolonged extreme heat, and with only a 2°C increase in average global temperature, that number is projected to drastically increase [3]. At the same time, the number of adults aged >65 yrs is rapidly growing. By 2050, the global percentage of older adults is expected to be 16.7%, or approximately 1.6 billion people [4]. The increase in extreme environmental heat coupled with an aging population is an existential threat to human health, as older adults are the most vulnerable population with respect to heat-related morbidity and mortality [5].

This Mini-Review focuses on navigating the cardiovascular challenges of aging in a warming world. Specifically, we begin by documenting recent (within 10 yrs) epidemiological evidence that the increased morbidity and mortality among older adults during extreme heat (i.e., during heat waves or heat events) is primarily of cardiovascular origin. We then discuss the mechanisms through which heat stress creates cardiovascular strain, and how aging exaggerates that strain on the heart as well as adversely affecting heat dissipation. This work involves seminal investigations into the mechanisms that lead to age-related decrements in skin vasodilation and a relative inability to increase cardiac output, as well as recent work investigating potential age-related impairments in myocardial blood flow. Finally, we discuss recent work that has aimed to identify precise critical environmental conditions in which these age-related decrements become apparent in the form of cardiovascular drift, perhaps signaling the onset of excess cardiovascular strain.

Cardiovascular morbidity and mortality during extreme heat

There is an abundance of epidemiological data supporting increased heat vulnerability among the older adult population. Many of those reports have been previously reviewed in detail [6–8]; therefore, we focus here only on select recently-published work (i.e., the past ~10 years) that focus on cardiovascular morbidity and mortality during extreme heat.

Adults over the age of 65 yrs experience hospitalization [9] and/or death [10] due to heat exposure at higher rates compared with any other age group. Most of the hospitalizations and deaths in this population are attributed to heat-induced cardiovascular sequalae. For example, during each summer over the past decade in New York City, there were approximately 580 deaths on average due to either a direct result of heat, or due to an underlying condition exacerbated by heat (Figure 1A) [10].

Figure 1.

Average total heat-related deaths (Panel A) and a breakdown of heat-exacerbated deaths (Panel B) during the summer months in New York City. The majority of heat-related deaths are due to heat exacerbating an underlying condition, rather than a direct result of heat stress. The most common underlying condition exacerbated by the heat, resulting in mortality, is CVD (New York City Department of Health) [10].

Extreme heat particularly exacerbates cardiovascular complications in adults with pre-existing cardiovascular disease (CVD). When temperatures exceed the 90^th percentile for a given region, the risk ratio for all-cause CVD, heart failure, ischemic heart disease, and stroke drastically increase [11]. Individuals with heart failure have been shown to have the greatest mortality risk during heat waves [12] and as temperatures continue to increase, the risk of heat-related ischemic heart disease in those with pre-existing CVD increases as well [13]. Further, a recent meta-analysis showed that a 1°C increase in temperature was associated with a 2% increase in mortality for a variety of CVDs, and a 12% increase as heat wave intensity increased (i.e., as the mean temperature of the heat wave increased) [14]. Of the individuals who had an underlying condition exacerbated by the heat in New York City over the past decade, 62% had CVD (Figure 1B) [10].

In addition to more cardiovascular events occurring during exposure to isolated, or anomalous, extreme heat waves or events, the increase in average ambient temperature is also associated with increased cardiovascular-related morbidity and mortality. Above a region-specific threshold temperature (i.e., a temperature that is unique to each region above which mortality begins to increase), a 1°C increase in temperature was associated with a 3% increase in cardiovascular mortality among older adults [15]. In the United States alone, cardiovascular mortality increased by 0.12% among older adults for each additional extreme-heat day per month, resulting in approximately 5,000 excess cardiovascular deaths attributed to extreme-heat days from 2008 – 2017 [16]. Projecting into the future, excess cardiovascular deaths associated with extreme heat days in the United States are projected to increase 187% among older adults between 2036 and 2065 [17].

Age-related changes in cardiovascular responses to whole-body heating

What underlies the epidemiological link between environmental heat stress and cardiovascular strain? The ability to increase cardiac output is imperative to allow for, and sustain, thermoregulatory effector responses (i.e., skin blood flow and sweating) to elevated body temperatures. As such, thermoregulatory demands during heat stress can place considerable strain on a compromised cardiovascular system in older adults.

Heat-related increases in cardiac output

Minson et al. [18] were the first to measure cardiac output in older adults during prolonged passive heating. In that study, young men’s cardiac output values doubled to 11 L/min, but only reached ~7 L/min in older men at a core temperature increase of 1°C [18]. Although the absolute heart rate (HR) response was similar between the two age groups (i.e., end HR ~120 bpm in young and ~110 bpm in older adults), the lower maximal HR of the older cohort was associated with a lower HR reserve (~45% in young and ~58% in older adults). Whereas young adults maintained stroke volume throughout the duration of heating, the authors noted a reduction in stroke volume among the older adults. The authors concluded that increases in cardiac output were limited in older adults by an inability to maintain stroke volume, thus causing a relative increase in the reliance on elevations in HR (i.e., a greater percentage of maximal HR and chronotropic reserve) and potentially increasing myocardial strain during heat stress.

Conversely, studies that included both men and women have suggested that older adults can maintain stroke volume, but have attenuated increases in HR [19]. Using echocardiography, Lucas et al. measured indices of diastolic and systolic function in young and older adults during passive heat stress to potentially explain the reduction in stroke volume observed by Minson et al. [18, 19]. In that study, older adults demonstrated a similar magnitude of heat-induced changes in systolic and diastolic indices relative to young adults while also maintaining stroke volume, although elevated left ventricular systolic strain (global longitudinal systolic strain) was noted to meet the hyperthermic demands compared to young adults. A follow up study [20] demonstrated that older adults maintained stroke volume throughout passive heat stress, with a leftward shift of the Frank-Starling relation. The authors attributed this finding to an increase in cardiac contractility in older adults to sustain increases in stroke volume, supported by a further increase in stroke volume when cardiac filling pressures were returned to normothermic levels via rapid volume loading. While the findings remain equivocal on maintenance of stroke volume in older adults, it is clear that (1) the magnitude of the rise in cardiac output during heat stress is attenuated in older compared to young adults, and (2) increases in cardiac output in older individuals are primarily driven by increases in HR and contractility, increasing the work of the left ventricle.

Altered supply-demand characteristics of the cardiac response in disease states exacerbates the problem. Barry et al. recently quantified myocardial blood flow at varying degrees of thermal strain [21]. Young and older adults with and without coronary artery disease were exposed to passive heat stress using a water-perfused suit to increase core temperature by 1.5°C. Myocardial blood flow increased in proportion to increases in core temperature. When expressed as a relative increase in relation to maximal values, young and healthy older adults exhibited myocardial blood flows up to 50 – 60% of their myocardial blood flow reserve; however, myocardial blood flow in the older adults with coronary artery disease potentially exceeded their myocardial reserve. Of particular note, heat-induced myocardial ischemia occurred in 35% of older adults with coronary artery disease, but not in healthy young or older adults.

Heat-induced cutaneous vasodilation

Along with the age-related changes in cardiac hemodynamics, Minson et al. [18] demonstrated substantially lower skin vasodilatory responses (~2.7 L/min) in older adults compared to young adults (~5.8 L/min). This attenuated response is explained, in part, by dysfunction of the active vasodilator system. Nitric oxide is required for full expression of cutaneous vasodilation during whole body heat stress. However, older adults have reduced nitric oxide bioavailability due, in part, to increases in both arginase activity and oxidative stress [22]. Additionally, older adults have a diminished release of cholinergic co-transmitters contributing to reflex cutaneous vasodilation [23]. As such, older adults must rely on a greater percentage of an already-compromised nitric oxide pathway to increase skin blood flow, limiting the maximal vasodilatory capacity of the aged vasculature [23]. Indeed, when arginase activity was both acutely and chronically inhibited, cutaneous vascular conductance increased in older adults during whole-body heating, likely due to increased nitric oxide bioavailability and improved nitric oxide and co-transmitter-mediated vasodilation [24]. Further, when arginase activity and oxidative stress were simultaneously reduced, there was an even greater skin blood flow response in older adults during heating.

Local and systemic treatment-induced restorations of cutaneous vasodilatory capacity in older adults called to question whether limitations in cardiac hemodynamics contribute to age-related reductions in skin blood flow responses. Greaney et al. [25] passively heated older adults following supplementation with oral sapropterin, a nitric oxide synthase cofactor, to correct the peripheral vasodilatory capacity of aged skin. The authors hypothesized that as a result of the normalized cutaneous vascular function, cardiac output would demonstrate a greater increase to match the increase in skin blood flow. However, no increase in cardiac output accompanied the increase in skin blood flow. These findings may suggest that sapropterin improved redistribution of blood from visceral circulations towards the skin, and the inability to further increase cardiac output is a consequence of primary aging. Alternatively, Gagnon et al. [26] implemented rapid volume loading during passive heat stress to determine whether cardiac function limited cutaneous vasodilatory capacity in older adults. While cardiac output and cutaneous vasodilation were augmented following volume loading, questions remain as to whether cutaneous vasodilation preceded the increase in cardiac output, or the increase in cardiac output allowed for greater cutaneous vasodilation.

In addition to reduced nitric oxide bioavailability and signaling, sympathetic control of reflex cutaneous vasodilation is impaired in older adults. As core and skin temperature increase, young adults exhibit robust increases in skin sympathetic nerve activity. However, older adults have an attenuated skin sympathetic outflow for a given increase in core temperature [27]. Likewise, the slope of the linear relation between sympathetic outflow and skin blood flow is reduced in older compared to young adults, suggesting poorer end-organ responsiveness and sensitivity of the aged cutaneous vasculature during heat stress. Importantly, skin sympathetic nerve activity was able to further increase during heating in older adults when a mental stress stimulus was added [27], eliminating the possibility of a ceiling effect. Collectively, those findings suggest that impaired heat-related increases in skin blood flow in older adults are mediated by alterations in (1) afferent thermoreceptor signaling, (2) central integration of afferent signals, and/or (3) end organ responsiveness and sensitivity to sympathetic nerve activity.

Heat-induced blood flow redistribution

To support the increased skin blood flow demand, blood flow is redistributed away from inactive, visceral regions, such as the splanchnic and renal circulations. During supine, passive whole-body heating, the entirety of the shunted blood goes towards the skin, as muscle blood flow does not increase during passive heating. Young adults have the capacity to reduce combined splanchnic and renal blood flows by ~1 L/min; however, older adults experienced less vasoconstriction in these circulations, redistributing 30% less blood flow [18]. A follow up study by Gagnon et al. suggested the reduced redistribution of blood flow during heat stress in older adults is explained by decreased sensitivity of the renal and splanchnic vasculatures to adrenergic stimulation, rather than a reduction in sympathetic outflow towards these regions [28], providing further evidence for reduced end organ responsiveness to sympathetic nerve activity.

Taken together, these studies demonstrate the impact of age on cardiovascular adjustments that occur in response to heat stress (see Figure 2). Attenuated increases in cardiac output in older adults are primarily due to an age-related reduction in HR, although older adults must work at a higher percentage of their HR reserve and increase cardiac contractility in order to maintain stroke volume – both of which serve to increase strain on an already-weakened cardiovascular system (e.g., decreased β-adrenergic responsiveness of the left ventricle that accompanies aging). Furthermore, impaired blood flow redistribution and skin blood flow responses, coupled with reduced sweat rates, results in greater heat storage (although this is context dependent; higher skin blood flow can result in greater convective heat gain, rather than heat loss, in very hot environments), thereby theoretically requiring further cardiovascular adjustments and increases in cardiovascular strain.

Figure 2.

The effect of age on cardiovascular responses to passive supine heating to the limits of thermal tolerance. Older adults have an attenuated increase in skin blood flow. The attenuated increase in skin blood flow is primarily due an attenuated increase in cardiac output coupled with less vasoconstriction of the splanchnic and renal circulations, resulting in less redistribution of blood flow to the periphery. Created Created in BioRender. Alexander, L. (2025) https://BioRender.com/xllxtrj from data published by Minson et al., [18] Journal of Applied Physiology 1998, 84(4):1323–32; American Physiological Society.

Most of the work highlighted in this section used water-perfused suits to investigate the mechanisms underlying age-related increases in risk associated with heat exposure. Cardiovascular responses (i.e., heart rate, blood pressure, etc.) may be exaggerated during heat exposures with water-perfused suits when compared to exposures using climate-controlled chambers, which more closely represent real-world exposures [29]. Nonetheless, recent studies using environmental chambers demonstrate age-related differences in the cardiovascular responses to heat stress [30, 31]. Further research is warranted in ecologically-valid settings to better understand the physiological underpinnings of heat-related cardiovascular risk in older adults and those with various comorbidities of aging.

Determining environmental risk for cardiovascular complications in older adults

The previous sections briefly detail epidemiological studies demonstrating a heightened cardiovascular vulnerability among older adults during heat events [5, 32, 33] and mechanistic studies characterizing age-related decrements in cardiovascular responses [18, 22, 23, 25, 34–36]. However, it is also important to consider the specific environmental conditions in which heat-induced cardiovascular strain begins to rapidly increase (i.e., increase from an already-elevated, but relatively stable cardiovascular strain associated with compensable heat stress) in order to limit morbidity and mortality during impending heat events.

Our laboratory originally developed, and has since refined, a unique, rigorous, and reproducible approach to identify specific critical environmental limits i.e., the combinations of air temperature and humidity at which thermoregulatory health is compromised for various populations, clothing ensembles, and exercise intensities [37–42]. This research paradigm systematically increases either ambient temperature (at a fixed absolute humidity) or humidity (at a fixed ambient temperature) to identify the environmental conditions beyond which heat production/gain exceeds the capacity for heat loss. Using this approach, Kamon et al. [37, 43] demonstrated that, similar to core temperature, HR can be maintained at equilibrium across multiple environments until a critical combination of temperature and humidity causes HR to progressively rise in young adults. They further noted that this progressive rise in HR occurred prior to thermal imbalance. However, these findings were anecdotal and no statistical analyses were performed, nor were the environments that elicited the beginning of this progressive rise in HR defined.

Ravanelli et al. [44] reported that in young adults at rest, a HR inflection (i.e., the onset of cardiovascular drift) occurred at a combination of 36°C dry-bulb temperature and 62% relative humidity in a warm-humid environment, and at 42°C and 38% relative humidity in a hot-dry environment. Gagnon et al. [45] conducted a follow up study in resting older adults and found that the critical humidity for a HR inflection occurred at an environmental combination of 42°C and ~55% relative humidity.

Our lab more recently showed that during metabolic rates reflecting activities of daily living in adults aged 65 – 92 yrs, a continuous rise in HR began at ~35°C and 53% relative humidity in warm-humid environments and at ~41°C and 24% relative humidity in hot-dry environments [46]. We further demonstrated an age-related decline in HR thresholds in warm-humid environments, and a linear decline in hot-dry environments. This age-related decline in the HR threshold mirrored the age-related decline of core temperature limits but systematically preceded the core temperature inflection (i.e., before thermal imbalance occurred). Although HR continues to increase progressively throughout our protocols and we see no evidence of it reaching a steady state at even higher uncompensable heat loads, whether or not heart rate will continuously rise during prolonged exposures in environments just above the heart rate inflection point has not yet been rigorously examined.

Although speculative, the progressive rise in HR likely occurred to continue maintenance of blood pressure and cardiac output as the limits of thermal compensability were approached. Regardless of age, in warm-humid environments, heat balance is limited by evaporative capacity of the environment as the gradient between ambient water vapor pressure and skin water vapor pressure narrows. However, in hot-dry environments in which there is essentially free evaporation, heat balance is limited primarily by maintenance of high sweat rates and by convective heat gain. High sweat rates associated with prolonged activity in hot environments can lead to dehydration and a reduction in plasma volume. Reduced diastolic filling as a consequence of lower plasma volume leads to reductions in stroke volume, thus increasing cardiovascular strain through compensatory increases in HR and contractility [47].

We have recently extended our previous findings [46] to identify the environmental conditions that result in a progressive rise in HR across a wide range of environmental conditions for older adults at metabolic rates reflecting activities of daily living. Those data (not previously published) identified the HR thresholds in environments ranging from 34 – 42°C and 20 – 60% relative humidity (Figure 3), covering environmental conditions that commonly occur during extreme heat events. By delineating safe from potentially unsafe environmental conditions at which excessive cardiovascular strain begins to occur (the onset of cardiovascular drift), these limits may provide information for the development of policy decisions, safety guidelines, and alert-based communication to mitigate both excess heat and cardiovascular-related morbidity and mortality among older adults.

Figure 3.

Environmental heart rate thresholds (onset of cardiovascular drift) across a range of hot temperatures and relative humidity for older adults during activities of daily living. The mean thresholds are shown by the thick black line. The dotted lines represent the 95% confidence interval. Dry-bulb temperature is represented on the x-axis, relative humidity on the left y-axis, and wet-bulb temperature by the curvilinear blue lines on the right y-axis. Environments above and to the right of the black threshold line represent environments that will elicit a progressive rise in heart rate at this low metabolic rate.

We have additionally demonstrated sex differences in heat stress vulnerability (i.e., critical environmental limits for maintenance of heat balance) among middle-aged and older men and women [48]. Using core temperature compensability curves in a traditional survival curve format, we demonstrated similar vulnerability in middle-aged (40 – 64 yrs) women compared with older (>65 yrs) men, whereas older women demonstrated greater vulnerability compared with age-matched men. When similarly examining heat vulnerability in terms of cardiovascular strain, data from a small subset of participants illustrate a leftward shift in the curve for maintaining a stable HR (i.e., cardiovascular drift occurring at lower combinations of temperature and humidity) in hot-dry and warm-humid environments for older women compared with age-matched men (Figure 4; unpublished data).

Figure 4.

Survival curves demonstrating the percentage of older adults for whom heart rate is maintained at a relative steady-state at a given dry-bulb temperature (T_db; Panel A) or water vapor pressure (P_a; Panel B). In hot-dry environments (A), curves for women (n = 6) were shifted significantly leftward compared with men (n = 10; P < 0.01). In warm-humid environments (B), there was a non-significant leftward shift for women (n = 6) compared with men (n = 6).

It is important to note that all-cause CVD mortality begins to increase at temperatures that are much lower than those at which we have demonstrated the onset of cardiovascular drift. For example, relative risk of all-cause CVD mortality starts to increase at ~22°C in Montreal, Canada and ~25°C in Los Angeles, CA, USA [11]. The cardiovascular adjustments required to support the physiological responses to even relatively low-grade heat stress causes an increase in cardiovascular strain relative to a thermoneutral environment [49], which may increase cardiovascular risk with prolonged exposures. Indeed, in our progressive heat stress trials, HR was elevated by ~10–20 bpm in the compensable heat stress conditions that preceded HR inflection points [46, 50]. The data presented herein characterize the upper limits of temperature and humidity for the maintenance of a relatively stable HR and, therefore, the cardiovascular drift associated with exceeding those limits may constitute a substantial increase in cardiovascular risk.

Conclusions

Older adults are at increased risk for heat-related morbidity and mortality during heat events. Epidemiological data consistently demonstrate that adults aged >65 yrs are more vulnerable than any other age cohort. Importantly, the majority of hospitalizations and mortality among older adults during heat events are due to cardiovascular-related complications. Aging is associated with impaired cardiovascular responses to heat stress and an abundance of work has identified the specific physiological mechanisms that contribute to these age-related alterations. As heat waves continue to become more frequent, severe, and long-lasting -- coupled with an aging global population -- billions of people will soon be negatively impacted by the warming climate. Recent work has aimed to identify the specific environmental conditions that potentially result in excess cardiovascular strain among older adults. Continued work in this area will further elucidate the environmental conditions in which older adults, or their caregivers, should take action to reduce excess heat stress, and consequently, cardiovascular strain that can result in heat-related cardiovascular morbidity and mortality.