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Heat Waves, Aging, and Human Cardiovascular Health


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Medicine & Science in Sports & Exercise: October 2014 - Volume 46 - Issue 10 - p 1891-1899
doi: 10.1249/MSS.0000000000000325
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The earth’s climate is warming, with global mean temperature increasing by 0.74°C from between the years of 1906 and 2005 (34). Humans are tropical animals and are therefore capable of surviving in, and adapting to, such relatively small changes in mean ambient temperatures. However, as mean global temperature rises, the frequency, severity, and relative length of heat waves increase (53). Heat waves can be functionally defined as an extended number of days with higher than normal temperatures. Prolonged exposure to high ambient temperatures induces a substantial stress on the human cardiovascular system, and although human beings are capable of withstanding extremely high temperatures for short periods, the cardiovascular strain induced by prolonged heat exposure contributes negatively to health outcomes. Indeed, during a heat wave, most of the excess morbidity and mortality are not directly heat related but are cardiovascular in origin, brought about by the increased cardiovascular challenge associated with thermoregulatory responses to heat stress (65).

Elderly individuals, even in the absence of overt cardiovascular disease, are the most vulnerable population during prolonged environmental heat exposure, experiencing significantly worse health outcomes than any other age cohort. Individuals older than 65 yr comprise most of the extra emergency room visits and deaths during heat waves (16,58). The global population of aged individuals is rapidly growing (1), meaning that an increasingly larger subset of the population will be susceptible to illness and death as climatic temperature continues to rise.

To defend against increasing core temperature, humans increase skin blood flow and sweat rate to dissipate heat. These effector responses are necessary for thermoregulation but place a great demand on the cardiovascular system by necessitating a relatively large increase in cardiac output (47,57). Decrements in skin blood flow are also observed and compounded with pathologies including hypertension (9,30,31) and hypercholesterolemia (27,29) as well as with common medications used in the primary and secondary prevention of cardiovascular disease (26,28). Even healthy aging is associated with an attenuated rise in skin blood flow (39) and decreased sweat gland output (2) in response to heat stress, but the integrated response to heat stress still places a great burden on a compromised (i.e. decreased adrenergic responsiveness) left ventricle.

The purpose of this review is to discuss the effect of heat stress on the aging cardiovascular system and, within that context, the projected effects of global warming on human cardiovascular health. This brief review was based on a President’s Lecture presented at the 60th Annual Meeting of the American College of Sports Medicine in 2013.


Climate change and global warming are (pardon the pun) hot topics, with their fair share of political controversy with respect to causation. There is little controversy, however, that over the past several decades, the average temperature of the earth has been steadily increasing (34). The year 2012 was the hottest year on record in the United States and one of the 10 warmest in global history (50). In fact, all 10 of the warmest years on record have occurred within the last 15 yr (18). October 2012 was the 332nd consecutive month with above-average global temperatures (50). This means that, as of the end of 2013, anyone born after April 1985 has never experienced a month with below-average temperatures (18).

Summers categorized as “hot”, which occurred 33% of the time from 1950 to 1981, now occur 75% of the time (20). James Hansen, of the National Aeronautics and Space Administration Goddard Institute for Space Studies and an adjunct professor in the Department of Earth and Environmental Sciences at Columbia University, has used the term “climate dice” to describe this change in the frequency of hot weather. In this analogy, each side of a die represents a temperature range. In a normally distributed climate, average weather, cold weather, and hot weather would each be represented by two sides of the die. Because the outcome of rolling a die is random, the probability of average, warm, or cool weather would be equal over the long term. With climate change, the sides of the die have changed. Only one side now represents cool weather, one side represents average weather, and four sides signify warmer than average weather; Hansen described this as “loaded dice.” With climate change, there will still be variability in temperature and cool weather will still occur, but it will occur much less frequently than warm weather (21). Evaluation of seasonal temperatures supports the increased frequency of warm weather. In the United States, from 1990 to 2010, 16 of 20 winters and 15 of 20 summers were warmer than the 1951–1980 average. For the same period in Europe, 16 of 20 winters and 19 of 20 summers have been above average in temperature (19). Along with proportionally warmer weather, more records of high temperatures are also being set. Since the year 2000, records of high temperatures have occurred twice as often as records of low temperatures (46). As these data clearly illustrate, the earth’s climate is warming well above normal historical temperatures, but what does that mean for human health, especially among the elderly?


Accompanying the rise in average global temperatures is a rise in the frequency and severity of heat waves. Over the past several decades, the frequency, duration, and severity of heat waves have increased (53). From 1951 to 1980, environmental heat waves covered on average 0.1%–0.2% of the earth’s surface at any given time; from 1981 to 2010, 10% of the planet experiences a heat wave at a given point in time (20). This means that the occurrence of a heat wave has been 50–100 times more likely over the last three decades. To account for this increase in heat wave frequency, one side of Hansen’s climate die has now changed from “warm” to “extremely hot” weather (21).

Numerous computer models predict that the frequency, intensity, and duration of heat waves will continue to increase over the course of the century. Meehl and Tebaldi (45) predicted a 25%–30% increase in the number of heat waves per year, accompanied by an increased heat wave duration. Nakano et al. (48) predicted an increase of more than 22 extra heat wave days per year in Japan. Hayhoe et al. (23) predicted that by the end of the 21st century, extremely deadly heat waves will occur in the city of Chicago as frequently as every 3 months (59).


The population of the world is rapidly aging. The number of people aged 65 and over in the United States has increased from 35 million in 2000 to over 41 million in 2011, and this segment of the population is projected to increase to nearly 80 million by the year 2040 (1). By 2050, there will be more people over 60 yr old than under 15 yr old in the world for the first time ever (64). To go along with the increase in the number of aged people, the “very old” population is also increasing. The number of people 80 yr old and above is increasing at the rate of 3.8% per year, which makes them the fastest growing age group across the world (64).

The increasing number of aged people increases health concerns during periods of elevated ambient temperatures. People over the age of 65 yr exhibit disproportionately larger increases in mortality during heat waves than those in younger individuals, with the majority of excess deaths during heat waves occurring in the elderly (10). With the rapidly growing number of older individuals on the planet, the number of people at risk of dying during a heat wave increases. With an expanded at-risk population, there exists the potential for a greater number of casualties during any single heat wave.


Humans evolved from tropical climates and are capable of withstanding even extremely high environmental temperatures—temperatures exceeding 200°F (6)—provided that 1) they can produce enough sweat, 2) the environment permits evaporation of that sweat, and 3) there is no direct contact with hot surfaces. However, physiological homeostasis in such extreme temperatures is only sustainable for short periods.

Despite the ability to tolerate extreme heat stress for short periods, prolonged moderate heat stress, such as that observed during a heat wave, represents a different set of stressors, and prolonged warm environmental temperatures are associated with an increased risk of mortality. For example, temperatures above the 90th percentile in California were found to increase risk of excess mortality by 4.3% for every 5.6°C increase in apparent temperature (4). (Note: Apparent temperature is a temperature index that combines the effects of air temperature, relative humidity, and wind speed.) In 15 European cities, an increase in apparent temperature of 1°C above a threshold temperature unique to each city was associated with a 3.12% increase in mortality in Mediterranean cities and a 1.84% increase in mortality in northern European cities (3).

Whereas elevated daily temperatures increase the mortality rate, severe heat waves—several consecutive days of hot weather—cause much greater increases in mortality. Two different heat waves within the past 20 yr received considerable attention because of innovations in recording morbidity and mortality statistics. In the summer of 1995, the Chicago heat wave was notable because minimum apparent temperatures remained above 31.5°C for 2 d (36). This very high minimum temperature prevented recovery from heat stress at night. Instead, the heat stress was continuous throughout the day and night. There were approximately 700 excess deaths during the Chicago heat wave compared with those during the same period in the previous year (67).

In the European heat wave centered around France in August 2003, temperatures were elevated by 11°C above the seasonal average for nine consecutive days. In total, the French heat wave is estimated to have caused almost 15,000 excess deaths over approximately 1 month (17,24,63). Excess deaths began to occur 3 d after the start of the heat wave, and mortality returned to normal 4 d after conclusion of the heat wave (17), demonstrating that is takes a prolonged period with elevated temperatures to increase mortality (Fig. 1).

Daily deaths (left axis) and minimum and maximum air temperatures (right axis) during the 2003 French heat wave. The abnormally hot daily temperatures in early August 2003 were followed by a consequent dramatic increase in daily mortality, mostly among the elderly. Redrawn from Dousset et al. (14).

It is hypothesized that the increase in mortality during heat waves, such as those in Chicago and France, may reflect a harvesting effect. Harvesting, or mortality displacement, means that the excess deaths during a heat wave occur in frail individuals whose death was only slightly expedited by the heat wave. The excess mortality is then counteracted by periods of reduced mortality after the heat wave. No clear consensus has been reached on the magnitude of the harvesting effect during heat waves. Some have reported that nearly all deaths during times of extreme temperature are accounted for by mortality displacement (7), whereas others have reported no mortality displacement (4,8). It is possible that the wide variation between studies is due to differences in preparedness for managing public health during heat waves among the cities studied. Differences in intensity and duration of heat waves also likely determine the degree of harvesting. A moderate harvesting effect of approximately 30% is often observed, especially when examining very severe heat waves or looking at large, varied populations (3,35,63). This suggests that some deaths during heat waves occur in those who were in poor health and had only a brief period left to live but that most deaths during heat waves occur in those with a normal remaining life expectancy.

Clearly, determinants of mortality during heat waves are not all physiological. Socioeconomic status and living conditions undoubtedly play a major role in mortality during heat waves. Odds of death during a heat wave are increased if one is elderly, is confined to bed, sleeps on the top floor of a building, lacks thermal insulation, or resides inside an urban heat island (49,59,65). In the French heat wave of 2003, excess mortality rates in deprived areas of Paris were twice as high as those in privileged areas of Paris (55). Although being frail and sick or living in an underprivileged region during a heat wave increases risk of death, there are countermeasures that decrease the risk of mortality during a heat wave. Dressing in light clothing, hydrating, owning air conditioning, having access to transportation, and having nearby social contacts are all associated with decreased mortality (49,59,65). Preparedness of residents or of a city to deal with severe heat waves can also affect mortality. Chicago experienced a heat wave in 1999 that was meteorologically very similar to the 1995 heat wave; however, in 1999, there were only 114 excess deaths compared with 700 in 1995 (52). Part of the drop in mortality is attributed to increased public awareness and an improved municipal response (52). Other interventions such as cooling centers have not been shown to be protective because of underuse (49). Regardless, steps can be taken to protect the most vulnerable populations, such as the old and sick, during heat waves to limit mortality.


Direct heat-related fatalities, such as death from heat stroke, number approximately 120 per year in the United States, which is more than any other individual environmental cause including death from cold, flooding, tornados, hurricanes, and lightning (51). However, the number of deaths linked to periods of excess heat or heat waves is much greater than those attributable to heat stroke. For example, the August 2003 heat wave in Europe resulted in 15,000 excess deaths in France alone and as many as 70,000 excess deaths across all of the European continent (17,24,56,63). The Chicago 1995 heat wave registered an average of 241 excess deaths per day, far outnumbering the average annual United States heat fatalities in a single day (35).

The reason for this difference between direct heat deaths and overall heat wave mortality is that direct effects of heat alone are not the primary cause of death for most of the excess deaths during heat waves. Of the excess deaths in the Chicago heat wave, only 4.7% listed excessive heat (i.e., heat stroke or hyperpyrexia) as the primary cause of death on death certificates, another 28.1% listed heat as a contributing cause, whereas 93.7% of excess deaths documented an underlying cardiovascular cause (Fig. 2) (35).

Mortality (green shaded area and red line) and maximum daily temperatures (dashed line) during the summer 1995 Chicago heat wave. Dates are shown along the x-axis. Mortality data in green represent the total death toll, whereas the superimposed red line depicts deaths from cardiovascular causes alone or from death certificates that mention combined cardiovascular and heat causes. Redrawn from Kaiser et al. (35).

Evaluation of deaths during two heat waves in Milwaukee likewise revealed cardiovascular disease as the primary cause of death in 51% and 64% of the deaths in the two heat waves, respectively (66). Although the vast majority of excess deaths during a heat wave are cardiovascular in origin, associated physiological strain on other systems contributes to the elevated mortality, too. An increase in respiratory deaths (12,33) and cerebrovascular deaths (12) also contribute to the increased mortality during heat waves that were not directly attributed to hyperthermia. Overall, there is a substantial increase in excess death during heat waves, but heat-related illness only contributes moderately to the increased mortality. Cardiovascular causes form the majority of contributing factors to excess deaths, especially so in the elderly.


Older humans have a much greater mortality risk during heat waves (59,65). Death from excessive environmental heat affects adults above age 50 at a higher rate than that in adults below 50, with the rate increasing exponentially beyond that point (15). In some instances, over 90% of excess deaths during heat waves occur in the elderly (10). Because most deaths during heat waves are cardiovascular in origin, the complex reasons for higher mortality in the aged can, at least in part, be understood by examining the cardiovascular responses of older and young, apparently healthy human subjects to passive heat stress.

The integrated cardiovascular responses of young, healthy men to passive supine heat stress were eloquently described by Rowell in the 1960s and 1970s (57). By increasing skin temperature to 40.5°C using a water-perfused suit, Rowell saw a doubling of resting cardiac output, slightly increased stroke volume, and a redistribution of blood flow from the splanchnic and renal circulations to the skin. Interestingly, despite a profound reduction in the right atrial mean pressure to almost zero, mean arterial pressure was well maintained and inotropic function of the heart increased (57). Together, these data demonstrated that blood volume is redistributed from the central to peripheral circulations to aid in thermoregulation (11) at the expense of increased ventricular work to pump blood in light of a profoundly reduced filling pressure (Fig. 3).

A, The change in central blood volume, measured by technetium-99 scanning, with passive heat stress compared with a time control. Blood volume in the overall thorax and centered around the heart and central vasculature is shown. Heat stress significantly lowered blood volume compared with time control. B, Ejection fraction at baseline, with passive heat stress and during a time control trial. Passive heat stress significantly increased ejection fraction compared with that in baseline and time control. Collectively, these data reflect the added strain on the left ventricle during passive heat stress, as contractility increased in light of a falling CVP, to pump blood to the skin. Redrawn from Crandall et al. (11).

Healthy older humans have an altered cardiovascular response to heat stress compared with that of their younger counterparts. During passive heating to the limits of thermal tolerance, young subjects increased cutaneous blood flow by approximately 5800 mL·min−1 compared with an increase of only 2700 mL·min−1 in older subjects (47). The increase in skin blood flow in young subjects came from both increased cardiac output (4800 mL min−1) and a redistribution of blood from both the splanchnic and renal circulations (1000 mL·min−1). In contrast, 70-yr-old subjects had an attenuated increase in cardiac output (2000 mL·min−1) coupled with a reduction in the ability to redistribute blood flow from the splanchnic and renal circulations (700 mL·min−1) (47) (Fig. 4).

Changes in cardiac output and renal, splanchnic, and cutaneous blood flow with passive heating to thermal tolerance (water-perfused suit) in young and older men. Young subjects increased cutaneous blood flow to a larger extent than did older subjects. The larger increase in cutaneous blood flow in the young men was accomplished by both raising cardiac output significantly more and by reducing renal and splanchnic blood flow to a higher degree compared with those in the older subjects. Redrawn from data published by Minson et al. (47).

One reason for the attenuated increase in cardiac output during passive heating in older subjects is their lack of ability to maintain stroke volume. With prolonged passive heating, central venous pressure (CVP) falls similarly in aged and young subjects (Fig. 5A) (47). The young subjects were able to maintain or slightly increase stroke volume by increasing contractility, whereas stroke volume declined progressively in the older subjects. Whereas the absolute HR response was similar in both age groups, HR as a percentage of maximum was higher in the older individuals at any given CVP (Fig. 5B). Thus, the older subjects relied on a greater percentage of their HR reserve to increase cardiac output during whole-body heat stress (47). In the aged, there is excess central cardiovascular strain and an attenuated increase in thermoregulatory skin blood flow. With such changes evident in apparently healthy older men free from overt heart disease, such increases in myocardial oxygen demand may prompt untoward events in those with clinical or subclinical disease.

Cardiac responses to prolonged passive heating as a function of time (A) and CVP (B) in young (19–28 yr,black circles) and older (64–81 yr, red circles) men. Only the initial 30 min of heating are shown in panel A. Older subjects had a significantly attenuated rise in cardiac output and a decrease in stroke volume compared with those in young subjects, despite a similar fall in CVP. Stroke volume was well maintained in the young men. As shown in panel B, the fall in CVP (right to left along the x-axis) due to venous blood pooling caused a similar increase in absolute HR (see panel A) but a larger rise in HR as a percentage of HRmax. HR reserve is consequently lower in the older men at any given level of heat stress (and CVP). Redrawn from data published by Minson et al. (47).

Along with a drop in cutaneous perfusion, aging is associated with a decreased sweat rate (60) and decreased sweat output per gland (2). Regional sweating patterns also change with aging, with the largest reductions in sweating occurring in the abdomen and less significant reductions occurring in the lower back, thigh, and arm (60). An attenuated evaporative heat loss results in greater heat storage in older men and women (41,42), which can exacerbate the cardiovascular strain described previously. Even though the sweating response in the aged is often attenuated, prolonged sweating during long-duration heat stress causes a significant reduction in plasma volume. This fall precipitates increases in red blood cell and neutrophil counts as well as increased plasma viscosity. Heat stress also causes the release of extra platelets into the circulation. These changes in blood properties contribute to increased susceptibility to cardiovascular death due to acute coronary events (37).

One method for assessing cardiovascular strain and damage during heat stress is by measuring the enzyme cardiac troponin I (cTnI). When myocardial cells are damaged, cTnI is released into the bloodstream (43). cTnI is elevated when examined postmortem in hyperthermia-related mortalities (68), indicating myocardial damage associated with the severe heat stress. cTnI has also been found to be elevated in aged subjects with nonexertional heat-related illnesses (13,22). An increase in cTnI is associated with decreased survival from a heat illness and is an independent prognostic factor for survival (Fig. 6) (13,22). This association provides evidence for myocardial damage being a contributing factor in deaths in the elderly during heat waves. Even a modest increase in core temperature (below the clinical criteria for heat stroke, 40°C) can cause myocardial damage.

Patient survival curves after emergency admission to hospitals during the week after the 2003 heat wave in France. Separate curves are drawn for patients (mean age, 84 yr) who had no elevation in cTnI (n = 252, green line), a moderate increase (up to 1.5 ng·mL−1, n = 165, orange line), and a severe increase in cTnI (>1.5 ng·mL−1, n = 97, red line). These data support the association between heat stress and cardiac strain in the elderly during environmental heat waves. Redrawn from data originally published by Hausfater et al. (22).


The ability to maintain core temperature during heat stress is in part dependent upon increasing cutaneous blood flow. When examining the integrated cardiovascular response to passive whole-body heating, skin blood flow has been calculated to increase to 7–8 L·min−1 in young subjects (57). With healthy aging, there is an attenuated skin blood flow response to passive, whole-body heating (40,47). Although central cardiovascular changes with aging contribute to the reduction in skin blood flow (47), there are also peripheral limitations to reflex cutaneous vasodilation. Nitric oxide (NO) is a potent vasodilator that is required for full expression of reflex vasodilation and contributes directly to approximately 30%–40% of the cutaneous vasodilatory response in young skin (25,38). Even though NO bioavailability is decreased in aged vasculature, aged humans rely primarily on compromised NO-mediated mechanisms to increase skin blood flow during heat stress (25). The reason for the increased dependency on NO-mediated vasodilation in aged skin is the decreased contribution of cholinergic cotransmitter(s) to reflex vasodilation (25).

Many peripheral factors contribute to the decreased NO bioavailability in aged human vasculature. In human skin, there is up-regulation of the enzyme arginase, which preferentially uses the common NO synthase (NOS) substrate, L-arginine, to produce urea and L-ornithine (31). Either localized supplementation of L-arginine or inhibition on arginase augments reflex cutaneous vasodilation in aged skin (31). Aging is also associated with increased oxidative stress including increased superoxide production from a variety of enzymatic and nonenzymatic sources. Superoxide reacts with NO to form peroxynitrite (OONO), then is degraded by superoxide dismutase (5). This reaction decreases NO bioavailability and functionally reduces vasodilation. Moreover, free radical species can also uncouple the NOS dimmer, which further decreases NO production and increases superoxide synthesis (30). Short-term antioxidant supplementation (ascorbate) serves to quench free radicals and increase reflex vasodilation in aged skin (30). However, ascorbate is a generalized antioxidant and can either decrease oxidant species and/or improve the availability of the essential NOS cofactor tetrahydrobiopterin (BH4). Aging, in general, is associated with reduced bioavailability of BH4, which potentiates NOS uncoupling and contributes to increased oxidant stress (54). Localized supplementation of BH4 increases NO-dependent vasodilation in aged human skin (61,62).

Along with NO-mediated vasodilation, cyclooxygenase (COX) pathways contribute to reflex vasodilation in young, healthy subjects (44). However, with aging, there is an increase in COX-derived vasoconstrictors and attenuated prostanoid-dependent vasodilation, which together may increase cutaneous vasoconstriction (32). Together, the attenuation of NO-, COX-, and cotransmitter-mediated vasodilation with aging demonstrates an overall loss in redundancy in vasodilator mechanisms with aging.

Although reflex cutaneous vasodilation is attenuated in aged skin, local pharmacological interventions can largely restore skin blood flow in the aged to match that in young people. However, it is currently not known if the aged cardiovascular system, including the compromised left ventricle, could support the increase in skin blood flow afforded by these pharmacological interventions.


The earth’s climate is rapidly warming, and the increased average daily temperature is accompanied by an increased frequency and severity of environmental heat waves. Passive thermal stress places a large demand on the cardiovascular system to pump blood to the skin. The increased cardiovascular demand of high ambient temperatures, with or without the added strain of physical exertion, can be especially challenging in aged humans who exhibit altered cardiovascular function and thermoregulatory ability. For these individuals, heat waves can often be fatal, as demonstrated by the large number of excess deaths—primarily of cardiovascular origin—in elderly individuals during heat waves.

With the number of older people rapidly increasing and the climate warming, cardiovascular deaths precipitated by prolonged periods of high ambient temperatures are of increasing concern. The integrated cardiovascular response to heat stress is an example of elegant homeostasis, yet alterations in the aged cardiovascular system limit the requisite increase in cardiac output while putting increased strain on a potentially compromised left ventricle. The result is an increased mortality among the elderly during environmental extremes of heat not from heat stroke but due to cardiovascular strain.

No funding was received for this work.

The authors have no conflicts of interest to report.

The contents of this review do not constitute endorsement by the American College of Sports Medicine.


1. A profile of older Americans: 2012 [cited 8/26/2013]. Available from:
2. Anderson RK, Kenney WL. Effect of age on heat-activated sweat gland density and flow during exercise in dry heat. J Appl Physiol (1985). 1987; 63 (3): 1089–94.
3. Baccini M, Biggeri A, Accetta G, et al. Heat effects on mortality in 15 European cities. Epidemiology. 2008; 19 (5): 711–9.
4. Basu R, Malig B. High ambient temperature and mortality in California: exploring the roles of age, disease, and mortality displacement. Environ Res. 2011; 111 (8): 1286–92.
5. Beckman JS. Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol. 1996; 9 (5): 836–44.
6. Blagden C. Experiments and observations in a heated room. Philos Trans. 1775; 65: 111–23.
7. Braga AL, Zanobetti A, Schwartz J. The time course of weather-related deaths. Epidemiology. 2001; 12 (6): 662–7.
8. Bustinza R, Lebel G, Gosselin P, Belanger D, Chebana F. Health impacts of the July 2010 heat wave in Quebec, Canada. BMC Public Health. 2013; 13: 56.
9. Carberry PA, Shepherd AM, Johnson JM. Resting and maximal forearm skin blood flows are reduced in hypertension. Hypertension. 1992; 20 (3): 349–55.
10. Conti S, Meli P, Minelli G, et al. Epidemiologic study of mortality during the Summer 2003 heat wave in Italy. Environ Res. 2005; 98 (3): 390–9.
11. Crandall CG, Wilson TE, Marving J, et al. Effects of passive heating on central blood volume and ventricular dimensions in humans. J Physiol. 2008; 586 (1): 293–301.
12. D’Ippoliti D, Michelozzi P, Marino C, et al. The impact of heat waves on mortality in 9 European cities: results from the EuroHEAT project. Environ Health. 2010; 9: 37.
13. Davido A, Patzak A, Dart T, et al. Risk factors for heat related death during the August 2003 heat wave in Paris, France, in patients evaluated at the emergency department of the Hospital Europeen Georges Pompidou. Emerg Med J. 2006; 23 (7): 515–8.
14. Dousset B, Gourmelon F, Laaidi K, et al. Satellite monitoring of summer heat waves in the Paris metropolitan area. Int J Climatol. 2011; 31 (2): 313–23.
15. Ellis FP. Mortality from heat illness and heat-aggravated illness in the United States. Environ Res. 1972; 5 (1): 1–58.
16. Ellis FP, Nelson F, Pincus L. Mortality during heat waves in New York City July, 1972 and August and September, 1973. Environ Res. 1975; 10 (1): 1–13.
17. Fouillet A, Rey G, Laurent F, et al. Excess mortality related to the August 2003 heat wave in France. Int Arch Occup Environ Health. 2006; 80 (1): 16–24.
18. Gillis J. Not Even Close: 2012 Was Hottest Ever in US. The New York Times. 2013. Sect. A:1.
19. Hansen J, Ruedy R, Sato M, Lo K. Global surface temperature change. Rev Geophys. 2010: 48.
20. Hansen J, Sato M, Ruedy R. Perception of climate change. Proc Natl Acad Sci U S A. 2012; 109 (37): E2415–23.
21. Hansen JE. Climate change is here—and worse than we thought. Washington Post. 2012. Sect. A:14.
22. Hausfater P, Doumenc B, Chopin S, et al. Elevation of cardiac troponin I during non-exertional heat-related illnesses in the context of a heatwave. Crit Care. 2010; 14 (3): R99.
23. Hayhoe K, Sheridan S, Kalkstein L, Greene S. Climate change, heat waves, and mortality projections for Chicago. J Great Lakes Res. 2010; 36: 65–73.
24. Hemon D, Jougla E. The heat wave in France in August 2003 [in French]. Rev Epidemiol Sante Publique. 2004; 52 (1): 3–5.
25. Holowatz LA, Houghton BL, Wong BJ, et al. Nitric oxide and attenuated reflex cutaneous vasodilation in aged skin. Am J Physiol Heart Circ Physiol. 2003; 284 (5): H1662–7.
26. Holowatz LA, Jennings JD, Lang JA, Kenney WL. Systemic low-dose aspirin and clopidogrel independently attenuate reflex cutaneous vasodilation in middle-aged humans. J Appl Physiol (1985). 2010; 108 (6): 1575–81.
27. Holowatz LA, Kenney WL. Acute localized administration of tetrahydrobiopterin and chronic systemic atorvastatin treatment restore cutaneous microvascular function in hypercholesterolaemic humans. J Physiol. 2011; 589 (Pt 19): 4787–97.
28. Holowatz LA, Kenney WL. Chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation in middle-aged humans. J Appl Physiol (1985). 2009; 106 (2): 500–5.
29. Holowatz LA, Santhanam L, Webb A, Berkowitz DE, Kenney WL. Oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolaemic humans. J Phys. 2011; 589 (Pt 8): 2093–103.
30. Holowatz LA, Thompson CS, Kenney WL. Acute ascorbate supplementation alone or combined with arginase inhibition augments reflex cutaneous vasodilation in aged human skin. Am J Physiol Heart Circ Physiol. 2006; 291 (6): H2965–70.
31. Holowatz LA, Thompson CS, Kenney WL. L-Arginine supplementation or arginase inhibition augments reflex cutaneous vasodilatation in aged human skin. J Physiol. 2006; 574 (Pt 2): 573–81.
32. Holowatz LA, Thompson CS, Minson CT, Kenney WL. Mechanisms of acetylcholine-mediated vasodilatation in young and aged human skin. J Physiol. 2005; 563 (Pt 3): 965–73.
33. Huynen MM, Martens P, Schram D, Weijenberg MP, Kunst AE. The impact of heat waves and cold spells on mortality rates in the Dutch population. Environ Health Perspect. 2001; 109 (5): 463–70.
34. Intergovernmental Panel on Climate Change. Climate Change 2007: Synthesis Report. Contribution of Working Groups I, II, and III to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change. Pachauri RK, Resinger A, editors. Geneva (Switzerland): Intergovernmental Panel on Climate Change; 2007. p. 104.
35. Kaiser R, Le Tertre A, Schwartz J, Gotway CA, Daley WR, Rubin CH. The effect of the 1995 heat wave in Chicago on all-cause and cause-specific mortality. Am J Public Health. 2007; 97 (1 Suppl): S158–62.
36. Karl TR, Knight RW. The 1995 Chicago heat wave: how likely is a recurrence? B Am Meteorol Soc. 1997; 78 (6): 1107–19.
37. Keatinge WR, Coleshaw SR, Easton JC, Cotter F, Mattock MB, Chelliah R. Increased platelet and red cell counts, blood viscosity, and plasma cholesterol levels during heat stress, and mortality from coronary and cerebral thrombosis. Am J Med. 1986; 81 (5): 795–800.
38. Kellogg DL, Crandall CG, Liu Y, Charkoudian N, Johnson JM. Nitric oxide and cutaneous active vasodilation during heat stress in humans. J Appl Physiol (1985). 1998; 85 (3): 824–9.
39. Kenney WL, Morgan AL, Farquhar WB, Brooks EM, Pierzga JM, Derr JA. Decreased active vasodilator sensitivity in aged skin. Am J Physiol. 1997; 272 (4 Pt 2): H1609–14.
40. Kenney WL, Tankersley CG, Newswanger DL, Hyde DE, Puhl SM, Turner NL. Age and hypohydration independently influence the peripheral vascular response to heat stress. J Appl Physiol (1985). 1990; 68 (5): 1902–8.
41. Larose J, Wright HE, Sigal RJ, Boulay P, Hardcastle S, Kenny GP. Do older females store more heat than younger females during exercise in the heat? Med Sci Sports Exercise. 2013; 45 (12): 2265–76.
42. Larose J, Wright HE, Stapleton J, et al. Whole body heat loss is reduced in older males during short bouts of intermittent exercise. Am J Physiol Regul Integr Comp Physiol. 2013; 305 (6): R619–29.
43. Lazzeri C, Bonizzoli M, Cianchi G, Gensini GF, Peris A. Troponin I in the intensive care unit setting: from the heart to the heart. Intern Emerg Med. 2008; 3 (1): 9–16.
44. McCord GR, Cracowski JL, Minson CT. Prostanoids contribute to cutaneous active vasodilation in humans. Am J Physiol Regul Integr Comp Physiol. 2006; 291 (3): R596–602.
45. Meehl GA, Tebaldi C. More intense, more frequent, and longer lasting heat waves in the 21st century. Science. 2004; 305 (5686): 994–7.
46. Meehl GA, Tebaldi C, Walton G, Easterling D, McDaniel L. Relative increase of record high maximum temperatures compared to record low minimum temperatures in the U S. Geophys Res Lett. 2009; 36: 23.
47. Minson CT, Wladkowski SL, Cardell AF, Pawelczyk JA, Kenney WL. Age alters the cardiovascular response to direct passive heating. J Appl Physiol (1985). 1998; 84 (4): 1323–32.
48. Nakano M, Matsueda M, Sugi M. Future projections of heat waves around Japan simulated by CMIP3 and high-resolution Meteorological Research Institute atmospheric climate models. J Geophys Res Atmos. 2013; 118 (8): 3097–109.
49. Naughton MP, Henderson A, Mirabelli MC, et al. Heat-related mortality during a 1999 heat wave in Chicago. Am J Prev Med. 2002; 22 (4): 221–7.
50. NOAA National Climatic Data Center SotCGAfO. 2012 [cited 2013 August 26]. Available from:
51. NOAA Office of Climate W, and Weather Services. Natural Hazard Statistics [cited 2013 August 20]. Available from:
52. Palecki MA, Changnon SA, Kunkel KE. The nature and impacts of the July 1999 heat wave in the midwestern United States: learning from the lessons of 1995. B Am Meteorol Soc. 2001; 82 (7): 1353–67.
53. Perkins SE, Alexander LV, Nairn JR. Increasing frequency, intensity and duration of observed global heatwaves and warm spells. Geophys Res Lett. 2012; 39: 20.
54. Raman CS, Li H, Martasek P, Kral V, Masters BS, Poulos TL. Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center. Cell. 1998; 95 (7): 939–50.
55. Rey G, Fouillet A, Bessemoulin P, et al. Heat exposure and socio-economic vulnerability as synergistic factors in heat-wave-related mortality. Eur J Epidemiol. 2009; 24 (9): 495–502.
56. Robine JM, Cheung SL, Le Roy S, et al. Death toll exceeded 70,000 in Europe during the summer of 2003. C R Biol. 2008; 331 (2): 171–8.
57. Rowell LB. Human cardiovascular adjustments to exercise and thermal stress. Physiol Rev. 1974; 54 (1): 75–159.
58. Semenza JC, McCullough JE, Flanders WD, McGeehin MA, Lumpkin JR. Excess hospital admissions during the July 1995 heat wave in Chicago. Am J Prev Med. 1999; 16 (4): 269–77.
59. Semenza JC, Rubin CH, Falter KH, et al. Heat-related deaths during the July 1995 heat wave in Chicago. New Engl J Med. 1996; 335 (2): 84–90.
60. Smith CJ, Alexander LM, Kenney WL. Nonuniform, age-related decrements in regional sweating and skin blood flow. Am J Physiol Regul Integr Comp Physiol. 2013; 305 (8): R877–85.
61. Stanhewicz AE, Alexander LM, Kenney WL. Oral sapropterin acutely augments reflex vasodilation in aged human skin through nitric oxide-dependent mechanisms. J Appl Physiol (1985). 2013; 115 (7): 972–8.
62. Stanhewicz AE, Bruning RS, Smith CJ, Kenney WL, Holowatz LA. Local tetrahydrobiopterin administration augments reflex cutaneous vasodilation through nitric oxide-dependent mechanisms in aged human skin. J Appl Physiol (1985). 2012; 112 (5): 791–7.
63. Toulemon L, Barbieri M. The mortality impact of the August 2003 heat wave in France: investigating the ‘harvesting’ effect and other long-term consequences. Popul Stud. 2008; 62 (1): 39–53.
64. United Nations Department of Economic and Social Affairs, Population Division. World Population Ageing, 1950–2050. New York (NY): United Nations; 2002. xlix, p. 483.
65. Vandentorren S, Bretin P, Zeghnoun A, et al. August 2003 heat wave in France: risk factors for death of elderly people living at home. Eur J Public Health. 2006; 16 (6): 583–91.
66. Weisskopf MG, Anderson HA, Foldy S, et al. Heat wave morbidity and mortality, Milwaukee, Wis, 1999 vs 1995: an improved response? Am J Public Health. 2002; 92 (5): 830–3.
67. Whitman S, Good G, Donoghue ER, Benbow N, Shou W, Mou S. Mortality in Chicago attributed to the July 1995 heat wave. Am J Public Health. 1997; 87 (9): 1515–8.
68. Zhu BL, Ishikawa T, Michiue T, et al. Postmortem cardiac troponin I and creatine kinase MB levels in the blood and pericardial fluid as markers of myocardial damage in medicolegal autopsy. Leg Med (Tokyo). 2007; 9 (5): 241–50.


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