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Effects of climatic temperature stress on cardiovascular diseases
European Journal of Internal Medicine 21 (2010) 164–167
Contents lists available at ScienceDirect
European Journal of Internal Medicine j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / e j i m
Review article
Effects of climatic temperature stress on cardiovascular diseases Xiaoshu Cheng ⁎,1, Hai Su 1 Department of Cardiology, Second Affiliated Hospital, Nanchang University, China
a r t i c l e
i n f o
Article history: Received 21 January 2010 Received in revised form 25 February 2010 Accepted 2 March 2010 Available online 29 March 2010 Keywords: Extreme climate Cold Heat Cardiovascular diseases
a b s t r a c t The climatic stress was anticipated to increase direct and indirect risks to human health via different pathways and mechanisms. Extremely high air temperature might trigger the onset of cardiovascular events in the vulnerable. Cold-related mortality was much less understood than heat-related one, and was considered another climatic example of the effects on the human health. Increases in mortality with cardiovascular diseases in extreme heat and cold weather had been studied in many regions. These results suggested that people died rapidly from climate-change related cardiovascular diseases before they were sent to hospital. Obviously, these findings reminded us that climatic stress can be considered as a new potential risk factor of sudden cardiovascular events in human health, and there was an urgent need for large-scale, prospective, community-based and international study of sudden cardiovascular events to explore deeply the risk factors to schedule preventive strategies. © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
1. Introduction The climate change was anticipated to have a long-term impact on human health. Extensive literature reviews displayed that the increases in temperature will bring higher weather-related morbidity and mortality, largely through deaths from cardiovascular and respiratory events [1–4]. Climate changes had increased direct and indirect risk to mankind's health via different pathways and mechanisms. World Health Organization (WHO) estimated that more than 150,000 deaths with 5 million “disability-adjusted life years” for diseases are affected by the change of climate in the latest three decades [1]. Bhaskaran et al. [5] systematically reviewed the studies which specifically focused on the effects of temperature on acute myocardial infarction. They identified a number of differences between studies in terms of population including demographics, location, local climate, study design, and statistical methodology. Based on these large and relatively well-controlled studies, the authors found detrimental effects of both hot and cold weather on the risk of myocardial infarction. Recently, particular attention has been paid to environmental effects on cardiovascular physiology and pathological states. Extremely high or low air temperature may trigger the development of cardiovascular illness in the vulnerable, especially the elderly of North America [6]. These results suggested that people died rapidly from climate-change related diseases before they could be sent to a hospital [7]. Obviously, these findings were vital for performing schedules ⁎ Corresponding author. No. 1, Minde Rd., Nanchang, China, 330006. Tel./fax: +86 791 6268844. E-mail address: [email protected] (X. Cheng). 1 These two authors contributed equally to this work.
before the arrival of climate change, if people wanted to effectively reduce the mortality brought by the variation. Unfortunately, a recent assessment had concluded that climate change presents real risks to human health and the United States government had offered insufficient funding to exacerbate various current health problems [8]. 2. Extreme heat temperature on human cardiovascular diseases The conclusion found in the bibliography displays that excess mortality due to cardiovascular diseases was the main reason for deaths caused by high temperature. The review conducted by Basu and Samet covered a total of 98 papers dating from as far back as 1957 to 2002, made their efforts to address the impact of extreme heat on public health [9]. A 3% increase in death rates per 1 °C increase in temperature for all-cause mortality for the hot regions where the temperature of the warmest months exceed 30 °C was reported by McMichael et al. [3]. Each 10 °F (approximately 4.7 °C) increase in mean daily temperature corresponded to a 2.6% (95% confidence interval (CI): 1.3, 3.9) increase for cardiovascular mortality in North America, with the most significant risk found for ischemic heart disease [10]. Increased mortality during heat waves has been attributed mainly to cardiovascular diseases (13–90%) and illness of the cerebrovascular (6–52%), especially among the elderly [11]. High temperature can increase platelet and red cell count, blood viscosity, and mortality due to coronary and cerebral diseases in experimental mice and elderly volunteers from UK [12,13]. Although the independent effects of heat wave and air pollution on daily mortality have been broadly explored, few studies have examined the interaction between high temperature and air pollution [14,15]. Additionally, the higher relative humidity was also associated with higher mortality due to acute myocardial infarction. A significant
0953-6205/$ – see front matter © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2010.03.001
X. Cheng, H. Su / European Journal of Internal Medicine 21 (2010) 164–167
seasonal change in death was found, with the average daily deaths caused by acute myocardial infarction in winter being almost 32% higher compared with summer [16]. The authors [17] considered the possibility that the age-related differences in cutaneous vasodilation were attributable to the difference in skin temperature, and high skin temperature could increase human heart rate. Reviewers [18] also noted that the functional nitric oxide (NO) was required for full expression of cutaneous vasodilation.
3. Extreme cold temperature on human cardiovascular diseases In healthy subjects, cold can trigger an increase in blood pressure due to the increased CO during the initial period of the test with an increase in muscle sympathetic nerve activity, while the increase in this activity elevated peripheral resistance in the later period [19]. Cold can also induce an increase in heart rate, systemic vascular resistance, plasma norepinephrine, levels of vasoconstrictor peptides, and blood pressure in Europeans [20]. Furthermore, cold can cause myocardial ischemia, arrhythmias and lead to heart failure decompensation. The association between cardiovascular mortality and cold spells was implemented in the population of the Czech Republic [21] over 21 year period from 1986 to 2006. The researchers found that cold spells were positively associated with mean excess cardiovascular mortality in all age groups and in both men and women. As similar to heat waves, cold stress had a considerable impact on mortality in central Europe country, with representing a public health threat of an importance. Cold-related mortality was much less understood than heat-related mortality, and was another example of the effects of climate on the human health. Increases in mortality with reducing temperatures in cold weather had been studied in many regions [22–29]. The effects of cold weather were generally most obvious in mortality caused by cardiovascular and respiratory illness [30,31]. Danet et al. [32] showed that a 10 °C decrease in atmospheric temperature was associated with a 13% increase in total coronary event rates, an 11% increase in incident and coronary death rates, and a 26% increase in recurrent event rates. Most of reports had demonstrated a significant winter increase in cardiovascular abnormalities and cardiac death in northern hemisphere, where the temperature was extreme cold in winter [33,34]. There was 53% more cases of acute myocardial infarction found during the winter compared with the summer [35]. Acute coronary syndrome admissions increased 30% to 70% when the average daily temperature was lower than 26.2 °C [36]. Traditional approach showed that daily cardiovascular event rates significantly increased with mean air temperature decrease (10 °C decrease was associated with 19% increase in daily cardiovascular event rates for people older than 65 years) [37]. For western people, there were 4.65% more cardiac and 4.99% more noncardiac deaths that occurred during the Christmas period [38]. Similar to full-body cold exposure, facial cooling could appropriately be used to examine the effects of cold-induced sympathetic activation on vascular function given that individuals were typically properly clothed in cold weather, and cold exposure was restricted to smaller body regions such as the face [39]. Changes in mean arterial pressure suggested that facial cooling may increase augmentation index independent of aortic pulse wave velocity. Facial cooling and the following peripheral vasoconstriction were associated with the increase in wave reflection and augmentation of the central systolic pressure, possibly explaining ischemia and cardiovascular deaths in the cold. The lags between cold weather and its effects on mortality are usually longer and the association is less direct, and geographically more variable. After heat waves, a following impact often occurs for several days, while cold spells may raise levels of mortality for several
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weeks and no following decreases of mortality rates below expected levels have been observed [30]. 4. Mechanisms of heat temperature on cardiovascular diseases Extreme climatic changes were associated with increased daily mortality in many regions around the world [26,40–43]. In clinical trial, Ockene et al. [44] reported that exposure to high temperature could increase plasma viscosity and serum cholesterol levels. Tsai et al. [45] deducted that high temperature might help precipitate coronary artery illness and cerebral infarction. The investigators suggested that the most probable reasons of death during the heat wave were thromboembolic diseases and malignant cardiac arrhythmias as well as heat-induced sepsis like shock [46]. High temperature has also been found to induce profound physiologic changes such as an increase in blood viscosity and cardiac output leading to dehydration, hypotension, and even endothelial cell damage [47]. Balloux et al. [48] showed that populations living in colder environments had lower mitochondrial diversity and that the genetic differentiation between pairs of populations correlates with difference in temperature. Their results indicated that natural selection mediated by climate has contributed to shape the current distribution of mtDNA sequences in humans. Therefore, the relationship between genetic polymorphisms due to climatic stress and cardiovascular diseases need to be further investigated. 5. Mechanisms of cold temperature on cardiovascular diseases It has been known that exposure to cold weather was considered to be one of the main factors affecting morbidity and mortality from cardiovascular illness, including sudden death [49]. Atherosclerotic coronary arteries have been indicated to constrict in response to coldrelated sympathetic outflow with cold pressor test, potentially changing the balance between myocardial oxygen supply and demand [50]. Emmett [51] reviewed that cardiovascular responses at rest and during exercise in the cold differ in patients with coronary arterial disease and healthy subjects. For example, according to a clinical trial study in patients with angina pectoris and coronary insufficiency, nearly half of the patients had more pronounced ECG variations in a cold room at − 15 °C than at room temperature [52]. Another study [53] showed a ST depression in the cold, which could be related to augmented heart work in these patients. Cold stress can induce increasing systemic vascular resistance with enhancing of the blood pressure (thus increasing oxygen demand). The authors [54] found that the mean systolic and diastolic blood pressure was highest in winter and lowest during the summer. Increased blood pressure was one of the most important risk factors for cardiovascular events. Cold stress can exacerbate hypertension in hypertensive patients [55,56]. The evident influence of temperature on cardiovascular mortality may be explained by multiple physiologic functions that are adjusted by ambient temperature. Cold stress can increase blood pressure, sympathetic nervous activities, and platelet aggregation [57,58]. In addition, acute-phase factors, reported as prognostic factors in unstable angina, such as C-reactive protein, fibrinogen, and factor VII activity, were all elevated in winter [59,60]. Cold temperature can cause direct cardiovascular stress due to variations in blood pressure, vasoconstriction, increasing in blood viscosity and levels of red blood cell count, plasma cholesterol, and plasma fibrinogen [61]. During cold weather, enhancement in haemoconcentration (erythrocyte count, plasma cholesterol and plasma fibrinogen levels) has been shown, which could contribute to arterial thrombosis [62]. For this reason, rapid coronary events could result from rupture of atheromatous plaques during hypertension and cold-related coronary spasm [63]. Cold triggers vasoconstriction in cutaneous tissue and this has been confirmed by laser Doppler flowmetry [64], strain gauge
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plethysmography [65] and finger skin temperature [66]. With regards to cutaneous cold-induced vasoconstriction, adrenergic α2 activity was increased [67]. Increased activity of adrenergic α2C mediated the augmented vasoconstriction to cooling in mouse arterial microvessels. Cold activated mitochondrial reactive oxygen species, Followed by activation of Rho/Rho kinase [68]. Rho/Rho kinase translocated adrenergic α2C-receptors from the Golgi to the plasma membrane by microtubule depolymerization. Latterly, it was reported that expression of the adrenergic α2C receptor was enhanced by estrogen [69]. Although it was seen in cutaneous arterioles in vivo, estrogen might enhance the expression of adrenergic α2C receptor in deep arteries. Adrenergic function was thought to be involved in the cold-related vasoconstriction, because inhibition of sympathetic adrenergic function significantly decreased the cutaneous vasoconstrictor response to direct local cooling [70]. The response of conduit arteries to ambient cold might be the result of the equilibrium between adrenergic vasoconstriction and vasodilatation, with the latter being mediated by endothelial function [50]. 6. Perspectives To examine the association between temperature and excess winter mortality, the authors [31] performed a ten-year study in Great Britain, and found that deaths from coronary heart disease were significantly increased in winter. The cold stress may be associated with the flu season and an enhancing of upper respiratory tract infection could make effects on the cardiovascular system. Three epidemiologic and one small clinical trial showed that influenza vaccination was associated with a 50% reduction in incidence of cardiovascular abnormality and sudden cardiac death. Based on this, influenza vaccination is able to prevent this cardiac pathogenesis [71]. These mechanisms may be important for developing new strategies in the preventing of sudden cardiovascular events. Although the authors developed a model of the weather-mortality relation that was potentially useful for projecting the consequences of climate-change scenarios in 11 cities in United States [26], however, the effect of extreme climatic change on cardiovascular disease is hard to predict, at least because that how the temperature–mortality association changes by gender, age, race, and many other factors is difficult to address. Taken together, we believe that climatic changes, especially for cold stress could be considered a new potential risk factor of sudden cardiovascular events in human health, and there is an urgent need for large-scale, prospective, community-based and international study of sudden cardiovascular events to explore deeply the risk factors to schedule preventive strategies. References [1] Patz JA, Campbell-Lendrum D, Holloway T, Foley JA. Impact of regional climate change on human health. Nature 2005;438(7066):310–7. [2] Epstein PR. Climate change and human health. N Engl J Med 2005;353:1433–6. [3] McMichael AJ, Woodruff RE, Hales S. Climate change and human health: present and future risks. Lancet 2006;367(9513):859–69. [4] Haines A, Patz JA. Health effects of climate change. JAMA 2004;291:99–103. [5] Bhaskaran K, Hajat S, Haines A, Herrett E, Wilkinson P, Smeeth L. Effects of ambient temperature on the incidence of myocardial infarction. Heart 2009;95:1760–9. [6] Ostro BD, Roth LA, Green RS, Basu R. Estimating the mortality effect of the July 2006 California heat wave. Environ Res 2009;109:614–9. [7] Linares C, Diaz J. Impact of high temperatures on hospital admissions: comparative analysis with previous studies about mortality. Eur J Public Health 2007;18: 317–22. [8] Ebi KL, Balbus J, Kinney PL, et al. Funding is insufficient to address the human health impacts of and public health responses to climate variability and change. Environ Health Perspect 2009;117:857–62. [9] Basu R, Samet JM. Relation between elevated ambient temperature and mortality: a review of the epidemiological evidence. Epidemiol Rev 2002;24:190–202. [10] Basu R, Ostro BD. A multicounty analysis identifying the populations vulnerable to mortality associated with high ambient temperature in California. Am J Epidemiol 2008;168:632–7.
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Contents lists available at ScienceDirect
European Journal of Internal Medicine j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / e j i m
Review article
Effects of climatic temperature stress on cardiovascular diseases Xiaoshu Cheng ⁎,1, Hai Su 1 Department of Cardiology, Second Affiliated Hospital, Nanchang University, China
a r t i c l e
i n f o
Article history: Received 21 January 2010 Received in revised form 25 February 2010 Accepted 2 March 2010 Available online 29 March 2010 Keywords: Extreme climate Cold Heat Cardiovascular diseases
a b s t r a c t The climatic stress was anticipated to increase direct and indirect risks to human health via different pathways and mechanisms. Extremely high air temperature might trigger the onset of cardiovascular events in the vulnerable. Cold-related mortality was much less understood than heat-related one, and was considered another climatic example of the effects on the human health. Increases in mortality with cardiovascular diseases in extreme heat and cold weather had been studied in many regions. These results suggested that people died rapidly from climate-change related cardiovascular diseases before they were sent to hospital. Obviously, these findings reminded us that climatic stress can be considered as a new potential risk factor of sudden cardiovascular events in human health, and there was an urgent need for large-scale, prospective, community-based and international study of sudden cardiovascular events to explore deeply the risk factors to schedule preventive strategies. © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
1. Introduction The climate change was anticipated to have a long-term impact on human health. Extensive literature reviews displayed that the increases in temperature will bring higher weather-related morbidity and mortality, largely through deaths from cardiovascular and respiratory events [1–4]. Climate changes had increased direct and indirect risk to mankind's health via different pathways and mechanisms. World Health Organization (WHO) estimated that more than 150,000 deaths with 5 million “disability-adjusted life years” for diseases are affected by the change of climate in the latest three decades [1]. Bhaskaran et al. [5] systematically reviewed the studies which specifically focused on the effects of temperature on acute myocardial infarction. They identified a number of differences between studies in terms of population including demographics, location, local climate, study design, and statistical methodology. Based on these large and relatively well-controlled studies, the authors found detrimental effects of both hot and cold weather on the risk of myocardial infarction. Recently, particular attention has been paid to environmental effects on cardiovascular physiology and pathological states. Extremely high or low air temperature may trigger the development of cardiovascular illness in the vulnerable, especially the elderly of North America [6]. These results suggested that people died rapidly from climate-change related diseases before they could be sent to a hospital [7]. Obviously, these findings were vital for performing schedules ⁎ Corresponding author. No. 1, Minde Rd., Nanchang, China, 330006. Tel./fax: +86 791 6268844. E-mail address: [email protected] (X. Cheng). 1 These two authors contributed equally to this work.
before the arrival of climate change, if people wanted to effectively reduce the mortality brought by the variation. Unfortunately, a recent assessment had concluded that climate change presents real risks to human health and the United States government had offered insufficient funding to exacerbate various current health problems [8]. 2. Extreme heat temperature on human cardiovascular diseases The conclusion found in the bibliography displays that excess mortality due to cardiovascular diseases was the main reason for deaths caused by high temperature. The review conducted by Basu and Samet covered a total of 98 papers dating from as far back as 1957 to 2002, made their efforts to address the impact of extreme heat on public health [9]. A 3% increase in death rates per 1 °C increase in temperature for all-cause mortality for the hot regions where the temperature of the warmest months exceed 30 °C was reported by McMichael et al. [3]. Each 10 °F (approximately 4.7 °C) increase in mean daily temperature corresponded to a 2.6% (95% confidence interval (CI): 1.3, 3.9) increase for cardiovascular mortality in North America, with the most significant risk found for ischemic heart disease [10]. Increased mortality during heat waves has been attributed mainly to cardiovascular diseases (13–90%) and illness of the cerebrovascular (6–52%), especially among the elderly [11]. High temperature can increase platelet and red cell count, blood viscosity, and mortality due to coronary and cerebral diseases in experimental mice and elderly volunteers from UK [12,13]. Although the independent effects of heat wave and air pollution on daily mortality have been broadly explored, few studies have examined the interaction between high temperature and air pollution [14,15]. Additionally, the higher relative humidity was also associated with higher mortality due to acute myocardial infarction. A significant
0953-6205/$ – see front matter © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2010.03.001
X. Cheng, H. Su / European Journal of Internal Medicine 21 (2010) 164–167
seasonal change in death was found, with the average daily deaths caused by acute myocardial infarction in winter being almost 32% higher compared with summer [16]. The authors [17] considered the possibility that the age-related differences in cutaneous vasodilation were attributable to the difference in skin temperature, and high skin temperature could increase human heart rate. Reviewers [18] also noted that the functional nitric oxide (NO) was required for full expression of cutaneous vasodilation.
3. Extreme cold temperature on human cardiovascular diseases In healthy subjects, cold can trigger an increase in blood pressure due to the increased CO during the initial period of the test with an increase in muscle sympathetic nerve activity, while the increase in this activity elevated peripheral resistance in the later period [19]. Cold can also induce an increase in heart rate, systemic vascular resistance, plasma norepinephrine, levels of vasoconstrictor peptides, and blood pressure in Europeans [20]. Furthermore, cold can cause myocardial ischemia, arrhythmias and lead to heart failure decompensation. The association between cardiovascular mortality and cold spells was implemented in the population of the Czech Republic [21] over 21 year period from 1986 to 2006. The researchers found that cold spells were positively associated with mean excess cardiovascular mortality in all age groups and in both men and women. As similar to heat waves, cold stress had a considerable impact on mortality in central Europe country, with representing a public health threat of an importance. Cold-related mortality was much less understood than heat-related mortality, and was another example of the effects of climate on the human health. Increases in mortality with reducing temperatures in cold weather had been studied in many regions [22–29]. The effects of cold weather were generally most obvious in mortality caused by cardiovascular and respiratory illness [30,31]. Danet et al. [32] showed that a 10 °C decrease in atmospheric temperature was associated with a 13% increase in total coronary event rates, an 11% increase in incident and coronary death rates, and a 26% increase in recurrent event rates. Most of reports had demonstrated a significant winter increase in cardiovascular abnormalities and cardiac death in northern hemisphere, where the temperature was extreme cold in winter [33,34]. There was 53% more cases of acute myocardial infarction found during the winter compared with the summer [35]. Acute coronary syndrome admissions increased 30% to 70% when the average daily temperature was lower than 26.2 °C [36]. Traditional approach showed that daily cardiovascular event rates significantly increased with mean air temperature decrease (10 °C decrease was associated with 19% increase in daily cardiovascular event rates for people older than 65 years) [37]. For western people, there were 4.65% more cardiac and 4.99% more noncardiac deaths that occurred during the Christmas period [38]. Similar to full-body cold exposure, facial cooling could appropriately be used to examine the effects of cold-induced sympathetic activation on vascular function given that individuals were typically properly clothed in cold weather, and cold exposure was restricted to smaller body regions such as the face [39]. Changes in mean arterial pressure suggested that facial cooling may increase augmentation index independent of aortic pulse wave velocity. Facial cooling and the following peripheral vasoconstriction were associated with the increase in wave reflection and augmentation of the central systolic pressure, possibly explaining ischemia and cardiovascular deaths in the cold. The lags between cold weather and its effects on mortality are usually longer and the association is less direct, and geographically more variable. After heat waves, a following impact often occurs for several days, while cold spells may raise levels of mortality for several
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weeks and no following decreases of mortality rates below expected levels have been observed [30]. 4. Mechanisms of heat temperature on cardiovascular diseases Extreme climatic changes were associated with increased daily mortality in many regions around the world [26,40–43]. In clinical trial, Ockene et al. [44] reported that exposure to high temperature could increase plasma viscosity and serum cholesterol levels. Tsai et al. [45] deducted that high temperature might help precipitate coronary artery illness and cerebral infarction. The investigators suggested that the most probable reasons of death during the heat wave were thromboembolic diseases and malignant cardiac arrhythmias as well as heat-induced sepsis like shock [46]. High temperature has also been found to induce profound physiologic changes such as an increase in blood viscosity and cardiac output leading to dehydration, hypotension, and even endothelial cell damage [47]. Balloux et al. [48] showed that populations living in colder environments had lower mitochondrial diversity and that the genetic differentiation between pairs of populations correlates with difference in temperature. Their results indicated that natural selection mediated by climate has contributed to shape the current distribution of mtDNA sequences in humans. Therefore, the relationship between genetic polymorphisms due to climatic stress and cardiovascular diseases need to be further investigated. 5. Mechanisms of cold temperature on cardiovascular diseases It has been known that exposure to cold weather was considered to be one of the main factors affecting morbidity and mortality from cardiovascular illness, including sudden death [49]. Atherosclerotic coronary arteries have been indicated to constrict in response to coldrelated sympathetic outflow with cold pressor test, potentially changing the balance between myocardial oxygen supply and demand [50]. Emmett [51] reviewed that cardiovascular responses at rest and during exercise in the cold differ in patients with coronary arterial disease and healthy subjects. For example, according to a clinical trial study in patients with angina pectoris and coronary insufficiency, nearly half of the patients had more pronounced ECG variations in a cold room at − 15 °C than at room temperature [52]. Another study [53] showed a ST depression in the cold, which could be related to augmented heart work in these patients. Cold stress can induce increasing systemic vascular resistance with enhancing of the blood pressure (thus increasing oxygen demand). The authors [54] found that the mean systolic and diastolic blood pressure was highest in winter and lowest during the summer. Increased blood pressure was one of the most important risk factors for cardiovascular events. Cold stress can exacerbate hypertension in hypertensive patients [55,56]. The evident influence of temperature on cardiovascular mortality may be explained by multiple physiologic functions that are adjusted by ambient temperature. Cold stress can increase blood pressure, sympathetic nervous activities, and platelet aggregation [57,58]. In addition, acute-phase factors, reported as prognostic factors in unstable angina, such as C-reactive protein, fibrinogen, and factor VII activity, were all elevated in winter [59,60]. Cold temperature can cause direct cardiovascular stress due to variations in blood pressure, vasoconstriction, increasing in blood viscosity and levels of red blood cell count, plasma cholesterol, and plasma fibrinogen [61]. During cold weather, enhancement in haemoconcentration (erythrocyte count, plasma cholesterol and plasma fibrinogen levels) has been shown, which could contribute to arterial thrombosis [62]. For this reason, rapid coronary events could result from rupture of atheromatous plaques during hypertension and cold-related coronary spasm [63]. Cold triggers vasoconstriction in cutaneous tissue and this has been confirmed by laser Doppler flowmetry [64], strain gauge
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plethysmography [65] and finger skin temperature [66]. With regards to cutaneous cold-induced vasoconstriction, adrenergic α2 activity was increased [67]. Increased activity of adrenergic α2C mediated the augmented vasoconstriction to cooling in mouse arterial microvessels. Cold activated mitochondrial reactive oxygen species, Followed by activation of Rho/Rho kinase [68]. Rho/Rho kinase translocated adrenergic α2C-receptors from the Golgi to the plasma membrane by microtubule depolymerization. Latterly, it was reported that expression of the adrenergic α2C receptor was enhanced by estrogen [69]. Although it was seen in cutaneous arterioles in vivo, estrogen might enhance the expression of adrenergic α2C receptor in deep arteries. Adrenergic function was thought to be involved in the cold-related vasoconstriction, because inhibition of sympathetic adrenergic function significantly decreased the cutaneous vasoconstrictor response to direct local cooling [70]. The response of conduit arteries to ambient cold might be the result of the equilibrium between adrenergic vasoconstriction and vasodilatation, with the latter being mediated by endothelial function [50]. 6. Perspectives To examine the association between temperature and excess winter mortality, the authors [31] performed a ten-year study in Great Britain, and found that deaths from coronary heart disease were significantly increased in winter. The cold stress may be associated with the flu season and an enhancing of upper respiratory tract infection could make effects on the cardiovascular system. Three epidemiologic and one small clinical trial showed that influenza vaccination was associated with a 50% reduction in incidence of cardiovascular abnormality and sudden cardiac death. Based on this, influenza vaccination is able to prevent this cardiac pathogenesis [71]. These mechanisms may be important for developing new strategies in the preventing of sudden cardiovascular events. Although the authors developed a model of the weather-mortality relation that was potentially useful for projecting the consequences of climate-change scenarios in 11 cities in United States [26], however, the effect of extreme climatic change on cardiovascular disease is hard to predict, at least because that how the temperature–mortality association changes by gender, age, race, and many other factors is difficult to address. Taken together, we believe that climatic changes, especially for cold stress could be considered a new potential risk factor of sudden cardiovascular events in human health, and there is an urgent need for large-scale, prospective, community-based and international study of sudden cardiovascular events to explore deeply the risk factors to schedule preventive strategies. References [1] Patz JA, Campbell-Lendrum D, Holloway T, Foley JA. Impact of regional climate change on human health. Nature 2005;438(7066):310–7. [2] Epstein PR. Climate change and human health. N Engl J Med 2005;353:1433–6. [3] McMichael AJ, Woodruff RE, Hales S. Climate change and human health: present and future risks. Lancet 2006;367(9513):859–69. [4] Haines A, Patz JA. Health effects of climate change. JAMA 2004;291:99–103. [5] Bhaskaran K, Hajat S, Haines A, Herrett E, Wilkinson P, Smeeth L. Effects of ambient temperature on the incidence of myocardial infarction. Heart 2009;95:1760–9. [6] Ostro BD, Roth LA, Green RS, Basu R. Estimating the mortality effect of the July 2006 California heat wave. Environ Res 2009;109:614–9. [7] Linares C, Diaz J. Impact of high temperatures on hospital admissions: comparative analysis with previous studies about mortality. Eur J Public Health 2007;18: 317–22. [8] Ebi KL, Balbus J, Kinney PL, et al. Funding is insufficient to address the human health impacts of and public health responses to climate variability and change. Environ Health Perspect 2009;117:857–62. [9] Basu R, Samet JM. Relation between elevated ambient temperature and mortality: a review of the epidemiological evidence. Epidemiol Rev 2002;24:190–202. [10] Basu R, Ostro BD. A multicounty analysis identifying the populations vulnerable to mortality associated with high ambient temperature in California. Am J Epidemiol 2008;168:632–7.
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