Effects of Extreme Ambient Temperature on Cardiovascular Outcomes: A Systematic Review

REVIEW ARTICLE Introduction: Extreme weather or climate, including heat waves and cold waves, is considered a health issue causing adverse effects on health, such as cardiovascular diseases (CVDs), mortality and morbidity. Thus, this systematic review aimed to study the impacts of extreme ambient temperature on cardiovascular outcomes. Material and Methods: This study was carried out based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Papers about the ambient temperature and cardiovascular outcomes were searched in the scientific database, including ISI, PubMed, Scopus, and Google Scholar, from January 1970 up to the end of 2020. We used the key terms, such as “heat wave”, “cold wave”, “extreme event”, “cardiovascular disease”, “mortality”, and “morbidity”. The thematic analysis method was used to determine all themes and analyze the data. Results: Among the 7631 searched and extracted papers, 20 articles met the eligibility criteria for including the process of final analysis. Effects of extreme events included mortality, morbidity, and hospitalization due to CVD. A relationship between extreme events and CVD mortality was confirmed for cerebrovascular diseases, including congestive heart failure (CHF), ischemic heart diseases (IHD), myocardial infarction (MI), cardiac arrhythmia, coronary heart disease (CHD), out-of-hospital cardiac arrest (OHCA), acute coronary syndrome (ACS), and blood pressure. Conclusion: The present study indicated the impact of extreme ambient temperature on CVD outcomes. The findings provided adaptation and preventive measures and strategies which can be used for CVD patients and managers to prevent CVD due to ambient temperature.


Introduction
Extreme weather or extreme climate, including heat waves and cold waves, related to excessive extreme temperatures in cold and warm season, is expected to impact health, such as increased cardiovascular diseases (CVDs), mortality, and morbidity 1,2 . CVD sharing the characteristics of acute attack and hard recovery, has become an main health issue 3 . CVDs are a group of diseases that include both the heart and blood vessels 4 . CVDs are one of the main causes of global mortality. According to estimation of World Health Organization (WHO), more than 17.9 million people die from cardiovascular, annually 5 .
CVDs cause adverse economic effects, such as disability, affect the productivity of active labor force, and result in reduced gross domestic product (GDP) and national income 6 . One of the main factors of CVD is exposure to extreme events, such as cold and heat waves. Both cold and heat temperatures are related to increased death due to CVDs. In addition, insignificant excess hospital emergency admissions due to CVDs are considered on both heat and cold waves 7 . Based on the latest measurement of CVD mortality rate vs. GDP per capita, 2017, CVD mortality rate is measured as the number of deaths per 100,000 individuals versus GDP per capita 8 .
The relation between heat wave and hospitalization is urgent and of short-term period, whereas that of cold waves is postponed but would last longer. Extreme ambient temperature events, especially heat waves, have been proved as the most hazardous of all environmental hazards and claim the largest numbers of patients 7 . The World Meteorological Organization (WMO) described heat wave as the daily maximum temperature that is higher than 32 °C and period of more than 3 days 9 . Exposure to heat waves composed with physical exertion can at the same time effect in systems of sympathetic and parasympathetic, increasing the possibility of atrial fibrillation 10 . Dehydration, raised hypotension and even endothelial cell damage, blood viscosity, and a higher possibility of thromboembolic diseases are the major pathophysiological mechanisms of the heat impacts on health 11 . Moreover, heat waves may impair the endothelial function, enhancing the risk for cardiovascular events 12 .
Cold waves can affect CVD stress due to blood pressure, vasoconstriction, rising in blood viscosity and count of red blood cell, plasma fibrinogen and cholesterol 13 . Cold stress is associated with increased blood pressure and platelet aggregation; raised vasoconstriction; increased blood viscosity and count of red blood cell, plasma fibrinogen and cholesterol; and higher hem concentration, all of which could causes thrombosis 7 . Numerous researches have proven extreme ambient temperature to be related to raise CVD mortality and morbidity. Several research studies have confirmed the effect of extreme events, such as cold and heat waves on cardiovascular mortality [14][15][16] . All of studies have evaluated the raised risk of CVD outcomes under various conditions, such as duration and intensity 16 . Vulnerable group, including elderly people, women, and outdoor employees are at higher risk than the other groups. Harmful impacts of heat waves among the older people and women are more severe than younger people and males 16 . The present systematic review aimed to study the effects of ambient temperature (heat and cold waves) on CVD outcomes, such as mortality, morbidity, and hospitalization.

Materials and Methods
In this research, the systematic review of papers related to ambient temperature and CVD was conducted based on the PRISMA guidelines 17 .

Criteria for Eligibility
In this research, the papers were selected and remained based on the criteria as follows: 1) The papers apparently addressing the ambient temperature and CVD. 2) Full texts of papers are available freely.
3) The papers published in English language. 4) The studies that included in all types of methodologies published in peer-reviewed journals. 5) The papers encompassing all types of CVD associated in ambient temperature.
The exclusion criteria were as follows: 1) The books, letters to the editor, editorials, clinical studies, abstracts, conference papers, presentations, theses, and commentaries.
2) The studies with irrelevant subjects and duplicate data.
3) The studies with ambiguous methodology or without results. 4) The studies including the association between ambient temperature with other diseases, such as respiratory or renal.

Study selection
Initially, duplicate studies were removed using the EndNote software. Remaining studies were assessed based on titles and abstracts and some irrelevant articles were removed. In the next step, two authors assessed the full texts of the retrieved studies critically based on eligibility criteria, independently. Then, the results of assessment were compared and in the case of any disagreement, they were resolved through consensuses. In case of any disagreement of opinions between the two previous authors, a third author was requested independently for final decision.

Data extraction
The determined information was extracted from the selected final studies using standard data extraction form. The collected data included 1) first author name 2) publication year 3) tittle 4) location 5) purpose of study 6) study design 7) exposure (heat wave/cold wave) 8) types of CVD 9) outcome 10) key results of articles along with the corresponding standard deviations were exploited from the selected studies.

Quality assessment and risk of bias
Assessment of quality for the final studies was conducted to separate low-quality articles from others and to avoid risk of bias. Given that the low-quality studies were of high level of bias, they were all removed from this study. Quality assessment or risk of bias for all of the assessed full texts of articles was independently and critically performed by two authors through the critical appraisal skills program (CASP) 19 , the strengthening the reporting of observational studies in epidemiology (STROBE) tools 20 , and checklists.

Ethical Issue
This research was completed in accordance with the ethical principles of, and was approved by, the research ethics committee of Iran University of Medical Sciences (IR.IUMS.REC. 1397.1376).

Results
A total of 7631 studies were found from the scientific databases and 8 articles were identified from other sources. Firstly, 2378 papers were removed using the EndNote because of duplication. Then, 5253 papers were assessed based on titles and abstracts for eligibility and 5127 papers were excluded. Then, full texts of the 126 remained papers were reviewed. Finally, 20 papers met the eligibility criteria for including the process of systematic review after considering type of articles and quality assessment as shown in Table 1. This table reveals first author name, publication year, tittle, location, aim of study, study design, exposure (heat wave/cold wave), types of CVD, outcome and key results of articles. Figure 1 demonstrates PRISMA flowchart encompassing study identification and selection process. PRISMA primarily focuses on review reports evaluating the study selection process. This process includes number of records identified through searching databases and additional documents searched through other database, records removed after duplicates, records screened, full-text papers reviewed for eligibility, full-text papers excluded with causes, and final studies included in article.   [48] Relationship between heat waves with increases in short-term risk of CVD mortality was confirmed. But relationship between cold waves with increased risk of CVD was not found.

Discussion
The purpose of present study was to systematic review and summarize key findings related to the impact of extreme events on cardiovascular outcomes, including mortality, CVD, and hospitalization attributed to CVD. The systematic review of the 20 included publications demonstrated that extreme events play a significant role in the cardiovascular outcomes. Several studies have proved increased risk of cardiovascular outcomes, such as mortality, CVD, and hospitalization. An association between extreme events and CVD mortality was observed for cerebrovascular diseases, congestive heart failure, ischemic heart disease, myocardial infarction, cardiac arrhythmia, coronary heart disease, out-of-hospital cardiac arrest, acute coronary syndrome, and blood pressure. (Figure 2) Congestive Heart Failure A syndrome in which the heart is not able to pump blood sufficiently named Heart failure (HF) that causes MI and hypertension 21 . CHF is a disease that results in pulmonary vascular congestion and decreased heart output. CHF is a chronic status that the pumping power of cardiac muscle is affected 22 . One of the risk factors of CHF is weather, especially heat wave. Many papers have studied relation between extreme temperature events and morbidity, mortality, and hospitalizations raise during heat and cold waves 23 . Based on some studies, the mortality rate due to CHF increased significantly at ambient high temperature 24,25 .

Ischemic Heart Disease (IHD)
The inadequate condition of oxygen within the heart muscles due to an imbalance between oxygen supply and demand, named IHD. This illness determined by reduced blood supply to the cardiac muscle. This event results from the obstruction in coronary arteries by atherosclerosis and thrombus 26 . Many research studies have shown the impact of heat wave on death due to IHD. Intensity and duration of heat waves feature stronger influences on IHD deaths. The period of heat waves has main effects on mortality. Heat waves with a period of three days shown an average IHD mortality raise of about 10%, days during longer heat waves are related to higher death rate of up to 19%. 27

Myocardial infarction
MI, or heart attack, is due to an atherosclerotic plaque rupture, leading to partial or complete thrombotic vessel occlusion 28 . Acute MI is one of the leading reasons of death worldwide. An MI causes impairment in diastolic and systolic function, making the patient prone to arrhythmias 29 . Ambient temperature is a major risk factor of AMI mortality 30 . Heat waves with temperature of above a threshold of 20°C to be related to an raised risk of MI 1-6 hours after exposure 31 . In cold weather the blood pressure decreases in the peripheral parts of the body. It increases viscosity and concentration of blood which may leading to higher clotting and, so, a greater rate of thrombosis 32 . Negative effects of cold wave on acute MI have been demonstrated in some studies 33 . Furthermore, some studies have shown that exposure to extremely high and extremely low temperature increases the rate of hospitalization due to AMI. Risks of heat waves may be different in population subgroups 34,35 .

Cardiac arrhythmia
Cardiac arrhythmia is considered a major risk factor for mortality due to CVDs, especially in the older people, in whom disorder heart function may aggravate pre-existing abnormalities. 36 .
Cardiac arrhythmias, including atrial fibrillation and flutter, are one of the types of CVDs in which the heartbeat is abnormal, very rapid, or slow. Some arrhythmias have no symptoms, and their particular reason may sometimes be unknown 37 . Based on recent evidence, acute exposure to heat and cold raise the possibility of cardiac arrhythmia, which is mainly due to paroxysmal tachycardia and other cardiac arrhythmias 38 . Also, emergency department (ED) visits due to arrhythmia is strongly related extreme ambient temperature. Arrhythmia-related emergency department visits decrease during fall and winter 37 .
Coronary heart disease CHD is one of the types of CVD that creates when the arteries of the cardiac cannot transfer sufficient oxygen-rich blood to the cardiac. CHD is developed by the buildup of plaque, a waxy substance, inside the lining of larger coronary arteries. This buildup can partially or totally block blood flow in the large arteries of the cardiac 39,40 . Risks of CHD hospitalizations with both heat and cold waves were investigated and confirmed 41 .
Also, there are limited epidemiological studies quantifying the ambient temperature-related burden of CVD death, especially CHD 42 .

Out-of-hospital cardiac arrest
OHCA is considered an important global human health challenge. The loss of mechanical heart function and the absence of systemic circulation are described as OHCA 43 . Cessation of cardiac mechanical activity that occurs outside of the hospital is named OHCA and is approved by the absence of symptom of circulation 44 .The potential effects of seasonal variation and ambient temperature on OHCA were investigated 45 . Some studies have shown that both clod and heat waves were significantly related to raised hospital emergency admission and death due to OHCA 45 .
Acute coronary syndrome ACS is one of the types CVD and leading numerous mortalities globally. ACS often shown a level of destruction to the coronary arteries by atherosclerosis; plaque rupture, thrombosis, and inflammation 46,47 . There was a significant seasonal fluctuation in the rate of ACS, and extreme ambient temperature may affect the onset of ACS 48 . Ambient temperature range associated significantly with daily emergency hospitalization due to ACS 48,49 . Diurnal ambient temperature fell below 17.0°C or the diurnal temperature range exceeded a threshold of 5.8°C. The risk level of ACS was higher than baseline data 48 .

Blood Pressure
Hypertension or blood pressure is one of the most important risk factors for CVD and is a one of the main causes of precocious death globally. Blood pressure is a crucial medical status that significantly raises the risks of heart, brain, kidney, and other illness. Based on the estimation of the WHO 1.13 billion people worldwide have hypertension 50 . Cold wave leading to vasoconstriction and tachycardia, both of which contribute to raised blood pressure and heart load 51 . Several studies have confirmed that blood pressure changes with temperature and extreme ambient temperature imparts a very short-term impact on blood pressure 52-54 .  Recommendation and measures CVD patients should be made aware of the raised risk of ambient temperatures. Health system especially, hospitals and emergency department should take into account the raised load of patients and demand of specific facilities during heat and cold waves 48 . Timely protective measures and adaptation strategies, such as identification of susceptible populations to heat-related CVD, using air conditioners in summer, avoiding outdoor activities, wearing light clothing, adequate hydration, development of heat shelters, also a well-developed early warning system and emergency service seem to decrease the burden of CVD outcomes 15,49,53 . Public information of impending cold waves, may be a way to encourage people especially vulnerable group, including the elderly and people with underlying heart disease to dress warmly 55 . The outcomes of heat and cold waves could be concerned in mass media and social media weather predicates when improper status is possible. Recommendation and warning on preventive behavior change should be given to CVD patients, before and during heat and cold days 41 .

Conclusion
The present systematic review demonstrated the impact of extreme ambient temperature on CVD outcome, including mortality, morbidity, and hospital admission. According to the results, extreme ambient temperature had a significant association to the CVD outcomes. Moreover, heat exposure and extreme ambient temperature, including cold and heat waves were related to a raised risk of CVD. Through identification of these effects, measures and strategies can be developed to have an impact on this major global health challenge. This comprehensive systematic review study presents a potential adaptation and preventive strategies for the relationship with extreme weather on CVD, and can also be used in the prevention of CVD due to ambient temperature. The results of this research can help policy-makers and administrators in developing standards for cold and heat waves, conduct necessary prevention, mitigation and preparations, developing more exact heat alarms, and taking activities to prevent or decrease temperaturerelated mortality and morbidity, to ultimately contribute to better human health.