Novel Strategies and Approaches in Hypertension Therapy

By Bentham Science Publishers

Hypertension has become a major public health problem in the last few decades. High blood pressure is a serious risk factor for premature cardiovascular disease and end organ damage including left-ventricular hypertrophy and congestive heart failure, which in-turn increases the risk of cardiovascular morbidity and mortality.
While studies of hypertension have been performed worldwide in a variety of epidemiological settings such as diabetes, renal function, obesity and thyroid disorders, there is a need to identify appropriate treatment strategies

Novel Strategies and Approaches in Hypertension introduces the reader to different aspects of hypertension treatment (environmental and occupational factors and different clinical settings that can trigger the disease). The book also covers special topics related to the use of new diagnostic biomarkers for hypertension patients, as well as endocrine and nutrition focused approaches to treat the condition.
This reference book will be useful for medical professionals involved in the management and care of patients affected with hypertension.

• Language: English
• Publisher: Bentham Science Publishers
• Release date: Oct 4, 2019
• ISBN: 9789811422720

Book preview

Environmental Aspects of Hypertension

Umesh Jayarajah¹, ³, Suranjith L. Seneviratne², ³, *

¹ Professorial Medical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka

² Institute of Immunity and Transplantation, Royal Free Hospital and University College London, London, UK

³ Department of Surgery, Faculty of Medicine, University of Colombo, Sri Lanka

Abstract

Environmental factors are an important cause of poor health globally. Hypertension is known to occur due to complex interactions between adverse lifestyles and environmental factors on a background of polygenic inheritance. Although pharmacological interventions have taken a prominent place, environmental factors and interventions have generally received less consideration. The short-term and long term impact of several environmental factors on blood pressure changes such as cold ambient temperature, exposure to loud noise, air pollution, high altitude, certain organic pollutants, and heavy metals have been recently reported. In this chapter, the current evidence on the effect of such environmental risk factors on blood pressure with its pathophysiological mechanisms and clinical relevance have been described in detail. As some of these effects are clinically relevant, clinicians, patients with hypertension or cardiovascular disease and individuals at high risk for cardiovascular disease would need to be aware of these environmental factors. Furthermore, close attention to monitoring blood pressure during such exposures is necessary and in individuals with hypertension, treatment schedules may need adjustment to ensure more optimal blood pressure control.

Keywords: Air pollution, Aircraft noise, Ambient temperature, Blood pressure, Cardiovascular diseases, Diastolic hypertension, Environmental factors, Heart disease, Heavy metals, High altitude, Hypertension, Lifestyle, Loud noise, Noise pollution, Organic pollutants, Pathophysiology, Risk factors, Sleep apnoea, Systolic hypertension, Work environment.

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* Corresponding author Suranjith L. Seneviratne: Institute of Immunity and Transplantation, Royal Free Hospital and University College London, London, UK; Tel: [phone]; E-mail: [e-mail]

INTRODUCTION

Hypertension occurs due to complex interactions between adverse lifestyles and environmental factors on a background of polygenic inheritance [1]. Recently, there has been a pandemic of metabolic disorders such as hypertension. Several

behavioural interventions and medications have been found to be effective in lowering blood pressure and reducing cardiovascular complications [1]. In clinical practice, although pharmacological interventions have taken a prominent place, environmental factors and interventions have generally received less consideration [2]. There is published evidence on the effects of environmental factors such as cold temperatures, high altitudes, loud noise, air pollution and heavy metal exposure in the causation of hypertension [2]. According to the report of the ‘Environmental Burden of Disease in European Countries’ project, particulate matter air pollution and noise pollution, result in >75% of the burden of disease attributable to environmental factors [3]. As they primarily affect cardiovascular diseases and risk factors, they in turn contribute significantly to an increase in disability adjusted life years [4]. Although the effect on blood pressure is generally small, owing to the global presence of hypertension, the overall effect is fairly significant. Thus, early identification of relevant environmental factors and their correction may have important clinical implications in the control of hypertension [2]. We have discussed the clinical effects and pathophysiological mechanisms of a range of environmental factors on blood pressure.

COLD AMBIENT TEMPERATURE RELATED HYPERTENSION

The association between seasonality/outdoor temperatures and cardiovascular disorders has been extensively studied [5-10] (Table 1). Several studies have described associations between changes in outdoor temperature during the year and morbidity and mortality rates from cardiovascular disease. An increased incidence of acute coronary events and stroke has been reported during winter [6]. This seasonal pattern in cardiovascular diseases may be explained by seasonal changes in blood pressure [9]. A number of studies done in several countries and varying climates have found an inverse relationship between ambient temperature and blood pressure. Yang et al., explored the relationship between blood pressure, outdoor temperature, and cardiovascular mortality in around 500,000 Chinese adults from both urban and rural regions prospectively followed up for seven years [9]. They found a strong relationship between monthly outdoor temperatures and blood pressure. The mean systolic blood pressure was 9 mm Hg higher in winter compared to summer. Above an outdoor temperature of 5°C, each 10°C decrease in temperature caused an increase in systolic blood pressure of 6.2mm Hg. Overall, there was a 41% increase in cardiovascular mortality during winter. The authors suggested the increase in cardiovascular events may at least partly be explained by an increase in blood pressure [11].

In a cross-sectional study of 1395 patients (89.3% of whom were hypertensive), Fedecostante et al., compared blood pressure measurements taken in the two hottest and two coldest months. Mean daytime systolic and diastolic blood pressure was significantly higher in winter [12]. Modesti et al., confirmed these findings when ambulatory blood pressure monitoring and temperature measurement were done in nearly 1900 patients referred to two Hypertension Units [13]. Temperature and seasonality were found to independently affect blood pressure, where the temperature had an inverse relationship with daytime systolic blood pressure and seasonality (expressed as the number of daylight hours), mainly affected night-time systolic blood pressure. An increase in daylight hours was associated with higher night-time blood pressure and could at least be partly due to a reduction in sleep quality [13]. A study on 2078 cardiac rehabilitation patients from Michigan, found a similar inverse association. A reduction in outdoor temperatures by 10.4o C during the prior 1 to 7 days was associated with a 3.6mm Hg increase in systolic blood pressure [14]. However, some studies have found nocturnal blood pressure to be higher during summer than winter months [12, 13, 15, 16]. Variations have also been observed in relation to indoor versus outdoor temperature exposures [13, 16, 17].

Table 1 Summary of studies on the effects of cold ambient environmental temperature on blood pressure.

Pathophysiology of Cold Ambient Temperature Related Hypertension

Cold weather leads to compensatory activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis so as to increase the body temperature. Increased sympathetic activity leads to stimulation of the juxtaglomerular apparatus and increased activity of the renin-angiotensin-aldosterone system causing sodium and water retention [18]. Due to poorly understood mechanisms, atherosclerotic coronary arteries undergo a higher degree of vasoconstriction in response to cold, leading to an imbalance in the myocardial oxygen demand and supply [19]. The cold pressor test evaluates sympathetic cardiovascular reactivity. Cold induced sympathetic responses lead to acute peripheral arteriolar vasoconstriction and affect the diastolic blood pressure, heart rate and cardiac load [20]. In addition, colder temperatures increase blood viscosity, red cell counts, plasma cholesterol, and plasma fibrinogen and promote platelet aggregation [21]. Increased cardiac load and hypercoagulability, may lead to acute coronary events, especially in those with pre-existing coronary vascular disease, atherosclerotic plaques and hypertension [22, 23].

Variations in systolic and diastolic blood pressure with outdoor temperature depend on the age [24]. Elderly people are more susceptible to seasonal blood pressure variations.

The Three-City Study was a prospective study conducted in 8801 participants 65 years or older, where oscillations in blood pressures in relation to temperature were analyzed [25]. An inverse relationship between environmental temperature and blood pressure was observed, with higher changes in blood pressure noted in older participants. In those aged between 65 - 74 years and older than 80 years, a 15°C decrease in outdoor temperature led to an increase in systolic blood pressure by 0.8 and 5.1mm Hg, respectively. The exact reasons for this observation are poorly understood, but may at least be partly due to reduced homeostatic responses due to impaired baroreflexes [26, 27]. Furthermore, increased atherosclerosis in the elderly may give result in an increased vasoconstrictor response. Such findings may explain greater cardiovascular mortality among the elderly during winter.

Outdoor temperature is only one of the environmental factors affecting the seasonality of hypertension and cardiovascular disease. Other known environmental factors include sunlight exposure, cold perception, changes in dietary and exercise habits, air pollution, disturbance in the circadian rhythm and sleep alterations [13, 28-31]. Studies have found longer life expectancy amongst women with active sun exposure. Thus lower sunlight exposure may be contributing to a higher incidence of cardiovascular diseases in winter [28]. In a random household survey of 1410 Chinese residents, more than half an hour's sun exposure daily (compared to none) was associated with a lower prevalence of hypertension [32]. Stephen et al analyzed relationships between blood pressure, sunlight exposure and plasma vitamin D concentrations in 1104 participants of the Reasons for Racial and Geographic Differences in Stroke (REGARDS) study. A significant inverse association between hypertension and Vitamin D levels and solar insolation was found. Adjusting for vitamin D levels, had no effect on the significant inverse association of solar insolation with blood pressure suggesting that the blood pressure lowering effect of sun exposure seems to be independent of Vitamin D levels [33]. This direct effect may be explained by the vasodilator effect of nitric oxide (NO). The skin contains considerable stores of nitrogen oxides, which are converted to NO by ultraviolet radiation and then transported to the systemic circulation. Human studies have shown NO to cause arterial vasodilatation and thus lower blood pressure. Furthermore, murine studies suggest similar mechanisms may lead to a reduction in the metabolic syndrome [34]. Additionally, increased sunlight exposure may lead to increased body temperatures, which then cause cutaneous vasodilatation, lower peripheral resistance and blood pressure [35].

Seasonal fluctuations in air pollution may contribute to variations in blood pressure. This is more relevant in urban areas, where air pollution is more commonly seen and characterized by both seasonal and daily fluctuations. For example, sulfur dioxide (SO2) levels that are known to have a blood pressure increasing effect, peaks during winter. SO2 is mainly derived from heating systems in buildings. Ozone (O3), linked to photochemical smog has a blood pressure lowering effect. It reaches a peak during the summer months and the central hours of a day [36].

Seasonal variations in sleep onset, duration and quality may influence blood pressure and cardiovascular disease. Obstructive sleep apnoea (OSA) is characterized by repetitive interruptions of pulmonary ventilation during sleep. It is commonly seen in obese individuals and known to be associated with increased cardiovascular morbidity and mortality [37]. Recent evidence points to OSA being the most prevalent secondary contributor to hypertension. It can cause or worsen hypertension in susceptible individuals [11]. The severity of OSA is inversely related to ambient temperature and directly related to atmospheric pressure, carbon monoxide levels and relative air humidity [31]. The seasonality of OSA remained significant even after adjustment for sex, age, body mass index, neck circumference, and relative air humidity.

Lifestyle factors such as increased food and salt intake, cause a seasonal change in blood pressure [38]. Lack of physical activity is a risk factor for hypertension and cardiovascular disease. As physical activity may be reduced in winter, it may contribute to the seasonality of hypertension [39]. There is some evidence to suggest that close monitoring of blood pressure during winter may be beneficial in hypertensive patients [17, 40, 41]. Some patients may require anti-hypertensive medication dose adjustments for optimal blood pressure control [42]. Although improved residential heating might be helpful in combating the hypertensive effects of cold, further large scale prospective studies are needed before implementing such findings into clinical practice [17, 43]. The use of practical lifestyle modifications (such as using space heaters, wearing warmer clothes and reducing cold outdoor exposures) may be beneficial.

NOISE EXPOSURE-RELATED HYPERTENSION

Loud noise and noise pollution have been associated with raised blood pressure and increased cardiovascular disease [44]. Exposure to loud noise even for brief periods may increase blood pressure within minutes [45, 46]. Chronic exposure to loud noise may increase the risk of overt hypertension [47-49]. Whether these are due to specific types of exposure or the timing of exposure needs further study. Increases in blood pressure are higher following nocturnal than day time exposure to loud noise [46]. Several studies have attempted to describe the relationship between noise exposure and hypertension (Table 2). Andren et al found a statistically significant increase in diastolic blood pressure at 95 decibels (dB) and proposed that repetitive loud noise could contribute to the development of hypertension [50]. Chronic noise exposure has been found to associate with raised urinary epinephrine and norepinephrine levels, increases in pulse rate and cholesterol levels, all of which may, in turn, contribute to increased blood pressure [51].

Table 2 Summary of studies on the effects of environmental noise exposure on blood pressure.

Industrial Noise Exposure and Hypertension

Several studies have looked at the association between industrial noise exposure and hypertension [52-57]. A case-control study that analyzed the effect of noise exposure after eliminating known confounding factors, found a significant positive association of hypertension with high amplitude noise exposure [57]. However, one needs to remember that confounding factors associated with noise exposure may themselves contribute to hypertension. For instance, Lercher et al., found that workers with increased noise exposure had significantly higher body mass index and alcohol consumption and did more night shifts, all factors that may independently contribute to raised blood pressure [55]. A large scale prospective study on 3106 employees in 21 Israeli industrial plants, did not find a clear relationship between noise exposure and either systolic or diastolic blood pressure, after following correction of confounding factors [58]. Another large study in 7,679 French workers, failed to show a significant association between blood pressure and noise exposure after adjusting for confounding factors such as age, body mass index, alcohol consumption and occupational category [59].

Road Traffic Noise Exposure and Hypertension

Chronic exposure to road traffic and/or railway or aircraft noise is known to increase blood pressure. Several studies have found adverse short-and long-term effects of noise on blood pressure [44]. A meta-analysis of 24 cross-sectional studies, found a 7% increase in the prevalence of hypertension for each 10dB increase in average traffic noise exposure [60]. Residing near roadways has been associated with raised blood pressure. Among more than 38,000 US women, residing within 50m of a major roadway was independently associated with a 13% higher incidence of hypertension [61]. An independent contribution of noise to increasing blood pressure has been supported by some but not all studies [62-64]. Considerable heterogeneity was noted among the studies, with respect to age, gender and study methodology and this may account for some of the conflicting findings. In the large HYENA study, road traffic noise was associated with hypertension in men but not in women [47]. Furthermore, in the Groningen study, road traffic noise was significantly associated with hypertension only in a subset of people aged between 45 and 55 years [65]. A large Danish cohort study in middle-aged subjects found a significant increase in systolic blood pressure for each 10dB increase in road traffic noise. This association was more significant in men and older subjects [66]. Similarly, a Spanish cohort study found road traffic noise to be significantly associated with systolic blood pressure [62]. In this study, indoor night-time noise levels were more consistently associated with systolic hypertension. A meta-analysis of 14 studies (n= 8,770 kindergarten and school children) found a relationship between road traffic noise and blood pressure [67]. A 5dB rise in road traffic noise at kindergarten/school was associated with a 0.48mmHg higher systolic blood pressure and a 0.22 mmHg higher diastolic blood pressure. One needs to be aware that these studies varied in the methodology used and most were cross-sectional. A prospective study that evaluated the association between road traffic/railway noise and hypertension found no association between chronic exposure to road traffic noise and hypertension but found a significant association with railway noise. The main limitation of this study was that hypertension was self-reported and thus may have been underestimated [66].

Several studies have analyzed the effect of noise exposure on pregnancy-induced hypertension. A large study of almost 77,000 Danish pregnant women found road traffic noise to be significantly associated with hypertension. A 10dB higher exposure to residential road traffic noise during the first trimester of pregnancy was associated with an increased risk of pre-eclampsia and pregnancy-induced hypertension. Adjusting for air pollution, slightly lowered the risk estimate [67]. A Lithuanian study on around 3,000 women, found a non- significant association between road traffic noise and gestational hypertension [68]. The concomitant exposure to air pollution (which is independently associated with hypertension), is a potential confounder in such studies [69].

Aircraft Noise Exposure and Hypertension

A relationship between aircraft noise and early-morning blood pressure was observed even within the physiological blood pressure range [70]. A prospective study was done in two groups of individuals near the Frankfurt airport exposed to night-time outdoor aircraft noise of 50 dB. One group was exposed for 75% and the other for 25% of the time and then followed up for three months. A statistically significant higher blood pressure (of 10/8 mm Hg) was seen in the group exposed for 75% of the time. The HYENA study, conducted in 4861 individuals residing near six major European airports for at least 5 years, found a dose-response association between night-time aircraft noise and prevalence of hypertension [47].

The RANCH study, conducted among 9-10-year-old children, reported an association between both daytime and nocturnal home noise exposure and blood pressure [71]. A meta-analysis of 4 cross-sectional and 1 cohort study examined the relationship between aircraft traffic