Fig. 1
Hypertension prevalence in six World Health Organization regions. Where: AFR WHO African Region, AMR WHO Region of the Americas, EMR WHO Eastern Mediterranean Region, EUR WHO European Region, SEAR WHO South-East Asia Region, WPR WHO Western Pacific Region (World Health Organisation 2014). Where: % raised blood pressure (SBP 140+ and/or DBP 90+ or on meds), ages 25+, age standardized
However, more recent findings provide a far more disturbing picture. A prospectively followed teachers’ cohort from South Africa [173 black (aged 47.5 ± 7.8 years; 186 white (aged 49.6 ± 9.9 years)] showed that Blacks had a substantially higher 24 h hypertension prevalence (66 %) as opposed to Whites (42 %) (Hamer et al. 2015; Malan et al. 2016). Furthermore, the composite cardiovascular disease (CVD) burden in this Black cohort over 3 years (defined as history of physician diagnosed heart disease, use of anti-hypertensives, anti-diabetic, or statin medications at either time point) was higher compared to Whites (49.1 vs. 32.0 %, p = 0.012) (Hamer et al. 2015). In another South African cohort study including 1,994 Blacks older than 30 years, hypertension prevalence was 48 % (Schutte et al. 2012) whereas it ranged from 19 to 48 % in cohorts from Ghana (Bosu 2010).
The large variation in separate studies’ data raises concern about the real situation. One possibility may be the lack of hypothesis driven prospective findings on hypertension prevalence in SSA. Another more controversial matter is that hypertension research did not receive enough attention over the last decade, with funding bodies mostly supporting infectious disease research in SSA (Peck et al. 2013; Tagoe and Dake 2011; World Health Organisation 2014) Fortunately enough, at present the attention seems to be shifting and Nigeria, one of many developing countries, recently reported that NCD’s have become a growing problem (Peck et al. 2013; World Health Organisation 2014). At a Tanzanian hospital this was also the case since NCDs accounted for half of all deaths. Here, hypertension was the second most common cause of death overall and the leading cause of death in patients >50 years old (Peck et al. 2013). Due to overwhelming evidence of hypertension as a causative factor for deaths in SSA (World Health Organisation 2014), it is of the utmost importance, therefore, to progress with hypothesis driven research on hypertension prevalence and secondary outcomes in prospective cohort studies.
The examination as to whether emotional stress is a causative factor for hypertension or other NCDs has largely been understudied in SSA. Currently, the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study is the only prospective cohort study in SSA where the study design (central neural control) was based on findings from studies over the previous 20 years (Malan et al. 2015). Cross-sectional data revealed that coping disability, cognitive emotional distress and a lack of social support were factors involved in NCDs development and progression in teachers from an urban environment (Malan et al. 2008, 2012, 2015; Venter et al. 2014). In this cohort, sympathetic hyperactivity was associated with cardiometabolic risk, namely hypertension prevalence, sympathovagal imbalance and depressed heart rate variability, all which contribute to vulnerability for cardiovascular risk (Lambert et al. 1994; Malan et al. 2013; Pal et al. 2014; Van Lill et al. 2011). It was also shown that factors leading to sympathetic hyperactivity included a stressful life and coping with continuous and taxing emotional demands (McEwen and Gianaros 2010). As a consequence, cardiometabolic demands will increase so to induce continuous adjustments by the brain to control sensitivity levels of organ systems in maintaining homeostasis (Gross 1998).
2 Central Neural Control of BP
As early as 1878 Claude Bernard postulated that maintenance of a stable internal environment is a prerequisite for the development of a complex functional nervous system (Gross 1998). Metabolic balance is maintained as neurons store glycogen as endogenous neuronal glycogen, which protects neuronal tolerance to hypoxic stress (Saez et al. 2014). Therefore, the brain maintains homeostasis by adjusting the sensitivity of target organs to neural and metabolic inputs (Gross 1998; McDougall et al. 2015; Saez et al. 2014) For example, the regular and continuous contractions of a normally functioning heart muscle must be able to respond to the changing requirements of the body’s tissues.
It is also important to note that BP is centrally controlled, whereby no set-point for BP exists in the central nervous system (Nishida et al. 2012). If a set point existed, the BP control system would become a completely closed, self-contained system always causing BP to return to the set level independent of demands in organs and tissues. This implies that organs and tissues will not be protected even though the circulatory system itself may be. Therefore, neural BP regulation seems to be dynamic and acts as a phasic control in the circulatory system essential for maintaining life (Gross 1998; Nishida et al. 2012) When cardiometabolic demands increase, it is essential that the cardiovascular system, an open system, is able to respond with compensatory increases in BP to maintain homeostasis. Whether hypertension is the result of a compensatory elevation of BP to maintain organ function has been questioned (Mancia et al. 2013). Surely, fluctuations in BP are deemed physiologically necessary when cardiometabolic demands increase in an attempt to maintain homeostasis. Hypertension, however, represents a permanent shift in normal values, necessary for optimal organ function, but leading to end-organ damage. The “safety” or threshold levels for BP still needs in-depth investigations as hypertension prevalence is increasing despite medical interventions or treatment regimens to lower BP.
Despite these views, a neurophysiological approach showed that increased cardiometabolic demands in a hypertensive individual will be taxing to neuronal health because depletion or attenuated neurotransmitter secretion may induce neural and adrenal fatigue and/or depression (Cabib 1996; De Kock et al. 2012, 2015; Dobrunz and Stevens 1997). Long-term changes in a neuron or synapse will result in a permanent change in a neuron’s excitatory properties and can cause synaptic fatigue (Cabib 1996). This may occur from much more or less activation that could potentially lead to synaptic depression. Indeed, short-term depression as well as habituation have been located in the sensory part of the defence response pathway, as well as at the axon terminals of sensory afferents in the brain stem (caudal pontine reticular nucleus) (Kvetnansky et al. 2009). In support, higher metabolic demands revealed reduced cerebral respiratory quotient in depressed subjects (Lambert et al. 1994). Neural fatigue or depression may thus impair metabolism in subcortical areas which regulate emotions such as the dorsolateral prefrontal cortex and the amygdala (Barton et al. 2007; LeDoux 2012; Taylor et al. 2013). A threat to homeostasis is thus sensed where the response has a degree of specificity depending, among other things, on the particular challenge to homeostasis, the organism’s perception of the stressor and its ability to cope with it (LeDoux 2012). An important feature of successful coping with stress is that physiological systems are not only turned-on efficiently by a particular stressor but are also turned-off again after cessation of the stressor to conserve resources. However, coping with chronic stress, will have a turned-off reaction when cardiometabolic demands increase in hypertensive individuals as cognitive or memory performance was related to blunted parietal cerebral cortex blood flow responses (Jennings et al. 2005). Whereas turned-on reactions in hypertensives resulted in compensatory regional cerebral blood flow in the mesencephalon (or midbrain) which correlated with prefrontal cerebral blood flow (Jennings et al. 2005). Once again, a set-point for BP can be questioned.
In support of this notion, central neural control of subcortical areas regulating emotion, such as the dorsolateral prefrontal cortex and the amygdala, was associated with impaired metabolism and depression (Barton et al. 2007; LeDoux 2012; Taylor et al. 2013). Linking emotional distress to vascular dysregulation is therefore one way to investigate increased cardiometabolic challenges (Akinroye 2013; Kadirvelu et al. 2012; Lambert et al. 2000; Malan et al. 1992, 1996). Defensive coping responses included increased cardiometabolic challenges, depletion of neurotransmitters and disturbed hemodynamics in urban-dwelling Blacks from the North-West region of South Africa (De Kock et al. 2012, 2015; Malan et al. 2008, 2012, 2013, 2015, 2016; Scheepers et al. 2016).
Central neural control is thus actively involved with emotional stress upon activation of stress response pathways. These pathways include the sympatho-adrenal medullary (SAM) and hypothalamic-pituitary-adrenal cortical axis (HPAA), both facilitating inflammatory, glycolysis and adrenergic responses (Taylor et al. 2013). Indeed, sympathetic hyperactivity is present in about 30 % of depressed patients, independent of hypertensive status (Barton et al. 2007). Other findings support the notion of sympathetic hyperactivity and neural fatigue, as attenuated acute stress pathway responses (De Kock et al. 2012; Taylor et al. 2013) and chronic defensiveness were shown in a SSA Black cohort. (Malan et al. 2015) Indeed, in this cohort, chronic depression in conjunction with hypertension prevalence was more prevalent in Blacks than in Whites (28.67 % vs. 5.29 · %; P ≤ 0.001) (Malan et al. 2016). Therefore, chronic emotional distress seems to facilitate higher metabolic demands and may even further contribute to increased risk of stroke (Taylor et al. 2013). In agreement, Biccard (Biccard 2008) also showed that Blacks from SSA are more likely to be diagnosed with symptomatic occlusive vascular disease or vascular dysregulation indicating increased stroke risk.
Additionally, recent studies support the notion that the cardiovascular system is regulated by cortical modulation (Mazzeo et al. 2014; Nagai et al. 2010; Stahrenberg et al. 2013). Insular cortex damage is suggested to be associated with cardiovascular system dysregulation such as ECG, cardiac stress (Tropinin T) and sympathovagal disturbances (Mazzeo et al. 2014; Nagai et al. 2010; Stahrenberg et al. 2013). Increased sympathetic nervous system activity therefore may serve as a pathophysiological event affecting the relationship between the insular cortex and cardiovascular dysregulation (Nagai et al. 2010). The insular cortex, amygdala and anterior cingulate gyrus are involved in processing the information related to emotional significance, such as the defence response to external stressors. Therefore, the insular cortex is implicated in BP control in cooperation with subcortical autonomic centres.
3 Factors Burdening Central Neural Control of BP
Important background factors are to be considered as possible obstacles for BP control in SSA. Social supportive systems are not in place (Kadirvelu et al. 2012) and Mayosi et al. (2012) urged the launch of an integrated model of health care at all levels in South Africa, which has to be supported by a robust surveillance system. However, upstream determinants of ill health, such as a lack of resources, poverty and insufficient quality education, may lie beyond the reach of the health sector in Africa (Seedat 2015). Therefore, if social support systems are not in place, self-management of NCDs in SSA will remain poor.
Another factor which may seriously compromise mental well-being is the level of violence in South Africa. According to a non-governmental organisation, registered as a non-profit company with the aim of protecting the rights of minorities, 17,805 persons were murdered in South Africa in 1 year (2014–2015) (National Development Plan 2016). That is an average of 48.8 murders per day. The country’s homicide figure has subsequently increased with 4.6 % since 2013/2014. Attempted murder showed an increase of 3.2 %, while robbery with aggravating circumstances increased drastically by 8.5 %. These figures are an example of the high levels of aggression currently prevailing in South Africa and unfortunately are also spreading to the youth. The impact of this threat on emotional health is documented in WHO reports on mental well-being (Lund et al. 2011; Reed et al. 2012; World Health Organisation 2008, 2010). Threats to well-being or survival, actual or potential may increase a vicious cycle of fear, not feeling safe and anxiety (Reed et al. 2012). Subsequent autonomic, cardiovascular and neuroendocrine activation and specific behaviour patterns have been associated with a hypervigilant state in an attempt to cope with these adverse or unexpected situations (World Health Organisation 2010). Vulnerability and an elevated risk of psychological distress will thus enforce increases in poor lifestyle habits and NCDs in an attempt to cope with these situations.
3.1 Stress Appraisal – The Defence Response
In more than 400 studies, little consensus could be found about how to conceptualize or classify how people cope with or appraise stress situations (Skinner et al. 2003). Coping functions at a number of levels and involves a plethora of behaviours, cognitions, and perceptions. At the highest level are sets of basic adaptive processes which intervene between stress and its psychological, social, and physiological outcomes. Coping inventories of Carver et al. (1989) and Amirkhan (1990) primarily focussed on problem-solving (defence) vs. emotional avoidance (defeat), and social support seeking behaviours. The above described defence response in two separate bi–ethnic gender group studies, performed 10 years apart, was related to similar outcomes, i.e. disturbed cardiometabolic responses (Malan et al. 2006, 2012, 2014). Given the focus of our review, our approach will be from a neurophysiological angle, as sensory perception and a hypervigilant state burden central neural control, thereby overloading an individual’s resources, so to induce neural and adrenal fatigue (De Kock et al. 2012, 2015; Malan et al. 2008, 2012, 2013, 2015; Scheepers et al. 2015, 2016). This concurs (Fig. 2) with most recent neuroscience research findings (LeDoux 2012).
Fig. 2
Proposed sensory-motor integrative defensive responses involve sensory perception and a state of consciousness of environmental changes (internal and external) in the thalamus. Memory processing or thoughts are implicated in the process. Downstream signalling in the insula region will activate emotional responses in the amygdala whereas the importance of the stimuli as a threat or a challenge is weighted in the hippocampus. The nucleus accumbens will regulate motivation for recognition of stimuli in the prefrontal cortex. The paraventricular nucleus in the hypothalamus will respond and activate the autonomic nervous system motor output pathway; considering the integrated emotional response in the ventral tegmentum area. Output signals will be conducted via the brain stem to the heart (Permission to use diagram granted by the artists: A de Kock and AJG du Plessis, April, 2016)
A defensive state is triggered by activity in survival circuits that detect threats and generate automatic defence and a general arousal state due to widespread release of aminergic neuromodulators (Moscarello and LeDoux 2013). Memory processing or thoughts are implicated in this process with emotions resulting from the cognitive processing of actual situations. Coping has been defined as “cognitive and behavioural efforts to manage specific external or internal demands (and conflicts between them) that are appraised as taxing to the resources of a person” (Amirkhan 1990). Coping resources can be divided into internal psychological resources (e.g. personality characteristics) and external environmental resources (e.g. social support). Coping also has behavioural facets (activities to deal with stress) as well as physiological implications (neuro-endocrine activity and cardiovascular reactivity) (Moscarello and LeDoux 2013).
Chronic stress experience, such as the psychosocial stress of an urban-dwelling lifestyle, and ultimately acculturation (Malan et al. 1992, 1996) may however exacerbate cardiovascular reactivity to acute stressors (Malan et al. 2006, 2012, 2013), and predispose to hypertension (Malan et al. 2006, 2012). When coping is successful, the vagal system is typically activated to decrease secretion of stress mediators and to normalise autonomic activity, whilst α2-adrenergic receptor binding activates a negative feedback loop to decrease norepinephrine levels (Huang et al. 2012). However, chronic stress, sleep deprivation or apnoea, sedentary lifestyles, stimulant abuse, abdominal obesity, insulin resistance, hypertension, and depression, can all cause chronic sympathetic hyperactivity with disruption of autonomic homeostasis (Curtis and O’Keefe 2002; Malan et al. 2013). Overwhelming or sustained stress may therefore interfere with coping ability, causing distress and hyperactivity of the SAM system, as the body tries to cope with increasing demands. As such neither the vagal system nor the negative feedback mechanism of the α2-adrenergic receptors will be able to reduce the amounts of norepinephrine released (Curtis et al. 2002; Huang et al. 2012; Malan et al. 2012). Concentrations will increase even further and may culminate in norepinephrine overload, enforcing a hypervigilant defensive coping state. Indeed, findings have revealed that prolonged SAM activation and/or norepinephrine overload can further increase vasoconstriction, alter cardiovascular stress responses, and facilitate hypertension, endothelial dysfunction as well as atherosclerosis risk (De Kock et al. 2012, 2015; Malan et al. 2008, 2012, 2013, 2015, 2016; Scheepers et al. 2016).
Cross-cultural differences in coping have been related to perspectives on the Self in a western context. The Self is the basis of what the individual thinks, feels and does and reflects the relative importance of the individual-self versus social-self (Chang 1996) The Self-construct, as social construct, is a cultural construct that shows cross-cultural variance. In collectivistic groups, the Self is defined as part of the inner group. Independency in collectivistic groups (in the Black African culture) means that the individual does not want to be a burden to his/her inner group (Van der Wateren 1997). Independency in individualistic cultures (in the White Western culture) indicates a need in the individual to act his/her own way (Triandis et al. 1990). In an urban environment, Black individuals may find it difficult to maintain their traditional way of life and in order to survive, may feel the need to abandon their traditional beliefs. The social support they experienced in a traditional setting will disappear (Malan et al. 1992, 1996, 2008; Vorster et al. 2005). Thus Whites might be able to find solutions for their own problems whereas Blacks depending on support and approval from their inner group might be more Indeed, they sought more social support, as coping strategy, to adapt in an urban environment (Malan et al. 2008, 2013, 2015).
In the African Black, it could imply that if defence coping on a long-term basis becomes untenable because the situation is judged as “no way out”, a shift towards defeat, neural fatigue or depression is a conceivable outcome (De Kock et al. 2012, 2015; Malan et al. 2006, 2008). This implies a physiological neural fatigue or reaction with enhanced sympathetic activity, especially vascular reactivity (Malan et al. 2006, 2012, 2013). On behavioural level, the urban Black individuals still reported a defence coping reaction style, but with a physiological reaction resembling emotional distress or neural fatigue (De Kock et al. 2012). The “normal” physiological reaction pattern changes where defence coping (in-control) is dissociated from the normal physiological reaction and is exhibited as a physiological neural fatigue or loss-of-control reaction. This pattern could indicate a physiological adaptation process where African Blacks with an inherent collectivistic cultural context are living in an individualistic cultural environment and, if anticipated support is not forthcoming, stress will be exacerbated (Ryff and Singer 2002). Adaptive learned behaviours of defensive coping Africans might therefore reflect life choices of smoking and alcohol consumption, which appears to be ineffective in handling normal challenges of daily life (Malan et al. 2014). Their enhanced vascular reactivity due to alpha-adrenergic stimulation and / or beta-adrenergic hyporesponsiveness (Malan et al. 2012, 2013) will have permissive effects on cortisol (De Kock et al. 2012, 2015), and may further impact on depression or distress via the HPAA (Björntorp 2001; Folkow 2000). Therefore, it appears that coping styles, as possible risk factors for cardiometabolic disturbance, may be contributing to the development of hypertension in an urban-dwelling environment.
Unpublished data in defensive coping African Black vs. Whites reinforce the notion of disruption in central neural control of BP. Defence coping increases activation of HPAA pathways during exposure to an acute mental stressor (Stroop 1935), similar to everyday life stress (Kidd et al. 2014). Responses to an acute mental stressor indicative of emotional distress are presented in Fig. 3. Vasoconstrictive responses (DBP) and lower cortisol responses are accompanied by increased insular region activation, high sensitive Troponin T release and 24 h silent ischemic events. Central neural control activation occurs via acutely increased metabolic changes, i.e. glucose responses which support the defence response. The pattern is maladaptive in urban-dwelling Blacks and emotional distress seems to disrupt homeostatic control. Hence, SAM activation will induce a depression in heart rate variability (HRV) to maintain central neural control.
Fig. 3
Adjusted central control (BP-glucose) and coronary artery risk markers including changes (Δ) during exposure to a 1 min mental stressor test in an ethnic cohort utilising defence coping, independent of concomitant confounders. *, P ≤ 0.05
3.2 Emotional Stress and an Urban-Dwelling Lifestyle
As early as 1929, Donnison (1929) screened approximately 1,000 male Kenyans, aged 15–80 years, living in primitive conditions in a native reserve. He showed that BP was similar or slightly lower in aged compared to younger Kenyans. Sobngwi et al. (2004) supported these findings, showing that lifetime exposure to urbanization was associated with increases in obesity, BP, and diabetes but not with age. Similarly Danaei et al. (2011) reported increases in systolic blood pressure (SBP) in 5.4 million participants from low to middle income countries when moving from a traditional rural area to an urbanized area. In Ghana West Africa, the odds ratios for being hypertensive were 1.9 (1.3–2.9; P < 0.01) for urban men and 1.9 (1.3–2.8; P < 0.0001) for urban women, independent of age (Agyemang 2006).
Since 1989, transition from an rural to an urban-dwelling environment in approximately 4,000 Black Africans from the Venda, Botswana and the North-West regions in South Africa, was related to cultural disruption, increases in emotional distress, hypertension prevalence (Malan L, et al. 2006, 2008, 2012; Malan NT, et al. 1992, 1996; Vorster et al. 2005) as well as vascular changes such as angiogenesis (Venter et al. 2014). Apart from cultural disruption, other aggravating factors, like crime, come into play emphasizing why an urban-dwelling lifestyle has been recognized as a potent psychosocial stressor for CVD risk (Björntorp 2001; Malan et al. 2006). Official crime statistics of 2016 in SSA recorded that in only one of the urban-dwelling areas in SSA about 78 % car hijackings, 74 % of car thefts, and 57 % of house robberies occurred compared to other urban-dwelling areas (South African Cities Urban Safety Reference Group (USRG) 2016). In agreement, BeLue et al., showed increased CVD risk in urban environments (BeLue et al. 2009).
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