Although twin studies have been valuable in exploring the relation between the genetic contribution to both cardiovascular reactivity to stress and essential hypertension, they are difficult to conduct due to the limited number of twins in the population and limited access to sets of twin data. Based upon the knowledge that hypertension aggregates in families (Paffenbarger, Thorne, and Wing, 1968; Stamler et al., 1971), a considerable amount of research has examined the genetic foundation of cardiovascular response to stress by comparing persons of different hypertensive parentage (for a review, see Fredrikson and Matthews, 1990). In most of these studies, categorization of young normotensive participants into those with or without a family history of hypertension is conducted through brief interviews of participants' biological parents regarding their hypertensive status, although a few studies have extended this definition to include parents with coronary heart disease and others have included information regarding hypertensive status of grandparents. In a meta-analytic review of 30 studies comparing cardiovascular reactions to stress between young adults with and without hypertensive parents, Fredrikson and Matthews (1990) found that offspring of hypertensive patients exhibited significantly greater heart rate and SBP reactions to all types of mental stressors as well as a significantly greater DBP response to active mental tasks (mental arithmetic, interpersonal encounter) than persons with nor-motensive parentage. Elevated blood pressure reactions to stress have also been reported among offspring of hypertensive monkeys in comparison to offspring of normotensive monkeys (Kirby et al., 1984). These findings are significant in that these exaggerated cardiovascular reactions are observed in these high-risk persons (and monkeys) before onset of essential hypertension, indicating that the commonly observed hyper-reactivity among borderline and sustained hypertensive patients is likely not a consequence of chronically elevated arterial pressures.
Nervous System Influences and Parental History of Hypertension Starting from the conclusions of works cited by Fredrikson and Matthews (1990), several investigators began to explore the physiological foundation for the commonly observed differences in cardiovascular response to stress between young adults with and without a parental history of hypertension. Foremost among these investigations were those that tested the hypothesis that these exaggerated cardiovascular reactions emanated from enhanced sympathetic nervous system activation (Anderson et al., 1987; Ditto and Miller, 1989; Manuck et al.,
1996; Miller and Ditto, 1991; Perini et al., 1990). Miller and Ditto (1991) reported significantly greater heart rate, blood volume pulse (reflecting increased vascular resistance via alpha-adrenergic activity), and forearm blood flow responses (reflecting decreased vascular resistance via beta-adrenergic activity) among offspring of hypertensives in comparison to offspring of normotensives, indicating that the enhanced cardiovascular response to mental stress involved both beta-adrenergic and alpha-adrenergic activation. Administration of selective beta-blocking and alpha-blocking agents resulted in attenuations of response parameters in the expected directions (beta-blockade eliminated the heart rate and forearm vascular resistance differences between groups), lending further support to the role of both beta-adrenergic and alpha-adrenergic activity in explaining the cardiovascular response differences observed among persons differing in hypertensive parentage. Other research has confirmed that disrupted vascular resistance may underlie the exaggerated cardiovascular responses that are commonly observed in this literature (Anderson et al., 1987; Ditto and Miller, 1989).
Studies comparing neuroendocrine responses to stress between offspring of hypertensive and normotensive parents also provide information regarding the role of the sympathetic nervous system in driving the observed cardiovascular response differences. In particular, if group differences in measures of epinephrine, norepinephrine, or cortisol were evident, greater sympathetic involvement could be presumed. Although increased levels of resting plasma norepinephrine (Horikoshi et al., 1985) and norepinephrine response to exercise were reported among individuals with hypertensive parents (Nielsen, Gram, and Pedersen, 1989), no differences in epinephrine between offspring of hypertensive and normotensive parents were reported. Other studies, however, have failed to find any differences in either norepi-nephrine or epinephrine levels or responses to mental and physical stressors among groups of offspring of hypertensive and normotensive persons (Manuck et al., 1996; Perini et al., 1990). Although less attention has been paid to cortisol response to stress than catecholamine response to stress, al'Absi and Wittmers (2003) reported an association between cortisol reactivity and cardiovascular reactivity among men and women at risk for hypertension in contrast to low-risk counter parts. Because the high-risk group in this study was defined on the basis of high resting SBPs and a parental history of hypertension, they reflected perhaps a subgroup of individuals at even greater risk for developing hypertension than those individuals who have hypertensive parents but relatively normal blood pressures. Therefore, it is unknown whether the increased cortisol response to stress observed in this study is unique to this subgroup of high risk participants.
Although activation of the sympathetic nervous system has been hypothesized to be at the root of the observed differences in cardiovascular response to stress among offspring of hypertensive and nor-motensive parents, it is also possible that the parasympathetic nervous system may be involved. To test this hypothesis, Miller (1994) measured cardiovascular responses to a variety of mental stressors among a group of persons with and without hypertensive parents. Congruent with previous work, they found elevated heart rate responses among participants with a hypertensive parent in contrast to those with nor-motensive parents. Parasympathetic involvement, as determined by measures of respiratory sinus arrhythmia, however, were not different between groups, suggesting that the observed difference in the magnitude of heart rate reactions was due to sympathetic, not parasympa-thetic, influences.
Despite the initial promise of this line of inquiry, several well-designed studies have failed to find any significant differences in cardiovascular reactivity to stress between young adults with and without hypertensive parents (Manuck et al., 1996; Perini et al., 1990; Ravogli et al., 1990). In response to the discrepant findings among studies examining the relation between cardiovascular response to stress and parental history of hypertension, Muldoon et al. (1993) conducted a comprehensive review of the entire literature exploring family history of hypertension, including studies that examined differences in intra-cellular sodium transport, renal functioning, cardiovascular morphology, and cardiovascular reactivity to stress. Among all of the physiological parameters considered, they found solid evidence for only two conclusions. First, persons with hypertensive parents tended to show enhanced left ventricular thickness and mass earlier than persons without hypertensive parents. And second, offspring of hypertensives exhibited abnormalities of the peripheral vasculature, as evidenced by in creased forearm blood flow responses to mental stress or the cold pressor task. According to these authors, evidence for the remaining variables, including direct comparisons of heart rate and blood pressure response to mental stress between persons with and without hypertensive parents, was insufficient for making definitive conclusions.
Parental History of Hypertension and Individual Difference Variables One reason that consistent observations of exaggerated cardiovascular responses to stress among offspring of hypertensive patients have not been made may be that the relation between these two variables is influenced by other individual difference variables. For example, as mentioned in Chapter 5, Light et al. (1999) found that the interaction between family history of hypertension and acute cardiovascular response to stress in predicting casual blood pressures prospectively was influenced by occurrence of high daily stress. In other words, the elevated cardiovascular reactions among persons of hypertensive parentage predicted onset of essential hypertension only among persons reporting regular exposure to high life stress. Presumably, persons who lead relatively stress-free lives may not develop chronically heightened blood pressures even if they have a positive family history of hypertension.
Several psychological individual difference parameters have also been shown to interact with parental history of hypertension in affecting the magnitude of behaviorally elicited cardiovascular reactivity. For example, research has shown that relations between parental history of hypertension and cardiovascular response to stress were observed among participants who inhibit anger expression, but not those who express anger openly (Holroyd and Gorkin, 1983; Vogele and Steptoe, 1993), among participants reporting heightened anxiety (Manuck et al., 1985; Miller, 1992), among individuals high on measures of de-fensiveness (Shapiro, Goldstein, and Jamner, 1995), and among persons who deny the experience and expression of emotion, particularly in association with a high need for social approval (Jorgensen, Gelling, and Kliner, 1992; Jorgensen and Houston, 1986; 1988). Several of these psychological characteristics (anger inhibition, defensiveness, anxiety) have also been shown to be related to increased ambulatory blood pressures during workdays among working women with hyper tensive parents (Goldstein and Shapiro, 2000). In this study, associations between these psychological characteristics and ambulatory blood pressures were not observed for offspring of normotensives or offspring with only one hypertensive parent. Although there has not been a substantial amount of empirical work in this area, studies that exist provide obvious hints that certain individual difference variables are worthy of further exploration with regard to their association with cardiovascular response to stress. Perhaps additional exploration of selected individual difference variables will result in a better understanding of the sources of inconsistent observations between parental history of hypertension and acute cardiovascular responses to stress that are prevalent in the literature.
Parental History of Hypertension and Behavioral Responses to Stress The relation between parental history of hypertension and acute cardiovascular reactivity is further complicated by observations that individuals with hypertensive parents have also been shown to exhibit behavioral response differences from offspring of normotensive parents (Baer et al., 1980; Frazer, Larkin, and Goodie, 2002; Semenchuk and Larkin, 1993). In addition to observing the clear behavioral differences during family interactions between hypertensive and normotensive fathers described in Chapter 5, Baer et al. (1980) also analyzed behavioral data of the children during these interactions. Thus this study provided a unique opportunity to evaluate behavioral responses of both hypertensive patients and their offspring within a single experimental session. Congruent with behavioral deficits of the hypertensive father, children of hypertensive fathers exhibited greater negative nonverbal (gaze aversion) and lesser positive verbal behaviors (agreements) than children of normotensive fathers. These findings suggest that hypertensive fathers may model a distinct behavioral style of coping with confrontation that is learned and practiced by their children.
Using multiple measures of behavioral and cardiovascular responses to social confrontation with a confederate, Semenchuk and Larkin (1993) reported that male offspring of hypertensives exhibited both increased SBP responses and less adaptive behavioral responses to the interpersonal challenges in comparison to sons of normotensives. Analysis of the specific behavioral rating categories showed that per sons with hypertensive parents paid less attention to the confederate's responses, used humor less, grimaced more, and used more disagreeing statements than persons of normotensive parentage. Frazer, Larkin, and Goodie (2002) replicated these findings using a sample of both young men and women with and without parental histories of hypertension. Similar behavioral differences were observed across interpersonal and non-interpersonal laboratory tasks; that is, offspring of hypertensives showed more disagreeing statements, put-downs, eye rolling, and sighing than offspring of normotensives. Correlational analyses from both of these studies revealed no correspondence between cardiovascular and behavioral response differences even though both were observed when contrasting persons with and without hypertensive parents. This suggests that offspring of hypertensive patients with the greatest SBP responses are not necessarily the same participants exhibiting the less adaptive social behaviors. In this regard, two orthogonal response differences exist among young adults with hypertensive parents, one involving elevated cardiovascular reactions and the other involving the display of less socially competent behaviors during confrontation and stress provocation.
Parental History of Hypertension and Neuropsychological Performance As described in Chapter 1, significant differences in performance on an array of neuropsychological tests have been observed between essential hypertensive and normotensive patients (see Waldstein et al., 1991). For the most part, based upon evidence that these differences in information processing disappeared following successful blood pressure regulation using anti-hypertensive treatment (Miller et al., 1984), it had been thought that the observed differences in information-processing speed and abstract reasoning that existed between hypertensive and normotensive patients represented a consequence of high blood pressure rather than a factor involved in its etiology. Despite this assumption, a few investigators have attempted to examine whether these neuropsychological deficits were apparent among individuals with hypertensive parents (McCann et al., 1990; Pierce and Elias, 1993; Thyrum et al., 1995; Waldstein et al., 1994). Although McCann et al. (1990) reported no differences on performance on a variety of neu-ropsychological tests between persons with and without hypertensive parents, the other three studies reported poorer performance among persons with hypertensive parents on tests of attention and memory (Pierce and Elias, 1993; Thyrum et al., 1995) as well as tests of visual perceptual and spatial skill and reaction time (Waldstein et al., 1994). Because the nature of the information-processing differences between persons with and without hypertensive parents was similar to deficits reported in comparisons of neuropsychological test performance between hypertensive and normotensive patients, these data suggested that perhaps these subtle deficits in information processing preceded onset of essential hypertension. Hypothetically, if these information-processing differences between persons differing in hypertensive parentage serve as a marker for underlying acute alterations in diminished cerebral blood flow during task performance, it might explain how these differences are apparent prior to the onset of essential hypertension. Alternatively, if young adults at risk for hypertension were aware of their deficits in information processing, they might find performance of cognitive stressors often used in studies of cardiovascular reactivity to stress among offspring of hypertensives more stressful than offspring of normotensives with relatively superior information-processing skills. However, these thoughts represent speculation at this point, as studies of cerebral blood flow during neuropsychological task performance among persons with and without hypertensive parents have yet to be conducted.
Parental History of Hypertension and Perception of Pain As described in Chapter 5, essential hypertension is associated with an increased tolerance of pain and decreased perception of pain (see France, 1999). As with research on cardiovascular reactivity to stress, behavioral responses to stress, and deficits in neuropsychological task performance, France and colleagues have extended this body of literature by examining perception of pain among individuals with a familial history of hypertension (Ditto, France, and France, 1997; France et al., 1994; France, Froese, and Stewart, 2002; France and Suchowiecki, 2001). Although various pain manipulations have been used in these studies, each reports significantly lower perception of pain accompanied by a higher tolerance of pain among individuals with a parental history of hypertension. These findings suggest that whatever the physiological mechanism is that is responsible for the reduced perception of pain among essential hypertensive patients (for example, baroreceptor activation), it is also present among offspring of hypertensives.
Some studies comparing young adults with and without a parental history of hypertension have revealed that the same exaggerated cardiovascular reactivity to stress that has been shown to distinguish hypertensive and normotensive patients is also observed among their offspring. Congruent with the literature on hypertensive patients, the observed differences in cardiovascular reactivity to stress between persons with and without hypertensive parents appears to be influenced by additional individual difference variables like exposure to daily stress, mode of anger expression, or degree of the need for social approval. Additionally, because persons with hypertensive parents have been shown to exhibit different behavioral responses during social confrontation, neuropsychological task performance, and sensitivity to pain than persons with normotensive parents, it is unclear to what extent each of these attributes contributes to the magnitude of their cardiovascular reactions to stress as well as their future risk for essential hypertension. From these observations, it is apparent that parental history of hypertension represents an important individual difference variable in explaining the relation between exposure to environmental stress and incidence of essential hypertension. However, the relation of this variable with hypertension is quite complex, involving interactions with acute behavioral and cognitive responses in addition to the hypothesized acute physiological response to stress.
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