Baroreceptor activation reduces reactivity to noxious stimulation: implications for hypertension.

The hypothesis was tested that an acute rise of blood pressure may reduce reactivity to noxious stimuli through a baroreceptor-mediated reduction of cerebral arousal. When blood pressure was raised by an infusion of phenylephrine, rats showed less running to terminate or avoid noxious stimuli than during saline infusions. This effect was not seen in rats with denervated baroreceptors. The results suggest that a rise of blood pressure could have motivational consequences significant for human hypertension.

Association of carotid atherosclerosis and left ventricular hypertrophy.

OBJECTIVES: This study was undertaken to determine the prevalence of carotid atherosclerosis in a large group of asymptomatic hypertensive and normotensive adults and to examine its relation to the presence of left ventricular hypertrophy. BACKGROUND: Both electrocardiographic and echocardiographic left ventricular hypertrophy predict an increased risk of cardiovascular events and mortality, including cerebrovascular disease, but the mechanism of association is unknown. METHODS: Four hundred eighty-six (277 normotensive and 209 untreated hypertensive) adults, free of clinical evidence of cardiovascular disease, were studied prospectively with echocardiography to determine left ventricular mass and carotid ultrasound to detect atherosclerosis and to measure common carotid artery dimensions. RESULTS: Carotid atherosclerosis was present in 16% of normotensive and 23% of hypertensive participants (p < 0.05) and was associated with older age, higher systolic and pulse pressures and larger left ventricular mass index ([mean +/- SD] 91 +/- 19 vs. 82 +/- 18 g/m2, p < 0.0001). The difference in mass persisted after adjustment for baseline differences in age and blood pressure. Subjects with left ventricular hypertrophy were twice as likely to have carotid atheromas (35% vs. 18%, p < 0.01). Logistic regression analyses, including standard risk factors, indicated that only age and left ventricular mass index independently predicted the presence of carotid plaque, both in the entire study group and when normotensive and hypertensive subjects were considered separately. CONCLUSIONS: We believe that the present study provides the first evidence that higher left ventricular mass as detected by echocardiography is associated with the presence of carotid plaque. The association between cardiac hypertrophy and systemic atherosclerosis may contribute to the pathogenesis of the high incidence of vascular events that is well documented in patients with left ventricular hypertrophy.

Relation of arterial structure and function to left ventricular geometric patterns in hypertensive adults.

OBJECTIVES: The present study sought to determine whether conduit artery structure and function vary according to the pattern of left ventricular adaptation to hypertension. BACKGROUND: Although left ventricular geometric pattern has been shown to predict cardiovascular events in hypertension, the arterial status in patients with the different patterns is unknown. METHODS: We evaluated arterial structure and function by carotid ultrasound and applanation tonometry in 271 unmedicated hypertensive patients classified by echocardiography as having normal ventricular geometry (n = 176), concentric remodeling (n = 54), concentric hypertrophy (n = 16) or eccentric hypertrophy (n = 25). RESULTS: All groups were similar in age, gender distribution and body size. Patients with concentric and eccentric hypertrophy had similar blood pressures (mean 173/100 and 171/99 mm Hg, respectively) and left ventricular mass, but compared with patients with normal left ventricular geometry and concentric remodeling, only those with concentric hypertrophy had increased arterial wall thickness (0.96 +/- 0.20 vs. 0.80 +/- 0.18 mm, p < 0.05), end-diastolic diameter (6.38 +/- 0.97 vs. 5.76 +/- 0.87 mm, p < 0.05), cross-sectional area (22.1 +/- 5.71 vs. 16.6 +/- 5.4 mm(1)2 p < 0.05) and elastic modulus (713 +/- 265 vs. 471 +/- 241 dynes/cm2 x 10(-5), p < 0.05). Patients with concentric remodeling and eccentric hypertrophy had similar values for these measures (0.85 +/- 0.22 and 0.89 +/- 0.21 mm, 5.67 +/- 0.77 and 6.04 +/- 0.44 mm, 17.2 +/- 5.4 and 19.7 +/- 5.9 mm2, 558 +/- 263 and 614 +/- 257 dynes/cm2 x 10(-6), respectively), despite lower systolic blood pressures in the former group (156/94 mm Hg, p < 0.001). The prevalence of plaque was comparable in patients with concentric (56%) and eccentric (42%) hypertrophy and significantly greater than that in patients [corrected] with normal geometry (21%). CONCLUSIONS: Among patients with generally mild, uncomplicated systemic hypertension, arterial structure and function are most abnormal when concentric left ventricular hypertrophy is present and may contribute to the more adverse outcome associated with this geometric pattern.

Silent and clinically overt stroke in older Japanese subjects with white-coat and sustained hypertension.

OBJECTIVES: We investigated whether white-coat hypertension is a risk factor for stroke in relation to silent cerebral infarct (SCI) in an older Japanese population. BACKGROUND: It remains uncertain whether white-coat hypertension in older subjects is a benign condition or is associated with an increased risk of stroke. METHODS: We studied the prognosis for stroke in 958 older Japanese subjects (147 normotensives [NT], 236 white-coat hypertensives [WCHT] and 575 sustained hypertensives [SHT]) in whom ambulatory blood pressure monitoring was performed in the absence of antihypertensive treatment. In 585 subjects (61%), we also assessed SCI using brain magnetic resonance imaging. RESULTS: Silent cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154), and 53% of SHT (n = 361); multiple SCIs (the presence of > or =2 SCIs) were found in 24% of NT, 25% of WCHT and 39% of SHT. During a mean 42-month follow-up period, clinically overt strokes occurred in 62 subjects (NT: three [2.0%]; WCHT: five [2.1%]; SHT: 54 [9.4%]), with 14 fatal cases (NT: one [0.7%]; WCHT: 0 [0%]; SHT: 13 [2.3%]). A Cox regression analysis showed that age (p = 0.0001) and SHT (relative risk, [RR] [95% confidence interval, CI]: 4.3 [1.3-14.2], p = 0.018) were independent stroke predictors, whereas WCHT was not significant. When we added presence/absence of SCI at baseline into this model, the RR (95% CI) for SCI was 4.6 (2.0-10.5) (p = 0.003) and that of SHT was 5.5 (1.8-18.9) versus WCHT (p = 0.004) and 3.8 (0.88-16.7) versus NT (p = 0.07). CONCLUSIONS: In older subjects the incidence of stroke in WCHT is similar to that of NT and one-fourth the risk in SHT. Although SCI is a strong predictor of stroke, the difference in stroke prognosis between SHT and WCHT was independent of SCI. It is clinically important to distinguish WCHT from SHT even after assessment of target organ damage in the elderly.

Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension.

The spectrum of left ventricular geometric adaptation to hypertension was investigated in 165 patients with untreated essential hypertension and 125 age- and gender-matched normal adults studied by two-dimensional and M-mode echocardiography. Among hypertensive patients, left ventricular mass index and relative wall thickness were normal in 52%, whereas 13% had increased relative wall thickness with normal ventricular mass ("concentric remodeling"), 27% had increased mass with normal relative wall thickness (eccentric hypertrophy) and only 8% had "typical" hypertensive concentric hypertrophy (increase in both variables). Systemic hemodynamics paralleled ventricular geometry, with the highest peripheral resistance in the groups with concentric remodeling and hypertrophy, whereas cardiac index was super-normal in those with eccentric hypertrophy and low normal in patients with concentric remodeling. The left ventricular short-axis/long-axis ratio was positively related to stroke volume (r = 0.45, p less than 0.001), with cavity shape most elliptic in patients with concentric remodeling and most spheric in those with eccentric hypertrophy. Normality of left ventricular mass in concentric remodeling appeared to reflect offsetting by volume "underload" of the effects of pressure overload, whereas eccentric hypertrophy was associated with concomitant pressure and volume overload. Thus, arterial hypertension is associated with a spectrum of cardiac geometric adaptation matched to systemic hemodynamics and ventricular load. Concentric left ventricular remodeling and eccentric hypertrophy are more common than the typical pattern of concentric hypertrophy in untreated hypertensive patients.

Relation of hemodynamic volume load to arterial and cardiac size.

OBJECTIVES: This study sought to assess the relation of Doppler stroke volume (SV) to cardiac and carotid artery size and to determine whether volume load accounts for the parallelism between the two. BACKGROUND: It has been suggested that altered hemodynamic volume load can modify the degree and pattern of left ventricular (LV) hypertrophy from that predicted from blood pressure (BP) alone. METHODS: We related Doppler echocardiographic SV in 342 normotensive or unmedicated asymptomatic hypertensive adults to echocardiographic LV mass, LV internal dimension (LVID), wall thickness, carotid ultrasound arterial lumen diameter, intimal-medial thickness (IMT) and cross-sectional area (CSA). RESULTS: SV was positively related to LV mass (r = 0.42), LVID (r = 0.45), ventricular wall thickness (r = 0.20 to 0.29) and carotid diameter (r = 0.23, all p < 0.0001); CSA (r = 0.17, p < 0.002); and IMT (r = 0.12, p = 0.03). In multivariate analyses controlling for awake ambulatory BP and the circumferential end-systolic stress/end-systolic volume index ratio, SV remained an independent predictor of LV mass and chamber size (both p < 0.0001) but not LV wall thickness. SV also predicted carotid diameter (p < 0.0002), CSA (p = 0.001) and, to a lesser degree, IMT (p = 0.02) after controlling for mean awake BP and age. In additional analyses, LV and carotid dimensions were significantly interrelated independent of SV. CONCLUSIONS: SV measured by invasively validated Doppler echocardiography is associated with LV and carotid artery enlargement and eccentric hypertrophy, independent of arterial pressure, LV contractility, age and body size; however, SV and other variables do not account for the previously documented parallelism between cardiac and arterial structure.

Relation of blood pressure variability to carotid atherosclerosis and carotid artery and left ventricular hypertrophy.

The relationship of blood pressure (BP) variability to cardiovascular target-organ damage is controversial. Studies examining BP variability and left ventricular (LV) hypertrophy have been contradictory, and only limited data on the relation of BP variability to carotid atherosclerosis and carotid artery hypertrophy exist. BP variability was assessed as the standard deviation and coefficient of variation of awake and asleep pressures in 511 normotensive or untreated hypertensive subjects who underwent ambulatory BP monitoring and cardiac and carotid ultrasonography. Although the presence of focal carotid plaque was associated with an increase in ambulatory pressures and pressure variability, the differences in variability were eliminated by adjustment for age and absolute pressures. Similarly, LV mass was significantly related to BP variability, but the significance of this finding was eliminated after adjustment for important covariates. In multivariate analyses, age was the primary determinant of carotid artery cross-sectional area, with a weak but independent contribution from awake systolic and diastolic BP variability in addition to absolute pressure. BP variability was not independently related to either carotid or LV relative wall thickness, both measures of concentric remodeling. In the present study, awake BP variability was weakly but independently associated with carotid artery cross-sectional area, a measure of arterial hypertrophy. However, neither systolic nor diastolic BP variability was independently associated with carotid atherosclerotic plaque or LV mass.

Home blood pressure monitoring.

Hypertension is estimated to affect 43 to 56 million adults or 24% to 31% of the US population and is emerging as a major health problem in some countries in the Third World. Hypertension contributes to all the major atherosclerotic cardiovascular disease outcomes.

Blood pressure monitoring outside the office for the evaluation of patients with resistant hypertension.

Although severe hypertension is associated with a poor prognosis, there exists a substantial number of patients who have persistently elevated blood pressures, but no signs of target organ damage, and nearly normal life expectancy. In such cases, measurement of blood pressure outside the clinic may give readings that are as much as 30 mm Hg lower than the clinic readings. The first step recommended in the identification of such patients is to use home blood pressure monitoring. If home blood pressures are low, 24-hour ambulatory blood pressure recording is indicated. If this also gives low readings, it is appropriate to treat patients according to their level of home blood pressure. Because of the unreliability of clinic pressures, ambulatory and home blood pressure monitoring may also be of value in assessing the response to treatment.

Ambulatory physical activity as a determinant of diurnal blood pressure variation.

There are reports that indicate that diurnal blood pressure (BP) variation, in addition to high BP per se, is related to target organ damage and the incidence of cardiovascular events. However, the determinants of diurnal BP variation are not adequately understood. We used actigraphy and ambulatory BP monitoring to study the diurnal variation of BP and physical activity in 160 adults. Within individuals, activity was more strongly related to pulse rate than to BP. The correlation between BP and activity was stronger during sleep than when awake, but the correlation between activity and pulse rate was higher during the awake period than during sleep. Between individuals, the sleep/awake ratio of systolic BP (SBP) was correlated with mean sleep activity (r=.17, P<0.05), mean awake activity (r=-0.16, P<0.05), and, especially, the ratio of sleep/awake activity (r=.24, P<0.01). Awake BP variability (SD of awake SBP) was positively correlated with awake activity (r=.16, P<0. 05). In regard to the effect of position, the standing-supine SBP difference was negatively correlated with the sleep/awake SBP ratio (r=-0.39, P<0.01) and positively correlated with awake SBP variability (r=.33, P<0.01). When we divided the subjects into 3 groups, 19 extreme dippers (with a sleep SBP decrease of >/=20% of awake SBP), 102 dippers (with decreases of >/=10% to <20%), and 39 nondippers (with decreases of <10%), no significant differences existed in awake activity among the groups. However, the nondippers exhibited greater sleep activity than extreme dippers (P<0.05) and an increased sleep/awake activity ratio compared with extreme dippers and dippers (P<0.01). Extreme dipping may also be associated with increased BP variability (P=0.08). Individual SBP responses to activity (the within-person slope of awake SBP regressed on activity) did not differ significantly among the 3 subgroups. In conclusion, physical activity is one of the determinants of ambulatory BP and its diurnal variation. We hypothesize that the association of sleep activity to sleep BP and dipping reflects differences in sleep quality.

Cortisol inactivation overload: a mechanism of mineralocorticoid hypertension in the ectopic adrenocorticotropin syndrome.

The more severe mineralocorticoid manifestations in the ectopic ACTH syndrome compared to pituitary Cushing's disease have been attributed to hypersecretion of 11-deoxycorticosterone. Another difference between the two forms of ACTH-excess, however, is a more severe degree of hypercortisolism in the ectopic syndrome. Cortisol can become a potent mineralocorticoid if its peripheral metabolism is interfered with as occurs in the syndrome of apparent mineralocorticoid excess. This mechanism also occurs in an experimental model of the apparent mineralocorticoid excess syndrome induced by licorice derivatives. We have tested the hypothesis that cortisol is a major mineralocorticoid in the ectopic ACTH syndrome because of two factors, marked hypersecretion and incomplete peripheral metabolism of cortisol as a result of an overload of metabolizing enzymes. Two measures of the peripheral metabolism of cortisol were found to be markedly decreased in two patients with the ectopic ACTH syndrome. The cortisol turnover quotients were 17.2 and 19.6 (normal = 215 +/- 98) and the ring A reduction constants were 11.8 and 13.8 (normal = 101 +/- 23). These values were comparable to that found in the syndrome of apparent mineralocorticoid excess and consistent with the hypothesis that cortisol is a significant functioning mineralocorticoid in the ectopic ACTH syndrome.

Elevated blood viscosity in patients with borderline essential hypertension.

In patients with borderline hypertension, total peripheral resistance (TPR) is either elevated or abnormally related to cardiac output. Since blood viscosity is one determinant of TPR, we compared various components of blood viscosity in 25 patients with borderline hypertension and 25 normal subjects. Under all experimental blood flow conditions examined, blood viscosity directly correlated with systolic and diastolic blood pressure (p less than 0.05 or better) and was greater in the hypertensive than in normal subjects. Venous hematocrit and plasma viscosity were higher in the hypertensive patients. These latter rheologic abnormalities accounted for the increased blood viscosity at higher shear rates. At lower shear rates, increased red cell aggregation, primarily mediated by elevated fibrinogen concentration, accounted for the higher blood viscosity in the hypertensive subjects. We conclude that even relatively small elevations in arterial pressure are associated with increased viscous resistance of blood to flow, and that the increased blood viscosity is a consequence of increased hematocrit, plasma viscosity, and red cell aggregation.

Cardiovascular responses to isometric exercise and standing in normotensive subjects during converting enzyme inhibition with teprotide.

The hemodynamic responses to isometric exercise (hand grip) were investigated in normotensive subjects during a 150 mEq (n = 8) sodium diet and a 10 mEq (n = 6) sodium diet both before and after the administration of the converting enzyme inhibitor teprotide. Although teprotide significantly decreased the mean arterial pressure during both sodium intakes, the normal pattern of hemodynamic response to hand grip was preserved, that is mean arterial pressure was increased by hand grip mainly because of an increase in cardiac output. Changes of plasma catecholamines during hand grip were not affected by teprotide. In addition, the hemodynamic responses to standing were not substantially altered by teprotide. When fainting occurred (in the seated position) following the administration of teprotide, it was associated not only with a decrease in arterial pressure but also with a concurrent reduction in cardiac output. We conclude that angiotensin inhibition by teprotide does not significantly impair sympathetically mediated cardiovascular responses.

Body fat and its distribution in relation to casual and ambulatory blood pressure.

This study was undertaken to evaluate the associations of body fat and its distribution with casual and ambulatory blood pressure in nonobese men. One hundred and thirty-five normotensive or mildly hypertensive (but untreated) men employed at three work sites were studied. Casual blood pressure was measured at the work site at initial screening and on a second occasion by a nurse. Ambulatory blood pressure was measured noninvasively for 24 hours on a workday and analyzed as work, home, and sleep blood pressure measurements. Anthropometric measurements included height, weight, and waist and hip circumferences. Blood pressure was highest while at work; home blood pressure was higher than screening blood pressure or nurse blood pressure, and sleep blood pressure was lowest. Weight and both waist and hip circumferences (but not their ratio) were all significantly correlated with screening, nurse, and sleep blood pressures but not with work or home blood pressures. Stepwise regression analysis showed that waist circumference was the best overall predictor of blood pressure. We suggest that in situations where blood pressure is the dependent variable, correlations with other variables may be closest for "basal" measures of blood pressure and may be obscured by the effects of daily activities on blood pressure.

How should diastolic blood pressure be defined during pregnancy?

Controversy exists concerning the most accurate method for defining diastolic blood pressure in pregnancy. Both disappearance (phase V) and muffling (phase IV) of Korotkoff sounds have been advocated. We previously reported an objective noninvasive method for measuring blood pressure, called K2 analysis, which in nonpregnant subjects was not different from intra-arterial diastolic blood pressure and was more accurate than the auscultatory technique. For determination of the relation of diastolic blood pressure (using K2) in pregnancy with muffling and disappearance of Korotkoff sounds, 58 women (42 hypertensive, 16 normotensive) underwent 556 blood pressure evaluations in the supine position at various stages of pregnancy. K2 analysis was compared with simultaneous auscultation by two observers, A1 (n = 461 observations; 364 hypertensive, 97 normotensive) and A2 (n = 415; 316 hypertensive, 99 normotensive). Overall, muffling was detected by observer A1 52.9% (244/461) and by observer A2 44.3% (184/415) of the time. When evaluated by clinical classification, muffling was found by both observers to be present less often in the hypertensive group (A1: 47.5%; A2: 37.3%) compared with the normotensive group (A1: 73.2%; A2: 66.7%) (P < .0001). When both observers were present (n = 348), they agreed that muffling was present only 112 times. Disappearance of sound was detected by both observers 98.3% (A1: 453/461; A2: 408/415) of the time. Muffling overestimated K2 diastolic pressure by 7 to 10 mm Hg, whereas there was no statistically significant difference between disappearance and K2 diastolic pressure for hypertensive subjects and a 2.5-mm Hg underestimation of K2 diastolic pressure for normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between job strain, alcohol, and ambulatory blood pressure.

"Job strain" (defined as high psychological demands and low decision latitude on the job) has been previously reported to be associated with increased risk of hypertension and increased left ventricular mass index (LVMI) in a case-control study of healthy employed men, aged 30-60 years, without evidence of coronary heart disease. We hypothesized that job strain would be associated with increased ambulatory blood pressure (AmBP). A total of 264 men at eight work sites wore an AmBP monitor for 24 hours on a working day. In an analysis of covariance model, job strain was associated with an increase in systolic AmBP of 6.8 mm Hg (p = 0.002) and diastolic AmBP of 2.8 mm Hg at work (p = 0.03) after adjusting for age, race, body mass index, Type A behavior, alcohol behavior, smoking, work site, 24-hour urine sodium, education, and physical demand level of the job. Alcohol use also had a significant effect on AmBP. However, among subjects not in high-strain jobs, alcohol had no apparent effect on AmBP at work. Instead, alcohol use and job strain interacted such that workers in high-strain jobs who drank regularly had significantly higher systolic AmBP at work (p = 0.007). Among the other risk factors, only age, body mass index, and smoking had significant effects on AmBP. Job strain also had significant effects on AmBP at home and during sleep as well as on LVMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolated elevation of diastolic blood pressure. Real or artifactual?

Not infrequently, blood pressure measurement by the standard auscultatory technique yields a normal systolic pressure with an elevated diastolic pressure. The relatively narrow pulse pressure of such a measurement raises concern about the accuracy of the blood pressure measurement. The purpose of this study was to assess the accuracy of auscultatory blood pressure measurements in patients with an uncommonly narrow pulse pressure, particularly patients with an elevated diastolic but normal systolic pressure. Auscultatory blood pressure measurements were compared with an objective noninvasive standard, called K2 analysis, which has been shown to be more accurate than the auscultatory technique. Blood pressure was measured simultaneously by auscultatory and K2 techniques in 175 subjects. Comparisons were performed (1) in the group as a whole, (2) in four clinical subgroups (normotensive [< 140/< 90 mm Hg, n = 69], hypertensive [> or = 140/> or = 90 mm Hg, n = 53], isolated systolic hypertensive [> or = 140/< 90 mm Hg, n = 38], and isolated diastolic hypertensive [< 140/> or = 90 mm Hg, n = 15]), and (3) in two subgroups whose ratio of pulse pressure to diastolic pressure was greater than or equal to 0.45 (n = 151) or less than 0.45 (n = 24). Subjects in the isolated diastolic hypertensive group and in the group with a pulse pressure ratio less than 0.45 were considered to have a narrow pulse pressure. In the group as a whole, consistent with previous auscultatory-K2 comparisons, systolic pressure was slightly higher and diastolic pressure slightly lower when measured by K2 versus the auscultatory technique (auscultatory, 145/85 mm Hg; K2, 147/83 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and determinants of cardiac and vascular hypertrophy in hypertension.

Hypertrophy of the capacitance arteries has recently been documented in hypertensive patients by noninvasive ultrasound techniques. To better define the prevalence and determinants of vascular hypertrophy and its potential association with ventricular hypertrophy in hypertension, we compared carotid and cardiac ultrasound findings in 172 normotensive and 172 unmedicated hypertensive subjects matched for age and sex. Despite similar body size, hypertension was associated with increased left ventricular wall thicknesses, mass, and mass index (89 versus 80 g/m2, P < .0001 for all comparisons) and increased carotid wall thickness (0.82 versus 0.77 mm) and cross-section area (17.1 versus 15.3 mm2, P < .005 for both comparisons). Among the 172 normotensive subjects, left ventricular hypertrophy was noted in 9 (5.2%) and arterial hypertrophy was found in 9 (5.2%), whereas ventricular hypertrophy was found in 21 (12.2%) and arterial hypertrophy in 19 (11%) hypertensive subjects. Arterial hypertrophy was found in 9% of hypertensive subjects with normal ventricular mass and in 24% with left ventricular hypertrophy (P < .05). Among hypertensive subjects carotid wall thickness and cross-sectional area were most strongly related to age and systolic pressure (P < .0001 for all comparisons), with little contribution form body size. Carotid relative wall thickness was only related to increasing age (P < .01). In contrast, left ventricular wall thickness and mass were strongly related to body size and systolic pressure (P < .0001 for comparisons) but not to age (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The substitutive role of ACTH in supporting aldosterone response to head-up tilt during acute renin suppression in patients with essential hypertension.

The relative contribution of the renin-angiotensin system, adenocorticotrophic hormone (ACTH) and plasma electrolytes in the response of plasma aldosterone to 30 minutes of 65 degrees head-up tilt was assessed in 10 essential hypertensive patients. Studies were carried out before and during acute blockade of renin release by propranolol, ACTH suppression by dexamethasone and combined renin and ACTH blockade. In control studies orthostasis induced significant increases only in plasma renin activity and aldosterone. In contrast, when the renin response to tilt was acutely suppressed by propranolol administration, the aldosterone response was nonetheless maintained but now appeared to be under ACTH control, since concurrent increases in cortisol were observed. During ACTH suppression aldosterone increased during tilt and so did renin. However, during combined ACTH and renin blockade aldosterone failed to increase during tilt. These studies suggest that the aldosterone secretory response to head-up tilt is normally mediated by the renin-angiotensin system but, when the renin response is suppressed, an ACTH response is elicited which assumes a backup role. However, when these two systems are blocked other factors appear unable to respond during tilt to support a normal aldosterone response.

Relation of exercise-induced myocardial ischemia to cardiac and carotid structure.

There is a strong relation of carotid atherosclerosis to coronary artery disease and left ventricular hypertrophy. In addition, abnormalities of carotid structure are strongly associated with abnormal left ventricular geometry and structure. However, little is known regarding the relation of exercise-induced ST depression to carotid atherosclerosis, carotid, or left ventricular structure in the absence of apparent coronary disease. The relationship of exercise ECG myocardial ischemia to the presence of carotid atherosclerosis and to carotid and left ventricular structure was assessed in 204 asymptomatic subjects free of clinical evidence of cardiovascular disease. Myocardial ischemia on the exercise ECG, defined by a chronotropically adjusted ST/HR slope of >3.47 microV/bpm, was associated with a nearly threefold greater likelihood of discrete carotid atherosclerosis (50% [6 of 12] versus 17% [29 of 192], P=.007) and with older age, male sex, higher systolic and diastolic blood pressures, greater left ventricular mass and mass index, and greater common carotid artery intimal-medial thickness and cross-sectional area index. Stepwise logistic regression analyses, including standard risk factors, revealed that only carotid artery cross-sectional area index (P=.0007) and systolic blood pressure (P=.005) independently predicted an abnormal chronotropically adjusted ST/heart rate slope. Moreover, among 132 subjects with > or = 10 microV of ST-segment depression, only left ventricular mass index and carotid artery cross-sectional area index were significant predictors of the chronotropically adjusted ST/heart rate slope response. Subendocardial ischemia on the exercise ECG is strongly associated with the presence of carotid atherosclerosis and is related to systolic blood pressure, carotid artery cross-sectional area index, and left ventricular mass index, independent of age, sex, and other cardiac risk factors. These findings provide additional insights into the relation between coronary and carotid atherosclerosis and suggest that an association among ischemia and left ventricular and carotid structural abnormalities may contribute to the pathogenesis of coronary events.