Preterm birth with placental evidence of malperfusion is associated with cardiovascular risk factors after pregnancy: a prospective cohort study.

OBJECTIVE: Preterm birth (PTB) is associated with excess maternal cardiovascular disease risk. We considered that women with PTB and placental evidence of maternal malperfusion would be particularly affected. DESIGN: Pregnancy cohort study. SETTING: Pittsburgh, PA, USA. POPULATION: Women with PTB (n = 115) and term births (n = 210) evaluated 4-12 years after pregnancy. METHODS: Cardiometabolic risk markers were compared in women with prior PTB versus term births; pre-eclampsia and growth restriction cases were excluded. Placental evidence of maternal vascular malperfusion (vasculopathy, infarct, advanced villous maturation, perivillous fibrin, intervillous fibrin deposition), acute infection/inflammation (chorioamnionitis, funisitis, deciduitus) and villitis of unknown aetiology (chronic inflammation) was used to classify PTBs. MAIN OUTCOME MEASURES: Carotid artery intima-media thickness (IMT), fasting lipids, blood pressure (BP) and inflammatory markers measured after delivery. RESULTS: Women with PTB and malperfusion lesions had higher total cholesterol (+13.5 mg/dl) and systolic BP (+4.0 mmHg) at follow up compared with women with term births, accounting for age, race, pre-pregnancy BMI, and smoking (P < 0.05). Women with PTB and malperfusion accompanied by inflammatory lesions had the most atherogenic profile after pregnancy (cholesterol +18.7, apolipoprotein B + 12.7 mg/dl; all P < 0.05), adjusted for pre-pregnancy features. Carotid IMT was higher in this group (+0.037 cm, P = 0.031) accounting for pre-pregnancy factors; differences were attenuated after adjusting for BP and atherogenic lipids at follow up (+0.027, P = 0.095). CONCLUSION: PTBs with placental malperfusion were associated with an excess maternal cardiometabolic risk burden in the decade after pregnancy. The placenta may offer insight into subtypes of PTB related to maternal cardiovascular disease. TWEETABLE ABSTRACT: Preterm births with placental malperfusion may mark women at higher cardiovascular disease risk.

Fish oil supplementation does not lower C-reactive protein or interleukin-6 levels in healthy adults.

BACKGROUND: The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may prevent a range of chronic conditions through anti-inflammatory actions. However, as clinical trials using these fatty acids for primary prevention are yet unavailable, their putative role in disease prevention rests, in part, on evidence of anti-inflammatory actions in healthy individuals. OBJECTIVE: To investigate in a double-blind, placebo-controlled clinical trial whether supplementation with a moderate dose of EPA+DHA reduces common biomarkers of chronic, systemic inflammation in healthy individuals. METHODS: A total of 261 healthy individuals aged 30-54 years who were free of inflammatory conditions and consumed ≤ 300 mg per day EPA+DHA were included in the study. Participants were randomly assigned to 18 weeks of either fish oil supplementation providing 1400 mg per day EPA+DHA or matching placebo. Outcome measures were serum levels of C-reactive protein (CRP) and interleukin (IL)-6. In a substudy, ex vivo cytokine production was measured. Missing data for CRP and IL-6 were estimated using regression imputation. Data analyses conformed to intention-to-treat principles. RESULTS: Participant blinding was verified. Red blood cell EPA+DHA increased by 64% in the active treatment group, but serum CRP and IL-6 were not affected by supplementation (P ≥ 0.20). Findings were consistent with and without imputed values and across subgroups. Similarly, EPA+DHA supplementation did not alter ex vivo production of four pro-inflammatory cytokines (P ≥ 0.20). CONCLUSIONS: Supplementation with 1400 mg EPA+DHA did not reduce common markers of systemic inflammation in healthy adults. Whether this or a higher dose affects other measures of inflammation, oxidative stress or immune function warrants examination.

PPARα gene polymorphisms modulate the association between physical activity and cardiometabolic risk.

BACKGROUND AND AIMS: Habitual physical activity is understood to help prevent type 2 diabetes and atherosclerotic cardiovascular disease via beneficial effects on both metabolism and the vascular system. However, individuals do not have uniform cardiometabolic responses to physical activity. Here we explore the extent to which variation in the proliferator-activated receptor-alpha (PPARα) gene, which modulates carbohydrate and lipid metabolism, vascular function, and inflammation, predicts the overall cardiometabolic risk (CMR) profile of individuals engaging in various levels of physical activity. METHODS AND RESULTS: 917 unrelated, community volunteers (52% female, of Non-Hispanic European ancestry) aged 30-54 years, participated in the cross-sectional study. Subjects were genotyped for 5 single nucleotide polymorphisms in the PPARα gene, from which common haplotypes were defined. A continuous measure of CMR was calculated as an aggregate of 5 traditional risk factors: waist circumference, resting blood pressure, fasting serum triglycerides, HDL-cholesterol and glucose. Regression models were used to examine the main and interactive effects of physical activity and genetic variation on CMR. One common PPARα haplotype (H-23) was associated with a higher CMR. This association was moderated by daily physical activity (B = -0.11, SE = 0.053, t = -2.05, P = 0.04). Increased physical activity was associated with a steeper reduction of CMR in persons carrying the otherwise detrimental H-23 haplotype. CONCLUSIONS: Variations in the PPARα gene appear to magnify the cardiometabolic benefits of habitual physical activity.

Hypertension labelling was associated with poorer self-rated health in the Third US National Health and Nutrition Examination Survey.

Individuals labelled as having hypertension tend to report poor self-rated health (SRH), but it is unclear whether this association is independent of actual hypertension, socioeconomic status and adiposity, and extends across racial and ethnic groups. In a cross-sectional study we compared hypertensive and normotensive individuals (N = 19,057) who varied in whether they had ever been labelled hypertensive. Blood pressure was measured in participants' homes and mobile examination centres in the United States as part of the Third National Health and Nutrition Examination Survey, 1988-1994. The main outcome measure was global SRH. Hypertensive labelling was associated with poorer SRH and was independent of established SRH predictors, antihypertensive medication use, body mass index, and hypertension status (adjusted odds ratio (OR) = 1.79, 95% confidence interval (CI), 1.61-1.99). Hypertension was also associated with poorer SRH (OR = 1.26; 95% CI 1.09-1.46) but this association was eliminated by adjustment for hypertensive labelling (OR 1.06; 95% CI 0.92-1.22). These effects were consistent across non-Hispanic white, non-Hispanic black, and Hispanic subgroups. Individuals labelled hypertensive are more likely to have lower SRH and this labelling effect predominates over that of actual hypertension. Public health efforts to increase the number of individuals screened for high blood pressure may successfully detect the presence of hypertension but may also reduce health-related quality of life as measured by global SRH.

White-coat hypertension and carotid artery atherosclerosis: a matching study.

BACKGROUND: Blood pressure (BP) measurements obtained in the clinic have long served as the basis for determining risk of hypertensive vascular disease, yet many patients with high BP in the physician's office are normotensive elsewhere. It remains unclear whether such patients with "white coat" hypertension elude the risk of atherosclerosis. METHODS: Community residents 40 to 70 years of age and not receiving any cardiovascular medications were recruited to participate in a study of cardiovascular risk factors. On the basis of clinic and daytime ambulatory BP and a threshold criterion of 140/90 mm Hg, subjects were classified as having persistent hypertension, white-coat hypertension, or persistent normotension. One-to-one matching was conducted in male participants on the basis of race and BP. Subjects with persistent hypertension and white-coat hypertension were matched on clinic BP, and those with white-coat hypertension and normotension were matched on daytime ambulatory BP. RESULTS: The 3 matched groups of men (n=40 in each group) were similar in age, smoking status, and fasting glucose and lipid levels. Compared with the normotensive subjects, subjects with either persistent or white-coat hypertension had greater mean body mass index, waist-hip ratio, and fasting insulin concentration. On the basis of standardized duplex ultrasound examination of the carotid arteries, mean maximal intimal-medial thickness and plaque index in subjects with white-coat hypertension were greater than among normotensive subjects and equal to that of the subjects with persistent hypertension. CONCLUSION: When compared with unmedicated individuals with comparable elevations in clinic BP, individuals with white-coat hypertension appear not to be protected from the atherosclerotic sequelae of hypertension.

Effects of acute psychological stress on serum lipid levels, hemoconcentration, and blood viscosity.

BACKGROUND: While there is substantial evidence that psychological stress enhances risk for coronary artery disease, the mechanisms underlying such an influence remain unclear. We examined the effects of short-term psychological stress on serum lipid levels, hemoconcentration, fibrinogen level, and plasma viscosity. METHODS: Forty-four healthy young adults were randomly assigned to perform a distinctly frustrating cognitive task for 20 minutes (stress condition) or to rest quietly for the same period (control condition). RESULTS: Relative to controls, stressed subjects showed significant increases in blood pressure and heart rate; total, low-density, and high-density lipoprotein cholesterol levels; hematocrit; hemoglobin level; and total protein concentration. Stressed subjects also showed significant reductions in plasma volume and increased plasma viscosity and estimated whole-blood viscosity compared with controls. A similar trend in fibrinogen level was not statistically significant. Individual differences in blood pressure and heart rate response to stress correlated highly with changes in total cholesterol levels and hematocrit. CONCLUSIONS: Our investigation provides further evidence that exposure to short-term mental stress elicits hemoconcentration with associated increases in serum lipid concentrations, hemostatic factors, and blood viscosity.

Acute cholesterol responses to mental stress and change in posture.

BACKGROUND: Serum lipid levels vary widely within individuals, but the causes of these fluctuations are poorly understood. One area of research concerns elevations in cholesterol concentration in response to emotional stress. In a laboratory-based experiment, we compared the effects of acute mental stress and postural change (standing) on serum cholesterol concentration. In addition, plasma volume was indirectly monitored to determine whether cholesterol changes with mental stress, if present, were a function of hemoconcentration. METHODS: Twenty-six men attended two laboratory sessions, each consisting of baseline (30 minutes), task (20 minutes), and recovery (30 minutes) periods. Subjects rested in the supine position during the baseline and recovery periods. During the task period of one session, subjects performed a mental task (Stroop test and mental arithmetic); during the other session, the subjects stood for the task period. RESULTS: Both mental stress and standing elicited significant elevations in heart rate, blood pressure, and plasma catecholamine concentrations, relative to the baseline and recovery periods. Both the mental and orthostatic tasks also significantly increased serum cholesterol concentration (by 0.10 and 0.57 mmol/L [3.7 and 21.9 mg/dL], respectively), as well as hemoglobin level and hematocrit. Cholesterol elevations with standing were reversible, while those resulting from mental stress persisted through the recovery period. When values were corrected for concomitant hemoconcentration, no net change in serum cholesterol level occurred during either task. CONCLUSIONS: Acute mental stress can produce rapid elevations in serum cholesterol concentration. It can also increase hemoglobin concentration and hematocrit (ie, reduce plasma volume). Therefore, increases in serum cholesterol level after acute mental stress are analogous to those with standing and may reflect hemoconcentration rather than altered lipoprotein metabolism.

Inverse relationship between fenfluramine-induced prolactin release and blood pressure in humans.

Although substantial evidence from experimental animals suggests that augmentation and reduction in serotonergic neurotransmission both affect arterial blood pressure (BP), it is unknown whether "tonic" central serotonergic activity is related to resting BP variability in humans. We tested this hypothesis in a community sample by evaluating the relationship between resting BP and a neuropharmacologic index of brain serotonergic activity (the fenfluramine challenge test). Subjects were 270 generally healthy men and women aged 25 to 60 years who were not receiving prescribed antihypertensive or psychotropic medications. The sample included 216 non-Hispanic whites and 47 blacks. Resting systolic BP ranged from 85 to 161 mm Hg and diastolic from 58 to 98 mm Hg. Each subject received 0.55 to 0.65 mg/kg D,L-fenfluramine hydrochloride, and the plasma prolactin concentration was measured over 3.5 hours. Analyses revealed a linear, inverse relationship between the maximum fenfluramine-induced prolactin rise and systolic and diastolic BP in whites: r=-0.36 and r=-0.29, respectively (P<0.001 for both). These relationships were not observed in the black participants. In whites, the prolactin response to fenfluramine remained a significant predictor of systolic and diastolic BPs in multivariate models including age, gender, body mass index, physical activity, smoking, and alcohol consumption (P135/85 mm Hg. These data reveal that in white but not black adults, fenfluramine-induced prolactin release correlates inversely with BP and may indicate a role of central serotonergic activity in the pathogenesis of hypertension.

Cerebral blood flow in hypertensive patients: an initial report of reduced and compensatory blood flow responses during performance of two cognitive tasks.

We asked whether the altered cerebral vasculature associated with essential hypertension might dampen or redirect the regional cerebral blood flow (rCBF) response to cognitive work. Relative rCBF was assessed with [(15)O]water positron emission tomography during a working memory task, a memory span task, and two perceptual control tasks. Unmedicated hypertensive patients and control subjects differed in rCBF response during both memory tasks. Hypertensives showed relatively diminished rCBF responses in right hemisphere areas combined with compensatory activation of homologous areas in the left cerebral cortex. Essential hypertension appears to selectively influence the circulatory reserve of portions of cerebral cortex and secondarily induce recruitment of other cortical areas to process certain tasks.

Recovery from major depression is not associated with normalization of serotonergic function.

BACKGROUND: Plasma prolactin response to fenfluramine, a serotonergic agent, is typically blunted in moderately to severely depressed adults when compared to healthy controls. It is not clear, however, whether this dysregulation represents an acute change during symptomatic depression or a chronic disturbance. METHODS: In the current study, the prolactin responses to D,L-fenfluramine (weight-adjusted oral dose) of 29 adults who had a history of at least one major depressive episode (DSM-III-R criteria), but not during the past year, were compared to the prolactin responses of 58 age-, sex-, and socioeconomic status-matched adults without a lifetime history of major depression. RESULTS: Individuals with a positive history of major depression had significantly lower peak prolactin responses than controls. This finding was not attributable to weight, fenfluramine bioavailability, or baseline prolactin levels. CONCLUSIONS: This is the first investigation to compare men and women with a history of depression but not depressed at the time of the fenfluramine challenge to a similar group of healthy controls. The results are consistent with the hypothesis that central serotonergic activity is persistently disturbed in adults who experience depressive episodes.

Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene.

BACKGROUND: Central nervous system (CNS) serotonergic activity correlates inversely with human aggressive behavior, and individual differences in aggressive disposition are at least partially heritable. This study was conducted to evaluate the possible association between measures of antagonistic behavior and an intronic polymorphism of the gene coding for tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis. METHODS: Locally recruited men and women (n = 251) were genotyped for the A218C polymorphism located in intron 7 of the TPH gene. All subjects were administered standard interview and questionnaire indices of aggression and anger-related traits of personality; in a portion of subjects, CNS serotonergic activity was assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). RESULTS: Persons having any TPH U allele scored significantly higher on measures of aggression and tendency to experience unprovoked anger and were more likely to report expressing their anger outwardly than individuals homozygous for the alternate L allele. In men, but not women, peak prolactin response to fenfluramine was also attenuated among subjects having any U allele, relative to LL homozygotes. CONCLUSIONS: Individual differences in aggressive disposition are associated with an intronic polymorphism of the TPH gene in a nonpatient sample of community-derived volunteers.

D,L-fenfluramine challenge test: experience in nonpatient sample.

The plasma prolactin response to a single-dose fenfluramine challenge is increasingly utilized in psychiatric research as an indirect and noninvasive measure of central serotonergic activity. However, the influences of age, gender, and body weight on prolactin response and characterization of physical and psychological symptoms evoked by fenfluramine remain poorly studied. In the current study, 83 nonpatient male and female volunteers, 25-60 years old, were administered a standardized fenfluramine challenge test (60 mg). Serial blood samples for plasma drug concentration and plasma prolactin concentration were obtained and side effects reported by participants were recorded. Analyses revealed that both plasma drug concentration and prolactin response were correlated with weight-relative dose (r = 0.43 and r = 0.38, respectively; p < 0.001). No significant relationship was noted between prolactin response and either age or gender. Symptoms during fenfluramine challenge were reported by 90% of subjects, most commonly fatigue, headache, lightheadedness, and difficulty concentrating. Overall side effect severity was related to weight-relative dose (r = 0.26; p < 0.05) and prolactin response (r = 0.42; p < 0.001). We conclude that fenfluramine challenge results should be reported as change in plasma prolactin relative to dose, and that in nonpatient samples the test is associated with frequent side effects.

Aggression, impulsivity, and central nervous system serotonergic responsivity in a nonpatient sample.

To test the hypothesis that traits of aggression and impulsivity correlate negatively with central serotonergic system function in a nonpatient population, a standard fenfluramine challenge (for assessment of serotonergic responsivity) and behavioral measurements germane to aggression/impulsivity were administered to a community-derived sample of 119 men and women. In men, peak prolactin responses to fenfluramine correlated significantly with an interview-assessed life history of aggression (r = -.40, p < .002), the Barratt Impulsiveness Scale (r = -.30, p < .03), and traits of Conscientiousness (r = +.30, p < .03), Neuroticism (r = -.31, p < .02) and Angry Hostility (r = -.35, p < .01) on the NEO-Personality Inventory. No significant relationships were observed across all women, although subanalyses restricted to postmenopausal subjects (in whom ovarian influences on prolactin secretion may be mitigated because of diminished estrogen) showed a pattern of behavioral associations somewhat similar to that seen in men. By extending documented relationships between an index of central serotonergic system function and traits of aggression and impulsivity to a more normative range of population variability than is represented in prior literature, this study supports speculation that these associations reflect a basic neurobehavioral dimension of individual differences.

Neuropsychological correlates of hypertension: review and methodologic considerations.

Essential hypertension is a chronic disorder having many potential physical and behavioral sequelae. This article evaluates the impact of hypertension on neuropsychological test performance. First, cross-sectional and longitudinal studies that examine the neuropsychological correlates of hypertension are reviewed. In general, hypertensives are found to perform more poorly than normotensives, particularly on tests of memory, attention, and abstract reasoning, and less consistently on tests of perception, constructional ability, mental flexibility, and psychomotor speed. Next, the influence of variables that may moderate relationships between hypertension and neuropsychological performance--such as age, education, and medication usage--are examined. Finally, potential mechanisms, both physiological and psychological, underlying associations between hypertension and neuropsychological performance are discussed.

Effects of lovastatin on cognitive function and psychological well-being.

PURPOSE: Animal research and cross-sectional studies suggest that serum lipid concentrations may influence cognitive function, mood, and behavior, but few clinical trials have studied these effects. SUBJECTS AND METHODS: In this double-blind investigation, 209 generally healthy adults with a serum low-density-lipoprotein (LDL) cholesterol level of 160 mg/dL or higher were randomly assigned to 6-month treatment with lovastatin (20 mg) or placebo. Assessments of neuropsychological performance, depression, hostility, and quality of life were conducted at baseline and at the end of the treatment period. Summary effect sizes were estimated as z scores on a standard deviation (SD) scale. RESULTS: Placebo-treated subjects improved between baseline and posttreatment periods on neuropsychological tests in all five performance domains, consistent with the effects of practice on test performance (all P <0.04), whereas those treated with lovastatin improved only on tests of memory recall (P = 0.03). Comparisons of the changes in performance between placebo- and lovastatin-treated subjects revealed small, but statistically significant, differences for tests of attention (z score = 0.18; 95% confidence interval (CI), 0.06 to 0.31; P = 0.005) and psychomotor speed (z score = 0.17; 95% CI, 0.05 to 0.28; P = 0. 004) that were consistent with greater improvement in the placebo group. Psychological well-being, as measured several ways, was not affected by lovastatin. CONCLUSION: Treatment of hypercholesterolemia with lovastatin did not cause psychological distress or substantially alter cognitive function. Treatment did result in small performance decrements on neuropsychological tests of attention and psychomotor speed, the clinical importance of which is uncertain.

Neurobehavioral effects of antihypertensive medications.

Although millions of hypertensive individuals receive chronic treatment with antihypertensive medication, the effect on the central nervous system by these drugs is poorly understood. Such treatment, while generally well tolerated, frequently produces symptoms of drowsiness, weakness, altered memory and impaired concentration. In addition to subjective evidence derived from patient reports, a large number of investigations have now been published which attempt to objectively assess the influence of antihypertensive medication on behavioral or cognitive performance. This paper summarizes and critically evaluates experimental studies of the effect of antihypertensive medication on subjects' performance of neuropsychological tasks and reviews the pharmacologic mechanisms by which these drugs may affect behavior. The literature is incomplete in its assessment of all domains of neuropsychological performance and all drug classes, and methodologic deficiencies are common. Nonetheless, the consensus of all studies and the findings of well-designed studies in particular do not identify any notable areas of performance impairment in patients receiving antihypertensive medication. Moreover, results suggest that, in certain instances, drug treatment may even enhance performance. In light of the limitations of the literature, however, an adequate understanding of the effects of antihypertensive therapy on behavioral functioning awaits completion of large, well-designed investigations including all major drug classes and thorough neurobehavioral assessments.

Effects of lovastatin on the immune system.

Laboratory investigations have demonstrated that blockade of HMG-CoA reductase in vitro reduces lymphocyte proliferation in response to mitogens as well as other facets of the immune system, such as natural killer cell cytotoxicity. However, in this randomized and double-blind clinical investigation, treatment with 20-mg lovastatin for 6 months did not significantly alter several enumerative and functional characteristics of circulating immune cells.

Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults.

The apolipoprotein E genotype (APOE) is an established risk factor for Alzheimer disease, with the age-at-onset occurring earlier in individuals having at least one APOE epsilon 4 allele, relative to the APOE epsilon 3 or APOE epsilon 2 isoforms. Moreover, nondemented older adults with the APOE epsilon 4 allele also show diminished cognitive performance, particularly on tests of learning and memory, and an accelerated decline in memory performance with increasing age. The current investigation extends the study of the APOE epsilon 4 allele and cognitive performance to healthy, middle-aged adults. A community sample of 220 non-Hispanic Caucasian men and women, aged 24-60 (average age = 46), were genotyped for the APOE polymorphism and completed a battery of neuropsychological tests. Multivariate analyses were conducted on measures of verbal learning and memory (e. g., learning a list of words and recalling them 30 min later), visual memory (e.g., reproducing a previously copied figure from memory), and attention span (e.g., repeating long lists of digits), after adjustments for age, and estimated IQ. Results indicated that performance on learning and memory tasks was significantly poorer in adults having any APOE epsilon 4 allele, relative to adults with APOE epsilon 2 and epsilon 3 genotypes (P <.01). Attention span did not differ by genotype. These findings, the first in a sample of middle-aged adults, suggest that the APOE polymorphism is a marker for age-related decline in memory (detectable prior to overt, clinical manifestations of memory loss), and/or a marker for individual differences in memory ability across the life span. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:707-711, 2000.

Family history studies in hypertension research. Review of the literature.

Reviewed in the present article are over 150 family history studies of essential hypertension. By comparing normotensive individuals with and without a family history of hypertension, these investigations seek to identify potential pathophysiologic factors that predate the development of high blood pressure. The research literatures summarized here represent four general areas: 1) cellular salt transport mechanisms, 2) dietary sodium, intravascular volume, and renal function, 3) cardiovascular morphology and physiology, and 4) cardiovascular reactivity. There is strong evidence of early cardiac morphologic changes (greater left ventricular wall thickness and mass) and altered peripheral vascular capacity and responsivity to pressor stimuli among normotensive individuals with a positive family history. In contrast, cardiac output, sodium consumption, intravascular volume, and cardiovascular responses to isometric exercise and standing do not differ in persons with and without a family history of hypertension. Other articles are characterized by inconsistent results, which may be a reflection of the heterogeneity of essential hypertension, but also may be due to methodological weaknesses. The latter include failure to confirm the blood pressure status of ostensibly hypertensive or normotensive family members and the use of relatively weak study designs (eg, where a positive history is defined by a single, hypertensive first-degree relative).

Absence of enhanced sympathoadrenal activity and behaviorally evoked cardiovascular reactivity among offspring of hypertensives.

To determine whether offspring of hypertensives show enhanced sympathetic nervous system activity, we evaluated several indices of sympathoadrenal activation and cardiovascular responsiveness to behavioral stimuli among 90 normotensive, young adult men having either one or two hypertensive parents (PH+(-), PH++) or normotensive parents only (PH--) (n = 30/group). Measurements included heart rate (HR) and blood pressure (BP) reactions to three mental stressors (the Stroop test, mental arithmetic, mirror tracing), a cold pressor test, postural adjustment (60 degrees upright tilt), isometric exercise and bicycle ergometry, as well as the 24-h excretion of catecholamines (epinephrine [E], norepinephrine [NE]) and venous plasma catecholamine concentrations, both at rest (seated and supine) and in response to the Stroop test and upright tilt. The three groups did not differ in age, education, body mass index (BMI), estimated aerobic fitness, resting HR, cardiac preejection period (PEP) and PEP:LVET (left ventricular ejection time) ratio, 24-h Na or K excretion, or fasting lipids, insulin or plasma renin activity. Resting systolic and diastolic BP varied as a function of parental hypertension, and were significantly higher in PH++ than among PH-- subjects (P < .05). No significant group difference was observed on any measure of plasma or urinary catecholamines, nor did offspring of hypertensives (PH++ or PH+-) showed greater HR or BP reactions than PH-- subjects to any of the several laboratory challenges. In sum, we find no evidence of enhanced sympathetic activity or heightened cardiovascular responsiveness among normotensive young adults who are familially predisposed to essential hypertension.