The pressor response to acute hyperlipidemia is enhanced in lean normotensive offspring of hypertensive parents

Family history is an important predictor of the cardiovascular risk factor cluster associated with insulin resistance. The dyslipidemia associated with insulin resistance may contribute to elevated blood pressure (BP). This study was undertaken to further explore the link between family history, dyslipidemia, and BP regulation. Twenty-three lean normal volunteers with a negative family history (FH-, n = 11) or positive family history (FH+, n = 12) of hypertension were evaluated under baseline conditions and during a 4-h infusion of intralipid and heparin (acute hyperlipidemia). Fasting blood was drawn for lipids including nonesterified fatty acids (NEFA). After 2 and 4 h of intralipid and heparin, blood was drawn for NEFA. The BP was measured at baseline and every 30 min after starting the intralipid and heparin infusion. Baseline triglycerides and very low density lipoprotein cholesterol concentrations were higher in FH+ than FH- subjects (P < .05). However, NEFA increased similarly in both groups during the infusion of intralipid and heparin. The BP and heart rate increased with acute hyperlipidemia in all subjects combined (P < .05). Despite the similar increase of NEFA, mean BP, pulse pressure, and pressure-rate product increased significantly in FH+ subjects but not in FH- volunteers with acute hyperlipidemia. Although systolic BP increased in both groups, the increase was greater in FH+ than in FH- volunteers during acute hyperlipidemia (14 +/- 2 v 10 +/- 2 mm Hg, P < .05). These results suggest that higher plasma lipids combined with a greater pressor response to hyperlipidemia may contribute to the development of high BP in subjects with a family history of hypertension.     

Renal abnormalities in normotensive insulin-dependent diabetic offspring of hypertensive parents.

To assess the effects of genetic predisposition of essential hypertension on early renal function in recent insulin-dependent diabetics, we studied inulin, para-aminohippuric, sodium, and lithium clearances in 69 unselected diabetics with (n = 20) and without (n = 49) a family history of essential hypertension. Despite similar metabolic control, glomerular filtration rate and mean arterial pressure were significantly higher in diabetics with than in those without a family history of hypertension. However, no difference was found between the two groups regarding renal vascular resistance, sodium excretion, or fractional proximal and distal sodium reabsorption. Renal responses to acute captopril (75 mg) administration were evaluated in 27 patients (six with family history of hypertension). Captopril decreased filtration fraction and mean arterial pressure similarly in both groups, whereas glomerular filtration rate and renal vascular resistance decreased more dramatically in diabetics with family history of hypertension. These findings indirectly suggest an abnormal response to angiotensin of vascular tone in recent diabetics with familial predisposition to hypertension. Renal response to acute nicardipine (2.5 mg i.v.) administration was analyzed in 24 patients (five with family history of hypertension). In both groups, nicardipine similarly decreased mean arterial pressure and renal vascular resistance and induced a marked natriuretic effect due to a predominant reduction in proximal reabsorption of sodium. However, the increase in sodium excretion was twofold to threefold more pronounced in diabetics with a family history of hypertension. Whether these early renal abnormalities may contribute to the risk of diabetic nephropathy, as suggested by retrospective studies, remains to be determined.     

Increased response to physical and mental stress in men with hypertensive parents.

Blood pressure and heart rate responses to isometric handgrip exercise were studied at age 31 and after 5 years in young nonhypertensive men with positive family histories of hypertension (n = 13) and in those with negative family histories of hypertension (n = 13) for two generations to test whether subjects with positive family histories established a pattern of increased blood pressure and heart rate responses during the 5-year follow-up period. At follow-up the response to mental stress (Stroop's color word test) was also studied. Baseline blood pressure and heart rate at rest did not differ, initially or at follow-up, between the groups. At the initial examination, absolute blood pressure levels were significantly higher during isometric handgrip exercise just before exhaustion in subjects with positive family histories. At follow-up the absolute blood pressure level (p < 0.001) and the blood pressure responses (p < 0.01-0.001) were found to be significantly increased during handgrip exercise in subjects with positive family histories compared with subjects with negative family histories. In subjects with positive family histories the diastolic blood pressure response was significantly higher (p < 0.01) at follow-up than initially and was significantly related (r = 0.70, p < 0.01) to changes in baseline diastolic blood pressure during the follow-up period. In subjects with negative family histories the systolic blood pressure response was somewhat lower at follow-up than initially. During the mental stress test, the blood pressure response was significantly greater in subjects with positive than with negative family histories.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular response to mental stress in normal adolescents with hypertensive parents. Hemodynamics and mental stress in adolescents

The hemodynamic response to mental stress (mental arithmetic) was studied in adolscents with varying risk factors for essential hypertension (EH), One group (genetic) consisted of normotensive well adolescents who had at least one parentnt with EH. Another group (labile) consisted of adolescents with labile hypertension each of whom also had at least one pare with EH. The control population consisted of normotensive adolescents with a negative family history of EH. Subjects with labile hypertension demonstrated a sustained increase in systolic and diastolic pressure and heart rate during stress. This response was significantly different than the control population (P less than THE CONTROL POPULATION (P LESS THAN 0.001). The stress response of the normotensive genetic population was qualitatively similar to the group with labile hypertension and significantly different than the controls in diastolic pressure and heart rate (p less than 0.001, less than 0.02). Post-stress plasma catecholamines were higher in the labile hypertensive and genetic groups than in the control group. These findings demonstrate increased central nervous system mediated adrenergic activity and cardiovascular response in labile hypertension and also in some normotensive subjects with a genetic risk for hypertension.     

Abnormal renal responses to calcium entry blockade in normotensive offspring of hypertensive parents

In nine young normotensive subjects with no family history of hypertension and nine age-matched normotensive subjects with one parent with essential hypertension, effective renal plasma flow (p-aminohippuric acid clearance), glomerular filtration rate (inulin clearance), and excretion of sodium and exogenously administered lithium were measured for 90 minutes before and after administration of a single 20-mg oral dose of the calcium entry blocker nifedipine. Segmental tubular handling of fluid and sodium was estimated using lithium clearance as a marker of proximal tubular reabsorption. Nifedipine did not cause any change in subjects with no family history of hypertension, but in those with one hypertensive parent there was a marked increase in effective renal plasma flow (from 644 +/- 39 to 847 +/- 42 [SEM] ml/min x 1.73 m2; p less than 0.001) and a decrease in filtration fraction (from 17.6 +/- 1.0 to 12.6 +/- 0.4%; p less than 0.001), while the glomerular filtration rate was unchanged, thus suggesting a prevailing efferent vasodilation. Sodium excretion rate (p less than 0.02) and fractional sodium excretion (p less than 0.025) increased slightly but significantly in subjects with one hypertensive parent, but not in normotensive subjects with no family history of hypertension. Lithium clearance also rose (from 29.0 +/- 2.0 to 32.8 +/- 1.9 ml/min, p less than 0.001), and the derived value of fractional proximal reabsorption diminished (from 75.8 +/- 1.0 to 71.3 +/- 1.2%, p less than 0.001). Estimated distal delivery of sodium and absolute distal sodium reabsorption both increased significantly (p less than 0.005), while fractional distal sodium reabsorption was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular structure and determinants in normotensive offspring of essential hypertensive parents.

OBJECTIVE: To assess whether currently normotensive offspring of essential hypertensive parents may have alterations in left ventricular mass (LVM) and function, and how these relate to some potential determinants. DESIGN AND METHODS: Echocardiographical indices of LVM (assessed by two-dimensional guided M-mode echocardiogram), 'clinic' blood pressure and daytime ambulatory blood pressure profiles, blood pressure responses to dynamic and isometric exercise testing, haematocrit, plasma and 24-h urinary electrolytes and catecholamines, and plasma angiotensin II were assessed on a defined Na+ intake in 31 normotensive lean sons of essential hypertensive parents (OHYP group) and 30 body mass index- and age-matched sons of normotensive parents (ONORM group). RESULTS: Clinic supine systolic blood pressure was higher in the OHYP than the ONORM group, but clinic diastolic and daytime ambulatory mean blood pressures, blood pressure loads and blood pressure during dynamic or isometric exercise did not differ significantly. LVM index (LVMI), interventricular septum thickness (IVST), posterior wall thickness (PWT), the IVST:PWT ratio, ejection fraction, fractional shortening, cardiac index and measured biochemical variables also did not differ significantly between groups. In the whole study population the LVMI correlated positively with the body mass index and negatively with plasma noradrenaline. CONCLUSIONS: In young lean men with one essential hypertensive parent and blood pressure still in the normal range, left ventricular structure and systolic function, as assessed by echocardiography, seem to be often unaltered and appropriate relative to the existing body habitus and blood pressure. Moreover, an early tendency for increasing resting blood pressure in genetically hypertension-prone humans may be more apparent under clinic than usual ambulatory conditions, whereas the blood pressure reactivity to physical stress seems to be largely normal at this stage.     

Sympathetic nerve activity and insulin sensitivity in normotensive offspring of hypertensive parents

Insulin resistance and elevated sympathetic nerve activity (SNA) are observed in young borderline hypertensive humans. A positive family history of hypertension (FH) is a strong risk factor for developing hypertension. To assess whether insulin resistance and increased sympathetic tone precede the onset of hypertension, we studied 17 young adults with and 17 without a documented family history of hypertension. Subjects were matched for age (33 ± 0.4 years in FH positive and 32 ± 0.5 years in FH negative; mean ± SE) and body mass index (BMI, 25 ± 1 kg/m² in both FH positive and FH negative subjects). We measured blood pressure (BP), heart rate (HR), muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow, and insulin sensitivity (total glucose uptake determined by an euglycemic/hyperinsulinemic clamp using stable isotope tracer infusion), and calculated forearm vascular resistance (FVR). Mean BP and HR were similar in both groups (86 ± 3 mm Hg and 61 ± 2 beats/min, and 85 ± 2 mm Hg and 62 ± 2 beats/min, respectively, in FH positive and negative respectively, P = ns). Baseline MSNA (24 ± 3 bursts/min in FH positive v 20 ± 3 bursts/min in FH negative, P = ns) and total glucose uptake [0.104 ± 0.014 mg/(kg × min × μU insulin/mL) in FH positive v 0.095 ± 0.014 mg/(kg × min × μU insulin/mL) in FH negative, P = ns] did not differ between the groups. Sympathetic and vascular responses to insulin were also similar in both groups. The increase in MSNA was 10 ± 2 bursts/min in FH positive and 10 ± 1 bursts/min in FH negative, P = ns. Thus, age- and weight-matched offspring with and without a FH of hypertension did not vary in MSNA or insulin sensitivity. These findings suggest that in the abscence of obesity and high arterial pressure, a FH of hypertension may not be accompanied by decreased insulin sensitivity or increased MSNA.     

Hyperinsulinemia and dyslipidemia in non-obese, normotensive offspring of hypertensive parents in northern India.

Insulin resistance contributes to initiation and acceleration of hypertension and atherosclerosis. This study attempted to detect occurrence of pre-hypertensive metabolic abnormalities, including hyperinsulinemia, in the offspring of hypertensive patients. Thirty-eight healthy offspring of hypertensive parents (group I, mean age 23.6+/-3.7 years) and 18 control offspring of normotensive parents (group II, mean age 24.2+/-2.8 years) were clinically examined, subjected to oral glucose tolerance test (OGTT), and the samples were analysed for blood glucose, insulin and lipid profile. Subjects in group I with fasting serum insulin <90 nmol/L constituted group Ia (n = 23, 62%) and those with >90 nmol/L constituted group Ib (n = 15, 38%). Both groups consisted of non-obese and normotensive subjects matched for body mass index and waist-hip ratio. There were no statistically significant differences in blood glucose levels between groups Ia, Ib and II during OGTT. Serum insulin levels during OGTT in group I were significantly higher than in group II (p<0.05), except at 30 min. Fasting insulin and 2 h post-OGTT insulin in group Ib were significantly higher than the other groups. Serum triglyceride levels, though within normal range, were higher in group I than group II (p<0.01). Similarly, high-density lipoprotein cholesterol levels in groups Ia and Ib were lower than those observed in group II (p<0.01). In conclusion, non-obese, normotensive offspring of hypertensive parents were observed to be hyperinsulinemic and dyslipidemic at an early age. These metabolic abnormalities may be associated with hypertension, glucose intolerance and accelerated atherosclerosis in adulthood.     

Twenty-four-hour blood pressure profiles in normotensive sons of hypertensive parents.

We investigated whether blood pressures are higher in normotensive offspring of hypertensive parents than in normotensive offspring of normotensive parents outside the physician's office and, if so, whether these higher blood pressures are dependent on the level of dietary sodium intake. We compared 24-hour ambulatory blood pressure profiles between 11 normotensive sons of two hypertensive parents and 11 normotensive sons of two normotensive parents; profiles were recorded after 1 week of a low sodium diet (10 meq/day) and after 1 week of a high sodium diet (200 meq/day). The sons of hypertensive parents were on average 6 years older than the sons of normotensive parents (47 +/- 5 [SD] versus 41 +/- 4 years, p < 0.05). The shift from low to high sodium diet did not significantly change the magnitude of differences in office or ambulatory blood pressures between the groups (i.e., no group-by-diet interaction); thus, we assessed group effects by contrasting blood pressure means for each group pooled across diets. Age-adjusted office blood pressure was higher in sons of hypertensive parents than in sons of normotensive parents (116 +/- 7/80 +/- 6 versus 111 +/- 7/75 +/- 6 mm Hg; p = 0.020 for systolic and p = 0.003 for diastolic blood pressure).(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced forearm blood flow during mental stress in children of hypertensive parents

This study compared changes in forearm blood flow, forearm vascular resistance, blood pressure, and heart rate elicited by mental stress (mental arithmetic) in 12 adolescents with a hypertensive parent and 13 age-matched adolescents with normotensive parents. The two groups did not differ in resting forearm blood flow, forearm vascular resistance, heart rate, or blood pressure. During mental stress, children with a family history of hypertension had a significantly greater increase in forearm blood flow than did children of normotensive parents (+37.5 +/- 8.0 vs +12.8 +/- 7.5%; p less than 0.05) and a trend toward reduced forearm vascular resistance (p = 0.08). Mental stress significantly increased systolic blood pressure (p less than 0.0001), diastolic blood pressure (p less than 0.001), and heart rate (p less than 0.03) in both groups. The blood pressure and heart rate responses to stress were not significantly different between groups. There was no evidence of a prolonged response or a different pattern of recovery in children with a family history of hypertension. This study indicates that regional blood flow responses underlying similar blood pressure increases during mental stress may be different in adolescents with and without a family history of hypertension.     

Psychosomatic factors in borderline hypertensive subjects and offspring of hypertensive parents

Psychosomatic factors, sympathoneural and sympathoadrenal as well as cardiovascular mechanisms, were studied in 24 patients 18-24 years of age with borderline hypertension, 50 age-matched normotensive offspring of hypertensive parents, and 49 controls with no family history of hypertension. They were compared by projective and questionnaire-based psychological tests and their circulatory and neurohormonal reactivity to mental (Stroop color-word conflict test and arithmetic test) and physical stressors (orthostasis and bicycle ergometry test) were measured. Borderline hypertensive subjects externalized aggression less (p less than 0.05) but internalized it more (p less than 0.05) and were more submissive (p less than 0.05) when compared with controls. Offspring of hypertensive parents showed a similar but weaker pattern. Both risk groups reported more positive interactions with their parents (genetic risk subjects versus controls, p less than 0.05; borderline hypertensive patients versus controls, p = 0.08) and had higher state-anxiety levels (p less than 0.05). There were more subjective symptoms of beta-adrenergic receptor-mediated functions (e.g., tachycardia, tremor) in borderline hypertensive subjects and offspring of hypertensive parents, elevated heart rates (analysis of repeated measures, p less than 0.001), and enhanced plasma norepinephrine concentrations (p less than 0.05) when compared with controls. These findings in subjects at risk for the development of hypertension suggest that psychosomatic factors and sympathetic overactivity are involved in the early phase of hypertension.     

Disparate effects of mental stress on plasma noradrenaline in young normotensive and hypertensive subjects

The response of blood pressure, heart rate and plasma catecholamines to a mental arithmetic and a cold pressor test was studied in 70 patients with mild essential hypertension and in 41 age- and sex-matched normotensives. Each group consisted of three prospectively stratified age classes: 20-29, 30-39 and 40-55 years. During mental arithmetic, hypertensives showed only a higher increment of systolic blood pressure (+17-19%) than normotensives (+12-15%). Plasma noradrenaline in the youngest normotensives (20-29 years) showed a small but significant decrease (-0.20 +/- 0.07 nmol/l) whereas the youngest hypertensives showed a small but significant increase of plasma noradrenaline (+0.14 +/- 0.04 nmol/l). The difference between both groups was highly significant (P less than 0.001). In the two older age classes there was no difference in plasma noradrenaline response between normo- and hypertensives. During the cold pressor test both the cardiovascular and plasma noradrenaline response were of the same magnitude in normo- and hypertensives. These data reinforce the concept that the increased sympathetic reactivity to mental stress in hypertensives may be restricted to the younger age.     

Blood pressure and its reactivity in the offspring of first cousin hypertensive and first cousin normotensive parents: a preliminary report.

The aim of this preliminary study was to determine whether young offspring of first cousin hypertensive parent(s), have higher blood pressure (BP) reactivity in response to their first BP measurement, as compared to the offspring of first cousin normotensive parents. The BP of 135 boys aged 9-10 years was measured, for the first time ever, after a 10-min supine rest, and subsequently, twice at 10-min intervals. The offspring of first cousin hypertensive parent(s) reacted with significantly higher systolic and diastolic BP than the offspring of normotensive first cousin parents in all three measurements. This study indicates that at an early age, the offspring of first cousin hypertensive parents, react with exaggerated BP response at their first casual BP measurement. We hypothesise that familial aggregation of BP may show more expression amongst the offspring of consanguineous marriage of hypertensive parent(s).     

Increased arterial stiffness in normoglycemic normotensive offspring of type 2 diabetic parents

Diabetes is associated with a reduction of arterial distensibility. Limited information exists regarding whether or how early this appears in the course of the disease. We studied 54 normoglycemic, normotensive, healthy offspring of 2 parents with type 2 diabetes mellitus and 55 age- and sex-matched healthy control subjects. Carotid diastolic diameter and systodiastolic change were measured by echo tracking (Wall Track System) and wall thickness by echocolor Doppler (Sonos 5500, Philips). Pulse pressure was measured by a semiautomatic device positioned on the brachial artery and arterial distensibility calculated by Reneman formula. Blood pressure, blood glucose, glycohemoglobin, and insulin sensitivity (homeostasis model assessment index) were normal or only slightly elevated and by and large similar in the 2 groups. Compared with control subjects, offspring of diabetic parents showed similar carotid diameters at diastole and a reduced increase in carotid diameter at systole (-16%), a reduced carotid artery distensibility (-30%), and an increased pulse pressure (+21.8%), all differences being statistically significant (P<0.05) and persisting in subgroups with elevated or normal body mass index values (<25 and >or=25 kg/m(2)). Carotid artery wall thickness was not different between the 2 groups. Thus, subjects with predisposition to diabetes show carotid artery stiffening even in the absence of blood pressure alterations, as well as substantial alterations of glucose metabolism, body mass index, and changes in carotid wall thickness. This suggests that, in diabetes, alterations in arterial mechanical properties represent an early phenomenon, which may occur in the absence of metabolic and blood pressure alterations.     

Blood pressure response to mental stress.

In a series of studies to explore the relationship of mental stress with blood pressure regulation, we have found that offspring of hypertensive parents exhibit a greater cardiovascular response to the stress of mental arithmetic compared to offspring of normotensive parents. The response is also greater in both adolescents and adults with borderline hypertension. However, there are racial differences in the stress-response pattern. In studying the interaction of sodium sensitivity with stress-reactivity, our data indicates that the cardiovascular response to central stress is not altered by sodium balance. The response to mental stress may be a useful marker for essential hypertension (EH), but does not appear to represent an isolated mechanism in the pathogenesis of EH.     

Renal functional reserve and microalbuminuria in offspring of hypertensive parents

Renal functional reserve, microalbuminuria, and plasma atrial natriuretic factor were measured in 21 offspring (9.5 +/- 0.5 years of age, mean +/- SEM) of hypertensive parents and in eight children (10 +/- 0.5 years of age) with no family history of hypertension who were used as a control group. Renal functional reserve was evaluated by measurement of the changes in creatinine clearance after an oral protein load of 45 g/m2. Atrial natriuretic factor levels were determined before and 60 minutes after the protein load, and microalbuminuria in fractional urine before and 120 minutes after the same stimulus as well as in a 24-hour urine collection. All children in the control group significantly increased their creatinine clearance after the protein load (preload, 122 +/- 12; 60 minutes, 144 +/- 9; 120 minutes, 154 +/- 11; 180 minutes, 144 +/- 9 ml/min/1.73 m2; all values were significant vs. preload, p less than 0.005). In contrast, only 13 of 21 offspring of hypertensive parents increased their creatinine clearance to values within 2 SD of the increase shown by the control group (preload, 144 +/- 11; 60 minutes, 153 +/- 7; 120 minutes, 202 +/- 13 ml/min/1.73 m2; p less than 0.001 vs. preload; 180 minutes, 214 +/- 19 ml/min/1.73 m2, p less than 0.001 vs. preload). The remaining eight offspring of hypertensive parents showed no detectable changes (nonresponders) (preload, 189 +/- 18; 60 minutes, 146 +/- 11; 120 minutes, 170 +/- 14; 180 minutes, 168 +/- 13 ml/min/1.73 m2; all values p = NS). No changes in atrial natriuretic factor after the protein load were observed in any group. Offspring of hypertensive parents presented higher microalbuminuria levels in 24-hour urine specimens (3.1 micrograms/min, tolerance factor [TF]2.2) than controls (2.1 micrograms/min, TF 1.5) (p less than 0.05). Although microalbuminuria increased significantly after the water load in the control group (p less than 0.05) and in the offspring of hypertensive parents (p less than 0.01), it returned to baseline at 120 minutes in the former but not in the latter (p less than 0.05 vs. baseline). The lack of renal functional reserve in nonresponders was significantly related (p less than 0.05) to the presence of higher levels of microalbuminuria. We conclude that the absence of renal functional reserve and increased microalbuminuria in some normotensive children who are offspring of essential hypertensive parents can indicate that subtle alterations in renal function may precede the onset of clinical hypertension.     

Echocardiographic parameters in athlete and nonathlete offspring of hypertensive parents

BACKGROUND: According to several reports, some cardiovascular signs of hypertension (left ventricular [LV] hypertrophy, impaired diastolic filling) can be found in the normotensive offspring of hypertensive parents. It is also well known that regular physical exercise decreases the risk of hypertension. AIM: The aim of the present study is to determine whether or not regular physical training influences these early hypertensive traits in the offspring of hypertensive parents. METHODS: Echocardiographic data of 215 (144 males, 71 females) 22- to 35-year-old nonathlete and athlete offspring of hypertensive (positive family history, FH+) and normotensive parents (negative family history, FH-) were compared in a cross-sectional design. RESULTS: In the nonathlete FH+ males and females, LV dimensions were not larger than in the FH- subjects. The E/A quotient was lower in the FH+ subjects in both genders. Absolute and heart rate adjusted isovolumetric relaxation times were slightly longer in the FH+ men than in their FH- peers. No differences were seen between athlete FH- and FH+ subjects. CONCLUSION: Regular physical exercise decreases the incidence of the adverse cardiac signs, which can be associated with hypertension in the normotensive offspring of hypertensive parents.