Essential hypertension in black and white subjects. Hemodynamic findings and fluid volume state.

Systemic hemodynamics (cardiac output, intraarterial pressure, total peripheral resistance) and intravascular volume (plasma volume and red cell mass) were measured in a population of 126 black and white patients, 51 with borderline hypertension and 75 with established essential hypertension. The findings were compared with those in 29 age-matched normotensive control subjects of both races. The white patients with established hypertension demonstrated a faster heart rate than the black patients (less than 0.05); this difference was more pronounced during upright tilt (p less than 0.02). No significant difference in cardiac index, total peripheral resistance, plasma volume or total blood volume was found between the two racial populations. Cardiac index correlated directly with plasma and total blood volume in black patients (r = 0.32, p less than 0.05) and white patients (r = 0.35, p less than 0.001) as well as in the whole study population (r = 0.36, p less than 0.001). The regression lines were similar in the two races. Further, a negative correlation was observed between the total peripheral resistance and plasma volume (r = -0.31, p less than 0.001) or total blood volume (r = -0.34, p less than 0.001), and it was similar in both races (blacks r = -0.48, p less than 0.01; whites r = -0.25, p less than 0.05). Age correlated significantly with total peripheral resistance in the white patients (r = 0.35, p less than 0.001) and in the total study population (r = 0.28, p less than 0.001). We conclude that, for every given age or level of arterial pressure, systemic hemodynamics are similar for the black and white patients with essential hypertension. These data, therefore, do not support the clinical impression that basic pathophysiology and hypertensive vascular disease are different in the black patient with essential hypertension.     

Immediate and short-term cardiovascular effects of fosinopril, a new angiotensin-converting enzyme inhibitor, in patients with essential hypertension.

Immediate and short-term cardiovascular effects of a new angiotensin-converting enzyme inhibitor, fosinopril, were assessed in 10 patients with mild to moderate essential hypertension. Administration of a 10 mg oral dose of fosinopril reduced mean arterial pressure (p less than 0.001) as a result of a 24% fall in total peripheral resistance (p less than 0.001). Short-term therapy (12 weeks) maintained the decrease in mean arterial pressure (p less than 0.05) by decreasing total peripheral resistance (p less than 0.01), without reflexive cardiac stimulation or expanding intravascular volume. Renal vascular resistance decreased (p less than 0.05) while renal blood flow, glomerular filtration rate and filtration fraction remained unchanged. The response pattern to mental, isometric and orthostatic stress was similarly unchanged. Left ventricular mass diminished by 11% (p less than 0.01); myocardial contractility was unaffected. Afterload was reduced (p less than 0.05), and velocity of circumferential fiber shortening and stroke volume increased (p less than 0.05). Thus, arterial pressure reduction produced by fosinopril was associated with improved systemic and renal hemodynamics and reduced left ventricular mass.     

Decrease in blood pressure and increase in total peripheral vascular resistance in supine resting subjects with normotension or essential hypertension

Hemodynamic changes in the supine resting position were investigated in 70 male subjects, consisting of 15 healthy volunteers with normotension (blood pressure of 113 +/- 7/70 +/- 5 mmHg, M +/- SD), 25 patients with borderline essential hypertension (143 +/- 12/90 +/- 6 mmHg) and 30 patients with established essential hypertension (166 +/- 13/108 +/- 6 mmHg). The supine position reduced blood pressure, heart rate, stroke volume and cardiac output (p less than 0.001), but increased total peripheral vascular resistance (p less than 0.001). The decrease in systolic blood pressure (p less than 0.01), stroke volume (p less than 0.05) and cardiac output (p less than 0.05), and the increase in total peripheral vascular resistance (p less than 0.01) were significantly greater in the borderline and established essential hypertensive groups than in the normotensive group. The results demonstrated that the decrease in blood pressure was due to a reduction in both heart rate and stroke volume, and that the decrease in stroke volume and increase in total peripheral vascular resistance seen in the supine position were greater in the hypertensive groups than in the normotensive group. These hyperresponses may contribute to the development and persistence of high blood pressure in patients with essential hypertension.     

Cardiovascular adaptation to obesity and hypertension

Hypertension and obesity are two disorders that are closely related; each occurs more frequently with the other than in an otherwise normal population. These two disorders, however, exert disparate effects on cardiovascular structure and function. The hallmark of essential hypertension is an increased total peripheral resistance, and hypertensive patients have a contracted intravascular volume and normal cardiac output but an increased left ventricular stroke work due to a high afterload. In contrast, obese patients have an increased intravascular volume, left ventricular filling pressure, cardiac output and a lower total peripheral and renal vascular resistance. Left ventricular adaptation will consist of eccentric hypertrophy in obesity regardless of the level of arterial pressure and concentric hypertrophy in lean hypertensive patients. Although obesity may mitigate the harmful effect of a chronically elevated total peripheral and renal vascular resistance and lessen target organ damage in essential hypertension, the combination of obesity and hypertension presents a double burden to the left ventricle and is associated with systolic and diastolic dysfunction and a propensity for high grade ventricular dysrhythmias. It is not surprising that congestive heart failure and sudden death are common sequelae of obesity hypertension. Weight reduction reduces arterial pressure by decreasing intravascular volume and cardiac output associated with a fall in sympathetic activity and reversal of cardiac hypertrophy. Therefore, weight loss unloads the heart from the two-fold burden caused by obesity and hypertension and should become a major goal in the prevention and treatment of heart disease.     

Hemodynamic, humoral and volume findings in systemic hypertension with isolated ventricular septal hypertrophy

To analyze the hemodynamic, endocrine and volume characteristics of isolated septal hypertrophy (ISH) in established systemic hypertension, 22 patients with ISH were compared to 23 patients with symmetric hypertrophy and to 28 without left ventricular (LV) hypertrophy. Mean arterial pressure and 24-hour ambulatory pressure readings did not differ between the 2 groups. At the same level of arterial pressure, patients with ISH had a high cardiac index (p less than 0.02) and a faster heart rate (p less than 0.05); consequently, total peripheral resistance was decreased (p less than 0.05). Although there was no change in intravascular volume, central blood volume was expanded (p less than 0.02), and the ratio of central to peripheral blood volume was increased (p less than 0.02), thereby indicating peripheral venoconstriction. Patients with isolated ISH had greater responses of diastolic pressure and heart rate (p less than 0.05) to isometric stress than the other 2 groups. A hyperdynamic circulatory state is a hemodynamic hallmark of ISH in early essential hypertension that might be produced by increased sympathetic activity.     

Hemodynamic effects of celiprolol in essential hypertension.

The immediate and short-term (2 week) hemodynamic and humoral effects of the beta-1 antagonist, beta-2 agonist, celiprolol, were compared with those of more prolonged atenolol therapy in 12 patients with essential hypertension. Celiprolol produced an immediate dose-dependent decrease in mean arterial pressure (113 +/- 3 to 102 +/- 2 mm Hg; p less than 0.001) and total peripheral resistance (49 +/- 3 to 38 +/- 1 U/m2; p less than 0.005) that was associated with an increased heart rate (67 +/- 1 to 73 +/- 2 beats/min; p less than 0.01) and cardiac index (2,347 +/- 129 to 2,708 +/- 111 ml/min/m2; p less than 0.01). Both celiprolol and atenolol reduced mean arterial pressure with short-term treatment (p less than 0.01); this was associated with a reduced total peripheral resistance with celiprolol (from 24 +/- 1 to 21 +/- 1 U/m2; p less than 0.02) and was not observed with atenolol. Moreover, in contrast with atenolol, celiprolol did not change heart rate or stroke and cardiac indexes. Splanchnic and forearm vascular resistances decreased with celiprolol (p less than 0.05) but not with atenolol; neither beta-blocking drug altered renal blood flow. These results demonstrate that the hemodynamic effects of celiprolol were strikingly different from atenolol; celiprolol reduced arterial pressure and total peripheral and certain vascular resistances without altering heart rate, cardiac index or regional blood flows. These effects may be explained by celiprolol's cardiac beta-1 receptor inhibitory and peripheral beta-2 receptor agonistic effects.     

Cardiovascular effects of isradipine in essential hypertension

The immediate and short-term cardiovascular effects of oral isradipine therapy were evaluated in 11 patients with mild to moderate systemic hypertension. Isradipine, 5 mg administered orally, induced a significant reduction in arterial pressure from 165 +/- 6/88 +/- 3 mm Hg to 140 +/- 5/76 +/- 2 mm Hg (p less than 0.001) within 2.5 hours by a decrease in total peripheral resistance associated with an increase in heart rate and cardiac output. Contrary to the acute effect, oral therapy with isradipine for 3 months reduced arterial pressure through a decrease in total peripheral resistance but without causing an increase in heart rate or cardiac output or activation of the sympathetic nervous system. Isradipine slightly reduced left ventricular mass and improved cardiac systolic function and left ventricular filling. Renal blood flow increased, and renal vascular resistance (p less than 0.01) and total blood volume (p less than 0.002) decreased without a change in either sodium excretion or body weight. Thus, isradipine, when given for 3 months, decreased arterial pressure by reducing total peripheral resistance without activation of reflexive mechanisms. Its favorable effects on systemic hemodynamics, total blood volume, renal blood flow, and cardiac structure and function suggest isradipine to be an excellent choice for antihypertensive therapy.     

Hypertension in obese subjects: distinct hypertensive subgroup

Obesity and hypertension are two closely associated conditions and obesity probably predisposes to hypertension. In this investigation we evaluated central, systemic haemodynamic and intravascular volume characteristics of 51 established hypertensive obese subjects subgrouped for degree of obesity. Subgrouping according to body mass index (BMI) was as follows: lean hypertensives, 17 subjects (BMI 23.00 +/- 0.45 Kg/m2); moderately obese, 19 subjects (BMI 26.92 +/- 0.30 Kg/m2); severely obese, 15 subjects (BMI 32.78 +/- 0.45 Kg/m2). Obese hypertensives were characterised by significantly increased cardiac output and total plasma volume (P less than 0.05) and by decreased total peripheral resistance (not significantly) and left ventricular ejection fraction (P less than 0.01). These changes appear to be related to the degree of obesity. Significant correlation coefficients between body mass index and cardiac output, total blood volume, total peripheral resistance and ejection fraction were also observed. In conclusion, established hypertension in the severely obese patient appears to be a separate haemodynamic entity.     

Obesity in hypertension: How innocent a bystander?

Hypertension and obesity frequently coexist in the same patient. However, the two disorders disparately affect cardiovascular function and structure. The presence of obesity significantly affects hypertensive target organ involvement. On one hand, obesity may tend to mitigate the harmful effects of a chronically elevated total peripheral and renal vascular resistance and lessen end-organ damage such as nephrosclerosis in essential hypertension. However, since both obesity and hypertension increase cardiac workload, although by different mechanisms, their presence in the same patient results in a double burden to the left ventricle. Congestive heart failure, sudden death, and coronary heart disease are common sequelae of obesity hypertension. Weight loss reduces arterial pressure by a decrease in intravascular volume and cardiac output associated with a fall in sympathetic activity. Intervention in obesity hypertension diminishes the dual hemodynamic burden imposed on the heart and becomes therefore a major objective in the prevention and treatment of heart disease.     

Enalapril improves systemic and renal hemodynamics and allows regression of left ventricular mass in essential hypertension

Enalapril, a new angiotensin-converting enzyme inhibitor, is an effective antihypertensive agent for both renovascular and essential hypertension. It is structurally different from captopril in that it does not possess a sulfhydryl group. The systemic and renal hemodynamic, biochemical and cardiac adaptive changes induced by enalapril were studied in 8 patients with essential hypertension before and after 12 weeks of therapy. Mean arterial pressure decreased from 110 to 90 mm Hg (p less than 0.01), and this was mediated through a decrease in total peripheral resistance from 42 +/- 3 to 32 +/- 3 U (p less than 0.01). Cardiac index and heart rate did not change. Renal plasma flow was increased in 6 of 8 patients and renal vascular resistance decreased from 123 +/- 6 to 91 +/- 7 U (p less than 0.001). Left ventricular mass index decreased from a mean of 166 +/- 29 to 117 +/- 8 g/m2 (p less than 0.05) without impaired myocardial contractility. Thus, enalapril lowers arterial pressure by reducing total peripheral resistance without reflexive cardiac effects. It also has favorable hemodynamic effects on the kidney. This is the first report of regression of LV mass with this agent in man.     

Hemodynamic study of 85 patients with borderline hypertension

Hemodynamic changes in supine and upright position (50 ° head-up tilt) and during exercise were studied in 40 normal subjects and 85 patients with borderline hypertension. The latter were classified in 2 groups, according to the level of cardiac index. In group I, with patients in the supine position, cardiac index, stroke index, heart rate and plasma volume were normal, but total peripheral resistance was increased (P < 0.01). During upright tilt, orthostatic decrease of mean arterial pressure (P < 0.05) was observed, and the increase in total peripheral resistance was not greater than in normal subjects. The hemodynamic response to exercise was similar to that of normal subjects. In patients in group II, cardiac index, stroke index and heart rate were increased (P < 0.001), but plasma volume was decreased (P < 0.01) and total peripheral resistance was below normal (P < 0.001). With patients in the upright position, diastolic orthostatic hypertension was observed (P < 0.001) and total peripheral resistance was greater than normal (P < 0.01) despite an abnormal fall of cardiac index (P < 0.05). The hemodynamic response to exercise indicated that total peripheral resistance did not decrease as in normal subjects and in patients of group I (P < 0.001). This study provides evidence that (1) total peripheral resistance is abnormal in patients with borderline hypertension, but only during upright tilt and exercise in patients with high cardiac index, and (2) 2 main disorders seem to be important in the early stage of hypertension: abnormality of blood volume (or blood volume distribution, or both) and impaired neurogenic activity.     

Echocardiographic functions and blood pressure levels in children and young adults from a biracial population: the Bogalusa Heart Study

M-mode echocardiograms were obtained on 651 healthy subjects, 7-22 years of age, whose diastolic blood pressure levels remained in the same height-, race-, and sex-specific decile during two biannual examinations. Echocardiographic measures of heart size and dynamics were compared across the total blood pressure distribution. Left ventricular stroke volume, cardiac output and ejection fraction, minor axis shortening, velocity of circumferential fiber shortening, and peripheral vascular resistance were correlated with blood pressure levels. There were positive correlations (p less than .001) of cardiac output and stroke volume with both systolic and diastolic blood pressure levels. Left ventricular output and stroke volume were associated with measures of body size, especially height, weight, ponderal index, and body surface area (p less than .001). The left ventricular output and stroke volume increased with age and with systolic blood pressure quintiles in the four race-sex groups. With adjustment for systolic blood pressure and measures of body size, white males had greater cardiac output (1.25 l/minute for ages 18-22 years, p = .01) and stroke volume than black males. Black males had higher peripheral resistance (4.5 mm Hg/(l/minute), p = .01) than whites. These results suggest that different hemodynamic mechanisms operate in the early phase of hypertension in blacks vs. whites in this population.     

Hemodynamic effects of massive peripheral edema

The possibility that noncardiac massive peripheral edema reduces venous distensibility was investigated in eight patients in the supine and 80-degree head-up tilt position before and after diuretic therapy. After clearance of the edema with diuretic therapy, total blood volume (TBV) was not significantly decreased; therefore, in the supine position the significant (2p less than 0.001) decrease of right atrial pressure, stroke volume, cardiac output, and cardiopulmonary blood volume (CBV) by the diuretics was due to an improvement in venous compliance which resulted in peripheral redistribution of CBV since the ratio CBV/TBV was decreased during diuretic therapy (2p less than 0.001). Furthermore, before diuretic therapy, tilt significantly decreased right atrial pressure, stroke volume, cardiac output, CBV, and the ratio CBV/TBV; but after diuretic therapy, the decrease of the same variables during tilt was significantly (2p less than 0.001) greater. These results indicate that marked peripheral edema considerably decreases venous compliance which can be improved with diuretic therapy.     

Effects of prostaglandin E1 on pulmonary circulation in patients with pulmonary hypertension.

The effects of prostaglandin E1 on pulmonary circulation and left ventricular performance have been studied in 20 patients with mitral valve disease and pulmonary hypertension. Prostaglandin E1 was administered intravenously over a period of 30 minutes. The dose used was 0.01 microgram/kg per min during the first 15 minutes and 0.02 microgram/kg per min subsequently. The first dose led only to an insignificant fall in left ventricular end-diastolic pressure. Infusion of prostaglandin E1 in a dose of 0.02 microgram/kg per min resulted in a significant fall in the pulmonary arterial pressure (P less than 0.001), total pulmonary resistance (P less than 0.001), left ventricular end-diastolic pressure (P less than 0.001), and aortic pressure (P less than 0.01), and an increase in the pulmonary blood volume (P less than 0.01), cardiac index (P less than 0.01), and heart rate (P less than 0.05). No significant differences were noted in stroke volume index or left ventricular dP/dt at 50 mmHg after prostaglandin E1. These results indicate that exogenously administered prostaglandin E1 causes active vasodilatation of the pulmonary vascular bed and has no inotropic action on the cardiac muscle.     

Hemodynamic changes associated with long-term antihypertensive therapy with new calcium antagonist

To evaluate the therapeutic efficacy of a new calcium antagonist, nicardipine in hypertension, the cardiovascular effects of chronic therapy were determined by echocardiography in 10 patients with uncomplicated mild to moderate hypertension. Significant declines were recorded in mean blood pressure (average; 11.7 +/- 0.8%) and total peripheral resistance (22.0 +/- 2.0%), accompanied by an increase in cardiac index (13.6 +/- 2.2%). In spite of the considerable degree of blood pressure reduction, heart rate and body weight were unchanged. The magnitude of the decline in total peripheral resistance was directly correlated to both the decrease in mean blood pressure (r = 0.701, p less than 0.02) and the increase in cardiac index (r = -0.953, p less than 0.01). These findings suggest that the hypotensive effect of this new calcium antagonist is due to peripheral vasodilation, and it appears to represent an effective adjunct for the treatment of mild to moderate hypertension.     

Extracellular and interstitial fluid volume in obesity with and without associated systemic hypertension

Fluid volumes and cardiac and renal hemodynamics were investigated in 44 obese men, 22 with normal blood pressure and 22 with sustained essential hypertension. For the same degree of obesity hypertensive patients had a higher value in extracellular (p less than 0.05) and interstitial fluid (p less than 0.01) volumes than normotensive subjects, while plasma volume, total body water, body cellular water, cardiac output, renal blood flow and glomerular filtration rate were similar. For the same level of blood pressure, the expansion of extracellular and interstitial fluid volume paralleled the degree of obesity. Thus, obese patients with hypertension have an absolute increase in extracellular and interstitial fluid volumes. The increase was related both to the degree of overweight and to the mechanisms of hypertension.     

Interrelation of the rheological properties of the blood and the state of central hemodynamics in patients with a stable form of hypertension

A study of 44 patients with second-stage essential hypertension (15 males and 29 females) demonstrated a significant positive correlation between packed cell volume and mean arterial BP (r = 0.794; p less than 0.001), packed cell volume and total peripheral resistance (r = 0.642; p less than 0.01), whole blood viscosity and mean arterial BP (r = 0.639; p less than 0.01), blood viscosity and total peripheral resistance (r = 0.512; p less than 0.05), and a significant negative correlation between packed cell volume and blood viscosity, on the one hand, and minute volume of the heart, on the other (r = -0.533; p less than 0.05, and r = -0.460; p less than 0.05), respectively). This may be due to both mechanical resistance to blood flow on the part of excessively viscous blood and reduced oxygen transport in blood of increased viscosity.     

Renal haemodynamic studies in obesity hypertension

Previous investigations have reported the systemic haemodynamic characteristics of obese hypertensive patients; however, their renal haemodynamics have not been explored. This report compares the renal and systemic haemodynamic findings in obese and lean normotensive and hypertensive patients. Our results demonstrate that both normotensive and hypertensive obese subjects had an increased renal blood flow, total blood volume and cardiac output, with decreased total peripheral and renal vascular resistances in comparison with lean normotensive and hypertensive patients. Body weight correlated directly and significantly with total blood volume, cardiac output and renal blood flow but indirectly with total peripheral resistance. Therefore, the elevated cardiac output and volume expansion found in obese patients were associated with increased renal perfusion; this increased renal blood flow accounts for the reduced renal vascular resistance in patients with obesity hypertension. Thus, we suggest that this effect of volume expansion in obesity could counteract the opposing effect of active vasoconstriction produced by the hypertensive disease and may account for the difference in prognosis of obese and lean hypertensive patients.     

Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure

Enalapril is a recently developed angiotensin-converting enzyme inhibitor that improves cardiac function at rest in patients with congestive heart failure. This study investigated the acute effects of enalapril on the cardiovascular response to exercise, and then evaluated the long-term effects of enalapril on exercise capacity and functional status during a 12 week placebo-controlled trial in patients with heart failure. Ten patients underwent hemodynamic monitoring while at rest and during incremental bicycle exercise before and after 5 to 10 mg of enalapril orally. At rest, enalapril decreased mean blood pressure 13% (p less than 0.01) and systemic vascular resistance 20% (p less than 0.05) and increased stroke volume index 21% (p less than 0.01). During maximal exercise, enalapril decreased systemic vascular resistance and increased both cardiac and stroke volume indexes. Enalapril acutely increased exercise duration (p less than 0.05) and maximal oxygen consumption (p less than 0.001). These 10 patients and an additional 13 patients were then randomized to either placebo or enalapril treatment and followed up for 12 weeks. Of the 11 patients assigned to active treatment, 73% considered themselves improved compared with 25% of the patients assigned to placebo treatment (p less than 0.02). During long-term treatment, exercise capacity increased in patients receiving enalapril (p less than 0.001) but was unchanged in patients receiving placebo (intergroup difference, p less than 0.05). During long-term treatment, no adverse effects of enalapril occurred. Thus, enalapril improves cardiac function at rest and during exercise. Compared with placebo, maintenance therapy with enalapril results in symptomatic improvement and increased exercise capacity.     

Dimorphic cardiac adaptation to obesity and arterial hypertension

Cardiovascular function and structure were evaluated by M-mode echocardiography and systemic hemodynamics in paired lean and obese patients, either hypertensive or normotensive. Compared to lean patients, obese patients had greater left atrial (p less than 0.0001), ventricular (p less than 0.001), and aortic root (p less than 0.002) diameters; posterior and septal wall thickness (p less than 0.001); and ventricular mass, cardiac output, stroke volume, and stroke work (all p less than 0.0001). Hypertensive patients had increased posterior wall thickness, end diastolic wall stress, stroke work (p less than 0.01), and a lower radius to posterior wall thickness ratio indicating concentric hypertrophy (p less than 0.001) when compared to normotensive patients. Cardiac adaptation to obesity consists of left ventricular dilatation and hypertrophy (eccentric hypertrophy) irrespective of arterial pressure levels. In contrast, essential hypertension solely produces concentric hypertrophy. Both obesity and hypertension increase left ventricular stroke work by disparate hemodynamic mechanisms; their presence in the same patient will tax the heart and increase the long-term risk of congestive failure.