Central artery pulse pressure in end-stage renal disease: the roles of aortic diameter, aortic stiffness and wave reflection.

In elderly subjects and patients with end-stage renal disease (ESRD), carotid pulse pressure (PP) is an independent and significant predictor of cardiovascular (CV) risk. Whereas in the elderly carotid diameter, but not carotid stiffness, is an associated CV risk factor, an opposite CV risk pattern was observed in ESRD patients that was associated with stiffness. Whether in ESRD patients arterial diameter, stiffness or both are involved in the mechanism(s) of increased carotid PP has never been investigated. Nondiabetic ESRD patients (n = 144) were compared with 57 control subjects matched for age, sex and mean blood pressure, but with higher brachial and carotid PP. Noninvasive echo-Doppler techniques and pulse wave velocity (PWV) and pulse wave analysis were used to evaluate cardiac and carotid arterial structures and functions using multiple stepwise regressions. In controls, carotid PP was associated only with stroke volume, arterial wave reflections and aortic PWV, but not aortic diameter. In ESRD patients, it was associated with wave reflections, aortic PWV, stroke volume and higher aortic diameter. In ESRD patients and controls, elevated carotid PP mainly reflected increased aortic PWV and earlier wave reflections. Aortic diameter had an impact only on ESRD patients, where it compensated for enhanced aortic stiffness and the more pronounced effect of reflected waves. This hemodynamic profile differs consistently from that in elderly subjects of the general population and selectively influences CV risk and drug treatment.

Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure.

BACKGROUND: Aortic pulse wave velocity (PWV) is a predictor of mortality in patients with end-stage renal failure (ESRF). The PWV is partly dependent on blood pressure (BP), and a decrease in BP can attenuate the stiffness. Whether the changes in PWV in response to decreases in BP can predict mortality in ESRF patients has never been investigated. METHODS AND RESULTS: One hundred fifty ESRF patients (aged 52+/-16 years) were monitored for 51+/-38 months. From entry until the end of follow-up, the changes of PWV in response to decreased BP were measured ultrasonographically. BP was controlled by adjustment of "dry weight" and, when necessary, with ACE inhibitors, calcium antagonists, and/or beta-blockers, in combination if necessary. Fifty-nine deaths occurred, including 40 cardiovascular and 19 noncardiovascular events. Cox analyses demonstrated that independent of BP changes, the predictors of all-cause and cardiovascular mortality were as follows: absence of PWV decrease in response to BP decrease, increased left ventricular mass, age, and preexisting cardiovascular disease. Survival was positively associated with ACE inhibitor use. After adjustment for all confounding factors, the risk ratio for the absence of PWV decrease was 2.59 (95% CI 1.51 to 4.43) for all-cause mortality and 2.35 (95% CI 1.23 to 4.41) for cardiovascular mortality. The risk ratio for ACE inhibitor use was 0.19 (95% CI 0.14 to 0.43) for all-cause mortality and 0.18 (95% CI 0.06 to 0.55) for cardiovascular mortality. CONCLUSIONS: These results indicate that in ESRF patients, the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes.

Impact of aortic stiffness on survival in end-stage renal disease.

BACKGROUND: Damage to large arteries is a major factor in the high cardiovascular morbidity and mortality of patients with end-stage renal disease (ESRD). Increased arterial stiffness and intima-media thickness, together with increased pulse pressure, are the principal arterial alterations. Whether increased aortic pulse-wave velocity (PWV), a classic marker of increased arterial stiffness, may predict all-cause and/or cardiovascular mortality has never been investigated. METHODS AND RESULTS: A cohort of 241 patients with ESRD undergoing hemodialysis was studied between April 1987 and April 1998. The mean duration of follow-up was 72+/-41 months (mean+/-SD). Mean age at entry was 51.5+/-16.3 years. Seventy-three deaths occurred, including 48 cardiovascular and 25 noncardiovascular fatal events. At entry, together with standard clinical and biochemical analyses, patients underwent echocardiography and aortic PWV measured by Doppler ultrasonography. On the basis of Cox analyses, 2 factors emerged as predictors of all-cause and cardiovascular mortality: age and aortic PWV. Hemoglobin and low diastolic pressure interfered to a smaller extent. After adjustment for all the confounding factors, an OR for PWV >12. 0 versus <9.4 m/s was 5.4 (95% CI, 2.4 to 11.9) for all-cause mortality and 5.9 (95% CI, 2.3 to 15.5) for cardiovascular mortality. For each PWV increase of 1 m/s in our study population, all-cause mortality-adjusted OR was 1.39 (95% CI, 1.19 to 1.62). CONCLUSIONS: These results provide the first direct evidence that in patients with ESRD, increased aortic stiffness determined by measurement of aortic PWV is a strong independent predictor of all-cause and mainly cardiovascular mortality.

Influence of body height on pulsatile arterial hemodynamic data.

OBJECTIVES: This study sought to present evidence that short stature is a hemodynamic liability, which could explain in part the inverse relation between body height and cardiovascular risk. BACKGROUND: Other explanations for the association of short stature with increased cardiovascular risk include advancing age, reduced pulmonary function, genetic factors, poor childhood nutrition and small-caliber coronary arteries. This study adds another factor-the physiologic effects of reduced body height on the arterial tree, which increase left ventricular work and jeopardize myocardial perfusion. METHODS: Four hundred two subjects were studied: 149 with end-stage renal disease and 253 with normal renal function. Measurements included blood pressure, body height, cardiac cycle length, carotid to femoral artery pulse wave velocity, carotid artery pulse waves (by applanation tonometry) and the arrival time of reflected waves. Calculations included the carotid augmentation index, carotid artery compliance and the diastolic to systolic pressure-time ratio (an index of myocardial supply and demand). RESULTS: On linear and stepwise multiple regression, body height correlated with all variables except mean blood pressure. CONCLUSIONS: The early systolic arrival of reflected waves in short people in this group acts to stiffen the aorta and increase the pulsatile effort of the left ventricle, even at the same mean blood pressures. Short stature also induces a faster heart rate, which increases cardiac minute work and shorten diastole. Stiffening lowers the aortic diastolic pressure and, coupled with a shortened diastole, could adversely influence myocardial supply. Although indirect, this evidence supports a physiologic hypothesis for the body height-cardiovascular risk association.

Influence of sex on arterial hemodynamics and blood pressure. Role of body height.

Systolic pressure is lower in premenopausal women than in age-matched men, but underlying alterations are not well characterized. Aging and body size alter arterial function, influencing pressure wave propagation and amplification in peripheral and central arteries. To assess the possibility that systolic pressure differences in women are related to smaller body size, we studied arterial function in 119 men and 104 women. Premenopausal and postmenopausal women were compared with age-matched men. The following parameters were measured: ankle-arm pressure index (Doppler), aortic and arterial distensibility (pulse wave velocity), systolic pressure and the effect and time delay of arterial wave reflections in the common carotid artery (applanation tonometry), and diameters of the abdominal aorta and aortic bifurcation and their ratio (aortic tapering, echography). Premenopausal women had lower brachial (P < .05) and ankle (P < .01) systolic pressures than age-matched men, whereas the ankle-arm pressure index was higher in men (P < .01). In the overall population the ankle-arm index was positively correlated with body height (P < .001). Carotid systolic pressure was similar in women and men, with an increased effect and earlier return of wave reflections in women (P < .01). The effect of wave reflections was inversely correlated with body height (P < .001) and positively associated with aortic tapering (P < .001), which was increased in women (P < .01). In premenopausal women the distensibility of brachial and femoral arteries was higher than in age-matched men (P < .01), whereas aortic distensibility was not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid arterial stiffness as a predictor of cardiovascular and all-cause mortality in end-stage renal disease.

Damage of large arteries is a major contributory factor to the high pulse pressure observed in patients with end-stage renal disease. Whether incremental modulus of elasticity (Einc), a classic marker of arterial stiffness, can predict cardiovascular mortality has never been investigated. A cohort of 79 patients with end-stage renal disease undergoing hemodialysis was studied between September 1995 and January 1998. Mean age at entry was 58+/-15 years. The duration of follow-up was 25+/-7 months, during which 10 cardiovascular and 8 noncardiovascular fatal events occurred. At entry, carotid Einc was calculated from measurements of diameter, thickness (echo-tracking technique), and pulse pressure (tonometry). Based on Cox analyses, 2 dominant factors emerged as predictors of all-cause and cardiovascular mortality: increased Einc and decreased diastolic blood pressure. Lipid abnormalities and the presence of previous cardiovascular events interfered to a smaller extent. After adjustment for confounding variables, the odds ratio for Einc >/=1 kPa-3 was 9.2 (95% confidence interval, 2.4 to 35.0) for all-cause mortality. These results provide the first direct evidence that in patients with end-stage renal disease undergoing hemodialysis, arterial alterations, as determined from carotid Einc, are strong independent predictors of all-cause and cardiovascular mortality.

Wave reflections and cardiac hypertrophy in chronic uremia. Influence of body size.

Arterial wave reflections (AWRs), an important determinant of cardiac afterload, are increased in hemodialysis patients. However, an association between AWRs and left ventricular hypertrophy has not been established in these subjects. We therefore sought an association between these two parameters in a cross-sectional study of two outpatient hemodialysis populations. AWRs were quantified (augmentation index, percent) as the ratio of the height of the late systolic peak to the total height of the carotid pulse wave recorded with a micromanometer-tipped probe. AWRs were determined in 44 hemodialysis patients, 22 with pronounced AWRs (group A: augmentation index > 12%), and 22 with small or moderate AWRs (group B: augmentation index < 12%). The groups were matched for age, sex, blood pressure, and hemodialysis duration. Left ventricular size was determined by echocardiography. Despite lower body size (P < .005) and similar blood pressure, cardiac output, peripheral resistance, and aortic pulse wave velocity, group A patients had greater left ventricular mass (P < .01). For the population as a whole, left ventricular mass and AWRs were positively correlated (P < .0001) independent of age, blood pressure, hemodialysis duration, or body size. Lesser body height was the principal factor associated with increased AWRs in group A (P < .001). We conclude that in hemodialysis patients AWRs are associated with the development of left ventricular hypertrophy and that small body height is a risk factor for long-term cardiovascular complications.

Large artery structure and function in hypertension and end-stage renal disease.

The cardiovascular complications in hypertension are ascribed to two different but associated alterations, namely atherosclerosis and arteriosclerosis. Whereas the former disturbs principally the conduit function and the delivery of an adequate blood flow to peripheral organs and tissues, the latter disturbs the cushioning function of large arteries, inducing an inadequate increase in systolic and pulse pressure. Arteriosclerosis represents a clinical form of accelerated ageing process and is characterized by a diffuse dilation and hypertrophy of large conduit arteries and stiffening of arterial walls. Independently from the ageing, structural changes are associated with several haemodynamic alterations such as increased in blood flow and flow velocity, and increased parietal stress due to increased arterial diameters and/or intraarterial pressure. The principal consequences of arterial stiffening are: (1) an increased left ventricular afterload with development of left ventricular hypertrophy and increased myocardial oxygen demand; (2) altered coronary perfusion and blood flow distribution; and (3) decreased perfusion reserve during haemodynamic stress. In the absence of controlled studies, it is difficult to propose therapeutic interventions aimed to prevent or treat arterial abnormalities in hypertensive patients. It has been shown that long-term administration of either calcium channel blockers and angiotensin converting enzyme inhibitors led to an improvement of vessel wall elasticity. Nevertheless, these studies did not conclude whether the improvement of elastic properties were due only to decrease in blood pressure or to alterations in intrinsic properties of arterial walls. More investigations should be necessary to investigate this important problem.

Antihypertensive effects and arterial haemodynamic alterations during angiotensin converting enzyme inhibition.

OBJECTIVE: To assess the respective roles of the anti-hypertensive and blood pressure-independent effects of angiotensin converting enzyme (ACE) inhibition in the changed arterial haemodynamics observed in hypertensive patients with end-stage renal disease (ESRD) treated by haemodialysis. DESIGN AND METHODS: Twelve hypertensive patients with ESRD were included in a double-blind, cross-over study comparing a single 20 mg dose of the ACE inhibitor quinapril versus placebo. Two study periods each of 172 h duration were separated by a 2-week placebo period. Repeated measurements of the following parameters were performed: brachial artery systolic blood pressure (SBP); diastolic blood pressure and mean blood pressure (using a mercury sphygmomanometer); carotid artery SBP and pulse pressure (by applanation tonometry); aortic stiffness (by pulse wave velocity); and the effect of arterial wave reflections in the common carotid artery (the augmentation index, by applanation tonometry). A radioimmunoassay was used to determine plasma angiotensin II levels. Quinaprilat pharmacokinetics were studied using a specific assay. Two-way (time-treatment) analysis of variance for repeated measures, analysis of covariance for two within-factors and a covariate changing with the level of the factor time (pressures measured at each time) and baseline values of the studied parameter as a second covariate were used for statistical analysis. RESULTS: Quinapril treatment induced a long-lasting decrease in arterial wave reflections, which was still observable 172 h after quinapril administration and still present after removing the effect of the decrease in blood pressure. The effect on wave reflections was associated with a more pronounced and sustained decrease in carotid SBP and pulse pressure than that in brachial SBP and pulse pressure. Quinapril administration also induced a long-lasting decrease in aortic pulse wave velocity, but this effect was entirely dependent on parallel changes in blood pressure. Arterial haemodynamic changes were not related to plasma angiotensin II or quinaprilat levels. CONCLUSIONS: The results of this controlled study indicate that, in ESRD patients, ACE inhibition results in a long-lasting, blood pressure-independent decrease in arterial wave reflections. The consequence of this was a decrease in pulsatile pressure load in the central arteries with increased aortic distensibility. The increased aortic distensibility resulted from the decrease in blood pressure. The observed arterial haemodynamic alterations suggest that ACE inhibition induced alterations in arterial wave reflections in the distal parts of the arterial tree.

Arterial calcinosis, chronic renal failure and calcium antagonism.

A progressive rise in arterial calcium content is the most characteristic age-associated alteration in the arterial wall and the decisive factor in arteriosclerotic degeneration. Experimental studies have demonstrated that calcium antagonists can prevent or retard the development of arterial calcinosis associated with vitamin D overload, hypertension or alloxan-induced diabetes. Although similar effects are more difficult to observe in humans, they have been demonstrated in patients with coronary artery disease and in patients with end-stage renal disease, which is characterised by an acceleration of the normal arterial aging process.

Arterial compliance and blood pressure.

As a result of the dual function of arteries, the conduit and cushioning functions, arterial pressure has 2 components: the steady component, characterised by mean blood pressure, and the pulsatile component, characterised by pulse pressure. Arterial compliance mostly depends on arterial intrinsic elastic properties, and is a determinant of the propagation speed of the pulse pressure wave. Decreased arterial compliance is responsible for both an increase in the incident pressure wave and the higher effect of reflected pressure waves. This increases systolic pressure and ventricular afterload, and generates left ventricular hypertrophy. Arterial structural changes that accompany the aging process result in a loss of distensibility and compliance. In essential as well as in secondary hypertension, arterial compliance is reduced, and age-related structural changes of the arterial wall are accelerated. Whether the change in arterial compliance is a passive consequence of the increase in blood pressure or is related to changes in the arterial wall structure remains unclear. Calcium antagonists improve the distensibility and compliance of large and small arteries, contributing significantly to the improvement in the management of essential and secondary hypertension.

Contributive factors to cardiovascular hypertrophy in renal failure.

Cardiovascular diseases are the leading cause of morbidity and mortality among end-stage renal disease (ESRD) patients. This is related to the accumulation of nonspecific cardiovascular risk factors in this population, aggravated by some specific features, proper to chronic uremia. The principal abnormalities observed in ESRD patients, with no history of cardiovascular disease, consist in an increased left ventricular mass and a chronic left ventricular dilation. The enlargement of the ventricular cavities is due to a chronic flow overload in which the anemia and dialysis arteriovenous fistula play a dominant role. The increase in ventricular mass is usually less pronounced than the ventricular dilation and for a given arterial pressure the ventricular mass-to-volume ratio is inadequately low. The "inadequate" cardiac hypertrophy is more frequently observed in patients with severe secondary hyperparathyroidism and results in a chronic increase in ventricular stress and oxygen consumption. On the other hand, ESRD patients with aluminum overload exhibit an increased ventricular mass which compensates for ventricular dilation. The echocardiographic indices of ventricular systolic function are normal, contrasting with a pronounced impairment of diastolic properties. The impairment of ventricular filling is in part related to the increased left ventricular mass.

Parathyroid hormone and cardiovascular effects of dihydropyridines in chronic renal failure.

We studied the influence of parathyroid gland activity on cardiovascular response to dihydropyridines (nicardipine (NIC), 80 mg/day for 4 weeks) in 20 hypertensive patients with end-stage renal failure (ESRF). Before the treatment hyperparathyroidism (HPTH) was estimated on the basis of serum parathormone (PTH), and bone histomorphometry (osteoclastic resorption surfaces (ORS), and number of osteoclasts (NO]. NIC induced a significant decrease in systolic (SAP) and diastolic (DAP) arterial blood pressure, but did not significantly change the heart rate (HR) or the SAP X HR (myocardial oxygen consumption estimate). Changes in SAP and DAP were correlated to baseline serum PTH (P less than .001), to ORS (P less than .01) and to NO (P less than .01). Furthermore, a significant decrease in blood pressure was observed only in patients with histological signs of hyperparathyroidism (ORS greater than 1%). In this subset of patients NIC induced a significant decrease in SAP X HR (P less than .02) which was correlated to PTH and histomorphometric indexes of HPTH (P less than .01). The results of the present study show that blood pressure response to dihydropyridines in ESRF is associated with parathyroid activity as judged from serum PTH and bone histomorphometry.

Cardiac hypertrophy and arterial alterations in end-stage renal disease: hemodynamic factors.

Left ventricular (LV) hypertrophy is the most common cardiovascular alteration observed in end-stage renal disease patients. LV hypertrophy results from chronic flow and pressure overload and combines features of concentric and eccentric hypertrophy. The causes of chronic flow overload are the presence of AV shunt, salt and water overload, and anemia. The pressure overload is related to alterations of physical properties of large arteries characterized by an increased arterial and aortic stiffness. The systolic function of hypertrophied ventricle is preserved, but the diastolic filling is impaired. The ventricular hypertrophy progresses over the time on hemodialysis together with a progressive worsening of both systolic and diastolic functions.

Pathophysiology of cardiovascular disease in hemodialysis patients.

Cardiovascular disease is the principal cause of morbidity and mortality in dialysis patients. The principal alterations responsible are left ventricular hypertrophy and arterial disease characterized by an enlargement and hypertrophy of arteries and the high prevalence of atheromatous plaques. Left ventricular hypertrophy is the consequence of combined effects of chronic hemodynamic overload and nonhemodynamic biochemical and neurohumoral factors characteristic of uremia. The hemodynamic overload is due to flow and pressure overload. The flow overload is tightly related to hyperkinetic circulation caused by anemia, arteriovenous fistula, or overhydration and is characterized by an enlargement of the left ventricular cavity. The pressure overload in these patients is more tightly related to abnormal geometry and function of large conduit arteries, principally the stiffening of arterial tree. The flow overload is also in large part responsible for remodeling of arterial tree, and as the heart and vessels are a coupled interactive physiological system, cardiac and vascular alterations occur in parallel, being induced to a great extent by the same hemodynamic abnormalities. The principal clinical consequences of left ventricular hypertrophy and arterial alterations are heart failure, ischemic heart disease, and peripheral artery disease. Cardiovascular alterations are only partly reversible, and efforts should be directed toward early prevention.

Arterial compliance in hypertension.

The arterial system has two distinct functions: to deliver an adequate supply of blood to body tissues (conduit function) and to smooth the pulsations resulting from intermittent ventricular ejection. A reduction in lumen diameter leads to an abnormal conduit function and has adverse effects (ischaemia) downstream, whilst stiffening of the vessel wall results in abnormal cushioning function and has adverse effects on the heart (increased ventricular stress and myocardial oxygen consumption). Arterial compliance, which may be evaluated using propagative models of the pulse and pulse wave velocity (PWV), is significantly reduced in hypertensive patients compared with age-matched control subjects. The use of antihypertensive drugs is not always associated with differing effects on arterial compliance. Whereas calcium channel blockers and ACE inhibitors decrease PWV for an equivalent fall in blood pressure, dihydralazine-like drugs are unable to modify PWV. This suggests that effects on the structure and function of the heart and blood vessels are dissociated from blood pressure lowering effects.

Effects of antihypertensive agents on carotid pulse contour in humans.

The aim of this study was to assess the influence of antihypertensive agents on arterial wave reflections (AWR) and carotid pulse pressure (PP) in humans. Twenty patients with hypertension (predominantly systolic) were studied. After one month of placebo therapy they were randomly assigned to atenolol (At) 50 mg/day or to nitrendipine (Ni) 40 mg/day. Carotid pressure waveform was recorded noninvasively by applanation tonometry using a Millar micromanometer-tipped probe. Arterial wave reflections were quantified as the ratio of the height of the late systolic peak (delta P) to the total height of carotid pulse pressure wave as an augmentation index (delta P/PP). Travel time of the reflected wave (delta tp) was timed from the foot of the pressure wave to the foot of the late systolic peak. Atenolol and Ni were equally effective in reducing sphygmomanometric brachial artery blood pressure (BP). Whereas At (p < 0.05) and Ni (p < 0.01) reduced the carotid PP, Ni (p < 0.01) but not At significantly reduced delta P/PP. Both agents increased the delta tp (p < 0.01) and decreased aortic PWV (p < 0.01). Nitrendipine was associated with a decrease in left ventricular ejection time (LVET) (p < 0.01), while At increased heart period (p < 0.01) and LVET. The LVET/delta tp ratio decreased after Ni (from 3.25 +/- 0.77 to 2.42 +/- 0.73; p < 0.01) but did not change after At. The study shows, that for the same effect on peripheral BP, Ni has a more pronounced effect on pressure wave in central arteries, resulting from an improvement in the timing between the ventricular ejection and AWRs.

Cardiovascular disease in renal failure.

Cardiovascular disease is prevalent in patients with chronic kidney disease and may account for 50% of all deaths. Left ventricular hypertrophy is the most frequent cardiac alteration in end-stage renal disease (ESRD) patients. It is due to a combination of hemodynamic and humoral factors. Volume overload and pressure overload are responsible for adaptative alterations of the heart and the vessels consider as a unique functional system. These alterations are first beneficial but their persistence leads to a detrimental process, mainly cardiac dilation and failure. Treatment of the hemodynamic overload could partially stabilize or reverse this evolution.

[Pressure-independent improvement of aortic distensibility in hypertensive hemodialysed patients]. / Amélioration pression-indépendante de la distensibilité aortique chez l'hémodialysé hypertendu.

Hypertensive patients undergoing hemodialysis (HPH) have a marked impairment of their large artery distensibility and an increased cardiovascular morbidity. We investigated twelve HPH (8 males, 4 females, 53 +/- 12 years of age, +/- SD) following a single dose of an ACE inhibitor (quinapril 20 mg) comparatively to a placebo in a randomised cross over study over a week (H0 to H172). We measured repeatedly blood pressure and aortic distensibility (carotid-femoral pulse wave velocity, PWV). Statistical analysis was made through repeated measure ANOVA and repeated measure analysis of covariance because of the tight link between pressure and arterial function. Blood pressure decreased (SAP: p < 0.01, DAP: p < 0.001), and PWV was significantly improved independently of the pressure decrease. ACE inhibitor reduces blood pressure in these patients and improves large arterial function independently of the blood pressure changes.

[Cardiovascular repercussions of chronic hemodialysis]. / Retentissement cardio-vasculaire de l'hémodialyse chronique.

Coronary disease and left ventricular failure are the two main causes of death in haemodialysis patients. In these particular patients it is the accumulation of several risk factors rather than accelerated atherogenesis which seems to be the responsible for the frequent manifestations of a coronary disease which is sometimes difficult to diagnose. Independently of any cardiovascular history, the so-called "uraemic cardiopathy" is characterized by left ventricular dilatation associated with an increased myocardial mass but with a low mass/volume ratio. The systolic function is preserved whereas the ventricular diastolic compliance is altered due to the left ventricular hypertrophy.