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Biomedical subjects

G London

Publications and source records attributed to G London.

At least 19 recordsLinked to original sources

Atherosclerosis versus arterial stiffness in advanced renal failure.

Epidemiological as well as clinical studies have shown that regardless of the severity of renal impairment the cardiovascular mortality in renal disease patients is very high compared to the general population. In uremia, cardiovascular disease is a combination of atherosclerosis, characterized by the presence of highly calcified plaques, and arteriosclerosis, an arterial wall alteration in response to both hemodynamic changes and humoral modifications such as inflammation or calcium-phosphate imbalance. Vascular endothelium, recognized as a large and complex endocrine organ strategically located between the wall of the blood vessel and the blood stream, could be the link between these two processes evolving during the same course.

Arteries↗

Electrophysiological response to dialysis: the role of dialysate potassium content and profiling.

UNLABELLED: The task of dialysis therapy is, amongst other things, to remove excess potassium (K+) from the body. The need to achieve an adequate K+ removal with the risk of cardiac arrhythmias due to sudden intra-extracellular K+ gradient advises the distribution of the removal throughout the dialysis session instead of just in the first half. The aim of the study was to investigate the electrical behavior of two different K+ removal rates on myocardial cells (risk of arrhythmia and ECG alterations). Constant acetate-free biofiltration (AFB) and profiled K+ (decreasing during the treatment) AFB (AFBK) were used in a patient sample to understand, first of all, the effect on premature ventricular contraction (PVC) and on repolarization indices [QT dispersion (QTd) and principal component analysis (PCA)]. The study was divided into two phases: phase 1 was a pilot study to evaluate K+ kinetics and to test the effect on the electrophysiological response of the two procedures. The second phase was set up as an extended cross-over multicenter trial in patient subsets prone to arrhythmias during dialysis. Phase 1: PVC increased during both AFB and AFBK but less in the latter in the middle of dialysis (298 in AFB vs. 200 in AFBK). The PVC/h in a subset of arrhythmic patients was 404 +/- 145 in AFB and 309 +/- 116 in AFBK (p = 0.0028). QT interval (QTc) prolongation was less pronounced in AFBK than in AFB. Phase 2: The PVC again increased in both AFB and AFBK but less in the latter mid-way through dialysis (79 +/- 19 AFB vs. 53 +/- 13 AFBK). Moreover, in the most arrhythmic patients the benefit accruing from the smooth K+ removal rate was more pronounced (103 +/- 19 in AFB vs. 78 +/- 13 in AFBK). CONCLUSION: It is not the K+ dialysis removal alone that can be destabilizing from an electrophysiological standpoint, but rather its removal dynamics. This is all the more evident in patients with arrhythmias who benefit from the K+ profiling during their dialysis treatment.

Adult↗

[Cardioprotection: an essential component for predialysis chronic renal failure treatment].

Cardiovascular (CV) disease in uremic patients is a major concern to the nephrologist because it represents the main cause of morbidity and mortality in chronic renal failure patients, both predialysis and while on dialysis therapy. CV mortality is 3 to 20 times higher in dialysis patients than in the general population at similar age. Of note, a high prevalence of CV comorbidity is already present at start of maintenance dialysis, and is predictive of subsequent mortality on dialysis. CV disease progresses over years prior to the onset of ESRD, because risk factors develop from the early stage of chronic renal insufficiency. However, CV disease may be prevented or attenuated in patients who benefit from early, regular care of CV risk factors. Mechanisms of uremic cardiopathy, the major cause of mortality in uremic patients, are multifactorial and their effects are cumulative. Risk factors for left ventricular hypertrophy are hypertension, anemia, fluid overload and arteriosclosis, all of which are amendable by therapy. Risk factors for accelerated atherosclerosis, responsible for ischemic cardiopathy and myocardial infarction, are both common factors (e.g., hypertension, tobacco smoking and diabetes) and factors more specific for the uremic state (e.g., dyslipidemia, hyperhomocysteinemia and oxidative stress), all of which also are amendable by proper therapy. As a result, mixed hypertensive and ischemic cardiomyopathy develops, ultimately leading to cardiac failure, together with accidents resulting from valvular and arterial calcifications (favored by calcium-phosphate disorders), and from occlusion of coronary, cerebral and peripheral arteries. Cardioprotective therapy thus has become a cornerstone in the management of chronic renal failure patients, in conjunction with renoprotective therapy. Cardioprotective strategy involves optimal treatment of hypertension, anemia, fluid overload, dyslipidemia, hyperhomocysteinemia and calcium-phosphate disorders, and smoking cessation. To achieve a maximal efficacy, such treatment has to be initiated as early as possible in the course of renal failure. Because of its complexity, the integrated combined nephrotective and cardioprotective therapy requires early and sustained guidance by a nephrologist throughout the whole predialysis period.

Anemia↗

[Combination of low-dose perindopril/indapamide versus atenolol in the hypertensive patient. Effects on systolic pressure and arterial hemodynamics. REASON Study].

In hypertension, consideration of systolic blood pressure (SBP) and pulse pressure (PP) is now well recognized from epidemiological and therapeutical points of view, after numerous years of interest in only diastolic blood pressure. SBP, and also PP, are tightly linked to mechanical properties of large arteries. It is now possible to investigate precisely, with very good repeatability, these mechanic properties. The REASON study is an international multicenter randomised, controlled, parallel-groups study in essential hypertensives. The very low dose perindopril/indapamide combination (Per/Ind: 2 mg/0.625 mg) was compared with atenolol (50 mg) for a 12-month active treatment period in terms of blood pressure reduction efficiency and change in large artery hemodynamics to attempt to relate changes in pressure and changes in arterial mechanics. 471 patients suffering from hypertension were included, 406 benefitted from the treatment for one year (per-protocol analysis) and 96 benefitted from arterial investigations (pulse wave velocity and aortic wave reflection with applanation tonometry). Changes in brachial and central SBP and PP were higher with Per/ind than with atenolol. The reduction in pulse wave velocity was similar with both drugs, but aortic wave reflections were more reduced with Per/Ind than with atenolol. The very low dose perindopril/indapamide decreases SBP and PP to a larger extent than does a betablocker after a 12-month treatment. Changes in arterial mechanics, non invasively measured, were the same (pulse wave velocity) or in favour of Per/Ind vs atenolol (higher reduction in aortic wave reflection, with higher reductions in central systolic and pulse pressures).

Atenolol↗

[Measurement of the carotid intima-media thickness. An innovative technique for assessing cardiovascular risk].

ASSESSMENT OF CARDIOVASCULAR RISK: Measurement of the intima-media thickness in the carotid artery is optimized by coupling high-resolution ultrasonography with automatic data processing systems, allowing improved precision. Although the optimal site of measurement remains controversial (common carotid, bifurcation, internal carotid), there appears to be a consensus on need for bilateral automatic measurement. The intima-media thickness is considered a marker of atheromatous disease and its diffusion. This parameter probably integrates the deleterious effect of different cardiovascular risk factors accumulated over decades. In addition, several prospective observation studies have reported a positive relationship between measurement of the intima-media thickness of the carotid artery and risk of cardiovascular events (myocardial infarction and stroke). DETECTION AID: Although the results issuing from epidemiology observation studies are still too preliminary, to evaluate the positive and negative predictive value for occurrence of clinical events in relation to different levels of thickness, this simple rapid and noninvasive measurement could be a useful tool for subjects with high cardiovascular risk. PERSPECTIVES: Measurement of arterial parameters, determined by high-resolution ultrasonography, will probably shortly become an integral part of the evaluation strategies for cardiovascular risk. Future comparative studies will provide an assessment of the comparative predictive value of these different parameters (quantitative structural analysis versus quantitative and qualitative analysis of the structure versus structural and functional analysis of the arteries).

Cardiovascular Diseases↗

Pathophysiology of cardiovascular damage in the early renal population.

In renal disease, mechanisms available to compensate for the reduced haemoglobin levels associated with anaemia include increased oxygen extraction from peripheral tissues and, primarily, increased blood flow and changes in blood flow distribution. Haemodynamic changes induced by anaemia include decreases in blood viscosity, peripheral vascular resistance and oxygen delivery, and an increase in sympathetic activity. The overall effect of anaemia is a chronic increase in cardiac output and cardiac work. Under normal conditions, the increased cardiac work and blood flow associated with anaemia results in adaptive left ventricular hypertrophy (LVH)/remodelling and adaptive arterial hypertrophy/remodelling. However, under uraemic conditions these changes lead to maladaptive hypertrophy and arteriosclerosis. In end-stage renal disease (ESRD) patients, increases in both left ventricular end-diastolic volume and mass are related to decreases in haemoglobin. Therefore, LVH progresses in parallel with changes in haemoglobin level and is associated with decreased survival in ESRD patients receiving renal replacement therapy. In conclusion, anaemia is a contributory factor to LVH in renal disease and cardiovascular damage starts at an early stage. Therefore, early intervention to treat anaemia in these patients can prevent or delay this damage.

Anemia↗

[Cardiac anomalies in chronic renal failure].

PRINCIPAL CARDIOVASCULAR COMPLICATIONS IN END STAGE RENAL DISEASE: Cardiovascular diseases are the leading causes of morbidity and mortality in end stage renal disease patients. Very often, complications observed are left ventricular hypertrophy and various forms of arterial degenerative lesions involving coronary arteries, less frequently pericarditis and calcifying valvulopathy are diagnosed. THE REASONS ARE COMPLEX: Risk factors can be either specific of uremia per se such as anemia, overhydration, fistula or the same as in the general population. Hemodynamic alterations including tensile stress or blood flow play a major role associated to various locally or generally generated substances whose role remains currently to be determined. THEIR TREATMENTS: Treatments of cardiovascular complications are not specific in this end stage renal disease population but are more often the treatment of the etiology: reduction of fistula blood flow, increase of hemoglobin, best control of weight gain between two hemodialysis sessions or blood pressure control.

Anemia↗

[Hypertension and pulse pressure].

Pulse pressure is an independent cardiovascular risk factor, mainly for myocardial infarction. The predictive value of pulse pressure is observed not only in hypertensive subjects above 50 years but also in patients with congestive heart failure, myocardial dysfunction and recurrent myocardial infarction. Treated hypertensive subjects are also at risk since, in many cases, diastolic blood pressure is normalized whereas systolic blood pressure remains elevated, thus leading to the picture of isolated systolic hypertension despite antihypertensive treatment.

Aged↗

[Evaluation of the individual absolute cardiovascular risk. A mathematical equation and/or arterial measurement?].

The latest recommendations about the management of cardiovascular risk factors take into account not only the level of risk factor but also the global risk profile of the patient. The reference for the calculated estimation of absolute cardiovascular risk remains the Framingham equation. Nevertheless, this estimation has a number of operational and conceptual limitations such as geographical and historical validity and its application to individual cases. Different results in the medical literature suggest that parameters of arterial structure or function measured simply, such as arterial rigidity, could be closely related to the level of individual cardiovascular risk by the integration of the deleterious effects of different vascular risk factors over decades of exposition. They could then be better predict cardiovascular effects than the result of a mathematical equation which only integrates some of the risk factors at a given point in time. These simple, rapid and non-invasive measurements could help identify subjects at high cardiovascular risk and also help the clinician in the orientation of preventive measures in subjects with cardiovascular risk factors.

Adult↗

Further study on the carotid baroreflex system in the cardiovascular deconditioning induced by head-down tilt.

HYPOTHESIS: The responses of the carotid baroreflex and of the peripheral sympathetic system to stimulations induced by either lower body negative pressure (LBNP -40 mmHg) or cold pressor test were investigated in eight volunteers before and after 48 h in the -6 degrees head-down tilt (HDT). METHODS: Geometry (diastolic diameter and pulsatile distention) and dynamics (cross-sectional compliance and tangential tension) of the bulb and the common carotid artery were investigated using ultrasonic devices, echotracking and aplanation tonometry. The activity of the sympathetic system was evaluated through measurements of plasma concentrations of catecholamines (CAs) and 3,4-dihydroxyphenyl glycol (DHPG). RESULTS: During LBNP -40 mmHg, the pulsed tangential tension was decreased and the pressure amplification, induced by the reflexion of the pressure wave, was increased with no difference between before and after HDT. Since cross-sectional compliance and distensibility coefficient remained unchanged and the carotid contour of the waveform unaltered, it is concluded that the carotid reflexogenic area reads the same message during LBNP whether the cardiovascular system was deconditioned or not. Nonetheless, during LBNP after 48 h HDT, the heart rate accelerated faster and CAs and DHPG concentrations increased out of proportion, suggesting that the peripheral sympathetic activity was more reactive after HDT than before. Finally, forearm vascular resistances were measured in response to cold pressor test; they increased in the same proportion after HDT when compared with before. CONCLUSION: Results indicate that the carotid baroreflex and the peripheral sympathetic system were not deficient after 48 h HDT.

Adolescent↗

Increased stiffness of radial artery wall material in end-stage renal disease.

The incremental elastic modulus (Einc), which is the slope of the relationship between stress and strain of arteries, is a marker of vascular wall material stiffness. Isobaric Einc is reduced at the site of the radial artery in patients with essential hypertension and increased at the site of the common carotid artery in subjects with end-stage renal disease (ESRD). Whether the changes in Einc are influenced by the topography of the vessels, the composition of the arterial wall, and/or by the presence of ESRD is largely ignored. Radial artery Einc was measured in 19 patients with ESRD and compared with the Einc of 89 subjects with essential hypertension and 20 normotensive control subjects. Transcutaneous measurements of radial artery internal diameter and wall thickness (echo-tracking device) and digital pulse pressure (Finapres) were allowed to calculate Einc under operational (ie, at the mean arterial pressure of each group) and isobaric (100 mm Hg) conditions, as well as for a given wall stress. Internal diameter and pulsatile changes in diameter were identical in the three groups. Wall thickness and mean blood pressure were significantly elevated in subjects with hypertension but not in ESRD patients. Circumferential wall stress was identical in the three groups. For the same operational wall stress, and therefore at the operational mean arterial pressure of each group, Einc (kPa x 10[3]) was increased in patients with ESRD (5.53+/-4.0 versus 3.3+/-2.4 in control subjects; P<.05) and normal in subjects with essential hypertension (3.87+/-4.0). Under isobaric conditions, Einc was also significantly lower in subjects with hypertension and elevated in patients with ESRD. Thus, at the site of a medium-sized muscular artery constantly devoid of atherosclerosis, the stiffness of wall material is increased in patients with ESRD. The demonstrated alterations of the arterial wall are independent of the level of blood pressure and tensile stress and should be related to the status ESRD.

Blood Pressure↗

Remodeling of the radial artery in response to a chronic increase in shear stress.

Chronic changes in large artery blood flow rates induce corresponding adjustments in arterial diameter, but little is known about structural adaptations of the vessel wall in humans. We used a high-resolution echo-tracking system to measure radial artery internal diameter, wall thickness, and mean blood flow on both arms of 11 patients with end-stage renal disease. Measurements were performed on the wrist side of the arteriovenous fistula. The contralateral radial artery was investigated as control. Wall cross-sectional area, circumferential wall stress, and mean wall shear stress were calculated. Results indicate a sixfold increase in blood flow on the side of the arteriovenous fistula compared with the control side, with a 1.4-fold increase in internal diameter. The diameter enlargement was sufficient to normalize wall shear stress. Changes in diameter were not associated with arterial wall hypertrophy because wall cross-sectional area was not increased and rather suggest a "remodeling" of the arterial wall. For the same level of blood pressure, circumferential wall stress was increased on the side of the arteriovenous fistula. These results suggest that the structural adaptations of the arterial wall to a chronic increase in blood flow normalize wall shear stress and overcome stretch-induced changes in the particular circumstance of arteriovenous fistula.

Adult↗

Aortic distensibility in normotensive, untreated and treated hypertensive patients.

BACKGROUND: Compared with normotensive subjects, untreated hypertensive patients show a decrease of their aortic distensibility. Whether antihypertensive treatment, by reducing blood pressure and changing functional and/or structural abnormalities of the arterial wall, may prevent or reverse the arterial damage due to the accelerated ageing process remains unclear. The objective of the present study was to determine, using a cross-sectional approach, whether aortic distensibility as measured by pulse wave velocity, in treated hypertensive patients whose diastolic blood pressure had been normalised for several months, was significantly improved over that of untreated hypertensive patients. METHODS: Carotid femoral pulse wave velocity was measured in 124 normotensive subjects and 388 hypertensive patients. The latter group included 164 treated patients with well controlled diastolic blood pressure and 224 untreated hypertensive subjects. The three groups did not differ in other cardiovascular risk factors. RESULTS: In each group there was a significant relationship between age and pulse wave velocity. When compared with untreated hypertensives, treated hypertensives with well controlled diastolic blood pressure had significantly lower blood pressure and pulse wave velocity according to age. However, although diastolic blood pressure of well controlled hypertensives was not significantly different from that of normotensive subjects, the aortic distensibility of the controlled hypertensives remained reduced showing two characteristics: a faster increase in pulse wave velocity with age and a negative relationship with HDL-cholesterol. CONCLUSION: These results suggest that long-term antihypertensive treatment and control of blood pressure using only diastolic blood pressure criteria may not fully reverse arterial alteration associated with hypertensive vascular disease.

Adolescent↗

The effect of haemodialysis on the pharmacokinetics of perindoprilat after long-term perindopril.

We have studied the pharmacokinetics of perindoprilat, the active metabolite of perindopril, in 7 hypertensive patients undergoing haemodialysis after short-term and long-term (1 month) perindopril. We also measured angiotensin-converting enzyme activity. Each subject took 2 mg of perindopril after a 4-hour haemodialysis. Serial blood samples were obtained each hour during dialysis and between dialysis (7 samples over 44 h). Perindoprilat steady state was reached within 5 haemodialysis sessions. There was a high degree of angiotensin converting enzyme inhibition after the first dose. Administration for 1 month did not modify the time to peak perindoprilat concentration but significantly increased the mean maximal concentration: 10.2 versus 26.8 ng.ml-1. The mean accumulation ratio was 3.5. The mean reduction in perindoprilat concentration after dialysis was greater than 50%. Perindoprilat haemodialysis clearance was 62 ml.min-1 after the first administration and 72 ml.min-1 after 1 month. Tolerance of perindopril was good throughout the study. Treatment can be begun with 2 mg of perindopril after haemodialysis in hypertensive patients undergoing haemodialysis.

Adult↗

Response to vaccination against tetanus in chronic haemodialysed patients.

We studied the response to vaccination against tetanus and the changes in the antibody titers 6 months after this vaccination in 66 haemodialysed patients with chronic renal failure. We also investigated the factors that may affect the quality of this immune response. After the booster injection 96.5% of patients had antitetanus antibody titres considered to be protective (0.06 HU/ml). However, the titre of these antibodies rapidly declined and after 6 months, only 62% of the haemodialysed patients had a titre greater than 0.06 HU/ml. Among the different factors considered, only age significantly impaired or reduced the immune response. In addition, the acquisition of protection against tetanus was independent of the response to vaccination against hepatitis B in the same subjects. This study showed the efficacy and safety of vaccination against tetanus in hemodialysed patients, though the antibody titres should be assayed several months after vaccination to confirm the persistence of immunization.

Adolescent↗