Panagiotis I. Georgianos

Effects of Low-Dose Atorvastatin on Arterial Stiffness and Central Aortic Pressure Augmentation in Patients With Hypertension and Hypercholesterolemia

BACKGROUNDnExperimental and clinical data suggest that statins exert anti-inflammatory and antiproliferative actions on vasculature beyond their lipid-lowering properties. Whether these pleiotropic effects of statins translate into a beneficial effect on arterial stiffness is not clear. This study aimed to evaluate the potential effects of low-dose atorvastatin treatment on arterial stiffness and central arterial pressure waveforms in patients with mild hypertension and hypercholesterolemia.nnnMETHODSnIn a double-blind, randomized, placebo-controlled fashion, 50 hypertensive and hypercholesterolemic patients were allocated to receive 10 mg of atorvastatin or placebo for 26 weeks. Arterial stiffness was assessed by aortic pulse-wave velocity (PWV) using a Sphygmocor device. Central arterial pressure waveform parameters were estimated by radial artery applanation tonometry. Heart rate-adjusted augmentation index (AIx(75)) was used as measure of wave reflections.nnnRESULTSnAt study end, aortic PWV (9.0 ± 1.5 vs. 10.9 ± 2.6 m/sec; P < 0.001) and AIx(75) (24.9% ± 9.7% vs 28.8% ± 11.8%; P < 0.001) were significantly lower in the atorvastatin group than that placebo group. Furthermore, decreases in central aortic systolic blood pressure and pulse pressure were evident at study-end with atorvastatin but not with placebo (130 ± 8 vs. 138 ± 6 mm Hg, P < 0.001; 48 ± 7 vs. 53 ± 6 mm Hg, P < 0.05, respectively). Atorvastatin-induced reductions in aortic PWV during follow-up showed significant associations with changes in AIx(75) and central aortic systolic blood pressure and pulse pressure.nnnCONCLUSIONSnThis study shows that low-dose atorvastatin treatment improves arterial stiffness and exerts a reduction on central aortic pressures. These effects may represent a potential mechanism of cardiovascular risk reduction observed with statin use.nnnCLINICAL TRIAL REGISTRATIONnClinicalTrials.gov Database Identifier Number: NCT01126684.

Hemodialysis Reduces Augmentation Index but Not Aortic or Brachial Pulse Wave Velocity in Dialysis-Requiring Patients

Background/Aims: Arterial stiffening characterizes the vasculature of end-stage renal disease (ESRD) patients and is a strong predictor of their cardiovascular morbidity and mortality. Previous studies evaluating the effect of hemodialysis on large artery elasticity gave contradictory results. This study aimed to investigate the impact of hemodialysis on arterial stiffness and wave reflections on chronic hemodialysis patients. Methods: A total of 51 stable ESRD patients on maintenance hemodialysis were evaluated before and after the first and second dialysis session of the week. Arterial stiffness was assessed by measuring aortic and brachial pulse wave velocity (PWV). Central arterial pressure waveform parameters were estimated by radial artery applanation tonometry. Heart rate-adjusted augmentation index [AIx(75)] was used as measure of wave reflections. Results: During both dialysis sessions systolic blood pressure (SBP) and pulse pressure (PP) at brachial artery and central aorta were reduced. AIx(75) was decreased in first and second weekly dialysis session (27.5 ± 1.2 vs. 21.0 ± 1.5, p < 0.001 and 24.7 ± 1.2 vs. 20.5 ± 1.5, p < 0.001, respectively). In contrast, aortic and brachial PWV remained unchanged during both dialysis sessions. Changes in AIx(75) during hemodialysis were associated with changes in central aortic SBP, PP and ejection duration. Conclusions: This study shows that hemodialysis does not acutely affect arterial stiffness, but reduces wave reflections from periphery. This dissociation between effects of hemodialysis on PWV and AIx(75) may reflect differential impact on large and small branches of the arterial tree.

Diverse effects of interdialytic intervals on central wave augmentation in haemodialysis patients

BACKGROUNDnIncreased arterial stiffness is a common finding and independent predictor of mortality in end-stage renal disease (ESRD) patients. A long interdialytic interval was associated with increased risk of cardiovascular death in patients receiving conventional haemodialysis (HD). This is the first study to examine the effects of a long (3-day) versus short (2-day) interdialytic period on arterial elasticity in HD patients.nnnMETHODSnSeventy ESRD patients receiving standard HD three times per week were studied at the start and end of a 3-day and a 2-day interdialytic interval. At each time point, applanation tonometry of peripheral arteries was performed to assess arterial stiffness and wave reflection parameters. Aortic and brachial pulse wave velocities (PWV) were recorded as measures of arterial stiffness and augmentation index (AIx) as a measure of wave reflections.nnnRESULTSnAIx, heart-rate-adjusted AIx and augmentation pressure were significantly increased during both interdialytic intervals, whereas aortic and brachial PWVs remained unchanged. The interdialytic increases in all the three AIx parameters were significantly higher during the 3-day interval in comparison to the 2-day interval (P < 0.001 for all comparisons). In contrast, no significant differences in interdialytic changes of aortic (P = 0.355) and brachial (P = 0.319) PWVs were noted between the two intervals. Mixed linear model analysis revealed that central aortic systolic blood pressure (SBP) and body weight, but not aortic or brachial PWV, were independent determinants of the change in heart-rate-adjusted AIx throughout the study.nnnCONCLUSIONSnAIx is increased between HD sessions, whereas arterial elasticity is not. This interdialytic increase in central wave augmentation is more pronounced during the 3-day interval, suggesting a mechanism possibly involved in the elevated cardiovascular risk of HD patients at this time point.

Comparative Epidemiology of Resistant Hypertension in Chronic Kidney Disease and the General Hypertensive Population

Until a few years ago, information regarding the epidemiology of resistant hypertension was obtained from indirect sources, such as cross-sectional studies on hypertension control in large cohorts from tertiary hypertension centers and outcome trials in hypertension. During the past 3 years, however, large population-based studies have provided direct epidemiologic data on resistant hypertension and estimated its prevalence at 8% to 12% of adult patients with hypertension. Chronic kidney disease (CKD), in particular, has been long considered a frequent underlying cause of resistant hypertension, however, recently, direct epidemiologic data for this entity in patients with CKD were brought to light again, suggesting an even higher prevalence of resistant hypertension (approximately 20%-35%) among such individuals. Furthermore, recent prospective cohort studies have suggested incident resistant hypertension to be associated with increased cardiovascular and renal risk in both the general hypertensive population and patients with CKD. This article discusses currently available data on epidemiology of resistant hypertension, providing a comparative overview of its prevalence, incidence, and prognosis in these two populations.

Hypertension in Dialysis Patients: Clinical Epidemiology, Pathogenesis, Diagnosis, and Treatment

In patients with end-stage renal disease (ESRD), hypertension is common, difficult to diagnose, and often poorly controlled. Blood pressure (BP) recordings obtained before or after hemodialysis display a flat or even U-shaped association with cardiovascular events or survival, but this may reflect their poor accuracy, since elevated BP recorded with home or ambulatory BP monitoring is directly associated with shorter survival. Sodium and volume excess is the prominent pathogenic mechanism of hypertension in dialysis patients, but non-volume-mediated pathways, such as activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, structural arterial wall alterations, endothelial dysfunction, sleep apnea, and the use of particular medications like erythropoietin-stimulating agents (ESAs), are also involved in the complex mechanistic background of hypertension in these individuals. Since sodium and volume excess is the most important cause, non-pharmacologic strategies such as dietary sodium restriction, individualized dialysate sodium prescription, and gradual dry-weight reduction should be the initial therapeutic approaches to achieve BP control. If hypertension remains poorly controlled, pharmacologic therapy should be commenced, taking into consideration the particular characteristics of antihypertensive agents. In this chapter, we discuss the epidemiology, pathogenesis, diagnosis, and treatment of hypertension among patients on dialysis in the light of currently available evidence.

The Effect of Convective Dialytic Modalities on Arterial Stiffness in End-Stage Renal Disease Patients

Among end-stage renal disease (ESRD) patients receiving hemodialysis, increased arterial stiffness is an independent cardiovascular risk predictor. Over the past few years, arterial stiffness attenuation has been increasingly recognized as a novel therapeutic target toward cardiovascular risk reduction in the dialysis population. Structural alterations related to the long-term arteriosclerotic process are difficult to modify; with the exception of blood pressure (BP)-lowering, there are no other therapeutic interventions with well-documented benefits in delaying the progression of arteriosclerosis among dialysis patients. Enhanced clearance of middle-to-high molecular weight solutes by combining convective and diffusive transport through hemodiafiltration and the associated benefits on microvascular endothelial function have generated the hypothesis that convective dialytic modalities may be advanta‐ geous in improving large-artery stiffness. This notion is supported by some clinical studies showing that switching ESRD patients from low-flux hemodialysis to highefficiency on-line hemodiafiltration was associated with significant reduction in arterial stiffness. These beneficial effects, however, were not confirmed in a recent subanaly‐ sis of the CONvective TRAnsport STudy (CONTRAST) trial. In this chapter, we summarize the currently available evidence on the effect of hemodiafiltration versus hemodialysis on arterial stiffness, discussing also the potential clinical implications of this effect.