常染色体显性多囊肾病患者动脉形态学、力学与部分功能性参数研究

目的 应用超声技术检测肾功能正常不同血压的常染色体显性多囊肾病(ADPKD)患者肱动脉与颈动脉形态学、力学与功能性部分参数，探讨ADPKD患者是否早期即存在心血管病危险因素。 方法 应用高频超声分别探测ADPKD高血压、ADPKD正常血压、原发性高血压及正常对照4组人群的肱动脉内皮依赖性舒张功能、颈动脉内中膜厚度(IMT)及颈动脉扩张性。 结果 (1) ADPKD高血压组反应性充血后肱动脉内径变化显著小于原发性高血压组和ADPKD正常血压组，而ADPKD正常血压组显著小于正常对照。(2) ADPKD高血压组和原发性高血压组IMT均显著高于ADPKD正常血压组和正常对照，而ADPKD正常血压组IMT也显著高于正常对照组。(3)ADPKD高血压组、原发性高血压组与ADPKD正常血压组、正常对照组比较，横断面扩张性(CD)和弹性模量增值(Einc)差异有统计学意义，而ADPKD正常血压组与正常对照组间差异也有统计学意义。 结论 肾功能正常的ADPKD高血压和正常血压患者存在显著的内皮功能受损、IMT增加和颈动脉扩张性降低，提示ADPKD早期就可能发生动脉粥样硬化。     

Viscoelastic properties of normal and atherosclerotic carotid arteries.

BACKGROUND: remodelling of the arterial wall occurs with ageing, even in the absence of atherosclerotic risk factors. With increasing age, arteries dilate, thicken, and get stiffer. The aim of this study was to correlate carotid artery stiffness with wall thickness and plaque presence between healthy individuals and patients with early and advanced atherosclerosis. METHODS: twenty healthy volunteers, 40 carotid segments and 90 patients, 174 carotid segments, with vascular disease were included in the study. The carotid artery was imaged longitudinally and measurements of the intimal-medial thickness (IMT) and plaque were obtained. Systolic and diastolic blood pressures were taken from each arm. The carotid artery stiffness (pressure-strain elastic modulus, Ep) was calculated in all sites from the changes in pressure and diameter. M-mode was used to detect the diameter change (systolic to diastolic) over five cardiac cycles. RESULTS: in the healthy volunteers there was no evidence of plaque or increased IMT. The mean IMT was significantly higher in the patients compared to control (0.83+/-0.27 mm vs. 0.54+/-0.08 mm, p <0.0001). The IMT had a poor correlation with Ep at lower thickness (r=0.24, p=0.08) but this association became stronger with increasing thickness (r=0.62, p<0.001). Arterial segments with an IMT 5 0.88 mm became significantly stiffer compared to the controls (p<0.001) and to patients with an IMT<0.88 mm (p <0.01). Carotid Ep was markedly greater in arterial segments with plaques than in those with increased IMT (p <0.001) and the controls (p<0.0001). CONCLUSIONS: carotid wall areas with small increase in IMT have a poor correlation with carotid artery stiffness. The carotid stiffness increases in areas with marked wall thickening and particularly in segments with plaque. The simultaneous study of vessel-wall elastic behaviour with IMT and plaque changes may increase our understanding of atherosclerotic progression and wall remodelling.     

Altered morphologic properties of large arteries in children with chronic renal failure and after renal transplantation

Increased intima-media thickness of the carotid arteries (cIMT) has been found in young adults with childhood-onset chronic kidney disease (CKD). The disease stage at which these patients first develop abnormalities of arterial texture is unknown. The objective of this study was to determine the onset and character of arterial changes in children aged 10 to 20 yr with different stages of CKD and to identify risk factors for early arteriopathy. High-resolution ultrasonography was conducted of common cIMT and femoral superficial artery IMT. Fifty-five children with stages 2 to 4 CKD (GFR 51 +/- 31 ml/min per 1.73 m2), 37 on dialysis, and 34 after renal transplantation (Rtx; GFR 73 +/- 31 ml/min per 1.73 m2) were studied. Control subjects were 270 healthy children, matched for age and gender. Compared with control subjects, cIMT, femoral superficial artery IMT (both as absolute values and as SD score of median of normal value), wall cross-sectional area, and lumen cross-sectional area of carotid artery were significantly increased in all patient groups and most markedly abnormal in dialysis patients. cIMT in CKD and Rtx patients was significantly lower in comparison with dialysis patients. cIMT correlated with mean past serum Ca x P product, the cumulative dose of calcium-based phosphate binders, and the time-averaged mean calcitriol dose. The cumulative phosphate binder intake, time-averaged Ca x P product, and young age were independent predictors of an increased cIMT. In children with CKD, thickening of IMT occurs early in the course of disease and is most marked in dialyzed patients. The changes may be partly reversible after Rtx.     

Urinary albumin excretion associated with arterial wall stiffness rather than thickness in type 2 diabetic patients

BACKGROUND: A close relationship has been reported between microalbuminuria and atherosclerosis in patients with diabetes mellitus. The aim of this study was to determine which of the 2 aspects of atherosclerosis, arterial thickening or stiffness, has more effect on levels of microalbuminuria in type 2 diabetic patients. METHODS: Twenty-four-hour urine samples of 167 Japanese type 2 diabetic patients (aged 58 +/- 12 years) without overt proteinuria were collected for quantitative analysis of urinary albumin excretion (UAE). Arterial stiffness was evaluated by measuring aortic pulse-wave velocity (PWV), and arterial thickness was measured by the intima-media thickness (IMT) of the carotid artery. RESULTS: The aortic PWV and carotid IMT were both significantly positively correlated with logarithmically transformed UAE (r=0.269, p<0.001; and r=0.188, p<0.05, respectively). Although there was a significant positive correlation between aortic PWV and carotid IMT (r=0.263, p<0.001), multiple regression analyses demonstrated that aortic PWV, but not carotid IMT, was a significant factor associated with log UAE, independent of other confounding factors (R2=0.246, p<0.0001). CONCLUSIONS: These results suggest that increased arterial stiffness, but not arterial thickness, is significantly associated with the increase in albuminuria, and that decreased arterial distensibility due to increased stiffness caused by atherosclerosis may be related to the progression of diabetic nephropathy in type 2 diabetic patients.     

A randomized, double-blind study of valsartan versus metoprolol on arterial distensibility and endothelial function in essential hypertension.

BACKGROUND: Antihypertensive drugs may have differential, pressure-independent effects on hypertension-associated alterations of arterial function. We compared the effects of a 12-week therapy with the AT(1)-receptor antagonist valsartan (Val) versus the beta-blocker metoprolol (Met) on arterial stiffness and endothelial function in mildly hypertensive patients at rest and during generalized sympathetic stimulation. METHODS: Sixty-eight patients (37 male, 31 female, 46 +/- 6 years) were randomized to Val (80-160 mg/d) or Met (50-100 mg/d). Effects of therapy on endothelial function, brachial and carotid artery distensibility coefficients, pulse wave velocity, carotid intima-media thickness and elastic modulus were assessed at rest and during the cold pressor test. RESULTS: Fifty-two patients were available for per protocol analysis. Blood pressure was comparably reduced in both treatment groups. Effects on endothelial function and large artery elastic wall properties did not differ significantly between the two antihypertensive treatment regimens. Trends did not differ significantly between groups for any parameter including carotid intima-media thickness and elastic modulus. CONCLUSION: Short-term treatment with Val and Met had similar effects on large artery functional vessel wall properties in a population of mildly hypertensive patients.     

Arterial remodeling associates with CKD progression

In CKD, large arteries remodel and become increasingly stiff. The greater pulsatile pressure reaching the glomerulus as a result of increased aortic stiffness could induce renal damage, suggesting that the stiffening and remodeling of large arteries could affect the progression of CKD. We measured carotid-femoral pulse wave velocity, aortic pressure and carotid remodeling and stiffness parameters in 180 patients with CKD (mean measured GFR, 32 ml/min per 1.73 m(2)) and followed them prospectively for a mean of 3.1 years. During follow-up, carotid stiffness significantly increased (+0.28 ± 0.05 m/s; P<0.0001) but aortic stiffness did not. Carotid intima-media thickness decreased significantly during follow-up and the internal diameter of the carotid increased, producing increased circumferential wall stress (+2.08 ± 0.43 kPa/yr; P<0.0001). In a linear mixed model, circumferential wall stress significantly associated with faster GFR decline after adjustment for risk factors of cardiovascular disease and progression of CKD. In a multivariable Cox model, carotid circumferential wall stress and pulse pressure independently associated with higher risk for ESRD. None of the arterial stiffness parameters associated with progression of CKD. In conclusion, maladaptive remodeling of the carotid artery and increased pulse pressure independently associate with faster decline of renal function and progression to ESRD.     

Estimated glomerular filtration rate and urinary albumin excretion are independently associated with greater arterial stiffness: the Hoorn Study

Mild renal insufficiency is a risk factor for cardiovascular disease (CVD). Both a decline in GFR and (micro)albuminuria are associated with greater cardiovascular mortality. In ESRD, arterial stiffness, an important cause of CVD, is known to be greater, but few data exist in individuals with mild renal insufficiency or microalbuminuria. This study investigated the association of impaired renal function expressed as lower GFR or greater urinary albumin excretion with arterial stiffness. In a population-based study in 806 individuals (402 men), mean age 68 yr (range 50 to 87), peripheral arterial stiffness (by compliance and distensibility of the carotid, brachial, and femoral arteries and by the carotid elastic modulus [E(inc)]) and central arterial stiffness (by total systemic arterial compliance, carotid-femoral transit time, and aortic augmentation index) were measured ultrasonically. GFR was estimated (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula. Urinary albumin excretion was expressed as urinary albumin/creatinine ratio (UACR). eGFR was 60.6 +/- 11.1 ml/min per 1.73 m(2). Median UACR was 0.57 mg/mmol (range 0.1 to 26.6). After adjustment for age, mean arterial pressure (MAP), gender, and glucose tolerance status (GTS), each 5-ml/min per 1.73 m(2) lower eGFR was associated with a lower distensibility coefficient of the carotid (regression coefficient beta -0.20 10(-3)/kPa; 95% confidence interval [CI] -0.34 to -0.07 10(-3)/kPa) and brachial artery (-0.15 10(-3)/kPa; 95% CI -0.28 to -0.03 10(-3)/kPa) and a greater carotid E(inc) (0.02 kPa; 95% CI 0.0004 to 0.04 kPa). No statistically significant association was found of eGFR with other arterial stiffness indices. After adjustment for age, MAP, gender, and GTS, a greater UACR (per quartile) was associated with a greater E(inc) (0.03 kPa; 95% CI 0.001 to 0.07 kPa) and a trend to a lower distensibility coefficient (-0.24 10(-3)/kPa; 95% CI -0.49 to 0.02 10(-3)/kPa) of the carotid artery. After adjustment for age, MAP, gender, and GTS, a greater UACR (per quartile) was in addition associated with a shorter carotid-femoral transit time (-1.67 ms; 95% CI -3.24 to -0.10 ms). These associations were not substantially changed by mutual adjustment for eGFR and UACR. In individuals with mild renal insufficiency, both a lower eGFR and a greater albumin excretion, even below levels that are considered to reflect microalbuminuria, are independently associated with greater arterial stiffness. Moreover, these associations were mutually independent. These findings may explain, in part, why eGFR and microalbuminuria are associated with greater risk for CVD and suggest that amelioration of arterial stiffness could be a target of intervention.     

Hypertension in primary immunoglobulin A nephropathy (Berger's disease): hemodynamic alterations and mechanisms

Twenty-two patients with primary IgA nephropathy (Berger's disease), 12 with normal and 10 with high blood pressure, were studied. The mean intra-arterial pressure was 88 +/- 6 mm Hg in the normotensive group and 113 +/- 10mm Hg in hypertensive patients; plasma renin activity was high in normotensives and normal in hypertensives. The glomerular filtration rate was 83 +/- 23 and 73 +/- 26 ml/m in 1.73 m2 in normotensive and hypertensive patients, respectively (p = n.s.). Blood volume was high in IgA nephropathy patients: 82 +/- 12 ml/kg body weight in normotensives and 96 +/- 7 ml/kg body weight in hypertensives. Mean arterial pressure was significantly correlated with blood volume (r = 0.541, p less than 0.01), but not with plasma renin activity and glomerular filtration rate. The cardiac index was high in both groups: 4.20 +/- 0.88 liters/min/m2 in normotensive and 3.95 +/- 0.87 liters/min/m2 in hypertensive patients. The total peripheral resistance index was significantly lower than normal in normotensives (1,659 +/- 387 dyn/s/cm-5/m2) and significantly higher (2,419 +/- 562 dyn/s/cm-5 m2) in hypertensives. The cardiac index did not correlate with blood volume and mean arterial pressure; a positive correlation was found between mean arterial pressure and peripheral vascular resistance (r = 0.630, p less than 0.01). No correlation was observed between blood volume and plasma renin activity. Our study indicates that hypertension in IgA nephropathy is primarily volume dependent, and that this increase in blood volume is not related to the deterioration of renal function. The role of the renin-angiotensin system in the maintenance of the hypertension is not well-defined.(ABSTRACT TRUNCATED AT 250 WORDS)     

Which parameter is more influential on the development of arteriosclerosis in hemodialysis patients?

Arteriosclerosis is characterized by stiffening of arteries. The incremental elastic modulus (Einc) measurement is a good marker of arterial wall stiffness. Metabolic, inflammatory and hemodynamic alterations cause structural changes and vascular complications in end stage renal disease. The aim of the present study was to evaluate the factors that may affect the development of arteriosclerosis by measurement of Einc in hemodialysis (HD) patients. Thirty-two patients (16 men; 16 female) on chronic HD with a mean age of 42.2 +/- 19.3 (range: 15-80) were included in the study. The carotid Einc was measured to determine arteriosclerosis by high-resolution echo-tracking system (Acuson Aspen, Acuson Corp., Mountain View, California, USA). Einc measurement was calculated from transcutaneous measurements of common carotid arterial (CCA) internal diameter and wall thickness and carotid pulse pressure. Common carotid compliance and distensibility were determined from changes in carotid artery diameter during systole and simultaneously measured carotid pulse pressure. Common carotid artery stuffiness (Einc) was influenced by age, systolic blood pressure (SBP), pulse pressure (PP), calcium (Ca) and alkaline phosphatase (ALP). The distensibility of CCA was correlated with age, SBP, diastolic blood pressure (DBP), PP, Ca, ALP, and parathormone (PTH). The inflammatory parameter, hs-CRP, was increased with Einc. The mean Einc measurement was found significantly increased in patient receiving vitamin D. In conclusion, the stiffening of carotid artery in HD patients is related not only to hemodynamic changes (increased SBP, PP) but also to metabolic (increased Ca) and to inflammation (increased hs-CRP). Carotid Einc is accepted independent risk factor for cardiovascular mortality. Because of the positive correlation between Einc and serum Ca, vitamin D and Ca containing phosphorus (P) binders should be used carefully.     

Cardiovascular remodelling and extracellular fluid excess in early stages of chronic kidney disease.

BACKGROUND: Patients with a mild to moderate decrease of glomerular filtration rate (GFR) are at risk of cardiovascular (CV) events and CV remodelling has been demonstrated in patients with advanced chronic kidney disease (CKD). However, early stages of CKD and the mechanisms involved in these modifications have not been studied. METHODS: A total of 104 patients with early CKD (mean GFR 60+/-21 ml/min/1.73 m(2)) had cardiac and vascular ultrasound study and measurement of extracellular fluid by multifrequence spectroscopic bioimpedance. RESULTS: GFR decline was associated with left ventricular (LV) remodelling or hypertrophy in 58 and 68% of DOQI-2 and DOQI-3 patients, respectively and impaired LV diastolic function. GFR decrease was also associated with common carotid remodelling and increased aorta stiffness. Cardiac and vascular remodelling were significantly associated with an excess of extracellular fluid (ECFe) evidenced as early as DOQI-2 stage. In multivariate analysis with adjustment for GFR, ECFe, age and systolic blood pressure (sBP), GFR was no longer independently associated with cardiac and vascular remodelling, whereas ECFe was an independent determinant of LV hypertrophy, left atrium enlargement, common carotid diameter and intima media thickness. CONCLUSION: This study shows that CV remodelling and ECF excess occurred at a very early stage of CKD. The independent association between ECF excess and cardiac and vascular remodelling and hypertrophy may be instrumental in the increased cardiovascular risk in CKD patients. Early therapeutic control of ECF may reduce CV events in CKD patients.     

The influence of peripheral vascular disease on the carotid and femoral wall mechanics in subjects with abdominal aortic aneurysm

AIM: Aortic and carotid stiffness is elevated in patients with abdominal aortic aneurysm (AAA). Peripheral vascular disease (PVD) frequently coexists with AAA and may further impair the arterial wall mechanics and increase the cardiovascular load. We therefore studied the elastic carotid and muscular femoral biomechanical properties and intima-media thickness (IMT) in this group of patients. METHODS: The elastic indices and IMTs of the common carotid and common femoral arteries were determined in 30 patients with AAA (15 with PVD) with a duplex scanner coupled with a wall tracking system. Fasting plasma creatinine level, glucose and lipid concentrations, and their physiologic variables known to influence the arterial wall mechanics were also assessed. RESULTS: Patients with AAA and PVD have significantly stiffer carotid (Petersen's elastic modulus, 2207 +/- 905 mm Hg versus 1268 +/- 432 mm Hg; P =.001; stiffness index, 22.73 +/- 9.63 versus 12.60 +/- 4.24; P =.001] and femoral (Petersen's elastic modulus, 4906 +/- 4057 mm Hg versus 2599 +/- 1169 mm Hg; P =.043; stiffness index, 49.02 +/- 40.04 versus 26.07 +/- 13.22; P =.044) arteries than subjects with AAA alone. Although patients with PVD have thicker carotid and femoral IMTs, no statistical difference was seen between the two groups. The subjects were matched for age, body mass index, heart rate, systolic and diastolic blood pressures, total vascular risk score, plasma creatinine level, and fasting lipid and glucose concentrations. CONCLUSION: Subjects with PVD and AAA have significantly stiffer carotid and femoral arteries, which may indicate increased cardiovascular load and may account for the highest mortality rate seen in these patients in the UK Small Aneurysm Trial. Therefore, treatment of associated cardiovascular risk factors is important and may have to be tailored on an individual basis according to the findings of the arterial wall mechanics.     

Carotid intima media thickness predicts cardiovascular diseases in Chinese predialysis patients with chronic kidney disease

Patients with chronic kidney disease (CKD) have a high risk for cardiovascular disease. Ultrasound measurements of the intima media thickness (IMT) in the carotid arteries is a strong predictor for cardiovascular events in the general population and dialysis patients. However, it is unclear whether carotid IMT is useful for the prediction of cardiovascular events in predialysis patients with CKD. The prediction power of carotid ultrasonography for cardiovascular event, rate of renal function decline, and all-cause mortality was tested in a cohort of 203 Chinese patients with stages 3 to 4 CKD. The average IMT was 0.808 +/- 0.196 mm; 121 (59.6%) patients had atherosclerotic plaques visualized. IMT correlated with patient age (r = 0.373, P < 0.001), serum LDL level (r = 0.164, P = 0.021), Charlson's comorbidity score (r = 0.260, P < 0.001), and serum C-reactive protein (r = 0.279, P < 0.001). Carotid IMT was significantly higher in patients with diabetes than in those without diabetes (0.930 +/- 0.254 versus 0.794 +/- 0.184; P = 0.002). At 48 mo, the cardiovascular event-free survival was 94.4, 89.8, 77.7, and 65.9% for IMT quartiles I, II, III, and IV, respectively (log rank test, P = 0.006). By multivariate analysis with the Cox proportional hazard model, each higher quartile of IMT conferred 41.6% (95% confidence interval 6.4 to 88.4%; P = 0.017) excess hazard for developing cardiovascular event. The actuarial survival at 48 mo was 96.3, 98.0, 95.7, and 85.7% for IMT quartiles I, II, III and IV, respectively (log rank test, P = 0.127), and the difference was not statistically significant after Cox proportional hazard model to adjust for confounders. Carotid IMT did not correlate with the rate of renal function decline in these patients. Carotid IMT is a strong predictor of cardiovascular disease in Chinese predialysis patients and may be usefully applied for risk stratification in this group of patients.     

Arterial stiffness and function in end-stage renal disease

Cardiovascular disease is a major cause of mortality in patients with end-stage renal disease, with damage to arteries as a major contributing factor. Arterial stiffness is a factor associated with high systolic and pulse pressure in these patients and is a strong independent factor associated with morbidity and mortality. Arterial stiffness is one of the principal factors opposing left ventricular ejection. The appropriate term to define the arterial factor(s) opposing left ventricular ejection is aortic input impedance. Aortic input impedance depends on TPR, arterial distensibility, and wave reflections. Distensibility defines the capacitive properties of arterial stiffness, whose role it is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of distensibility. These parameters are blood pressure dependent; arteries become stiffer at high pressure. While distensibility provides information about the elasticity of the artery as a hollow structure, the elastic incremental modulus characterizes the properties of the arterial wall biomaterials independent of vessel geometry. Alternatively, arterial distensibility can be evaluated by measuring pulse wave velocity, which increases with the stiffening of arteries. Arterial stiffening increases left ventricular afterload and alters the coronary perfusion. With increased pulse wave velocity, the wave reflections affects the aorta during systole, which increases systolic pressures and myocardial oxygen consumption and decreases diastolic blood pressure and coronary flow. The arterial stiffness is altered primarily in association with increased collagen content and alterations of extracellular matrix and calcification of the arterial wall. The arterial stiffening estimated by changes in aortic pulse wave velocity and intensity of wave reflections are independent predictors of survival in end-stage renal disease and in the general population. Improvement of arterial stiffening could be obtained by antihypertensive treatments as observed with calcium-channel blockers and angiotensin-converting enzyme inhibitors. Angiotensin-converting enzymes inhibitors increase AC and reduce wave reflections. It has been shown that reversibility of aortic stiffening and use of angiotensin-converting enzyme inhibitors had a favorable independent effect on survival in hypertensive patients with advanced renal disease.     

Oral ADSORBENT AST-120 decreases carotid intima-media thickness and arterial stiffness in patients with chronic renal failure

BACKGROUND/AIM: Intima media thickness (IMT) and stiffness of the carotid arteries is related to coronary artery disease, and chronic renal failure patients are at high risk for such diseases. An oral adsorbent, AST-120 (Kremezin; Kureha Chemical Industry, Tokyo, Japan), can delay the progression of chronic renal failure in undialyzed uremic patients. The aim of the present study was to determine whether AST-120 affects carotid artery IMT and pulse wave velocity (PWV) in patients with chronic renal failure not undergoing dialysis. METHODS: Fifty patients with non-diabetic chronic renal failure were randomly divided into two groups: 30 patients (18 men and 12 women; mean age 53.5 years; mean serum creatinine 3.2 mg/dl) who were given AST-120 (6.0 g/day) and 20 patients (12 men and 8 women; mean age 52.0 years; mean serum creatinine 3.5 mg/dl) who were not given AST-120. Thirty healthy age-matched subjects (18 men and 12 women; mean age 51.5 years; mean serum creatinine 0.9 mg/dl) were also included. The treatment period was 24 months. IMT and arterial stiffness were measured before and after treatment. RESULTS: The slope of the reciprocal serum creatinine concentration over time became significantly less steep in the AST-120 group than in the non-AST-120 group (p < 0.001). Before treatment, carotid artery IMT differed little between the AST-120 group (0.90 +/- 0.22 mm) and the non-AST-120 group (0.88 +/- 0.20 mm). IMT in these two groups was significantly greater than IMT in the control group (0.64 +/- 0.14 mm) (p < 0.01). Carotid IMT in the AST-120 group decreased slightly but not significantly to 0.84 +/- 0.20 mm after 12 months and then significantly after 24 months to 0.78 +/- 0.18 mm (p < 0.05). Carotid IMT in the non-AST group showed little change throughout the experimental period. PWV differed little between the AST-120 group (1,980 +/- 330 cm/s) and the non-AST group (1,940 +/- 360 cm/s) before treatment. PWV values in these two groups were significantly greater than PWV in the control group (1,280 +/- 240 cm/s) (p < 0.01). After 12 and 24 months, PWV in the AST-120 group decreased significantly to 1,840 +/- 280 cm/s (p < 0.05) and to 1,780 +/- 260 cm/s (p < 0.05), respectively; however, PWV in the non-AST group showed a slight increase during the experimental period. CONCLUSION: The data suggest that AST-120 may reduce arterial stiffness and IMT in non-diabetic chronic renal failure patients before dialysis.     

Arterial distensibility and pulse wave velocity in patients with primary hyperparathyroidism before and after parathyroidectomy

AIMS: There is evidence that secondary hyperparathyroidism alters arterial vessel wall properties. However, it is unclear whether effects of parathyroid hormone (PTH) on the vascular wall are direct or permissive and related to hypertension and renal failure. To assess early direct effects of PTH on large artery wall properties isobaric distensibility (DC), pulse wave velocity (PWV) and intima-media thickness (IMT) were studied before and after parathyroidectomy (Ptx) in patients with primary hyperparathyroidism (pHPT). METHODS: DC and IMT of the brachial and carotid artery were measured by echo-tracking and tonometry, PWV by the automatic Complior-device at baseline and 6 months after Ptx in 20 patients with pHPT (data mean +/- SEM, age 45+/-5 years, PTH 240+/-61 ng/l). Cardiovascular risk factors like diabetes, hypertension, renal insufficiency and hypercholesterolemia were excluded. Twenty healthy volunteers matched for age, sex and blood pressure served as controls. RESULTS: Six months after Ptx, PTH decreased to normal; however, blood pressure levels and vessel wall parameter remained unchanged. At baseline, there were no significant differences in brachial and carotid IMT (0.48+/-0.04 and 0.62+/-0.04 mm vs. 0.47+/-0.06 and 0.61+/-0.06 mm), radial and aortic PWV (9.1+/-0.4 and 9.9+/-0.7 m/s vs. 9.2+/-0.5 and 10.0+/-0.6 m/s), brachial and isobaric carotid DC (10.1+/-1.4 and 19.5+/-3.4 10(-3)/kPa vs. 9.1+/-0.9 and 20.4+/-3.2 10(-3)/kPa) or artery diameter between patients and controls. CONCLUSIONS: Structural and viscoelastic properties of large arteries are not disturbed and not influenced by parathyroidectomy in patients with early pHPT devoid of hypertension and renal disease. We conclude that increased PTH levels per se are not associated with alterations of mechanical arteriall wall properties; permissive factors like renal insufficiency may be necessary to mediate vessel wall alterations in patients with hyperparathyroidism.     

老年慢性肾脏病患者骨密度水平与颈动脉IMT的相关性研究

目的研究不同分期老年慢性肾脏病(CKD)患者颈动脉粥样硬化与骨密度水平的关系,为CKD不同分期老年人群骨质疏松症与心血管疾病的防治提供相关的理论及临床指导。方法以本院门诊及住院的老年CKD非透析治疗患者为研究对象,健康老人为对照组,采用双能X线吸收法(DXA)测定腰椎骨和股骨区的骨密度水平(BMD),同时采用彩色多普勒超声探查颈动脉内膜-中层厚度(IMT)及粥样斑块的情况;应用SPSS18.0软件包,统计分析骨密度水平与颈动脉粥样硬化的关系。结果 CKD患者骨密度水平均比健康对照组显著降低(-2.4SD±0.18比-0.8SD±0.24,P0.01);在非透析CKD患者中,肾小球滤过率(GFR)与骨密度水平呈现正相关,各组间比较差异有统计学意义(P0.05或P0.01);CKD患者颈动脉内膜中层厚度(IMT)(0.78±0.21比0.71±0.24 mm,P0.01)及斑块形成(66.6%比36%,P0.01)、颈动脉硬化的患病率(66.6%比36%,P0.01)较健康对照组均显著升高;直线相关分析显示,骨密度水平与hs CRP、TG、血磷、i PTH、血红蛋白(Hb)呈正相关(P0.05或P0.01),与GFR、血钙、血白蛋白(SAlb)、IMT、斑块形成、颈动脉硬化的患病率呈负相关(P0.05或P0.01);多因素逐步回归分析显示,年龄、收缩压、糖尿病、吸烟、药物以及BMD是CKD患者颈动脉病变的独立危险因素。CKD患者IMT比对照组显著增厚(P0.01),其颈动脉粥样斑块总检出率66%,对照组的总检出率仅为36%(P0.01),CKD中晚期患者的颈动脉IMT增厚和粥样斑块的阳性率更为明显(P0.05)。结论各期CKD患者骨密度水平均显著降低,且与颈动脉病变相关,骨质疏松可能是CKD患者并发动脉粥样硬化的危险因素之一。动脉粥样硬化斑块的形成,与患者的年龄、血脂、CKD不同分期及骨密度均有显著相关性,骨质疏松的危险因素与之亦有共同点。骨质疏松与动脉粥样硬化高度相关,二者互为因果。     

Renal artery calcified plaque associations with subclinical renal and cardiovascular disease

BACKGROUND: The prognostic significance of renal artery calcified plaque (RAC) and its relationship with renal function, albuminuria, and systemic atherosclerosis are unknown. METHODS: Calcified atherosclerotic plaque was measured in the renal arteries of 96 unrelated Caucasian subjects with type 2 diabetes mellitus (DM) using four-channel multidetector-row computed tomography (MDCT4). Renal artery calcium was measured as the sum of ostial and main renal artery calcium scores. Participants also underwent MDCT scanning to measure coronary artery calcium (CAC), carotid artery calcium, common iliac artery calcium, infra-renal aorta calcium, and B-mode ultrasound to measure carotid artery intima-medial thickness (IMT). Spearman's rank correlation coefficients were used to assess associations between RAC and measures of subclinical renal and cardiovascular disease. Partial correlation coefficients were computed to adjust for the potential confounding effects of age, gender, body mass index (BMI), DM duration, smoking, and serum cholesterol and triglyceride levels. RESULTS: Characteristics of the study group were 54% (52/96) female with a mean +/- SD (median) age 62.8 +/- 8.4 (62.5) years, DM duration 10.6 +/- 6.3 (8.0) years, hemoglobin A1C 7.5 +/- 1.5 (7.2)%, BMI 32.1 +/- 6.3 (31.1) kg/m(2), serum creatinine concentration 1.11 +/- 0.18 (1.10) mg/dL, urine albumin:creatinine ratio (ACR) 105.3 +/- 423.1 (17.6) mg/g, modified MDRD equation glomerular filtration rate (GFR) 64.3 +/- 12.6 (63.6) mL/min, RAC 372 +/- 799 (101), CAC 1819 +/- 2594 (622), carotid artery calcium 264 +/- 451 (72), and B-mode ultrasound carotid IMT 0.70 +/- 0.12 (0.69) mm. Sixty-five percent of subjects (62/96) had detectable RAC. Renal artery calcium was significantly associated with CAC (r= 0.50, P < 0.0001), carotid artery calcium (r= 0.58, P < 0.0001), common iliac artery calcium (r= 0.45, P < 0.0001), infra-renal aorta calcium (r= 0.70, P < 0.0001), IMT (r= 0.40, P= 0.0004), diastolic blood pressure (r=-0.33, P= 0.0009), BMI (r=-0.19, P= 0.0573), and age (r= 0.54, P < 0.0001). There was no association between RAC and GFR (r=-0.15, P= 0.1637) or between RAC and urine ACR (r= 0.07, P= 0.5083). CONCLUSION: Renal artery calcium is strongly associated with older age, diastolic blood pressure, BMI, carotid artery IMT, and coronary, carotid, common iliac artery, and infra-renal aorta calcium in Caucasians with type 2 diabetes mellitus. Renal artery calcium, similar to CAC and IMT, appears to be a useful noninvasive marker of subclinical atherosclerosis. However, RAC is not significantly associated with either GFR or albuminuria.     

Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: role of calcium-phosphorus metabolism

In children, cardiac abnormalities such as increased left ventricular mass (LVM) and diastolic dysfunction develop at the time of mild to moderate chronic renal insufficiency (CRI) and progress as renal function deteriorates. It was hypothesized that in this age group, vascular abnormalities develop early in the course of chronic kidney disease (CKD) in parallel with cardiac abnormalities and become more severe as end-stage disease is reached. Echocardiography and ultrasound of the carotid artery were performed on 44 patients with CKD stages 2 to 4 (CRI group), 16 patients who were on maintenance dialysis, and 35 healthy individuals. Carotid artery intima-media thickness (cIMT) was measured and distensibility and stiffness were calculated to assess carotid artery structure and function. Both the CRI and dialysis groups had greater cIMT, higher LVM index, and poorer diastolic function than the control subjects (P < 0.0001). Children who were on dialysis had greater cIMT and higher LVM index than those with CRI (P < 0.001) and greater arterial stiffness than both CRI patients and control subjects (P < 0.001). Arterial compliance was similar in CRI and control subjects. In all patients with CKD (CRI and dialysis), increased calcium-phosphorus product predicted increased cIMT. Increased serum phosphorus and intact parathyroid hormone predicted increased arterial stiffness. Elevated intact parathyroid hormone was a predictor of increased LVM index and poor diastolic function. In dialysis patients, the cumulative dose of phosphate binders and calcitriol predicted abnormal vascular structure and function. It is concluded that vascular abnormalities are already present in children and adolescents during early stages of CKD; they are more severe in children who are on maintenance dialysis and are related to abnormal calcium-phosphorus metabolism.     

Role of renal hemodynamics in the exaggerated natriuresis of essential hypertension

Extracellular fluid volume expansion is known to produce exaggerated natriuresis in essential hypertension. In order to assess the role of hemodynamic and intrarenal physical factors upon natriuretic response to central volume expansion, two hour water immersion (WI) experiments were made in six uncomplicated essential hypertensives and six normotensive healthy controls. Before and during WI we measured mean arterial pressure (MAP), urine flow (V/min), sodium (UNaV) and potassium (UKV) excretion, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and intrarenal (wedged) venous pressure (IRVP). In comparison with normotensive controls, the exaggerated natriuretic response in hypertensives (P less than 0.05 for UNaV during WI) was associated with an enhanced vasodilating response as demonstrated by a greater increase in ERPF (P less than 0.05) and by a more pronounced fall in calculated renal precapillary resistances (P less than 0.05). A more significant increase in IRVP was found in hypertensive group (P less than 0.05). Glomerular filtration rate (GFR) did not change in either group during WI. MAP, unchanged in normotensives, was significantly reduced in hypertensives (P less than 0.05), while remaining in the hypertensive range. These findings suggest that intrarenal physical factors play a major role in determining the exaggerated natriuresis during WI in hypertensive man.     

Which Parameter Is More Influential on the Development of Arteriosclerosis in Hemodialysis Patients?

Arteriosclerosis is characterized by stiffening of arteries. The incremental elastic modulus (Einc) measurement is a good marker of arterial wall stiffness. Metabolic, inflammatory and hemodynamic alterations cause structural changes and vascular complications in end stage renal disease. The aim of the present study was to evaluate the factors that may affect the development of arteriosclerosis by measurement of Einc in hemodialysis (HD) patients. Thirty-two patients (16 men; 16 female) on chronic HD with a mean age of 42.2 ± 19.3 (range: 15–80) were included in the study. The carotid Einc was measured to determine arteriosclerosis by high-resolution echo-tracking system (Acuson Aspen, Acuson Corp., Mountain View, California, USA). Einc measurement was calculated from transcutaneous measurements of common carotid arterial (CCA) internal diameter and wall thickness and carotid pulse pressure. Common carotid compliance and distensibility were determined from changes in carotid artery diameter during systole and simultaneously measured carotid pulse pressure. Common carotid artery stuffiness (Einc) was influenced by age, systolic blood pressure (SBP), pulse pressure (PP), calcium (Ca) and alkaline phosphatase (ALP). The distensibility of CCA was correlated with age, SBP, diastolic blood pressure (DBP), PP, Ca, ALP, and parathormone (PTH). The inflammatory parameter, hs-CRP, was increased with Einc. The mean Einc measurement was found significantly increased in patient receiving vitamin D. In conclusion, the stiffening of carotid artery in HD patients is related not only to hemodynamic changes (increased SBP, PP) but also to metabolic (increased Ca) and to inflammation (increased hs-CRP). Carotid Einc is accepted independent risk factor for cardiovascular mortality. Because of the positive correlation between Einc and serum Ca, vitamin D and Ca containing phosphorus (P) binders should be used carefully.