Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease.

To test the predictive values of and independent contributions to cardiovascular and all-cause mortality of various arterial parameters exploring characteristics of the arterial wall at different sites, we studied prospectively 110 stable end-stage renal disease patients on hemodialysis. These parameters involved carotid diameter, carotid intima-media thickness, carotid compliance, carotid distensibility, carotid incremental elastic modulus, aortic diameter, aortic pulse wave velocity, and the presence of arterial calcifications measured at the sites of the carotid artery, abdominal aorta, iliofemoral axis, and legs. The presence of calcifications was analyzed semiquantitatively as a score (0 to 4) according to the number of arterial sites with calcifications. During a follow-up of 53+/-21 months (mean+/-SD), 25 cardiovascular and 14 noncardiovascular deaths occurred. In univariate analysis, the carotid incremental elastic modulus was the most closely related to prognosis. Risk of death increased with the number of vascular sites involved by calcifications. Moreover, information (in terms of prediction) given by carotid elastic incremental modulus was additive to the presence and extent of vascular calcification-related prediction value. Adjusted hazard ratios of all-cause and cardiovascular mortality for an increase of 1 unit in calcification score were 1.9 (95% confidence interval [CI], 1.4 to 2.6) and 2.6 (95% CI, 1.5 to 4.4), respectively (P<0.001 for both). Adjusted hazard ratios of all-cause and cardiovascular mortality for a 1-SD increase in carotid incremental elastic modulus were 1.6 (95% CI, 1.2 to 2.2) and 1.7 (95% CI, 1.2 to 2.4), respectively (P<0.01 for both). The results of this study showed that the presence and extent of vascular calcifications were strong predictors of cardiovascular and all-cause mortality. Carotid incremental elastic modulus gave additional predictive value.

Arterial stiffening and vascular calcifications in end-stage renal disease.

BACKGROUND: Epidemiological studies have identified aortic stiffness as an independent predictor of cardiovascular mortality in end-stage renal disease (ESRD) patients. In these patients, aortic pulse wave velocity (PWV) was associated with mediacalcosis, but the influence of arterial calcifications on the viscoelastic properties of large arteries was not well characterized. The purpose of the present study was to analyse the influence of arterial calcifications on arterial stiffness in stable haemodialysed patients. METHODS: We studied 120 stable ESRD patients on haemodialysis. All patients underwent B-mode ultrasonography of common carotid artery (CCA), aorta, and femoral arteries to determine CCA distensibility, the elastic incremental modulus (Einc), and the presence of vascular calcifications. All patients underwent measurement of aortic PWV and echocardiogram. The presence of calcifications was analysed semiquantitatively as a score (0 to 4) according to the number of arterial sites with calcifications. RESULTS: Our observations indicate that arterial and aortic stiffness is significantly influenced by the presence and extent of arterial calcifications. The extent of arterial calcifications is in part responsible for increased left ventricular afterload, and is inversely correlated with stroke volume. The influence of calcifications is independent of the role of ageing and blood pressure. Arterial calcifications density increases with age, duration of haemodialysis, the fibrinogen level, and the prescribed dose of calcium-based phosphate binders. CONCLUSIONS: The results of this study showed that the presence of vascular calcifications in ESRD patients was associated with increased stiffness of large capacity, elastic-type arteries, like the aorta and CCA. The extent of arterial calcifications increased with the use of calcium-based phosphate-binders.

Postischemic vasodilation, endothelial activation, and cardiovascular remodeling in end-stage renal disease.

BACKGROUND: Cardiovascular complications are the major cause of death in end-stage renal disease (ESRD) patients. These complications are associated with concomitant cardiac and vascular remodeling, including left ventricular (LV) hypertrophy and hypertrophy of arterial walls. The endothelium influences the process of arterial remodeling. ESRD patients are characterized by the development of both cardiovascular remodeling and endothelial dysfunction. METHODS: Common carotid artery (CCA) intima-media thickness (IMT), CCA diameter, CCA distensibility, LV mass, and function were determined in 60 stable ESRD patients on hemodialysis and 34 age-, sex-, and blood pressure (BP)-matched controls, and their relationships with endothelial alterations were estimated by forearm postischemic vasodilation [flow debt repayment (FDR)] measured by venous plethysmography. We also evaluated the relationships between FDR and several cardiovascular risk factors or markers of inflammatory response or endothelial activation, for example, duration of dialysis, BP, smoking habits, cholesterol, parathormone (PTH), serum albumin, plasma fibrinogen, C-reactive protein (CRP), plasma homocysteine, plasminogen activator inhibitor (PAI-1), and von Willebrand factor (vWF). RESULTS: ESRD patients had increased LV mass, CCA diameter and CCA IMT, and had decreased CCA distensibility (P < 0.05). While the postischemic peak flow was comparable in controls and ESRD patients (29.2 +/- 9.1 vs. 27.9 +/- 0.2 mL/100 mL/min), FDR was lower in ESRD patients (116 +/- 31 vs. 88 +/- 32%, P < 0.001) because of the shorter duration of vasodilation (127 +/- 36 vs. 96 +/- 32 s, P < 0.001). The time to complete FDR was longer in ESRD patients (110 +/- 54 vs. 162 +/- 72 s, P < 0.001). ESRD patients had lower high-density lipoprotein cholesterol and serum albumin (P < 0.01) and higher triglycerides, fibrinogen, plasma homocysteine, vWF (P < 0.01), and PAI-1 (P < 0.05). For ESRD patients, significant negative age- and pressure-independent correlations were established between FDR and CCA diameter, duration of dialysis, and PAI-1. FDR was positively correlated with serum albumin. FDR and time to FDR were negatively correlated with CCA IMT and LV mass. CCA distensibility was positively associated with FDR (P < 0.001) and negatively with time to FDR (P < 0.001). The PAI-1 concentration was positively correlated with CCA IMT (P < 0.01) and negatively with CCA distensibility (P < 0.001). CONCLUSIONS: Our data provide the first evidence that cardiac and arterial remodeling in ESRD patients are inversely related to forearm reactive hyperemia. The diminished hyperemic response is due to the shorter duration of hyperemia and is associated with higher concentrations of serum markers of endothelial activation, suggesting that, in ESRD patients, endothelial dysfunction may be a factor influencing cardiovascular 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.

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.

Arteriosclerosis and antihypertensive response to calcium antagonists in end-stage renal failure.

The relationship between the presence of arterial calcinosis and the antihypertensive response to calcium blockers was studied in 40 hypertensive patients with end-stage renal failure (ESRF) on chronic hemodialysis, before and during 16 weeks after administration of nitrendipine in monotherapy. In a double-blind, placebo-controlled, randomized study, nitrendipine reduced systolic blood pressure regardless of the presence or absence of arterial calcifications. The antihypertensive effect was significantly more pronounced in subjects with aortic calcium deposits in comparison with patients without clinical signs of arteriosclerosis (p less than 0.01). The diastolic blood pressure was significantly reduced only in patients with aortic calcifications, and remained unchanged in subjects with noncalcified aorta. The aortic pulse wave velocity decreased significantly in patients with aortic calcifications (p less than 0.001), but remained unaffected in patients with noncalcified vessels. Multivariate regression analysis showed that the antihypertensive action of nitrendipine was correlated to the presence of aortic calcium deposits independent of age or baseline blood pressure levels. The results of the present study indicate that an overt arteriosclerosis as demonstrated by the presence of aortic calcifications on abdominal radiographs is a good indication for the use of dihydropyridines in patients with ESRF.

Arteriosclerosis and antihypertensive response to calcium antagonists in end-stage renal failure.

The relationship between the presence of arterial calcinosis and the antihypertensive response to calcium blockers was studied in 40 hypertensive patients with end-stage renal failure (ESRF) on chronic hemodialysis, before and during 16 weeks after administration of nitrendipine in monotherapy. In a double-blind, placebo-randomized study, nitrendipine reduced systolic blood pressure regardless of the presence or absence of arterial calcifications. The antihypertensive effects were significantly more pronounced in subjects with aortic calcium deposits in comparison with patients without clinical signs of arteriosclerosis (p less than 0.01). Diastolic blood pressure was significantly reduced only in patients with aortic calcifications, and remained unchanged in subjects with noncalcified aorta. Aortic pulse wave velocity decreased significantly in patients with aortic calcifications (p less than 0.001), but remained unaffected in patients with noncalcified vessels. Multivariate regression analysis showed that antihypertensive action of nitrendipine was correlated with the presence of aortic calcium deposits independently of age or baseline blood pressure levels. The results of the present study indicate that an overt arteriosclerosis as demonstrated by the presence of aortic calcifications on abdominal radiographs is a good indication for use of dihydropiridines in patients with ESRF.

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.

Uremic cardiomyopathy: an inadequate left ventricular hypertrophy.

Echocardiographic study of the left ventricle was performed in 57 selected, normotensive hemodialysis patients in comparison to 40 healthy controls matched for sex, age and blood pressure. The statistically significant abnormalities in uremic patients were an enlargement of the left ventricular end-diastolic diameter (LVEDiD) (5.58 +/- 0.60 vs. 5.05 +/- 0.5 cm; P less than 0.001) and an increase in the left ventricular radius to posterior wall-thickness ratio (r/Th) (3.65 +/- 0.68 vs. 3.27 +/- 0.44; P less than 0.001). Enlargement of the ventricle was related to anemia (P less than 0.001) and the hemodynamic effect of arteriovenous fistula. Ventricular radius to wall thickness ratio was inversely related to systolic arterial pressure in controls (P less than 0.001) and patients (P less than 0.01) with a significant upward shift of the regression in dialysis patients (P less than 0.001). In dialysis patients, the left ventricular posterior wall thickness (LVPWT) was inversely correlated to serum parathormone (PTH) level (P less than 0.001), and r/Th ratio was positively correlated to serum PTH (P less than 0.001). Bone biopsy was performed in 28 patients. Histomorphometric indexes of osteitis fibrosa were in dialysis patients, correlated to echocardiographic abnormalities; osteoclasts number was inversely correlated to LVPWT (P less than 0.001) and positively related to r/Th ratio (P less than 0.001). Osteoclastic resorption surfaces and LVPWT were inversely correlated (P less than 0.001), while a positive correlation between r/Th ratio and osteoclastic resorption surfaces was observed (P less than 0.001). Osteoblastic surfaces and tetracycline double-labeled surfaces were also correlated to LVPWT (P less than 0.001) and r/Th ratio (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)