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Background and objectives: Cardiovascular disease is the main cause of mortality in chronic kidney disease (CKD) patients. Vitamin D might have beneficial effects on vascular health. The aim of this study was to determine the prevalence of vitamin D deficiency (25-hydroxyvitamin D [25D] ≤ 15 ng/ml) and insufficiency (25D levels between 16 and 30 ng/ml) in a cohort of patients at different CKD stages and the relationships between vitamin D serum levels, vascular calcification and stiffness, and the mortality risk. Design, setting, participants & measurements: One hundred forty CKD patients (85 men, mean age 67 ± 12 yr; CKD stages 2 [8%], 3 [26%], 4 [26%], 5 [7%], and 5D [(33%]) were allocated for a prospective study. Serum levels of 25D and 1,25-dihydroxyvitamin D, aortic calcification score, and pulse wave velocity (PWV) were evaluated. Results: There was a high prevalence of vitamin D deficiency (42%) and insufficiency (34%). Patients with 25D ≤ 16.7 ng/ml (median) had a significantly lower survival rate than patients with 25D >16.7 ng/ml (mean follow-up, 605 ± 217 d; range, 10 to 889; P = 0.05). Multivariate adjustments (included age, gender, diabetes, arterial pressure, CKD stage, phosphate, albumin, hemoglobin, aortic calcification score and PWV) confirmed 25D level as an independent predictor of all-cause mortality. Conclusions: Vitamin D deficiency and insufficiency were highly prevalent in this CKD cohort. Low 25D levels affected mortality independently of vascular calcification and stiffness, suggesting that 25D may influence survival in CKD patients via additional pathways that need to be further explored.

Treatment with erythropoietin and AT1 blockers is protective in experimental acute cerebral ischemia, with promising results in pilot clinical studies in human stroke. This paper examines the effects of using both agents as combination therapy in acute ischemic stroke.We used the single carotid ligation stroke model in the gerbil. Six groups of 50 gerbils were treated either with placebo, erythropoietin (intraperitoneally, 5000 IU/kg, 2 and 48 h after stroke), olmesartan (10 mg/kg per day in drinking water started 36 h after stroke), ramipril (2.5 mg/kg per day in drinking water started 36 h after stroke), erythropoietin + olmesartan, or erythropoietin + ramipril. Long-term (1 month) Kaplan-Meyer survival curves were obtained, and survivors were submitted at day 30 to immediate (object recognition test) and spatial (Morris water maze) memory function tests.Erythropoietin alone and olmesartan alone, but not ramipril, significantly increased survival at day 30 compared with untreated controls (38, 30 and 6% versus 12%, respectively). Combined treatment with erythropoietin and olmesartan further increased the survival rate to 56%, whereas combined therapy with erythropoietin and ramipril decreased 30-day survival to 24% (P0.0001, erythropoietin + olmesartan versus erythropoietin + ramipril). Untreated stroke survivors had markedly altered performances in both the object recognition test (P = 0.0007) and the Morris water maze (P0.0001) tests at day 30 compared with normal gerbils. In erythropoietin-treated animals, ramipril therapy had no beneficial effect whereas olmesartan fully restored normal response to the memory tests.Post-infarct treatment with olmesartan combined with early erythropoietin therapy has a protective effect on survival, and markedly improves long-term memory dysfunction in this experimental model.

Adynamic (or aplastic) bone disease is a bone histologic pattern characterized by decreased bone formation rate, low cellularity, and normal or decreased osteoid thickness. It was first described in symptomatic patients undergoing dialysis who were overloaded with aluminum because of contaminated dialysate or chronic ingestion of aluminic phosphate binders; the evidence of the overload was extensive coloration (more than 25%) with aurin tricarboxylic acid, whereas the Perls stain coloration for iron was negative. We have, however, reported these histologic changes in asymptomatic patients with uremia who were never exposed to aluminum, in two patients before end-stage renal failure and in six patients undergoing dialysis. The main step in the prevention of adynamic bone disease is the absolute exclusion of aluminum exposition even by so-called "safe doses" of aluminum phosphate binders because in the long term they are never actually safe. Because idiopathic adynamic bone disease may nevertheless occur, parathyroid hormone suppressive treatment by oral calcium taken with meals as phosphate binders (+/- 1 alpha-hydroxyvitamin D3 derivatives) should be carefully monitored by measurements of plasma concentrations of not only calcium and phosphate but also of intact parathyroid hormone levels. In order to have normal bone formation rate levels, patient intact parathyroid hormone levels should be between one and three times the upper limit of the normal level. Although adynamic bone disease may not be a true bone disease when not due to aluminum, it is a risk factor for increased incidence of hypercalcemia and hyperphosphatemia and therefore for metastatic calcifications. Therefore, when hypercalcemia occurs with hyperphosphatemia and normal intact parathyroid hormone in patients treated with 1 alpha-hydroxyvitamin D3, it is proposed that the latter drug should be discontinued first, whereas oral calcium is increased to correct hyperphosphatemia, and calcium concentration is decreased in the dialysate to prevent hypercalcemia, even though plasma parathyroid hormone may increase up to three times the upper limit of the normal level. In patients previously exposed to aluminum, a deferoxamine test should be performed and a deferoxamine treatment started if the test is positive.

To the Editor: The aims of this letter are to congratulate the authors for the results of Conduit Artery Function Evaluation (CAFE) study1 and to challenge the difference in heart rate as a preponderant explanation for the differences in central systolic blood pressure (SBP) between amlodipine- and atenolol-based treatment. On the basis of the Regression of Arterial Stiffness in a Controlled Double-Blind Study (REASON), in which perindopril plus indapamide (Per/Ind) was compared with atenolol alone for 12 months in hypertensive subjects,2 …

To the Editor: The MOSES study1 has unequivocally shown that in patients with a history of cerebrovascular events, a blood pressure (BP)–lowering treatment based on eprosartan is more protective against both cerebrovascular event recurrence and cardiac complications than a treatment based on nitrendipine. Of paramount importance is the fact that this superiority was documented with similar BP decrease in both treatment arms and no difference in baseline BP. Furthermore, BP was monitored not only by office BP but also by 24-hour ambulatory BP at baseline and after 12, 24 and 48 months of follow-up. The office BP-lowering effect of eprosartan was even slightly smaller (1.5 and 0.6 mm Hg for the systolic and diastolic BP, respectively), which formally excludes any BP bias. Can we therefore postulate that a specific BP-independent stroke preventive effect of eprosartan is the only possible explanation for this better cardiovascular protection compared with nitrendipine? To answer this question, it is important to carefully look at the add-on therapy. Interestingly as pointed out by the authors, the add-on therapy was comparable with the exception of the use of angiotensin-converting enzyme …

To the Editor: We read with great interest the article by Bains et al1 in which they hypothesize that the blood pressure–independent susceptibility of spontaneous hypertensive rats (SHR) to stroke could be explained by increased angiotensin II levels in the brain nuclei. Indeed, they convincingly documented that resistance to death of magnocellular neurons of paraventricular nucleus (PVN) after injection of an N -methyl-d-aspartate receptor agonist (NMDAa) is present in normotensive rats but absent in SHR and that preadministration of saralasin into these nuclei of SHR generated resistance of these cells to NMDAa-induced death, by preventing the angiotensin II–mediated increase of neuronal excitability, which is secondary to inhibition of a D-type specific potassium conductance. Indeed, inhibition of this conductance results in higher frequency of depolarization in the penumbra surrounding a focal brain ischemia and, therefore, results in increased infarct size. However, while the authors stressed the potential pathophysiological significance of their observation by recalling that the AT1 receptor antagonist losartan protects SHR against stroke even at nonantihypertensive dose,2 they unfortunately did not examine the effect of specific AT1 receptor blockade in their experimental model, and we wonder why they have chosen saralasin, a nonspecific angiotensin II …

To the Editor: A series of articles recently published in Stroke strongly suggest that age-adjusted stroke incidence is increasing. After a marked decline since the 1960s, the stroke mortality rate has plateaued since 1990 in both Japan1 and the United States.2 The in-hospital case-fatality rate for stroke, however, is declining in the United States,3 mainly because of better acute stroke treatment, although detection of milder cases of stroke through neuroimaging improvement may contribute to this trend.4 On the contrary, the age-adjusted stroke hospitalization rate increased by 18.6% between 1988 and 1997 in the United States.3 Even though the institution of more lenient criteria for hospitalization may partially explain it, this phenomenon strongly suggests an actual increase of age-adjusted stroke incidence,4 which could account for the leveling off of the stroke mortality rate despite the decrease of stroke case-fatality. Since the increased rate of hospitalization after stroke was limited to elderly patients >65 years, we quite agree with Tu4 that the stroke incidence increase may be due to more successful prevention of coronary heart disease (CHD) by increasing a population at higher risk for stroke, since CHD per se increases this risk.5 However, we are more reluctant to admit the role of aging per se, since the stroke …

To the Editor: We read with interest the review article on stroke and encephalopathy after cardiac surgery1 and the related editorial.2 We agree that assessing these complications provides a unique clinical opportunity for evaluating preventive strategies because patients at higher risk can be identified before surgery. We would like to add to the list of potential cerebroprotective agents proposed (gangliosides, glutamate receptor antagonists, antioxidants) the angiotensin AT1 receptor blockers (AT1RB). Both …

To the Editor: We would like to commend Dr Lawes and collaborators1 on their thorough overview of antihypertensive therapy and stroke. However, we take issue with their conclusion that “initiating and maintaining BP reduction for stroke prevention is a more important issue than choice of initial agent.” This may well be true for most antihypertensive drugs, but not for the …