Acute effects of cinacalcet on arterial stiffness and ventricular function in hemodialysis patients: A randomized double-blinded crossover study.

BACKGROUND: Serum calcium concentration (Ca) plays an essential role in a vascular muscle tone and myocardial contractility. Previously, we showed that acutely lowering Ca by hemodialysis reduced arterial stiffness. Cinacalcet is a calcimimetic that lowers Ca and parathyroid hormone (PTH). The aim of the present study was to examine whether acute lowering of Ca by cinacalcet improves vascular stiffness and myocardial diastolic dysfunction. METHOD: This is a double-blinded randomized placebo-controlled crossover study that included 21 adult patients with end-stage kidney disease undergoing chronic hemodialysis. Subjects were assigned to placebo-cinacalcet (30 mg) or cinacalcet-placebo sequence. After each treatment period (7 days), aortic, brachial, and carotid stiffness were determined by examining carotid-femoral pulse wave velocity (cf-PWV), carotid-radial PWV (cr-PWV), and carotid distension. A central pulse wave profile was determined by radial artery tonometry and cardiac function was evaluated by echocardiography. RESULTS: Cinacalcet reduced PTH (483 [337-748] to 201 [71-498] ng/L, P < .001) and ionized Ca (1.11 [1.08-1.15] to 1.05 [1.00-1.10] mmol/L, P = .04). Cinacalcet did not reduced cf-PWV significantly (12.2 [10.4-15.4] to 12.2 [11.0-14.6] m/s, P = .16). After adjustments for mean blood pressure, sequence, carryover, and treatment effects, cf-PWV was not significantly lowered by cinacalcet (-0.35 m/s, P = .139). There were no significant changes in central blood pressures, brachial and carotid stiffness, and echocardiographic parameters. CONCLUSION: In this study, 30 mg daily cinacalcet for 1 week did not have any significant impact on peripheral and central blood pressures, arterial stiffness parameters, or cardiac function (NCT01250405).

Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension.

Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure. Also, although a serum lipid panel remains part of the routine laboratory testing for patients with hypertension, fasting and nonfasting collections are now considered acceptable. For individuals with secondary hypertension arising from primary hyperaldosteronism, adrenal vein sampling is recommended for those who are candidates for potential adrenalectomy. With respect to the treatment of hypertension, a new recommendation that has been added is for increasing dietary potassium to reduce blood pressure in those who are not at high risk for hyperkalemia. Furthermore, in selected high-risk patients, intensive blood pressure reduction to a target systolic blood pressure ≤ 120 mm Hg should be considered to decrease the risk of cardiovascular events. Finally, in hypertensive individuals with uncomplicated, stable angina pectoris, either a ß-blocker or calcium channel blocker may be considered for initial therapy. The specific evidence and rationale underlying each of these recommendations are discussed. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will continue to provide annual updates.

The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment. This report provides the updated evidence-based recommendations for 2015. This year, 4 new recommendations were added and 2 existing recommendations were modified. A revised algorithm for the diagnosis of hypertension is presented. Two major changes are proposed: (1) measurement using validated electronic (oscillometric) upper arm devices is preferred over auscultation for accurate office blood pressure measurement; (2) if the visit 1 mean blood pressure is increased but < 180/110 mm Hg, out-of-office blood pressure measurements using ambulatory blood pressure monitoring (preferably) or home blood pressure monitoring should be performed before visit 2 to rule out white coat hypertension, for which pharmacologic treatment is not recommended. A standardized ambulatory blood pressure monitoring protocol and an update on automated office blood pressure are also presented. Several other recommendations on accurate measurement of blood pressure and criteria for diagnosis of hypertension have been reorganized. Two other new recommendations refer to smoking cessation: (1) tobacco use status should be updated regularly and advice to quit smoking should be provided; and (2) advice in combination with pharmacotherapy for smoking cessation should be offered to all smokers. The following recommendations were modified: (1) renal artery stenosis should be primarily managed medically; and (2) renal artery angioplasty and stenting could be considered for patients with renal artery stenosis and complicated, uncontrolled hypertension. The rationale for these recommendation changes is discussed.

Aortic-brachial stiffness mismatch and mortality in dialysis population.

We hypothesized that increased aortic stiffness (central elastic artery) combined with a decrease in brachial stiffness (peripheral muscular artery) leads to the reversal of the physiological stiffness gradient (ie, mismatch), promoting end-organ damages through increased forward pressure wave transmission into the microcirculation. We, therefore, examined the effect of aortic-brachial stiffness mismatch on mortality in patients in need of dialysis. In a prospective observational study, aortic-brachial arterial stiffness mismatch (pulse wave velocity ratio) was assessed using carotid-femoral pulse wave velocity divided by carotid-radial pulse wave velocity in 310 adult patients on dialysis. After a median follow-up of 29 months, 146 (47%) deaths occurred. The hazard ratio (HR) for mortality related to PWV ratio in a Cox regression analysis was 1.43 (95% confidence interval [CI], 1.24-1.64; P<0.001 per 1 SD) and was still significant after adjustments for confounding factors, such as age, dialysis vintage, sex, cardiovascular disease, diabetes mellitus, smoking status, and weight (HR, 1.23; 95% CI: 1.02-1.49). The HRs for changes in 1 SD of augmentation index (HR, 1.35; 95% CI, 1.12-1.63), carotid-femoral pulse wave velocity (HR, 1.29; 95% CI, 1.11-1.50), and carotid-radial pulse wave velocity (HR, 0.80; 95% CI, 0.67-0.95) were statistically significant in univariate analysis, but were no longer statistically significant after adjustment for age. In conclusion, aortic-brachial arterial stiffness mismatch was strongly and independently associated with increased mortality in this dialysis population. Further studies are required to confirm these finding in lower-risk groups.

The impact of warfarin on the rate of progression of aortic stiffness in hemodialysis patients: a longitudinal study.

BACKGROUND: Accelerated progression of aortic stiffness in patients with advanced chronic kidney disease is not well explained by the traditional cardiovascular risk factors. We hypothesized that vitamin K deficiency may result in an accelerated progression of aortic stiffness in the pro-calcifying uremic milieu. METHOD: Eighteen hemodialysis (HD) patients on warfarin were matched to 54 HD patients without warfarin (control). Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. In the control group, spontaneous vitamin K deficiency was defined as proteins induced by vitamin K deficiency/absence-II >median. RESULTS: At baseline, clinical characteristics and cf-PWV were similar. Adjusted cf-PWV increased by 0.86 ± 1.87 m/s in control and by 2.24 ± 2.68 m/s in warfarin group (P = 0.024). After adjustments for confounders, warfarin therapy was independently associated with progression of aortic stiffness (P = 0.016). The rate of progression of aortic stiffness showed a linear trend in response to vitamin K status and warfarin therapy, suggesting that at least part of the effects are mediated through reduced availability of vitamin K. The unadjusted and adjusted hazard ratio (HR) of warfarin therapy on mortality were, respectively, 2.40 (P = 0.006) and 2.53 (P = 0.006). In a forward conditional Cox regression analysis, age, albumin, augmentation index (AIx) and a cf-PWV > 13.8 m/s at the time of follow-up (HR: 2.11, P = 0.05) were independent determinants of mortality, whereas warfarin use was not retained as an independent factor. Finally, control patients with poor vitamin K status had an intermediate survival as compared with controls with better vitamin K status and patients with warfarin (P = 0.01). CONCLUSION: This is the first study to show a temporal association between warfarin, functional vitamin K deficiency and progression of aortic stiffness in HD patients. These findings suggest that the net cardiovascular benefit of long-term warfarin therapy may need to be reevaluated in this population.

The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

Herein, updated evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in Canadian adults are detailed. For 2014, 3 existing recommendations were modified and 2 new recommendations were added. The following recommendations were modified: (1) the recommended sodium intake threshold was changed from ≤ 1500 mg (3.75 g of salt) to approximately 2000 mg (5 g of salt) per day; (2) a pharmacotherapy treatment initiation systolic blood pressure threshold of ≥ 160 mm Hg was added in very elderly (age ≥ 80 years) patients who do not have diabetes or target organ damage (systolic blood pressure target in this population remains at < 150 mm Hg); and (3) the target population recommended to receive low-dose acetylsalicylic acid therapy for primary prevention was narrowed from all patients with controlled hypertension to only those ≥ 50 years of age. The 2 new recommendations are: (1) advice to be cautious when lowering systolic blood pressure to target levels in patients with established coronary artery disease if diastolic blood pressure is ≤ 60 mm Hg because of concerns that myocardial ischemia might be exacerbated; and (2) the addition of glycated hemoglobin (A1c) in the diagnostic work-up of patients with newly diagnosed hypertension. The rationale for these recommendation changes is discussed. In addition, emerging data on blood pressure targets in stroke patients are discussed; these data did not lead to recommendation changes at this time. The Canadian Hypertension Education Program recommendations will continue to be updated annually.

Vascular remodeling and media calcification increases arterial stiffness in chronic kidney disease.

BACKGROUND: Cardiovascular disease is the most common cause of death in patients with chronic kidney disease (CKD). Arterial stiffness and calcification are non-traditional risk factors of cardiovascular disease in CKD. In CKD rats, we investigated the involvement of smooth muscle cells differentiation to osteoblast-like cells and blood vessel wall remodeling, associated with media calcification, in arterial stiffness. METHOD: CKD with vascular calcification was induced by subtotal nephrectomy followed by treatment with a high calcium and phosphate diet, and vitamin D supplementation (Ca/P/VitD). At week 3-6, hemodynamic parameters and pulse wave velocity (PWV) were assessed. Vascular media calcification and remodeling were determined by histological von Kossa staining and confocal immunofluorescence analysis of osteocalcin, elastin, α-smooth muscle actin (α-SMA) and collagen-1. RESULTS: Treatment of CKD rats with Ca/P/VitD, but not normal animals, induced a significant increase in pulse pressure and PWV (p < 0.05) and marked calcification in the media. In calcification areas, de novo expression of osteocalcin was observed, whereas α-SMA immunofluorescence levels were reduced (p < 0.01). The immunofluorescence levels of elastin were also reduced, which was related to disruption of elastic lamella. In contrast, collagen-1 immunofluorescence levels in areas of calcification were increased (p < 0.01). Changes in both α-SMA and elastin inversely correlated with the PWV. CONCLUSION: This study indicate that smooth muscle cells differentiation to osteoblast-like cells and the associated media remodeling, which includes disruption of elastic lamellas and deposition of collagen are, at least in part, associated with the increased arterial stiffness observed in CKD rats with vascular calcification.

Determinants of progression of aortic stiffness in hemodialysis patients: a prospective longitudinal study.

Aortic stiffness is associated with increased cardiovascular mortality in patients with chronic kidney disease. However, the rate of progression of arterial stiffness and the role of cardiovascular risk factors in the progression of arterial stiffness has never been established in a longitudinal study. In a prospective, longitudinal, observational study, carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were assessed in 109 hemodialysis patients at baseline and after a mean follow-up of 1.2 years. We examined the impact of age, atherosclerotic cardiovascular disease, diabetes mellitus, dialysis vintage, and pentosidine (a well-characterized, advanced glycation end products) on the rate of progression of aortic stiffness. The annual rate of changes in carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were 0.84 m/s per year (95% confidence interval, 0.50-1.12 m/s per year) and -0.66 m/s per year (95% confidence interval, -0.85 to -0.47 m/s per year), respectively. Older subjects, and patients with diabetes mellitus or atherosclerotic cardiovascular disease had higher aortic stiffness at baseline, however, the rate of progression of aortic stiffness was only determined by plasma pentosidine levels (P=0.001). The degree of baseline aortic stiffness was a significant determinant of the regression of brachial stiffness (P<0.001) suggesting that the regression of brachial stiffness occurs in response to central aortic stiffness. These findings suggest that traditional cardiovascular risk factors may play some role in the progression of aortic stiffness before development of advanced chronic kidney disease, and that the enhanced rate of progression of aortic stiffness in chronic kidney disease patients on dialysis are probably determined by more specific chronic kidney disease-related risk factors such as advanced-glycation end products.

The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2013. This year's update includes 2 new recommendations. First, among nonhypertensive or stage 1 hypertensive individuals, the use of resistance or weight training exercise does not adversely influence blood pressure (BP) (Grade D). Thus, such patients need not avoid this type of exercise for fear of increasing BP. Second, and separately, for very elderly patients with isolated systolic hypertension (age 80 years or older), the target for systolic BP should be < 150 mm Hg (Grade C) rather than < 140 mm Hg as recommended for younger patients. We also discuss 2 additional topics at length (the pharmacological treatment of mild hypertension and the possibility of a diastolic J curve in hypertensive patients with coronary artery disease). In light of several methodological limitations, a recent systematic review of 4 trials in patients with stage 1 uncomplicated hypertension did not lead to changes in management recommendations. In addition, because of a lack of prospective randomized data assessing diastolic BP thresholds in patients with coronary artery disease and hypertension, no recommendation to set a selective diastolic cut point for such patients could be affirmed. However, both of these issues will be examined on an ongoing basis, in particular as new evidence emerges.

Neutralization of tumor necrosis factor-alpha reduces renal fibrosis and hypertension in rats with renal failure.

BACKGROUND: Increased production of tumor necrosis factor-α (TNF-α) in chronic kidney disease may be involved in the progression of renal failure and injury, and cardiovascular disease. We investigated the effect of TNF-α neutralization on renal failure, inflammation and fibrosis, and blood pressure in rats with renal failure. METHODS AND RESULTS: Renal failure was induced by renal mass reduction and the animals were treated with PEG-sTNFR1, a pegylated form of soluble TNF type 1 receptor that neutralizes TNF-α, for 6 weeks. Systolic, diastolic and mean arterial pressures were higher in renal failure rats that were associated with increased serum creatinine, albuminuria and renal injury comprised of blood vessel media hypertrophy, focal and segmental glomerulosclerosis, tubular atrophy and interstitial inflammation and fibrosis. These changes were associated with greater levels of TNF-α, transforming growth factor (TGF)-ß1, nuclear transcription factor NF-ĸB and cytosolic phospho-IĸB-α, and inflammatory markers expression (ICAM-1, VCAM-1 and MCP-1). Moreover, endothelin (ET)-1 production was also increased, whereas nitric oxide (NO) release was decreased. TNF-α neutralization reduced hypertension, albuminuria and renal inflammation and fibrosis, which were coupled to a reduction in renal NF-ĸB activation, inflammatory markers expression, TGF-ß1 and ET-1 production, and an increase in NO release. CONCLUSION: Neutralization of TNF-α in rats with renal failure decreases NF-ĸB activity that is associated with a reduction in renal TGF-ß1 and ET-1 production, and an improvement of NO release. These effects likely reduce renal inflammation and fibrosis, and blood pressure indicating a pivotal role for TNF-α, at least, in the progression of renal injury.

The 2012 Canadian hypertension education program recommendations for the management of hypertension: blood pressure measurement, diagnosis, assessment of risk, and therapy.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2012. The new recommendations are: (1) use of home blood pressure monitoring to confirm a diagnosis of white coat syndrome; (2) mineralocorticoid receptor antagonists may be used in selected patients with hypertension and systolic heart failure; (3) a history of atrial fibrillation in patients with hypertension should not be a factor in deciding to prescribe an angiotensin-receptor blocker for the treatment of hypertension; and (4) the blood pressure target for patients with nondiabetic chronic kidney disease has now been changed to < 140/90 mm Hg from < 130/80 mm Hg. We also reviewed the recent evidence on blood pressure targets for patients with hypertension and diabetes and continue to recommend a blood pressure target of less than 130/80 mm Hg.

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.

Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.

eNOS gene delivery prevents hypertension and reduces renal failure and injury in rats with reduced renal mass.

BACKGROUND: Impaired nitric oxide (NO) release in chronic renal failure has been implicated in the pathogenesis of hypertension and the progression of renal insufficiency. We investigated whether gene delivery of the endothelial NO synthase (eNOS) improves NO release and reduces blood pressure and renal failure and injury in rats with reduced renal mass. METHODS: Renal failure was induced by renal artery branches ligation. Two weeks later, rats with renal failure were divided into three groups and received an intravenous injection of the vehicle or the adenovirus that expresses eNOS or ß-galactosidase (ß-gal). Systolic blood pressure, renal parameters and histopathology were assessed at Week 4 after gene delivery. RESULTS: At the end of the study, systolic blood pressures, serum creatinine, proteinuria, urinary endothelin-1 (ET-1) excretion and renal cortex ET-1 levels were increased, whereas plasma and urine NO(2)/NO(3) were reduced in renal failure rats as compared to normal controls. Renal injury comprised blood vessel media hypertrophy, focal and segmental glomerular sclerosis, tubular atrophy and interstitial fibrosis. Gene delivery of eNOS, but not ß-gal, prevented an increase in systolic blood pressure and proteinuria, and a reduction in plasma and urine NO(2)/NO(3). eNOS gene delivery also reduced a rise in serum creatinine, urinary ET-1 excretion and renal cortex ET-1 levels, and the renal vascular, glomerular and tubular injury. CONCLUSION: This study indicates that eNOS gene delivery in rats with renal failure improves NO release, which likely prevents the aggravation of hypertension and slows down the progression of renal failure and injury.

Active renin mass concentration to determine aldosterone-to-renin ratio in screening for primary aldosteronism.

BACKGROUND: Active renin mass concentration (ARC) is independent of the endogenous level of angiotensinogen, and less variable and more reproducible than plasma renin activity. Reference values for the aldosterone-to-renin ratio (ARR) using ARC are still undefined. The objective of the present study was to determine the threshold of ARR using ARC measurement to screen for primary aldosteronism. METHODS: A total of 211 subjects were included in the study, comprising 78 healthy normotensive controls, 95 patients with essential hypertension, and 38 patients with confirmed primary aldosteronism (20 with surgery-confirmed aldosterone-producing adenoma and 18 with idiopathic adrenal hyperplasia). Blood samples were drawn from ambulatory patients and volunteers in the mid-morning without specific dietary restriction for measuring plasma aldosterone concentration, ARC, and serum potassium. RESULTS: Most normotensive controls and essential hypertension patients had ARR results below 100 pmol/ng, a value which corresponded to 3.3 times the median of these two groups. CONCLUSION: Patients with ARR values above this level should be considered for further investigation (confirmatory tests) or for repeat testing should ARR values be borderline. This study indicates that ARC can be used reliably in determining ARR for primary aldosteronism screening.

The 2011 Canadian Hypertension Education Program recommendations for the management of hypertension: blood pressure measurement, diagnosis, assessment of risk, and therapy.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2011. The major guideline changes this year are: (1) a recommendation was made for using comparative risk analogies when communicating a patient's cardiovascular risk; (2) diagnostic testing issues for renal artery stenosis were discussed; (3) recommendations were added for the management of hypertension during the acute phase of stroke; (4) people with hypertension and diabetes are now considered high risk for cardiovascular events if they have elevated urinary albumin excretion, overt kidney disease, cardiovascular disease, or the presence of other cardiovascular risk factors; (5) the combination of an angiotensin-converting enzyme (ACE) inhibitor and a dihydropyridine calcium channel blocker (CCB) is preferred over the combination of an ACE inhibitor and a thiazide diuretic in persons with diabetes and hypertension; and (6) a recommendation was made to coordinate with pharmacists to improve antihypertensive medication adherence. We also discussed the recent analyses that examined the association between angiotensin II receptor blockers (ARBs) and cancer.

Impact of dialysate calcium concentration on the progression of aortic stiffness in patients on haemodialysis.

BACKGROUND: Higher dialysate calcium (DCa) can result in an acute and transient increase in arterial stiffness. The aim of the present study is to evaluate the impact of DCa on the progression of arterial stiffness, calcium balance and bone metabolism in haemodialysis (HD) patients over a 6-month period. Method. We randomly assigned 30 patients on chronic HD to be dialysed with a DCa of 1.12 or 1.37 mmol/L for a period of 6 months. Aortic stiffness and brachial stiffness were respectively measured by carotid-femoral pulse wave velocities (cf-PWV) and carotid-radial pulse wave velocity (cr-PWV) at baseline and at 3 and 6 months. Central pulse pressure (PP) and augmentation index were determined by radial artery tonometry. Dialysis calcium balance and parathyroid hormone (PTH) were measured monthly. Procollagen type-1 amino-terminal propeptide (P1NP) and C-terminal telopeptide of type-I collagen (CTX) were measured as markers of bone formation and resorption, respectively. Data was analysed by linear mixed model. RESULTS: Twenty-seven patients (66 ± 13 years old) with a mean duration of HD of 5.8 ± 3.6 months completed the study. At baseline, the groups were similar with respect to age, serum levels of calcium, phosphate and PTH, blood pressure (BP), cf-PWV and cr-PWV. The cf-PWV at baseline and 3 and 6 months were, respectively, 13.4 ± 4.2, 14.7 ± 3.31 and 13.6 ± 2.5 m/s in the DCa 1.12 group and 14.6 ± 5.9, 15.8 ± 7.8 and 17.0 ± 7.0 m/s in the DCa 1.37 group. After correction for mean BP, cf-PWV increased with DCa 1.37 as compared to DCa 1.12 (Time-DCa interaction P = 0.002). However, there were no significant effects of DCa on progression of cr-PWV, central PP or augmentation index. During the intervention period, the mean PTH was slightly higher in the DCa 1.12 group as compared to the DCa 1.37 group (325 ± 185 versus 211 ± 128 ng/L, P = 0.054), and dialysis calcium balance was -8.1 ± 4.4 versus -0.2 ± 4.7 mmol/session, respectively, in groups with DCa 1.12 and DCa 1.37 (P = 0.0001). Treatment with DCa 1.12 mmol/L resulted in increasing levels of CTX as compared to DCa 1.37 (P = 0.02), whereas the P1NP levels did not change significantly in either group. CONCLUSIONS: In this study, aortic stiffness progressed with DCa 1.37, while it remained stable with DCa 1.12 over a 6-month period. These results suggest that higher DCa concentrations could be a risk factor for the progression of aortic stiffness in HD patients. In the context of limited oral calcium, the long-term safety of DCa 1.12 on bone metabolism remains to be established.

Age-related and blood pressure-independent reduction in aortic stiffness after kidney transplantation.

OBJECTIVES: Aortic stiffness is a novel cardiovascular risk factor in patients with chronic kidney disease (CKD). The purpose of the present study is to examine whether there is a blood pressure-independent improvement in aortic stiffness 3 months after successful kidney transplantation (KTx), and whether this improvement is age-dependent. METHOD: In this prospective, longitudinal observational study, we studied hemodynamic and biological parameters prior to and 3 months after a KTx in 52 stage 5 CKD patients. Aortic stiffness was measured by carotido-femoral pulse wave velocity (c-f PWV) and enhanced central wave reflection was evaluated by the heart rate-adjusted central augmentation index (AIx) by means of arterial tonometry. Endothelin-1, L-arginine, asymmetric dimethylarginine (biomarkers of endothelial dysfunction), pentosidine (advanced glycation end-products) and mineral metabolism parameters were also measured. RESULTS: After adjusting for the reduction in mean blood pressure, c-f PWV decreased significantly from 12.1 ± 3.3 to 11.6 ± 2.3 m/s (P < 0.05). In an analysis stratified by age, this improvement was only present in patients older than 50 years of age as compared with patients younger than 50 years of age (-5.5 ± 2.2 vs. 2.1 ± 1.9%, P < 0.05). AIx decreased from 22 ± 11 to 14 ± 13% (P < 0.01), but this reduction was not age-dependent. We also observed a similar degree of improvement in the biomarker levels of endothelial dysfunction and pentosidine in both groups. CONCLUSION: This study shows for the first time that there is an age-dependent improvement in aortic stiffness after KTx. These observations suggest that older patients may have an added cardiovascular risk reduction after a successful KTx.

2010 Canadian Hypertension Education Program (CHEP) recommendations: the scientific summary - an update of the 2010 theme and the science behind new CHEP recommendations.

The present article is a summary of the theme, the key recommendations for management of hypertension and the supporting clinical evidence of the 2010 Canadian Hypertension Education Program (CHEP). In 2010, CHEP emphasizes the need for health care professionals to stay informed about hypertension through automated updates at www.htnupdate.ca. A new interactive Internet-based lecture series will be available in 2010 and a program to train community hypertension leaders will be expanded. Patients can also sign up to receive regular updates in a pilot program at www.myBPsite.ca. In 2010, the new recommendations include consideration for using automated office blood pressure monitors, new targets for dietary sodium for the prevention and treatment of hypertension that are aligned with the national adequate intake values, and recommendations for considering treatment of selected hypertensive patients at high risk with calcium channel blocker/angiotensin-converting enzyme inhibitor combinations and the use of angiotensin receptor blockers.

The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: part I - blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension. EVIDENCE: MEDLINE searches were conducted from November 2008 to October 2009 with the aid of a medical librarian. Reference lists were scanned, experts were contacted, and the personal files of authors and subgroup members were used to identify additional studies. Content and methodological experts assessed studies using prespecified, standardized evidence-based algorithms. Recommendations were based on evidence from peer-reviewed full-text articles only. RECOMMENDATIONS: Recommendations for blood pressure measurement, criteria for hypertension diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic testing, diagnosis of renovascular and endocrine causes of hypertension, home and ambulatory monitoring, and the use of echocardiography in hypertensive individuals are outlined. Changes to the recommendations for 2010 relate to automated office blood pressure measurements. Automated office blood pressure measurements can be used in the assessment of office blood pressure. When used under proper conditions, an automated office systolic blood pressure of 135 mmHg or higher or diastolic blood pressure of 85 mmHg or higher should be considered analogous to a mean awake ambulatory systolic blood pressure of 135 mmHg or higher and diastolic blood pressure of 85 mmHg or higher, respectively. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. To be approved, all recommendations were required to be supported by at least 70% of task force members. These guidelines will continue to be updated annually.

The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy.

OBJECTIVE: To update the evidence-based recommendations for the prevention and treatment of hypertension in adults for 2010. OPTIONS AND OUTCOMES: For lifestyle and pharmacological interventions, randomized trials and systematic reviews of trials were preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the general lack of long-term morbidity and mortality data in this field. Progressive renal impairment was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease. EVIDENCE: A Cochrane Collaboration librarian conducted an independent MEDLINE search from 2008 to August 2009 to update the 2009 recommendations. To identify additional studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS: For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to 1500 mg (65 mmol) per day in adults 50 years of age or younger, to 1300 mg (57 mmol) per day in adults 51 to 70 years of age, and to 1200 mg (52 mmol) per day in adults older than 70 years of age; perform 30 min to 60 min of moderate aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m(2) to 24.9 kg/m(2)) and waist circumference (less than 102 cm for men and less than 88 cm for women); limit alcohol consumption to no more than 14 standard drinks per week for men or nine standard drinks per week for women; follow a diet that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources, and that is low in saturated fat and cholesterol; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on the patient's global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in patients with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, considerations for initial therapy should include thiazide diuretics, angiotensin- converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. The combination of ACE inhibitors and ARBs should not be used, unless compelling indications are present to suggest consideration of dual therapy. Agents appropriate for first-line therapy for isolated systolic hypertension include thiazide diuretics, long-acting dihydropyridine CCBs or ARBs. In patients with coronary artery disease, ACE inhibitors, ARBs or betablockers are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. In selected high-risk patients in whom combination therapy is being considered, an ACE inhibitor plus a long-acting dihydropyridine CCB is preferable to an ACE inhibitor plus a thiazide diuretic. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian lipid treatment guidelines. Selected patients with hypertension who do not achieve thresholds for statin therapy, but who are otherwise at high risk for cardiovascular events, should nonetheless receive statin therapy. Once blood pressure is controlled, low-dose acetylsalicylic acid therapy should be considered. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 80% consensus. These guidelines will continue to be updated annually. SPONSORS: The Canadian Hypertension Education Program process is sponsored by the Canadian Hypertension Society, Blood Pressure Canada, the Public Health Agency of Canada, the College of Family Physicians of Canada, the Canadian Pharmacists Association, the Canadian Council of Cardiovascular Nurses, and the Heart and Stroke Foundation of Canada.