Philip A. McFarlane

The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy

OBJECTIVE To update the evidence-based recommendations for the prevention and management of hypertension in adults for 2009. OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was 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 lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction 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 2007 to August 2008 to update the 2008 recommendations. To identify additional published 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 less than 2300 mg (100 mmol)/day (and 1500 mg to 2300 mg [65 mmol to 100 mmol]/day in hypertensive patients); perform 30 min to 60 min of 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 (smaller than 102 cm for men and smaller than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a diet that is reduced in saturated fat and cholesterol, and that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on by the patients global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those 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, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin- converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as the initial treatment of hypertension if the systolic blood pressure is 20 mmHg above the target or if the diastolic blood pressure is 10 mmHg above the target. The combination of ACE inhibitors and ARBs should not be used. Other agents appropriate for first-line therapy for isolated systolic hypertension include long- acting dihydropyridine CCBs or ARBs. In patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors 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. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered. VALIDATION All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.

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 years 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.

Guidelines for the management of chronic kidney disease

New guidelines for the management of chronic kidney disease have been developed by the Canadian Society of Nephrology (Appendix 1 contains the full-text guidelines; available at [www.cmaj.ca/cgi/content/full/179/11/1154/DC1][1]). These guidelines describe key aspects of the management of chronic

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 patients 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.

Hemodialysis Vascular Access Modifies the Association between Dialysis Modality and Survival

Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach. We identified 40,526 incident adult dialysis patients from the Canadian Organ Replacement Register (2001 to 2008). Compared with the 7412 PD patients, 1-year mortality was similar for the 6663 HD-AVF/AVG patients but was 80% higher for the 24,437 HD-CVC patients (adjusted HR, 1.8; 95% confidence intervals [CI], 1.6 to 1.9). During the entire period of follow-up, HD-AVF/AVG patients had a lower risk for death, and HD-CVC patients had a higher risk for death compared with patients on PD. In conclusion, the use of CVCs in incident HD patients largely accounts for the early survival benefit seen with PD.

Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.

Cardiovascular disease in kidney donors: matched cohort study

Objective To determine whether people who donate a kidney have an increased risk of cardiovascular disease. Design Retrospective population based matched cohort study. Participants All people who were carefully selected to become a living kidney donor in the province of Ontario, Canada, between 1992 and 2009. The information in donor charts was manually reviewed and linked to provincial healthcare databases. Matched non-donors were selected from the healthiest segment of the general population. A total of 2028 donors and 20 280 matched non-donors were followed for a median of 6.5 years (maximum 17.7 years). Median age was 43 at the time of donation (interquartile range 34-50) and 50 at the time of follow-up (42-58). Main outcome measures The primary outcome was a composite of time to death or first major cardiovascular event. The secondary outcome was time to first major cardiovascular event censored for death. Results The risk of the primary outcome of death and major cardiovascular events was lower in donors than in non-donors (2.8 v 4.1 events per 1000 person years; hazard ratio 0.66, 95% confidence interval 0.48 to 0.90). The risk of major cardiovascular events censored for death was no different in donors than in non-donors (1.7 v 2.0 events per 1000 person years; 0.85, 0.57 to 1.27). Results were similar in all sensitivity analyses. Older age and lower income were associated with a higher risk of death and major cardiovascular events in both donors and non-donors when each group was analysed separately. Conclusions The risk of major cardiovascular events in donors is no higher in the first decade after kidney donation compared with a similarly healthy segment of the general population. While we will continue to follow people in this study, these interim results add to the evidence base supporting the safety of the practice among carefully selected donors.

Successful Pregnancies on Nocturnal Home Hemodialysis

BACKGROUND AND OBJECTIVES Women of childbearing age on conventional hemodialysis (CHD) have decreased fertility when compared with the general population. Even in women who conceived, maternal morbidity and fetal mortality remained elevated. We hypothesized that nocturnal hemodialysis (NHD) (3 to 6 sessions per week, 6 to 8 h per treatment), by augmenting uremic clearance, leads to a more hospitable maternal environment and therefore superior outcomes in fertility and pregnancy compared with CHD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS This is a descriptive cohort study of all female patients achieving pregnancy and delivering a live infant while on NHD at the University Health Network, St. Michaels Hospital, and Humber River Regional Hospital from 2001 to 2006 in Toronto, Canada. Our primary objective was to describe maternal and fetal outcomes in addition to the changes in biochemical parameters after conception in our cohort. RESULTS Our cohort included five patients (age range, 31 to 37 yr) who had seven pregnancies while on NHD and delivered six live infants. All had previously been on CHD, but none conceived during that time. In all patients, the amount of hemodialysis was increased (from a weekly mean of 36 +/- 10 to 48 +/- 5 h; P < 0.01) after pregnancy was diagnosed. Mean predialysis blood urea and mean arterial BP were maintained within normal physiological parameters. The mean gestational age of the cohort was 36.2 +/- 3 wk and the mean birth weight was 2417.5 +/- 657 g. The maternal and fetal complications observed in the cohort included intrauterine growth restriction or small for gestational age (n = 2), preterm delivery (<32 wk) (n = 1), and shortened cervix threatened labor (n = 1). Anemia was accentuated during pregnancy, and intravenous iron and erythropoietin requirements were increased. To maintain normal physiological indices for plasma phosphate, an augmented dialysate phosphate supplementation regimen was required. CONCLUSIONS NHD may allow for improved fertility. Delivering a live infant at a mature gestational age is feasible for patients on NHD. Our cohort tended to have fewer maternal and fetal complications compared with historical controls. Hemoglobin and phosphate levels must be monitored with treatment adjusted accordingly.

Enhanced chemo-responsiveness in patients with sleep apnoea and end-stage renal disease

Although sleep apnoea is very common in patients with end-stage renal disease, the physiological mechanisms for this association have not yet been determined. The current authors hypothesised that altered respiratory chemo-responsiveness may play an important role. In total, 58 patients receiving treatment with chronic dialysis were recruited for overnight polysomnography. A modified Read rebreathing technique, which is used to assess basal ventilation, ventilatory sensitivity and threshold, was completed before and after overnight polysomnography. Patients were divided into apnoeic (n = 38; apnoea/hypopnoea index (AHI) 35±22 events·h-1) and nonapnoeic (n = 20; AHI 3±3 events·h-1) groups, with the presence of sleep apnoea defined as an AHI >10 events·h-1. While basal ventilation and the ventilatory recruitment threshold were similar between groups, ventilatory sensitivity during isoxic hypoxia (partial pressure of oxygen (PO2) 6.65 kPa) and hyperoxia (PO2 19.95 kPa) was significantly greater in apnoeic patients. Overnight changes in chemoreflex responsiveness were similar between groups. In conclusion, these data indicate that the responsiveness of both the central and peripheral chemoreflexes is augmented in patients with sleep apnoea and end-stage renal disease. Since increased ventilatory sensitivity to hypercapnia destabilises respiratory control, the current authors suggest this contributes to the pathogenesis of sleep apnoea in this patient population.

Suboptimal initiation of dialysis with and without early referral to a nephrologist

BACKGROUND Our objective was to examine patients who initiate renal replacement therapy (RRT) at 10 representative Canadian centers, characterize their initiation as inpatient or outpatient and describe their initial type of dialysis access, duration of pre-dialysis care and clinical status at the time of dialysis initiation. We also examined the impact of an optimal dialysis start (i.e. initiated as an outpatient with an arteriovenous fistula, arteriovenous graft or peritoneal dialysis catheter) on subsequent health outcomes. METHODS Charts of consecutive incident RRT patients were identified from 1 July to 31 December 2006. Information was collected until 6 months after the initiation or until death, transplant or transfer. RESULTS Three hundred and thirty-nine incident RRT patients were studied: 39.6% initiated as an inpatient; 54% started hemodialysis (HD) with a central venous catheter; 15.3% had <1 month predialysis care, while 64.6% had >1 year. Optimal starts occurred in 39.5% of patients. For HD patients, optimal starts occurred in 19.8%. Suboptimal starts were noted in patients referred <12 months prior to end-stage renal disease (44%) and in patients referred earlier (56%). The composite end point of death, transfusion or subsequent hospitalization was significantly reduced with an optimal start [hazard ratio 0.47 (95% confidence interval 0.32-0.68), P = 0.0001]. CONCLUSIONS Suboptimal initiation of dialysis is common in patients referred early or late. The benefits of early referral are lost if dialysis is initiated suboptimally. There is a need to identify factors that lead to suboptimal initiation despite early referral.