Michel Vallée

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.

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.

Characterization of UDP-glucuronosyltransferases active on steroid hormones ☆

In recent years, the enzymes which are involved in the formation of DHT in steroid target tissues have been well investigated, however, enzymes responsible for the catabolism and elimination of steroids in these tissues, in particular the uridine diphospho-glucuronosyltransferase (UGT) family of enzymes, have received much less attention. We have recently demonstrated that human and monkey are unique in having high plasma levels of C19 steroid glucuronides. These circulating conjugates have been proposed to reflect the peripheral conversion of adrenal and gonadal C19 steroids to potent androgens, especially DHT. In humans, the presence of steroid UGT activities is found in the liver and several extrahepatic tissues including the prostate, mammary gland and ovary. In addition, UGT activities were observed in breast and prostate tumor cell lines such as MCF-7 and LNCaP, respectively. In agreement with the presence of steroid conjugating enzymes in extrahepatic tissues, UGT cDNA clones, which encode steroid conjugating proteins, have been isolated from libraries constructed from human and monkey prostate mRNA. The presence of UGT transcripts and proteins in extrahepatic tissues in both species, as determined by Northern blot, ribonuclease protection, specific RT-PCR, in situ hybridization, Western blot and immunocytochemistry analysis, indicate the relevance of steroid glucuronidation in tissues other than the liver. Knowing that both the human prostate and the human prostate cancer LNCaP cell line express steroid metabolizing proteins, including UGT enzymes, regulation of UGT mRNA and protein levels, as well as promoter activity was studied in these cells. The results demonstrate a differential regulation between the two highly related isoforms UGT2B15 and UGT2B17, where only the expression of UGT2B17 was affected following treatments of LNCaP cells with androgens, growth factors or cytokines. Steroid conjugation by UGT enzymes is potentially involved in hormone inactivation in steroid target tissues, thus modifications in UGT expression levels may influence hormonal responses.

THE MONKEY AND HUMAN URIDINE DIPHOSPHATE-GLUCURONOSYLTRANSFERASE UGT1A9, EXPRESSED IN STEROID TARGET TISSUES, ARE ESTROGEN-CONJUGATING ENZYMES

Considering the physiologic importance of the steroid response, which is regulated in part by steroid levels in a given tissue, relatively little is known about steroid glucuronidation, which is widely accepted as a major pathway involved in the catabolism and elimination of steroid hormones from the human body. In a previous study, it was ascertained that the monkey may be the most appropriate model in which to examine the role of steroid glucuronidation. Northern blot analysis of simian RNA, hybridized with human UGT complementary DNA (cDNA) probes demonstrate the similarity of the transcripts. The simian UGT1A09 cDNA isolated from a liver library is 2396 bp and contains an open reading frame encoding 530 amino acids. The predicted primary structure is most homologous to the human UGT1A9 (hUGT1A9) enzyme, which share 93% identity. Stable transfection of the monkey UGT1A09 (monUGT1A09) cDNA into HK293 cells, expresses a microsomal protein with an apparent molecular mass of 55 kDa. Of the more than 30 end...

Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKD

BACKGROUND AND OBJECTIVES Hyperkalemia affects up to 10% of patients with CKD. Sodium polystyrene sulfonate has long been prescribed for this condition, although evidence is lacking on its efficacy for the treatment of mild hyperkalemia over several days. This study aimed to evaluate the efficacy of sodium polystyrene sulfonate in the treatment of mild hyperkalemia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In total, 33 outpatients with CKD and mild hyperkalemia (5.0-5.9 mEq/L) in a single teaching hospital were included in this double-blind randomized clinical trial. We randomly assigned these patients to receive either placebo or sodium polystyrene sulfonate of 30 g orally one time per day for 7 days. The primary outcome was the comparison between study groups of the mean difference of serum potassium levels between the day after the last dose of treatment and baseline. RESULTS The mean duration of treatment was 6.9 days. Sodium polystyrene sulfonate was superior to placebo in the reduction of serum potassium levels (mean difference between groups, -1.04 mEq/L; 95% confidence interval, -1.37 to -0.71). A higher proportion of patients in the sodium polystyrene sulfonate group attained normokalemia at the end of their treatment compared with those in the placebo group, but the difference did not reach statistical significance (73% versus 38%; P=0.07). There was a trend toward higher rates of electrolytic disturbances and an increase in gastrointestinal side effects in the group receiving sodium polystyrene sulfonate. CONCLUSIONS Sodium polystyrene sulfonate was superior to placebo in reducing serum potassium over 7 days in patients with mild hyperkalemia and CKD.

Association of Dialysis Modality with Risk for Infection-Related Hospitalization: A Propensity Score–Matched Cohort Analysis

BACKGROUND AND OBJECTIVES Peritonitis is a well known complication of peritoneal dialysis (PD), whereas in hemodialysis (HD), bacteremia can be life threatening. Whether patients undergoing PD have higher risk than HD patients for infection-related hospitalizations (IRH) remains unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A propensity score-matched retrospective cohort of patients undergoing long-term dialysis between January 2001 and December 2007 was assembled. Propensity scores were calculated using multivariable (demographic characteristics, smoking, body mass index, comorbid conditions, and laboratory data) logistic regression to estimate probability of receiving PD versus HD. A comparison of IRH risk by dialysis modality was estimated using a counting-process survival model. RESULTS A total of 910 pairs of patients were matched by propensity scores. During a median follow-up of 2.1 years (interquartile range, 1.1-3.5 years), 341 patients were hospitalized once for an infection, 123 twice, and 106 at least three times. PD was associated with an increased risk for IRH compared with HD (propensity-matched hazard ratio [HR], 1.52). PD was associated with a reduced risk for septicemia (HR, 0.31) and pneumonia (HR, 0.58) but also an increased risk for dialysis-related infectious hospitalizations (HR, 3.44), defined as all cases of peritonitis and vascular access-related bacteremia, but not all septicemia cases. CONCLUSIONS PD patients are at higher risk for IRH than are HD patients. This risk is mostly explained by dialysis-related infections. However, further studies are needed to evaluate whether the severity of those hospitalizations is similar and whether this increased risk for IRH is associated with worse outcomes.

Ten-year experience with fungal peritonitis in peritoneal dialysis patients: antifungal susceptibility patterns in a North-American center

OBJECTIVE To describe the clinical and microbiological features associated with fungal peritonitis in peritoneal dialysis (PD) patients at Hôpital Maisonneuve-Rosemont, from August 1996 to July 2006. METHODS Cases were retrieved from the microbiology laboratory culture registry. Antifungal susceptibility was determined by the Clinical and Laboratory Standards Institute M27A3 method. RESULTS Among 288 PD patients (total follow-up of 7258 patient-months), nine were found with fungal peritonitis. Candida spp were identified in all of them, with a majority of non-albicans Candida species. Resistance to fluconazole, itraconazole, or voriconazole was as frequent as potential resistance to amphotericin B. No isolate was resistant to caspofungin and one was resistant to micafungin. Prior bacterial peritonitis was frequent (67%). All patients had their PD catheter removed and all of them survived. CONCLUSIONS In our institution, fungal peritonitis in PD patients is rare. All cases were caused by Candida species. Variable susceptibility patterns were observed, which may influence the initial empirical antifungal therapy and underscore the importance of individual speciation and susceptibility testing of invasive Candida isolates.

A case of an aortic dissection in a young adult: a refresher of the literature of this "great masquerader"

Aortic dissection is often misdiagnosed, especially among young patients, and it is associated with a high mortality rate. We present here a case of fatal acute aortic dissection in a young man who was misdiagnosed with pericarditis. We reviewed the literature of acute aortic dissection in young people and we focused particularly on clinical presentations, outcomes and investigations of aortic dissection. We report a case of a 33-year-old man with a history of uncontrolled hypertension with acute pleuretic chest pain who was transferred to our hospital for suspected pulmonary embolism and died of acute hemorragic pericardial effusion from an ascendant aortic dissection. We should never rule out aortic dissection off our differential diagnosis on the sole basis of a patient’s young age.

Reporting on sex-based analysis in clinical trials of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker efficacy

BACKGROUND Clinical practice recommendations for hypertension do not make recommendations specific to men or women. However, the sex hormones appear to modulate differently the renin-angiotensin system (RAS), which plays a central role in the regulation of blood pressure. Today, little is known about the effects of sex on the efficacy of therapies that antagonize the RAS, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). OBJECTIVE To identify randomized controlled trials evaluating the efficacy of ACEIs and ARBs in preventing major cardiovascular outcomes, determine what proportion of the trial participants were female, and evaluate whether there was any evidence of a sex difference in the efficacy of these agents. METHODS A systematic review of the literature was conducted to identify randomized controlled trials that used either ACEIs or ARBs for the treatment of hypertension. RESULTS Thirteen ACEI trials and nine ARB trials were identified. Sex-specific outcome data were available in six of the ACEI trials and three of the ARB trials. These trials enrolled 74,105 patients; 39.1% were women. Seven of the nine trials indicated that ACEIs or ARBs may be slightly more beneficial in men. The magnitude of these differences, in most trials, was small. CONCLUSIONS Sex-specific data are reported in 43% of large hypertension clinical trials. Review of the trials reporting sex-specific effect sizes indicates that ACEIs and ARBs may be more effective in men.