Hypertension: Prasad R

Khan NA, Hemmelgarn B, Herman RJ, Bell CM, Mahon JL, Leiter LA, Rabkin SW, Hill MD, Padwal R, Touyz RM, Larochelle P, Feldman RD, Schiffrin EL, Campbell NR, Moe G, Prasad R, Arnold MO, Campbell TS, Milot A, Stone JA, Jones C, Ogilvie RI, Hamet P, Fodor G, Carruthers G, Burns KD, Ruzicka M, DeChamplain J, Pylypchuk G, Petrella R, Boulanger JM, Trudeau L, Hegele RA, Woo V, McFarlane P, Vallée M, Howlett J, Bacon SL, Lindsay P, Gilbert RE, Lewanczuk RZ, Tobe S, Anonymous00150. · Division of General Internal Medicine, University of British Columbia, Vancouver, Canada. · Can J Cardiol. · Pubmed #19417859 No free full text.

Abstract: 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 patient's 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.

Padwal RS, Hemmelgarn BR, Khan NA, Grover S, McKay DW, Wilson T, Penner B, Burgess E, McAlister FA, Bolli P, Hill MD, Mahon J, Myers MG, Abbott C, Schiffrin EL, Honos G, Mann K, Tremblay G, Milot A, Cloutier L, Chockalingam A, Rabkin SW, Dawes M, Touyz RM, Bell C, Burns KD, Ruzicka M, Campbell NR, Vallée M, Prasad R, Lebel M, Tobe SW, Anonymous00149. · Division of General Internal Medicine, University of Alberta, Edmonton, Canada. · Can J Cardiol. · Pubmed #19417858 No free full text.

Abstract: OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension. OPTIONS AND OUTCOMES: The diagnosis of hypertension is dependent on appropriate blood pressure measurement, the timely assessment of serially elevated readings, the degree of blood pressure elevation, the method of measurement (office, ambulatory, home) and associated comorbidities. The presence of cardiovascular risk factors and target organ damage should be ascertained to assess global cardiovascular risk and determine the urgency, intensity and type of treatment required. EVIDENCE: MEDLINE searches were conducted from November 2007 to October 2008 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. Key messages include continued emphasis on the expedited, accurate diagnosis of hypertension, the importance of global risk assessment and the need for ongoing monitoring of hypertensive patients to identify incident type 2 diabetes. 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 were required to be supported by at least 70% of task force members. These guidelines will continue to be updated annually.

Zaltzman JS, Nash M, Chiu R, Prasad R. · Director of Renal Transplantation, Division of Nephrology, Dept of Medicine, University of Toronto, St Michael's Hospital, 30 Bond St, Toronto, Ontario, Canada M5B 1W8. · Nephrol Dial Transplant. · Pubmed #15031353 links to  free full text

Abstract: BACKGROUND: Allograft nephropathy, regardless of aetiology, leads to progressive renal injury and eventual graft loss. In native kidney disease, treatment of hypertension, in particular with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), has proven beneficial in retarding renal function decline. In the present study, we reviewed the clinical course of a renal transplant recipient cohort that was prescribed either an ACEi or ARB for biopsy-proven allograft nephropathy. METHODS: Patients were followed from the time of post-biopsy initiation of ACEi/ARB and were stratified based on biopsy findings. Outcomes of interest included safety, allograft survival, renal function and change in slope of renal function pre- and post-ACEi/ARB. RESULTS: The 5 year allograft survival after biopsy diagnosis of allograft nephropathy was 83%. Serum creatinine was 191+/-97 (86-377) micromol/l at the time of biopsy and 228+/-102 (102-575) micromol/l at last follow-up. The slopes of reciprocal creatinine vs time were used to calculate the decline in renal function and were compared pre- and post-ACEi/ARB. The mean slope+/-SD was -0.06+/-0.21 l/micromol x 10(-3) per month in the 12 months prior to therapy and -0.03+/-0.09 l/micromol x 10(-3) per month following therapy. The absolute difference in slopes was 0.03 (P =<0.0001). CONCLUSIONS: Treatment with ACEi/ARB may be beneficial in the management of allograft nephropathy.

Kloner RA, Weinberger M, Pool JL, Chrysant SG, Prasad R, Harris SM, Zyczynski TM, Leidy NK, Michelson EL, Anonymous00145. · The Heart Institute, Good Samaritan Hospital, University of Southern California, Los Angeles 90017-2308, USA. · Am J Cardiol. · Pubmed #11249891 No free full text.

Abstract: The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema.

Ushewokunze S, Haja Mydin HN, Prasad R, Mendelow AD. · Department of Neurosurgery, Newcastle General Hospital, Regional Neurosciences Centre, Newcastle-upon-Tyne, UK. · Br J Neurosurg. · Pubmed #19016120 No free full text.

Abstract: Selecting patients who will benefit from a permanent CSF diversion procedure in benign intracranial hypertension (BIH) or communicating hydrocephalus due to normal pressure hydrocephalus (NPH) has inherent problems. The percutaneous introduction of a lumbar subcutaneous shunt (LSS) under local anaesthesia facilitates both a prolonged CSF drainage under aseptic conditions and also elicits an adequate clinical response. We describe the technique of a lumbar subcutaneous shunt and our experience with its use in patients with BIH and NPH. Postprocedure changes in the patients' clinical status were noted. Patients with a transient clinical improvement underwent a subsequent definitive CSF diversion; those with a sustained clinical improvement or no change in symptoms had no further procedure.

Kaur G, Mishra S, Sehgal A, Prasad R. · Department of Physiology/Genetic Centre, Government Medical College and Hospital, Sector-32, College Building, Chandigarh, India. · Mol Cell Biochem. · Pubmed #18373068 No free full text.

Abstract: The present study was intended to appraise the oxidant and antioxidant status in preeclampsia women. Seventy-seven preeclampsia women with severe variety having average B.P. of 170/140 mmHg with proteinuria; 47 preeclampsia women with mild variety having average B.P. of 138/100 mmHg were compared to 56 healthy pregnant women and 15 non-pregnant women for oxidant and antioxidant status. Lipid peroxidation was assessed by measuring malondialdehyde (MDA), and antioxidant status was assessed by measuring antioxidant enzymes N.B.; superoxide dismutase (SOD), glutathione peroxidase, catalase and vitamins viz; A, E, C and reduced glutathione (GSH). Lipid peroxidation was significantly higher in severe preeclampsia women. Antioxidant status was also compromised as is evident from decreased GSH levels and increased SOD activities not only in severe preeclampsia but also in normal pregnancy and mild preeclampsia women compared to non-pregnant women. Decreased antioxidant enzyme activity viz catalase and glutathione peroxidase was observed in pregnancy as compared to non-pregnant women. The levels of vitamin E which act as an antioxidant were significantly elevated in preeclampsia compared to that of normal pregnancy. These findings conclude that initially the oxidative stress due to pregnancy-induced hypertension is critically combated by the intricate defensive mechanism of natural antioxidant system of the body. It appears that this imbalance between oxidant and antioxidant is the effect of disease and not the causative factor.

Rajwal SR, Davison SM, Prasad R, Brownlee K, McClean P. · Children's Liver and GI Unit, St. James's University Hospital, Leeds, UK. · Pediatr Transplant. · Pubmed #17976130 No free full text.

Abstract: HPS is defined as arterial hypoxemia because of pulmonary vasodilation as a result of cirrhotic or non-cirrhotic portal hypertension. This report describes a teenager with HPS because of primary sclerosing cholangitis/autoimmune hepatitis overlap syndrome requiring OLT. HPS resolved completely within three months of OLT, but recurred again at 12 months post-OLT following liver dysfunction secondary to a biliary stricture. She underwent a second OLT successfully and remains well two yr and three months post-second OLT. Recurrent HPS after OLT may occur because of graft dysfunction and as this novel case illustrates, retransplantation may lead to a successful outcome.

Mathur G, Prasad R, Robinson A, Rodrigues E, Wong P. · No affiliation provided · Int J Cardiol. · Pubmed #17442427 No free full text.

Abstract: We studied the utility of ABPM in patients with elevated clinic BP on 1-2 antihypertensive medications (group B, N=117), compared with those on no medications (group A, N=76) and on > or =3 medications (group C, N=110). 35% of patients in group B had adequately controlled 24-h BP based on ABPM, compared with 22.4% in group A (P=0.06) and 19.1% in group C (P=0.007). Antihypertensive treatment was not escalated in patients with adequately controlled BP. This suggests that ABPM has an important role in therapeutic decision-making for patients on 1-2 antihypertensive medications.

Singh UK, Prasad R, Mishra OP, Jayswal BP. · Department of Pediatrics, Nalanda Medical College, Patna, India. · Indian J Pediatr. · Pubmed #17202633 No free full text.

Abstract: OBJECTIVE: Miltefosine, an alkyl phospholipid has been found effective against visceral leishmaniasis (VL) in adults in various studies. The authors safety, tolerance and efficacy of Miltefosine and compared with available gold standard anti-Ieishmanial drug, Amphotericin B, a parenteral formulation in children with VL. METHODS: All consecutive children aged 1 yr to 14 yr, presented with fever, splenomegaly and positive LD body in splenic smear examination, admitted in pediatric ward of Nalanda Medical college and Child care center between 1st July 03 to 30th June 05 were taken for study. Patients were randomized into four groups. Group-l and 2 patients were given Miltefosine in dose of 2.5 mg/Kg day o.d. or b.i.d. per orally to a maxiIpum of 100 mg and group 3 and 4 Amphotericin B at a dose of 1 mg/Kg/day (total: 15 mg/Kg). All patients were followed at completion of therapy, 3 months and 6 months for clinical response, splenic size and parasitologically. RESULTS: Out of 125 children, 44 were in group-I, 20 in group-2, 38 in group-3 and 23 in group- 4, 124 patients had parasitological cure with relapse in one patient of group 1 during follow up. One patient in-group II had no response with first course but became parasitologically negative with 2nd course of Miltefosine. In-group I, one patient had persistent splenomegaly and found to have associated portal hypertension. Final cure rate with Miltefosine and Amphotericin B was 93.2%, 95%, 92.1% and 91.3% in-group 1, 2, 3 and 4 respectively, which are statistically insignificant. Majority of patients had pancytopenia. Eievated". AL T (>3 times of normal) were seen in 28, 11, 19 and 13 patients of group 1, 2, 3 and group 4 respectively which returned to normal in subsequent follow up. Raised BUN was observed more in patients who got Amphotericin B i.e. 65.42% and 73.91 % in-group 3 and 4 respectively. GI side effects i.e. diarrhea and vomiting were observed in 26 and 23 patients in-group 1 and 2 respectively. CONCLUSION: Miltefosine is safe, well tolerable, and highly effective and has same efficacy as Amphotericin B in newly diagnosed and SAG resistant children with visceral leishmaniasis.

Singh UK, Prasad R, Kumar R, Jaiswal BP. · Department of Pediatrics, Nalanda Medical College, Patna 800 020, India. · Indian Pediatr. · Pubmed #17202605 links to  free full text

Abstract: Sixty four children (38 boys and 26 girls), aged 1 yr to 14 yr, presenting with fever, splenomegaly and positive LD body in splenic smear examination, admitted to pediatric ward of Nalanda Medical college and Child care center between 1st July 03 to 30th June 04 were taken for study. Patients were categorized into two groups: 44 were in Group I (Patients who had not received prior antileishmanial drug) and 20 in Group II (Patients who had received 30 days course of SAG; 20 mg per kg per day). All patients were given Miltefosine in dose of 2.5 per kg per day od or bid per orally to a maximum of 100 mg and were followed at completion of therapy, 1 month and 6 months for clinical response, splenic size and parasite density. 63 patients had parasitological cure with relapse in one patient of Group I during follow up. One patient in Group II had no response with first course but became parasitologically negative with 2nd course of Miltefosine. In Group I, one patient had persistent splenomegaly and found to have associated portal hypertension. GI side effects i.e. diarrhea and vomiting were observed in 26 and 23 patients respectively. Majority of patients had pancytopenia. Elevated ALT (> 3 times of normal) were seen in 28 and 11 patients of Group I and Group II respectively which returned to normal in subsequent follow up. The final cure rates were 93.2 percent and 95 percent in Groups I and II respectively.

Kaur G, Kapoor N, Mohan P, Sri Nageswari K, Singh MJ, Prasad R. · Department of Physiology, Prayas Building, Government Medical College, Sector 38, Chandigarh 160 038, India. · J Biochem Mol Biol Biophys. · Pubmed #12186749 No free full text.

Abstract: The erythrocytes are widely used as model cells for studies of sodium-potassium pump (Na(+)-K(+) pump) in health and disease. Hence, to explore the possible role of the Na(+) transport across the cell membrane in the pathogenesis of pregnancy-induced hypertension (PIH), the present study was conducted to assess the Na(+)-K(+) pump functions in relation to its intrinsic kinetic properties using erythrocytes (RBC). Erythrocyte sodium concentration in pregnancy-induced hypertensive women was significantly (p<0.01) lower in comparison to normotensive pregnant women. On the contrary erythrocyte potassium was significantly higher (p<0.01) in PIH women as compared to normotensive pregnant women. Observed alterations in Na(+) and K(+) concentrations in erythrocytes were associated with significantly (p<001) increased Ouabain-sensitive sodium efflux rate and rate constants in erythrocytes from PIH women. Further, kinetic studies revealed that increased Ouabain-sensitive efflux rate constant in RBC from PIH women was accompanied by increased maximal velocity (V(max)) of Na(+)-K(+) pump. However, the affinity constant (K(m)) was unaltered in both the groups. Therefore, these findings suggest that increased Na(+)-K(+) pump activity in RBC of PIH women could be due to either increased numbers of Na(+)-K(+) pump units of increased numbers of active subunits of Na(+)-K(+) pump possibly due to specific plasma factors in PIH women.