7th Brazilian Guideline of Arterial Hypertension: Chapter 8 - Hypertension and Associated Clinical Conditions

MVB Malachias C Amodeo RB Paula AC Cordeiro Júnior LBNC Magalhães LC Bodanese

Diabetes mellitus

The association of AH and DM doubles the CV risk and has increased the AH prevalence, which is related to the elevation in overweight and obesity rates, as well as the increase in the elderly population.11 Grossman E, Messerli FH, Goldbourt U. High blood pressure and diabetes mellitus: are all antihypertensive drugs created equal. Arch Intern Med. 2000;160(16):2447-52. The incidence of AH in type 1 diabetic patients increases from 5%, at the age of 10 years, to 33%, at the age of 20 years, and to 70%, at the age of 40 years.22 Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension. 1992;19(5):403-18. There is a strict relationship between the development of AH and the presence of albuminuria in that population.33 Kidney Disease Improving Global Outcomes. Definition and classification of CKD. Kidney Int Suppl. 2013;3(1):19-62. That increase in the AH incidence can reach 75-80% in patients with diabetic kidney disease.44 Mogensen CE, Hansen KW, Pedersen MM, Christensen CK. Renal factors influencing blood pressure threshold and choice of treatment for hypertension in IDDM. Diabetes Care. 1991;14 Suppl 4:13-26. Approximately 40% of patients with a recent diagnosis of DM have AH.55 Hypertension in Diabetes Study (HDS): I. Prevalence of hypertension in newly presenting type 2 diabetic patients and the association with risk factors for cardiovascular and diabetic complications. J Hypertens. 1993;11(3):309-17. In approximately 50% of type 2 diabetic patients, AH occurs before the development of albuminuria. All diabetic hypertensives are at high CV risk. In addition to all complementary tests recommended for hypertensives, diabetic patients require the search for urine albumin excretion, fundoscopic eye exam and assessment of probable postural hypotension, which can characterize the presence of autonomic nervous system dysfunction.66 James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-20. Erratum in: JAMA. 2014;311(17):1809.

The BP targets to be achieved are still controversial. However, there is recent consensus on a BP target < 130/80 mm Hg. (GR: IIb; LE: B). For the NPT of AH in diabetic individuals, all recommendations expressed in Chapter 6 apply. The therapeutic choice should be based on drug efficacy and tolerability. Considering that all diabetic patients are at high CV risk, the initial treatment includes the association of at least two drugs of different classes.77 Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, et al. Effects of intensive blood pressure control in type 2 diabetes mellitus. ACCORD Study Group. N Engl J Med. 2010;362(17):1575-85. In diabetic hypertensives without nephropathy, all antihypertensive drugs can be used. In the presence of diabetic nephropathy, however, RAAS inhibitors are preferred.88 Turnbull F, Neal B, Algert C, Chalmers J, Chapman N, Cutler J, et al; Blood Pressure Lowering Tratment Trialists´collaboration. Effects of different blood pressure lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively-designed overviews of randomized trials. Arch Intern Med. 2005;165(12):1410-9. (GR: I; LE: A). Simultaneous use of ACEI and ARB should be avoided because of the risk of complications.99 Mancia G, Schumacher H, Redon J, Verdecchia P, Schmiever R, Jennings G, et al. Blood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET). Circulation. 2011;124(16):1727-36.,1010 Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al; ALTITUDE Investigators. Cardiorenal endpoints in a trial of aliskiren for type 2 diabetes, New Engl J Med. 2012;367(23):2204-13. Although worsening insulin resistance, BB are useful for BP control in diabetic patients, especially when used in combinations to treat hypertensives with CAD or HF.1111 Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al; Task Force Members. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281-357.

Metabolic syndrome

Metabolic syndrome (MS) is characterized by the coexistence of CVRFs (low HDL-C, high triglycerides, AH and dysglycemia) either associated or not with central obesity (identified by the AC measure). The definitions of MS differ according to different entities. In 2009, those entities convened a task force to conciliate the different definitions of MS.1212 Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640-5. The criteria are described in Chapter 4 about CV risk stratification. The presence of AH in MS increases global CV risk. The initial treatment is based on lifestyle changes in association or not with the use of drugs. Because nonpharmacological measures isolated do not control BP, pharmacological treatment is required whenever BP ≥ 140/90 mm Hg.1313 Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735-52. Erratum in: Circulation. 2005;112(17):e298. There is no evidence of benefit in the use of antihypertensive agents for MS with normal BP levels. When dysglycemia is present, the preferred drugs to begin AH treatment in MS are RAAS blockers and CCB.1313 Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735-52. Erratum in: Circulation. 2005;112(17):e298.

14 Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. National Institutes of Health. Obes Res. 1998;6 Suppl 2:51S-209S. Erratum in: Obes Res. 1998;6(6):464.

15 World Health Organization. (WHO). Obesity: preventing and managing the global epidemic: report on a WHO consultation. (Technical Report Series 894). Geneva, Switzerland: World Health Organization; 2000.

16 Canadian guidelines for body weight classification in adults. Ottawa (Canada): Health Canada Publications Centre; 2003. (Publication ID No. 4645).

17 Khan NA, McAlister FA, Rabkin SW, Padwal R, Feldman RD, Campbell NR, et al. Canadian Hypertension Education Program. The 2006 Canadian Hypertension Education Program recommendations for the management of hypertension, part II: therapy. Can J Cardiol. 2006;22(7):583-93.

18 Hara K, MatsushitaY, Horikoshi M, Yoshiike N, Yokoyama T, Tanaka H, et al. A proposal for the cutoff point of waist circumference for the diagnosis of metabolic syndrome in the Japanese population. Diabetes Care. 2006;29(5):1123-4.
-1919 Brandão AP, Brandão AA, Nogueira AR, Suplicy H, Guimarães JI, Oliveira JE. Sociedade Brasileira de Cardiologia. I Diretriz brasileira de diagnóstico e tratamento da síndrome metabólica. Arq Bras Cardiol. 2005;84(supl 1):1-28.

Coronary artery disease

The treatment of AH associated with CAD, which includes patients after myocardial infarction, with chest angina and myocardial revascularization, should preferably comprise BBs, ACEIs and ARBs, in addition to statins and acetylsalicylic acid. Beta-blockers have proven highly beneficial after AMI, especially within 2 years from the acute event.2020 Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665. Similarly, ACEIs tested on that condition have also proven beneficial.2121 Borghi C, Bacchelli S, Degli Esposti D, Bignamini A, Magnani B, Ambrosioni E. Effects of the administration of an angiotensin-converting enzyme inhibitor during the acute phase of myocardial infarction in patients with arterial hypertension. SMILE Study Investigators. Survival of Myocardial Infarction Long-term Evaluation. Am J Hypertens. 1999;12(7):665-72.,2222 Gustafsson F, Kober L, Torp-Pedersen C, Hildebrandt P, Ottesen MM, Sonne B, et al. Long-term prognosis after acute myocardial infarction in patients with a history of arterial hypertension. TRACE study group. Eur Heart J. 1998;19(4):588-94. In patients with chronic CAD and multiple RFs, such as AH, ACEIs have shown a favorable effect to reduce relevant clinical outcomes.2323 Arnold JM, Yusuf S, Young J. Prevention of heart failure in patients in the heart outcomes prevention evaluation (HOPE) study. Circulation. 2003;107(9):1284-90. (GR: I; LE: A). Regarding BP target, it is worth considering the likelihood of the J curve effect, demonstrated in different studies,2424 Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A, et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med. 2006;144(12):884-93.

25 Sleight P, Redon J, Verdecchia P, Mancia G, Gao P, Fagard R, et al; ONTARGET investigators. Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study. J Hypertens. 2009;27(7):1360-9.

26 Zanchetti A, Mancia G. Longing for clinical excellence: a critical outlook into the NICE recommendations on hypertension management--is nice always good? J Hypertens. 2012;30(4):660-8.
-2727 Mancia G, Parati G, Bilo G, Gao P, Fagard R, Redon J, et al. Ambulatory blood pressure values in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Hypertension. 2012;60(6):1400-6. in which the excessive BP reduction, mainly in DBP, can precipitate CV events in patients with obstructive CAD. Additional drugs to meet target BP (BP < 130/80 mm Hg) are CCBs and thiazide DIUs.2828 Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, et al. Clinical practice guidelines for the management of hypertension in the community a statement by the American Society of Hypertension and the International Society of Hypertension. J Hypertens. 2014;32(1):3-15. (GR: IIa; LE: B).

Stroke

Stroke is the most common manifestation of the vascular damage caused by AH. In transient ischemic attack (TIA), the neurologic deficit is solved in 24 hours, with no clinically detectable sequelae.

Pharmacological treatment of AH in the patient with previous stroke

Chronically, the effective antihypertensive therapy, maintaining BP < 130/80 mm Hg, has played a decisive role in the secondary prevention of all types of stroke and TIA.2929 Rashid P. Leornardi-Bee J. Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke. 2003;34(11):2741-8.

30 PATS Collaborating Group. Poststroke antihypertensive treatment study: a preliminary result. Chin Med J (Engl). 1995;108(9):710-7.

31 Gueyffier F, Boissel JP, Boutitie F, Pocock S, Coope J, Cutler J, et al. Effect of antihypertensive treatment in patients having already suffered from stroke. Gathering the evidence. The INDANA (IN-dividual Data Analysis of Antihypertensive intervention trials) Project Collaborators. Stroke. 1997;28(12):2557-62.

32 PROGRESS Collaborative Group. Randomised trial of a perindopril based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358(9287):1033-41. Erratum in: Lancet. 2001;358(9292):1556; Lancet. 2002;359(9323):2120.

33 Liu L, Wang Z, Gong L, Zhang Y, Thijs L, Staessen JA, et al. Blood pressure reduction for the secondary prevention of stroke: a Chinese trial and a systematic review of the literature. Hypertens Res. 2009;32(11):1032-40.

34 Schrader J. Luders S. Kulschewski A, Hammersen F, Plate K, Berger J, et al; MOSES Study Group. Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention: principal results of a prospective randomized controlled study (MOSES). Stroke. 2005;36(6):1218-26.
-3535 Yusuf S, Diener HC, Sacco RL, Cotton D, Ounpuu S, Lawton WA, et al; ProFESS Study Group. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med. 2008;359(12):1225-37. (GR: IIa; LE: B). As long as BP is reduced, any antihypertensive drug can be used.2020 Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.,3636 White CL, Pergola PE, Szychowski JM, Talbert R, Cervantes-Arriaga A, Clark HD, et al; SPS3 Investigators. Blood pressure after recent stroke: baseline findings from the secondary prevention of small subcortical strokes trial. Am J Hypertens. 2013;26(9):1114-22.,3737 Paul SL, Thrift AG. Control of hypertension 5 years after stroke in the North East Melbourne Stroke Incidence Study. Hypertension. 2006;48(2):260-5. There is no clinical evidence allowing a definitive conclusion about the preferential use of ARBs as compared to other antihypertensive drugs for the secondary prevention of stroke.3434 Schrader J. Luders S. Kulschewski A, Hammersen F, Plate K, Berger J, et al; MOSES Study Group. Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention: principal results of a prospective randomized controlled study (MOSES). Stroke. 2005;36(6):1218-26.,3535 Yusuf S, Diener HC, Sacco RL, Cotton D, Ounpuu S, Lawton WA, et al; ProFESS Study Group. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med. 2008;359(12):1225-37. There is currently no evidence showing the effectiveness of beginning antihypertensive therapy for SBP < 140 mm Hg for patients with a previous stroke. (GR: III; LE: B).

Chronic kidney disease

For patients with that disease, BP reduction is the most effective measure to reduce CV risk and to slow kidney damage progression, regardless of the antihypertensive drug used.3838 Kidney Disease: Improving Global Outcomes (KDIGO) Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International Supplements. 2013;3(1):1-150.,3939 Casas JP, Chua W, Loukogeorgakis S, Vallance P, Smith L, D'Hingorani AD, et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005;366(9502):2026-33. (GR: I; LE: A). Special attention should be paid to patients with high albuminuria, which determines the unfavorable course of kidney disease4040 Ruggenenti P, Perna A, Mosconi L, Matalone M, Pisoni R, Gaspari F, et al. Proteinuria predicts end-stage renal failure in non-diabetic chronic nephropathies. The "Gruppo Italiano di Studi Epidemiologici in Nefrologia" (GISEN). Kidney Int Suppl. 1997;63:S54-7. and increases CV risk.4141 Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, et al; Chronic Kidney Disease Prognosis Consortium. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375(9731):2073-81. (GR: IIa; LE: A). Elderly patients with renovascular disease, CAD and risk for postural hypotension often require customization of the antihypertensive treatment.4040 Ruggenenti P, Perna A, Mosconi L, Matalone M, Pisoni R, Gaspari F, et al. Proteinuria predicts end-stage renal failure in non-diabetic chronic nephropathies. The "Gruppo Italiano di Studi Epidemiologici in Nefrologia" (GISEN). Kidney Int Suppl. 1997;63:S54-7. (GR: IIa; LE: C). Usually, BP levels < 130/80 mm Hg are recommended, especially for those with albuminuria > 30 mg/g of creatinine and diabetic patients.4242 Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ, et al. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease study. Ann Intern Med. 2005;142(5):342-51.,4343 Appel LJ, Wright JT Jr, Greene T, Agodoa LY, Astor BC, Bakris GL, Cleveland WH, et al; AASK Collaborative Research Group. Intensive blood pressure control in hypertensive chronic kidney disease. N Engl J Med. 2010;363(10):918-29. In such patients, maintaining BP < 130/80 mm Hg reduces albuminuria and the risk for stroke, but there is no evidence that it decreases CV events and mortality.4444 Bangalore S, Kumar S, Lobach I, Messerli FH. Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and Bayesian random-effects meta-analyses of randomized trials. Circulation. 2011;123(24):2799-810.,4545 Reboldi G, Gentile G, Angeli F, Ambrosio G, Mancia G, Verdecchia P. Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients. J Hypertens. 2011;29(7):1253-69. (GR: IIa; LE: A). However, it is controversial whether BP reduction to those levels is associated with better CKD course and with a reduction in mortality.77 Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, et al. Effects of intensive blood pressure control in type 2 diabetes mellitus. ACCORD Study Group. N Engl J Med. 2010;362(17):1575-85.,4646 Upadhyay A, Earley A, ShaHaynes SM, Uhlig K. Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier. Ann Intern Med. 2011;154(8):541-8.,4747 McBrien K, Rabi DM, Campbell N, Barnieh L, Clement F, Hemmelgarn BR, et al. Intensive and standard blood pressure targets in patients with type 2 diabetes mellitus systematic review and meta-analysis. Arch Intern Med. 2012;172(17):1296-303. (GE: IIb; LE: B). The present guideline suggests the adoption of BP targets shown in Chart 1.

Chart 1
Blood pressure targets for patients on conservative treatment, according to kidney disease etiology and albuminuria

Choice of antihypertensive drug: stage 1 to 5 chronic kidney disease on conservative treatment

Thiazide DIUs are recommended, because they are effective in stages 1, 2 and 3 CKD, while loop DIUs are recommended for stages 4 and 5 CKD. That drug class reduces CV morbidity and mortality,4848 Verbeke F, Lindley E, Van Bortel L, Vanholder R, London G, Cochat P, et al. A European Renal Best Practice (ERBP) position statement on the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Blood Pressure in Non-dialysis-dependent Chronic Kidney Disease. Nephrol Dial Transplant. 2014;29(3):490-6.,49ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial 2008 (ALLHAT). JAMA. 2002;288(23):2981-97. Erratum in: JAMA. 2004;291(18):2196. being considered the choice for association in CKD.3838 Kidney Disease: Improving Global Outcomes (KDIGO) Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International Supplements. 2013;3(1):1-150.,49ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial 2008 (ALLHAT). JAMA. 2002;288(23):2981-97. Erratum in: JAMA. 2004;291(18):2196.,5050 Rahman M, Ford CE, Cutler JA, Davis BR, Piller LB, Whelton PK, et al; ALLHAT Collaborative Research Group. Long-term renal and cardiovascular outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants by baseline estimated GFR. Clin J Am Soc Nephrol. 2012;7(6):989-1002. (GR: I; NE: A). The ACEIs and ARBs are widely used for CKD, being effective for AH control and albuminuria reduction.5151 Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, et al; ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370(9590):829-40.

52 Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: Results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000;355(9200):253-9.

53 Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al; RENAAL Study Investigators: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861-9.

54 Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R; Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870-8.
-5555 Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997;349(9069):1857-63. (GR: I; LE: A). Regarding direct renin inhibitors and mineralocorticoid receptor antagonists, both with an antiproteinuric action, there is no evidence for their use in clinical practice.5656 Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK; AVOID Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008;358(23):2433-46.

57 Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006;70(12):2116-23.
-5858 Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis. 2008;51(2):199- 211. The risk of hyperpotassemia should be considered, especially with the latter. The double RAAS block is controversial. The combination of ACEI with ARB5959 Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372(9638):547-53.,6060 Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckortt W, et al; VA NEPHRON-D Investigators. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013; 369(20):1892-903. Erratum in: N Engl J Med. 2014;158:A7255. or of a renin inhibitor with ACEI or ARB1010 Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al; ALTITUDE Investigators. Cardiorenal endpoints in a trial of aliskiren for type 2 diabetes, New Engl J Med. 2012;367(23):2204-13. has resulted in more acute kidney damage and hyperpotassemia, leading to a ban on that strategy from nephrological practice. (GR: I; LE: A). However, in a recent study on adult polycystic kidney disease6161 Schrier RW, Abebe KZ, Perrone RD, Torres VE, Braun WE, Steinman TI, et al; HALT-PKD Trial Investigators. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med. 2014;371(24):2255-66. and a meta-analysis on diabetic patients with CKD,6262 Palmer SC, Mavridis D, Navarese E, Craig JC, Tonelli M, Salanti G, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet. 2015;385(9982):2047-56. the association of IECA and ARB has delayed the course of nephropathy without causing severe hyperpotassemia and acute kidney damage. (GR: IIb; LE: B). However, the double RAAS block remains contraindicated. (GR: I; LE: A). The CCBs are effective, especially for combined use with ACEI or ARB, being associated with a reduction in CV events.6363 Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caufield M, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366(9489):895-906.,6464 Bakris GL, Sarafidis PA, Weir MR, Dahlof B, Pitt B, Jamerson K, et al; ACCOMPLISH Trial Investigators. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomized controlled trial. Lancet. 2010;375(9721):1173-81. Other options include BBs, adrenergic inhibitors of central action, and, occasionally, direct acting vasodilators, such as minoxidil and hydralazine.

Approach to stage 5 chronic kidney disease on kidney replacement therapy

Most studies on AH in patients with CKD undergoing dialysis is based on measuring pre-dialysis BP levels. However, BP obtained in that way is known to have large variability, in addition to being usually overestimated, as it is underestimated when obtained after dialysis.6565 Agarwal R, Peixoto AJ, Santos SF, Zoccali C. Pre- and postdialysis blood pressures are imprecise estimates of interdialytic ambulatory blood pressure. Clin J Am Soc Nephrol. 2006;1(3):389-98.,6666 Rohrscheib MR, Myers OB, Servilla KS, Adams CD, Miskulin D, Bedrick EJ, et al; DCI Medical Directors. Age-related blood pressure patterns and blood pressure variability among hemodialysis patients. Clin J Am Soc Nephrol. 2008;3(5):1407-14. In those patients, BP should be preferably measured outside the dialysis centers, in the interdialytic intervals.6767 Agarwal R, Andersen MJ, Bishu K, Saha C. Home blood pressure monitoring improves the diagnosis of hypertension in hemodialysis patients. Kidney Int. 2006;69(5):900-6. (GR: IIa; LE: B). Home BP measures are more reproducible than those obtained before and after dialysis, have a fair association with both 44-hour ABPM and CV prognosis in patients undergoing dialysis.6868 Bansal N, McCulloch CE, Rahman M, Kusek JW, Anderson AH, Xie D, et al; CRIC Study Investigators. Blood pressure and risk of all-cause mortality in advanced chronic kidney disease and hemodialysis: the chronic renal insufficiency cohort study. Hypertension. 2015;65(1):93-100.

69 Agarwal R, Satyan S, Alborzi P, Light RP, Tegegne GG, Mazengia HS, et al. Home blood pressure measurements for managing hypertension in hemodialysis patients. Am J Nephrol 2009;30(2):126-34.
-7070 Agarwal R. Blood pressure and mortality among hemodialysis patients. Hypertension. 2010;55(3):762-8. (GR: IIa; LE: B). In addition, a randomized study has shown that therapeutic decisions based on HBPM associate with better interdialytic BP control assessed with 24-hour ABPM as compared to pre-dialysis BP measurement.7171 da Silva GV, de Barros S, Abensur H, Ortega KC, Mion D Jr; Cochrane Renal Group Prospective Trial Register: CRG060800146. Home blood pressure monitoring in blood pressure control among haemodialysis patients: an open randomized clinical trial. Nephrol Dial Transplant. 2009;24(12):3805-11. Regarding ABPM, it is worth noting that, although the 44-hour long exam is considered gold-standard for assessment of hemodialysis patients, its technical difficulties favor the use of 24-hour ABPM and home BP measurements.

The association between BP and mortality in patients with CKD undergoing dialysis has a "U" distribution for SBP and DBP, thus, both elevated and reduced levels relate to bad prognosis.7070 Agarwal R. Blood pressure and mortality among hemodialysis patients. Hypertension. 2010;55(3):762-8. (GR: IIa; LE: B). There are not enough studies to support with satisfactory level of evidence the diagnosis of AH in patients undergoing dialysis; however, the most accepted pre- and post-hemodialysis BP levels for that purpose are ≥ 140/90 mm Hg and ≥ 130/80 mm Hg, respectively.7070 Agarwal R. Blood pressure and mortality among hemodialysis patients. Hypertension. 2010;55(3):762-8.,7171 da Silva GV, de Barros S, Abensur H, Ortega KC, Mion D Jr; Cochrane Renal Group Prospective Trial Register: CRG060800146. Home blood pressure monitoring in blood pressure control among haemodialysis patients: an open randomized clinical trial. Nephrol Dial Transplant. 2009;24(12):3805-11. (GR: IIa; LE: C). A study with 326 hemodialysis patients has associated better prognosis with mean SBP levels between 120 and 130 mm Hg, in HBPM, and between 110 and 120 mm Hg, in ABPM.6868 Bansal N, McCulloch CE, Rahman M, Kusek JW, Anderson AH, Xie D, et al; CRIC Study Investigators. Blood pressure and risk of all-cause mortality in advanced chronic kidney disease and hemodialysis: the chronic renal insufficiency cohort study. Hypertension. 2015;65(1):93-100. (GR: IIb; LE: B).

Because, in that population, hypervolemia plays a major role in AH etiology, the therapeutic management should consider that variable, focusing the treatment on gradual control of "dry weight", via salt and water restriction, in addition to promoting adequate ultrafiltration during hemodialysis sessions.7171 da Silva GV, de Barros S, Abensur H, Ortega KC, Mion D Jr; Cochrane Renal Group Prospective Trial Register: CRG060800146. Home blood pressure monitoring in blood pressure control among haemodialysis patients: an open randomized clinical trial. Nephrol Dial Transplant. 2009;24(12):3805-11.

72 Levin NW, Kotanko P, Eckardt KU, Kasiske BL, Chazot C, Cheung AK, et al. Blood pressure in chronic kidney disease stage 5D - report from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney Int. 2010;77(4):273-84.

73 K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005;45(4 Suppl 3):S1-S153.

74 Horl MP, Horl WH. Dialysis: normovolemia is a therapeutic target for hypertension. Nat Rev Nephrol. 2009;5(8):438-9.
-7575 Agarwal R, Alborzi P, Satyan S, Light RP. Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial. Hypertension. 2009;53(3):500-7. (GR: IIa, LE: B). The choice of antihypertensive drugs should be individualized and based on characteristics, such as comorbidities, and drug's cardioprotective effect, intra- and interdialytic pharmacokinetic characteristics, and side effects.7171 da Silva GV, de Barros S, Abensur H, Ortega KC, Mion D Jr; Cochrane Renal Group Prospective Trial Register: CRG060800146. Home blood pressure monitoring in blood pressure control among haemodialysis patients: an open randomized clinical trial. Nephrol Dial Transplant. 2009;24(12):3805-11.,7272 Levin NW, Kotanko P, Eckardt KU, Kasiske BL, Chazot C, Cheung AK, et al. Blood pressure in chronic kidney disease stage 5D - report from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney Int. 2010;77(4):273-84. (GR: IIa; LE: C).

In kidney-transplanted patients, CCBs are a good option for AH treatment, because they are effective antihypertensive agents that antagonize arteriolar vasoconstriction caused by cyclosporine.7676 Grzesk G, Wicinski M, Malinowski B, Grzesk E, Manyslak S, Odrawaz-Sypniewska G, et al: Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular smooth muscle cells. Mol Med Rep. 2012;5(6):1469-74. The RAAS blockers can improve the transplant outcome in patients with increased urine albumin excretion. Diuretics, BBs, central action sympatholytic drugs and vasodilators can be used based on clinical judgement.7777 Cross NB, Webster AC, Masson P, O'connell PJ, Craig JC. Antihypertensives for kidney transplant recipients: systematic review and meta-analysis of randomized controlled trials. Transplantation. 2009;88(1):7-18.,7878 Weir MR, Burgess ED, Cooper JE, Fenves AZ, Goldsmith D, McKay D, et al. Assessment and Management of Hypertension in Transplant Patients. J Am Soc Nephrol. 2015;26(6):1248-60.

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    Sept 2016
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