Recent Update in The Management of Hypertension

Size: px

Start display at page:

Download "Recent Update in The Management of Hypertension"

Polly Black
5 years ago
Views:

1 REVIEW ARTICLE Salim Lim ABSTRACT Hypertension is still the leading cause of death worldwide. Hypertension increases not only the risk for progression of chronic kidney disease (CKD) but also for cardiovascular (CV) morbidity and mortality. For most patients it is the systolic blood pressure rather than the diastolic blood pressure that most strongly predicts adverse events. The optimal target for BP control for most hypertensive patients is < 140/90 mmhg, or < 130/80 mmhg for patients with diabetes and CKD. Certain lifestyle measures such as weight reduction, smoking cessation, restriction of dietary sodium intake, moderation of alcohol intake and an increase in physical activity can lower BP. Except for progression of proteinuric kidney disease and congestive heart failure (CHF), it is the achieved BP and not the class of agent that is most important in reducing morbid outcomes. If BP is more than 20/10 mmhg above the goal, therapy should be initiated with 2 drugs, one of which should be a thiazide-type diuretic. A strong consideration should be given to initiate antihypertensive therapy in patients with kidney disease with renin-angiotensin-aldosterone system (RAAS) blockers, usually in concert with diuretics. Patients with proteinuria > 1 g/day despite optimal BP control with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) monotherapy may bene t from a combination therapy. is 46% more than can be attributed to tobacco use, high BP s closest competitor (Figure 1). It is well known that hypertension increases not only the risk for progression of CKD but also for CV morbidity and mortality. 2 Despite increasing awareness of hypertension among the public and the doctors, national surveys in the United States continue to show substantial underdiagnosis, undertreatment, and poor rates of BP control. 3 The failure to achieve better BP control is related to poorly organized health care systems, the expense of antihypertensive medicines, compliance problems related to need for multiple medicines, the unpleasant side effects of the drugs and the fact that high BP is relatively silent until its complications strike. Key words: hypertension, systolic blood pressure, proteinuria, microalbuminuria. INTRODUCTION What is the leading cause of death worldwide? The great infectious disease such as tuberculosis or malaria? Maybe it is AIDS? Perhaps it is smoking? How about malnutrition or its opposite, obesity? Surprisingly, it is none of these. Ezzati et al analyzed the worldwide attributable mortality due to 26 health risk factors for the World Health Organization and concluded that high BP was the single factor responsible for 12.8% of all deaths worldwide, or more than 7 million deaths per year. 1 This Department of Internal Medicine, Husada Hospital, Jakarta Figure 1. Worldwide deaths attributable to selected leading risk factors (source: World Health Organization) DEFINITION OF HYPERTENSION The Seventh Joint National Committee Report (JNC 7) now defines three levels of elevated BP. 2 (Table 1) Stage 1 hypertension is de ned as systolic blood pressure (SBP) between 140 to 159 mmhg and/or diastolic blood pressure (DBP) between 90 to 99 mmhg. Stage 2 hypertension refers to all levels of SBP >160 and/or DBP > 100 mmhg. JNC 7 introduced the classi cation of BP between 120 to 139 mmhg SBP or 80 to 89 mmhg DBP as prehypertension based on the risk of progression and associated CV risk. Patients with BP in the 130/80 to 139/89 mm Hg range 186

2 Vol 39 Number 4 October - December 2007 are at twice the risk to develop hypertension as those with lower values. 4 lower BP targets (<130/80 mmhg) for patients with diabetes and CKD. 2,11 HYPERTENSION AND PROGRESSION OF KIDNEY DISEASE Epidemiologic studies indicate that hypertension is closely associated with progression of kidney disease. Several trials involving proteinuric renal diseases consistently demonstrate a relationship between reduction in proteinuria during antihypertensive therapy and the probability of slowing disease progression. 5-8 A recent post hoc analysis of non-diabetic patients in the African-American Study of Kidney Disease (AASK) indicates that the greater the magnitude of reduction in proteinuria following the initial six months of BP treatment, the greater the slowing of glomerular ltration rate (GFR) decline, a relationship that was independent of BP level. 9 This relationship with proteinuria reduction is also seen in the outcomes of the COOPERATE trial, i.e., those with an additional 25% to 30% reduction in proteinuria, had less progression to endstage renal disease (ESRD) and doubling of creatinine compared to the comparator groups at similar levels of BP. 10 Both JNC 7 and Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend HYPERTENSION AND CARDIOVASCULAR DISEASE (CVD) There was a fear in the past that reducing BP too far might increase the risk of CV mortality. This is related to the concept of the J curve, where lowering BP below a certain level that maintains coronary perfusion increases CV risk in those with coronary heart disease. However, results from randomized controlled trials have con rmed that a further reduction in BP among normotensive individuals (baseline BP < 140/90 mmhg) indeed lowers the risk of CV events In a meta-analysis involving almost one million participants, there was a linear association between both SBP and DBP and risk of CV mortality down to 115 mmhg SBP and 75 mmhg DBP. 15 For every 10 mmhg lower usual SBP or 5 mmhg lower usual DBP during long-term follow-up, there is a 40% reduction in risk of death from stroke and a 30% reduction in risk of death from ischemic heart disease. Thus, the current evidence con rms that the risk of CV events follows a linear relationship with BP and achieving further BP reductions within the so-called normal range indeed reduces the risk of CV events. 187

3 Salim Lim Acta Med Indones-Indones J Intern Med TREATMENT OF HYPERTENSION The long-term follow-up studies of the Multiple Risk Factor Intervention Trial have revealed that for most patients it is the SBP rather than the DBP that most strongly predicts adverse events. 16 Most patients with hypertension will reach the DBP goal once SBP is at goal. Therefore, the primary focus should be on achieving the SBP goal. The JNC 7 guideline recommend the optimal target for BP control for most hypertensive patients is < 140/90 mmhg, or < 130/80 mmhg for patients with diabetes and CKD. 2 LIFESTYLE MODIFICATION Recent trial has shown that certain lifestyle measures can lower BP. Recommendations for all patients with hypertension include weight reduction in those individuals who are overweight or obese, smoking cessation, restriction of dietary Na + intake to <100 mmol/d (2.4 g of sodium or 6 g of salt), moderation of alcohol intake and an increase in physical activity. 17 Lifestyle modi cations can reduce BP, enhance antihypertensive drug ef cacy and decrease risk of CVD. WHEN TO START PHARMACOLOGIC TREATMENT? The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT) make clear the consequences of failing to intervene early in the course of hypertension in those with multiple CV risk factors. Subjects who achieved the BP goal within the first six months had a lower CV event rate than those who achieved the goal after six months. 18,19 Those who are 20/10 mmhg above goal BP should be started on combination therapy. Therefore, the initial BP-lowering agents need to be from drug classes with a compelling indications and low side effect pro le, shown to reduce CV events and are well tolerated. 20 (Table 2) DOES THE SPECIFIC DRUG USED MATTER? A series of recent trials, especially the antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), has provided strong evidence that except for progression of proteinuric kidney disease and CHF, it is the achieved BP and not the class of agent that is most important in reducing morbid outcomes ,19,21 Thiazide-type diuretics should be used for most patients with hypertension either alone or in combination because many trials have con rmed that they can prevent the CV complications of hypertension. Whereas reductions in proteinuria (> 300 mg/d) are strongly associated with decreased progression of kidney disease, reductions in microalbuminuria (> 30 and < 300 mg/d) correlate with decreased CV mortality. 22,23 Absence or very low levels of albuminuria is associated with low CV risk, whereas the CV risk increases markedly with increasing amount of albumin in the urine (even within the now considered normal range). However, for albuminuria to be a target for therapy, one needs to prove that lowering of albuminuria perse is cardioprotective. The Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND-IT) is the only randomized trial to study the effect of albuminuria lowering in microalbuminuric healthy individuals. Asselbergs et al indeed showed that the lowering of albuminuria with the ACE inhibitor fosinopril tended to be cardioprotective. 24 A recent post hoc analysis of the LIFE trial found similar results in hypertensive patients: The more the angiotensin II antagonist losartan lowered albuminuria, the more the patient was cardioprotected, irrespective of the effect on other CV risk factors. 25 Although microalbuminuria has been discovered as a strong and independent indicator of increased CV risk among hypertensive individuals, it has not penetrated all guidelines. ANTIHYPERTENSIVE THERAPY IN CHRONIC KIDNEY DISEASE In patients with CKD, the goal of antihypertensive therapy is to slow the deterioration of renal function and prevent CVD. The ACE inhibitor and ARB have demonstrated favorable effects on the progression of diabetic and nondiabetic renal disease. 5-7,9,10 The greater the magnitude of reduction in proteinuria, the greater the slowing of GFR decline that is independent of BP level. ACE inhibitor and ARB should also be used in advanced CKD since in all trials, the patients who garner the greatest bene t from such agents are those with the most advanced form of kidney disease. A rise in serum creatinine by as much as 35% above baseline during ACE inhibitor or ARB therapy is acceptable and not a reason to withhold treatment unless hyperkalemia develops. 2 In addition, a number of recent clinical trials have noted that the incidence of new-onset diabetes was reduced with ACE inhibitor and ARB. 19,21,26 COMBINATION THERAPY WITH ACE INHIBITOR AND ARB IN CKD A number of investigations have reported that dual blockade of the RAAS with ACE inhibitor and ARB in combination is superior to single blockade with either 188

4 Vol 39 Number 4 October - December

5 Salim Lim Acta Med Indones-Indones J Intern Med ACE inhibitor or ARB in both diabetic and nondiabetic nephropathy. 10,27-29 The notion that the combination of an ACE inhibitor and an ARB should be used only for proteinuric renal disease and not for BP reduction is supported further by a meta-analysis of studies that used the combination. 30 In my opinion, patients with proteinuria > 1 g/day despite optimal BP control with ACE-inhibitor or ARB monotherapy may bene t from a combination therapy. IS COMBINATION THERAPY RISKY? Bakris et al reported that ARB did not cause an increase in serum potassium to the same degree as ACE inhibitor in the presence of renal insuf ciency. 31 These differential effects on serum potassium were related to a relatively smaller reduction in plasma aldosterone as a result of the ARB and were not related to changes in GFR. Therefore, hyperkalemia with combination therapy is determined mainly by the ACE inhibitor. The incidence of hyperkalemia in the COOPERATE trial was 7.9% in the combination therapy group, 9.3% in the trandolapril group, and 4.4% in the losartan group. 10 Patients should be regularly monitored for hyperkalemia. Co-administration of drugs that interfere with renal potassium excretion such as nonsteroidal anti-in ammatory drugs or spironolactone should be avoided. In addition, patients should follow a low-potassium diet with speci c counseling against the use of salt substitutes that contain potassium. CONCLUSION High BP is still the leading cause of death worldwide. For most patients it is the systolic rather than the diastolic BP that most strongly predicts adverse events. Except for progression of proteinuric kidney disease and CHF, it is the achieved BP and not the class of agent that is most important in reducing morbid outcomes. Physicians should focus on achieving a BP goal of < 140/90 mmhg for most hypertensive patients, or < 130/80 mmhg for patients with diabetes and CKD. A strong consideration should be given to initiate antihypertensive therapy in patients with kidney disease with RAAS blockers, usually in concert with diuretics. Patients with proteinuria > 1 g/day despite optimal BP control with ACE inhibitor or ARB monotherapy may bene t from a combination therapy. REFERENCES 1. Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ. Comparative Risk Assessment Collaborating Group: Selected major risk factors and global and regional burden of disease. Lancet. 2002;360: Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA. 2003;289: Hajjar I, Kotchen TA. Trends in the prevalence, awareness, treatment and control of hypertension in the United States, JAMA. 2003;290: Vasan RS, Larson MG, Leip EP, et al. Assessment of frequency of progression to hypertension in non-hypertensive participants in The Framingham Heart Study. Lancet. 2000;358: Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345: Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with Type 2 diabetes and nephropathy. Reduction of Endpoints in Non- Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) Study Group. N Engl J Med. 2001;345: The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular ltration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349: Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G. The effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease. Modi cation of Diet in Renal Disease Study Group. N Engl J Med. 1994;330: Lea J, Greene T, Hebert L, Lipkowitz M, Massry S, Middleton J, Rostand SG, Miller E, Smith W, Bakris GL. The relationship between magnitude of proteinuria reduction and risk of end-stage renal disease: Results of the African American study of kidney disease and hypertension. Arch Intern Med. 2005;165: Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-ii receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): A randomised controlled trial. Lancet. 2003;361: K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Am J Kidney Dis. 2004;43: Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342: Fox K. European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators: Ef cacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: Randomised, doubleblind, placebo-controlled, multicentre trial (the EUROPA Study). Lancet. 2003;362: Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, et al. CAMELOT Investigators: Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: The CAMELOT study: A randomized controlled trial. JAMA. 2004;292: Lewington S, Clarke R, Qizilbash N et al. Age-speci c relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:

6 Vol 39 Number 4 October - December Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall ndings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Int Med. 1992;152: Apple LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM. Dietary approaches to prevent and treat hypertension: A scienti c statement from the American Heart Association Hypertension. 2006;47: Dahlof B, Sever PS, Poulter PS, Wedel H, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendro umethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): A multicentre randomized controlled trial. Lancet. 2005;366: Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: The VALUE randomised trial. Lancet. 2004;363: Williams B, Poulter NR, Brown MJ, Davis M, et al. British Hypertension Society: Guidelines for management of hypertension: Report of the fourth working party of the British Hypertension Society 2004 BHS IV. J Hum Hyperten. 2004;18: ALLHAT Of cers and Coordinators for the ALLHAT Collaborative Research Group. 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 (ALLHAT). JAMA. 2002;288: Kistorp C, Raymond I, Pedersen F, Gustafsson F, Faber J, Hildebrandt P. N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA. 2005;293: Yuyun MF, Khaw KT, Luben R, Welch A, Bingham S, Day NE, Wareham NJ. Microalbuminuria independently predicts allcause and cardiovascular mortality in a British population: The European Prospective Investigation into Cancer in Norfolk (EPIC- Norfolk) population study. Int J Epidemiol. 2004;33: Asselbergs FW, Diercks GFH, Hillege H, van Boven AJ, et al. Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT) Investigators: Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004;110: Ibsen H, Wachtell K, Olsen MH, Borch-Johnsen K, Lindholm LH, Mogensen CE, Dahlof B. Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: The LIFE Study. Kidney Int Suppl. 2004;92:S56-S Dahlof B, Devereux RB, Kjeldsen SE, Julius S, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomized trial against atenolol. Lancet. 2002;359: Campbell R, Sangalli F, Perticucci E, Aros C, Viscarra C, et al. Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int. 2003;63: Mogensen CE, Neldam S, Tikkanen I, Oren S, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and noninsulin dependent diabetes: The candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000;321: Izzo JL Jr, Weinberg MS, Hainer JW, Kerkering J, Tou CK. Antihypertensive efficacy of candesartan-lisinopril in combination vs. up-titration of lisinopril: The AMAZE trials. J Clin Hypertens. (Greenwich) 2004;6: Doulton TW, He FJ, MacGregor GA. Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension. 2005;45: Bakris G, Siomos M, Richardson D, Janssen I, Bolton W, Hebert L, Agarwal R, Catanzaro D; for the VAL-K Study Group. ACE inhibition or angiotensin receptor blockade: Impact on potassium in renal failure. Kidney Int. 2000;58:

Hypertension is a major risk factor for

Hypertension is a major risk factor for OPTIMAL RISK MANAGEMENT OF THE HYPERTENSIVE PATIENT WITH MULTIPLE RISK FACTORS * Keith C. Ferdinand, MD, FACC ABSTRACT To determine the risk of cardiovascular disease in patients with hypertension, it