MANAGEMENT OF HYPERTENSION IN ETHNIC MINORITIES

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1 Hypertension MANAGEMENT OF HYPERTENSION IN ETHNIC MINORITIES Take the online multiple hoie questions assoiated with this artile (see page 1104) CONSEQUENCES See end of artile for authors affiliations Correspondene to: Dr Jawad M Khan, University Department of Mediine, City Hospital, Birmingham B18 7QH, UK; jawad.khan@ swbh.nhs.uk H Jawad M Khan, D Gareth Beevers Heart 2005; 91: doi: /hrt ypertension, urrently defined as a blood pressure. 140 mm Hg (systoli) and/or. 90 mm Hg (diastoli), is a ommon problem. In a western adult population the prevalene of hypertension exeeds 20%. 1 The prevalene of hypertension inreases with age and is higher in ethni minority groups in the UK. In the Health Survey for England (2001) the prevalene of hypertension was 3.3% in those aged, 40 years, 27.9% in those aged between years, and 49.9% in those aged 80 years and older. 2 The two main ethni origin groups within the UK are the Afro-Caribbean and South Asians. The majority of studies have reported a higher prevalene and signifiantly higher mean blood pressure levels among both Afro-Caribbean populations and South Asians ompared to their white ounterparts. 3 In a south London ommunity based study, ompared with whites, age and sex standardised prevalene ratios for hypertension were 2.6 in people of Afrian desent and 1.8 in those of South Asian origin. 4 However, average blood pressure varies between different subgroups of South Asians, being highest in Sikhs, similar to whites in Muslims, and intermediate in Hindus. 5 In addition, Indians have higher blood pressures, Pakistanis lower blood pressures, with Bangladeshis having even lower blood pressures than the native white population. 6 OF HYPERTENSION FOR ETHNIC MINORITIES Hypertension is a major risk fator for ardiovasular and erebrovasular disease, the major auses of death in the UK and other western ountries. Reent studies indiate substantial ethni differenes in ardiovasular mortality. 7 For example, ompared to whites, Afro-Caribbean and people of Afrian desent have a higher inidene of stroke 8 and end stage renal failure, 9 whereas oronary artery disease is less ommon. Conversely, South Asians (defined as people originating from the Indian subontinent and East Afria) have a higher inidene of oronary heart disease. 8 There is inreased prevalene of left ventriular hypertrophy (LVH) in Afro-Caribbeans. This is thought to be, in part, due to their higher night time blood pressure with a smaller degree of noturnal blood pressure dip. LVH is an independent preditor of morbidity and mortality. Ethni differenes in morbidity and mortality may, in part, be explained by the differenes in other ardiovasular risk fators. Both diabetes mellitus and obesity are ommon in ethni minority groups, with a high prevalene among Afro-Caribbean females. 1 Plasma lipid onentrations, however, show a different pattern with South Asians having higher onentrations than whites and Afro-Caribbeans having lower values. This may, in part, explain why, despite a high prevalene of hypertension and type 2 diabetes mellitus, oronary heart disease is less ommon in Afro-Caribbean than the other two ethni groups. 10 PATHOPHYSIOLOGY OF HYPERTENSION IN ETHNIC MINORITIES The pathophysiology of hypertension differs in blak adults ompared to South Asians and whites. For example, hypertension in this population is ommonly of the low renin type (fig 1); sensitivity of blood pressure to salt intake is often inreased, and the ability to exrete ingested salt is impaired (60 70%). 11 This leads to an overall expansion of intravasular volume. Obesity is espeially prevalent in blak women and is assoiated with an inrease in total body sodium ontent. 12 Intake of dietary potassium, in the form of fruit and vegetables, is generally lower in blaks than in whites. Blak patients may also have relatively higher onentrations of intraellular alium. 13 All of these fators are assoiated with an inreased inidene of hypertension. MANAGEMENT OF HYPERTENSION IN ETHNIC MINORITIES Treatment with lifestyle modifiations Lifestyle modifiations an result in improvements in blood pressure ontrol. A 3.18 kg redution in body weight an signifiantly redue blood pressure. 15 An inrease in potassium intake may 1105 Heart: first published as /hrt on 14 July Downloaded from on 15 July 2018 by guest. Proteted by opyright.

2 1106 Figure 1 Plasma renin in blak and white hypertensive patients. Adapted from Freis et al. 14 also signifiantly redue blood pressure in normokalaemi hypertensive patients. 16 This ours, in part, beause of a natriureti effet of potassium. In view of the inreased sensitivity of blak patients to salt, restriting dietary salt intake to less than 6 g daily is partiularly effetive at reduing blood pressure (fig 2). 17 Approximately 10% of hypertensive blak adults (the perentage is higher in those who are very overweight) have an extremely high dietary sodium intake (that is, 24 hour urinary sodium exretion of mmol per day, equivalent to a salt intake of g daily) that is not suspeted by either the patient or the physiian. In these patients, it is impossible to ontrol blood pressure adequately without using a diureti or providing very speifi dietary ounselling to identify food(s) high in sodium. Optimising weight, redution in unsaturated fat intake, and regular exerise also improves ardiovasular risk profiles. Treatment with antihypertensive drugs South Asians appear to respond to antihypertensive drug treatment in a similar manner to whites. 2 However, there is insuffiient information on this point and South Asians are under-represented in studies. The exellent blood pressure lowering effiay of diuretis and alium hannel antagonists in hypertensive blak patients is related to their harateristi volume expansion, salt sensitivity and low renin profile (figs 3 5). Diuretis should be used for initial treatment unless there is an absolute or relative ontraindiation (for example, gout). Randomised ontrolled trials have shown that diuretis redue hypertension related morbidity and mortality in blak as well as in white populations, but there is evidene of a greater derease in blood pressure among hypertensive blak patients when ompared to white patients when they reeive an equivalent dose of a diureti. 19 Hydrohlorothiazide in a dosage of mg daily is a good hoie but, if the onentration of serum reatinine is 2 mg/dl (177 mmol/l) or more, thiazide diuretis are usually ineffetive, and a loop-type diureti should be substituted. 20 Calium hannel blokers are also extremely effetive antihypertensive drugs in blak patients. 21 Angiotensin onverting enzyme (ACE) inhibitors, b blokers, and angiotensin reeptor antagonists are generally less effetive as monotherapy in blak hypertensives, beause of the tendeny towards a low renin state and a lower ardia output, with inreased peripheral resistane. For example, with b bloker treatment, there was an average redution in blood pressure of about 7/7 mm Hg in blak patients ompared with an average redution of about 15/11 mm Hg in white patients. 24 Inreasing the dosage of the ACE inhibitor provides a slightly greater average lowering of blood pressure (to a total of about 10/8 mm Hg), but the derease is still less than desirable. 25 Ensuring a low dietary salt intake an improve the blood pressure response to ACE inhibitors in blak patients. 26 The effetiveness of b blokers and ACE inhibitors, in lowering blood pressure, an be inreased if diuretis are used as initial or seond line drug treatment in blak patients with hypertension. The ombination of diuretis and ACE inhibitors or b blokers produes equivalent lowering of blood pressure in whites and blaks, perhaps as a result of diureti indued stimulation of renin release. This is true even for Figure 2 Effet of salt restrition on blood pressure in Europeans and Afro- Caribbeans. PRA, plasma renin ativity (ng/ml/hour); DBP, 24 hour diastoli blood pressure (mm Hg); SBP, 24 hour systoli blood pressure; UNa, urinary sodium exretion (mmol/day). Adapted from He et al. 18 Heart: first published as /hrt on 14 July Downloaded from on 15 July 2018 by guest. Proteted by opyright.

3 Figure 3 Response of whites and blaks to differing antihypertensive mediation: Veterans Administration study. AB, a reeptor blokers; ACE, angiotensin onverting enzyme inhibitors; BB, b blokers; Ca, alium hannel blokers, Th, thiazide diuretis. Adapted from Materson, et al. 21 ombination-type drugs that ontain as little as mg of hydrohlorothiazide. 27 Most hypertensive blak patients require two or more antihypertensive drugs to ontrol systoli blood pressure to, 140 mm Hg and diastoli blood pressure to, 90 mm Hg. In the Veterans Affairs ooperative study, 28 only 46% of blak hypertensive patients with stage 1 or stage 2 disease ahieved a diastoli blood pressure below 90 mm Hg with monotherapy. However, in situations where a b bloker or an ACE inhibitor is indiated, the use of high doses and/or the addition of a diureti improves the blood pressure response in blak populations. Examples inlude the use of b blokers after myoardial infartion and the use of ACE inhibitors in patients with systoli heart failure (that is, ejetion fration, 40%) or those with type 1 diabetes (formerly known as insulin dependent diabetes) with proteinuria. These Figure 4 Effet of age and ethniity on response to antihypertensive mediation. Aten, atenolol; Capt, aptopril; Clon, lonidine; Dilt, diltiazem; HCTZ, hydrohlorothiazide; Pla, plaebo; Praz, prazosin. Adapted from Materson et al Heart: first published as /hrt on 14 July Downloaded from on 15 July 2018 by guest. Proteted by opyright.

4 1108 ompelling indiations apply equally to blak and white patients. In these ases, the protetive effet of the drugs is due to more than just redution of blood pressure. In blak hypertensive patients with type 2 (non-insulin dependent) diabeti nephropathy, evidene now shows that non-dihydropyridine alium hannel antagonists (as well as ACE inhibitors) an slow the hroni progression of renal disease. 29 However, there is evidene of signifiant under use of these drugs for these onditions in both raial groups. 22 There is limited information to date about the effiay and tolerability of angiotensin reeptor antagonists in blak patients. One subgroup analysis of patients treated with valsartan suggests that it may redue mean blood pressure, but the mean redution is less than that seen for other ethni groups. 30 ALLHAT With the inlusion of over patients, ALLHAT (antihypertensive and lipid-lowering treatment to prevent heart attak trial) 32 is the largest randomised ontrolled trial of antihypertensive treatment to date. Patients aged 55 years and older, with hypertension and at least one other risk fator for oronary heart disease (CHD) for example, type 2 diabetes mellitus, previous myoardial infartion or stroke, left ventriular hypertrophy or smoking were inluded in the study. They were randomised to either hlorthalidone, amlodipine, lisinopril, or doxazosin and assessed on the basis of morbidity and mortality from oronary artery disease. The study inluded 35% ( patients) blak patients. The blak patients were younger, had higher diastoli blood pressure levels, higher mean fasting gluose values, and greater inidene of diabetes at baseline. 27 There were no signifiant differene in primary outomes of non-fatal myoardial infartion or fatal CHD between hlorthalidone, amlodipine, and lisinopril in the blak patients. In addition, in terms of seondary end points namely, all ause mortality, stroke, ombined CHD, and ardiovasular disease there were no signifiant differenes between Management of hypertension in patients from ethni minorities: key points In a western adult population the prevalene of hypertension exeeds 20% Hypertension is a major risk fator for ardiovasular and erebrovasular disease The pathophysiology of hypertension differs in blak adults ompared to South Asians and whites South Asians appear to respond to antihypertensive drug treatment in a similar manner to whites There is exellent blood pressure lowering effiay of diuretis and alium hannel antagonists in hypertensive blak patients ACE inhibitors, b blokers, and angiotensin reeptor antagonists are generally less effetive as monotherapy in blak hypertensives hlorthalidone and amlodipine. In omparison to lisinopril, hlorthalidone treatment was assoiated with a lower risk of stroke, ombined oronary artery disease, and ombined ardiovasular death. The differenes may be explained, in part, by the lesser blood pressure lowering effets of angiotensin onverting enzyme inhibitors in blak Amerians. In terms of ombined ardiovasular death, hlorthalidone was favourable ompared to doxazosin. There was a redued relative risk of heart failure with hlorthalidone ompared to amlodipine, lisinopril, and doxazosin. CONCLUSION Hypertension is assoiated with signifiant morbidity and mortality, some of whih an be redued with effetive blood pressure lowering. The prevalene of hypertension is greater in ethni minority groups, ompared to whites, within the UK. The management of hypertensives from ethni minorities should reognise their different responses to drug Heart: first published as /hrt on 14 July Downloaded from on 15 July 2018 by guest. Proteted by opyright. Figure 5 Meta-analysis of monotherapy in blak and white hypertensives. Adapted from Sehgal. 31

5 treatment, the predisposing fators, and the ardiovasular onsequenes of hypertension.... Authors affiliations J M Khan, D G Beevers, University Department of Mediine, City Hospital, Birmingham, UK In ompliane with EBAC/EACCME guidelines, all authors partiipating in Eduation in Heart have dislosed potential onflits of interest that might ause a bias in the artile REFERENCES 1 Mayet J, Brady A. Hypertension: speial issues in different ethni groups. New perspetives in hypertension. Brady, Petrie: Merit Publishing International, 2003: Beevers DG, Lip GYH, O Brien E. ABC of hypertension, 4th ed. London: BMJ Publishing Group, 2001:12. 3 Lane DA, Lip GYH, Ethni differenes in hypertension, blood pressure ontrol in the UK. QJM 2001;94: An exellent review detailing the prevalene, treatment, and linial impliations of hypertension in ethni minority groups in the UK. The review larifies the onfliting epidemiologial data on ethni differenes in blood pressure in the UK. 4 Cappuio FP, Cook DG, Atkinson RW, et al. Prevalene, detetion, and management of ardiovasular risk fators in different ethni groups in South London. Heart 1997;78: MKeigue PM, Shah B, Marmot MG. Relationship of entral obesity and insulin resistane with high diabetes prevalene and ardiovasular risk in South Asians. Lanet 1991;344: Agyemang C, Bhopal RS. Hypertension and oronary heart disease in South Asians. The epidemi of oronary heart disease in South Asian populations: auses and onsequenes. South Asian Heart Foundation, 2003:108. Data from an authoritative book on ardiovasular disease in the South Asian population in the UK. The book was published by the South Asian Heart Foundation and desribes evidene based pratie to redue the high burden of ardiovasular disease in South Asians. 7 Cruikshank JK, Beevers DG, Osbourne VL, et al. 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BMJ 2004;328: Latest update of the BHS inorporating new epidemiologial data on ardiovasular disease risk and the importane of systoli hypertension as a determinant of risk. The guidelines hope to address the suboptimal management of hypertensive patients in the UK. 18 He FJ, Markandu ND, Sagnella GA, et al. Salt restrition in Europeans and Afro-Caribbeans. Hypertension 1998;32: Veterans Administration Cooperative Study Group on Antihypertensive Agents. Comparison of propranolol and hydrohlorothiazide for the initial treatment of hypertension: I. Results of short-term titration with emphasis on raial differenes in response. JAMA 1982;248: An early study showing evidene of the inreased effiay and sensitivity of blak patients to thiazide diuretis ompared to whites. The study showed that rae was an important determinant in deiding first line drug treatment. 20 Laragh JH, Cannon PJ, Stason WB, et al. Physiologi and linial observations on furosemide and etharyni aid. Ann N Y Aad Si 1966;139: Materson BJ, Reda DJ, Cushman WC, et al. Single-drug therapy for hypertension in men. A omparison of six antihypertensive agents with plaebo. N Engl J Med 1993;328: An exellent study with diret omparison of six antihypertensive drugs with plaebo in mild to moderately severe hypertension. Effiay aording to age and rae was also determined, showing that antihypertensive treatment should be tailored to individual patients. 22 Ventura HO, Frohlih ED, Messerli FH, et al. Cardiovasular effets and regional blood flow distribution assoiated with angiotensin onverting enzyme inhibition (aptopril) in essential hypertension. Am J Cardiol 1985;55: Soumerai SB, MLaughlin TJ, Spiegelman D, et al. Adverse outomes of underuse of beta-blokers in elderly survivors of aute myoardial infartion. JAMA 1997;277: Hall WD, Israili ZI. The use of ACE inhibitors in blaks and whites. In: Shahter M, ed. ACE inhibitors: urrent use and future prospets. 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Am J Hypertens 1995;8(12 pt 2):91S 3S. 29 Bakris GL, Copley JB, Viknair N, et al. Calium hannel blokers versus other antihypertensive therapies on progression of NIDDM assoiated nephropathy. Kidney Int 1996;50: Oparil S, Dyke S, Harris F, et al. The effiay and safety of valsartan ompared with plaebo in the treatment of patients with essential hypertension. Clin Ther 1996;18: Sehgal AR. Meta analysis of monotherapy in blak and white hypertensives. Hypertension 2004;43: A omprehensive meta-analysis on more than patients quantitating how often blak and white patients have similar responses to speifi antihypertensive drugs. 32 ALLHAT Offiers and Coordinators for the ALLHAT Collaborative Researh Group. Major outomes in high risk patients randomised to angiotensinonverting enzyme inhibitor or alium hannel bloker versus diureti. The antihypertensive and lipid-lowering treatment to prevent heart attak trial (ALLHAT). JAMA 2002;288: With over patients ALLHAT was the largest randomised ontrol trial of antihypertensive treatment to date and inluded blak patients. It showed that thiazide type diuretis provided effetive treatment at low ost Heart: first published as /hrt on 14 July Downloaded from on 15 July 2018 by guest. Proteted by opyright.