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OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Prof. Gregory Y. H. Lip
There are well-recognised ethnic differences in cardiovascular disease in the United Kingdom. In particular, black or Afro-Caribbean populations are at high risk of hypertension and related complications, such as cerebrovascular disease and renal damage, whilst coronary artery disease is rare. By contrast, south Asians (those from the Indian subcontinent) have a high prevalence of cardiovascular disease.
Much of the epidemiology, pathophysiological studies and clinical trials of antihypertensive therapy have been based on data from predominantly white Caucasian populations. Nonetheless, hypertension is a global problem, and all ethnic groups suffer the burden of this condition. This burden is illustrated by United Kingdom (UK) data that if all hypertensive patients in the UK reduced their systolic blood pressure to <140 mm Hg, approximately 21 400 stroke deaths, 41 400 ischaemic heart disease (IHD) deaths, and 125 600 events (non-fatal stroke or IHD) could be prevented . Despite the overwhelming evidence of the benefits of BP reduction, less than one in ten people in the UK achieve adequate control of their blood pressure – but it is hard to imagine what the situation might be in many non-Western countries, where such epidemiological and public health data are less available for non-white caucasian populations. Certainly, physiological and pharmacological responses may be influenced by ethnicity as a result of genetic factors, environmental factors and/or their interaction.
Nonetheless, a word of caution is needed. Within western countries it is easy to classify ‘ethnic groups’ too broadly, as race and ethnicity are not necessarily the same. Indeed, classification of race or ethnicity on skin colour is relatively subjective, imprecise and unreliable. For example, there are clear differences in coronary risk factors in Indians, Pakistani and Bangladeshi populations in a British city, but together these people might have been classed as ‘Indo-Asian’ and are clearly different .
From the hypertension perspective, the Afro-Caribbean ethnic group has been relatively well studied in North America, but one problem arises as to whether these data can be fully applicable to the predominantly first generation African and west Indian migrant populations in the United Kingdom, or similar ethnic populations in either Africa or the West Indies. In a study from a multiethnic community in Birmingham, England, the prevalence of hypertension and mean blood pressures were substantially higher among Afro-Caribbeans compared with white caucasians, whilst south-Asian men had similar rates of hypertension and mean blood pressures to white caucasians . In this analysis of 2853 subjects [76% white caucasians; 16% Afro-Caribbean; and 8% South-Asian], the overall prevalence of hypertension was highest in both Afro-Caribbean women (34%) and men (31%), when compared with white caucasians (13% and 19% respectively). When compared with white caucasians, Afro-Caribbeans had much higher mean systolic blood pressure, with higher mean diastolic blood pressures evident among Afro-Caribbean women. In contrast, South-Asian men had a similar prevalence of hypertension to white caucasians (16%).
Oriental populations from the Far East do have fairly good epidemiological data, and large trials such as SYST-CHINA and STONE have been conducted in Oriental populations . Data on hypertension in Indo-Asians are more limited, but some clinical and treatment data do exist.
In Afro-Caribbeans, the traditional approach has been to start treatment with diuretics or calcium antagonists, as the beta-blockers or ACE inhibitors (or angiotensin receptor blockers (ARBs)) tend to be less effective at blood pressure lowering, in view of the low renin state in this ethnic group. However, whether this efficacy at blood pressure lowering translated to better outcomes was uncertain until recent data from clinical trials. Indeed, two clinical trials have helped formulate the recently published guidelines on the management of high blood pressure in African Americans, with the publication of the Consensus statement of the Hypertension In African Americans Working Group of the International Society On Hypertension In Blacks.
The African American Study of Kidney disease and hypertension (AASK) The African American Study of Kidney disease and hypertension (AASK) study compared 3 drug strategies (ACE inhibitors, beta-blockers and calcium channel blockers) and their effects on hypertension nephrosclerosis in 1,094 American black patients [6,7]. All patients had a clinical diagnosis of hypertension nephrosclerosis. Although the mean blood pressure was similarly lowered, the ACE inhibitor, ramipril, reduced the decline in kidney function to a greater extent than did metoprolol or amlodipine . Furthermore, ramipril reduced clinical events by 46% when compared to amlodipine. Thus, an ACE inhibitor should still be prescribed for blacks with renal disease. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) involved 42,418 hypertensive patients with 50% women, 35% blacks and 36% diabetics. The doxazosin arm was stopped early due to an excess of cardiovascular events, especially heart failure. In the final results from ALLHAT, the incidence of fatal coronary heart disease and nonfatal myocardial infarction did not differ with the three classes of drugs (thiazides, ACE inhibitors, calcium antagonist) tested. However, the thiazide diuretic, arm had fewer combined cardiovascular disease events, particularly fewer strokes and less heart failure. Importantly, however, patients treated with lisinopril or amlodipine had much higher systolic blood pressures in comparison to patients who received chlorthalidone, especially amongst the African American and other black patients.
Thus, whilst the overall relative risk of stroke was 15% greater for lisinopril than chlorthalidone in the trial, for black patients the stroke risk was even higher at 40%. The poor effect of lisinopril in blacks could also be compounded by the choice of second-line antihypertensive agents (atenolol, clondine and reserpine) which may be less effective in blacks. In contrast, the AASK study used thiazide diuretics as second line agents.
The Hypertension in African American Working (HAAW) Group guidelines The recent consensus statement of the Hypertension in African American Working (HAAW) Group emphasises the need to control blood pressure whilst protecting against target organ damage. The guidelines state that as initial monotherapy, the beta-blockers, ACE inhibitors and ARBs are less effective at lowering blood pressure when compared to white patients, due to the intrinsically low renin state in this ethnic group. Indeed, plasma renin activity falls with increasing age, and even thoughout all age bands, Afro-Caribbeans have lower plasma renin activity levels than white Caucasians. In contrast, the thiazide diuretics and calcium channel blockers have much greater blood pressure lowering efficacy as monotherapy in Afro-Caribbeans, than other drug classes. Furthermore, alpha-blockers should not be used as first-line agents, especially in patients at risk of heart failure – in view of the data from ALLHAT. Whilst beta-blockers, ACE-inhibitors and ARBs are generally less effective as low-dose monotherapy, the use of very large doses or the addition of a diuretic or a calcium channel blocker as a second agent, would sufficiently lower blood pressure. If there are ‘compelling indications’ for prescribing beta-blockers, ACE inhibitors or ARBs in certain groups of patients with hypertension (eg. ‘high risk’ or presence of target organ damage, including heart failure, coronary artery disease or nephropathy), these indications should be applied equally to Afro-Caribbeans.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
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3. Bhopal R, Unwin N, White M, Yallop J, Walker L, Alberti KG et al. Heterogeneity of coronary heart disease risk factors in Indian, Pakistani, Bangladeshi, and European origin populations: cross sectional study. BMJ 1999;319:215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10417082
4. Ueshima H, Zhang XH, Choudhury SR. Epidemiology of hypertension in China and Japan. J Hu. Major cardiovascular events in hypertensive patients randomised to Angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12484509 JAMA 2002; 288: 2421-2431. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12435255
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