Left Ventricular Hypertrophy the Problem and Possible Solutions

Transcription

1 The Journal of International Medical Research 2005; 33 (Suppl 1): 3A 11A Left Ventricular Hypertrophy the Problem and Possible Solutions P GOSSE Cardiology Service Arterial Hypertension, Hospital Saint-André, Bordeaux, France Left ventricular hypertrophy (LVH), which describes pathological changes in cardiac structure, is a powerful and reversible predictor of cardiovascular risk. There is a continuous relationship between left ventricular mass (LVM) and the likelihood of cardiovascular events, with no cut-off between the absence of such events and heightened risk. A correlation between LVH and blood pressure is well established. There is a paradox, however, that the structural changes to the heart as a result of increased workload due to high blood pressure appear to promote cardiovascular disease. This may be partially explained by the fact that ambulatory blood pressure measurements correlate more closely with LVH than resting blood pressure. Blood pressure variation throughout the day is also emerging as an important correlate of LVH, and a strong association has been identified between an early morning rise in blood pressure and increased LVM. Use of anti-hypertensive agents not only lowers blood pressure, but can also bring about LVH regression. The pathological role of angiotensin II in LVH and target-organ damage within the cardiovascular continuum suggest that agents targeting the renin angiotensin aldosterone system (RAAS), such as the angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, may prove particularly effective and may confer beneficial effects in addition to the lowering of blood pressure. The angiotensin II receptor blockers may be very appropriate treatment options because of their placebo-like tolerability and the possibility of more complete blockade of the RAAS. Within this class of anti-hypertensive agents, pharmacological differences may mean that some agents afford greater cardioprotection than others. KEY WORDS: LEFT VENTRICULAR HYPERTROPHY; LEFT VENTRICULAR MASS; PATHOPHYSIOLOGY; HYPERTENSION; TREATMENT; ANGIOTENSIN II RECEPTOR BLOCKERS Introduction Left ventricular hypertrophy (LVH) is, in simple terms, an adaptive response to chronic exposure of the heart to an increased workload, a common cause being systemic hypertension. At the cellular level, the cardiomyocytes expand in thickness and length, but with little or no increase in the number of cells, to compensate for the increased haemodynamic stress on the ventricular wall. 1 In addition, as distinct from the hypertrophy seen in growth and as a result of exercise and physical training, fibroblasts proliferate with abnormal accumulation of collagen, leading to fibrosis. 1 The overall 3A

2 effect of these histological changes is an increase in left ventricular mass (LVM). In LVH, normal cardiac function becomes compromised. 2 The accumulation of fibrillar collagen within the adventitia of the intramyocardial coronary arteries and interstitial spaces brings about ventricular stiffness and decreases coronary flow reserve. Increased ventricular stiffness can lead to abnormal diastolic function and heart failure, with preserved systolic function. 3 The decreased coronary flow reserve increases the risk of cardiac ischaemia, potentially lethal cardiac arrhythmias and myocardial infarction. 4 In addition, the fibrosis disrupts the electrical and mechanical behaviour of the hypertrophied myocardium. Reduced cardiac contractility may finally occur as a result of increased workload and myocardial ischaemia. Left ventricular hypertrophy is widely recognized as a powerful, but reversible, risk factor for cardiovascular morbidity and mortality. Indeed, after age, LVH is the single strongest predictor of cardiovascular events, cardiovascular death and total mortality. 5 Epidemiological studies have shown that LVH is an independent risk factor for cardiovascular morbidity and mortality and for all-cause mortality in the general population, 6 as well as in individuals already at higher risk, such as those with hypertension 7 or coronary artery disease. 8 The risk is magnified even in hypertensive individuals with increases in echocardiographically detected LVM too small to be defined as LVH. 9,10 Findings from the Bordeaux cohort who were initially untreated reinforce this correlation (Fig. 1) and confirm that very small increases 1.0 LVM/h 2.7 quintiles 5th = 77 4th = 60 3rd = 52 2nd = 44 1st = 35 Event-free survival ratio Follow-up (months) FIGURE 1: Age-, sex-, and blood pressure-adjusted event-free survival curves for left ventricular mass (LVM) indexed to height to the power 2.7 in 520 patients of the Bordeaux cohort followed up over 102 ± 42 months with 56 cardiovascular events recorded 4A

3 in LVM still impact on cardiovascular risk, independently of other variables. 11 Screening for LVH Diagnosis of LVH is not a simple matter. LVH is undetectable on physical examination. 3 Using voltage criteria and QRS duration, electrocardiograms can identify LVH with high specificity, but poor sensitivity. 12 Repolarization abnormalities (ST changes) are frequent, but can be regarded as a witness of reduced perfusion of the internal layers of the myocardial wall rather than being a specific marker of LVH. 13 Echocardiography, which is about eight-fold more sensitive, 14 has become the reference method to detect LVH. It provides a safe and noninvasive method for evaluating cardiac anatomy and function, and has been extensively used in clinical trials. More recently, magnetic resonance imaging has been developed that allows high-resolution visualization of the entire heart and gives an accurate measurement of LVM, in a manner that is independent of shape or perfusion. 15 The technique, which provides interstudy reproducibility in normal, dilated and hypertrophic hearts and is superior to twodimensional echocardiography, 16 is now accepted as the method of choice for LVM determination in clinical investigations and for serial evaluation of selected patients. As yet, it is not routinely used for diagnosis. The definition of LVH depends on the method by which the LVM is indexed (i.e. height, body surface area or height to the power 2.7, which appears to be particularly sensitive). 17 The cut-off proposed in the literature displays important differences between one study and another, 17 and the definition of the cut-off from the analysis of normal populations may not provide the most useful criterion. In the light of large variability in LVM measurements provided by echocardiography even in normal subjects, the calculation of the 95th percentile usually leads to a high cut-off value. Consequently, LVH is better defined in terms of risk prediction, there being a strong link between increased LVM and increased incidence of cardiovascular complications. 6 LVH and hypertension Numerous studies have demonstrated a correlation between LVM and blood pressure. This is logical as increased LVM can be regarded as a response to greater workload associated with high blood pressure, and could be considered a useful adaptation to a chronic increase in myocardial strain. There is, however, a paradox that LVH appears to promote cardiovascular disease. Three possible explanations have been proposed. 18 One possibility is that, as a marker of cardiovascular risk, LVH integrates the effect of various factors the main one being blood pressure with these effects being integrated over time. Two arguments support this hypothesis: first, LVH is a risk factor for not only cardiac disease but also for other cardiovascular events, such as stroke; 19 secondly, ambulatory blood pressure measurements correlate more closely with LVH than resting blood pressure, as discussed later. The second hypothesis is that, although LVH is an adaptive process, it is limited. The initial advantages of lowering parietal stress may be gradually overridden by the stimulated myocyte growth and the consequent remodelling of the left ventricular chamber. 1 This hypothesis, however, is not supported by the observation that the correlation between LVM and cardiovascular risk is continuous, with no obvious threshold. 11 The third hypothesis is that there is a clear distinction between physiological and pathological LVH from the outset. The proliferation of interstitial tissue and 5A

4 accumulation of collagen is possibly stimulated by different mechanisms to those causing myocyte hypertrophy. 16 Systolic blood pressure is more closely related to LVM than diastolic blood pressure. Other haemodynamic factors that can contribute to LVH include increased arterial stiffness of the aorta 20 and increased blood viscosity, 21 both of which increase the workload of the heart, and thus stimulate hypertrophic changes. Other factors may contribute to LVH; for example, the prevalence of LVH correlates strongly and independently with alcohol consumption, obesity and age. 18 Increased LVM correlates even more closely with 24-h mean ambulatory blood pressure than with isolated clinic measurements (Table 1) As a result, 24-h mean values of ambulatory blood pressure are now regarded as more sensitive predictors of LVH. 27 Furthermore, treatment-induced reductions in LVM are reflected in corresponding reductions in 24-h mean blood pressure, but correlation between 24-h mean blood pressure and LVM is still relatively weak. 26 Other parameters, such as blood pressure recorded during activity, the difference between daytime and night-time values, and blood pressure recorded when the subject arises in the morning, have been proposed as being of greater prognostic value. 28 Most people, including those with hypertension, display a circadian variation in blood pressure, with levels being highest during the day and lowest in the middle of the night. 28 At the time of awakening, there is a surge in blood pressure. 29 This rapid elevation in blood pressure is accompanied by an acceleration in cardiac rhythm, with no significant correlation between the two parameters. The increase in blood pressure on rising has been linked to the overall variability in blood pressure, but appears independent of the mean blood pressure over 24 h. 29 In previously untreated patients with hypertension, both LVM and left ventricular wall thickness correlate with systolic blood pressure on arising. Two other studies have found that in treated and untreated hypertensive patients with a morning surge in blood pressure, LVM indexes are significantly higher. 30,31 It is interesting to note that the time of the early morning surge in blood pressure coincides with the peak incidence of acute cardiovascular events, 32 thus providing further evidence for the link between early morning blood pressure surge TABLE 1: Studies examining the relationship between clinic and ambulatory systolic blood pressures (SBP) in hypertensive subjects and left ventricular mass Correlation coefficients Number Clinic Daytime Night-time 24-h mean studied SBP SBP SBP SBP Rowlands et al Devereux and Pickering a White et al Verdecchia et al Gosse et al a Hypertensive plus normal subjects. 6A

5 and LVH. More recently, it has been demonstrated that, in elderly Japanese subjects, those with the greatest morning blood pressure experience a significantly higher incidence of silent and overt cerebrovascular events. 33 Other aspects of blood pressure variability may impact on LVH. In patients with similar 24-h mean blood pressures, those who do not exhibit the normal circadian variation and display little or no night-time fall in blood pressure (i.e. non-dippers ) have higher LVM values compared with normal dippers. 34 It has been proposed that blunted reduction in nocturnal blood pressure, if it persists over a period of time, may play a pivotal role in the development of some expressions of targetorgan damage, such as LVH and intimamedia thickening, during the early phase of essential hypertension. 34 Whatever the mechanisms, LVH appears more and more as a surrogate endpoint for morbid events in hypertension and thus deserves special attention. It fulfils most of the conditions of a substitute criterion, 35 with lower LVM during anti-hypertensive treatment being associated with lower incidences of clinical endpoints. 36 LVH and the role of the renin angiotensin aldosterone system The Framingham Heart Study has shown that LVH is reversible and responds well to the lowering of blood pressure. 37 Increasing use of anti-hypertensive therapy over the period was associated with a reduced prevalence of high blood pressure and a concomitant decline in LVH in the general population. In part, this is thought to explain the considerable decline in mortality from cardiovascular disease observed since the late 1960s. However, this is not cause for complacency. The renin angiotensin aldosterone system (RAAS) orchestrates many of the cellular, biochemical and pathological changes that initiate and perpetuate LVH, with angiotensin II playing a key role (Fig. 2). 38 Elevated levels of circulating angiotensin II and aldosterone have been shown to correlate positively with increased LVM and reduced left ventricular function. 39,40 Thus, pharmacological interruption of the RAAS offers a potent method of preventing hypertension and regressing LVH, as well as protecting other target organs from angiotensin-ii-induced damage. Recently, a meta-analysis was conducted on data from double-blind, randomized, controlled trials performed up until September 2002 that evaluated the effects of diuretics, β-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on echocardiographically evaluated LVM in essential hypertension. 41 The meta-analysis revealed that treatments targeting the RAAS resulted in the most substantial reductions in LVM. Clinical studies have consistently shown that treatment of mildly hypertensive patients with ACE inhibitors 42,43 or ARBs 3,44 brings about LVH regression through mechanisms that seem partially independent of their ability to reduce blood pressure. Angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers The mechanisms of action of ACE inhibitors and ARBs differ. Formation of angiotensin II from angiotensin I is prevented by ACE inhibitors; however, angiotensin II can be generated by alternative enzymatic pathways, such as chymase present in the heart, that 7A

6 Local Angiotensin Circulating Vasoconstriction Fibrosis Myocardial remodelling Hypertension Myocyte hypertrophy Left ventricular hypertrophy Increased ventricular stiffness Reduced cardiac contractility Decreased coronary flow reserve Abnormal diastolic function and congestive heart failure FIGURE 2: The role of angiotensin II in left ventricular hypertrophy and cardiac pathophysiology 38 are not susceptible to ACE inhibition. 45,46 In contrast, the ARBs prevent the binding of angiotensin II to the type 1 receptors present in various tissue; thus, the deleterious effects of angiotensin II are overcome irrespective of whether it is produced systemically or locally and by whatever mechanism. 47 Extensive data have shown that ARBs have an important role in LVH management. 48 In clinical studies, ARBs have been shown to bring about regression of LVM The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, for example, has demonstrated that treatment with losartan, plus hydrochlorothiazide and other medications when needed for blood pressure control, resulted in greater LVH regression in patients than did conventional atenolol-based treatment. 53 Conclusions If allowed to advance, LVH is a considerable cause of cardiovascular disease and death. LVH regression by aggressive control of blood pressure may make a valuable contribution to improving prognosis. In the light of the important role that angiotensin II plays within the cardiovascular continuum, pharmacological targeting of the RAAS may confer additional benefits in terms of LVH reversal and improved prognosis to that provided by effective blood pressure alone using other anti-hypertensive agents. The ARBs, a class of anti-hypertensive agents with well-established efficacy and a placebo-like safety profile, 54 may prove especially valuable, by providing more complete blockade of angiotensin II than 8A

7 ACE inhibitors. Evidence is amassing that use of ARBs may be a superior therapeutic option for LVH management. Pharmacological differences within the class, such as duration of action, may differentiate between the cardioprotective properties of the commercially available ARBs. In the future, well-designed, sufficiently powered, long-term outcome studies using accurate measurement of LVM may provide conclusive evidence for the beneficial effects of ARBs on LVH, 55,56 with the ultimate goal being the reduction in cardiovascular morbidity and mortality in high-risk patients. Conflicts of interest No conflicts of interest were declared in relation to this article. Copyright 2005 Cambridge Medical Publications References 1 Massie BM: Myocardial hypertrophy and cardiac failure: a complex interrelationship. Am J Med 1983; 75: Diez J, Querejeta R, Lopez B, Gonzalez A, Larman M, Martinez Ubago JL: Losartandependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation 2002; 105: Kahan T: The importance of left ventricular hypertrophy in human hypertension. J Hypertens 1998; 16 (Suppl 7): S23 S29. 4 Tin LL, Beevers DG, Lip GY: Hypertension, left ventricular hypertrophy, and sudden death. Curr Cardiol Rep 2002; 4: Levy D, Anderson KM, Savage DD, Kannel WB, Christiansen JC, Castelli WP: Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham Heart Study. Ann Intern Med 1988; 108: Levy D, Murabito JM, Anderson KM, Christiansen JC, Castelli WP: Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH: Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991; 114: Ghali JK, Liao Y, Simmons B, Castaner A, Cao G, Cooper RS: The prognostic role of left ventricular hypertrophy in patients with or without coronary artery disease. Ann Intern Med 1992; 117: Schillaci G, Verdecchia P, Porcellati C, Cuccurullo O, Cosco C, Perticone F: Continuous relation between left ventricular mass and cardiovascular risk in essential hypertension. Hypertension 2000; 35: Vasan RS, Larson MG, Levy D, Evans JC, Benjamin EJ: Distribution and categorization of echocardiographic measurements in relation to reference limits: the Framingham Heart Study: formulation of a height- and sex-specific classification and its prospective validation. Circulation 1997; 96: Cipriano C, Gosse P, Bemurat L, Mas D, Lemetayer P, N tela G, et al: Prognostic value of left ventricular mass and its evolution during treatment in the Bordeaux cohort of hypertensive patients. Am J Hypertens 2001; 14: Jern S: Assessment of left ventricular hypertrophy in patients with essential hypertension. Blood Press Suppl 1997; 2: Turk J: ST-T segment changes in patients with essential hypertension. Cor Vasa 1982; 24: Levy D, Labib S, Anderson K, Christiansen J, Kannel W, Castelli W: Determinants of sensitivity and specificity of electrocardiographic criteria for left ventricular hypertrophy. Circulation 1990; 81: Shapiro EP: Evaluation of left ventricular hypertrophy by magnetic resonance imaging. Am J Card Imaging 1994; 8: Grothues F, Smith GC, Moon JC, Bellenger NG, Collins P, Klein HU, et al: Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol 2002; 90: Gosse P, Jullien V, Jarnier P, Lemetayer P, Clementy J: Echocardiographic definition of left ventricular hypertrophy in the hypertensive: which method of indexation of left ventricular mass? J Hum Hypertens 1999; 13: Gosse P, Dallocchio M: Left ventricular hypertrophy: epidemiological prognosis and associated critical factors. Eur Heart J 1993; 14 (Suppl D): Fustinoni O: Editorial comment left ventricular hypertrophy: an unseemly risk factor for stroke? Stroke 2003; 34: Girerd X, Laurent S, Pannier B, Asmar R, Safar M: Arterial distensibility and left ventricular hypertrophy in patients with sustained essential hypertension. Am Heart J 1991; 122 9A

8 (4 Pt 2): Devereux RB, Pickering TG, Alderman MH, Chien S, Borer JS, Laragh JH: Left ventricular hypertrophy in hypertension. Prevalence and relationship to pathophysiologic variables. Hypertension 1987; 9 (2 Pt 2): II53 II Rowlands DB, Ireland MA, Glover DR, McLeay RA, Stallard TJ, Littler WAL: The relationship between ambulatory blood pressure and echocardiographically assessed left ventricular hypertrophy. Clin Sci (Lond) 1981; 61 (Suppl 7): 101s 103s. 23 Devereux RB, Pickering TG: Relationship between the level, pattern and variability of ambulatory blood pressure and target organ damage in hypertension. J Hypertens 1991; 9 (Suppl 8): S34 S White WB, Dey HM, Schulman P: Assessment of the daily blood pressure load as a determinant of cardiac function in patients with mild-tomoderate hypertension. Am Heart J 1989; 118: Verdecchia P, Schillaci G, Guerrieri M, Gatteschi C, Benemio G, Boldrini F, et al: Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 1990; 81: Gosse P, Ansoborlo P, Jullien V, Lemetayer P, Clementy J: Ambulatory blood pressure and left ventricular hypertrophy. Blood Press Monit 1997; 2: Mancia G, Zanchetti A, Agabiti-Rosei E, Benemio G, De Cesaris R, Fogari R, et al: Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. Circulation 1997; 95: Staessen JA, Bieniaszewski L, O Brien E, Gosse P, Hayashi H, Imai Y, et al: Nocturnal blood pressure fall on ambulatory monitoring in a large international database. Hypertension 1997; 29: Gosse P, Lasserre R, Minifie C, Lemetayer P, Clementy J: Blood pressure surge on rising. J Hypertens 2004; 22: Ikeda T, Yamamoto K, Okada J, Hyayashida M, Yamada C, Kasatani T, et al: Morning rise in blood pressure associates with hypertensive cardiovascular complications. J Hypertens 2002; 20 (Suppl 4): S Matsuo K, Kosugi T, Kamiya H, Yoshii K, Okada J, Gomi T, et al: Morning rise in blood pressure is a risk factor for cardiovascular complications in treated hypertensive patients. J Hypertens 2002; 20 (Suppl 4): S Mulcahy D: Circadian variation in cardiovascular events. Blood Press Monit 1998; 3: Kario K, Pickering TG, Umeda Y, Hoshide S, Hoshide Y, Morinari M, et al: Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study. Circulation 2003; 107: Cuspidi C, Macca G, Sampieri L, Fusi V, Severgnini B, Michev I, et al: Target organ damage and non-dipping pattern defined by two sessions of ambulatory blood pressure monitoring in recently diagnosed essential hypertensive patients. J Hypertens 2001; 19: Gosse P, Herpin D: Can regression of left ventricular hypertrophy be proposed as a substitute criterion in trials of morbidity/ mortality in hypertension (in French)? Arch Mal Coeur Vaiss 2000; 93 (11 Suppl): Devereux RB, Wachtell K, Gerdts E, Boman K, Nieminen MS, Papademetriou V, et al: Prognostic significance of left ventricular mass change during treatment of hypertension. JAMA 2004; 292: Erhardt L: Endothelial dysfunction and cardiovascular disease: the promise of blocking the renin angiotensin system. Int J Clin Pract 2003; 57: Bouzeghrane F, Thibault G: Is angiotensin II a proliferative factor of cardiac fibroblasts? Cardiovasc Res 2002; 53: Schlaich MP, Schobel HP, Langenfeld MR, Hilgers K, Schmieder RE: Inadequate suppression of angiotensin II modulates left ventricular structure in humans. Clin Nephrol 1998; 49: Schlaich MP, Schobel HP, Hilgers K, Schmieder RE: Impact of aldosterone on left ventricular structure and function in young normotensive and mildly hypertensive subjects. Am J Cardiol 2000; 85: Klingbeil A, Schneider M, Martus P, Messerli F, Schmieder RE: A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med 2003; 115: Agabiti-Rosei E, Ambrosioni E, Dal Palu C, Muiesan ML, Zanchetti A: ACE inhibitor ramipril is more effective than the beta-blocker atenolol in reducing left ventricular mass in hypertension. Results of the RACE (ramipril cardioprotective evaluation) study on behalf of the RACE study group. J Hypertens 1995; 13: Garavaglia GE, Messerli FH, Nunez BD, Schmieder RE, Frohlich ED: Angiotensin converting enzyme inhibitors. Disparities in the mechanism of their antihypertensive effect. Am J Hypertens 1988; 1 (3 Pt 3): 214S 216S. 44 Wachtell K, Dahlof B, Rokkedal J, Papademetriou V, Nieminen MS, Smith G, et al: Change of left ventricular geometric pattern after 1 year of antihypertensive treatment: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Am Heart J 2002; 144: Hollenberg NK, Fisher ND, Price DA: Pathways for angiotensin II generation in intact human tissue: evidence from comparative pharmacological interruption of the renin system. Hypertension 1998; 32: Mervaala E, Muller DN, Schmidt F, Park JK, 10A

9 Gross V, Bader M, et al: Blood pressureindependent effects in rats with human renin and angiotensinogen genes. Hypertension 2000; 35: McConnaughey MM, McConnaughey JS, Ingenito AJ: Practical considerations of the pharmacology of angiotensin receptor blockers. J Clin Pharmacol 1999; 39: Dahlof B: Left ventricular hypertrophy and angiotensin II antagonists. Am J Hypertens 2001; 14: Cuspidi C, Muiesan ML, Valagussa L, Salvetti M, Di Biagio C, Agabiti-Rosei E, et al: Comparative effects of candesartan and enalapril on left ventricular hypertrophy in patients with essential hypertension: the candesartan assessment in the treatment of cardiac hypertrophy (CATCH) study. J Hypertens 2002; 20: Dahlof B, Zanchetti A, Diez J, Nicholls MG, Yu CM, Barrios V, et al: Effects of losartan and atenolol on left ventricular mass and neurohormonal profile in patients with essential hypertension and left ventricular hypertrophy. J Hypertens 2002; 20: Malmqvist K, Kahan T, Edner M, Held C, Hagg A, Lind L, et al: Regression of left ventricular hypertrophy in human hypertension with irbesartan. J Hypertens 2001; 19: Thurmann PA: Angiotensin II antagonism and the heart: valsartan in left ventricular hypertrophy. Cardiology 1999; 91 (Suppl 1): Devereux RB, Dahlof B, Gerdts E, Boman K, Nieminen MS, Papademetriou V, et al: Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial. Circulation 2004; 110: Siragy HM: Angiotensin receptor blockers: how important is selectivity? Am J Hypertens 2002; 15: Gosse P, Dubourg O, Gueret P: Regression of left ventricular hypertrophy with echocardiography: some lessons from the LIVE study. J Hypertens 2003; 21: Verdecchia P, Angeli F, Borgioni C, Gattobigio R, de Simone G, Devereux RB, et al: Changes in cardiovascular risk by reduction of left ventricular mass in hypertension: a metaanalysis. Am J Hypertens 2003; 16: Address for correspondence Dr P Gosse Cardiology Service Arterial Hypertension, Hospital Saint-André, 1 rue Jean Burguet, Bordeaux Cedex, France. philippe.gosse@chu-bordeaux.fr 11A