Left ventricular (LV) hypertrophy is a form of pre-clinical cardiac disease that may be induced by either pressure or volume myocardial overload, as well as genetic factors and a variety of other stimuli. Pressure overload, as exemplified by aortic stenosis, and volume overload, as exemplified by regurgitant aortic or mitral valve disease or chronic anaemia, initiates growth of cardiac myocytes and increase in connective tissue without notable derangements in the interstitial architecture. As a result, myocyte shortening may translate into efficient ventricular contraction with preserved diastolic properties. In hypertensive patients, there is often a combination of pressure and volume overload resulting in a mixture of myocyte elongation, needed to accommodate a higher ventricular chamber volume, and myocyte thickening, stimulated by the greater afterload.1,2
LV hypertrophy is a cardinal manifestation of pre-clinical cardiovascular disease3 that strongly predicts myocardial infarction, stroke and cardiovascular death in patients with hypertension4 in members of the general population5 and in patients with or without angiographic coronary artery disease.6 The risk of death or non-fatal complications is increased two- to four-fold in the presence of LV hypertrophy, independently of age, gender and other risk factors.4–6 Further risk stratification may be obtained by characterisation of LV geometrical patterns.4 Longitudinal studies in hypertensive patients7–9 and the general population10 have reported that individuals in whom LV hypertrophy regressed had lower rates of subsequent morbidity/ mortality than those in whom LV mass increased. As a result, prevention or reversal of hypertensive LV hypertrophy has been widely accepted as a desirable goal. However, until recently, available studies relating to changes in echocardiographic LV mass or electrocardiographic indices in terms of prognosis have suffered from relatively small sample sizes, incomplete knowledge of blood pressure and treatment during follow-up and variably incomplete analyses.11 Furthermore, it was uncertain how best to reverse hypertensive LV hypertrophy because most published studies have been relatively small and commonly have been of short duration, lacked comparative agents, had un-blinded reading of echocardiograms or were performed in non-representative populations.12
Larger trials have not been definitive because of confounding effects of concomitant non-drug therapy, high subject drop-out or absence of LV hypertrophy before therapy.13,14 More recently, the Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial enrolled hypertensive patients with electrocardiographic LV hypertrophy in a prospective, double-blind, randomised study large enough (n=9,193) to determine whether a greater reduction in morbid events is achieved by either use of losartan compared with the comparative agent (atenolol) or regression compared with persistence or progression of electrocardiographic LV hypertrophy.15–17
As part of the LIFE trial, >10% of study participants were enrolled in the LIFE echocardiography substudy in which echocardiograms were performed at study baseline and yearly thereafter.18 The echocardiography population was representative of the main LIFE study in age, blood pressure and prevalences of cardiovascular diseases and diabetes at baseline, but differed from the remaining LIFE participants in being disproportionately male, due predominately to participation in the echocardiographic substudy of several Veterans’ Administration Hospitals in the US and a centre in Norway that recruited participants from the all-male Oslo Heart Study. Height and heart rate were higher and body mass index lower in the echocardiography substudy participants. A higher population of blacks were enrolled in the echocardiography substudy compared with the overall LIFE population to assess possible ethnic differences in LV geometry and the performance of electrocardiographic indices of LV hypertrophy.18
Assessment of Left Ventricular Hypertrophy
Because of the importance of assessing LV hypertrophy as a marker of cardiac risk, several methods have been developed to estimate LV mass. Although electrocardiography carries independent prognostic information, echocardiography is more sensitive for assessing LV hypertrophy.19,20 Furthermore, to date, echocardiography remains the only modality that has been anatomically validated in humans for estimation of LV mass.21 Use of a standardised protocol and training of sonographers are required to limit variability of echocardiographic measurements. Data from the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) documented excellent interstudy variability and show the ability to detect small changes of LV mass in modestly sized populations.22 Palmieri et al. reported that the short-term between-study variability had high interclass correlation (ρ=0.93; see Figure 1), an estimator of variability between replicate measurements, resulting in LV mass ±34g or ±18g in a single patient with ≥90 or ≥80% likelihood to be true changes, respectively.22
Lately, both 3D echocardiography23 and cardiac magnetic resonance imaging24 have been shown to have lower variability than 2D echocardiography, and magnetic resonance imaging has now been used in population-based studies.25 However, there are still no human necropsy comparison data to validate magnetic resonance imaging.
This has led to controversy in terms of image modality for detection of LV hypertrophy.26,27 The current data suggest that 41 patients are needed per treatment arm to provide statistical power of 90% at an error level of 1% to detect a between-group difference of at least 10g/m2. Similarly, 3D echocardiography requires 15 patients per arm and magnetic resonance imaging requires 14 patients per arm. Thus, echocardiographic LV mass remains an excellent bioassay for clinical studies of LV hypertrophy that require moderate or large population sizes to obtain sufficient clinical end-points or to encompass participants with varied characteristics.22,23
Left Ventricular Mass Index and Left Ventricular Geometry
Echocardiographic partition values for LV hypertrophy/body surface area were suggested by Hammond et al.28 to be 134g/m2 for men and 110g/m2 for women. However, more recent data derived from the PRESERVE trial, using newer echocardiographs in reference populations that met more stringent criteria of normality,29,30 suggest partition values of 116g/m2 for men and 104g/m2 for women or 115 and 96g/m2, respectively. A comparison of the LIFE echocardiography study participants versus apparently normal adults showed that indexation of LV mass for height2.7 avoided the underestimation of the prevalence of LV hypertrophy in overweight and obese patients that occurs with indexation of LV mass by body surface area. In addition, patients recruited by LV mass indexed for body surface area have higher blood pressure, whereas patients recruited by LV mass indexed for height2.7 have a higher prevalence of obesity (see Table 1). In view of increasing obesity worldwide, indexation by the allometric power of height becomes increasingly important.
The combination of LV mass index (LVMI) and relative wall thickness has been used to identify three abnormal LV geometrical patterns,4,31 known as concentric remodelling (normal LVMI with increased relative wall thickness), eccentric hypertrophy (increased LVMI and normal relative wall thickness) and concentric hypertrophy (increased LVMI and increased relative wall thickness). Relative wall thickness has been calculated either as the ratio of 2x posterior wall thickness/LV internal diameter32 or as the ratio of (interventricular septal + posterior wall thickness)/LV internal diameter.33,34 Analyses of data from a working population from New York suggests the partition value of relative wall thickness to be 0.43.30,35
Different studies have shown quite different prevalences of LV hypertrophy depending on the population studied and the methods used for calculation of LVMI and relative wall thickness. Studies have used a variety of partition values for LV mass and relative wall thickness to identify LV hypertrophy and geometrical remodelling and therefore have arrived at very different prevalences of abnormal geometry.35 Concentricity, i.e. increased relative wall thickness, is associated with low weight,36 older age37 and black ethnicity,25,38 independent of body composition. However, it remains controversial whether higher relative wall thickness is a genetic variation or a reflection of the composite influence of greater pressure than volume–load and a response to offset increased wall stress.34 The relationship between LVMI and relative wall thickness seems to be important, as several studies have shown that stratification by different geometrical patterns gives valuable information in terms of morbidity and mortality.4,39–43 In some studies, subjects with concentric hypertrophy (i.e. increased LVMI and relative wall thickness) had the highest incidence of cardiovascular events and death, those with eccentric hypertrophy or concentric remodelling had intermediate rates and those with normal LV geometry had the fewest complications.4,39–43
Although it has been suggested that treatment of LV geometry would be beneficial, previous studies did not find independent prognostic information of LV geometry when taking LV mass at baseline into account.40,41,43
Treating Left Ventricular Hypertrophy and Geometry
Systematic antihypertensive treatment is effective in reducing LV mass and relative wall thickness. In the LIFE trial, one year of antihypertensive treatment that reduced blood pressure by 23/11mmHg resulted in a reduction of LVMI by 15g/m2 or >12%.44 Similarly, relative wall thickness was reduced by an absolute 4% or proportionately by almost 10%. LV geometry improved significantly as normal geometry increased from <20% at baseline to >50% after one year of treatment. Concentric LV geometry was especially reduced, with concentric hypertrophy prevalence reduced from 25% to only 6%. As a consequence, only one in six patients with either concentric remodelling or hypertrophy at baseline had the same geometrical pattern after one year of treatment (see Figure 2). Greater early reduction in LV mass was associated with female gender and reduction in body mass index, systolic and pulse pressure and Doppler stroke volume. Reduction in relative wall thickness was associated with lower diastolic blood pressure, lower LV ejection fraction and increased stroke volume.44 Data from the LIFE echocardiographic study additionally showed that a further reduction of LV mass and relative wall thickness occurred during the second year of systematic antihypertensive therapy, during a period where blood pressures decreased only slightly with even further increase in the prevalence of normal geometry.45 The clinical implication is that treatment of LV hypertrophy should have at least a two-year duration to achieve maximum benefit even if there is no further reduction in blood pressure.
Prognostic Significance of Treating Left Ventricular Hypertrophy
Despite benefits from blood pressure reduction, Devereux et al. demonstrated a substantial associated benefit in terms of cardiovascular morbidity and mortality from reduction in echocardiographic LV mass.46 During 4.8 years of systematic antihypertensive treatment, in-treatment reduction of LVMI by 25.3g/m2 (one standard deviation) was associated with a 22% reduction in composite end-points, a 38% reduction in cardiovascular mortality and a 24% reduction in fatal and non-fatal stroke independent of the effect of blood pressure lowering and randomised treatment regimen in the LIFE study. Similar time-varying Cox analyses showed that in-treatment absence of LV hypertrophy, treated as a yes–no diagnosis, was associated with a 42% reduction in composite end-points, a 66% reduction in cardiovascular mortality and a 52% reduction in fatal and non-fatal myocardial infarction, also adjusted for the effect of blood pressure lowering (see Figure 3). This report, and a parallel one showing independent association of lower electrocardiographic indices of LV hypertrophy with reduced rates of cardiovascular events in the entire LIFE population,47 provided the first demonstration of a blood-pressure-independent effect of LV mass reduction on prognosis. In addition, reduction in LV hypertrophy translates into a reduction in sudden cardiac death.48 These findings support the concept of reducing cardiac target organ damage as a goal of antihypertensive treatment. In another analysis from the LIFE study, losartan was more effective than atenolol in reducing echocardiographic LV mass49 or relevant electro- cardiographic indices.50 Further analyses of the LIFE echocardiographic data showed that even though LV geometry changed significantly during treatment, time-varying LV geometry predicted higher risk of composite end-points (HR 2.99 [1.16–7.71] for concentric remodelling, HR 1.79 [1.17–2.73] for eccentric hypertrophy and HR 2.71 [1.13–6.45] for concentric hypertrophy when adjusting for randomised treatment, Framingham risk score, race and time-varying systolic blood pressure).51 This suggests that concentric LV geometry carries the most risk, extending an observational study by Muiesan et al. in a group of 436 hypertensive patients in which persistent or new development of concentric LV geometry was associated with higher risk of cardiovascular morbidity and mortality during prospective follow-up.52
Left Ventricular Systolic Function in Patients with Left Ventricular Hypertrophy
Assessment of LV systolic performance by the ratio of observed LV endocardial fractional shortening (FS) to the value predicted by the level of end-systolic stress in normal individuals53,54 may appear to identify LV function as ‘supranormal’ in hypertensive patients compared with normal controls, even in the absence of LV hypertrophy.53,55,56 LV midwall shortening (MWS), in relation to stress, provides a different impression of the integrity of systolic performance; MWS may be impaired in hypertensive patients with normal or supranormal LV ejection fraction. Wachtell et al. confirmed that LV endocardial FS or MWS were lower with higher LV mass and relative wall thickness either alone or in combination.57 In the subgroup with concentric LV hypertrophy, we found that >40% had overt LV systolic dysfunction, manifested by endocardial FS or MWS below the 2.5th percentile of normal values (see Figure 4). Even in the subgroup with normal LV geometry we found impaired LV systolic performance in 10% of cases, i.e. five times more commonly than in the reference population.30,58 Furthermore, it was observed that hypertensive patients with normal geometry or with eccentric LV hypertrophy had high end-systolic stress compared with normal adults. Previously reported in mildly hypertensive adults,59 this result also reflects the Laplace relationship, which indicates that high relative wall thickness tends to normalise wall stress. Moreover, impaired endocardial FS was most prevalent in eccentric LV hypertrophy, while impaired MWS was most prevalent with concentric remodelling or, especially, concentric hypertrophy.
The clinical significance of impaired LV systolic performance in hypertensive patients is not yet fully clarified; however, there are numerous reports of patients with heart failure and ‘normal’ LV systolic chamber function.60 In the Framingham Heart Study in participants 40–89 years of age and free of chronic heart failure, Levy et al.61 found that hypertension antedated the development of heart failure. After adjusting for age and heart failure risk factors in proportional hazard regression models, the hazard of developing heart failure in hypertensive compared with normotensive subjects was about two-fold higher in men and three-fold higher in women. Multivariate analyses revealed that hypertension had a high population-attributable risk of chronic heart failure, accounting for 39% of cases in men and 59% in women. Survival following the onset of hypertensive heart failure was bleak: only 24% of men and 31% of women survived for five years. Furthermore, recent reports support a relationship between depressed systolic midwall mechanics and abnormal diastolic LV filling in patients with high LV mass.62,63
Changes in Left Ventricular Systolic Function During Antihypertensive Treatment
Systematic antihypertensive treatment can substantially change systolic performance. Lowering blood pressure by 27/13mmHg in the LIFE echocardiography study resulted in a slight reduction in endocardial FS, while MWS increased from 15.4 to 16.8% and stress- corrected MWS, a measure of myocardial contractility, increased from 97 to 105%. In addition, Wachtell et al. found that patients with or without LV mass regression had a mild reduction of endocardial FS during antihypertensive treatment. However, only patients with LV mass decrease had significant improvement in MWS and stress- corrected MWS (see Figure 5). Finally, multivariate analyses confirmed that these improvements were related to changes in LV mass, relative wall thickness and stroke volume.64 These findings indicate that partial normalisation of blood pressure and LV mass can result in reversal of both supranormal LV chamber function and the low function of average myocardial fibres at the LV midwall that is often impaired in hypertensive heart disease. Furthermore, Gerdts et al. reported that hypertensive women in the LIFE echocardiography study retained higher LV ejection fraction and stress-corrected MWS compared with men, despite less hypertrophy regression during long-term antihypertensive treatment.65 The clinical significance of this is that LV systolic function can be improved by systematic antihypertensive treatment even in patients with preserved LV ejection fraction.
Prognostic Significance of Treating Systolic Function in Left Ventricular Hypertrophy and Preserved Left Ventricular Systolic Function
In a study of 294 hypertensive patients receiving varying treatment, de Simone et al.66 showed that depressed MWS predicted adverse outcomes, especially in the subgroup with LV hypertrophy, whereas endocardial FS did not. This was subsequently confirmed in other observational studies.67,68 Data from the LIFE echocardiographic study further expanded knowledge of treatment effects on LV systolic function. Analysis in hypertensive patients with preserved ejection fraction showed that higher in-treatment endocardial FS was associated with 35% fewer subsequent fatal and non-fatal myocardial infarctions and 49% less incident heart failure, whereas in-treatment stress-corrected endocardial FS was not associated with any end- points. By contrast, improved in-treatment MWS was associated with a 16% reduction in the risk of the composite end-point of stroke, myocardial infarction and cardiovascular mortality, a 33% reduction in the risk of the component fatal and non-fatal myocardial infarction and 43% less incident heart failure. Improvement in stress-corrected MWS was in addition to improvement in rate of myocardial infarction (35% reduction), also associated with a 50% reduction in heart failure when adjusting for time-varying diastolic blood pressure and time- varying LVMI, relative wall thickness and randomised treatment.69 The clinical significance of this is that antihypertensive treatment and reduction in LV hypertrophy also improve LV systolic function, and even small improvements in LV systolic function, especially at the midwall, translate into less cardiovascular morbidity and mortality.69
Left Ventricular Diastolic Function in Patients with Left Ventricular Hypertrophy
It has been accepted ever since the early demonstration that electrocardiographic P-wave abnormality preceded evidence of LV hypertrophy that the evolution of hypertensive LV hypertrophy is initiated by abnormalities of LV diastolic function, in the presence of preserved LV systolic function. It is well-established that LV relaxation is often abnormal in hypertensive patients with70 or without71 LV hypertrophy, suggesting that abnormal relaxation might be an early response to cardiac overload caused by hypertension.71,72 Increased cardiac myocyte volume, myocardial ischaemia caused by hypertensive microvascular disease and a mismatch between increased oxygen demand and reduced coronary flow reserve may all contribute to the abnormal diastolic relaxation.73
Data from the LIFE echocardiography study found very high prevalences (>80%) of abnormal diastolic LV-filling patterns in hypertensive patients with electrocardiographic LV hypertrophy.62 Most of these patients had a decreased E/A ratio and prolonged deceleration time, readily recognised manifestations of impaired early LV diastolic relaxation, but an appreciable minority had a ‘pseudonormal’ LV filling pattern. Furthermore, isovolumic relaxation time, A-peak, atrial filling fraction and left atrial dimension, an indirect index of atrial overload due to abnormal diastolic function, differed significantly among the four LV geometrical patterns.62 There was also a strong association between higher LV mass and worse LV early diastolic relaxation as manifested by the prolonged isovolumic relaxation time.
This association remained significant in regression analyses that took into account other variables also associated with longer isovolumic relaxation time, including male gender, lower peak early LV-filling velocity and higher deceleration time, briefer mitral valve opening time and lower pulse pressure/stroke volume ratio. Among the minority of LIFE patients with normal LV mass, isovolumic relaxation time was significantly longer in those with concentric LV remodelling characterised by high relative wall thickness than in those with normal relative wall thickness (i.e. normal geometry). On the other hand, in the presence of LV hypertrophy, relative wall thickness was not a significant correlate of isovolumic relaxation time. This finding suggests that increased LV mass is a stronger stimulus to impaired LV relaxation than is a concentric LV geometrical pattern. These observations also suggest that for antihypertensive therapy to be optimally beneficial for LV filling, it would be desirable to normalise not only LV mass but also relative wall thickness.
This observation of a strong association between abnormal filling and concentric LV hypertrophy has been confirmed by de Simone in data from the Hypertension Genetic Epidemiology Network (HyperGEN) study.74 It has been speculated that LV wall thickness and cavity dimension contribute to diastolic dysfunction,75 but this has not been confirmed in all studies.76
Wachtell et al. reported from the LIFE echocardiography study a relationship between LV diastolic abnormality and abnormal LV systolic function.77 Impaired LV early diastolic relaxation, as manifested by prolonged isovolumic relaxation time, was associated with lower LV systolic myocardial function independently of age and other relevant co-variates (see Figure 6). In addition, lower levels of stress-corrected LV MWS and early diastolic relaxation were both related to higher LV mass, but the relation between prolonged isovolumic relaxation time and reduced LV systolic midwall function remained significant when LV mass was taken into account.
Although the clinical significance of prolonged isovolumic relaxation time and other abnormalities of LV filling have not yet been fully clarified, there are numerous reports of patients with heart failure and apparently normal LV systolic function.60 Levy et al. concluded in a study from Framingham that hypertension was the most common risk factor for chronic heart failure, and it contributed to the pathogenesis of a large proportion of heart failure cases in a population-based sample.61 There are several reports that hypertension and LV hypertrophy play an important role in the development of heart failure. Available population-based studies document significant prediction of cardiovascular events by indices of LV diastolic dysfunction,78–80 but to date have not related them specifically to congestive heart failure among hypertensive adults. However, it remains controversial whether heart failure patients with preserved LV systolic function by exclusion have LV diastolic heart failure.81–84
Change in Left Ventricular Diastolic Function During Antihypertensive Treatment
In view of the strong relations between LV mass and relative wall thickness and transmitral flow variables, Wachtell et al. examined whether reduction in LV mass and relative wall thickness as well as blood pressure by systematic antihypertensive treatment over one year could improve diastolic transmitral flow variables.85 Blood pressure lowering by 23/11mmHg resulted in more normal isovolumic relaxation time and E/A ratio while LV in-flow deceleration time increased. The directionally opposite changes in isovolumic relaxation time and deceleration time indicate improvements in both active LV relaxation (manifested by the shortened isovolumic relaxation time) and passive chamber stiffness during early diastole.86 Furthermore, the prevalences of normal transmitral filling increased while prevalences of abnormal relaxation and pseudonormal pattern decreased and restrictive filling pattern remained unchanged (see Figure 7).85 Patients with LV mass reduction had significant improvement in left atrial diameter, isovolumic relaxation time, E/A ratio and mitral valve deceleration time. However, patients without LV mass reduction had no change in their diastolic filling variables. Further multivariate analyses showed that isovolumic relaxation time shortening was independently associated with reduction in LV mass, increase in E/A ratio was independently associated with reduction in diastolic blood pressure and increase in the deceleration time was independently associated with reduced end-systolic relative wall thickness. Although antihypertensive therapy resulted in LV mass or relative wall thickness regression and significant improvement of diastolic filling variables, abnormalities of diastolic LV filling remained common after one year of observation.
These results support the finding by Yalcin and co-workers87 that six months of antihypertensive treatment with perindopril in 24 patients led to a reduction in LV mass and left atrial volume and an increased E/A ratio, but contrasts with a study by Cuspidi in a small population (n=39) in which six months of antihypertensive treatment had no significant effect on LV diastolic filling parameters.88
The clinical implication is that regression of hypertensive LV hypertrophy and of concentric LV geometry is associated with partial normalisation of several LV diastolic filling variables, including the isovolumic relaxation time, E/A ratio and mitral valve deceleration time, independent of the reduction in blood pressure, thus indicating direct effects of normalisation of LV geometry on diastolic filling parameters. The complexity of factors influencing LV diastolic filling is highlighted by the fact that the deceleration time of early diastolic filling passive inflow increased at the same time as the isovolumic relaxation time decreased. This implies that the deceleration time was affected in opposite directions, being lengthened by impaired relaxation and shortened by increased LV stiffness due to increased relative wall thickness and probable alterations in myocardial connective tissue. A strong relation between invasively measured early diastolic chamber stiffness and shortened deceleration time was reported in an experimental study by Little et al.86 and in a human study by Garcia et al.89 Treatment-improved relaxation predominated in shortening the isovolumic relaxation time, while reducing passive LV chamber stiffness predominated in prolonging the deceleration time of early diastolic transmitral flow. The improvement of diastolic dysfunction parameters may contribute to the ability of blood pressure reduction to prevent congestive heart failure, and highlights the potential of normalisation of LV geometry by antihypertensive therapy to prevent or treat congestive heart failure in hypertensive patients with LV hypertrophy an LV diastolic dysfunction, a condition for which no direct treatment exists.90
Prognostic Significance of Treating Diastolic Function in Left Ventricular Hypertrophy
Several studies indicate that an abnormal E/A ratio predicts poor outcome in patients with hypertension,91 dilated cardiomyopathy92 and myocardial infarction93 and in samples of the general population.78,79
Although improvements of the LV structure also improve LV diastolic function variables, a further question would be whether this improvement in diastolic function translates into a reduction in subsequent cardiovascular morbidity and mortality. Data from the LIFE echocardiography study showed that more than four years of systematic antihypertensive therapy resulted in an increase in the prevalence of normal transmitral flow pattern from 28 to 46% of patients (see Figure 8).94 However, although antihypertensive treatment often resulted in a marked increase in the prevalence of normal mitral valve flow pattern, this ‘normalisation’ of diastolic function was not associated with reduced cardiovascular morbidity and mortality when adjusting for blood pressure, left atrial size, LV mass and treatment in time-varying Cox analyses. Although there is a possibility that this interpretation is a result of a type II error, it is also quite possible that maintenance of normal diastolic filling pattern at baseline or normalisation of abnormal transmitral flow during treatment is of lesser importance compared with reduction of blood pressure and of LV hypertrophy in terms of cardiovascular morbidity and mortality in treated hypertensive patients with target organ damage at baseline. It is also possible that maximum improvement in LV diastolic filling patterns requires several years of aggressive antihypertensive treatment, which means that enough time may not have been allowed to show an effect on cardiovascular morbidity and mortality.94 The strong relation between E/A ratio and cardiovascular events in a prior study with 11 years of follow-up supports this interpretation.91
Finding and treating cardiac target organ damage in hypertensive patients has been given more emphasis in the current European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines.95 The definition of hypertension depends on different levels of blood pressure and on the presence of target organ damage, and also coincides with the intensity of antihypertensive treatment.
One to two decades ago, data suggested that LV hypertrophy predicted cardiovascular morbidity and mortality. More recent studies have clarified the importance of indexation and utilisation of correct partition values to identify LV hypertrophy. Furthermore, systematic treatment is effective in reducing LV hypertrophy and normalising LV geometry. Finally, reduction in LV mass, absence of LV hypertrophy and, to a lesser degree, normalisation of relative wall thickness reduce cardiovascular morbidity and mortality quite significantly, independent of the blood pressure reduction, emphasising the importance of choosing pharmacotherapy that is known to effectively reverse LV mass.
Recent trials have also clarified the high prevalence of abnormal myocardial function and contractility, even when patients have preserved LV ejection fraction, and have shown that reduction in LV mass and relative wall thickness by systematic antihypertensive treatment is in turn associated with improvement in LV myocardial function. Furthermore, recent data suggest that the improvement of LV systolic myocardial function in patients with preserved LV ejection fraction is associated with a reduction in cardiovascular morbidity and mortality independently of the blood pressure and LV mass reduction, emphasising the importance of choosing pharmacotherapy known to effectively increase myocardial contractility.69
Finally, recent trials show high prevalences of LV diastolic abnormalities in hypertensive patients with LV hypertrophy. Data also document relations between LV systolic and diastolic abnormality, completely isolating abnormal LV diastolic function uncommon in hypertensive patients with LV hypertrophy. Furthermore, recent data suggest that systematic antihypertensive treatment over almost five years partially normalises transmitral flow variables and that this normalisation is associated with LV mass regression. However, normalisation of LV diastolic function was not, as is the case with LV systolic function, found to be associated with an improvement of cardiovascular morbidity and mortality in hypertensive patient with LV hypertrophy.94 However, it is possible that it may take longer than five years for normalisation of LV diastolic function to affect cardiovascular morbidity and mortality.
Therefore, in the short term (i.e. five years), clinicians should focus on blood pressure reduction, finding LV hypertrophy in hypertensive patients, reducing LV hypertrophy if present and improving LV systolic myocardial function, even when hypertensive patients have preserved LV ejection fraction, in order to reduce cardiovascular morbidity and mortality. Improvement of LV diastolic function may result in improved exercise tolerance and also less heart failure, but appears to be of lesser importance than blood pressure reduction, LV hypertrophy regression and improvement of myocardial function for prevention of major cardiovascular events.