Sampling

CHAPTER FIVE

4. Most of the hypertensives with DD had LVH on Echo.

Interestingly, even controls without Echo LVH (normal LVMI for sex) also showed impaired LV diastolic filling.

The prevalence of LVDD in NDHT in this study is almost similar to that of Kingue et al¹²⁰ in a study in Black African hypertensive population in Cameroon (67%). Balogun et al¹² reported a lower prevalence of 46% in their study on hypertensives though in a private tertiary teaching hospital setting. The selection, the characteristics and the early presentation of those patients might have accounted for the lower prevalence in their study. A similar study by Ike et al¹¹⁹ deposed a prevalence of 82.86%, which was much higher than in this study. The strict exclusion and inclusion criteria in this study could partly explain the difference.

DD is a continuum and it is made up of 4 different pathologic filling patterns aside the normal pattern of filling.^151,160 It begins with the impaired relaxation and progressed to the restrictive pattern (reversible or irreversible) through the pseudonormalised form. These patterns evolve from one to another in a single individual, with changes in HHD evolution, loading conditions and treatment.^32,33 The study has shown the various patterns.

The impaired relaxation pattern is the commonest detectable abnormality of filling pattern in hypertensives.^55,129,161 The result of the study agrees with the finding of the above studies where the impaired relaxation pattern was found in more than two third (84.9%) of the hypertensives with DD. It was observed that most of the

hypertensives with DD also had echo-detected LVH (60.2%) with only 39.8% not having Echo LVH. SH places increased tension on the myocardium and leads to an increase in the left ventricular wall thickness and ventricular diameter. This will subsequently affect LV filling through prolongation of relaxation.⁴¹

The pseudonormalized pattern, which is the moderate stage of diastolic dysfunction occurred in only 12(12.9%) of the hypertensives with DD most of them with normal left ventricular mass index. The addition of the Doppler pulmonary venous flow indices like S/D ratio and IVRT and DT of the DTMI assisted in the characterization of diastolic dysfunction. However, none of the normotensive controls showed the restrictive pattern of LVDD. The restrictive pattern was seen in 2(2.2%) of the hypertensives with diastolic dysfunction.

Studies in Asia on the prevalence of diastolic dysfunction by Masliza et al¹²¹ found a lower incidence of 18.6% (32 out of 198) in their NDHT’s and 6(3.4%) among the controls. The higher prevalence noted in this study might be due to the prevalent low socio-economic status of the population. Balogun et al¹² and Oyati et al³³ had each alluded to the fact that the poor state of the economy is among the factors militating against hypertensives presenting early for cardiac evaluation. It is also an established fact that untreated hypertension and its complications are more severe in Blacks than in the other races.^17,76

Age, blood pressure, heart rate, LV systolic performance, left

independent variables that have been reported to influence LV filling.23,25,97,106,162 The result of this study is in conformity with the relationship between age and diastolic function in hypertensives as reported in these other studies.^25,44,153 The age didn’t differ significantly between the hypertensives and the normotensive controls (P=0.896) in this study. Age, on multiple linear regression analyses, consistently correlated with indices of diastolic function especially when the hypertensives were regressed as a group. LVDD was found in this study to increase with age and most of the NDHT’s were in the 50-54 years age range (22.6%). Paolo et al⁴⁴ observed that age influenced greatly the diastolic Doppler indices. They finally concluded that age and heart rate and not structural abnormalities were the most powerful predictors of LV filling indices. Eduardo et al²⁵ in Brazil and Verdecchia et al¹⁵³ in Italian untreated hypertensives had also reported that age significantly affect diastolic performance in addition to BP and heart rate (HR). The former also pointed out that more than 80% of their elderly population showed inversion of the E/A ratio. The European study group on HF with normal SF also alluded to same and had suggested varying cutoff point for the E/A ratio be used to define DD in HF especially in those less than or older than 50 years.⁷⁶ Yuzo had corroborated the same effect of age on relaxation abnormality.¹²⁵ Age is associated with increased deposition of collagen in the subendocardial and subepicardial layers. This reduces the metabolism of the myocardium thus making the collagen becoming stiff and subsequent reduction of the LV compliance. Age

also leads to alterations in excitation–contraction coupling, reduced uptake of calcium ions and hence a compensatory increase in atrial contribution to LV filling¹⁶².

The difference in the mean SBP and DBP in all the groups are statistically significant (p<0.001). However, only DBP showed consistent correlation with the DTMI and the PVF parameters especially in hypertensives with Echo-LVH. Most of the NDHT (81.3%) with DD were in stage 2 of the JNC7. The relationship between clinic BP measurement and LVDF has remained controversial. Verdecchia et al¹⁵⁸, White et al¹⁸³ and Ito et al¹⁸⁴ had suggested that ambulatory (continuous) BP measurements (AMBP) correlated better with the DTMI parameters. No such relationship was found by Gardin et al.¹⁸⁵

This study demonstrated a negative correlation between the DBP and the AT, a finding that is similar to that of Gardin et al. The use of AMBP monitoring might unravel the observation by Verdecchia et al¹⁵⁸ and White et al¹⁸³ that was earlier highlighted in another study. The asynchrony of relaxation of the myocardium induced by SH,⁷² in addition to the increase in collagen content of the myocardium, fibrosis, and the reduction in the myocardial adenosine triphosphate might help explain the pathogenetic mechanisms.

HR correlated negatively with DT (a sensitive index of impaired LV compliance) in the delayed presenters in this study but not in the early presenters. This result is in agreement with the study by Palatino et al⁴⁸ and Fouad et al⁴⁵ in which heart rate was among the

also noted by Ike in his study.¹¹⁹ Tachycardia is a compensatory reaction that helps maintain CO. It however impacts negatively on the filling period. It decreases the early filling velocity and increases the late atrial filling velocity. This will ultimately lead to a decrease in the IVRT and the DT.

ARD at the sinus of Valsalva is related to uncontrolled SH, body size and increasing age.^186,187 It has been suggested that the intra-aortic distending pressure is greater in hypertensives and hence affects its dynamic stretch and elasticity.¹⁸⁷ It will lead to dilatation of the aortic root and subsequent regurgitation.

SH and dyslipidaemia are among the traditional risk factors that can potentiate the effect of the other. It has been observed that there is an enhanced influx of fatty acids into the myocytes of dyslipidaemic patients and this might be enhanced in individuals with HBP.¹⁵⁵ The increased myocyte accumulation would lead to lipotoxicity and subsequent alterations in the LV structure and function.^155,188 DD has been noted to decrease myocardial efficiency in an otherwise healthy obese young woman.¹⁸⁹ In this study TC and TG correlated with the E-wave and E/A ratio in NDHT. The exact cause of DD is not known but could probably be due to the relative state of energy depletion resulting from the oxidation of a less efficient fuel (fatty acids), intracellular lipid deposition and structural changes favouring LVH have been suggested. Others include accumulation of toxic lipid intermediate and or generation of free oxygen radicals with

subsequent apoptosis and the disruption of the excitation-contraction coupling.155,188-190

Sex was found to correlate positively with the PVF S-wave and the Ar-wave in the early presenters. Bella et al³⁷ and Leggett et al¹⁹¹ had shown that though the peak E and A wave velocities are higher in females, the E/A ratio still remains similar. This underscores the need to assess LVDF in women especially the elderly ones with prompt medical intervention so as to reduce the higher prevalence of HF with normal systolic function in them. The observed gender differences could be due to the smaller feminine facie and the mitral annular size producing a compensatory increase in early and late filling. An additive genetic effect has been postulated by the HyperGen group.³⁷

LVMI correlated inversely on simple analysis with some Doppler diastolic indices. However, on multiple linear regression, only age, ARD and HR remained the only correlates. The finding in this study is similar to those of other studies in relation to standard diastolic indices like E/A ratio and IVRT.^158,183 However, the negative correlation with S-wave and the S/D ratio in the early presenters and in the normotensive controls persisted even after multiple regression.

This must have been due to the fact these Doppler indices are not routinely studied and hence not noted in our environment. DD is seen more in hypertensives with echo LVH, though its absence does not exclude DD.^44-48 Most of the hypertensives in this study with DD had LVH suggesting that the compensatory increase in the muscle mass

results from activation of foetal cardiac and growth genes,¹⁹² disproportionate accumulation of fibrillar collagens, and an increased oxygen demand with subsequent ischaemia. Greater LV muscle mass and reduced oxygen supply by the atherosclerotic narrowing of the large arteries and changes in microcirculation in the face of increased oxygen demand commonly seen in hypertensive individuals have also been suggested to play a role.^193,194 The finding of DD and LVH thus implies a higher mortality and hence the need to study these abnormalities.

The result of antihypertensive therapy that enhances regression of LVM or RWT is highly debatable. The LIFE study investigators found a significant improvement in LV diastolic filling parameters after 1 year of antihypertensive therapy in HBP patients with LVH as regards active relaxation and passive chamber stiffness when compared with patients without regression independent of BP reduction.⁴⁹ Mayet at al found in London, that it was after 4 years of therapy that the regression of LVM in 26 patients with HBP resulted in improvement in LVDF.¹⁹⁵

Emphasis in the past has been on the study of SF in HBP, the role of LV diastolic filling abnormalities as a cause of HHF is now increasingly being appreciated. In this study, 62% of the hypertensives had various patterns of DD and their LV systolic performance variables (EF and FS) were still within normal limits.

These corroborate other studies that DD precedes SD.^31-36

E/A RATIO

2.2 2.0

1.8 1.6

1.4 1.2

1.0 .8

.6 .4

AGE

80

70

60

50

40

30

Figure 6: Scatter Graph of Age and E/A ratio in Early Presenters

CHAPTER SIX