Ir J Med Sci DOI 10.1007/s11845-014-1173-5
ORIGINAL ARTICLE
Influence of age and gender on Doppler index of diastolic function in Chinese hypertensive patients D. Zhu • B. Chen • X. Feng • Z. Li • W. Li • Y. Nie • X. Ma • Y. Yu • W. Gao
Received: 27 December 2013 / Accepted: 5 July 2014 Ó Royal Academy of Medicine in Ireland 2014
Abstract Aim This paper explores age- and gender-specific changes in Doppler echocardiographic index-E0 of left ventricular diastolic function. Methods The study involved 366 hypertensive patients (197 men and 169 women) who were aged from 20 to 90 years (mean 58.60 ± 15.68 years), without a diagnosis of any other disease. Early diastolic mitral inflow velocity (E), late diastolic mitral annular velocity (A), and E/A ratio were measured with pulse wave Doppler. Early diastolic mitral annular velocity (E0 ) and E/E0 ratios were measured with tissue Doppler imaging of lateral mitral annulus. Diastolic indices were highly correlated with age. Results Among those aged 20–29, E0 was significantly higher in female than in male. In patients aged 30–39, 40–49, 50–59, 60–69 and 70–79 years, E0 was similar in both genders. Among those aged 80–89 years, E0 was significantly lower in female than in male. Overall (n = 366) predictors of the lowest quartile of E0
D. Zhu and X. Feng contributed equally to this work. D. Zhu B. Chen (&) X. Feng Z. Li W. Li Y. Nie X. Ma Y. Yu W. Gao Department of Cardiology, Peking University Third Hospital, 49 Huayuan-Bei Road, Beijing 100191, China e-mail: [email protected] D. Zhu B. Chen X. Feng Z. Li W. Li Y. Nie X. Ma Y. Yu W. Gao Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing 100191, China D. Zhu B. Chen X. Feng Z. Li W. Li Y. Nie X. Ma Y. Yu W. Gao Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China
(E0 \ 8.00 cm/s) were age (P \ 0.0001; v2 = 67.35; OR 1.28; 95 % CI 1.26–1.30) and female gender (P \ 0.05; v2 = 5.76; OR 1.56; 95 % CI 1.19–1.94). Conclusions Age-related changes in diastolic indices correlated with gender among hypertensive patients. Diastolic function deteriorated more significantly among elderly women compared with elderly men. The study may explain the increased incidence of diastolic heart failure in elderly women with hypertension. Keywords Aging Women Left ventricular diastolic function Echocardiography
Introduction Hypertension is an important risk factor for cardiovascular diseases and stroke [1, 2]. Recently, several studies have demonstrated impaired diastolic function in hypertensive patients generally [3]. In patients with hypertension, increased cardiac load and hyperactivated neuroendocrine function may lead to myocardial cell hypertrophy and interstitial fibrosis, increased ventricular volume and mass, decreased myocardial compliance and increased stiffness, resulting in left ventricular diastolic dysfunction [2]. Previous studies indicated that heart failure in hypertensive patients, especially female, was generally associated with diastolic rather than systolic dysfunction [4–7]. The gender-specific differences underlying etiology or prognosis of heart failure may partially explain the higher death rate of female patients [8]. It is, therefore, crucial to determine the independent predictive indicators of left ventricular diastolic dysfunction in hypertensive patients. Conventional Doppler imaging (CDI) of left ventricular (LV) diastolic function includes mitral and pulmonary vein
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Doppler flow imaging modalities [9–11]. However, due to preload dependency, the conventional index is limited in its inability to diagnose myocardial dysfunction rapidly and accurately [12]. Currently, Doppler tissue imaging (DTI) is the method of choice for assessing cardiac diastolic function [13–15]. Due to its relative independence from preload effects, the tissue Doppler-derived myocardial early diastolic velocity (E0 ) appears to be a reliable index of diastolic function [13–15]. In healthy subjects, these methods are affected by aging [16]. However, the effect of age and gender on diastolic function of hypertensive patients is still unknown. Therefore, this study was designed to examine the association between age and gender, and DTI parameters of diastolic function-E0 obtained at the lateral mitral annulus in hypertensive patients.
Subjects and methods Study population We evaluated Doppler echocardiographic indices of left ventricular diastolic function in 366 patients (197 men and 169 women) who were aged from 20 to 90 years (mean 58.60 ± 15.68 years), with a history of hypertension (defined as blood pressure C140/90 mmHg [17] or taking antihypertensive medication) (Table 1). None had a history of any other cardiovascular disease including diabetes mellitus, coronary artery disease or acute myocardial infarction, stroke or transient ischemic events, significant valvular heart disease, or congestive heart failure. Other exclusion criteria were age \20 years and any resting ECG abnormalities. The study period was between January and December, 2012. This study was conducted in accordance Table 1 Baseline clinical demographics (n = 366)
Demographic and clinical features
with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Peking University Third Hospital. Written informed consent was obtained from all participants. Procedure We used a VIVID 7 (Vingmed, GE, Horten, Norway) scanner with a 3.3-MHz multiphase array probe for the Doppler echocardiography studies, conducted under the supervision of experienced cardiologists. The study commenced with each patient lying in the left decubitus position for probe insertion. The echocardiographic techniques were performed and cardiac dimensions and volumes calculated in accordance with the guidelines of the American Society of Echocardiography [18]. Transmitral pulsed Doppler was recorded in the apical 4-chamber view: early (E) and atrial (A) peak velocities (m/s), peak velocity E/ A ratio, and E velocity deceleration time (ms) were obtained. Pulse wave tissue Doppler imaging was performed using the Doppler tissue imaging function of the instrument. Sample volume was located on the lateral side of the mitral annulus. Early (E0 ) mitral annulus velocities and the E/E0 ratio were obtained. Blood pressure and the heart rate were tested on the day of the echocardiographic evaluation. Statistical analysis The study subjects were divided into different decades, and the mean and standard deviation (SD) or percentage for each age group calculated. The Kolmogorov–Smirnov test was used to test for normal distribution of continuous variables. Variables with two groups were compared with Male and female groups
P
Total (n = 366)
Male (n = 197) Female (n = 169)
(M vs F)
Mean age (years)
58.60 ± 15.68
57.36 ± 16.22
60.16 ± 14.79
0.094
Mean body mass index (kg/m2)
26.89 ± 3.98
27.09 ± 5.02
25.92 ± 2.92
0.076
Mean blood pressure (mmHg)
a
Female patients had a higher diuretic usage than the male groups
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Systolic
139.20 ± 21.17
139.63 ± 23.80
138.68 ± 19.45
0.734
Diastolic
78.28 ± 13.73
80.00 ± 18.34
76.21 ± 7.88
0.105
Mean heart rate (beats/min)
74.96 ± 14.37
75.11 ± 12.95
74.79 ± 16.21
0.547
Medication, n (%) Angiotensin-converting enzyme inhibitors
135 (36.9)
83 (42.1)
52 (31)
0.169
Angiotensin-receptor blockers
119 (32.5)
67 (34.2)
52 (31)
0.385
Calcium antagonists
143 (39.1)
75 (38.2)
68 (40.5)
0.216
Beta-blockers
301 (82.2)
155 (78.9)
146 (86.2)
0.225
Diuretics
96 (26.2)
29 (14.5)
67 (39.7)a
\0.001
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the Student’s t test. One-way ANOVA was used to compare data for more than two groups. The association between age and echocardiographic indices was investigated with linear regression. A logistic regression model was used to assess the association between predictors and E0 . All analyses involved use of SPSS 17.0 (SPSS Inc., Chicago, IL, USA). A P value \0.05 (two-tailed) was considered statistically significant.
diastolic indices and age: E (R = -0.315; P \ 0.0001) and E/A (R = -0.692; P \ 0.0001) correlated negatively and significantly with age. In contrast, A (R = 0.700; P \ 0.0001) and deceleration time of E (R = 0.453; P \ 0.0001) correlated positively and significantly with age. Figure 2 shows relationship between tissue Dopplerderived diastolic indices and age. E0 correlated negatively and significantly with age (R = -0.599; P \ 0.0001). On the other hand, E/E0 (R = 0.333; P \ 0.0001) correlated positively and significantly with age.
Results Gender-specific changes in diastolic indices Characteristics of patients Patient characteristics are summarized in Table 1. No significant differences were identified between the sexes in age, blood pressure or heart rate except that the female patients had a higher diuretic usage than the male groups (P \ 0.001). Echocardiographic indices among all age groups are shown in Table 2. Age-specific changes in diastolic indices The general relationship between age and LV diastolic indices is shown in Figs. 1 and 2. Figure 1 shows the relationship between conventional Doppler-derived LV
Comparative data between the sexes in each age group are shown in Fig. 3. Among those aged 20–29 years, E0 was significantly higher in the female than in the male. In patient age groups of 30–39, 40–49, 50–59, 60–69 and 70–79 years, E0 was similar in both sexes. Among those aged 80–89 years, E0 was significantly lower in the female than in the male. E0 progressively declined with aging in both sexes, but more so in the male than in the female, suggesting that LV relaxation was more significantly impaired in the women than in the men among the elderly subjects. E0 correlated negatively and significantly with age in both the male (R = -0.531; P \ 0.0001) and the female patients (R = -0.700; P \ 0.0001).
Table 2 Echocardiographic results (n = 366) Age group
20–29 (n = 36)
30–39 (n = 38)
40–49 (n = 48)
50–59 (n = 46)
60–69 (n = 88)
70–79 (n = 84)
80–89 (n = 26)
M/F
19/17
24/14
30/18
28/18
36/52
46/38
14/12
E (cm/s)
0.93 ± 0.41
0.82 ± 0.11
0.78 ± 0.17
0.66 ± 0.11
0.71 ± 0.17
0.71 ± 0.20
0.65 ± 0.13
M
0.90 ± 0.03
0.83 ± 0.12
0.72 ± 0.14
0.65 ± 0.11
0.62 ± 0.11
0.66 ± 0.13
0.68 ± 0.13
F
0.96 ± 0.22
0.80 ± 0.11
0.89 ± 0.16
0.69 ± 0.11
0.76 ± 0.18
0.77 ± 0.26
0.62 ± 0.14
A (cm/s)
0.54 ± 0.93
0.66 ± 0.11
0.79 ± 0.13
0.80 ± 0.14
0.93 ± 0.15
0.99 ± 0.15
1.06 ± 0.12
M
0.61 ± 0.06
0.66 ± 0.13
0.78 ± 0.13
0.77 ± 0.13
0.89 ± 0.14
0.99 ± 0.17
1.03 ± 0.09
F
0.45 ± 0.00
0.66 ± 0.07
0.80 ± 0.13
0.85 ± 0.15
0.95 ± 0.16
0.99 ± 0.12
1.08 ± 0.15
E/A M
1.77 ± 0.37 1.49 ± 0.24
1.28 ± 0.30 1.31 ± 0.36
1.02 ± 0.29 0.96 ± 0.26
0.84 ± 0.16 0.85 ± 0.15
0.78 ± 0.23 0.72 ± 0.18
0.73 ± 0.23 0.68 ± 0.15
0.62 ± 0.10 0.65 ± 0.09
F
2.13 ± 0.05
1.21 ± 0.06
1.14 ± 0.31
0.83 ± 0.17
0.83 ± 0.24
0.79 ± 0.29
0.58 ± 0.11
DT (ms)
198 ± 13.43
219.50 ± 51.2
241.12 ± 48.10
258.72 ± 60.26
280.23 ± 61.06
284.24 ± 59.33
305.20 ± 43.92 314.45 ± 47.04
M
208.11 ± 8.67
225.18 ± 55.21
248.87 ± 47.6
268.07 ± 48.46
287.89 ± 47.68
299.41 ± 59.40
F
185.00 ± 0.00
207.00 ± 40.80
228.22 ± 47.44
244.17 ± 74.26
274.92 ± 68.78
265.87 ± 54.52
293.89 ± 39.43
E0 (cm/s)
17.54 ± 4.07
11.88 ± 2.06
11.26 ± 2.61
9.50 ± 2.34
9.54 ± 2.54
8.12 ± 2.03
7.66 ± 2.30
M
15.04 ± 2.23
11.65 ± 2.19
11.27 ± 2.91
8.82 ± 2.41
9.49 ± 2.75
8.18 ± 1.88
8.09 ± 2.47
F
21.14 ± 2.12
12.40 ± 1.71
11.24 ± 2.09
10.56 ± 1.82
9.57 ± 2.41
8.06 ± 2.23
7.13 ± 2.10
E/E0
5.25 ± 1.13
6.63 ± 1.29
6.83 ± 1.88
7.13 ± 2.31
7.34 ± 2.15
8.83 ± 3.27
8.60 ± 2.16
M
6.00 ± 0.87
6.73 ± 1.24
6.40 ± 1.89
7.64 ± 2.77
6.61 ± 2.09
8.09 ± 2.56
8.64 ± 2.84
F
4.29 ± 0.49
6.40 ± 1.43
7.56 ± 1.69
6.33 ± 0.97
7.85 ± 2.07
9.74 ± 3.80
8.56 ± 1.01
Data are presented as mean ± SD M indicates male, F female, DT left ventricular deceleration time
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Fig. 1 Relationship between conventional Doppler-derived diastolic indices and age. E and E/A correlated negatively with age (a, c); A and DT correlated positively with age (b, d). DT indicates deceleration time of the early transmitral flow velocity
Fig. 2 Relationship between tissue Doppler-derived diastolic indices and age. a E0 correlated negatively with age; b E/E0 correlated positively with age
Predictors of impaired LV relaxation
Discussion
Study population was further divided into quartiles, according to the E0 value (Table 3). Overall (n = 366) predictors of the lowest quartile of E0 (E0 \ 8.00 cm/s) were age (P \ 0.0001; v2 = 67.35; OR 1.28; 95 % CI 1.26–1.30) and female gender (P \ 0.05; v2 = 5.76; OR 1.56; 95 % CI 1.19–1.94).
Hypertension is characterized by a gradual increase in LV mass, which may result in diastolic dysfunction due to LV stiffness with impaired relaxation. It is likely that prompt screening of patients with diastolic abnormalities has favorable prognosis and survival [19]. Echocardiography most commonly with mitral inflow CDI has been used
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Fig. 3 Comparison between men and women in each age group. E0 was significantly higher in female than in male among those aged 20–29 years; E0 was significantly lower in female than in male among those aged 80–89 years. Data are presented as mean, *P \ 0.05; # P \ 0.01
Table 3 Logistic regression analysis of predictors of impaired LV relaxation and E0 Independent variables
Odds ratio
P
Multivariate logistic regression model Age (?10 years)
1.28
0.000
Female sex (vs male sex)
1.56
0.015
Systolic
1.15
0.190
Diastolic
3.00
0.244
Heart rate (?10 bpm)
0.03
0.867
Blood pressure (?20 mmHg)
successfully and with high reproducibility to detect LV diastolic dysfunction [20]. However, several studies have shown that TDI was relatively preload independent and associated with good sensitivity to detect abnormalities of LV diastolic function [21]. Multiple studies showed that in healthy subjects, E0 gradually decreased with aging, more significantly compared with E, A and E/A, suggesting that the TDI parameter E0 is a more sensitive indicator of reduction in the LV diastolic function than conventional mitral valve flow pattern (MVFP) [22, 23]. In this study, we evaluated the effects of age and gender on TDI in patients with hypertension. The principal finding of this study is that the changes in diastolic indices of hypertensive patients were age-related and also genderspecific. In the elderly, diastolic function decreased more significantly in the female than in the male. These findings showed that, in patients with hypertension, diastolic function changed with advancing age and may explain the relatively high incidence of diastolic heart failure in old women as the studies of Klapholz [24], Kasner [5] and Masoudi [6].
Age-related decline of LV diastolic function detected by TDI has already been reported [25]. Munagala [25] demonstrated that in healthy subjects E0 decreased with advancing age, reflecting impaired LV relaxation. Although the effect of diastolic functional indicators on prognosis of healthy subjects is not clear, they have been proven to correlate with the exercise capacity [26]. Studies by Masugata [27] have established that LV function as assessed by TDI, demonstrates age-related deterioration in hypertensive patients. Our study increased the sample size to confirm that age is the strongest determinant of all diastolic indices, especially E0 , suggesting that in patients with hypertension, age-dependent cut-off values should be considered. Our findings not only reinforced the previous results in patients with hypertension but also illustrated that the agerelated changes in the diastolic function indices were gender-specific. Our study and De Sutter’ [28] are all available regarding the gender-specific differences in LV diastolic function of hypertensive patients but we had a wider community and the patients ranged in age from 20 to 90. Okura’s findings [16] indicate that in healthy subjects, the postmenopausal state possibly correlates with left ventricular diastolic dysfunction. In fact, natural menopause usually occurring between the ages of 45 and 60 is also the period when the LV diastolic function in female decreases below that of male. Studies have proved that estrogen directly dilates arteries [29]. Additionally, estrogen can promote nitric oxide secretion [30] and inhibit smooth muscle cell proliferation [31]. Recently, it has been found that hypertension is related to estrogen deficiency [32] and estrogen replacement therapy can improve pulse wave velocity in menopausal hypertensive patients [33]. Lack of estrogen protection may be responsible for postmenopausal LV diastolic dysfunction in elderly hypertensive women. Findings of this study are of great significance to studies on diastolic dysfunction in hypertensive patients and increased morbidity due to diastolic heart failure in senile hypertensive women. In the past decade, prognosis of patients with systolic heart failure has improved, compared with patients with diastolic heart failure [34]. Heart failure in patients with preserved global LV systolic function is associated with significant annual mortality [35], with similar reductions in quality of life and exercise performance as systolic heart failure [36]. Epidemiological and clinical studies have consistently demonstrated that elderly women with hypertension constituted a major proportion of population with diastolic heart failure [37]. The findings may be attributed to a lack of knowledge about the baseline pathophysiology of patients with diastolic heart failure. Our study results may further improve understanding of diastolic heart failure, a disease that is frequently encountered but not fully researched.
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A few limitations exist. Most of the patients with hypertension used antihypertensive medication, which may have affected diastolic function. In addition, estimation of our results and septum Doppler values of mitral annulus may not be unbiased since only the mitral annulus lateral wall velocity was routinely measured. Generally, E0 measured by the mitral annulus lateral wall is higher than the value measured by the mitral annulus septum whereas E/E0 is usually low. Finally, age-dependent and gender-specific variations preclude determination of normal values accepted universally. Age-related changes in diastolic indices were genderspecific among hypertensive patients. Diastolic function deteriorated more significantly in the elderly women than in the elderly men. The study may explain the increased incidence of diastolic heart failure in elderly women with hypertension.
10.
11.
12.
13.
14.
15. Acknowledgments This work was supported by grants from the National Natural Science Foundation of China (No. 81200167) and Specialized Research Fund for the Doctoral Program of Higher Education (No. 20120001120131) Conflict of interest
None.
16.
17.
References 1. Lewington S, Clarke R, Qizilbash N et al (2002) Age-specific relevance of usual blood pressure to vascular mortality: a metaanalysis of individual data for one million adults in 61 prospective studies. Lancet 360:1903–1913 2. Van den Hoogen PC, Feskens EJ, Nagelkerke NJ et al (2000) The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world. Seven Countries Study Research Group. N Engl J Med 342:1–8 3. Yip GW, Fung JW, Tan YT et al (2009) Hypertension and heart failure: a dysfunction of systole, diastole or both? J Hum Hypertens 23:295–306 4. Frazier CG, Alexander KP, Newby LK et al (2007) Associations of gender and etiology with outcomes in heart failure with systolic dysfunction: a pooled analysis of 5 randomized control trials. J Am Coll Cardiol 49:1450–1458 5. Kasner M, Westermann D, Steendijk P et al (2007) Utility of Doppler echocardiography and Tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction. Circulation 116:637–647 6. Masoudi FA, Havranek EP, Smith G et al (2003) Gender, age, and heart failure with preserved left ventricular systolic function. J Am Coll Cardiol 41:217–223 7. Yancy CW, Lopatin M, Stevenson LW et al (2006) Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the acute decompensated heart failure national registry (ADHERE) database. J Am Coll Cardiol 47:76–84 8. Bella JN, Palmieri V, Kitzman DW et al (2002) Gender difference in diastolic function in hypertension (the HyperGEN study). Am J Cardiol 89:1052–1056 9. Appleton CP, Jensen JL, Hatle LK et al (1997) Doppler evaluation of ventricular diastolic function: a technical guide for
123
18.
19.
20.
21.
22.
23.
24.
25.
26.
obtaining optimal flow velocity recordings. J Am Soc Echocardiogr 10:271–292 Nagueh SF, Appleton CP, Gillebert TC et al (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 22:107–133 Tschope C, Paulus WJ (2009) Is echocardiographic evaluation of diastolic function useful in determining clinical care? Doppler echocardiography yields dubious estimates of left ventricular diastolic pressures. Circulation 120:810–820 Abali G, Tokgozoglu L, Ozcebe OI et al (2005) Which Doppler parameters are load independent? A study in normal volunteers after blood donation. J Am Soc Echocardiogr 18:1260–1265 Farias CA, Rodriguez L, Garcia MJ et al (1999) Assessment of diastolic function by tissue Doppler echocardiography: comparison with standard transmitral and pulmonary venous flow. J Am Soc Echocardiogr 12:609–617 Ommen SR, Nishimura RA, Appleton CP et al (2000) Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 102:1788–1794 Sohn D, Chai I, Lee D et al (1997) Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 30:474–480 Okura H, Takada Y, Yamabe A et al (2009) Age- and genderspecific changes in the left ventricular relaxation: a Doppler echocardiographic study in healthy individuals. Circ Cardiovasc Imaging 2:41–46 Mancia G, De Backer G, Dominiczak A et al (2007) 2007 guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the European society of cardiology (ESC). Eur Heart J 25:1105–1187 Schiller NB, Shah PM, Crawford M et al (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American society of echocardiography committee on standards, subcommittee on quantitation of twodimensional echocardiograms. J Am Soc Echocardiogr 2:358–367 Bulpitt CJ, Palmer AJ, Fletcher AE et al (1994) Optimal blood pressure control in treated hypertensive patients. Report from the Department of Health Hypertension Care Computing Project (DHCCP). Circulation 90:225–233 Oki T, Tabata T, Yamada H et al (1998) Left ventricular diastolic properties of hypertensive patients measured by pulsed tissue Doppler imaging. J Am Soc Echocardiogr 11:1106–1112 Eidem BW, McMahon CJ, Ayres NA et al (2005) Impact of chronic left ventricular preload and afterload on Doppler tissue imaging velocities: a study in congenital heart disease. J Am Soc Echocardiogr 18:830–838 Nagueh SF, Sun H, Kopelen HA et al (2001) Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler. J Am Coll Cardiol 37:278–285 Vitarelli A, Conde Y, Cimino E et al (2008) Assessment of ascending aorta distensibility after successful coarctation repair by strain Doppler echocardiography. J Am Soc Echocardiogr 21:729–736 Klapholz M, Maurer M, Lowe AM et al (2004) Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry. J Am Coll Cardiol 43:1432–1438 Munagala VK, Jacobsen SJ, Mahoney DW et al (2003) Association of newer diastolic function parameters with age in healthy subjects: a population-based study. J Am Soc Echocardiogr 16:1049–1056 Okura H, Inoue H, Tomon M et al (2000) Impact of Dopplerderived left ventricular diastolic performance on exercise capacity in normal individuals. Am Heart J 139:716–722
Ir J Med Sci 27. Masugata H, Senda S, Goda F et al (2009) Influences of hypertension and diabetes on normal age-related changes in left ventricular function as assessed by tissue Doppler echocardiography. Clin Exp Hypertens 31:400–414 28. De Sutter J, De Backer J, Van de Veire N et al (2005) Effects of age, gender, and left ventricular mass on septal mitral annulus velocity (E0 ) and the ratio of transmitral early peak velocity to E0 (E/E0 ). Am J Cardiol 15:1020–1023 29. Faria AF, de Souza MA, Geber S (2011) Vascular resistance of central retinal artery is reduced in postmenopausal women after use of estrogen. Menopause 18:869–872 30. Jessup JA, Wang H, MacNamara LM et al (2013) Estrogen therapy, independent of timing, improves cardiac structure and function in oophorectomized mRen2. Lewis rats. Menopause 20:860–868 31. Ling S, Dai A, Dilley RJ et al (2004) Endogenous estrogen deficiency reduces proliferation and enhances apoptosis-related death in vascular smooth muscle cells: insights from the aromatase-knockout mouse. Circulation 109:537–543
32. Moro´n FJ, Gala´n JJ, Ruiz A (2007) Controlled ovarian hyperstimulation pharmacogenetics: a simplified model to genetically dissect estrogen-related diseases. Pharmacogenomics 8:775–785 33. Tsioufis C, Tzioumis K, Dimitriadis K et al (2005) Nondipping status does not attenuate the conjugated estrogen-induced improvement in aortic stiffness in postmenopausal women with untreated hypertension. Am J Hypertens 18:607–611 34. Owan TE, Hodge DO, Herges RM et al (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355:251–259 35. MacCarthy PA, Kearney MT, Nolan J et al (2003) Prognosis in heart failure with preserved left ventricular systolic function: prospective cohort study. BMJ 327:78–79 36. Kitzman DW, Little WC, Brubaker PH et al (2002) Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 288:2144–2150 37. Bhatia RS, Tu JV, Lee DS et al (2006) Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 355:260–269
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ORIGINAL ARTICLE
Influence of age and gender on Doppler index of diastolic function in Chinese hypertensive patients D. Zhu • B. Chen • X. Feng • Z. Li • W. Li • Y. Nie • X. Ma • Y. Yu • W. Gao
Received: 27 December 2013 / Accepted: 5 July 2014 Ó Royal Academy of Medicine in Ireland 2014
Abstract Aim This paper explores age- and gender-specific changes in Doppler echocardiographic index-E0 of left ventricular diastolic function. Methods The study involved 366 hypertensive patients (197 men and 169 women) who were aged from 20 to 90 years (mean 58.60 ± 15.68 years), without a diagnosis of any other disease. Early diastolic mitral inflow velocity (E), late diastolic mitral annular velocity (A), and E/A ratio were measured with pulse wave Doppler. Early diastolic mitral annular velocity (E0 ) and E/E0 ratios were measured with tissue Doppler imaging of lateral mitral annulus. Diastolic indices were highly correlated with age. Results Among those aged 20–29, E0 was significantly higher in female than in male. In patients aged 30–39, 40–49, 50–59, 60–69 and 70–79 years, E0 was similar in both genders. Among those aged 80–89 years, E0 was significantly lower in female than in male. Overall (n = 366) predictors of the lowest quartile of E0
D. Zhu and X. Feng contributed equally to this work. D. Zhu B. Chen (&) X. Feng Z. Li W. Li Y. Nie X. Ma Y. Yu W. Gao Department of Cardiology, Peking University Third Hospital, 49 Huayuan-Bei Road, Beijing 100191, China e-mail: [email protected] D. Zhu B. Chen X. Feng Z. Li W. Li Y. Nie X. Ma Y. Yu W. Gao Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing 100191, China D. Zhu B. Chen X. Feng Z. Li W. Li Y. Nie X. Ma Y. Yu W. Gao Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China
(E0 \ 8.00 cm/s) were age (P \ 0.0001; v2 = 67.35; OR 1.28; 95 % CI 1.26–1.30) and female gender (P \ 0.05; v2 = 5.76; OR 1.56; 95 % CI 1.19–1.94). Conclusions Age-related changes in diastolic indices correlated with gender among hypertensive patients. Diastolic function deteriorated more significantly among elderly women compared with elderly men. The study may explain the increased incidence of diastolic heart failure in elderly women with hypertension. Keywords Aging Women Left ventricular diastolic function Echocardiography
Introduction Hypertension is an important risk factor for cardiovascular diseases and stroke [1, 2]. Recently, several studies have demonstrated impaired diastolic function in hypertensive patients generally [3]. In patients with hypertension, increased cardiac load and hyperactivated neuroendocrine function may lead to myocardial cell hypertrophy and interstitial fibrosis, increased ventricular volume and mass, decreased myocardial compliance and increased stiffness, resulting in left ventricular diastolic dysfunction [2]. Previous studies indicated that heart failure in hypertensive patients, especially female, was generally associated with diastolic rather than systolic dysfunction [4–7]. The gender-specific differences underlying etiology or prognosis of heart failure may partially explain the higher death rate of female patients [8]. It is, therefore, crucial to determine the independent predictive indicators of left ventricular diastolic dysfunction in hypertensive patients. Conventional Doppler imaging (CDI) of left ventricular (LV) diastolic function includes mitral and pulmonary vein
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Doppler flow imaging modalities [9–11]. However, due to preload dependency, the conventional index is limited in its inability to diagnose myocardial dysfunction rapidly and accurately [12]. Currently, Doppler tissue imaging (DTI) is the method of choice for assessing cardiac diastolic function [13–15]. Due to its relative independence from preload effects, the tissue Doppler-derived myocardial early diastolic velocity (E0 ) appears to be a reliable index of diastolic function [13–15]. In healthy subjects, these methods are affected by aging [16]. However, the effect of age and gender on diastolic function of hypertensive patients is still unknown. Therefore, this study was designed to examine the association between age and gender, and DTI parameters of diastolic function-E0 obtained at the lateral mitral annulus in hypertensive patients.
Subjects and methods Study population We evaluated Doppler echocardiographic indices of left ventricular diastolic function in 366 patients (197 men and 169 women) who were aged from 20 to 90 years (mean 58.60 ± 15.68 years), with a history of hypertension (defined as blood pressure C140/90 mmHg [17] or taking antihypertensive medication) (Table 1). None had a history of any other cardiovascular disease including diabetes mellitus, coronary artery disease or acute myocardial infarction, stroke or transient ischemic events, significant valvular heart disease, or congestive heart failure. Other exclusion criteria were age \20 years and any resting ECG abnormalities. The study period was between January and December, 2012. This study was conducted in accordance Table 1 Baseline clinical demographics (n = 366)
Demographic and clinical features
with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Peking University Third Hospital. Written informed consent was obtained from all participants. Procedure We used a VIVID 7 (Vingmed, GE, Horten, Norway) scanner with a 3.3-MHz multiphase array probe for the Doppler echocardiography studies, conducted under the supervision of experienced cardiologists. The study commenced with each patient lying in the left decubitus position for probe insertion. The echocardiographic techniques were performed and cardiac dimensions and volumes calculated in accordance with the guidelines of the American Society of Echocardiography [18]. Transmitral pulsed Doppler was recorded in the apical 4-chamber view: early (E) and atrial (A) peak velocities (m/s), peak velocity E/ A ratio, and E velocity deceleration time (ms) were obtained. Pulse wave tissue Doppler imaging was performed using the Doppler tissue imaging function of the instrument. Sample volume was located on the lateral side of the mitral annulus. Early (E0 ) mitral annulus velocities and the E/E0 ratio were obtained. Blood pressure and the heart rate were tested on the day of the echocardiographic evaluation. Statistical analysis The study subjects were divided into different decades, and the mean and standard deviation (SD) or percentage for each age group calculated. The Kolmogorov–Smirnov test was used to test for normal distribution of continuous variables. Variables with two groups were compared with Male and female groups
P
Total (n = 366)
Male (n = 197) Female (n = 169)
(M vs F)
Mean age (years)
58.60 ± 15.68
57.36 ± 16.22
60.16 ± 14.79
0.094
Mean body mass index (kg/m2)
26.89 ± 3.98
27.09 ± 5.02
25.92 ± 2.92
0.076
Mean blood pressure (mmHg)
a
Female patients had a higher diuretic usage than the male groups
123
Systolic
139.20 ± 21.17
139.63 ± 23.80
138.68 ± 19.45
0.734
Diastolic
78.28 ± 13.73
80.00 ± 18.34
76.21 ± 7.88
0.105
Mean heart rate (beats/min)
74.96 ± 14.37
75.11 ± 12.95
74.79 ± 16.21
0.547
Medication, n (%) Angiotensin-converting enzyme inhibitors
135 (36.9)
83 (42.1)
52 (31)
0.169
Angiotensin-receptor blockers
119 (32.5)
67 (34.2)
52 (31)
0.385
Calcium antagonists
143 (39.1)
75 (38.2)
68 (40.5)
0.216
Beta-blockers
301 (82.2)
155 (78.9)
146 (86.2)
0.225
Diuretics
96 (26.2)
29 (14.5)
67 (39.7)a
\0.001
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the Student’s t test. One-way ANOVA was used to compare data for more than two groups. The association between age and echocardiographic indices was investigated with linear regression. A logistic regression model was used to assess the association between predictors and E0 . All analyses involved use of SPSS 17.0 (SPSS Inc., Chicago, IL, USA). A P value \0.05 (two-tailed) was considered statistically significant.
diastolic indices and age: E (R = -0.315; P \ 0.0001) and E/A (R = -0.692; P \ 0.0001) correlated negatively and significantly with age. In contrast, A (R = 0.700; P \ 0.0001) and deceleration time of E (R = 0.453; P \ 0.0001) correlated positively and significantly with age. Figure 2 shows relationship between tissue Dopplerderived diastolic indices and age. E0 correlated negatively and significantly with age (R = -0.599; P \ 0.0001). On the other hand, E/E0 (R = 0.333; P \ 0.0001) correlated positively and significantly with age.
Results Gender-specific changes in diastolic indices Characteristics of patients Patient characteristics are summarized in Table 1. No significant differences were identified between the sexes in age, blood pressure or heart rate except that the female patients had a higher diuretic usage than the male groups (P \ 0.001). Echocardiographic indices among all age groups are shown in Table 2. Age-specific changes in diastolic indices The general relationship between age and LV diastolic indices is shown in Figs. 1 and 2. Figure 1 shows the relationship between conventional Doppler-derived LV
Comparative data between the sexes in each age group are shown in Fig. 3. Among those aged 20–29 years, E0 was significantly higher in the female than in the male. In patient age groups of 30–39, 40–49, 50–59, 60–69 and 70–79 years, E0 was similar in both sexes. Among those aged 80–89 years, E0 was significantly lower in the female than in the male. E0 progressively declined with aging in both sexes, but more so in the male than in the female, suggesting that LV relaxation was more significantly impaired in the women than in the men among the elderly subjects. E0 correlated negatively and significantly with age in both the male (R = -0.531; P \ 0.0001) and the female patients (R = -0.700; P \ 0.0001).
Table 2 Echocardiographic results (n = 366) Age group
20–29 (n = 36)
30–39 (n = 38)
40–49 (n = 48)
50–59 (n = 46)
60–69 (n = 88)
70–79 (n = 84)
80–89 (n = 26)
M/F
19/17
24/14
30/18
28/18
36/52
46/38
14/12
E (cm/s)
0.93 ± 0.41
0.82 ± 0.11
0.78 ± 0.17
0.66 ± 0.11
0.71 ± 0.17
0.71 ± 0.20
0.65 ± 0.13
M
0.90 ± 0.03
0.83 ± 0.12
0.72 ± 0.14
0.65 ± 0.11
0.62 ± 0.11
0.66 ± 0.13
0.68 ± 0.13
F
0.96 ± 0.22
0.80 ± 0.11
0.89 ± 0.16
0.69 ± 0.11
0.76 ± 0.18
0.77 ± 0.26
0.62 ± 0.14
A (cm/s)
0.54 ± 0.93
0.66 ± 0.11
0.79 ± 0.13
0.80 ± 0.14
0.93 ± 0.15
0.99 ± 0.15
1.06 ± 0.12
M
0.61 ± 0.06
0.66 ± 0.13
0.78 ± 0.13
0.77 ± 0.13
0.89 ± 0.14
0.99 ± 0.17
1.03 ± 0.09
F
0.45 ± 0.00
0.66 ± 0.07
0.80 ± 0.13
0.85 ± 0.15
0.95 ± 0.16
0.99 ± 0.12
1.08 ± 0.15
E/A M
1.77 ± 0.37 1.49 ± 0.24
1.28 ± 0.30 1.31 ± 0.36
1.02 ± 0.29 0.96 ± 0.26
0.84 ± 0.16 0.85 ± 0.15
0.78 ± 0.23 0.72 ± 0.18
0.73 ± 0.23 0.68 ± 0.15
0.62 ± 0.10 0.65 ± 0.09
F
2.13 ± 0.05
1.21 ± 0.06
1.14 ± 0.31
0.83 ± 0.17
0.83 ± 0.24
0.79 ± 0.29
0.58 ± 0.11
DT (ms)
198 ± 13.43
219.50 ± 51.2
241.12 ± 48.10
258.72 ± 60.26
280.23 ± 61.06
284.24 ± 59.33
305.20 ± 43.92 314.45 ± 47.04
M
208.11 ± 8.67
225.18 ± 55.21
248.87 ± 47.6
268.07 ± 48.46
287.89 ± 47.68
299.41 ± 59.40
F
185.00 ± 0.00
207.00 ± 40.80
228.22 ± 47.44
244.17 ± 74.26
274.92 ± 68.78
265.87 ± 54.52
293.89 ± 39.43
E0 (cm/s)
17.54 ± 4.07
11.88 ± 2.06
11.26 ± 2.61
9.50 ± 2.34
9.54 ± 2.54
8.12 ± 2.03
7.66 ± 2.30
M
15.04 ± 2.23
11.65 ± 2.19
11.27 ± 2.91
8.82 ± 2.41
9.49 ± 2.75
8.18 ± 1.88
8.09 ± 2.47
F
21.14 ± 2.12
12.40 ± 1.71
11.24 ± 2.09
10.56 ± 1.82
9.57 ± 2.41
8.06 ± 2.23
7.13 ± 2.10
E/E0
5.25 ± 1.13
6.63 ± 1.29
6.83 ± 1.88
7.13 ± 2.31
7.34 ± 2.15
8.83 ± 3.27
8.60 ± 2.16
M
6.00 ± 0.87
6.73 ± 1.24
6.40 ± 1.89
7.64 ± 2.77
6.61 ± 2.09
8.09 ± 2.56
8.64 ± 2.84
F
4.29 ± 0.49
6.40 ± 1.43
7.56 ± 1.69
6.33 ± 0.97
7.85 ± 2.07
9.74 ± 3.80
8.56 ± 1.01
Data are presented as mean ± SD M indicates male, F female, DT left ventricular deceleration time
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Fig. 1 Relationship between conventional Doppler-derived diastolic indices and age. E and E/A correlated negatively with age (a, c); A and DT correlated positively with age (b, d). DT indicates deceleration time of the early transmitral flow velocity
Fig. 2 Relationship between tissue Doppler-derived diastolic indices and age. a E0 correlated negatively with age; b E/E0 correlated positively with age
Predictors of impaired LV relaxation
Discussion
Study population was further divided into quartiles, according to the E0 value (Table 3). Overall (n = 366) predictors of the lowest quartile of E0 (E0 \ 8.00 cm/s) were age (P \ 0.0001; v2 = 67.35; OR 1.28; 95 % CI 1.26–1.30) and female gender (P \ 0.05; v2 = 5.76; OR 1.56; 95 % CI 1.19–1.94).
Hypertension is characterized by a gradual increase in LV mass, which may result in diastolic dysfunction due to LV stiffness with impaired relaxation. It is likely that prompt screening of patients with diastolic abnormalities has favorable prognosis and survival [19]. Echocardiography most commonly with mitral inflow CDI has been used
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Fig. 3 Comparison between men and women in each age group. E0 was significantly higher in female than in male among those aged 20–29 years; E0 was significantly lower in female than in male among those aged 80–89 years. Data are presented as mean, *P \ 0.05; # P \ 0.01
Table 3 Logistic regression analysis of predictors of impaired LV relaxation and E0 Independent variables
Odds ratio
P
Multivariate logistic regression model Age (?10 years)
1.28
0.000
Female sex (vs male sex)
1.56
0.015
Systolic
1.15
0.190
Diastolic
3.00
0.244
Heart rate (?10 bpm)
0.03
0.867
Blood pressure (?20 mmHg)
successfully and with high reproducibility to detect LV diastolic dysfunction [20]. However, several studies have shown that TDI was relatively preload independent and associated with good sensitivity to detect abnormalities of LV diastolic function [21]. Multiple studies showed that in healthy subjects, E0 gradually decreased with aging, more significantly compared with E, A and E/A, suggesting that the TDI parameter E0 is a more sensitive indicator of reduction in the LV diastolic function than conventional mitral valve flow pattern (MVFP) [22, 23]. In this study, we evaluated the effects of age and gender on TDI in patients with hypertension. The principal finding of this study is that the changes in diastolic indices of hypertensive patients were age-related and also genderspecific. In the elderly, diastolic function decreased more significantly in the female than in the male. These findings showed that, in patients with hypertension, diastolic function changed with advancing age and may explain the relatively high incidence of diastolic heart failure in old women as the studies of Klapholz [24], Kasner [5] and Masoudi [6].
Age-related decline of LV diastolic function detected by TDI has already been reported [25]. Munagala [25] demonstrated that in healthy subjects E0 decreased with advancing age, reflecting impaired LV relaxation. Although the effect of diastolic functional indicators on prognosis of healthy subjects is not clear, they have been proven to correlate with the exercise capacity [26]. Studies by Masugata [27] have established that LV function as assessed by TDI, demonstrates age-related deterioration in hypertensive patients. Our study increased the sample size to confirm that age is the strongest determinant of all diastolic indices, especially E0 , suggesting that in patients with hypertension, age-dependent cut-off values should be considered. Our findings not only reinforced the previous results in patients with hypertension but also illustrated that the agerelated changes in the diastolic function indices were gender-specific. Our study and De Sutter’ [28] are all available regarding the gender-specific differences in LV diastolic function of hypertensive patients but we had a wider community and the patients ranged in age from 20 to 90. Okura’s findings [16] indicate that in healthy subjects, the postmenopausal state possibly correlates with left ventricular diastolic dysfunction. In fact, natural menopause usually occurring between the ages of 45 and 60 is also the period when the LV diastolic function in female decreases below that of male. Studies have proved that estrogen directly dilates arteries [29]. Additionally, estrogen can promote nitric oxide secretion [30] and inhibit smooth muscle cell proliferation [31]. Recently, it has been found that hypertension is related to estrogen deficiency [32] and estrogen replacement therapy can improve pulse wave velocity in menopausal hypertensive patients [33]. Lack of estrogen protection may be responsible for postmenopausal LV diastolic dysfunction in elderly hypertensive women. Findings of this study are of great significance to studies on diastolic dysfunction in hypertensive patients and increased morbidity due to diastolic heart failure in senile hypertensive women. In the past decade, prognosis of patients with systolic heart failure has improved, compared with patients with diastolic heart failure [34]. Heart failure in patients with preserved global LV systolic function is associated with significant annual mortality [35], with similar reductions in quality of life and exercise performance as systolic heart failure [36]. Epidemiological and clinical studies have consistently demonstrated that elderly women with hypertension constituted a major proportion of population with diastolic heart failure [37]. The findings may be attributed to a lack of knowledge about the baseline pathophysiology of patients with diastolic heart failure. Our study results may further improve understanding of diastolic heart failure, a disease that is frequently encountered but not fully researched.
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A few limitations exist. Most of the patients with hypertension used antihypertensive medication, which may have affected diastolic function. In addition, estimation of our results and septum Doppler values of mitral annulus may not be unbiased since only the mitral annulus lateral wall velocity was routinely measured. Generally, E0 measured by the mitral annulus lateral wall is higher than the value measured by the mitral annulus septum whereas E/E0 is usually low. Finally, age-dependent and gender-specific variations preclude determination of normal values accepted universally. Age-related changes in diastolic indices were genderspecific among hypertensive patients. Diastolic function deteriorated more significantly in the elderly women than in the elderly men. The study may explain the increased incidence of diastolic heart failure in elderly women with hypertension.
10.
11.
12.
13.
14.
15. Acknowledgments This work was supported by grants from the National Natural Science Foundation of China (No. 81200167) and Specialized Research Fund for the Doctoral Program of Higher Education (No. 20120001120131) Conflict of interest
None.
16.
17.
References 1. Lewington S, Clarke R, Qizilbash N et al (2002) Age-specific relevance of usual blood pressure to vascular mortality: a metaanalysis of individual data for one million adults in 61 prospective studies. Lancet 360:1903–1913 2. Van den Hoogen PC, Feskens EJ, Nagelkerke NJ et al (2000) The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world. Seven Countries Study Research Group. N Engl J Med 342:1–8 3. Yip GW, Fung JW, Tan YT et al (2009) Hypertension and heart failure: a dysfunction of systole, diastole or both? J Hum Hypertens 23:295–306 4. Frazier CG, Alexander KP, Newby LK et al (2007) Associations of gender and etiology with outcomes in heart failure with systolic dysfunction: a pooled analysis of 5 randomized control trials. J Am Coll Cardiol 49:1450–1458 5. Kasner M, Westermann D, Steendijk P et al (2007) Utility of Doppler echocardiography and Tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction. Circulation 116:637–647 6. Masoudi FA, Havranek EP, Smith G et al (2003) Gender, age, and heart failure with preserved left ventricular systolic function. J Am Coll Cardiol 41:217–223 7. Yancy CW, Lopatin M, Stevenson LW et al (2006) Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the acute decompensated heart failure national registry (ADHERE) database. J Am Coll Cardiol 47:76–84 8. Bella JN, Palmieri V, Kitzman DW et al (2002) Gender difference in diastolic function in hypertension (the HyperGEN study). Am J Cardiol 89:1052–1056 9. Appleton CP, Jensen JL, Hatle LK et al (1997) Doppler evaluation of ventricular diastolic function: a technical guide for
123
18.
19.
20.
21.
22.
23.
24.
25.
26.
obtaining optimal flow velocity recordings. J Am Soc Echocardiogr 10:271–292 Nagueh SF, Appleton CP, Gillebert TC et al (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 22:107–133 Tschope C, Paulus WJ (2009) Is echocardiographic evaluation of diastolic function useful in determining clinical care? Doppler echocardiography yields dubious estimates of left ventricular diastolic pressures. Circulation 120:810–820 Abali G, Tokgozoglu L, Ozcebe OI et al (2005) Which Doppler parameters are load independent? A study in normal volunteers after blood donation. J Am Soc Echocardiogr 18:1260–1265 Farias CA, Rodriguez L, Garcia MJ et al (1999) Assessment of diastolic function by tissue Doppler echocardiography: comparison with standard transmitral and pulmonary venous flow. J Am Soc Echocardiogr 12:609–617 Ommen SR, Nishimura RA, Appleton CP et al (2000) Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 102:1788–1794 Sohn D, Chai I, Lee D et al (1997) Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 30:474–480 Okura H, Takada Y, Yamabe A et al (2009) Age- and genderspecific changes in the left ventricular relaxation: a Doppler echocardiographic study in healthy individuals. Circ Cardiovasc Imaging 2:41–46 Mancia G, De Backer G, Dominiczak A et al (2007) 2007 guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the European society of cardiology (ESC). Eur Heart J 25:1105–1187 Schiller NB, Shah PM, Crawford M et al (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American society of echocardiography committee on standards, subcommittee on quantitation of twodimensional echocardiograms. J Am Soc Echocardiogr 2:358–367 Bulpitt CJ, Palmer AJ, Fletcher AE et al (1994) Optimal blood pressure control in treated hypertensive patients. Report from the Department of Health Hypertension Care Computing Project (DHCCP). Circulation 90:225–233 Oki T, Tabata T, Yamada H et al (1998) Left ventricular diastolic properties of hypertensive patients measured by pulsed tissue Doppler imaging. J Am Soc Echocardiogr 11:1106–1112 Eidem BW, McMahon CJ, Ayres NA et al (2005) Impact of chronic left ventricular preload and afterload on Doppler tissue imaging velocities: a study in congenital heart disease. J Am Soc Echocardiogr 18:830–838 Nagueh SF, Sun H, Kopelen HA et al (2001) Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler. J Am Coll Cardiol 37:278–285 Vitarelli A, Conde Y, Cimino E et al (2008) Assessment of ascending aorta distensibility after successful coarctation repair by strain Doppler echocardiography. J Am Soc Echocardiogr 21:729–736 Klapholz M, Maurer M, Lowe AM et al (2004) Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry. J Am Coll Cardiol 43:1432–1438 Munagala VK, Jacobsen SJ, Mahoney DW et al (2003) Association of newer diastolic function parameters with age in healthy subjects: a population-based study. J Am Soc Echocardiogr 16:1049–1056 Okura H, Inoue H, Tomon M et al (2000) Impact of Dopplerderived left ventricular diastolic performance on exercise capacity in normal individuals. Am Heart J 139:716–722
Ir J Med Sci 27. Masugata H, Senda S, Goda F et al (2009) Influences of hypertension and diabetes on normal age-related changes in left ventricular function as assessed by tissue Doppler echocardiography. Clin Exp Hypertens 31:400–414 28. De Sutter J, De Backer J, Van de Veire N et al (2005) Effects of age, gender, and left ventricular mass on septal mitral annulus velocity (E0 ) and the ratio of transmitral early peak velocity to E0 (E/E0 ). Am J Cardiol 15:1020–1023 29. Faria AF, de Souza MA, Geber S (2011) Vascular resistance of central retinal artery is reduced in postmenopausal women after use of estrogen. Menopause 18:869–872 30. Jessup JA, Wang H, MacNamara LM et al (2013) Estrogen therapy, independent of timing, improves cardiac structure and function in oophorectomized mRen2. Lewis rats. Menopause 20:860–868 31. Ling S, Dai A, Dilley RJ et al (2004) Endogenous estrogen deficiency reduces proliferation and enhances apoptosis-related death in vascular smooth muscle cells: insights from the aromatase-knockout mouse. Circulation 109:537–543
32. Moro´n FJ, Gala´n JJ, Ruiz A (2007) Controlled ovarian hyperstimulation pharmacogenetics: a simplified model to genetically dissect estrogen-related diseases. Pharmacogenomics 8:775–785 33. Tsioufis C, Tzioumis K, Dimitriadis K et al (2005) Nondipping status does not attenuate the conjugated estrogen-induced improvement in aortic stiffness in postmenopausal women with untreated hypertension. Am J Hypertens 18:607–611 34. Owan TE, Hodge DO, Herges RM et al (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355:251–259 35. MacCarthy PA, Kearney MT, Nolan J et al (2003) Prognosis in heart failure with preserved left ventricular systolic function: prospective cohort study. BMJ 327:78–79 36. Kitzman DW, Little WC, Brubaker PH et al (2002) Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 288:2144–2150 37. Bhatia RS, Tu JV, Lee DS et al (2006) Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 355:260–269
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