http://informahealthcare.com/ceh ISSN: 1064-1963 (print), 1525-6006 (electronic) Clin Exp Hypertens, 2014; 36(8): 538–544 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/10641963.2014.881839

ORIGINAL ARTICLE

Left ventricular diastolic function evaluated by the E/e’ ratio is impaired in patients with masked uncontrolled hypertension Takahiro Komori, Kazuo Eguchi, Tomoyuki Kabutoya, Joji Ishikawa, Satoshi Hoshide, and Kazuomi Kario

Clin Exp Hypertens Downloaded from informahealthcare.com by Imperial College London on 02/18/15 For personal use only.

Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan

Abstract

Keywords

Background: Masked uncontrolled hypertension (MUH), defined as controlled office blood pressure (BP) but uncontrolled out-of-office BP in treated hypertensives, is a risk factor for cardiovascular disease. We tested the hypothesis that MUH is associated with a greater degree of diastolic dysfunction than controlled hypertension (CH) or uncontrolled hypertension (UH). Methods and results: We studied 299 treated patients who had at least one cardiovascular risk factor (age, 63 ± 10 years; male sex, 43%), consisting of 94 (31.4%) patients with UH, 46 (15.4%) with MUH, 56 (18.7%) with treated white-coat hypertension (WCH), and 103 (34.4%) with CH. We performed office and home BP monitoring, electrocardiography, echocardiography and blood tests. Diastolic dysfunction was defined as an E-wave to e’-wave (E/e’) ratio 8 measured by Doppler echocardiography. The value of E/e’ was higher in the MUH (8.3 ± 2.7) and UH (8.3 ± 2.7) groups than in the CH group (7.3 ± 2.3; p ¼ 0.08, p ¼ 0.02, respectively). In multivariable analysis, MUH was associated with a significantly higher likelihood of diastolic dysfunction than CH (odds ratio 2.90 versus CH, p50.01) after adjusting for significant covariates. Conclusions: MUH and UH were associated with a greater degree of diastolic dysfunction than CH. Even in treated patients, out-of-office BP is important to stratify the risk of cardiovascular disease.

Blood pressure, diastolic function, echocardiography, hypertension

Introduction Masked hypertension (MH) is defined by the combination of normal office blood pressure (BP) and high out-of-office BP. It has been reported that MH is associated with advanced target organ damage, such as left ventricular hypertrophy (LVH) (1,2), increased relative wall thickness (RWT) (3), thickening of the carotid wall (2,4), and microalbuminuria. Like sustained hypertension, MH has been reported to be associated with poor cardiovascular prognosis (5). In treated hypertensive patients, it is frequently observed that office BP is controlled, but out-of-office BP is not well controlled. This condition is termed masked uncontrolled hypertension (MUH) (6). Studies in treated hypertensive patients have reported that the prevalence of MUH is from 9 to 23% (7,8). These values are similar to those for MH in untreated subjects. The cardiovascular prognosis of MUH, like that of MH, is poor (9). In addition, one study in treated hypertensive patients suggested that MUH has a worse prognosis than uncontrolled hypertension (UH) (7). The reason for the poor cardiovascular prognosis of MUH is not clear, although the possible mechanisms may be higher-risk Correspondence: Kazuomi Kario, MD, PhD, Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, 3311-1, Yakushiji, Shimotsuke, Tochigi 329-0498, Japan, Tel: +81-285-58-7344. Fax: +81-285-44-5317. E-mail: kkario@ jichi.ac.jp

History Received 21 July 2013 Revised 29 September 2013 Accepted 9 October 2013 Published online 31 January 2014

profiles and insufficient antihypertensive treatment in patients with MUH (10). Diastolic dysfunction is commonly seen in hypertensive patients (11). It is one of the most important mechanisms of so-called heart failure with preserved ejection fraction (12,13). Diastolic dysfunction is also associated with mortality from all causes as well as that from cardiovascular disease (14–16). In elderly hypertensive patients, diastolic dysfunction evaluated by the E-wave to A-wave (E/A) ratio was one of the significant predictors of cardiovascular mortality (17). The E-wave to e0 -wave (E/e0 ) ratio is a measure of diastolic function by Doppler imaging, and a more sensitive measure of diastolic function than the E/A ratio. A high E/e0 ratio predicts cardiovascular disease in hypertensive patients (18). Only one study has reported that MH was associated with diastolic dysfunction in an untreated adult population (19). However, it has not been clearly shown that MUH is associated with diastolic dysfunction. MUH is difficult to diagnose (20), and thus there may be a period of insufficient antihypertensive treatment in patients with MUH. We hypothesized that MUH would be associated with a greater degree of diastolic function than controlled hypertension (CH) or UH, and that this association would be proven attributable to the insufficient antihypertensivetreatment regimens in MUH patients. Thus, we designed this study to clarify these two hypotheses in treated patients who had at least one cardiovascular risk factor.

Clin Exp Hypertens Downloaded from informahealthcare.com by Imperial College London on 02/18/15 For personal use only.

DOI: 10.3109/10641963.2014.881839

Diastolic function in masked uncontrolled hypertension

539

Methods

Blood pressure classification

Study participants

In the present study, all patients were classified into four groups based on home and office BP levels (24). CH was defined as office BP5140/90 mmHg (both) and home BP5135/85 mmHg (both). Treated white-coat hypertension (WCH) was defined as office BP  140/90 mmHg (either) and home BP5135/85 mmHg (both). MUH was defined as office BP5140/90 mmHg (both) and home BP  135/85 mmHg (either). UH was defined as office BP  140/90 mmHg (either) and home BP  135/85 mmHg (either).

We recruited a total of 344 patients who had been seen in outpatient clinics at Jichi Medical University Hospital. Enrolled patients had at least one of the following risk factors: diabetes mellitus, dyslipidemia, hypertension, smoking, chronic kidney disease, sleep apnea syndrome, metabolic syndrome and chronic obstructive pulmonary disease; some of the patients were receiving treatment for one or more of these conditions. We excluded patients with atrial fibrillation, ischemic heart disease, cerebrovascular disease, aortic dissection, a history of heart failure, chronic renal failure on hemodialysis, and significant noncardiovascular disease (e.g. cancer or collagen disease). We also excluded the patients with untreated normotensive subjects (N ¼ 45). Finally, 299 patients with a complete set of data were analyzed. At baseline, these patients underwent a medical interview, blood and urine tests, electrocardiography, and echocardiography. The clinical histories of the patients were obtained from interviews by the physicians in charge. Diabetes mellitus was defined as fasting blood glucose of more than 126 mg/dl or the use of antidiabetic medications (21). Dyslipidemia was defined as a total cholesterol level of more than 240 mg/dl, triglyceride level of more than 150 mg/dl (22), or the use of lipid-lowering drugs. Habitual drinking was defined as drinking alcohol more than 5 days per week regardless of the amount. Smoking was defined as a current smoking habit. Chronic kidney disease was defined as proteinuria and/or an estimated glomerular filtration ratio less than 60 ml/min/1.73 m2 (23). Proteinuria for the diagnosis of chronic kidney disease was defined as dipstick proteinuria of ± or greater (23). The duration of hypertension and antihypertensive treatment were obtained from a questionnaire. Body mass index (BMI) was calculated as body weight (kg)/body height2 (m2). Home blood pressure measurements Home BP was measured three times each in the morning and evening for 14 consecutive days. The patients were instructed to place the cuff on the nondominant arm, take a 5-min rest before the first reading, and take a 15-second pause between intervals. Morning BP was measured within 1 hour after waking, after urination, and before breakfast. Evening BP was measured just before going to bed and at least 1 hour after taking a bath. Home BP was taken by an oscillometric device (HEM-5001; Omron Healthcare, Kyoto, Japan). The mean value of the measurements was calculated for each patient and used for the analysis. Office blood pressure measurements Office BP was measured by each physician. It was measured at enrollment and at the end of the home BP measurement period, using the same device as used for home BP. At each office visit, three consecutive readings were taken at 15-second intervals after a 5-min rest in a sitting position. The average of the three office BPs was used for the analyses.

Echocardiography Echocardiography was performed with an ultrasound system (Prosound 5500; Aloka, Tokyo, Japan) at the end of the home BP measurement and was based on the American Society of Echocardiography (ASE) guidelines (25). The end diastolic dimensions of the left ventricle (LVIDd), interventricular septum (IVS), posterior wall thickness (PWT), and left atrial dimension (LAD) were measured by M-mode, and occasionally by B-mode, in the parasternal long axis view. The left ventricular ejection fraction was calculated by the Teichholz method (26). LVM was calculated from LVIDd, IVS, and PWT according to Devereux’s formula (27), and normalized to body surface area and height2.7 to obtain the LVM index. Relative wall thickness was calculated as (2  PWT)/LVIDd (25). Left ventricular filling was evaluated by the mitral inflow velocity. The mitral inflow was recorded from the apical four-chamber view with the pulsed Doppler sample volume placed between the mitral leaflet tips. The peak velocities of E- and A-waves were obtained. The mitral annulus velocity was measured by tissue Doppler imaging using the pulsed-wave Doppler mode. The e0 -wave was measured from the apical four-chamber view with the pulsed Doppler sample volume placed at the septal corner of the mitral annulus. The ratio of E/A and the ratio of E/e0 were calculated. E/A reflects LV relaxation and LV filling pressure, E/e0 estimates the left ventricular filling pressures in which e0 -wave is a measure of LV relaxation. These have been established as indices of diastolic function (28–30). Moderate diastolic dysfunction was defined as E/A 40.8 and deceleration time 5200 ms, or E/e0 8, as described in the ASE guidelines (28). Statistical analysis The data were expressed as means ± SD or percentages. Oneway analysis of variance was performed to detect differences among the UH, MUH, WCH, and CH groups, and Tukey’s Honestly Significant Difference test was performed for multiple pairwise comparisons of the means among the groups. The factors associated with E/A, E/e0 , and the LVM index among the four groups were analyzed with stepwise multivariable logistic regression analyses. Significant variables such as age, male sex, BMI, current smoking, diabetes, duration of hypertension, duration of hypertension treatment, alpha blocker use, office systolic BP (SBP), office diastolic BP (DBP), home morning SBP, home morning DBP, home morning HR, home evening SBP, home evening DBP, home evening HR, IVS, PWT, RWT, LVM index, and A-wave were included the stepwise multivariable model to examine the

540

T. Komori et al.

Clin Exp Hypertens, 2014; 36(8): 538–544

significance of their associations with E/e0 . The multivariable analyses to identify factors associated with E/A and the LVM index among the four groups were performed similarly. The limit of statistical significance was set at p50.05. All statistical analyses were performed with SPSS software, version 13.0 (IBM-SPSS, Armonk, NY).

Results

Clin Exp Hypertens Downloaded from informahealthcare.com by Imperial College London on 02/18/15 For personal use only.

Subject characteristics The characteristics of the study patients are shown in Table 1. Age and the prevalence of diabetes were higher in the UH group than in the other groups. Sex, BMI, waist circumference, the prevalence of hypertension, and the number of antihypertensive drugs were similar among the four groups. Habitual smoking rate was higher in the MUH group than in the other groups. Alpha blocker use was most frequent in the UH group (14%) (p50.01). Office SBP and DBP were significantly higher in the WCH and UH groups than in the other groups. Home morning and evening BP were significantly higher in the MUH and UH groups than in the CH and WCH groups. Echocardiographic characteristics As shown in Table 2, IVS, PWT and RWT were higher in the MUH and UH groups than in the CH and WCH groups. LAD

was largest in the UH group. The LVM index was significantly higher in the UH group than in the CH and WCH groups (both p50.05). With regard to diastolic function, E/A was significantly lower in the UH group than in the CH group (p50.01), but otherwise there were no differences between any pairs of groups (Figure 1). On the other hand, E/e0 was significantly higher in the UH group (p ¼ 0.02) than in the CH group (Figure 2). E/e0 in the MUH group was marginally higher than in the CH group (p ¼ 0.08). However, this association was statistically significant when all patients including normotensives was analyzed (Supplementary. Figure 2). On the other hand, the e0 -wave was significantly lower in the MUH group than in the CH and WCH groups (both p50.05). Associations of home and office BP with diastolic function With regard to the correlations between BP parameters and the markers of diastolic function, office SBP (r ¼ 0.19), home morning SBP (r ¼ 0.20), and home evening SBP (r ¼ 0.23) were significantly correlated with E/A (all p values 50.01). However, office DBP (r ¼ 0.08, p ¼ 0.18), home morning DBP (r ¼ 0.08, p ¼ 0.16), and home evening DBP (r ¼ 0.05, p ¼ 0.38) were not correlated with E/A. On the other hand, home morning SBP (r ¼ 0.14, p ¼ 0.02), home evening SBP (r ¼ 0.22, p50.01), and office DBP (r ¼ 0.15,

Table 1. Baseline characteristics. Variables Age (years) Male sex (%) Body mass index (kg/m2) Waist (cm) Current smoking (%) Diabetes (%) Dyslipidemia (%) Duration of hypertension (years) Duration of hypertension treatment (years) Cardiovascular drugs BP medication (%) Number of BP medications RAS inhibitors (%) Calcium channel blockers (%) b-blockers (%) a-blockers (%) Diuretics (%) Aldosterone antagonists (%) Blood pressure Office SBP (mmHg) Office DBP (mmHg) Office HR (bpm) Home morning SBP (mmHg) Home morning DBP (mmHg) Home morning HR (bpm) Home evening SBP (mmHg) Home evening DBP (mmHg) Home evening HR (bpm)

UH (N ¼ 94) 66 ± 11 39 25.0 ± 3.9 83 ± 11 9 38*xx 32 11.7 ± 11.1* 9.9 ± 9.6* 83 2.1 ± 1.4 57 65 16 14*,x 23 4 154 ± 10**,x 84 ± 11** 71 ± 12 152 ± 12**,xx 80 ± 10** 64 ± 9 143 ± 12**,xx 74 ± 9** 68 ± 9

MUH (N ¼ 46)

WCH (N ¼ 56)

CH (N ¼ 103)

p Value

61 ± 11y 46 26.1 ± 4.1 85 ± 11 22 xx 28 30 7.9 ± 6.9 7.3 ± 6.8

62 ± 10 50 24.4 ± 3.2 83 ± 9 2 11 29 8.6 ± 8.3 7.3 ± 7.6

62 ± 9 40 24.9 ± 3.4 82 ± 9 10 21 44 7.9 ± 7.8 6.5 ± 7.1

0.03 0.54 0.14 0.47 50.01 50.01 0.16 0.02 0.03

91 1.9 ± 1.2 63 57 11 11 28 4

84 1.6 ± 1.1 52 45 9 2 27 5

84 1.9 ± 1.0 61 49 16 3 21 4

0.62 0.24 0.62 0.05 0.56 50.01 0.78 0.98

131 ± 8 **,xx,yy 80 ± 10xx 74 ± 12 146 ± 9**,xx,yy 85 ± 11**,x,y 67 ± 9* 140 ± 9**,xx 79 ± 10**,xx,yy 72 ± 10*,y

149 ± 9** 88 ± 11** 72 ± 10 133 ± 8 79 ± 10 65 ± 7 124 ± 8 71 ± 9 69 ± 8

126 ± 10 78 ± 10 71 ± 10 129 ± 7x 75 ± 9 63 ± 7 121 ± 8 69 ± 8 68 ± 8

50.01 50.01 0.54 50.01 50.01 0.06 50.01 50.01 0.03

UH: uncontrolled hypertension; MUH: masked uncontrolled hypertension; WCH: treated white-coat hypertension; CH: controlled hypertension; RAS: renin-angiotensin system; SBP: systolic blood pressure; DBP diastolic blood pressure; HR: heart rate. *p50.05 versus CH. **p50.01 versus CH. xp50.05 versus WCH. xxp50.01 versus WCH. yp50.05 versus UH. yyp50.01 versus UH.

Diastolic function in masked uncontrolled hypertension

DOI: 10.3109/10641963.2014.881839

541

Table 2. Echocardiographic parameters. UH (N ¼ 94)

MUH (N ¼ 46)

WCH (N ¼ 56)

CH (N ¼ 103)

p Value

10.7 ± 1.9**,xx 45 ± 4 10.2 ± 1.7**,xx 38.3 ± 5.3x 75 ± 8 0.46 ± 0.09*,xx 102 ± 32 49.7 ± 14.4**,x 67 ± 12 87 ± 15**,x 205 ± 42 8.5 ± 2.2** 32

10.4 ± 1.9 45 ± 4 10.3 ± 1.6*,x 38.2 ± 5.4 74 ± 9 0.46 ± 0.11x 104 ± 28 47.3 ± 10.0 65 ± 14 79 ± 17y 200 ± 50 8.4 ± 2.8**,x 38

9.7 ± 2.0 46 ± 4 9.3 ± 1.6 36.4 ± 5.4 75 ± 9 0.41 ± 0.09 94 ± 29 43.5 ± 11.8 67 ± 15 79 ± 15 201 ± 41 9.6 ± 2.4 19

9.6 ± 1.8 45 ± 5 9.4 ± 1.6 36.9 ± 4.7 73 ± 9 0.42 ± 0.09 91 ± 25 43.5 ± 11.6 67 ± 15 75 ± 17 203 ± 46 9.7 ± 2.5 20

50.01 0.63 50.01 0.07 0.55 50.01 0.02 50.01 0.78 50.01 0.76 50.01 0.051

Variables

UH: uncontrolled hypertension; MUH: masked uncontrolled hypertension; WCH: treated white-coat hypertension; CH: controlled hypertension; IVS: interventricular septum; LVIDd: end diastolic dimensions of left ventricle; PWT: posterior wall thickness; LAD: left atrial dimension; EF: ejection fraction; RWT: relative wall thickness; LVM: left ventricular mass; Dct: deceleration time. LVM index (g/m2): LVM/body surface area; LVM index (g/m2.7): LVM/height2.7 *p50.05 versus CH. **p50.01 versus CH. xp50.05 versus WCH. xxp50.01 versus WCH. yp50.05 versus UH.

P < 0.01

10.0

1.00

P = 0.02

0.94 P = 0.08

0.87 9.0

0.85

0.90

8.3 8.3

0.79 0.80

E/e'

8.0

E/A ratio

Clin Exp Hypertens Downloaded from informahealthcare.com by Imperial College London on 02/18/15 For personal use only.

IVS (mm) LVIDd (mm) PWT (mm) LAD (mm) EF (%) RWT LVM index (g/m2) LVM index (g/m2.7) E-wave (cm/s) A-wave (cm/s) Dct (msec) e0 -wave (cm/s) Percentage of e0 58 (%)

0.70

7.3

7.3

WCH

CH

7.0

0.60 6.0 0.50 UH

MUH

WCH

CH

Figure 1. Diastolic function evaluated by the E/A ratio in each blood pressure category. Data are shown as the mean ± SEM. UH: uncontrolled hypertension; MUH: masked uncontrolled hypertension; WCH: treated white-coat hypertension; CH: controlled hypertension.

p50.01) were significantly correlated with E/e0 , but office SBP (r ¼ 0.09, p ¼ 0.14), home morning DBP (r ¼ 0.08, p ¼ 0.19), and home evening DBP (r ¼ 0.25, p ¼ 0.68) were not. Age was correlated with E/A (r ¼ 0.44, p50.01) and E/e0 (r ¼ 0.12, p ¼ 0.04). Table 3 shows the results of multivariable logistic regression analyses adjusting for significant covariates. MUH and UH were not associated with diastolic dysfunction when defined by E/A 40.8 and deceleration time 5200 ms. On the other hand, when compared to the CH group, MUH was significantly associated with diastolic

UH

MUH

Figure 2. Diastolic function evaluated by the E/e0 ratio in each blood pressure category. Data are shown as the mean ± SEM. Abbreviations are the same as in Figure 1.

dysfunction, defined as E/e0 8, even after adjusting for significant covariates. However, UH was marginally associated with diastolic dysfunction (Table 3). The results were not changed by adding HR at the time of echocardiography to the models. We also analyzed the factors associated with LVH defined by an LVM index 51 g/m2.7. However, MUH and UH were not associated with LVH when adjusted by significant covariates (data not shown). We performed additional analysis which included patients with untreated normotension. The results were essentially the same with the present analysis. The data are available as Supplementary Tables and Figures.

542

T. Komori et al.

Clin Exp Hypertens, 2014; 36(8): 538–544

Table 3. Factors associated with diastolic function evaluated by E/e0 . Variables Office DBP (mmHg) LVM index (g/m2.7) Categorical variables MUH vs. CH WCH vs. CH UH vs. CH

Odds ratio

95% CI

p Value

0.96 1.03

0.93–0.98 1.00–1.05

2.90 1.80 1.82

1.34–6.28 0.82–3.98 0.93–3.54

50.01 0.02 0.05 50.01 0.14 0.08

Abbreviations are the same as in Tables 1 and 2.

Clin Exp Hypertens Downloaded from informahealthcare.com by Imperial College London on 02/18/15 For personal use only.

Discussion In the present cohort of treated patients with cardiovascular risk factors, the group with MUH had a significantly greater degree of diastolic dysfunction. To the best of our knowledge, only a few studies have reported an association between MUH and diastolic dysfunction evaluated by tissue Doppler imaging (19,31,32). This study confirmed this association, and added the new findings that, even in treated patients, insufficient antihypertensive therapy could pose a risk of cardiac functional change. Masked uncontrolled hypertension and hypertensive target organ damage In this study, LVM index was higher in the MUH and UH groups than in the CH and WCH groups. This is in agreement with previous results in which MUH and UH were associated with similar degrees of hypertensive target organ damage in the heart, and have greater hypertensive target organ damage than in CH and WCH (1–3,7). In another report, subjects with MUH exhibited nocturnal hypertension and morning hypertension (33). The pressure overload during the night time and early morning periods may have created a susceptibility to hypertensive target organ damage. Another reason for the advanced hypertensive target organ damage may have been an activation of the sympathetic nervous system, although such activation has only been reported for untreated subjects with MH, and has not previously been studied in patients with MUH (34). In this study, home morning and evening HR were highest in the MUH group, and this could indicate an activation of the sympathetic nervous system in MUH. According to a basic study, norepinephrine may trigger a hypertrophic process of myocardial cells (35). These neurohumoral abnormalities may cause LVH and myocardial fibrosis. Taken together, these results suggest that advanced LVH in MUH is derived from pressure overload and activation of the sympathetic nervous system. Masked uncontrolled hypertension and diastolic function The MUH group showed diastolic dysfunction when evaluated by tissue Doppler imaging. E/e0 was significantly higher, and e0 -wave was lower in the MUH group than in the CH group. On the other hand, E/A was lowest in the UH group among the 4 groups. Diastolic function is related to myocardial relaxation and passive left ventricular properties, and is modulated by myocardial tone (36). In hypertensive patients, increased afterload induces systolic wall stress and

thickening of the ventricular wall. The wall is thickened as a result of the transition of cardiac fibroblasts to myofibroblasts (37). In addition, chronic activation of the renin-angiotensin system increases extracellular matrix fibrillar collagen (38). In fact, there is a study which showed that angiotensin receptor blockade improved LV relaxation in hypertensive patients. In the VALIDD (Valsartan in Diastolic Dysfunction) study, e0 -wave was improved by adding valsartan in hypertensive patients (39). In the present study, the BP control in the MUH patients was as poor as that in the UH patients, and the renin-angiotensin system and sympathetic nervous system could have been chronically activated in MUH (34). These factors could be associated with impaired diastolic function, especially LV relaxation in the MUH patients. In the present study, diastolic function evaluated by E/e0 was similar between the MUH and UH groups. However, MUH was a significant factor associated with diastolic dysfunction evaluated by E/e0 , and UH was marginally associated with E/e0 . One of the possible explanations for this finding is that short-term BP variability may be greater in patients with MUH than in those with UH. In the present study, the large differences between office and home BP levels in the MUH group were considered to reflect increased shortterm BP variability. Short-term BP variability has been reported to be associated with hypertensive organ damage (40,41). MUH patients may have exaggerated short-term BP variability due to increased stress or increased physical activity during the daytime. This phenomenon has been reported in MH patients (42,43), which contains similar pathophysiology to MUH. Another explanation for the diastolic dysfunction in the MUH group is the duration of hypertension. The duration of hypertension and that of antihypertensive treatment were longest in the UH group, followed by the MUH, WCH and CH groups. Generally, MUH and MH are difficult to diagnose (20). This is because patients and their doctors often underestimate the actual levels of BP in the office, and thus the duration of uncontrolled hypertension could be even longer in MUH than in UH. In the present study, morning hypertension was seen frequently in both the MUH and UH groups, which could be one of the reasons for the frequent use of alpha blockers in both the groups. The other reason for advanced diastolic dysfunction in MUH is the effect of smoking. The percentage of smoking was highest in the MUH group in this study. Several reports have shown the association between cigarette smoking and diastolic dysfunction. Specifically, acute (44,45) and chronic (46) cigarette smoking has been found to impair left ventricular diastolic function. Thus, our finding of advanced diastolic dysfunction in MUH is supported by the pathophysiological mechanisms of MUH. Study limitations There were some limitations in this study. First, the number of patients was relatively small. Second, our study patients were heterogeneous. Second, MUH was defined by home BP monitoring and not by ambulatory BP monitoring. However, it has been accepted that MUH can be diagnosed by home BP monitoring (42,43).

DOI: 10.3109/10641963.2014.881839

Clin Exp Hypertens Downloaded from informahealthcare.com by Imperial College London on 02/18/15 For personal use only.

Conclusions In a cohort of patients with at least one cardiovascular risk factor, the diastolic dysfunction and the extent of LVH were advanced in patients with MUH, and the degree of both effects was similar to that in the patients with UH. The results of this study convey an important clinical message – namely, the assessment of BP is insufficient in patients with cardiovascular risk factors. Even when the office BP seems to be controlled, out-of-office BP is sometimes high irrespective of the diagnosis of hypertension or normotension in patients who have cardiovascular risk factors. These high-risk factors are sometimes left untreated and could cause cardiac structural and functional change that could eventually develop to cardiovascular disease. Physicians should bear in mind the importance of measuring out-of-office BP at least once in order to stratify the risk of patients with cardiovascular risk factors.

Declaration of interest The authors have no specific funding to report in relation to this research and no conflicts of interest to disclose.

References 1. Hernandez del-Rey R, Armario P, Martin-Baranera M, et al. Cardiac damage in hypertensive patients with inverse white coat hypertension. Hospitalet study. Blood Press 2003;12:89–96. 2. Liu JE, Roman MJ, Pini R, et al. Cardiac and arterial target organ damage in adults with elevated ambulatory and normal office blood pressure. Ann Intern Med 1999;131:564–72. 3. Bjorklund K, Lind L, Zethelius B, et al. Isolated ambulatory hypertension predicts cardiovascular morbidity in elderly men. Circulation 2003;107:1297–302. 4. Matsui Y, Eguchi K, Ishikawa J, et al. Subclinical arterial damage in untreated masked hypertensive subjects detected by home blood pressure measurement. Am J Hypertens 2007;20:385–91. 5. Bobrie G, Clerson P, Menard J, et al. Masked hypertension: a systematic review. J Hypertens 2008;26:1715–25. 6. Obara T, Ohkubo T, Kikuya M, et al. Prevalence of masked uncontrolled and treated white-coat hypertension defined according to the average of morning and evening home blood pressure value: from the Japan Home versus Office Measurement Evaluation Study. Blood Press Monit 2005;10:311–16. 7. Bobrie G, Chatellier G, Genes N, et al. Cardiovascular prognosis of ‘‘masked hypertension’’ detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA 2004;291: 1342–9. 8. Obara T, Ohkubo T, Funahashi J, et al. Isolated uncontrolled hypertension at home and in the office among treated hypertensive patients from the J-HOME study. J Hypertens 2005;23:1653–60. 9. Pierdomenico SD, Lapenna D, Bucci A, et al. Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension. Am J Hypertens 2005;18:1422–8. 10. Tomiyama M, Horio T, Yoshii M, et al. Masked hypertension and target organ damage in treated hypertensive patients. Am J Hypertens 2006;19:880–6. 11. Slama M, Susic D, Varagic J, Frohlich ED. Diastolic dysfunction in hypertension. Curr Opin Cardiol 2002;17:368–73. 12. Kane GC, Karon BL, Mahoney DW, et al. Progression of left ventricular diastolic dysfunction and risk of heart failure. JAMA 2011;306:856–63. 13. Chinnaiyan KM, Alexander D, Maddens M, McCullough PA. Curriculum in cardiology: integrated diagnosis and management of diastolic heart failure. Am Heart J 2007;153:189–200. 14. Aljaroudi W, Alraies MC, Halley C, et al. Impact of progression of diastolic dysfunction on mortality in patients with normal ejection fraction. Circulation 2012;125:782–8.

Diastolic function in masked uncontrolled hypertension

543

15. Achong N, Wahi S, Marwick TH. Evolution and outcome of diastolic dysfunction. Heart 2009;95:813–18. 16. Zhang Y, Safar ME, Iaria P, et al. Prevalence and prognosis of left ventricular diastolic dysfunction in the elderly: the PROTEGER study. Am Heart J 2010;160:471–8. 17. Schillaci G, Pasqualini L, Verdecchia P, et al. Prognostic significance of left ventricular diastolic dysfunction in essential hypertension. J Am Coll Cardiol 2002;39:2005–11. 18. Sharp AS, Tapp RJ, Thom SA, et al. Tissue Doppler E/E0 ratio is a powerful predictor of primary cardiac events in a hypertensive population: an ASCOT substudy. Eur Heart J 2010;31:747–52. 19. Oe Y, Shimbo D, Ishikawa J, et al. Alterations in diastolic function in masked hypertension: findings from the masked hypertension study. Am J Hypertens 2013;26:808–15. 20. Cohen DL, Townsend RR. Masked hypertension: an increasingly common but often unrecognized issue in hypertension management. J Clin Hypertens (Greenwich) 2010;12:522–3. 21. Report of the Expert Committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183–97. 22. National Cholesterol Education Program. Second Report of the Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). Circulation 1994; 89:1333–445. 23. Japanese Society of Nephrology. Evidence-based practice guideline for the treatment of CKD. Clin Exp Nephrol 2009;13:537–66. 24. Parati G, Stergiou GS, Asmar R, et al. European Society of Hypertension guidelines for blood pressure monitoring at home: a summary report of the Second International Consensus Conference on Home Blood Pressure Monitoring. J Hypertens 2008;26: 1505–26. 25. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005; 18:1440–63. 26. Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocardiographic volume determinations: echocardiographicangiographic correlations in the presence of absence of asynergy. Am J Cardiol 1976;37:7–11. 27. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 1977;55:613–18. 28. Nagueh SF, Appleton CP, Gillebert TC, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 2009;22:107–33. 29. Masuyama T, Popp RL. Doppler evaluation of left ventricular filling in congestive heart failure. Eur Heart J 1997;18:1548–56. 30. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000;102: 1788–94. 31. Marchesi C, Maresca AM, Solbiati F, et al. Masked hypertension in type 2 diabetes mellitus. Relationship with left-ventricular structure and function. Am J Hypertens 2007;20:1079–84. 32. Ng CM, Yiu SF, Choi KL, et al. Prevalence and significance of white-coat hypertension and masked hypertension in type 2 diabetics. Hong Kong Med J 2008;14:437–43. 33. Hoshide S, Ishikawa J, Eguchi K, et al. Masked nocturnal hypertension and target organ damage in hypertensives with wellcontrolled self-measured home blood pressure. Hypertens Res 2007;30:143–9. 34. Grassi G, Seravalle G, Trevano FQ, et al. Neurogenic abnormalities in masked hypertension. Hypertension 2007;50:537–42. 35. Long CS, Ordahl CP, Simpson PC. Alpha 1-adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells. J Clin Invest 1989;83:1078–82. 36. Leite-Moreira AF. Current perspectives in diastolic dysfunction and diastolic heart failure. Heart 2006;92:712–18. 37. Muller-Brunotte R, Kahan T, Lopez B, et al. Myocardial fibrosis and diastolic dysfunction in patients with hypertension: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). J Hypertens 2007;25:1958–66.

544

T. Komori et al.

Clin Exp Hypertens Downloaded from informahealthcare.com by Imperial College London on 02/18/15 For personal use only.

38. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part II: causal mechanisms and treatment. Circulation 2002;105:1503–8. 39. Solomon SD, Janardhanan R, Verma A, et al. Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial. Lancet 2007;369: 2079–87. 40. Mancia G, Parati G. The role of blood pressure variability in endorgan damage. J Hypertens Suppl 2003;21:S17–23. 41. Parati G, Pomidossi G, Albini F, et al. Relationship of 24-hour blood pressure mean and variability to severity of target-organ damage in hypertension. J Hypertens 1987;5:93–8. 42. Pickering TG, Eguchi K, Kario K. Masked hypertension: a review. Hypertens Res 2007;30:479–88.

Clin Exp Hypertens, 2014; 36(8): 538–544

43. Pickering TG, Miller NH, Ogedegbe G, et al. Call to action on use and reimbursement for home blood pressure monitoring: executive summary: a joint scientific statement from the American Heart Association, American Society of Hypertension, and Preventive Cardiovascular Nurses Association. Hypertension 2008;52:1–9. 44. Alam M, Samad BA, Wardell J, et al. Acute effects of smoking on diastolic function in healthy participants: studies by conventional doppler echocardiography and doppler tissue imaging. J Am Soc Echocardiogr 2002;15:1232–7. 45. Gembala MI, Ghanem F, Mann CA, Sorrell VL. Acute changes in left ventricular diastolic function: cigarette smoking versus nicotine gum. Clin Cardiol 2006;29:61–4. 46. Yilmaz A, Yalta K, Turgut OO, et al. The effect of smoking on cardiac diastolic parameters including Vp, a more reliable and newer parameter. Cardiol J 2007;14:281–6.

e' ratio is impaired in patients with masked uncontrolled hypertension.

Masked uncontrolled hypertension (MUH), defined as controlled office blood pressure (BP) but uncontrolled out-of-office BP in treated hypertensives, i...
221KB Sizes 0 Downloads 0 Views