Clinical methods and pathophysiology 311

Effects of lifestyle modification on central blood pressure in overweight and obese men Ryota Higashinoa, Asako Miyakia, Hiroshi Kumagaia, Youngju Choia, Nobuhiko Akazawaa, Song-Gyu Raa, Yoko Tanabea, Miki Etob, Rina Soa, Kiyoji Tanakab, Ryuichi Ajisakab and Seiji Maedab Objective It has recently been recognized that increased central blood pressure is a predictor of cardiovascular disease. Central blood pressure is higher in obese individuals than in nonobese individuals. However, the effect of lifestyle modification on central systolic blood pressure in obese individuals is unclear. The aim of this study was to determine whether lifestyle modification decreases central blood pressure in overweight and obese men. Methods Thirty-nine overweight and obese men (age, 49±2 years; BMI, 30±1 kg/m2) were recruited into our study. We measured central systolic blood pressure and brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, before and after a 12-week lifestyle modification that included aerobic exercise and dietary modification.

Conclusion This study showed for the first time that lifestyle modification-induced weight loss decreases central systolic blood pressure in overweight and obese men. The decrease in central systolic blood pressure was associated with the reduction in arterial stiffness. These results suggest that lifestyle modification-induced reduction in arterial stiffness may contribute toward the decreased central systolic blood pressure in overweight c 2013 and obese men. Blood Press Monit 18:311–315 Wolters Kluwer Health | Lippincott Williams & Wilkins. Blood Pressure Monitoring 2013, 18:311–315 Keywords: arterial stiffness, central blood pressure, obesity, weight loss a Graduate School of Comprehensive Human Sciences and bDivision of Sports Medicine, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

Results After the 12-week program, body mass, BMI, and waist circumstance decreased significantly. Central systolic blood pressure and baPWV were significantly decreased after the lifestyle modification in overweight and obese men. Furthermore, there was a significant correlation between the lifestyle modification-induced change in central systolic blood pressure and that in baPWV.

Correspondence to Seiji Maeda, PhD, Division of Sports Medicine, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8574, Japan Tel: + 81 29 853 2683; fax: + 81 29 853 2986; e-mail: [email protected]

Introduction

aerobic exercise decreases arterial stiffness in obese men [8,9]. It has been reported that increased arterial stiffness contributes toward increased central systolic blood pressure [10]. However, the effect of lifestyle modification (i.e. aerobic exercise and dietary modification) on central systolic blood pressure in obese individuals is unclear. The aim of this study was to determine whether lifestyle modification decreases central blood pressure in overweight and obese men.

The prevalence of obesity has been increasing steadily worldwide. It is well known that obesity is associated strongly with hypertension and is an independent risk factor for cardiovascular disease [1,2]. Obesity contributes toward the pathogenesis of hypertension by several mechanisms, including stiffened arteries, increased cardiac output, peripheral resistance, and sympathetic nervous system activation [3]. Recently, it has been shown that central blood pressure is relevant for the prediction and pathophysiology of cardiovascular disease [4,5]. Central blood pressure is the aortic root pressure, mainly composed of reflected wave pressure, and can directly affect left ventricular afterload [6]. A previous study has shown that central systolic blood pressure is higher in obese individuals than in nonobese individuals [7]. Therefore, central systolic blood pressure is an important risk factor for cardiovascular disease in obese individuals. Lifestyle modification is a key strategy for the prevention of cardiovascular disease in obese individuals. In previous studies, we showed that dietary modification or habitual c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins 1359-5237

Received 9 April 2013 Revised 22 July 2013 Accepted 11 September 2013

Methods Participants

Thirty-nine overweight and obese men (age, 49±2 years; BMI, 30±1 kg/m2) participated in this study. All participants had no apparent cardiovascular disease. None of the participants had performed regular physical exercise before the study. Fifteen participants were taking hypertensive, hypercholesterolemia, or hypoglycemic medication and four participants were smokers. All study procedures and potential risks were explained to the participants and all participants provided written DOI: 10.1097/MBP.0000000000000006

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312 Blood Pressure Monitoring 2013, Vol 18 No 6

informed consent to participate in the study. This study was reviewed and approved by the Institutional Review Broad at the University of Tsukuba. Study design

Overweight and obese men were observed before and after the 12-week lifestyle modification program that included aerobic exercise and dietary modification. All measurements (except for the exercise test) were performed following an overnight fast that included abstinence from caffeine. Participants were studied in a resting condition in a quiet, temperature-controlled room (24–261C). All measurements were performed after a resting period of at least 20 min. Exercise intervention

The exercise protocol used in this study is the same as that described in our previous study [9]. Participants joined aerobic exercise classes 3 days a week at the University of Tsukuba during the intervention. The activities consisted of 10–15 min of stretching, followed by 40–60 min of walking or jogging, followed by a 20–30min cooling down period. The participants were supervised by two or three physical trainers. During the first 2 months, exercise consisted only of walking, with a Borg’s scale target range of 11 (light) to 13 (fairly hard). The distance walked was 3.5 km during the first month and 4.5 km during the second month. In the last month, the participants performed a combination of a 3-km brisk walk and a 1-km mid-intensity jog, with a Borg’s scale target ranging from 13 (fairly hard) to 15 (hard). Dietary modification

The dietary modification protocol has been reported as a low-calorie diet intervention with effects on coronary heart disease risk factors [8]. Briefly, all participants in the study were instructed to eat meals consisting of an average of 420 kcal of protein, 840 kcal of carbohydrate, and 420 kcal of fat per day (total, 1680 kcal/day). Participants maintained daily food diaries during the 12-week intervention period and learned about proper nutrition (well-balanced protein, carbohydrate, fat, amino acids, vitamins, and minerals) through weekly lectures and consultations with skilled dieticians. Hemodynamics

Arterial pulse waveforms of the left radial artery were measured noninvasively using an automated tonometric system (HEM-9000AI; Omron Healthcare, Kyoto, Japan) with the participants in a seated position. Radial arterial waveforms from this device, the first (P1) and second systolic peaks (P2) were automatically identified using the fourth derivative wave as the second and third zero crossing points, respectively. The augmentation index was defined as the ratio of the height of P2 to that of P1 [11]. In addition, the augmentation index was normalized by 75 bpm in heart rate (augmentation

index@75) because this index is influenced by heart rate [12]. Brachial blood pressure was measured simultaneously in the right brachium using an oscillometric device incorporated into HEM-9000AI. Pulse pressure was calculated as the brachial systolic blood pressure minus brachial diastolic blood pressure. Late systolic blood pressure in the radial artery, which reflects central systolic blood pressure, was used as an estimate of central systolic blood pressure. Central systolic blood pressure estimated by the HEM-9000AI is very close to invasively recorded aortic central systolic blood pressure [13]. Arterial stiffness was measured with brachial-ankle pulse wave velocity (baPWV). The baPWV was determined from the pulse waveforms recorded from both forearms and both ankles using a semiautomated device (Form PWV/ ABI; Colin Medical Technology, Komaki, Japan) [14]. Heart rate in the supine position was also recorded using this device. Metabolic risk factors for atherosclerosis

After an overnight fast, venous blood samples were drawn from an antecubital vein in all participants before and after the 12-week lifestyle modification program. Blood samples were analyzed for total cholesterol, triglycerides, highdensity lipoprotein cholesterol, low-density lipoprotein cholesterol, plasma blood glucose, and homeostasis model of insulin resistance. Samples were collected in tubes containing clotting activators for serum isolation and were allowed to clot for 2 h at room temperature. Then, they were centrifuged at 3000 rpm for 10 min at 41C. After separation, serum was dispensed into plain microtubes and stored at – 801C until further analysis. For plasma glucose measurements, venous blood samples were collected in tubes containing sodium fluoride–EDTA. Samples were immediately centrifuged and handled as detailed above. Peak oxygen uptake

Peak oxygen uptake was determined during a graded exercise test using an 818E cycling ergometer (Monark, Stockholm, Sweden). After a 2-min warm up at 30 W, the participant started with a workload of 15 W/min until volitional exhaustion occurred. Pulmonary ventilation and gas exchange were measured, breath by breath, using an Oxycon Alpha online data acquisition system (Mijnhardt, Breda, The Netherlands). Measurement of individual maximal oxygen uptake was obtained between 8 a.m. and 12 p.m. Statistical analysis

Data are expressed as mean±SE. To evaluate differences in the levels before and after lifestyle modification in our participants, the paired Student t-test was used. Effect of medications and smoking on hemodynamics was tested using covariance analysis. Analyses were carried out using the Statistical Package for Social Science version 16 for Windows (IBM, Armonk, New York, USA), and P less than 0.05 was considered statistically significant for all analyses.

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Weight loss and central blood pressure Higashino et al. 313

Table 1 shows the participants’ characteristics before and after the 12-week lifestyle modification program. Body mass, BMI, and waist circumstance decreased markedly in all participants after the lifestyle modification. Moreover, we found that total cholesterol, low-density lipoprotein cholesterol, triglycerides, homeostasis model of insulin resistance index, insulin, and fasting blood glucose levels were significantly decreased, and high-density lipoprotein cholesterol was significantly increased after the lifestyle modification. Peak oxygen uptake was significantly increased after the lifestyle modification. Table 2 shows the participants’ hemodynamics before and after the modification program. Following the program, brachial systolic blood pressure, brachial diastolic blood pressure, mean arterial pressure, pulse pressure, and heart rate were significantly decreased. Figure 1 shows the changes in central systolic blood pressure, which was markedly decreased after the program. Figure 2 shows the change in the augmentation index before and after the lifestyle modification. The augmentation index decreased significantly after the modification. Furthermore, baPWV was significantly decreased after the program (Fig. 3). Figure 4 shows the relationship between the delta and percent change in central systolic blood pressure and that in baPWV. Analysis of covariance showed that the effect of lifestyle modification on hemodynamics was statistically independent of medications and smoking.

modification-induced change in central systolic blood pressure and that in baPWV. Therefore, the present study showed that lifestyle modification-induced weight loss can decrease central blood pressure in overweight and obese men. Furthermore, we suggest that lifestyle modification-induced reduction in arterial stiffness may contribute toward the decreased central systemic blood pressure in overweight and obese men. Roman et al. [4] reported that central blood pressure may be more relevant for predicting cardiovascular disease than

Hemodynamics of overweight and obese men before and after a 12-week lifestyle modification

Table 2

Brachial SBP (mmHg) Brachial DBP (mmHg) Pulse pressure (mmHg) Heart rate (beats/min)

Table 1 Characteristics of overweight and obese men before and after a 12-week lifestyle modification

47±2 170±1 84.4±2.2 29.1±0.7 205.6±8.6 49.1±1.8 166.1±24.7 101.7±5.2 10.0±1.9 2.6±0.5 31.7±0.8

– – 74.1±2.0* 25.6±0.6* 185.4±6.4* 57.5±2.1* 74.7±5.3* 93.7±1.8* 5.4±0.8* 1.3±0.2* 35.0±1.1*

Data are expressed as mean±SE. HDL, high-density lipoprotein; HOMA-IR, homeostasis model of insulin resistance; LDL, low-density lipoprotein. Significant difference vs. before lifestyle modification, *P < 0.01.

117±2* 277±2* 40±1* 59±2*

P < 0.01

(mmHg)

130 120 110 100

Before

After

Central systolic blood pressure before and after the 12-week lifestyle modification. Data are expressed as mean±SE.

Fig. 2

Augmentation index @75

Age (years) Height (cm) Body mass (kg) BMI (kg/m2) Total cholesterol (mg/dl) HDL cholesterol (mg/dl) Triglyceride (mg/dl) Fasting blood glucose (mg/dl) Insulin (mU/ml) HOMA-IR VO2max (ml/min/kg)

After

132±3 87±2 45±2 67±2

140

P < 0.01

(%) Before

After

Fig. 1

Discussion In this study, we examined the effect of lifestyle modification (i.e. aerobic exercise and dietary modification) on central blood pressure in 39 overweight and obese men. After the modification program, body mass, BMI, and waist circumstance decreased markedly and metabolic risk factors for atherosclerosis improved. Central systolic blood pressure decreased significantly after the lifestyle modification. Furthermore, we found that baPWV decreased significantly after the program. There was a significant correlation between the lifestyle

Before

Data are expressed as mean±SE. DBP, diastolic blood pressure; SBP, systolic blood pressure. Significant difference vs. before lifestyle modification, *P < 0.01.

Central systolic blood pressure

Results

90 85 80 75 70

Before

After

Augmentation index@75 before and after the 12-week lifestyle modification. Data are expressed as mean±SE.

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314 Blood Pressure Monitoring 2013, Vol 18 No 6

Fig. 3

Fig. 4

(cm/s)

(a)

P < 0.01

1450

100

1300 1250 1200

r = 0.408 P < 0.05

200

1350

Before

After

Change in baPWV

baPWV

1400

(cm/s) 300

Brachial-ankle pulse wave velocity (baPWV) before and after the 12-week lifestyle modification. Data are expressed as mean±SE.

0 −100 −200 −300 −400 −500

Lifestyle modification, such as habitual aerobic exercise and dietary modification, is a key strategy for the prevention of cardiovascular disease. However, the effect of lifestyle modification on central blood pressure in overweight and obese men had been unclear. In the present study, we showed that lifestyle modificationinduced weight loss decreased central systolic blood pressure in overweight and obese men. The present study also showed that the augmentation index, an index of central blood pressure and left ventricular afterload [13,16], decreased after the lifestyle modification. Recently, we have reported that aerobic exercise training alone did not decrease central blood pressure in postmenopausal women [17]. In the present study, we investigated whether the combination of aerobic exercise training and dietary modification for 12 weeks can decrease central blood pressure in overweight and obese men. We showed that central blood pressure decreased

−60

−40

−20

0

20 (mmHg)

Change in central systolic blood pressure (b) 20 15 Change in baPWV (%)

the standard measure of brachial blood pressure. A previous study showed that central blood pressure is higher in obese individuals than in nonobese individuals [7]. In this study, central systolic blood pressure was significantly decreased in overweight and obese men after the 12-week lifestyle modification program. Brachial systolic blood pressure is mainly a product of forward wave pressure, whereas central systolic blood pressure is mainly a product of reflected wave pressure and can directly evaluate left ventricular afterload [6,15]. It is well known that reflected wave pressure merges with the incident wave during the systole and augments central systolic blood pressure in stiffened arteries [10]. Our novel finding is that central systolic blood pressure was significantly decreased following the 12-week lifestyle modification and there was a significant correlation between the change in central systolic blood pressure and that in baPWV. Taken together, it is possible that the decrease in central systolic blood pressure following the lifestyle modification was induced by a decrease in augmentation pressure because of lowered arterial stiffness.

r = 0.421 P < 0.01

10 5 0 −5 −10 −15 −20 −25 −40 −20 0 20 Change in central systolic blood pressure (%)

The relationship between the change in central systolic blood pressure and that in brachial-ankle pulse wave velocity (baPWV). (a) Delta change, (b) percent change.

significantly after the program in overweight and obese men. Taken together, it is considered that lifestyle modification by a combination of aerobic exercise and dietary modification can decrease central blood pressure in overweight and obese men. Prolonged increase in left ventricular afterload has been considered primarily responsible for left ventricular mass development with hypertension [18]. It has been known that the increase of left ventricular mass is an independent predictor of cardiovascular disease mortality [19]. It is well recognized that the augmentation index is a prominent index of left ventricular afterload [16]. Increased augmentation index indicates an early return of reflected pulse waves at the peripheral vasculature wall, and that could increase left ventricular mass by causing a hypoxic condition in

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Weight loss and central blood pressure Higashino et al. 315

myocardial tissue [16,18]. Hashimoto et al. [16] reported that antihypertensive treatment can decrease left ventricular mass and augmentation index, and the changes in these were significantly correlated in the patients with hypertension. In this study, we observed that the augmentation index decreased significantly after the lifestyle modification in overweight and obese men. Therefore, it is possible that lifestyle modification decreases left ventricular afterload in overweight and obese men. Conclusion

The present study showed that a 12-week lifestyle modification (i.e. aerobic exercise and dietary modification) decreased central systolic blood pressure in overweight and obese men. We also showed that arterial stiffness was decreased after the lifestyle modification in overweight and obese men. Moreover, the lifestyle modification-induced changes in central blood pressure were correlated with those in arterial stiffness. These results suggest that lifestyle modification-induced reduction in arterial stiffness may contribute toward the decreased central systemic blood pressure in overweight and obese men.

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Acknowledgements This work was supported by Grants-in-Aid for Scientific Research (21300234 and 21650179) from the Japan Society for the Promotion of Science.

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Conflicts of interest

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There are no conflicts of interest. 17

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Effects of lifestyle modification on central blood pressure in overweight and obese men.

It has recently been recognized that increased central blood pressure is a predictor of cardiovascular disease. Central blood pressure is higher in ob...
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