Inverse Relationship Between Physical Activity and Arterial Stiffness in ...

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O'Donovan, Gormley, and Hussey are with the School of. Medicine, Discipline of Physiotherapy, Trinity College Dublin,. Ireland. Lithander, Raftery, and Mahmud ...
Journal of Physical Activity and Health, 2014, 11, 272-277 http://dx.doi.org/10.1123/jpah.2012-0075 © 2014 Human Kinetics, Inc.

Official Journal of ISPAH www.JPAH-Journal.com ORIGINAL RESEARCH

Inverse Relationship Between Physical Activity and Arterial Stiffness in Adults With Hypertension Cuisle O’Donovan, Fiona E. Lithander, Tara Raftery, John Gormley, Azra Mahmud, and Juliette Hussey Background: Physical activity has beneficial effects on arterial stiffness among healthy adults. There is a lack of data on this relationship in adults with hypertension. The majority of studies which have examined physical activity and arterial stiffness have used subjective measures of activity. The aim of this study was to investigate the relationship between objectively measured habitual physical activity and arterial stiffness in individuals with newly diagnosed essential hypertension. Methods: Adults attending an outpatient hypertension clinic were recruited into this cross sectional study. Physical activity was measured using a triaxial accelerometer. Pulse wave velocity (PWV) and augmentation index (AIx) were measured using applanation tonometry. Participant’s full lipid profile and glucose were determined through the collection of a fasting blood sample. Results: Fifty-three adults [51(14) years, 26 male] participated, 16 of whom had the metabolic syndrome. Inactivity was positively correlated with PWV (r = .53, P < .001) and AIx (r = .48, P < .001). There were significant inverse associations between habitual physical activity of all intensities and both AIx and PWV. In stepwise regression, after adjusting for potential confounders, physical activity was a significant predictor of AIx and PWV. Conclusion: Habitual physical activity of all intensities is associated with reduced arterial stiffness among adults with hypertension. Keywords: exercise, blood pressure, cardiovascular Arterial stiffness is known to play an important role in the pathophysiology of cardiovascular disease. Pulse wave velocity (PWV) is the speed with which the arterial pulse, generated by ventricular ejection, travels down the aorta and is an established surrogate marker of arterial stiffness. It has been shown to have a better predictive value than classic cardiovascular (CV) risk factors, such as blood pressure (BP),1 and is an independent prognosticator of CV mortality in the general population2 and those with hypertension.3 Augmentation Index (AIx), is a composite of PWV, arterial wave reflection and left ventricular ejection and reflects stiffness of the small and medium-sized muscular arteries and arterioles. AIx can indicate total CV risk, even in apparently healthy people.4 While PWV and AIx are closely related, it is well established that these markers can diverge in many clinical conditions and particularly may not show the same pharmacological response to a O’Donovan, Gormley, and Hussey are with the School of Medicine, Discipline of Physiotherapy, Trinity College Dublin, Ireland. Lithander, Raftery, and Mahmud are with the Dept of Clinical Medicine, Trinity College Dublin, Ireland. Lithander is also with the Dept of Nutrition and Dietetics, University of Canberra, Australia. Mahmud is also with the Royal College of Surgeons, Ireland.

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drug. Therefore, it is recommended that for a comprehensive assessment of the cardiovascular system and its response to pharmacological and nonpharmacological interventions, both PWV and AIx be assessed. Determinants of arterial stiffness include age, blood pressure,5 and modifiable factors including physical activity.6 Cross sectional data suggest that habitual physical activity is inversely associated with arterial stiffness in healthy adults.6,7 There is some evidence to suggest that vigorous exercise in particular is associated with more compliant arteries.8 Many studies in this area, however, have assessed habitual physical activity using subjective measures such as questionnaires, which can lead to both under and over reporting of activity.8,9 Accelerometers enable activity levels to be measured objectively and for activity performed to be categorized into various intensities such as light, moderate, vigorous, and time spent being inactive, through the use of cut off points.10 Among those with hypertension, there is a lack of data on the relationship between habitual physical activity and arterial stiffness. Kraft and colleagues11 have shown no significant relationship between aerobic fitness and arterial stiffness in a cross-sectional study of hypertensive adults. There is also evidence to suggest that an acute bout of aerobic exercise has no effect on arterial stiffness in adults with hypertension.12 Moreover, chronic exercise intervention studies also report no effect on stiffness in

Physical Activity and Arterial Stiffness   273

this population.12,13 Ferrier et al13 found no change in large artery compliance with aerobic exercise training lasting 8 weeks in those with isolated systolic hypertension. Similarly, Aizawa and colleagues12 found that neither maximal aerobic exercise nor 20 weeks aerobic training altered the arterial compliance of elderly patients with hypertension. Fitness and both acute and chronic exercise are known to have beneficial effects on arterial stiffness in healthy populations including the elderly,6,7,14 suggesting that individuals with hypertension may respond differently. The primary aim of this cross sectional study was to examine the relationship between objectively measured habitual physical activity and arterial stiffness in adults with essential hypertension. A secondary aim was to examine the association between exercise of various intensities and arterial stiffness.

Methods Fifty-three patients were recruited (mean age 51 years, 26 males) from the hypertension clinic at Saint James’s Hospital, Dublin 8, Ireland. Inclusion criteria were essential hypertension, aged between 25–80 years-old and willing to wear an RT3 accelerometer for 7 consecutive days. Exclusion criteria were limitations to daily physical activities, advanced arthritis and those in need of a walking aid. All participants gave written informed consent and Ethical approval was granted from the SJH/ AMNCH Research Ethics Committee. Medications recorded refer to regular use. All measurements were carried out after a 12-hour overnight fast, and patients had abstained from alcohol and smoking for the previous 12 hours. Height and weight were recorded using a stadiometer and scales (SECA Mod 220, Germany). Brachial blood pressure (BP) was measured using an oscillometric technique (Omron Model HEM 705-CP). Three BP readings were taken at 1-minute intervals, and the mean was used for data analysis. Aortic pulse wave velocity (PWV) was measured using an automated system (Complior; Artech Medical). Augmentation pressure (AP), augmentation index (AIx), and AIx corrected for a heart rate of 75 beats per minute (AIx75) were recorded using radial applanation tonometry (SphygmoCor, AtCor Medical, West Ryde, Australia). Both of these systems have been shown to be reliable with acceptably low levels of error (standard error of the mean = 0.69 for both the Sphygmocor and the Complior15). AIx was adjusted for heard rate since it is known to be dependent on heart rate.16 Applanation tonometry is a non invasive method of deriving central arterial pressures. Pressure waves from the radial and carotid artery were recorded by placing a highly sensitive tonometer over relevant pulse points. A validated transfer factor was then automatically applied to derive the corresponding central waveform and estimate central arterial pressure.17 This was done using the system software of the Sphygmocor (SphygmoCor, AtCor Medical, Version 8.0). Two measurements were performed in each subject.

When examining these wave forms augmentation pressure is the difference in pressure between the first and second systolic peaks. AIx is the difference between the first and second systolic peaks expressed as a percentage of the pulse pressure. PWV was measured using the foot to foot method with an automated system (Complior, Artech Medical) as described elsewhere.18 Physical activity was objectively measured for 7 days with an accelerometer, (RT3 triaxial accelerometer, Stayhealthy, Inc. Monrovia, California) as described elsewhere.19 The RT3 accelerometer collects data of acceleration on 3 planes and combines them into counts per minute. These counts can then be categorized, using validated cut off points, into 4 intensities: inactive, light, moderate, and vigorous.10 Fasting venous blood samples were obtained from the antecubital fossa and analyzed as described elsewhere.20 Results from the venous blood samples were used to determine whether participants had the metabolic syndrome. The metabolic syndrome was considered present when 3 of the following 5 risk factors were present, dysglycemia, raised blood pressure, elevated triglyceride levels, low high-density lipoprotein cholesterol levels, and obesity.21 Results were analyzed using SPSS Version 16.0, P < .05 considered significant. Normality was tested by examining the measures of central tendency and the skewness value relative to its standard error. A Kolmogorov Smirnov test for normality was conducted on data collected with P < .05 indicating deviation from normality.22 For correlation and means testing, missing cases were excluded pairwise. To test if there was an independent relationship between indices of arterial stiffness and activity levels, linear stepwise regression analysis was performed. In this analysis mean arterial pressure, HR, age, sex, BMI, and physical activity were chosen as independent variables. Missing values were replaced with the mean.

Results Baseline characteristics and physical activity data are presented in Tables 1 and 2, respectively. All variables were not obtained from all participants due to practical limitations including the availability of research staff, access to equipment, and time constraints during the busy outpatient clinic. Data on PWV were available for n = 20, data on AIx were available for n = 29, data on AP were available for n = 29, and data on AIx75 were available for n = 29. Hemodynamic variables were normally distributed. All intensities of activity (light, moderate and vigorous) were positively skewed with the exception of light intensity activity. For this reason activity data are reported in median and quartiles. Time spent inactive was normally distributed. Quality control parameters for measures taken with the Sphygmocor and Complior were within manufacturer recommendations. There was no significant difference in activity levels between those with the metabolic syndrome and those

Table 1  Baseline Characteristics Mean (SD)

n

51 (14)

53

Height (cm)

167.3 (9.7)

53

Weight (kg)

84.09 (18.04)

53

Age (y)

29.9 (5.1)

53

Waist circumference (cm)

101.1 (13.0)

32

Glucose (mmol/L)

5.93 (2.51)

43

Triglycerides (mmol/L)

1.44 (0.75)

47

Cholesterol (mmol/L)

4.83 (1.01)

47

Low Density Lipoprotein (mmol/L)

2.81 (0.82)

41

High Density Lipoprotein (mmol/L)

1.44 (0.38)

47

BMI

(kg.m-2)

Creatinine (mmol/L)

74.90 (14.81)

49

n (%)

Total

Metabolic syndrome present

16(36.4)

44

Medicated for hypertension

32(69.6)

46

Categorical data

Indices of arterial stiffness

Mean (SD)

n

PWV (m·s-1)

10.73 (2.58)

20

AP (mmHg)

14.21 (9.38)

29

AIx (%)

29.52 (12.60)

29

AIx75 (%)

27.76 (11.89)

29

  Systolic (mmHg)

145.26 (19.20)

31

  Diastolic (mmHg)

89.68 (11.58)

31

  Systolic (mmHg)

133.27 (20.27)

30

  Diastolic (mmHg)

90.57 (11.53)

30

Mean arterial pressure (mmHg)

104.80 (13.23)

30

Brachial blood pressure

Aortic blood pressure

Abbreviations: BMI, body mass index; PWV, pulse wave velocity; AP, augmentation pressure; AIx, augmentation index, AIx75, augmentation index corrected to a heart rate of 75 bpm.

Table 2  Daily Minutes at Each Activity Intensity, n = 53 Median

25th percentile

75th percentile

Inactive

1078

1016

1140

Light

325

278

365

Moderate

27

14

41

Vigorous

1

0

2

47.17

n = 25

% achieving ACSM guidelines*

* ACSM (American College of Sports Medicine) guidelines advise all healthy adults to participate in at least 30 minutes of moderate activity 5 days a week.16

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Physical Activity and Arterial Stiffness   275

without (P > .5 for all intensities of activity), those taking and not taking medications for blood pressure (P > .1 for all intensities of activity), and between younger (below 51 years) and older subjects (P > .1 for all intensities of activity). A significant inverse correlation was found between BMI and minutes spent in vigorous activity (ρ = –0.34, P = .012). Activity levels were not significantly correlated with any other anthropometric measure or with age. Brachial SBP was significantly and positively correlated with minutes spent inactive (ρ = 0.37, P = .039), and significantly and negatively correlated with minutes spent in light activity (ρ = –0.39, P = .044). Aortic systolic blood pressure was significantly positively associated with minutes spent inactive (ρ = 0.37, P = .048), but not significantly related to minutes spent being active. All indices of arterial stiffness (PWV, AP, AIx, AIx75) were positively correlated with inactive minutes and negatively correlated with minutes spent carrying out physical activity (Table 3). In stepwise regression analysis, significant models emerged for PWV and AIx. Minutes spent in light activity, and in moderate plus vigorous activity significantly contributed to the prediction of PWV and AIx respectively (Table 4).

Discussion The current cross-sectional study demonstrated an inverse relationship between physical activity, even of light intensity, and arterial stiffness. Individuals who were inactive had significantly higher systolic BP, PWV, and AIx. Those who engaged in physical activity, irrespective of intensity, had reduced arterial stiffness. These results concur with much of the literature on healthy adults. Heffernan and colleagues23 demonstrated an inverse relationship between physical activity and indices of arterial stiffness in a group of prehypertensive older adults. Aoyagi et al7 and Gando et al24 both showed an inverse relationship between physical activity and stiffness in participants of various ages including older adults. This suggests that habitual physical activity may have a similar association with arterial stiffness in those with hypertension as it does with their healthy peers. The novelty of the current study is that habitual physical activity was assessed objectively among those with diagnosed hypertension. It is noteworthy that less than half of the participants achieved recommended activity guidelines.25 Similar to findings by Aoyagi et al,7 current

Table 3  Correlation Coefficients (r-value or ρ Where Appropriate) With Their Significance (P-value) Between Activity Minutes and Indices of Arterial Stiffness PWV m.s-1 (P) Inactive

AP mmHg (P)

Aix % (P)

AIx75% (P)

0.55*(0.01)

0.43* (0.02)

0.44* (0.02)

0.38* (0.04)

Light

–0.52* (0.02)

–0.39* (0.04)

–0.41* (0.03)

–0.40* (0.03)

Moderate

–0.49* (0.03)

–0.41* (0.03)

–0.40* (0.03)

–0.39* (0.03)

Vigorous

–0.34 (0.14)

–0.39* (0.04)

–0.45* (0.01)

–0.23 (0.23)

Moderate+vigorous

–0.42 (0.07)

–0.43* (0.02)

–0.42* (0.02)

–0.40* (0.03)

20

29

29

29

n Observations

* Indicates a statistically significant correlation. Abbreviations: PWV, pulse wave velocity; AP, augmentation pressure; AIx, augmentation index, AIx75, augmentation index corrected to a heart rate of 75 bpm.

Table 4  Regression Models β

P

   Mean Arterial Pressure

0.283

P < .05

    Minutes spent in light activity

–0.309

P < .05

   Mean Arterial Pressure

0.494

P < .001

   Heart rate

–0.405

P < .001

Predictor variable Model for PWV: F2,50 = 7.38, P < .05  Adjusted R2 = 0.197. Significant variables were as follows:

Model for Augmentation index: F4,48 = 16.72, P < .001.  Adjusted R2 = 0.547. Significant variables were as follows:

   Age

0.165

P < .05

    Minutes spent in moderate+vigorous activity

–0.073

P < .05

276  O’Donovan et al

data showed lower blood pressure in physically active participants. A lack of moderate and vigorous exercise among participants rendered comparison between exercise intensities difficult however it can be seen from Table 3 that correlations between indices of arterial stiffness and both minutes spent in light compared with moderate intensity exercise were similar. In regression analysis however, minutes spent in moderate and vigorous activity combined significantly contributed to the prediction of AIx, indicating that exercise intensity may be an important factor in the effect that activity has on arterial health. There are numerous hypotheses which may explain the association between arterial stiffness and physical activity. These include improvements in insulin sensitivity,26 increases in parasympathetic activity,27 modulation of the sympathetic-adrenergic tone of smooth muscle cells in the arterial wall,28 enhancement of the sympathoinhibitory effect of nitric oxide (NO),29 increased basal NO production or the up-regulation in NO availability,30 or greater shear stress leading to improved endothelial function.31,32 Further research is needed to determine the mechanisms which may lead to an increase in arterial compliance with habitual activity. There was no significant difference in activity levels between those with missing hemodynamic variables and those who had all measures taken, which indicates that the data presented is representative of the population of adults studied. One limitation of this study is that data on socioeconomic status, education, alcohol consumption and smoking were unavailable. Furthermore due to the cross sectional nature of this study, it could be argued that participants with stiffer arteries were less physically active because their health was poorer. But as there were no significant differences in activity levels between those with the metabolic syndrome and those without, those taking and not taking medications, and between younger and older subjects this is unlikely. Finally, although a strength of this study is that physical activity was objective measured, accelerometry does not collect other useful information such as what activities participants performed, or their rate of perceived exertion (RPE) which may have yielded interesting results. In conclusion, minutes spent being inactive correlated significantly and positively with indicators of arterial stiffness, while minutes spent in light, moderate and vigorous activity were all negatively associated with indices of arterial stiffness examined. This confirms the beneficial effects of habitual physical activity of all intensities on hemodynamic parameters, and suggests that physical activity, even of a low intensity, should be promoted in this population of adults with hypertension.

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