Download Regular physical activity prevents development of

European Heart Journal Advance Access published December 11, 2008
CLINICAL RESEARCH
European Heart Journal
doi:10.1093/eurheartj/ehn533
Regular physical activity prevents development
of left ventricular hypertrophy in hypertension
Paolo Palatini 1*, Pieralberto Visentin 1, Francesca Dorigatti 1, Chiara Guarnieri 1,
Massimo Santonastaso 2, Susanna Cozzio 3, Fabrizio Pegoraro 4,
Alessandra Bortolazzi 5, Olga Vriz 6 and Lucio Mos 6, on behalf of the HARVEST
Study Group
1
Clinica Medica 4, University of Padova, via Giustiniani, 2, 35128 Padova, Italy; 2Town Hospital, Vittorio Veneto, Italy; 3Town Hospital, Trento, Italy; 4Town Hospital, Mirano, Italy;
Town Hospital, Rovigo, Italy; and 6Town Hospital, San Daniele del Friuli, Italy
5
Received 25 March 2008; revised 7 October 2008; accepted 18 November 2008
Aims
The longitudinal relationship between aerobic exercise and left ventricular (LV) mass in hypertension is not well
known. We did a prospective study to investigate the long-term effect of regular physical activity on development
of LV hypertrophy (LVH) in a cohort of young subjects screened for Stage 1 hypertension.
.....................................................................................................................................................................................
Methods
We assessed 454 subjects whose physical activity status was consistent during the follow-up. Echocardiographic LV
mass was measured at entry, every 5 years, and/or at the time of hypertension development before starting treatand results
ment. LVH was defined as an LV mass 50 g/m2.7 in men and 47 g/m2.7 in women. During a median follow-up
of 8.3 years, 32 subjects developed LVH (sedentary, 10.3%; active, 1.7%, P ¼ 0.000). In a logistic regression, physically
active groups combined (n ¼ 173) were less likely to develop LVH than sedentary group with a crude OR ¼ 0.15
(CI, 0.05–0.52). After controlling for sex, age, family history for hypertension, hypertension duration, body mass,
blood pressure, baseline LV mass, lifestyle factors, and follow-up length, the OR was 0.24 (CI, 0.07–0.85). Blood
pressure declined over time in physically active subjects (25.1 + 17.0/20.5 + 10.2 mmHg) and slightly increased
in their sedentary peers (0.0 + 15.3/0.9 + 9.7 mmHg, adjusted P vs. active ¼ 0.04/0.06). Inclusion of changes in
blood pressure over time into the logistic model slightly decreased the strength of the association between physical
activity status and LVH development (OR ¼ 0.25, CI, 0.07–0.87).
.....................................................................................................................................................................................
Conclusion
Regular physical activity prevents the development of LVH in young stage 1 hypertensive subjects. This effect is independent from the reduction in blood pressure caused by exercise.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Exercise † Hypertension † Left ventricle † Hypertrophy
Introduction
Although leading health organizations endorse regular exercise for
the prevention and treatment of hypertension and its complications,1 most studies of exercise training have focused on its
blood pressure effects. There is substantial evidence that regular
physical activity lowers blood pressure2,3 and enhances endothelial
vasodilator function4 in hypertensive subjects, but very little is
known about the effects of physical activity on left ventricular
(LV) mass (LVM) in hypertension. In normotensive subjects, endurance sports activities increase LVM and may lead to LV hypertrophy
(LVH).5,6 In cohorts with hypertension, increased LVM has been
shown to be an important predictor of cardiovascular events independent of blood pressure level.7,8 Thus in hypertensive individuals,
exercise could facilitate the development of LVH, counteracting the
beneficial effects on blood pressure. However, a paradoxical effect
of exercise on LVM has been described in hypertensive subjects, as
some short-term studies in mild to severe hypertensive patients
have shown that regular physical activity may lead to favourable
changes in LV structure and mass.9 – 12
The effect of regular aerobic exercise on the risk of developing
LVH has never been assessed in long-term studies of hypertensive
* Corresponding author. Tel: þ39 049 8212278, Fax: þ39 049 8754179, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2008. For permissions please email: [email protected].
Page 2 of 8
subjects because of the confounding effect of antihypertensive
treatment. The aim of the present study was to examine the longterm effect of regular physical activity on the risk of developing
LVH in the participants of the Hypertension and Ambulatory
Recording VEnetia STudy (HARVEST), a prospective longitudinal
study of young subjects screened for stage 1 hypertension.13 – 15
The HARVEST cohort is particularly suitable for studying the longterm effects of exercise because in many participants blood
pressure remained below the threshold for treatment for a long
period of time.
Methods
Study population
The HARVEST is a long-term prospective study of 18- to 45-year-old
individuals, initiated in April 1990, investigating the origin of hypertension with regard to physiological,13 clinical,14 and genetic15 characteristics. Never-treated subjects screened for stage 1 hypertension
(systolic blood pressure between 140 and 159 mmHg and/or diastolic
blood pressure between 90 and 99 mmHg) were enrolled. Patients
with diabetes mellitus, nephropathy, and cardiovascular disease were
excluded.13 – 15 Patients clinical characteristics are reported in
Table 1. The higher prevalence of men among our study participants
confirms previous observations of a much higher prevalence of men
in the young, stage 1 segment of the hypertensive population.16 The
HARVEST study is conducted in 17 Hypertension Units in Italy.
Patient’s recruitment was obtained with the collaboration of the
local general practitioners who were instructed during local meetings.
Consecutive patients with the above-mentioned clinical characteristics
seen in the offices of the general practitioners and willing to participate
in the study were eligible for recruitment and were sent to the referral
Centers. Patients files, blood, and urine samples are periodically collected by five monitors and taken to the coordinating office in
Padova, where they are processed.
Procedures
The procedures followed were in accordance with the institutional
guidelines. At baseline, all subjects underwent physical examination,
anthropometry, blood chemistry, and urine analysis. Participants completed questionnaires about their medical history, family history of
hypertension, physical activity, and dietary habits including coffee
intake, alcohol use, and cigarette smoking. Categorization of lifestyle
factors in the present study was based on previously published data
showing the effects of various types of lifestyle factor categorization
on blood pressure and target organ damage in the HARVEST population.13,17 Physical activity was assessed using a standardized questionnaire.13 Briefly, activities were classified on the basis of relative
intensity, adapting the activity intensity codes established and validated
by the Minnesota Heart Survey.18 Subjects were categorized as sedentary, if they did not regularly perform any physical activity; mild exercisers, if they performed leisure-time physical activities, such as
walking, gardening, yard working, etc.; and exercisers, if they performed sports such as running, jogging, cycling, swimming, soccer,
tennis, etc. at least once a week during the previous 2 months.
Within the exercisers, the subjects performing competitive sports
(competitive athletes) were separated from those not involved in competition (amateurs).
Smoking habits were categorized as non-smokers (Class 0) and
smokers (1 or more cigarettes per day, Class 1). Coffee consumption
was categorized according to the number of caffeine-containing cups
P. Palatini et al.
of coffee drunk per day: non-drinkers (0 cups/day), moderate drinkers
(1 – 3 cups/day), and heavy drinkers (4 or more cups/day). Alcohol
intake was calculated by summing the total number of millilitres of
daily alcohol consumption of wine, beer, and liqueurs according to
the formula of Criqui et al.19 Subjects were then categorized as nondrinkers (Class 0), light drinkers (,50 g/day, Class 1), and moderate
to heavy drinkers (50 g or more of alcohol/day, Class 2). Duration
of hypertension was defined as number of months from the first detection of high blood pressure to the baseline assessment. Details about
the interview, lifestyle assessment, and criteria used for subject’s classification according to lifestyle were reported elsewhere.13,17 Baseline
blood pressure was the mean of six readings obtained during two
visits performed 2 weeks apart. Body mass index (BMI) was considered
as an index of adiposity (weight divided by height squared). The study
was approved by the HARVEST Ethics Committee and by the Ethics
Committee of the University of Padova, and written informed
consent was given by the participants.
Echocardiography
Subjects were studied with M-mode and two-dimensional echocardiography according to the previously described procedure.13 For the
present analysis, only the baseline and the last available echocardiogram were considered. LV internal diameter and wall thickness were
measured at end-diastole, according to the suggestions of the
American Society of Echocardiography.20 All measurements were
made blind by two observers according to the American Society of
Echocardiography21 at the Coordinating Center at the University of
Padova laboratory. All baseline and follow-up readings were taken
from anonymous recordings and were read by the same two investigators. Three consecutive beats obtained during quiet respiration
were measured and averaged. Relative wall thickness was defined as
the ratio of interventricular septum end-diastolic thickness þ LV posterior wall end-diastolic thickness to LV end-diastolic diameter. LVM
was calculated according to the following formula: 0.8 [1.04
(IVS þ LVDD þ PWT)3 2 LVDD3]þ0.6 g.22 All echocardiographic
data were indexed by height to the allometric power of 2.7.23 LVH
was defined as an LVM 50 g/m2.7 in men and 47 g/m2.7 in
women. To evaluate the reproducibility of the echocardiographic
measurements, 33 baseline echocardiograms were re-examined 5
years later. These echocardiograms were selected at random
without knowledge of the patient’s identity or previous evaluation
results. The coefficient of variation resulted in 9.8% for intraventricular
septum thickness, 9.6% for posterior wall thickness, 3.7% for LV enddiastolic diameter, and 8.1% for LVM.
Follow-up
In the HARVEST study, office blood pressure and lifestyle habits are
assessed monthly during the first 3 months of follow- up, then after
6 months, and every 6 months thereafter. After baseline examination,
subjects are given general information about non-pharmacological
measures by the HARVEST investigators, following the suggestions
of current guidelines on the management of hypertensive
patients.1,24 – 27 To ensure homogeneous counselling by doctors participating in the study, training in current international guidelines was
provided to them throughout the study duration. HARVEST participants are followed until they develop sustained hypertension requiring
antihypertensive treatment according to the guidelines available at the
time. Subjects who do not meet the criteria for treatment are checked
at 6 month intervals unless they drop-out. To identify the subjects with
sustained hypertension, we followed the guidelines of the British
Hypertension Society until 199924,25 and then the 1999 WHO/ISH
Variable
Physical activity
P-value
.............................................................................................
...........................................................
Total (n 5 454)
Sedentary (n 5 281)
Active (n 5 173)
Unadjusted
Adjusted for age and sex
Age (years)
33.1 + 8.4
34.3 + 8.3
31.1 + 8.3
0.000
0.001a
2
.............................................................................................................................................................................................................................................
BMI (kg/m )
24.9 + 3.2
25.2 + 3.4
24.4 + 3.0
0.006
0.006
Duration of hypertension (months)b
Baseline systolic blood pressure (mmHg)
24.0 (7.0–60.0)
145.9 + 10.6
24.0 (6.0–60.0)
145.1 + 10.6
26.0 (7.0–64.0)
147.2 + 10.5
0.2
0.04
0.1
Baseline diastolic blood pressure (mmHg)
93.6 + 5.3
94.0 + 5.0
92.9 + 5.6
0.03
0.5
Baseline heart rate (b.p.m.)
Systolic blood pressure after 6 months (mmHg)
74.6 + 9.5
141.2 + 11.5
76.0 + 9.7
141.1 + 12.1
72.2 + 8.7
141.3 + 10.5
0.000
0.8
0.000
0.7
Diastolic blood pressure after 6 months (mmHg)
90.6 + 7.6
91.5 + 7.5
89.4 + 7.5
0.007
0.3
Female gender, n (%)
Parental hypertension, n (%)
137 (30.2)
282 (62.1)
107 (38.1)
169 (60.1)
30 (17.3)
113 (65.3)
0.000
0.4
Cigarette smokers, n (%)
83 (18.3)
62 (22.1)
21 (12.1)
0.004
Alcohol drinkers, n (%)
Coffee drinkers, n (%)
201 (44.3)
326 (71.8)
126 (44.8)
213 (75.8)
75 (43.4)
113 (65.3)
0.7
0.009
Follow-up change in systolic blood pressure (mmHg)
22.0 + 16.2
0.0 + 15.3
25.2 + 17.0
0.001
0.04
Follow-up change in diastolic blood pressure (mmHg)
Follow-up change in heart rate (b.p.m.)
0.4 + 9.9
23.5 + 11.1
0.9 + 9.7
23.5 + 11.2
20.5 + 10.2
23.4 + 10.9
0.1
0.7
0.06
0.8
0.03
Follow-up change in body weight (kg)
2.4 + 6.7
2.7 + 7.3
2.1 + 6.3
0.4
Follow-up length (days)b
3046 (2043–4029)
3048 (1947– 3821)
2839 (1890– 4068)
0.9
Regular physical activity prevents development of LVH
Table 1 Clinical characteristics of the study subjects by physical activity status
Values are given as mean + SD unless otherwise specified. Follow-up changes were adjusted also for baseline values.
a
Adjusted for sex.
b
Median (inter-quartile range).
Page 3 of 8
Page 4 of 8
guidelines,26 and the 2003 ESC/ESH guidelines.27 The definition of sustained hypertension is based on at least six clinic blood pressure readings taken on two subsequent visits within 1 month.15,17 The second
endpoint visit is performed immediately before starting antihypertensive treatment and the final echocardiogram is performed in
between. In the present study, median follow-up for the whole
cohort was 8.3 (inter-quartile range, 5.6–11.0) years. Other details
on follow-up procedures were reported elsewhere.15,17
Data analysis
The present study was performed in 521 participants with consistent
physical activity habits and who had not LVH at baseline evaluation
(Figure 1). Subjects who remained in the same class of physical activity
throughout the follow-up were said to have consistent habits. Among
the 136 participants with inconsistent physical activity habits, 67
improved their habits during the follow-up whereas the other 69
decreased or quitted physical activity. Subjects who decreased or discontinued regular exercise were slightly younger than those with consistent activity habits (31.7 + 8.1 vs. 33.1 + 8.4 years, P , 0.01), but
did not differ from the 173 subjects in active follow-up (31.1 + 8.3
years). No subject changed his/her physical activity habits because of
detection of LVH or cardiac disease.
Sixty-seven subjects with consistent habits were excluded from the
analysis because the echocardiographic images were technically unsatisfactory. Thus, the final calculations were performed in 454 participants. The characteristics of the 454 subjects considered for this
P. Palatini et al.
analysis were compared with those of the rest of the HARVEST participants with baseline echocardiographic assessment (n ¼ 425) and
with those of the subjects with inconsistent physical activity habits
(n ¼ 136). The only significant difference between the sample considered for this study and the rest of the group was BMI, which was
smaller in the former (24.9 + 3.2 kg/m2) than the latter (25.5 +
3.4 kg/m2, P ¼ 0.002). No significant difference emerged between
the 454 subjects considered for the present analysis and the 136 subjects with inconsistent habits for age, gender, baseline blood pressure,
heart rate, and BMI. Thus, the 454 study subjects can be considered
representative of the whole population.
Subjects were initially grouped into four categories of physical
activity habits (see above). As only a few active subjects developed
LVH during the follow-up, for most analyses the three categories of
active subjects were grouped together. Differences between the
groups (sedentary vs. active) were assessed with the t-test for the variables normally distributed. Data were adjusted for age and sex by the
use of linear regression analysis. Non-normally distributed data, presented as median and inter-quartile range, were analysed by the
Mann – Whitney test. The significance of differences in categorical variables was assessed with the x2 test and Fisher’s exact test. Follow-up
changes in echocardiographic data were evaluated using a general
linear model, with the value for the measurement of interest serving
as the dependent variable and physical activity group, age, sex, BMI,
systolic blood pressure, diastolic blood pressure, hypertension duration, parental hypertension, smoking, alcohol and coffee use, baseline
echocardiographic variables, and follow-up length serving as independent variables. In Table 2, orthogonal contrasts for independent
groups, estimated by comparing the combined active groups with
the sedentary group, are reported. Logistic regression was used with
LVH as an outcome variable. Multiple logistic regression was used to
adjust for possible confounders. The variables found to be associated
with outcome at univariable analysis and/or believed to be of prognostic importance were sex, age, BMI, family history for hypertension, duration of hypertension, follow-up length, coffee intake, smoking status,
alcohol consumption, systolic and diastolic blood pressures, and baseline LVM. Other explanatory variables included in the models were
follow-up changes in blood pressure and body weight. To assess
whether there was an interactive effect of physical activity with sex,
age, BMI, or lifestyle factors on the risk of subsequent LVH, we
added an interaction term to the model that contained physical activity
group and each of the above clinical variables. Odds ratios were calculated from the logistic models. A two-tailed probability value of ,0.05
was considered significant. Data are presented as mean + SD unless
specified or as percentages. Analyses were performed using Statistica
version 6 (Stat Soft, Inc., Tulsa, OK, USA) and Systat version 10
(SPSS Inc., Evanston, IL, USA).
Results
Figure 1 Flow chart of patients selected for the present analysis. CV, cardiovascular; LVH, left ventricular hypertrophy.
The number of subjects categorized as sedentary was 281 and of
those categorized as active was 173. Among the active subjects,
75 were mild exercisers, 65 were amateurs, and 35 were competitive athletes. During the follow-up, 29 sedentary subjects (10.3%),
2 mild exercisers (2.7%), 1 amateur (1.5%), and no athlete (0%)
developed LVH (P ¼ 0.006). Among the subjects with new-onset
LVH, there was a parallel increase in LV wall thickness (0.14 +
0.15 mm) and LV diastolic diameter (3.2 + 3.9 mm) during the
follow-up with little change in relative wall thickness (þ0.7%). As
the rate of LVH was low among the three active groups, for
Page 5 of 8
Regular physical activity prevents development of LVH
Table 2 Baseline and follow-up echocardiographic data indexed by height2.7 in the subjects divided according to their
physical activity status
Variable
Baseline
Follow-up
...............................................................
...............................................................
Sedentary
P-value
Sedentary
281
173
41.4 + 9.0*
2.3 + 0.4
39.0 + 7.2
2.1 + 0.3
Active
Active
P-value
...............................................................................................................................................................................
n
281
173
LVMI (g/m2.7)
IVSd (mm/m2.7)
39.9 + 8.8
2.3 + 0.4
38.4 + 8.1
2.1 + 0.3
0.09
0.08
0.02
0.09
PWd (mm/m2.7)
2.2 + 0.4
2.0 + 0.3
0.04
2.2 + 0.4
2.0 + 0.3
0.04
LVDD (mm/m2.7)
11.9 + 4.5
11.3 + 4.3
0.31
12.2 + 4.9*
11.4 + 4.3
0.07
RWT (%)
37.3 + 5.0
36.3 + 4.3
0.15
36.7 + 5.1*
36.3 + 4.2
0.74
LVMI, left ventricular mass indexed for height; IVSd, interventricular septum thickness in diastole; PWd, left ventricular posterior wall thickness in diastole; LVDD, left ventricular
end-diastolic diameter; RWT, relative wall thickness. P-values are adjusted for age, sex, BMI, systolic blood pressure, diastolic blood pressure, hypertension duration, parental
hypertension, smoking, alcohol and coffee use. *P , 0.01 vs. baseline. Follow-up vs. baseline P-values are adjusted also for baseline echocardiographic variables and follow-up
length.
subsequent analyses the active subjects were grouped together.
Clinical characteristics of the sedentary vs. active individuals are
shown in Table 1. Active subjects were younger and leaner than
sedentary ones, were more frequently male, had lower heart
rate, and were less likely to smoke cigarettes or drink coffee.
After adjustment for age and sex, baseline blood pressure did
not differ significantly between the groups. Blood pressure
declined during the first 6 months of follow-up without significant
differences between the two groups. At baseline, active subjects
had smaller interventricular septal thickness and LV posterior
wall thickness than sedentary subjects (Table 2). End-diastolic
diameter and relative wall thickness did not differ significantly
between the groups. LVM was slightly but insignificantly smaller
in the active than the sedentary subjects.
Follow-up
During the follow-up, there was a decline in systolic blood
pressure among the active subjects and virtually no change
among the sedentary ones (Table 1). In the active group, there
was a slight decline also in diastolic blood pressure, but the difference with the sedentary group did not attain the level of statistical
significance. Heart rate showed a similar slight decline in the two
groups. Both groups gained weight during the period of observation, and the increase in body weight was smaller among the
active than the sedentary subjects. Among the sedentary subjects,
there was a significant increase in LV end-diastolic diameter and
LVM and a decrease in relative wall thickness, whereas wall thicknesses did not change significantly (Table 2). No significant change
in any echocardiographic finding was observed in the active group.
At follow-up end, LVM and LV wall thicknesses were greater in the
sedentary than the active individuals. To examine differences in the
mean LVM between the time periods, a general linear model was
used. After adjustment for relevant covariates including baseline
LVM (see Methods), a significantly greater increase in LVM was
observed in the sedentary than the active subjects (Table 3). The
between-group difference was no longer significant when baseline
LVM was excluded from the model. No significant differences
between the two groups were observed for the changes
Table 3 Follow-up changes in echocardiographic data
indexed by height2.7 in the subjects divided according to
their physical activity status
Variable
Sedentary Active
Unadjusted
P-value
Adjusted
P-valuea
..................................................................................
n
281
173
LVMI (g/m2.7)
1.4 + 6.5
0.6 + 7.1 0.19
0.03
IVSd (mm/m2.7)
PWd (mm/m2.7)
0.0 + 0.1
0.0 + 0.1
0.0 + 0.1 0.55
0.0 + 0.1 0.99
0.73
0.88
LVDD (mm/m2.7) 0.1 + 0.4
0.0 + 0.3 0.04
0.25
0.0 + 0.1
0.0 + 0.1 0.21
0.95
RWT (%)
LVMI, left ventricular mass indexed for height; IVSd, interventricular septum
thickness in diastole; PWd, left ventricular posterior wall thickness in diastole;
LVDD, left ventricular end-diastolic diameter; RWT, relative wall thickness.
a
Adjusted for age, sex, BMI, systolic blood pressure, diastolic blood pressure,
hypertension duration, parental hypertension, smoking, alcohol, coffee use,
follow-up length, and by baseline echocardiographic data.
in the other echocardiographic variables except for unadjusted
LV end-diastolic diameter. Among the active subjects, similar
marginal changes in LVM were observed in the three groups
[0.7 + 7.6 g/m2.7 in the mild exercisers, 0.8 + 7.2 g/m2.7 in the
amateurs, and 0.2 + 6.1 g/m2.7 in the competitive athletes (all
P . 0.9)]. LVM at follow-up end was 39.1 + 7.5 g/m2.7 in the
mild exercisers, 39.3 + 7.4 g/m2.7 in the amateurs, and 38.2 +
6.3 g/m2.7 in the competitive athletes without significant differences
between the three groups (all P . 0.8).
In simple correlation analyses, changes in LVM during
the follow-up correlated with changes in systolic blood pressure
(r ¼ 0.11, P ¼ 0.016) and with changes in diastolic blood pressure
(r ¼ 0.09, P ¼ 0.047). After adjustment for age and sex, these
relationships remained significant for diastolic blood pressure
(P ¼ 0.038) but not for systolic blood pressure (P ¼ 0.076). No
relationship was found between changes in LVM and changes in
body weight (r ¼ 20.03, P ¼ 0.5). Adjusted and unadjusted
changes in LV end-diastolic diameter were unrelated to changes
in blood pressure or body weight (all P . 0.4).
Page 6 of 8
P. Palatini et al.
Table 4 Odds ratios and 95% confidence interval for
development of left ventricular hypertrophy according
to physical activity status in 454 HARVEST participants
(active vs. sedentary)
Model
Variables included
OR (95% CI)
P-value
Model 1
Unadjusted
0.15 (0.05– 0.52)
0.002
Model 2
Adjusted for age, sex, BMI,
SBP, DBP, HT duration,
parental HT, follow-up
length, smoking, alcohol
and coffee use
0.24 (0.07– 0.85)
0.027
Model 3
Model 2 þ baseline left
ventricular mass index
0.24 (0.07– 0.85)
0.026
Model 4
Model 3 þ follow-up
change in SBP and DBP
0.25 (0.07– 0.87)
0.029
Model 5
Model 4 þ follow-up
change in body weight
0.26 (0.07– 0.90)
0.033
................................................................................
Results of a logistic model. SBP, systolic blood pressure; DBP, diastolic blood
pressure; HT, hypertension; BMI, body mass index; OR, odds ratio.
New-onset LVH
Sedentary subjects developed LVH more frequently than their
active counterpart (10.3 vs. 1.7%, P ¼ 0.000). Results of logistic
regression assessing the risk of LVH associated with being active
or sedentary at baseline and during follow-up are given in Table 4.
In bivariate analysis, the risk of LVH was statistically significantly
smaller in the active subjects compared with the sedentary ones.
After taking into account age, sex, parental hypertension, hypertension duration, follow-up length, smoking status, alcohol and coffee
intake, and baseline blood pressure, BMI, and LVM, the association
of physical activity status with LVH incidence remained statistically
significant. Inclusion of changes in blood pressure and body weight
during the follow-up did not materially change these findings.
Other independent predictors of LVH in the final logistic model
were age (P ¼ 0.05) and baseline BMI (P ¼ 0.01). No interactive
effects were noted between physical activity group and sex, age,
BMI, or lifestyle factors on LVH development.
Discussion
In this homogeneous cohort of subjects screened for stage 1
hypertension, subjects who performed regular physical activity
had a lower risk of developing LVH than sedentary subjects.
After 8 years of follow-up, LVM remained virtually unchanged
among the participants who engaged in leisure or sports activities,
whereas it increased significantly among the sedentary subjects.
The impact of exercise on LVH development was independent
of several confounding factors including blood pressure and BMI
at baseline. The relationship between physical activity status and
later LVH was also independent of changes in blood pressure
and body weight during the follow-up.
Exercise and LVH in hypertension
Previous echocardiographic studies have demonstrated that LVH is an
independent predictor of cardiovascular morbidity and mortality7,8
and that regression of LVM is associated with a reduction in
risk.28,29 Regular physical activity in normotensive individuals is
associated with an increase in the end-diastolic dimension, wall
thickness, and LVM.5,6 Thus, exercise training, and competitive athletics in particular, might have deleterious effects on the heart in
hypertension favouring the development of LVH. Only did a few
studies evaluate the effects of aerobic exercise on LV structure
and size in patients with hypertension. A decrease in blood pressure
accompanied by a slight reduction in LVM was observed by Baglivo
et al.9 in a small group of middle-aged hypertensive subjects after 16
months of endurance exercise training. Similar results were
obtained by Kokkinos et al.10 in a group of medically treated
African-American men with severe hypertension after 16 weeks
of aerobic exercise. A regression of LVM and concentric LV remodelling, which correlated with a reduction in systolic blood pressure,
was found also in older persons with mild or moderate hypertension who performed endurance exercise for 7 months.11
Reductions in LVM and wall thickness have been found by Zanettini
et al.12 in an uncontrolled trial of aerobic exercise in 14 patients with
mildly elevated diastolic blood pressure. Finally, a trend towards a
reduction in LVM (P ¼ 0.08) after regular endurance exercise with
or without weight management was observed by Hinderliter
et al.30 in overweight individuals with high normal or mildly elevated
blood pressure. At variance with those results, no significant
changes in LVM were noted by Reid et al.31 after 12 weeks of exercise, weight loss, or both in 23 obese individuals with a mean baseline blood pressure of 131/84 mmHg.
These data indicate that regular aerobic exercise is able to
decrease rather than increase LVM in hypertensive individuals.
However, the above results have been obtained in short-term
intervention studies performed in small groups of subjects who
were sedentary at the time of baseline investigation. Little is
known on the long-term effects of exercise on LVM in physically
active subjects with mildly elevated blood pressure at baseline
assessment. In our study, active participants had already a slightly
smaller LVM than their sedentary counterpart at baseline.
However, this difference increased during the 8 years of follow-up
and only 1.7% of the active subjects compared with 10.3% of the
sedentary ones developed LVH. The low rate of new-onset LVH
among the active participants did not allow us to evaluate
whether the beneficial effects of exercise on LVH development
were related to the intensity of physical activity and whether competitive athletics had a less favourable impact on LVH than leisure
activities. However, when LVM was considered as a continuous
variable, similar negligible follow-up changes in LVM were observed
in the three active groups. In particular, competitive athletics did
not appear to cause any deleterious effect on the left ventricle
and no athlete developed LVH during the 8 years of observation.
Possible mechanisms of the effect of
regular aerobic exercise on LVM
The reason why exercise has beneficial effects on LVM of hypertensive individuals in the long term is unclear. One possible explanation is that the effect of exercise may be due to the reduction in
blood pressure caused by regular physical activity.2,3 Indeed, in the
present study, there was a relationship between changes in blood
Page 7 of 8
Regular physical activity prevents development of LVH
pressure during the follow-up and changes in LVM. An effect of
exercise-related weight reduction on LVM has been demonstrated
in obese hypertensive patients.32,33 However, in the present study,
both active and sedentary subjects gained weight during the
follow-up and changes in weight were unrelated to changes in
LVM. In addition, when follow-up changes in body weight and
blood pressure were incorporated in the logistic model, the association of physical activity status with new-onset LVH remained significant indicating that also other mechanisms may be operative.
Reduction in vascular resistance, blood volume, and cardiac
output, enhanced endothelial vasodilator function, suppression of
the activity of the renin –angiotensin –aldosterone system,
reduction of insulin resistance, and reduction in sympathetic
nervous system activity, which are known to occur after a programme of physical activity,4,34,35 are plausible mechanisms by
which exercise training may prevent LVM growth in hypertension,
mechanisms that go beyond the established benefits of exercise on
blood pressure reduction. Indeed, previous studies of the present
cohort have shown that among the HARVEST participants, subjects performing sports activities have lower plasma renin activity36
and urinary catecholamines13 than their sedentary peers. In the
present study, similar marginal changes in LVM were observed
across the three active groups. This may represent the net result
of opposite effects of physical activity on the heart of hypertensive
patients. A higher level of physical activity would induce a more
intense physiologic stimulus to LVH but would also determine a
stronger activation of those mechanisms which may attenuate
the LV growth in hypertension.
A slight decrease in heart rate (23.5 b.p.m.) was observed in
both groups during the follow-up. This may be ascribed to a progressive reduction in the alarm reaction to the doctor’s visit which
is known to occur during a long period of observation.37 The fact
that the heart rate decline was of similar magnitude in the active
and the sedentary subjects suggests that their activity status was
consistent during the follow-up.
Study limitations
A limitation of our investigation is that, given the observational
nature of the study, we cannot establish a definite cause–effect
relationship between exercise and changes in LVM. However, a
relationship between endurance exercise and LVM decline has
been demonstrated in intervention studies. Other limitations of
the study include the lack of knowledge about any potential
dietary changes in the studied population. Other nonpharmacological measures which might influence LVM were recommended by doctors to the HARVEST study participants.
However, the increment in body weight that we observed also
in the active group suggests that the favourable effect on LVM
was not due to the improvement of dietary habits. In addition,
the effect of exercise on LVH development was independent of
follow-up changes in body weight. Another possible limitation is
that the range of physical activity level in the active subjects category was very wide. However, active subjects were grouped
together because we observed similar changes in echocardiographic data across the three active groups. In logistic regressions,
we tried to control for several possible confounders. However, we
cannot exclude that other factors not taken into account in the
present analysis might also have affected the echocardiographic
data during the course of the study. Finally, this study has a
limited generalizability to women and other age and ethnic
groups, and further studies are needed for confirmation of these
findings.
Conclusions
Regular physical activity is recommended among other nonpharmacological measures for reducing blood pressure in subjects
with stage 1 hypertension before initiating drug therapy. However,
evidence that exercise prevents end-organ damage or cardiovascular events has been lacking. Our study demonstrates that exercise
not only has favourable effects on blood pressure but also prevents
development of LVH. These findings support a strategy of exercise
training as an initial approach in the management of sedentary
patients with mildly elevated blood pressure. Physically active
people should be encouraged to continue their exercise programmes even if they perform competitive athletics.
Conflict of interest: none declared. The sources of funding had
no role in the design, conduct, analysis, or reporting of the study or
in the decision to submit the manuscript for publication.
Funding
The study was funded by the University of Padova, Padova, Italy, and
from the Associazione ‘18 Maggio 1370’, San Daniele del Friuli, Italy.
Appendix
List of the Centers participating in the HARVEST study:
Belluno—Cardiologia: G. Catania, R. Da Cortà; Cremona—Div.
Medica: G. Garavelli; Dolo—Div. Medica: F.P., S. Laurini; Mirano—
Cardiologia: D. D’Este; Padova—Clinica Medica 4: F.D., V. Zaetta,
P. Frezza, P. Bratti, D. Perkovic, C.G., A. Zanier; Pordenone—Centro
Cardioreumatologico: G. Cignacco, G. Zanata; Rovereto – Ala —Div.
Medica: M. Mattarei, T. Biasion; Rovigo—Cardiologia: P. Zonzin, A.B.;
San Daniele del Friuli—Area di Emergenza: L.M., S. Martina, O.V.;
San Donà di Piave—Cardiologia: L. Milani, C. Canali; Trento—Div.
Medica: P. Dal Ri, S.C.; Treviso—Div. Nefrologia: G. Calconi,
P. Gatti; Vittorio Veneto—Div. Medica: M.S., E. Cozzutti,
R. Garbelotto, A. Mazzer. Trial Coordinator: P.P.
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