Elevated serum neutrophil elastase is related to prehypertension and airflow limitation in obese women
BMC Women?'?s Health
Elevated serum neutrophil elastase is related to prehypertension and airflow limitation in obese women
Mervat M El-Eshmawy 0
Eman H El-Adawy 0
Amany A Mousa 0
Amany E Zeidan 1
Azza A El-Baiomy 2
Elham R Abdel-Samie 2
Omayma M Saleh 0
0 Internal Medicine Department, Specialized Medical Hospital, Faculty of Medicine, Mansoura University , Mansoura , Egypt
1 Chest Department, Faculty of Medicine, Mansoura University Hospital, Mansoura University , Mansoura , Egypt
2 Clinical Pathology Department, Faculty of Medicine, Mansoura University , Mansoura , Egypt
Background: Neutrophil elastase level/activity is elevated in a variety of diseases such as atherosclerosis, systolic hypertension and obstructive pulmonary disease. It is unknown whether obese individuals with prehypertension also have elevated neutrophil elastase, and if so, whether it has a deleterious effect on pulmonary function. Objectives: To determine neutrophil elastase levels in obese prehypertensive women and investigate correlations with pulmonary function tests. Methods: Thirty obese prehypertensive women were compared with 30 obese normotensive subjects and 30 healthy controls. The study groups were matched for age. Measurements: The following were determined: body mass index, waist circumference, blood pressure, lipid profile, high sensitivity C-reactive protein, serum neutrophil elastase, and pulmonary function tests including forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. Results: Serum neutrophil elastase concentration was significantly higher in both prehypertensive (405.8 111.6 ng/ml) and normotensive (336.5 81.5 ng/ml) obese women than in control non-obese women (243.9 23.9 ng/ml); the level was significantly higher in the prehypertensive than the normotensive obese women. FEV1, FVC and FEV1/FVC ratio in both prehypertensive and normotensive obese women were significantly lower than in normal controls, but there was no statistically significant difference between the prehypertensive and normotensive obese women. In prehypertensive obese women, there were significant positive correlations between neutrophil elastase and body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low density lipoprotein cholesterol, high sensitivity C-reactive protein and negative correlations with high density lipoprotein cholesterol, FEV1, FVC and FEV1/FVC. Conclusion: Neutrophil elastase concentration is elevated in obese prehypertensive women along with an increase in high sensitivity C-reactive protein which may account for dyslipidemia and airflow dysfunction in the present study population.
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Background
The seventh report of the Joint National Committee
(JNC-7) proposed a new classification distinguishing
between individuals with normal blood pressure and
established hypertension. The report categorized people
with systolic blood pressure between 120 and 139 mm
Hg or diastolic blood pressure between 80 and 89 mm
Hg as having prehypertension [1]. Data from the 1999
and 2000 National Health and Nutrition Examination
Survey (NHANES III) suggested that the prevalence of
prehypertension among adults in the United States was
approximately 31% [2]. Prehypertension is a risk factor
for overt hypertension [3] and future cardiovascular
disease events [4]. Prospective observational studies suggest
the risk of cardiovascular death begins at 115/75 mm
Hg and doubles for every 20/10 mm Hg increment in a
linear fashion [5].
Leukoprotease activity was first described early in the
20th century but human neutrophil elastase (NE) was
only identified relatively recently [6]. Intracellular NE is
a key effector molecule of the innate immune system,
with potent antimicrobial activity against Gram negative
bacteria [7], spirochetes [8] and fungi [9]. Its
bestknown extracellular manifestation is connective tissue
digestion. NE is capable of digesting virtually every type
of matrix protein, including elastin [10]. Because of its
unique elastic recoil properties, elastin is vital for
conferring elasticity on arteries, lungs, ligaments and skin
[11]. Biologically, NE is considered a secretagouge for
cytokines [12] and a modulator of inflammation [13].
Alpha-1 antitrypsin is the major specific inhibitor for
NE [14]. Alpha-1 antitrypsin is an acute phase protein
derived from liver and its concentration rises during
inflammation; it inhibits NE to prevent tissue injury in
target organs [15]. Other protease inhibitors ordinarily
present in human serum are a1-antichymotrypsin and
a2-macroglobulin [16].
Elevation of NE levels/activity has been demonstrated
in a variety of pathological conditions including cystic
fibrosis [17], acute respiratory distress syndrome,
bronchiectasis, chronic obstructive pulmonary disease
[18], type2 diabetes mellitus, atherosclerosis [19], aortic
stiffness and systolic hypertension [20]. Such changes
have been explained by a possible protease/anti-protease
imbalance. This imbalance might be due to an increased
elastase load following neutrophil influx, a reduction in
the levels or activity of the circulating inhibitors of
this enzyme, or increased non-apoptotic neutrophil
death [21].
It is unknown whether obese individuals with
prehypertension also have elevated NE, and if so, whether it
has a deleterious effect on pulmonary function. The aim
of the present study was to investigate the level of
serum elastase in obese prehypertensive women and to
investigate correlations with pulmonary function tests.
Methods
Ninety females were enrolled in the study, divided into
three groups (Table 1). Group 1 included 30 obese
prehypertensive women. Group 2 included 30 obese
normotensive women. Group 3 included 30 non-obese,
age-matched normotensive women (control group). The
mean ages were 33.5 7.7, 34.4 9 and 36.5 5.2,
respectively. The obese patients were attending obesity
clinics at the Specialized Medical Hospital. All patients
signed an informed consent to be included in our study.
The study was approved by the local ethical committee
of Mansoura University Hospital, Internal Medicine
Department.
Table 1 Subjects characteristics
Blood pressure was categorized according to the
JNC7 (1). Normal blood pressure was defined as not being
on antihypertensive medication and having systolic
blood pressure less than 120 mm Hg and diastolic blood
pressure less than 80 mm Hg. Prehypertension was
defined as not being on antihypertensive medication and
having a systolic blood pressure of 120-139 mm Hg
or diastolic blood pressure of 80-89 mm Hg on three
occasions. Blood pressure was taken in the sitting
position after 10 min rest using a random-zero
sphygmomanometer.
All participants were subjected to thorough medical
history and clinical examination, and anthropometric
measurements were performed as follows: height was
measured to the nearest 0.5 cm; body weight was
measured to the nearest 0. (...truncated)