ISSN 035-2899, 37(2012) br.4 p.229-232

Biljana Lazovic (1), Zoran Stajic (1), Sanja Mazic( 2), Marina Đelić (2)
(1) Departement of Internal Medicine, Zemun Clinical Hospital Center, Belgrade, Serbia (2) Faculty of Medicine, University of Belgrade, Serbia, Institute of Physiology

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that is not fully reversible. Spirometry is the gold standard for diagnosing and monitoring progression of COPD which is defined by irreversible lung function impairment with a reduced FEV1/vital capacity (VC) ratio less than 70% of the predicted. The Global Initiative for chronic obstructive lung disease (GOLD) criteria classify COPD into four stages based primarily on lung function impairments as stage I (FEV1>=80%), II (FEV1 50-79%), III (FEV1 30-50%) and IV (FEV1<30% of the predicted) [1].
In COPD patients, unrelated disorders are relatively under recognized [2]. Those patients have much comorbiditiy like: cardiovascular diseases, osteoporosis, diabetes, and metabolic syndrome, more commonly than expected by chance. These associations are greater than expected from common aetiological factors, such as smoking, suggesting that these comorbidities may be causally associated with the mechanisms of COPD, probably due to systemic inflammation [3, 4].
Metabolic syndrome is a set of risk factors that includes: abdominal obesity, a decreased ability to process glucose (increased blood glucose and/or insulin resistance), atherogenic dyslipidemia (elevated triglycerides levels, small low-density lipoprotein [LDL] particles, low high-density lipoprotein cholesterol [HDL-C] levels, raised blood pressure and prothrombotic and inflammatory states [5]. Patients who have this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or diabetes type 2. Recently, the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adults Treatment Panel III) (ATP III) have highlighted the importance of the metabolic syndrome and provided guidelines for the screening of this syndrome. The ATP III guidelines define the metabolic syndrome as a new secondary target for cardiovascular risk reduction therapy beyond low-density lipoprotein cholesterol (LDL-C) lowering. According to the ATP III report, the diagnosis of the metabolic syn-drome requires 3 or more of the following criteria: waist circumference exceeding 102 cm and 88 cm for men and women, respectively, fasting triglycerides of 150 mg/dL or more (≥1.69 mmol/L), HDL-C less than 40 mg/dL (<1.0 mmol/L) for men and less than 50 mg/dL (<1.3 mmol/L) for women, blood pressure exceeding 130/85 mm Hg, and fasting plasma glucose levels of 110 mg/dL or more (≥6.1 mmol/L) [6].
The root cause of most cases of metabolic syndrome can be traced back to poor eating habits and a sedentary lifestyle. Some cases occur in those already diagnosed with hypertension and in those with poorly controlled diabetes; a few are thought to be linked to genetic factors that are still being researched [6]. On the basis of this, we suspected that patients with COPD would be at risk for the metabolic syndrome since these patients are limited by respiratory symptoms and adopted to a sedentary lifestyle, increasing their risk for weight gain and insulin resistance.
This study was undertaken to evaluate the presence of the metabolic syndrome in COPD patients.

MATERIAL AND METHODS

In a year and a half period, among 232 patients suffering from COPD we revealed 60 patients, who had metabolic syndrome according to the criteria. The diagnosis of COPD was made previously according to the GOLD criteria. Inclusion criteria apart from spirometric findings (FEV1/FVC<0.7, and FEV1<=80% of predicted) were no signs of exacerbation and use of systemic corticosteroid in the preceding 3 months. Among them, 57 were Caucasians and 3 belonged to the Roma population. The NCEP APT III criteria previously described was used for checking the presence of the metabolic syndrome. Individuals also met the criteria for hypertension if they were taking antihypertensive, and diabetes if they used oral hypoglycemic agents or insulin. Body weight, height, and waist circumference were obtained in all participants. Waist circumference was measured by a single observer using an inelastic tape at the midpoint between the lowest rib and the iliac crest. Blood pressure measurements were taken according to the American Heart Association’s recommendations. Blood pressure was taken from both arms and the higher measurement was used for te analysis [6, 7]. Participants were asked to fast for 12 hours before blood sampling. We analyzed serum glucose concentration, triglycerides, HDL-C and LDL-C levels and a standard pulmonary function test (spirometry-three consecutive measurement), arterial PaO₂ and PaCO₂.
Descriptive statistics were used to evaluate baseline characteristics. Data are reported as mean ±SD or proportions and 95% confidence intervals.
Statistical analysis was performed by unpaired t test, chi square test and Fisher exact test. A value of P <0.05 was considered statistically significant.

RESULTS

The pulmonary function tests of the COPD group are presented in Table 1. Mean values for arterial PaO₂ and PaCO₂ were within normal range.
Baseline characteristics of all participants are given in Table 2. All women were postmenopausal. No woman was on hormone replacement therapy (HRT). Statistically important difference among women and men was found in HDL levels, usage of antihypertensive, hypolipemic and oral hypoglicemic therapy, as well as in obesity (p<0.05). Abdominal obesity, elevated blood pressure, and elevated triglycerides were the principal features of the metabolic syndrome observed in this group of COPD patients.

Table 1. Characteristic of parameters of pulmonary function test and blood gasses

FVC indicates forced vital capacity; FEV1, forced expiratory volume in first second;FEV1/FVC, forced expiratory volume in first second /forced vital capacity ratio; PaO₂, partial pressure of oxygen; and PaCO₂, partial pressure of carbon dioxide. Values are mean ± SD.

All the features of the metabolic syndrome were present in the same proportion of COPD men and COPD women Indeed, 58.3% patients had central obesity, hypertension had 85% pts, dyslipidemic were 52%, 37% had diabetes mellitus, 43.3% were smokers, 13.3% non smokers, and 43.4 ex-smokers. Metabolic syndrome had almost 2/3 pts.

Table 2. Characteristics of patients suffered from COPD and metabolic syndrome

Obesity is defined as a BMI ≥ 30 kg/m².

DISCUSSION

To our knowledge, there are a few reports regarding the metabolic syndrome in COPD patients. Our results suggest that the presence of the metabolic syndrome may be frequent in patients with COPD, especially in older population. In our study, the overall prevalence of the metabolic syndrome COPD patients is 25, 9 (men 15.5, women 10.3). Men smoked 46.78 packs/year and women 31.3. This could be one of explanations for higher prevalence in men because smoking induces systemic inflammation which may cause metabolic syndrome.
Also, this is a group of elderly pts (aged 68.78), with many comorbid conditions, but 60% of metabolic syndrome is very high, which needs more future investigations.
Interestingly, HDL-C levels were elevated in men with COPD. Tisi et al reported a finding and hypothesized that the increased work of breathing might constitute a chronic exercise stimulus for the respiratory muscles, resulting in an increase in HDL-C levels [8]. Although possible, it is doubtful that respiratory muscles may have such a systemic impact. It has also been suggested that the effects of some drugs, such as β2-agonists, might be responsible for an increased level of HDL-C [9]. However, salbutamol administered at a 0.8 mg daily dosage is not known to interfere with the lipoprotein profile [10]Inhaled corticosteroids could be responsible for the raised HDL-C levels, although inhaled high-dose budesonide (1600 mcg daily) has no major effect on lipid profile in patients with asthma [11]. Other mechanisms unknown at this time may be responsible for the increased HDL-C levels encountered in COPD patients. In our study men had higher level of HDL-C which could be explained with frequent physical activity. They walked for more than 30 minutes daily unlike women. Apart from that, it is interesting to emphasize that the features of the metabolic syndrome were encountered in the same proportion between genders.
It is known that oral corticosteroid therapy induces visceral obesity and diabetes and those glucocorticoids can be produced locally by the visceral adipocyte from inactive 11-keto forms through the enzyme 11-hydroxysteroid dehydrogenase type 1 [12]. An increased activity of this enzyme produces a syndrome of central obesity accompanied by diabetes, dyslipidemia, and hypertension. It is important to emphasize that our patients did not use oral corticosteroid in the 3 months prior the evaluation. COPD patients often result in a sedentary lifestyle and physical deconditioning, which could explain the higher prevalence of the metabolic syndrome.
In conclusion, our findings suggest that the features of the metabolic syndrome may be equally frequent in men and women with COPD. These findings provide a potential explanation for the increased risk for cardiovascular disease in these patients. As the prevalence of metabolic syndrome is high, it implies that screening for features of metabolic syndrome is necessary. Screening can prevent and decrease mortality rate of cardiovascular disease as well as of diabetes mellitus and all its consequences.

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