A syndrome of sleep apnea in morbid obesity

Received: May 26, 2017; Accepted: June 23, 2017; Published: June 26, 2017 Abbreviations : NP: nocturnal pulse oximetry, BMI: body mass index, ESS: Epworth sleepiness scale, SBP: Systolic blood pressure (mmHg), DAP: Diastolic blood pressure (mmHg), LM: Lean mass (Kg), FM: Fat mass (Kg), % BF: Percentage of body fat, Glyc: Basal glycemia (mg/dl), Ins: Basal Insulin (IU), Chol: Cholesterol (mg/dl), Tgc: Triglycerides (mg/dl), DLCO: Diffusion of CO (%), KCO: DLCO/ alveolar ventilation (%), PIM: Inspiratory mouth pressure at residual volume (cm H2O), PEM: Expiratory pressure in the mouth at total lung capacity (cmH2O), PO2 and PCO2: Partial pressures in arterial blood of O2 and CO2 (mmHg), SO2: O2 arterial saturation (%), Neck: perimeter of neck (cm),W/H: waist/hip index, LM: Lean mass (Kg), % BF: Percentage of body fat (%), FVC: forced vital capacity (%), FEV1: Forced expiratory volume in the first second (%), TLC: Total lung capacity (%), FRC: Functional residual capacity (%), RV: Residual volume (%), PO2: Blood pressure of oxygen (mmHg), PCO2: Blood pressure of carbon dioxide (mmHg), SO2: arterial oxygen saturation (%), Min SO2: Minimum night oxygen saturation (%), Noct SO2: Basal nocturnal oxygen saturation (%), ODI: Number of nocturnal oxygen desaturations greater than 4% per hour, Insp Pres: Continuous inspiratory pressure in the airway (cm H2O), Expi Pres: Continuous expiratory pressure in the airway (cmH2O). Introduction


Introduction
Sleep Apnea Syndrome (SAS) is a pathology of high prevalence in the general population, which affects men predominantly, increases with age and is frequently associated with obesity [1,2]. The importance of SAS is due to its high morbidity (arterial hypertension, arrhythmias, myocardial infarction and stroke) [3], which causes higher mortality [4].
Obesity has important cardiovascular consequences, with arterial hypertension and affectation of myocardial function [5]. From the respiratory point of view, two syndromes have been associated: Alveolar hypoventilation syndrome and SA [6]. In morbid obesity (MO), the incidence of SAS is 12 to 30 times higher than in the general population [7] and it is recommended that sleep studies be performed routinely in this circumstance [8]. The presence of MO and SAS have a high risk of sudden cardiovascular death, even in the absence of other conventional risk factors [9].
The incidence of SAS in MO varies according to sex with a clear predominance of men [10], with the accumulation of visceral fat being an important risk factor for SAS in obese subjects [11]. However, there are few studies in patients with MO in which comparisons are established by sex or by type of obesity, and the number of patients included in the study is small.
In this study we evaluated, in a large sample of patients with MO, the prevalence of respiratory disorders during sleep and the influence of sex and the type of obesity in them.

Material and methods
At weight 40 kg/m 2 (the hospital level, patients with no BMI (body mass index) in kilograms/height in meters squared) were selected, who were to be submitted to a very low calorie diet (450 Kcal/day) for weight reduction and the following parameters were determined, grouped by sex: age (years), weight (kg), height (cm), BMI (kg/m 2 ), neck circumference, waist at the level of the navel (cm) and hip at the level of major trochanters (cm), waist/hip index (W/H). Central or android type obesity was considered with a W/H index > 1 in males and > 0.9 in females [12]. Systolic blood pressure (SBP) and diastolic blood pressure (mmHg) were measured. Body composition was calculated by means of bioelectrical impedanciometry (Holtein), determining the lean mass (kg), fat mass (FM) (kg) and the percentage of body fat (% BF). Hematocrit (Ht), basal glucose (mg/dl), basal insulin (IU), total cholesterol (TC), triglycerides (TGC) and HDL, LDL and VLDL cholesterol fractions).
At the respiratory functional level, we performed: In the respiratory functional parameters, the men with pathological NP had a lower FVC and PIM, compared to the rest. In women, there was a lower PO 2 and SO 2 in those with pathological NP (Tables 3,4).
In the OM and SAS groups, women were older (50 ± 11 years), and had a higher BMI (50 ± 6 kg/m 2 ) than men (44 ± 12 years and 46 ± 7 kg/m 2 ) (p <0.002 and p <0.01 respectively). They were also different in the type of obesity and body composition. Men had greater neck circumferences and a central predominance in obesity type, while women had higher fat mass, higher percentage of body fat and lower lean mass (Table 5). Between the two groups there were no differences in pulmonary function parameters ( Table 6), but in gasometry and NP. Males had higher mean PO 2 and SO 2 mean diurnal, lower SO 2 mean nocturnal and lower SO 2 minimum nocturnal, requiring higher pressures of DPAP than females (Table 7).

Discussion
The untreated SAS has important cardio-respiratory consequences, which condition an increase in morbidity and mortality. In most SASassociated mortality studies, there is a decrease in long-term survival [20]. The most important causes in the increase of the mortality were the cardio-vascular ones [21].
The influence of obesity on the SAS is conditioned by its distribution, mainly due to its location in the upper airway (VAS). There is a greater velo-pharyngeal collapsibility in obese patients with thick necks [22]. The measurement of this fatty deposit in the VAS can be verified with dynamic NMR [23]. Thus, a good correlation (r = 0.63) was observed between SAS and neck circumference [24] or with the measurement of skin folds [25]. On the other hand, upper body obesity or android obesity, measured as waist-to-hip ratio, conditions a greater severity of SAS [26]. The abdominal CT scan has shown that the accumulation of visceral fat is a risk factor for SLE in obese patients [11].
These alterations in high ways occur in different ways according to sex, which would explain the different incidence of SAS in men and The spirometric, plethysmographic and diffusion values of CO were calculated as a percentage of the theoretical, according to the ECSC tables [15], while in the maximum respiratory pressures the tables were used for the Mediterranean population of Morales el al [16].
Daytime somnolence was assessed using the Epworth scale [17], translated and validated in Spanish [18]. Nocturnal pulse oximetry (NP) [19] was performed with a continuous recording, assessing falls in SO 2 , greater than 4% (ODI), being the pathological record with more than 10 ODI per hour. The minimum night SO 2 was recorded. Positive double airway pressure (DPAP) was placed in the nasal mask until normalization of NP, recording inspiratory pressures (cm H 2 O), expiratory pressure (cm H 2 O) and system tolerance. Patients were divided into two groups, depending on whether NP was normal or pathological.
Statistical analysis used the Statistical Package for Social Science (SPSS 9.0 for Windows). In the comparisons of means the Student's t was used for independent variables, assessing the equality of variances with the Levene test. The level of significance was set at p <0.05.
Men with pathological NP had older age, higher BMI (lower stature with similar weight), higher W/H index, and higher values on the drowsiness scale than those with normal BP. Women with pathological NP had older age, weight, BMI, waist, hip, index, and diurnal drowsiness compared to those with normal NP (Table 1).
In men, according to NP results, there were no differences in blood pressure, body composition and analytical determinations, but in women there was higher SBP and baseline glycemia in the pathological NP group (  women. Thus, between 30 and 60 years the prevalence of SAS in men is 4% and in women of 2%, there is a greater activity of the genioglossus muscle that dilates the upper airway, induced by progesterone [27]. There is also a different neck morphology according to sex, with differences in fat deposition in the neck with greater soft tissue in the upper airway of men [28].
Our results confirm these facts. Comparing normal and SAS men, we found a higher BMI in MO with pathological NP, at the expense of a shorter size with similar weight, as well as a waist/upper index hip. This would tell us about a different distribution of body fat, central type or android. As for body composition, there are no differences in the amount of lean mass and fat mass in these patients. It has also been shown that age is higher in patients with pathological PN, possibly because of age-dependent development of a type of central obesity.
As for women is the total weight, both fat mass and lean mass, regardless of height, which conditions a pathological NP. Although both the hip and waist circumference are superior, in the pathological, an android type distribution is maintained. Likewise, the age is higher, perhaps due to the higher prevalence of SAS in postmenopausal women [29] whose hormonal changes would lead to a greater distribution of central type fat, as has already been demonstrated in other studies [26].
We have verified, in patients with MO and SAS a wider neck in men, with an android type corporal distribution in them. In contrast, women with SAS and MO are older than men, they have more BMI at the expense of greater fat mass and percentage of body fat and have lower lean mass.
On the other hand, we have seen a higher SBP in women with pathological NP as well as superior basal glycemia, in concordance with studies associating SAS with arterial hypertension and elevated insulin resistance [25]. However, in men we have not checked these differences.
In addition to cardiovascular risk, nocturnal respiratory changes condition lower quality of life. Thus, we have seen, in men as well as in women, greater daytime sleepiness, which sometimes becomes invalidating regarding the difference of the respiratory parameters between MO with or without SAS, differences have been described. On the one hand, there is a 50% hypercapnia (PCO 2 > 42 mmHg), conditioned by lower VC, TLC and FEV 1 [30]. On the other hand, the decrease in VC in patients with SAS is associated with hypertension and central type obesity. In moderately obese patients, those with SAS have lower FEV 1 , FVC, TLC and PO 2 and higher PCO 2 than control [31]. The presence of SAS in MO induces greater diurnal hypoxemia [32]. The FRC has shown a negative correlation with the ODI [33]. As for diffusion, an increase in DLCO and KCO has been reported in the obese with SAS, which correlates more with BMI than with SAS itself [35].
FVC and PIM, in women the functional parameters were similar, with a decrease in PO 2 and in Sat. of O 2 . These differences would be justified by their different degree and type of obesity. Comparing men and women with MO and SAS, there are no differences in respiratory functional parameters, but we have observed a lower PO 2 and Sat. of O 2 in women, although men with SAS and MO have a Sat. O 2 lower, requiring higher pressures of BiPAP with similar ODI. These data coincide with other studies that demonstrate that, in MO, men have a higher severity of nocturnal respiratory disorders [36].
The treatment of MO can improve SAS and the respiratory and gasometric parameters [37,38]. This SAS resolution with weight loss is associated with a decrease in the collapsibility of the upper airway [39] with an improvement in glottal and pharyngeal function [40]. However, SAS may reappear if there is a new weight gain [41], or even without an increase in weight [42]. This indicates that the overweight is not the only pathogenic factor of the SAS, the anatomic-functional situation of the upper airway being more important.