Impact of the obstructive sleep apnea syndrome on left ventricular remodeling among people with different body weight

Materials and methods. The study involved 74 patients with OSAS. All subjects were divided into two groups: with obesity and with normal body weight. Patients with hypertension, diabetes mellitus or any other known cardiac and renal diseases, with central sleep apnea were excluded from the study. 20 healthy people were included in the control group. Each patient underwent a clinical evaluation, 24-hour ambulatory blood pressure monitoring, cardiorespiratory monitoring, transthoracic echocardiography. Pearson correlation analysis, univariate and multivariate regression analysis were performed.

Влияние синдрома обструктивного апноэ сна на ремоделирование левого желудочка у пациентов с разной массой тела Obstructive sleep apnea syndrome (OSAS) characterized by recurrent episodes of complete or partial obstruction of the upper airway during sleep, has widely gained interest since its initial description more than 40 years ago [1].OSAS is associated with hypertension, insulin resistance, atrial fibrillation, stroke, and increased cardiovascular disease (CVD) morbidity and mortality.Disruption of sleep leads to increased sympathetic activation, metabolic changes, vasoconstriction, acute tachycardia, acute blood pressure elevation that results in increased left ventricular (LV) after load [1].
Left ventricular hypertrophy (LVH) is one of the well-knowing CVD risk factors and of ten associate with OSAS [2].However, how OSAS impacts on left ventricular remodeling isn`t completely clear.On the one hand, LVH could be as a result of the OSAS itself.Some studies have shown that LVH is a common complication of OSAS and even without the potential cardiovascular disease, left ventricular systolic and diastolic dysfunction (LVSD and LVDD) and LVH were associated with OSAS.LVMI strongly correlate with OSAS severity and prevalence of LVH among patients with severe OSAS is high [3].But other authors claim that LHV could be caused by the OSAS comorbidities such as hypertension, obesity and metabolic deregulations, and the LVMI differ significantly only between the patients with the OSAS who suffer from hypertension, obesity, and/or diabetes mellitus [2].Furthermore, obesity is an additional risk factor for development of LVH and increasing of CVD risk.

Purpose
The aim of the current study is to estimate the structural changes of LV among people with unrecognized OSAS and different body weight.

Materials and methods
Subjects of this study were recruited from 418 consecutive adults with OSAS who underwent overnight cardiorespiratory monitoring between November 2011 and August 2016.All subjects didn`t have previous treatment of OSAS.Our present research was approved by the clinical research ethic committee of SI "Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine".Written informed consent was obtained from all patients.
Each patient underwent a clinic ale valuation during consultation, biological tests, electrocardiogram (Cardio Sens, XAI-Medica, Ukraine), 24-hour ambulatory blood pressure monitoring (ABPM-04, Meditech, Hungry).Hypertension was defined as blood pressure ≥125/80 mmHg during ABP M and/or use of antihypertensive medication.When first stage of investigation was completed, patients with hypertension, diabetes mellitus or any other known cardiac and renal diseases, with central sleep apnea were excluded from the study.Finally, 74 (52 men and 22 woman) eligible patients were enrolled.All these patients underwent transthoracic echocardiography.Body mass index (BMI) of the patients were calculated as weight divided by height square (kg•m 2 ).According to BMI, all subjects were divided in to two groups.The first group includes participants with obesity (BMI ≥30 kg•m 2 ) (46 subjects), the second groupwith normal body weight (28 subjects).Twenty two healthy people were included in the control group.The mean age and gender were similar between the groups.
Cardiorespiratory monitoring was conducted for OSAS diagnosis by Somno check 2.0 (Weinmann, Germany).The apnea-hypopnea index (AHI) was defined as the number of apneas and hypopnea as per hour of sleep.According to the American association of sleep medicine [4], the severity of OSAS was classified as mild (5≤ AHI <15 events/ hour), moderate (15≤ AHI ≤30 events/hour) and severe (AHI >30 events/hour).Desaturation index (DI) was defined as the percentage of sleep time with oxygen saturation <90 %.Clinical characteristic of enrolled patients are shown in Table 1.
Statistical analysis.The quantitative variables were expressed as means ± SD.Categorical variables were presented as percentages.The differences in each variable were evaluated by the Student's t-test for continuous variables and the χ 2 test for categorical variables.The relationships between parameters were evaluated by Pearson correlation analysis and univariate regression analysis.Multivariate Original research logistic regression analysis using statistically significant variables from the univariate analysis was performed to identify variables that were independently associated with LVH.A P value <0.05 was considered to indicate a statistically significant difference between groups.Calculations were performed using SPSS-software (Version 13.0; SPSS, Chicago, IL).

Results and discussions
The demographic, cardio-monitoring and echocardiographic parameters were compared between the groups.Echocardiographic measures in obtained patients.
Estimated LVM was increased in group I in comparison with the group II and control group (268.7 ± 65.15; 161.3 ± 43.2; 127.56 ± 21.74 respectively, Р = 0.008; 0.005).LVMI (g/m) was also significantly increased in patients with obesity and OSA (47 ± 1.8 vs. 40 ± 1.5, P < 0.01).Significant differences between group II and control group concerning LVMI and LVM weren`t admitted.The LVMI was increased parallel to an increase in the OSAS severity in the groups I and II, but that increasing failed to constitute statistical significance in group II (P = 0.095).
Ten patients from all enrolled subjects were diagnosed with LV hypertrophy.Nine (90 %) of these patients were in group I.All these patients had severe OSAS (AHI, (36.55 ± 8.41) e/h).Concentric remodeling was diagnosed in 9 patients (8 patients from group I and 1 patient from group II) and concentric hypertrophy observed in one patient.In comparison with group without LVH patients with diagnosed LVH have higher level of AHI (38.2 ± 17.8 vs. 24.6 ± 13.3) and DI (6.3 ± 3.2 Vs.18.6 ± 8.8) (P = 0.011).
Statistically significant positive correlations were detected between the BMI and cardio-respiratory parameters-the AHI, mean SaO 2 , the lowest SaO 2 , and DI SaO 2 <90 % (r = 0.232; P = 0.003; r = 0.44; P = 0.010; r = 0.28; P = 0.01; and r = 0.38; P = 0.007 respectively).The LVMI was positively correlated with DI (r = 0.74, P = 0.011) even after adjustment for the BMI (r = 0.27; P value = 0.042).There were no statistically significant correlations between the LVMI and the AHI (r = 0.16, P = 0.082).The LVM correlate with mean SaO 2 (r = -0.22,P = 0.06), and the lowest SaO 2 (r = -0.18,P = 0.06).Positive significant correlation was detected between PWT d and DI (r = 0.35, P = 0.001) and non-significant correlation was detected between IVS d and AHI (r = -0.26;P = 0.072).The univariate regression analysis showed that the lowest SaO 2 , DI, AHI were associated with LVMI.Multivariate regression analyses adjusted for age, gender, BMI, the lowest SaO 2 , mean SaO 2 , AHI and DI were performed to assess the contribution of the variables in LV changes.A 1 % decrease in the lowest SaO 2 saturation was associated with a LVMI increase of 2.5 gr (P = 0.02), increase in IVS d of 0.08 cm (P < 0.05) and an increase in PWT d thickness of 0.03 cm.An increase DI in 1 % lead to increasing of LVMI of 2.6 gr and PWT d thickness of 0.05 cm.
The results of our analysis highlight the importance of hypoxia severity, not just the AHI, in promoting cardiac remodeling.Results of our study have confirmed in some studies.The Wisconsin Sleep Cohort Study [6] showed a significant association with baseline AHI severity and LVH, but relationships became non-significant when BMI was added to the model.Mean SaO 2 and DI were independent predictors of LVM and LVMI in adjusted logistic regression models in this study.In our study we confirm a stronger correlation for DI than for AHI.We didn't obtain significant difference for mean SaO 2 for all participants of our study and differences were significant only for patients with severe OSAS.Furthermore, in the study of Seyed Hashem Sezavar et al. [7].LV hypertrophy not only occurred more frequently in those with severe OSAS (66 %), but an increase in the LVMI was strongly correlated with arise in the DI even after adjustment for the BMI.All patients with LVH in our study have severe OSAS.But hypertension patients didn't exclude from these studies [7] and that fact could influence the results.
Our study has several limitations.Our study was across-sectional study, and included small amount of subjects, that could distort results.The study included considerably fewer female patients and patients older 65 years meeting our criteria, that also could influence study`s results.

Table 1 .
Clinical characteristic of enrolled patients

Table 2 .
Echocardiographic measures in obtained patients