Rashid Nadeem

Serum inflammatory markers in obstructive sleep apnea: a meta-analysis.

STUDY OBJECTIVES Obstructive sleep apnea (OSA) has been linked to and is associated with increased cardiovascular and cerebrovascular morbidity. Ongoing inflammatory responses play an important role in this association. Multiple small size studies addressing the profile of the inflammatory markers in OSA are available therefore we performed a meta-analysis. METHODS Systematic review of medical literature was conducted using PubMed, Cochrane, and EMBASE databases from 1968 to 2011 by utilizing the key words obstructive sleep apnea, C-Reactive protein, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and Selectins. Inclusion criteria were: full text English articles; studies with adult population; reported values for at least one of the markers of interest; with at least two separate groups (subjects with OSA and control group); OSA was defined as AHI of ≥ 5/h. RESULTS Five hundred and twelve studies were reviewed for inclusion with 51 studies pooled for analysis (30 studies for CRP, 19 studies for TNF-α, 8 studies for ICAM, 18 studies for IL-6, six studies for VCAM and 5 studies for Selectins). The levels of inflammatory markers were higher in patients with OSA compared to control group. Standardized pooled Mean differences were calculated to be 1.77 for CRP, 1.03 for TNF-α, 2.16 for IL-6, 4.22 for IL-8, 2.93 for ICAM, 1.45 for Selectins and 2.08 for VCAM. CONCLUSIONS In this meta-analysis, the levels of systemic inflammatory markers were found to be higher in OSA patients compared to control subjects.

Effect of obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis.

BACKGROUND Obstructive sleep apnea (OSA) is associated with obesity, metabolic syndrome, and dyslipidemia, which may be related to decrease androgen levels found in OSA patients. Dyslipidemia may contribute to atherosclerosis leading to increasing risk of heart disease. METHODS Systematic review was conducted using PubMed and Cochrane library by utilizing different combinations of key words; sleep apnea, obstructive sleep apnea, serum lipids, dyslipidemia, cholesterol, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and triglyceride (TG). Inclusion criteria were: English articles, and studies with adult population in 2 groups of patients (patients with OSA and without OSA). A total 96 studies were reviewed for inclusion, with 25 studies pooled for analysis. RESULTS Sixty-four studies were pooled for analysis; since some studies have more than one dataset, there were 107 datasets with 18,116 patients pooled for meta-analysis. All studies measured serum lipids. Total cholesterol pooled standardized difference in means was 0.267 (p = 0.001). LDL cholesterol pooled standardized difference in means was 0.296 (p = 0.001). HDL cholesterol pooled standardized difference in means was -0.433 (p = 0.001). Triglyceride pooled standardized difference in means was 0.603 (p = 0.001). Meta-regression for age, BMI, and AHI showed that age has significant effect for TC, LDL, and HDL. BMI had significant effect for LDL and HDL, while AHI had significant effect for LDL and TG. CONCLUSION Patients with OSA appear to have increased dyslipidemia (high total cholesterol, LDL, TG, and low HDL).

Patients with Obstructive Sleep Apnea Display Increased Carotid Intima Media: A Meta-Analysis

Background. Obstructive sleep apnea (OSA) is associated with coronary artery disease. Intermittent hypoxia associated with OSA increases sympathetic activity and may cause systemic inflammation, which may contribute to atherosclerosis leading to an increase in the size of carotid intima media thickness (CIMT). Methods. PubMed and Cochrane library were reviewed by utilizing different combinations of key words: sleep apnea, carotid disease, intima media thickness, and carotid atherosclerosis. Inclusion criteria were English articles; studies with adult population with OSA and without OSA; CIMT recorded by ultrasound in mean and standard deviation or median with 95% confidence interval; and OSA defined as apnea hypopnea index of ≥5/h. A total of 95 studies were reviewed for inclusion, with 16 studies being pooled for analysis. Results. Ninety-five studies were reviewed, while 16 studies were pooled for analysis; since some studies have more than one data set, there were 25 data sets with 1415 patients being pooled for meta-analysis. All studies used ultrasound to measure CIMT. CIMT standardized difference in means ranged from −0.883 to 8.01. The pooled standardized difference in means was 1.40 (lower limit 0.996 to upper limit 1.803, (P < 0.0001). Conclusion. Patients with OSA appear to have increased CIMT suggestive of an atherosclerotic process.

Effect of CPAP treatment for obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis.

STUDY OBJECTIVE Patients with obstructive sleep apnea (OSA) frequently exhibit higher rates of dyslipidemia, a risk factor for cardiovascular and cerebrovascular disorders. Treatment for OSA by CPAP may improve cholesterol metabolism. This meta-regression analysis (MA) estimates the effect of CPAP treatment on dyslipidemia. METHODS PubMed and Cochrane libraries were searched by utilizing different combinations of keywords: CPAP, obstructive sleep apnea, serum lipids, dyslipidemia, cholesterol, total cholesterol (TC), low density lipoprotein, LDL, high density lipoprotein, HDL, triglyceride, and TG. Inclusion criteria were: (1) English articles and (2) studies with an adult population with the diagnosis of OSA who were treated with CPAP. The OSA group must have cholesterol profile including TC, LDLc, HDLc, and TG, without and with CPAP treatment. Fifty-four studies were reviewed, while 29 studies pooled for MA. RESULTS Thirty-four datasets from 29 studies with 1,958 subjects pooled. Treatment duration range was from 2 days to 1 year. TC standardized mean differences (SMD) ranged from -41.5 to -0.077, pooled mean difference (PMD) was -5.660 (LL -6.715 to UL -4.606, p < 0.001). SMD in LDL ranged from -3.7 to 0; PMD was -0.488 (LL -0.715 to UL -0.261, p < 0.001). HDL SMD ranged from -0.498 to 1.94. The PMD was 0.207 (LL 0.05 to UL 0.364, p < 0.01). TG SMD ranged from -9.327 to 1.98; PMD was -0.054 (LL -0.124 to UL 0.016, p < 0.129). CONCLUSIONS CPAP treatment for OSA seems to improve dyslipidemia (decrease in total cholesterol and LDL, and increase in HDL). It does not appear to affect TG levels.

The Effects of Continuous Positive Airways Pressure Therapy on Cardiovascular End Points in Patients With Sleep-Disordered Breathing and Heart Failure: A Meta-Analysis of Randomized Controlled Trials

In patients with sleep‐disordered breathing and heart failure, continuous positive airway pressure has been found to be associated with an improvement in cardiovascular end points. We conducted a systematic review of the current literature and a meta‐analysis to pool data from 15 published randomized controlled trials. End points analyzed were left ventricular ejection fraction, diastolic blood pressure, systolic blood pressure, heart rate, and mortality. A fixed effects model was used for end points demonstrating homogeneity among included studies, whereas a random effects model was used for end points demonstrating heterogeneity among included studies. A significant improvement in left ventricular ejection fraction was noted with continuous positive airway pressure (mean difference, 5.05%; 95% confidence interval [CI]: 3.72 to 6.38), diastolic blood pressure (mean difference, −1.67; 95% CI: −3.09 to −0.25), and heart rate (mean difference, −5.92; 95% CI: −10.12 to −1.72). No significant changes in mortality (odds ratio, 0.63; 95% CI: 0.40 to 1.00) and systolic blood pressure were noted (mean difference, −6.35; 95% CI: −16.11 to 2.41). The analysis also revealed the need for additional studies to clarify the associations noted and the presence of publication bias with small studies with a paucity of small studies with negative results. In this meta‐analysis, treatment with continuous positive airways pressure was associated with improvements in ejection fraction, diastolic blood pressure, and heart rate in patients with sleep‐disordered breathing and congestive heart failure.

Role of Anemia in Home Oxygen Therapy in Chronic Obstructive Pulmonary Disease Patients.

Anemia is a known comorbidity found in chronic obstructive pulmonary disease (COPD) patients. Hypoxemia is common and basically due to ventilation/perfusion (V/Q) mismatch in COPD. Anemia, by decreasing arterial oxygen content, may be a contributing factor for decreased delivery of oxygen to tissues. The objective of this study is to determine if anemia is a factor in qualifying COPD patients for home oxygen therapy. The study was designed as a retrospective, cross-sectional, observational chart review. Patients who were referred for home oxygen therapy evaluation were selected from the computerized patient record system. Demographic data, oxygen saturation at rest and during exercise, pulmonary function test results, hemoglobin level, medications, reason for anemia, comorbid diseases, and smoking status were recorded. The &khgr;2 tests, independent sample t tests, and logistic regression were used for statistical analysis. Only 356 of total 478 patient referrals had a diagnosis of COPD over a 2-year period. Although 39 of them were excluded, 317 patients were included in the study. The overall rate of anemia was 38% in all COPD patients. Anemia was found significantly more frequent in COPD patients on home oxygen therapy (46%) than those not on home oxygen therapy (18.5%) (P < 0.0001). Mean saturation of peripheral oxygen values were significantly lower in anemic COPD patients both at rest and during exercise (P < 0.0001). Also, in COPD patients, age, Global Initiative for Chronic Obstructive Lung Disease class, smoking status, hemoglobin level, hematocrit, percent of forced expiratory volume in first second, forced expiratory volume in first second/forced vital capacity, residual volume/total lung volume, percent of carbon monoxide diffusion capacity were significantly different between home oxygen therapy and those not on home oxygen therapy (P < 0.05). Multivariate logistic regression showed that anemia remained a strong predictor for long-term oxygen therapy use in COPD patients after adjusting for other significant parameters. Anemic COPD patients are more hypoxic especially during exercise than those who are not anemic. We conclude that anemia is a contributing factor in qualifying COPD patients for home oxygen therapy.

The role of severity of obstructive sleep apnea measured by apnea-hypopnea index in predicting compliance with pressure therapy, a meta-analysis.

Obstructive sleep apnea (OSA) is associated with diabetes, hypertension, stroke, coronary artery disease, and premature death. Positive airway pressure (PAP) is the mainstay of therapy. Despite its effective treatment with PAP therapy, noncompliance remains high. Many factors determine compliance. The role of severity of OSA measured by the apnea–hypopnea index (AHI) remains controversial. Meta-analysis of studies examining this role of AHI was performed. A systematic review of the medical literature was conducted using PubMed and Cochrane library by utilizing different combinations of key words: sleep apnea, AHI, compliance, and nonadherence. Inclusion criteria were English articles; Studies with adult population; with 2 groups of patients (compliant and noncompliant); Studies utilizing objective definition of compliance (PAP usage of >4 hours per night for 70% of days or usage >5 d/wk and for >4 hours per night). Studies were analyzed by standard methods of meta-analysis. The studies were heterogeneous for AHI; therefore, the random effect model was used. Six hundred forty-one manuscripts were found. Of these, 230 were found to be appropriate for full text evaluation. Thirty-one met inclusion criteria. Twelve of these studies used objective criteria for PAP compliance and were hence included in meta-analysis. All the subjects had OSA determined by polysomnography, for whom PAP was employed. Compliance to PAP therapy was evaluated after a period of time ranging from 4 weeks to 8 years. There were 1438 subjects included in the meta-analysis; 886 subjects were PAP compliant, whereas 552 subjects were noncompliant. A greater AHI was found in PAP compliant patients. The mean difference between compliant and noncompliant groups was 5.9 (95% confidence interval: 0.19–11.67, P < 0.05). Patients with mild OSA are less likely to be compliant with PAP therapy. These patients should receive aggressive management particularly at the start of therapy with close follow-up to increase compliance.

Effect of Visualization of Raw Graphic Polysomnography Data by Sleep Apnea Patients on Adherence to CPAP Therapy

BACKGROUND: CPAP is considered to be the cornerstone of therapy for obstructive sleep apnea. However, adherence to this treatment is frequently poor, which may lead to ongoing symptoms, including daytime sleepiness and poor cognitive function. We aimed to determine the efficacy of showing patients their raw graphic polysomnography (PSG) data in increasing their CPAP adherence. METHODS: The subjects were patients with obstructive sleep apnea (n = 37, diagnosed on prior PSG), who were prospectively randomized into an experimental arm or a control arm. The patients in the experimental arm (n = 18) were shown detailed PSG data, including graphic data from PSG prior to prescription of CPAP. The patients in the control arm (n = 19) were shown the non-graphic paper report of the PSG. Adherence data, collected using CPAP devices with internal microprocessors (adherence cards), was read at 4 weeks after treatment initiation. RESULTS: There was no difference in age (57.3 ± 11.8 y vs 55.5 ± 11.6 y, P = .64), body mass index (BMI) (32.7 ± 6.3 kg/m2 vs 32.3 ± 6.6 kg/m2, P = .85), and apnea-hypopnea index (36.0 ± 27.8 events/h vs 30.5 ± 19.1 events/h, P = .48) between the experimental and control arms. There was no difference in percent of days CPAP was used (58% vs 64%, P = .59) and average number of hours each night CPAP was used (3.9 ± 2.1 h vs 4.1 ± 2.5 h, P = .76) between the experimental and control arms, respectively. In multi logistic regression models, which included age, BMI > 30 kg/m2, apnea-hypopnea index, and experimental intervention, only BMI was found to increase likelihood of improved adherence (odds ratio = 13.3, P = .007). CONCLUSIONS: Showing patients raw graphic PSG data does not seem to improve adherence to CPAP. BMI is a very strong predictor of CPAP adherence.

Effect of Positive Airway Pressure Therapy on Body Mass Index in Obese Patients With Obstructive Sleep Apnea Syndrome: A Prospective Study.

Because obesity is a common cause of obstructive sleep apnea syndrome (OSAS), weight loss can be an effective treatment. OSAS also may cause weight gain in some patients. Effective treatment of sleep apnea may facilitate weight loss in obese patients. We hypothesize that positive airway pressure (PAP) therapy is associated with weight loss in obese patients with OSAS. This was a single-center observational prospective cohort study. Forty-five patients were diagnosed with OSAS after polysomnographic analysis in sleep laboratory and underwent continuous positive airway pressure titration. Patients were followed for 3 months in terms of change in body mass index (BMI) and compliance with PAP therapy. Of the 45 patients recruited, 3 patients were eliminated because of miss recruitment. Nine patients had incomplete data, and the rest (n = 33) were included for analysis. The mean age was 54.9 ± 16.9 years (mean ± SD), 93.9% were male, and 90.9% were whites. Mean apnea–hypopnea index was 36.3 ± 28.17 events per hour. Mean BMI before treatment was 34.7 ± 3.9 kg/m2. Fifteen patients (45.5%) were compliant with therapy of OSAS with PAP. There was no difference in age, gender, neck circumference, BMI, and apnea–hypopnea index of patients compliant to therapy when compared with those who were not. There was a significant decrease in BMI in patients compliant with PAP therapy compared with noncompliant patients (−1.2 ± 0.7 vs. 0.3 ± 0.9 kg/m2, P ⩽ 0.001). PAP therapy may cause significant loss of weight within 3 months in obese patients with OSAS. Further study is needed to elucidate the physiological basis of this change.

Potential Augmentation of the Risk of Ischemic Cerebrovascular Accident by Chronic Obstructive Pulmonary Disease in Patients with Atrial Fibrillation

BACKGROUND Atrial fibrillation (AF) is a potent risk factor for ischemic cerebrovascular accident (ICVA). Inflammation is a potential pathogenic factor for atherosclerosis and ICVA. Chronic obstructive pulmonary disease (COPD) is associated with increased inflammatory markers. Subjects who frequently experience COPD and AF together may have higher risk of ICVA. The objective of the study is to compare the prevalence of ICVA in patients with atrial fibrillation and COPD together versus atrial fibrillation alone. METHODS Subjects diagnosed with COPD, AF, and ICVA were categorized into 3 groups: COPD, AF, and COPD plus AF. Prevalence of ICVA was compared. Confounding factors affecting ICVA risk were recorded: age, diabetes, hypertension, peripheral vascular disease, dyslipidemia, and congestive cardiac failure. RESULTS Total charts reviewed were 500: COPD alone 244, AF alone 188, and both together 68. ICVA was documented in 132 (26.4%) subjects. Prevalence of ICVA was 11.8% (COPD alone), 29.8% (AF alone), and 39.7% (AF plus COPD). COPD plus AF group had ICVA 2.05 (95% confidence interval [CI], 1.203-3.94; P = .007) times compared with others. ICVA was also higher in patients with AF only versus COPD only (P < .001). Logistic regression showed AF plus COPD was a stronger predictor of ICVA (P = .001) than AF only (P = .07) or COPD only (P = .8). Odds ratio for ICVA was 2.85 (CI, 1.57-5.16; P = .001) for AF plus COPD versus 1.81 (CI, .94-3.47; P = .71) for AF only and 1.08 (CI, .58-2.10; P = .8) for COPD only. CONCLUSIONS COPD may increase the risk of ischemic stroke in subjects with AF. Presence of COPD may increase the risk of ischemic stroke in subjects with AF.