H. Klar Yaggi

Cardiovascular Consequences of Sleep Apnea

Cardiovascular disease has been the leading cause of death since 1900. Strategies for cardiovascular disease and prevention have helped to reduce the burden of disease, but it remains an important public health challenge. Therefore, understanding the underlying pathophysiology and developing novel therapeutic approaches for cardiovascular disease is of crucial importance. Recognizing the link between sleep and cardiovascular disease may represent one such novel approach. Obstructive sleep apnea (OSA), a common form of sleep-disordered breathing, has a high and rising prevalence in the general adult population, attributable in part to the emerging epidemic of obesity and enhanced awareness. OSA has been independently linked to specific cardiovascular outcomes such as hypertension, stroke, myocardial ischemia, arrhythmias, fatal and nonfatal cardiovascular events, and all-cause mortality. Treatment of OSA may represent a novel target to reduce cardiovascular health outcomes.

The Ratio of FEV1 to FVC as a Basis for Establishing Chronic Obstructive Pulmonary Disease

RATIONALE The lambda-mu-sigma (LMS) method is a novel approach that defines the lower limit of normal (LLN) for the ratio of FEV1/FVC as the fifth percentile of the distribution of Z scores. The clinical validity of this threshold as a basis for establishing chronic obstructive pulmonary disease is unknown. OBJECTIVE To evaluate the association between the LMS method of determining the LLN for the FEV1/FVC, set at successively higher thresholds, and clinically meaningful outcomes. METHODS Using data from a nationally representative sample of 3,502 white Americans aged 40-80 years, we stratified the FEV1/FVC according to the LMS-LLN, with thresholds set at the 5th, 10th, 15th, 20th, and 25th percentiles (i.e., LMS-LLN5, LMS-LLN10, etc.). We then evaluated whether these thresholds were associated with an increased risk of death or prevalence of respiratory symptoms. Spirometry was not specifically completed after a bronchodilator. MEASUREMENTS AND MAIN RESULTS Relative to an FEV1/FVC greater than or equal to LMS-LLN25 (reference group), the risk of death and the odds of having respiratory symptoms were elevated only in participants who had an FEV1/FVC less than LMS-LLN(5), with an adjusted hazard ratio of 1.68 (95% confidence interval, 1.34-2.12) and an adjusted odds ratio of 2.46 (95% confidence interval, 2.01-3.02), respectively, representing 13.8% of the cohort. Results were similar for persons aged 40-64 years and those aged 65-80 years. CONCLUSIONS In white persons aged 40-80 years, an FEV1/FVC less than LMS-LLN5 identifies persons with an increased risk of death and prevalence of respiratory symptoms. These results support the use of the LMS-LLN5 threshold for establishing chronic obstructive pulmonary disease.

Continuous Positive Airway Pressure: evaluation of a Novel Therapy for Patients with Acute Ischemic Stroke

BACKGROUND New approaches are needed to treat patients with stroke. Among acute ischemic stroke patients, our primary objectives were to describe the prevalence of sleep apnea and demonstrate the feasibility of providing auto-titrating continuous positive airway pressure (auto-CPAP). A secondary objective was to examine the effect of auto-CPAP on stroke severity. METHODS Stroke patients randomized to the intervention group received 2 nights of auto-CPAP, but only those with evidence of sleep apnea received auto-CPAP for the remainder of the 30-day period. Intervention patients received polysomnography 30 days post-stroke. Control patients received polysomnography at baseline and after 30 days. Acceptable auto-CPAP adherence was defined as ≥ 4 h/night for ≥ 75% nights. Change in stroke severity was assessed comparing the NIH Stroke Scale (NIHSS) at baseline versus at 30 days. RESULTS The 2 groups (intervention N = 31, control N = 24) had similar baseline stroke severity (both median NIHSS, 3.0). Among patients with complete polysomnography data, the majority had sleep apnea: baseline, 13/15 (86.7%) control patients; 30 days, 24/35 (68.6%) control and intervention patients. Intervention patients had greater improvements in NIHSS (-3.0) than control patients (-1.0); P = 0.03. Among patients with sleep apnea, greater improvement was observed with increasing auto-CPAP use: -1.0 for control patients not using auto-CPAP; -2.5 for intervention patients with some auto-CPAP use; and -3.0 for intervention patients with acceptable auto-CPAP adherence. CONCLUSIONS The majority of acute stroke patients had sleep apnea. Auto-CPAP was well tolerated, appears to improve neurological recovery from stroke, and may represent a new therapeutic approach for selected patients with acute cerebral infarction.

Adult Obstructive Sleep Apnea/Hypopnea Syndrome: Definitions, Risk Factors, and Pathogenesis

The objectives of this article are to (1) understand how respiratory event definitions and syndrome threshold values affect prevalence estimates of obstructive sleep apnea in adults, (2) recognize important risk factors for obstructive sleep apnea in adults, and (3) understand current theories of the underlying mechanisms for airway obstruction during sleep.

Auto-Titrating Continuous Positive Airway Pressure for Patients With Acute Transient Ischemic Attack A Randomized Feasibility Trial

Background and Purpose— Transient ischemic attack (TIA) patients are at risk of recurrent vascular events. The primary objectives were to evaluate among TIA patients the prevalence of sleep apnea and among patients with sleep apnea auto-titrating continuous positive airway pressure (auto-CPAP) adherence. The secondary objective was to describe among TIA patients with sleep apnea the recurrent vascular event rate by auto-CPAP use category. Methods— All intervention patients received auto-CPAP for 2 nights, but only intervention patients with evidence of sleep apnea received auto-CPAP for the remainder of the 90-day period. Intervention patients received polysomnography at 90 days after TIA. Control patients received polysomnography at baseline and at 90 days. Acceptable auto-CPAP adherence was defined as ≥4 hours per night for ≥75% of nights. Vascular events included recurrent TIA, stroke, hospitalization for congestive heart failure, myocardial infarction, or death. Results— We enrolled 70 acute TIA patients: 45 intervention and 25 control. The majority of patients had sleep apnea: 57% at baseline and 59% at 90 days. Among the 30 intervention patients with airflow obstruction, 12 (40%) had acceptable auto-CPAP adherence, 18 (60%) had some use, and none had no use. Three intervention patients (12%) had recurrent events compared with 1 (2%; P=0.13) control patient. The vascular event rate was highest among sleep apnea patients with no CPAP use: none, 16%; some, 5%; acceptable adherence 0% (P=0.08). Conclusions— Sleep apnea is common among acute TIA patients. It appears feasible to provide auto-CPAP in the acute TIA period. Larger studies should evaluate whether a strategy of diagnosing and treating sleep apnea can reduce recurrent vascular events after TIA.

Phenotype of normal spirometry in an aging population.

RATIONALE In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]). OBJECTIVES To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories. METHODS Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. Georges Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm). MEASUREMENTS AND MAIN RESULTS Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. Georges Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories. CONCLUSIONS GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the normal range for multiple phenotypes. These results suggest that among adults with GLI-defined normal spirometry, GOLD may misclassify normal phenotypes as having respiratory impairment.

Circumstances and consequences of falls among people with chronic stroke

Falls are common after stroke; however, circumstances and consequences are relatively unknown. Our objectives were to identify the differences between fallers and non-fallers among people with chronic stroke, identify the circumstances of fall events, and examine the consequences of the falls. This is a secondary data analysis; all participants included sustained a stroke. Variables included demographics, stroke characteristics, and comorbidities. Falls were collected via self-report, and circumstances and consequences were derived from participant description of the event and categorized as appropriate. Among 160 participants, 53 (33%) reported a fall during the 1 yr period. Circumstances of falls were categorized as intrinsic or extrinsic. Location and circumstance of the fall were included: 70% occurred at home and 40% were associated with impaired physical or mental state (e.g., inattention to tying shoes). Additionally, 21% of falls were associated with activities of daily living and mobility and 34% with slips or trips. The majority who fell sustained an injury (72%). Injuries ranged from bruising to fractures, and 55% of those with an injury sought medical care (32% to emergency department). Poststroke falls are associated with an alarming rate of injury and healthcare utilization. Targeting mental and physical states may be key to fall prevention.

The effect of gender on the prevalence of hypertension in obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) causes systemic hypertension. However, there is conflicting data on the effect of gender on susceptibility to hypertension in OSA. Some show no gender differences in the prevalence of hypertension while others report either female or male propensity to have hypertension in the context of OSA. The inconsistencies in the results appear to be due to lack of full range of sleep apnea severity and insufficient number of women in the studies. We examined the effect of gender on prevalent hypertension in a cohort with a large representation of females with OSA. METHODS A cross-sectional study of a large cohort of subjects referred for sleep disorder evaluation. RESULTS The cohort comprised of 736 with OSA and 315 without OSA. OSA was defined as apnea-hypopnea index (AHI) of 5/h. There were 529 men and 207 women in the OSA group with mean+/-SD age of 50+/-13 and 51+/-14 years, respectively. The control group consisted of 154 men and 161 women with mean+/-SD age of 44+/-15 and 43+/-14 years, respectively. The AHI in the OSA group varied from 5 to 197 with a median of 24 and a mean of 36 (interquartile range: 11-53). Multiple logistic regression analyses, modeling the association between AHI and hypertension and considering other covariates, showed that odds of hypertension increased with increasing age, BMI, and AHI. There was evidence that men were at higher risk for hypertension than women OR 1.82 (95%CI 1.01, 3.20) at the highest quartile of BMI. CONCLUSIONS We have shown that the prevalence of hypertension increases with increasing age and severity of OSA, and markedly obese men may have a nearly 2-fold greater risk for hypertension than women in this clinic-based population.

Use of Lambda-Mu-Sigma-Derived Z Score for Evaluating Respiratory Impairment in Middle-Aged Persons

BACKGROUND: The lambda-mu-sigma (LMS) method calculates the lower limit of normal for spirometric values as the 5th percentile of the distribution of Z scores. Conceptually, LMS-derived Z scores account for normal age-related changes in pulmonary function, including variability and skewness in reference data. Evidence is limited, however, on whether the LMS method is valid for evaluating respiratory impairment in middle-aged persons. OBJECTIVE: To evaluate the association of LMS-defined respiratory impairment (airflow limitation and restrictive pattern) with mortality and respiratory symptoms. METHODS: We analyzed spirometric data from white participants ages 45–64 years in the Third National Health and Nutrition Examination Survey (NHANES III, n = 1,569) and the Atherosclerosis Risk in Communities study (ARIC, n = 8,163). RESULTS: LMS-defined airflow limitation was significantly associated with mortality (adjusted hazard ratios: NHANES III 1.90, 95% CI 1.32–2.72, ARIC 1.28, 95% CI 1.06–1.57), and respiratory symptoms (adjusted odds ratios: NHANES III 2.48, 95% CI 1.75–3.51, ARIC 2.27, 95% CI 1.98–2.62). LMS-defined restrictive-pattern was also significantly associated with mortality (adjusted hazard ratios: NHANES III 1.98, 95% CI 1.08–3.65, ARIC 1.38, 95% CI 1.03–1.85), and respiratory symptoms (adjusted odds ratios: NHANES III 2.34, 95% CI 1.44–3.80, ARIC 1.89, 95% CI 1.46–2.45). CONCLUSIONS: In white middle-age persons, LMS-defined airflow limitation and restrictive-pattern were significantly associated with mortality and respiratory symptoms. Consequently, an approach that reports spirometric values based on LMS-derived Z scores might provide an age-appropriate and clinically valid strategy for evaluating respiratory impairment.

Staging the Severity of Chronic Obstructive Pulmonary Disease in Older Persons Based on Spirometric Z‐Scores

Among older persons, the use of spirometric Z‐scores as calculated by the Lambda‐Mu‐Sigma (LMS) method has a strong scientific rationale for establishing a diagnosis of chronic obstructive pulmonary disease (COPD), but its clinical validity in staging COPD severity is not yet known. The current study has therefore evaluated the association between LMS‐staged COPD and health outcomes, in two separate cohorts of older persons.