Extended Risk Factors for Stroke Prevention

Sleep apnea and atrial fibrillation: the spell of Groundhog Day.

Sleep is generally considered to be a protected period, when the cardiovascular system benefits from the restorative influences of the sleeping brain. However, the dynamics of cardiovascular control during sleep can tax the capacity of the diseased coronary circulation and myocardium with surges in sleep-state–related autonomic activity and disruptions in airway function and central nervous system regulation. In this regard, sleep may constitute an autonomic stress test for the heart. The scope of sleep-related risk for atrial and ventricular arrhythmias is substantial. The major subgroups susceptible to adverse influences of surges in autonomic activity during sleep are those with ischemic heart disease, heart failure, and channelopathies (Table).1 It is significant that 20% of myocardial infarctions and 15% of sudden deaths occur at night in the United States.2 Most atrial arrhythmias in patients younger than 61 years of age have nocturnal onset.3 The young are not immune to risk, as sudden infant death syndrome (SIDS) claims 2500 lives in the United States annually.4 Cardiovascular risk is compounded by comorbid factors, most notably apnea, which affects an estimated 4% to 9% of the general population5 and is considerably more prevalent among obese individuals.6 The more common form is obstructive sleep apnea (OSA), with partial or complete collapse of the pharynx. Half of heart failure patients experience either OSA or central sleep apnea (CSA) with central nervous system–mediated periodic breathing, commonly referred to as Cheyne-Stokes respiration. Such cardiorespiratory disturbances profoundly alter autonomic nervous system activity and increase risk of arrhythmia, hypertension, and myocardial infarction. View this table: Table. Patient Groups at Potentially Increased Risk for Nocturnal Cardiac Events It is surprising, as recently underscored by Malhotra and Loscalzo,7 that the significance of cardiovascular risk during sleep may not be duly recognized within the cardiology community. The reasons are …

Sleep-disordered breathing (SDB), which includes obstructive sleep apnea (OSA) as its most extreme variant, is characterized by intermittent episodes of partial or complete obstruction of the upper airway during sleep that disrupts normal ventilation and sleep architecture and is typically associated with snoring and daytime sleepiness. SDB is common, with an incidence in middle-aged men and women of 4% and 2%, respectively.1 Major risk factors for SDB include obesity, male gender, increasing age, and abnormalities of craniofacial morphology.2 There is an increasing perception that SDB/OSA via various mechanisms increases cardiovascular morbidity and mortality (Figure 1). However, many risk factors for SDB/OSA, such as obesity and male gender, are the same as for hypertension and cardiovascular disease.3 Thus, only recently has there been converging evidence that SDB is a risk factor for their development.4–6 Moreover, there is increasing information to indicate that SDB/OSA is linked to metabolic, vascular, hematologic, and genetic markers associated with increased cardiovascular disease risk. In addition, central sleep apnea (CSA), another form of SDB, appears to be an important factor that influences morbidity and mortality among those with heart failure (HF). Nevertheless, responsible mechanisms, the role of SDB as a risk factor “independent” of associated comorbidities, and whether treatment of SDB will mitigate this risk are unknown and remain to be determined. Figure 1. This illustrates the range of cardiovascular diseases and potential mechanisms that may be associated with sleep-disordered breathing. As illustrated in this figure, there is likely an interaction between multiple potential mechanisms, particularly in individuals who may have a genetic susceptibility for sleep-disordered breathing. This report summarizes the proceedings of a workshop sponsored by the National Center on Sleep Disorders Research and the National Heart, Lung, and Blood Institute on September 12 to 13, 2002, to assess a broad array …

Relation of the Severity of Obstructive Sleep Apnea in Response to Anti-Arrhythmic Drugs in Patients With Atrial Fibrillation or Atrial Flutter

POSTER PRESENTATIONS

Elevated thromboembolic risk is observed in patients with atrial fibrillation. The arrhythmia often co-exists with other diseases like obstructive sleep apnea (OSA), which adds to the thrombogenic profile and makes the proper assessment of thromboembolic risk difficult. The aim of the study was to establish how the prevalence of thromboembolic risk factors differs in patients with and without OSA. CHA2DS2-VASc score was used to assess thromboembolic risk in continuous atrial fibrillation patients prequalified for atrial fibrillation ablation. All 266 patients included in the study had a polygraphy examination. Patients were divided into a group with apnea-hypopnea index (AHI) <15/h, and those with AHI 15/h or above, who were considered as having OSA. The study population was aged 57.6 ± 10.1 years, and 65.0% of the subjects were male. OSA was diagnosed in 47 patients. In OSA patients, the following CHA2DS2-VASc risk factors had significantly higher prevalence: congestive heart failure (6.5 vs. 0.5%; P = 0.02), arterial hypertension (93.5 vs. 70.9%; P = 0.01), diabetes mellitus (26.1 vs. 6.8%; P = 0.003), and history of vascular disease (23.9 vs. 8.2%; P = 0.006) than in non-OSA patients. Nonsignificant differences were noticed in the history of stroke, age categories, or sex. After dividing patients into four groups, that is non-OSA, mild OSA, moderate OSA, and severe OSA the same risk factors as previously stated remained significant (P < 0.05). The strongest contributors, responsible for elevated thromboembolic risk observed in atrial fibrillation patients with OSA are congestive heart failure, arterial hypertension, diabetes mellitus, and vascular disease. Higher comorbidity burden is another argument for including OSA into the risk assessment schemes in atrial fibrillation patients.

Background: The relationship between obstructive sleep apnea (OSA) and heart failure (HF) has been under-researched especially in postmenopausal women. We therefore evaluated relationship between OSA risk factors and HFpEF and HFrEF in post-menopausal women. Methods: We performed a prospective analysis of a subset of participants who had adjudicated heart failure outcomes (n=42,362) in the Women Health Initiative Observational, Clinical Trial, and Extension Studies (1998-Present). The cohort was followed over an average of 13.4 years. Inverse probability weighting was employed to account for potential selection bias. Cox proportional hazards regression was used to examine the association between OSA risk factors and time to first hospitalized HF. Type of heart failure was determined using the ejection fraction (EF) obtained from 2D echocardiography. EF of ≥45% was categorized as HFpEF, and EF of &lt; 45% was categorized as HFrEF. Models were adjusted for age, race/ethnicity, education, income, marital status, systolic blood pressure, waist-to-hip ratio, diabetes, coronary heart disease, atrial fibrillation, use of hormone replacement therapy, use of sleep medications, modified Charlson comorbidity index, smoking, alcohol consumption, physical activity, and hysterectomy. We also created an OSA summary score (obesity, snoring, poor sleep quality, sleep fragmentation, daytime sleepiness, and hypertension) based on the Berlin questionnaire, which reliably predicts OSA, to examine its relationship with HF. Results: Of the 42,362 women, 1,054 (2.49%) had preserved EF, and 631 (1.49%) had reduced EF. Four of the 6 risk factors (obesity (HR=1.51, 95% CI 1.29-1.76), snoring (HR=1.23, 95% CI 1.04-1.45), sleep fragmentation (HR=1.15, 95% CI 1.01-1.31), and hypertension (HR=1.46, 95% CI 1.31-1.62)) were associated HFpEF after adjusting for confounders. Each additional OSA risk factor in an OSA summary score compared to no risk factors significantly increased the risk of HFpEF in a dose-response fashion (HR=1.36, 1.61, 2.01, 1.97, 2.02, and 2.74 for scores of 1-6, respectively; P trend &lt;0.001) and not HFrEF (P trend =0.26). Only hypertension was associated with HFrEF (HR=1.39, 95% CI 1.22-1.60). Conclusion: Having more OSA risk factors increases the risk of HFpEF but not HFrEF in postmenopausal women. Early recognition and management of OSA risk factors may play an important role in reducing risk of HFpEF in this population.

The aim was to determine the feasibility of using an unattended 2-channel device to screen for obstructive sleep apnea in a population of high-risk patients using a targeted, case-finding strategy. The case finding was based on the presence of risk factors not symptoms in the studied population. The study took place from June 2007 to May 2008 in rural and metropolitan Queensland and New South Wales. Family doctors were asked to identify patients with any of the following: BMI > 30, type 2 diabetes, treated hypertension, ischemic heart disease. Participants applied the ApneaLink+O2 at home for a single night. The device recorded nasal flow and pulse oximetry. Data were analyzed by proprietary software, then checked and reported by either of two sleep physicians. 1,157 patients were recruited; mean age 53 ± 14.6, M/F% = 62/38, mean BMI = 31.8, obesity = 35%, diabetes = 16%, hypertension = 39%, IHD = 5%, Mean Epworth Sleepiness Scale score (ESS) = 8.3. The prevalence of unrecognized OSA was very high: 71% had an AHI > 5/h, 33% had an AHI > 15/h, and 16% had an AHI > 30/h. The ApneaLink+O2 device yielded technically adequate studies in 93% of cases. The study shows that a "real world" simple low cost case finding and management program, based on unattended home monitoring for OSA, can work well in a population with risk factors and comorbidities associated with OSA, independent of the presence of symptoms. The prevalence of unrecognized OSA was very high.

Obstructive sleep apnea syndrome (OSAS) is a chronic condition characterized by recurrent episodes of partial or complete upper airway collapse during sleep. OSAS presents with intermittent hypoxia, increased respiratory effort, sleep fragmentation, and disruptive snoring together with daytime somnolence. Observational data showed that OSAS is associated with an increased risk of cardiovascular (CV) events. The increased incidence of cardiac arrhythmias (atrial fibrillation, ventricular arrhythmias, and sudden cardiac death) and heart failure could help explain the high CV mortality associated with OSAS. Since all these complications are manifestations of atherosclerotic vascular disease, it was postulated that OSAS may promote atherosclerosis. Therefore, it is relevant to investigate potential associations of OSAS with established vascular risk factors. Hypertension is an established CV risk factor associated with the presence of OSAS. This association may be independent of the presence of obesity. Treatments for OSAS may achieve small decreases in blood pressure (BP). Intermittent hypoxia promotes persistent elevations of BP by enhancing sympathetic tone, while inducing oxidative stress, inflammation, and endothelial dysfunction. The OSASrelated hypertension has a diastolic predominance and a nondipping pattern, while resistant hypertension is frequent due to increased levels of plasma aldosterone. Of interest, it was suggested that OSAS and hypertension may have additive independent effects on atherosclerosis. In this context, hypertension may not be the only CV risk factor associated with OSAS. The predominance of small dense low-density lipoprotein (sdLDL) particles is considered a predictor of CV events. In this issue of Angiology, Sopkova et al report that the presence of metabolic syndrome (MetS), but not OSAS, independently predicted the small size of lowdensity lipoprotein particles in patients with OSAS. MetS is a cluster of risk factors that include abdominal obesity, insulin resistance, elevated BP, and atherogenic dyslipidemia (levels of high triglycerides [TG] and low highdensity lipoprotein cholesterol [HDL-C]). MetS is considered a proinflammatory and procoagulant state associated with increased sympathetic activity, endothelial dysfunction, and higher cholesterol concentration of the atherogenic sdLDL. Thus, MetS promotes atherogenesis and increases the risk of CV events. In the study by Sopkova et al, among MetS components, levels of low HDL-C and high TG were the major independent determinants of sdLDL in patients with OSAS. This is in accordance with our previous findings that increased levels of TG and waist circumference comprise the main predictors of increased concentration of sdLDL in MetS. This finding implies that increased atherogenesis in OSAS may, at least in part, be mediated by the presence of MetS. All components of MetS, including hypertension, insulin resistance, and low HDL-C, together with high levels of TG are frequent in patients with OSAS. Furthermore, HDL may be dysfunctional in these patients. Habitual snoring, as a surrogate marker of OSAS, was associated with the number of MetS components in a dose-dependent manner. Therefore, it is not surprising that the prevalence of MetS is increased in patients with OSAS. In this context, OSAS was considered as a ‘‘manifestation of MetS.’’ Also, the coexistence of these conditions has been termed as ‘‘syndrome Z.’’ It is difficult to settle a causal relationship between MetS and OSAS since they share common predisposing factors. These factors include increased age, obesity, and unhealthy lifestyle (sedentary lifestyle, smoking, and excessive alcohol intake). Interestingly, it was suggested that the association of MetS, or its components, with OSAS may be independent of

Atrial fibrillation and stroke: unrecognised and undertreated

Editorial: Modifying Cardiovascular Risk Factors: Newer Advances in Cardiovascular Metabolism and Diagnostic Technologies.

Establishing new approaches for the prevention and treatment of stroke relies on identifying modifiable risk factors that contribute to the development of this complex disease. Mendelian randomization (MR) studies, analogous to naturally occurring randomized trials, can assess causality of potentially modifiable biomarkers and offer new insights into biological pathways. Stroke is the second leading cause of death worldwide and the chief determinant of long-term disability. Stroke is a heterogeneous disease arising from several distinct underlying pathologies and is typically classified as ischemic or hemorrhagic, and further subclassified using imaging data. Ischemic stroke (IS), including its 3 main subtypes: small vessel disease, large vessel disease, and cardioembolic stroke, accounts for ≈80% of stroke and is the result of an interrupted blood supply, leading to localized areas of ischemia in the brain. Small vessel disease may be a consequence of nonatherosclerotic, as well as atherosclerotic, mechanisms that result in an occlusion of the small perforating arteries, whereas large vessel disease results from occlusions or emboli from plaque rupture in larger vessels, such as a carotid artery. Cardioembolic stroke arises typically from emboli from the heart. By contrast, hemorrhagic stroke is a consequence of intracerebral hemorrhage (bleeding into the brain) or subarachnoid hemorrhage (bleeding into the subarachnoid space). These diverse stroke subtypes have distinct underlying pathologies reflecting different risk factor distributions. MR studies, using genetic variants as instrumental variables, afford a powerful approach to assessing causality of risk factors and avoid biases inherent in observational studies, including confounding and reverse causation. This review considers the contribution of MR studies to stroke epidemiology and their relevance to understanding risk factors and new therapeutic targets for stroke. Meta-analyses of large prospective studies have enhanced our knowledge of classical and emerging risk factors for stroke.1–4 Classical risk factors for stroke include nonmodifiable characteristics, …

Cardiac Arrhythmias in Obstructive Sleep Apnea (from the Akershus Sleep Apnea Project)

INTRODUCTION: Prior studies have documented a higher prevalence of atrial fibrillation (AF) in those with obstructive sleep apnea (OSA). OSA has been associated with AF recurrence following cardioversion and ablation, and with prevalent and incident AF in cross-sectional and retrospective studies. Central sleep apnea (CSA) also has been associated with AF in patients with heart failure. However, data from prospective cohorts are sparse and few studies have evaluated the association of CSA with AF in population studies. METHODS: We assessed the association of OSA and CSA with incident AF among 3,420 subjects without a history of AF in the Sleep Heart Health Study (SHHS), a prospective, community-based study designed to evaluate the cardiovascular consequences of sleep disordered breathing. Subjects underwent overnight polysomnography at baseline and were followed over time for the development of incident AF, documented at any time after baseline polysomnogram until the end of follow-up. OSA was defined as an obstructive apnea-hypopnea index ≥ 5 and CSA was defined as a central apnea index ≥ 5. RESULTS: At baseline, the sample include 1499 men (44.4%) with a mean age of 62.4 (±10.9); 1569 (45.9%) subjects met criteria for mild to severe OSA and 54 (1.6%) for CSA. Over a mean follow-up of 8.2 years, 382 cases of incident AF were identified. The prevalence of both OSA and CSA was higher among those who developed AF compared to those who did not (OSA 49% vs 44%, p=0.001 and CSA 5% vs 1.2%, p=0.001). After adjustment for multiple AF risk factors, CSA was associated with an approximately 2-fold increased odds of incident AF (RR=2.38, 95% CI, 1.15-4.94; p = 0.02). The association persisted after exclusion of 258 subjects with a history of heart failure (RR=2.78, 95% CI, 1.28-6.04; p = 0.01). We did not find a significant association of OSA with incident AF (Table). CONCLUSION: In our prospective, community-based cohort baseline CSA was associated with incident AF.

Recent Trends in the Incidence, Treatment, and Prognosis of Patients With Heart Failure and Atrial Fibrillation (the Worcester Heart Failure Study)