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Sleep apnoea's detriment: part of the proof is in
the lipids.
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| Subject: |
Cardiovascular diseases
(Risk factors) Cardiovascular diseases (Prevention) Sleep disorders (Complications and side effects) Sleep disorders (Diagnosis) Sleep disorders (Care and treatment) Sleep disorders (Patient outcomes) Low density lipoproteins (Health aspects) |
| Author: | Mehra, Reena |
| Pub Date: | 02/01/2010 |
| Publication: | Name: Indian Journal of Medical Research Publisher: Indian Council of Medical Research Audience: Academic Format: Magazine/Journal Subject: Biological sciences; Health Copyright: COPYRIGHT 2010 Indian Council of Medical Research ISSN: 0971-5916 |
| Issue: | Date: Feb, 2010 Source Volume: 131 Source Issue: 2 |
| Geographic: | Geographic Scope: United States Geographic Code: 1USA United States |
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| Accession Number: | 229718080 |
| Full Text: |
Sleep disordered breathing (SDB), an entity characterized by
repetitive upper airway obstruction, represents a prevalent disorder
affecting millions of individuals. The implications of untreated SDB are
far-reaching including decrements in quality of life and furthermore,
based upon recent data, increased cardiovascular risk and mortality
(1,2). Hyperlipidaemia and derangements of lipids such as low density
lipoprotein (LDL) and high density lipoprotein (HDL) are also common
with an estimated prevalence of 54.9 per cent for men and 46.5 per cent
for women, and are major risk factors for coronary heart disease (3).
Cholesterol profiles of atherogenic dyslipidaemia are key components of
the metabolic syndrome which encompasses substantive cardiovascular risk
factors, and overall connotes increased cardiovascular risk and
mortality (4,5). Given the common underlying microenvironment, the term
Syndrome Z has been coined to incorporate SDB with other commonly
recognized metabolic syndrome risk factors including hypertension,
central obesity, insulin resistance and measures of atherogenic
dyslipidaemia- specifically hypertrygliceridaemia (>150 mg/dl) and
low HDL levels (<40 mg/dl in men and <50 mg/dl in women) (6).
Although it is plausible that SDB, through mechanisms of enhanced
intermittent sympathetic nervous activation, intermittent hypoxia,
ventilatory overshoot hyperoxia, and sleep disruption may lead to
alterations in lipid metabolism; the clarity of these mechanistic
pathways and degree by which obesity mediates these relationships
continue to be active areas of investigation. In this issue Chou and colleagues (7) report on a Taiwanese referral-based study demonstrating that unlike the apnoea hypopnoea index; the oxygen desaturation index defined as the frequency of 4 per cent oxygen desaturation episodes per hour of sleep was significantly associated with hypercholesterolaemia (>200 mg/dl) and hypertriglyceridaemia (>150 mg/dl) even after taking into account confounding factors such as obesity as defined by body mass index. The findings from Chou and colleagues add to growing literature highlighting the importance of the specific role of SDB-related intermittent hypoxia in lipid metabolism. Intermittent hypoxia may impact key steps of hepatic lipid metabolism including enhancing lipid biosynthesis and lipoprotein secretion and affecting reverse cholesterol transport. Provocative animal experiments have demonstrated that intermittent hypoxia may be important means by which dyslipidaemia may occur. Specifically, exposure of lean mice to 5 days of intermittent hypoxia increased serum cholesterol and phospholipid levels, upregulated pathways of triglyceride and phospholipid biosynthesis and inhibited pathways of cholesterol uptake in the liver. Interestingly, in this study, intermittent hypoxia increased total cholesterol and HDL, but not LDL (8). The same group has identified intermittent hypoxia-related upregulation of hepatic stearoyl coenzyme A desaturase-1 (SCD-1), an enzyme that, in a hypoxic environment, is expected to increase triglyceride synthesis more than cholesterol and is expected to enhance hepatic release of lipids (9,10), and has also described the development of steatohepatitis in severe obesity in response to hypoxic stress (11). Clinical research data are sparse and discrepant regarding the presence of an association between SDB and dyslipidaemia, and whether any of the noted relationships are independent of obesity (12-17). Data from the Cleveland Family Study have demonstrated that over a 5 yr period of time, cholesterol is a risk factor for incident SDB defined by the apnoea hypopnoea index. These data suggest that individuals with elevated cholesterol levels may represent a phenotype of augmented SDB risk (18). In summary, given the disparity in results published so far, more clinical research as provided by Chou and colleagues (7) is needed to better characterize the relationships between SDB and dyslipidaemia, particularly from epidemiologic cohorts enrolling community dwelling individuals that would have limited referral bias. In particular, examination of measures of intermittent hypoxia as it relates to cholesterol profiles would be of interest as only limited data are published in this regard. Investigating the relationship of intermittent hypoxia and oxidative stress mechanisms as it relates to lipid metabolism would be of interest to identify culprit pathways resulting in atherosclerosis. Understanding other mechanisms linking SDB and lipid dysregulation are of great importance as well, particularly the role of sympathetic nervous system activation as most research thus far has focused upon intermittent hypoxia pathophysiology. Reena Mehra Division of Pulmonary, Critical Care & Sleep Medicine, University Hospitals Case Medical Center & Case Western Reserve University Cleveland, OH, USA Address for correspondence: Medical Director, Adult Sleep Services University Hospital Case Medical Center Case School of Medicine Division of Pulmonery, Critical Care & Iris S. & Best L. Wolstein Building 2103 Cornell Road, Room 6125 Cleveland, OH 44106-7291, USA reena.mehra@case.edu References (1.) Young T, Finn L, Peppard P E, Szklo-Coxe M, Austin D, Nieto FJ, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 2008; 31 : 1071-8. (2.) Marshall NS, Wong KK, Liu PY, Cullen SR, Knuiman MW, Grunstein RR. Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study. Sleep 2008; 31 : 1079-85. (3.) Arnett DK, Jacobs Jr DR, Luepker RV, Blackburn H, Armstrong C, Claas SA. Twenty-year trends in serum cholesterol, hypercholesterolemia, and cholesterol medication use: the Minnesota Heart Survey, 1980-1982 to 2000-2002. Circulation 2005; 112 : 3884-91. (4.) Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24 : 683-9. (5.) Hu G, Qiao Q, Tuomilehto J, Balkau B, Borch-Johnsen K, Pyorala K. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. Arch Intern Med 2004; 164 : 1066-76. (6.) Wilcox I, McNamara SG, Collins FL, Grunstein RR, Sullivan CE. "Syndrome Z": the interaction of sleep apnoea, vascular risk factors and heart disease. Thorax 1998; 53 (Suppl 3) : S25-8. (7.) Chou Y-T, Chuang L-P, Li H-Y, Fu J-Y, Lin SW, Yang CT, et al. Hyperlipidaemia in patients with sleep-related breathing disorders: Prevalence & risk factors. Indian J Med Res 2010; 131 : 121-5. (8.) Li J, Thorne LN, Punjabi NM, Sun CK, Schwartz AR, Smith PL, et al. Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 2005; 97 : 698-706. (9.) Savransky V, Jun J, Li J, Nanayakkara A, Fonti S, Moser AB, Steele KE, et al. Dyslipidemia and atherosclerosis induced by chronic intermittent hypoxia are attenuated by deficiency of stearoyl coenzyme A desaturase. Circ Res 2008; 103 : 1173-80. (10.) Li J, Savransky V, Nanayakkara A, Smith PL, O'Donnell CP, Polotsky VY. Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia. J Appl Physiol 2007; 102 : 557-63. (11.) Polotsky VY, Patil SP, Savransky V, Laffan A, Fonti S, Frame LA, et al. Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity. Am J Respir Crit Care Med 2009; 179: 228-34. (12.) Parish JM, Adam T, Facchiano L. Relationship of metabolic syndrome and obstructive sleep apnea. J Clin Sleep Med 2007; 3 : 467-72. (13.) Okada M, Takamizawa A, Tsushima K, Urushihata K, Fujimoto K, Kubo K. Relationship between sleep-disordered breathing and lifestyle-related illnesses in subjects who have undergone health-screening. Intern Med 2006; 45 : 891-6. (14.) Newman AB, Nieto FJ, Guidry U, Lind BK, Redline S, Pickering TG, et al. Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study. Am J Epidemiol 2001; 154 : 50-9. (15.) Maekawa M, Shiomi T, Usui K, Sasanabe R, Kobayashi T. Prevalence of ischemic heart disease among patients with sleep apnea syndrome. Psychiatry Clin Neurosci 1998; 52 : 219-20. (16.) Levinson PD, McGarvey ST, Carlisle CC, Eveloff SE, Herbert PN, Millman RP. Adiposity and cardiovascular risk factors in men with obstructive sleep apnea. Chest 1993; 103 : 1336-42. (17.) Kono M, Tatsumi K, Saibara T, Nakamura A, Tanabe N, Takiguchi Y, et al. Obstructive sleep apnea syndrome is associated with some components of metabolic syndrome. Chest 2007; 131 : 1387-92. (18.) Tishler PV, Larkin EK, Schluchter MD, Redline S. Incidence of sleep-disordered breathing in an urban adult population: the relative importance of risk factors in the development of sleep-disordered breathing. Jama 2003; 289 : 2230-7. |
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