0
Original Research: SLEEP MEDICINE |

Obstructive Sleep Apnea, Hypertension, and Their Interaction on Arterial Stiffness and Heart Remodeling* FREE TO VIEW

Luciano F. Drager, MD; Luiz A. Bortolotto, MD, PhD; Adelaide C. Figueiredo, BSc; Bruno Caldin Silva, MS; Eduardo M. Krieger, MD, PhD; Geraldo Lorenzi-Filho, MD, PhD
Author and Funding Information

*From the Hypertension Unit (Drs. Drager, Bortolotto, and Krieger, and Mr. Silva) and Sleep Laboratory, Pulmonary Division (Ms. Figueiredo and Dr. Lorenzi-Filho), Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.

Correspondence to: Geraldo Lorenzi-Filho, PhD, Sleep Laboratory, Pulmonary Division, Heart Institute (InCor), University of São Paulo Medical School, Av Dr Enéas Carvalho de Aguiar, 44, CEP 05403–904, São Paulo, Brazil; e-mail: geraldo.lorenzi@incor.usp.br



Chest. 2007;131(5):1379-1386. doi:10.1378/chest.06-2703
Text Size: A A A
Published online

Study objectives: Obstructive sleep apnea (OSA) and hypertension are independently associated with increased stiffness of large arteries that may contribute to left ventricular (LV) remodeling. We sought to investigate the impact of OSA, hypertension, and their association with arterial stiffness and heart structure.

Design: We studied 60 middle-aged subjects classified into four groups according to the absence or presence of severe OSA with and without hypertension. All participants were free of other comorbidities. The groups were matched for age, sex, and body mass index.

Measurements and results: Full polysomnography, pulse-wave velocity (PWV), and transthoracic echocardiography were performed in all participants. Compared with normotensive subjects without OSA, PWV, left atrial diameter, interventricular septal thickness, LV posterior wall thickness, LV mass index, and percentage of LV hypertrophy had similar increases in normotensive OSA and patients with hypertension and no OSA (p < 0.05 for all comparisons), with a significant further increase in PWV, LV mass index, and percentage of LV hypertrophy in subjects with OSA and hypertension. Multivariate regression analysis showed that PWV was associated with systolic BP (p < 0.001) and apnea-hypopnea index (p = 0.002). The only independent variable associated with LV mass index was PWV (p < 0.0001).

Conclusions: Severe OSA and hypertension are associated with arterial stiffness and heart structure abnormalities of similar magnitude, with additive effects when both conditions coexist. Increased large arterial stiffness contributes to ventricular afterload and may help to explain heart remodeling in both OSA and hypertension.

Figures in this Article

Obstructive sleep apnea (OSA) is a common and frequently underdiagnosed condition characterized by recurrent episodes of partial or complete obstruction of the upper airway during sleep, decrease in oxygen saturation, and daytime somnolence.1OSA patients frequently have several risk factors for cardiovascular disease development, such as obesity, hypertension, and diabetes.24 These risk factors are entangled in such a way that it is difficult to isolate the relative contribution of OSA to cardiovascular risk. OSA is independently associated with several cardiovascular diseases, including hypertension, ischemic heart disease, atrial fibrillation, cerebrovascular disease, and heart failure.56 However, the magnitude of OSA effects, as compared to other risk factors for cardiovascular disease, is not well established.

Obstructive apneas are accompanied by recurrent hypoxia, arousals from sleep, and generation of exaggerated negative intrathoracic pressure that can directly or indirectly be harmful to the cardiovascular system by several pathways, such as sympathetic activation, inflammation, oxidative stress, and endothelial dysfunction.7The involvement of the structure and function of large arteries is an attractive unifying target. We have described the presence of early signs of atherosclerosis in otherwise healthy OSA subjects8as characterized by increased arterial stiffness, evaluated by pulse-wave velocity (PWV). PWV is a sensitive and validated marker of cardiovascular risk, including premature coronary artery disease, atherosclerosis, stroke, and cardiovascular mortality.911 Increased PWV, independent of BP, contributes significantly to increased left ventricular (LV) afterload and to LV hypertrophy.1214 Evidence suggests that OSA is associated with LV hypertrophy; however, PWV was not measured in these studies.1517 In addition, hypertension and other confounding variables were not fully controlled.1517 Hypertension is a well-known cause of decreased vascular compliance and heart hypertrophy.1819 These alterations may be present even in patients treated for hypertension.20 OSA and hypertension are tightly linked,2 and the number of OSA patients with hypertension is extremely high, ranging from 35 to 70%.2125 Conversely, approximately 30% of patients presenting with hypertension also have OSA.22 Despite this evidence, the majority of OSA patients are not recognized.

We performed this study to compare arterial stiffness evaluated by PWV as well as left-chamber morphology as determined by echocardiographic measurements in severe OSA, hypertension, and their interaction. We tested the following hypotheses: (1) OSA is associated with increased arterial stiffness and heart remodeling similar in magnitude to that of treated hypertension; and (2) the association of OSA and treated hypertension has additive deleterious effects on arterial stiffness and heart remodeling. To this end, we carefully selected otherwise healthy subjects, free of other risk factors for cardiovascular disease, to evaluate the isolated effect of each variable of interest, namely OSA and hypertension.

We initially recruited consecutive patients from Sleep Laboratory, Heart Institute (InCor), University of São Paulo Medical School with suspected OSA and no other medical disorder except hypertension. During the study period, we screened 500 patients. The majority (94%) were excluded because of one or more comorbidities, including diabetes, smoking habit, and chronic use of medications. Control subjects and hypertension patients were recruited from the hospital staff and their relatives. The local Ethics Committee approved the protocol, and all participants gave written informed consent.

We only studied subjects with no OSA or severe OSA (apnea-hypopnea index [AHI] < 5 events/h and > 30 events/h, respectively). OSA patients had recent diagnoses and were not treated. The study design allowed us to isolate four groups, as follows: (1) volunteers without OSA and hypertension (control subjects); (2) OSA patients without hypertension; (3) non-OSA patients with hypertension; and (4) OSA patients with hypertension. The groups were matched for age (± 5 years), sex, and body mass index (BMI) [± 2 kg/m2]. Exclusion criteria involved age > 60 years; BMI > 40 kg/m2; diabetes mellitus; secondary hypertension; cerebrovascular, aortic, heart, and valvular heart diseases; renal failure; arrhythmias; smoking; and chronic use of nonsteroidal antiinflammatory drugs, including oral anticoagulants, and statins. Ten control subjects and 12 OSA patients had their PWV previously reported.8 All overlapped participants underwent transthoracic echocardiography and repeated PWV measurements.

All participants underwent a standard overnight polysomnography (EMBLA; Flagra hf. Medical Devices; Reykjavik, Iceland) as previously described.8 Apnea was defined as complete cessation of airflow for at least 10 s, associated with an arousal or oxygen desaturation of 3%. Hypopnea was defined as a significant reduction (> 50%) in respiratory signals for at least 10 s associated with an arousal or desaturation of 3%, as previously described.8

Hypertension was diagnosed according to current guidelines.26 BP measurements were determined on separate occasions by three or more readings of systolic and diastolic (phase V) BP obtained at 5-min intervals with a conventional mercury sphygmomanometer, after participants had been seated for at least 15 min. Experienced physicians who were not involved in the study performed all measurements. The cutoff point for hypertension was 140/90 mm Hg.26Additionally, all participants performed 20 min of continuous noninvasive BP recording using a Portapres device (TNO Biomedical Instrumentation; Amsterdam, the Netherlands)27 before analysis of arterial stiffness, in order to re-evaluate our previous classification in normotensive or hypertensive in the four groups. Means of six stable measurements during vascular measurements were used for the final analysis.

Resistant hypertension was considered when high BP could not be reduced to < 140/90 mm Hg with an appropriate triple-drug regimen, including an oral diuretic with all agents administered at or near maximal dosages. All patients with resistant hypertension performed a previous evaluation to discard secondary hypertension. In our study, all hypertensive patients were receiving medications for BP control. In order to avoid acute effects of antihypertensive treatment, patients did not receive medications on the day PWV was measured, as previously described.2829

All participants underwent echocardiography and had vascular properties evaluated while awake within 2 weeks after undergoing polysomnography. Carotid-femoral PWV was analyzed with a noninvasive automatic device (Complior; Colson; Garges les Gonesses, France) by an experienced observer blinded to the clinical characteristics. Briefly, common carotid artery and femoral artery pressure waveforms were recorded noninvasively using a pressure-sensitive transducer (TY-306-Fukuda; Fukuda; Tokyo, Japan). The distance between the recording sites (D) was measured, and PWV was automatically calculated as PWV = D/t, where (t) means pulse transit time.30 Measurements were repeated over 10 different cardiac cycles, and the mean is used for the final analysis. Because systolic BP has direct influence on PWV, we also adjusted PWV for the mean systolic BP in all groups.

Echocardiographic images were obtained in the parasternal long-axis and short-axis, the apical long-axis, and the apical four-chamber view according to current standards,31by personnel blinded to the results of polysomnography and PWV. Left atrial diameter (LAD), LV end-diastolic internal dimension (LVEDD), LV end-systolic internal dimension, interventricular septal thickness (IVST), and LV posterior wall thickness (LVPWT) were determined from M-mode measurements. In addition, we obtained the LV ejection fraction and LV mass measurements. LV mass index was calculated as 0.8 × (1.04[(IVST + LVPWT + LVEDD)3 – (LVEDD)3]) + 0.6 g/body surface area. LV mass indices > 134 g/m2 in men and > 110 g/m2 in women were considered indicative of hypertrophy.32 Blood samples were drawn for determination of glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, and RBC count.

Statistical Analysis

Data were analyzed with statistical software (SPSS 10.0; SPSS; Chicago, IL). Quantitative variables are expressed as mean ± SEM. Comparisons between groups were made by two-way analysis of variance. The Bonferroni correction was used for multiple comparisons. A multivariate analysis was performed with age, BMI, systolic and diastolic BP, pulse pressure, cholesterol and glucose levels, AHI, total sleep time with saturation < 90%, and minimal oxygen saturation as the independent variables and PWV as the dependent variable. In addition, to investigate possible factors associated with LV mass index, we performed multivariate analysis with age, BMI, systolic and diastolic BP, pulse pressure, PWV, AHI, total sleep time with saturation < 90%, and minimal oxygen saturation as independent variables; p < 0.05 was considered significant.

The four groups studied were similar in respect to several of the well-known risk factors for cardiovascular diseases, including age, sex, BMI, and cholesterol levels (Table 1 ). Glucose levels were in the normal range in all participants. Control subjects and normotensive OSA patients were not receiving any medications. In the hypertension and the OSA-plus-hypertension groups, the number of antihypertensive medications, the time from hypertension diagnosis, as well as BP values at the time of the study were similar (Table 1). The percentage of hypertensive patients who were receiving diuretics, β-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor antagonists was also similar in all groups (data not shown).

PWV was 8.7 ± 0.3 m/s for control subjects, 10.2 ± 0.2 m/s for the OSA group, 10.7 ± 0.3 m/s for the hypertension group, and 12.1 ± 0.4 m/s for the OSA-plus-hypertension group (p < 0.0001). Compared with control subjects, PWV had a similar increase in the OSA and hypertension groups (p < 0.05); a further significant increase was observed in OSA-plus-hypertension subjects (p < 0.01). These results were similar and the differences remained significant after adjustments for systolic BP (Fig 1 ).

Echocardiography measurements were significantly different among groups (Fig 2 ). Compared with control subjects, LAD, IVST, LVPWT, and LV mass index had a similar increase in the OSA and hypertension groups (p < 0.05 for all parameters). A further increase in LV mass index (p < 0.05) and percentage of LV hypertrophy (p < 0.05) was observed in OSA-plus-hypertension patients (Fig 2, bottom left, E, and bottom right, F).

In the multivariate analysis performed on the whole study sample, PWV was positively related to systolic BP (r = 0.62; p < 0.001) and AHI (r = 0.40; p = 0.002). The only variable independently associated with LV mass index in multivariate analysis was PWV (Fig 3 ).

Our study provides several new insights on the association between OSA and cardiovascular diseases: (1) OSA is not only associated with increased arterial stiffness as previously shown8 but also with early signs of heart remodeling as demonstrated by increased LAD, IVST, LVPWT, LV mass index, and percentage of LV hypertrophy; (2) the magnitude of arterial stiffness and heart remodeling associated with OSA is similar to that for treated hypertension; (3) the coexistence of OSA and treated hypertension is associated with additive effects on arterial stiffness as well as heart remodeling, particularly with regards to LV mass index and percentage of LV hypertrophy; (4) arterial stiffness is an important factor associated with LV mass index in both OSA and hypertension patients, suggesting a possible mechanism involved in heart remodeling in OSA. The results cannot be explained by any other cardiovascular risk factors that were controlled in this study.

PWV is an accurate, noninvasive index of arterial stiffness and is an independent marker for cardiovascular disease.33 Several factors including aging, smoking, hypercholesterolemia, diabetes mellitus as well as hypertension alter the structural properties and function of the vascular wall.33 OSA patients have several risk factors for increased PWV, making it difficult to isolate the relative role of OSA in vascular alterations. Studies8,34have showed a clear association between OSA and impaired arterial properties in otherwise apparently healthy patients. Our study extend these previous findings by showing that the magnitude of PWV alterations associated with severe OSA were similar to that observed in treated hypertension. In addition, we observed a further increase in PWV when both conditions were present. Our middle-aged OSA and hypertension groups had mean values of PWV of approximately 10.4 m/s, similar to those found in sedentary, healthy people who were 15 to 20 years older.3536 When OSA was associated with hypertension, the mean PWV was 12.1 m/s, comparable to the values encountered in the highest risk subgroup for all-cause and cardiovascular mortality of patients with hypertension and end-stage renal disease.3738 The information provided by the present study is of particular relevance to clinical practice because the association of OSA and hypertension among OSA patients is very common, ranging from 35 to 70%.2125

The link between OSA, LV dysfunction, and congestive heart failure was suggested by epidemiologic studies.5 Previous studies1517,39that were not able to fully control for confounding variables suggested that OSA is associated with changes is heart structure, including LV hypertrophy. Usui et al40 recently reported in a well-controlled study that OSA was associated with an increased prevalence of LV hypertrophy in patients with nonischemic dilated cardiomyopathy. Our study extends these findings by showing early structural changes associated with severe OSA patients with no overt cardiovascular disease. The echocardiographic pattern in our apparently healthy OSA patients shares several similarities with those described by Usui et al.40 Accordingly, we found greater IVST and LVPWT for a given end-diastolic dimension, indicating concentric hypertrophy. Interestingly enough, all the heart structure findings observed in severe OSA were similar to those of hypertension (Fig 2). We also found additive effects on LV mass index (Fig 2, bottom left, E) and percentage of LV hypertrophy (Fig 2, bottom right, F) in patients with OSA and hypertension.

To the best of our knowledge, this is the first study to show early signs of LA remodeling characterized by a discrete but significant LA increase in OSA patients compared with appropriate control subjects (Fig 2, top left, A). Cloward et al39 previously reported that LA enlargement is common in OSA patients, but the study included patients with several confounding factors and did not include a control group. An enlarged left atrium is an independent risk factor for atrial fibrillation.41Therefore, our data may help to explain the strong association between OSA and atrial fibrillation that has been reported.42

Heart remodeling associated with OSA can be explained by several mechanisms. Acutely, recurrent hypoxia may have a direct effect on the aorta, promoting reduction in the amount of glycosaminoglycans and collagen,43and also on the heart.4445 During obstructive apneas, the patients generate negative intrathoracic pressure against an occluded upper airway, which increases LV transmural pressure, an important determinant of LV afterload.46 Cyclic increases in the BP at the end of apnea also contribute to increase LV afterload.46 Our study suggests that PWV is a possible mechanism that chronically contributes to heart remodeling in OSA patients (Fig 3). In normal circumstances, the aorta and some of the proximal large vessels store approximately 50% of the LV stroke volume during systole and act as an elastic buffering chamber (the Windkessel function).,1314 Increased arterial stiffness observed in OSA patients with and without hypertension contributes to increased LV afterload, which ultimately leads to increased LV mass and LAD. This is a well-known mechanism in hypertension47; and, accordingly with our results, the same seems to occur with OSA, with and without hypertension.

Our study has some limitations. First, we did not perform a detailed evaluation of diastolic function of the heart, which has been shown to be altered in OSA patients.48Second, the direct comparison of the effects of two distinct conditions (OSA and hypertension) must be made with caution. All OSA patients had a severe disease that was not being treated, whereas all hypertension patients were receiving treatment (although their mean systolic BP were not fully controlled, remaining in stage 1 hypertension). However, it is well recognized that hypertensive patients receiving optimal treatment present higher PWV and are at increased risk for cardiovascular disease than normotensive patients.49 Therefore, our study design corresponds to what is commonly seen in clinical practice.

In conclusion, the results of our study are in line with previous findings and extend the current knowledge by showing that severe OSA and treated hypertension are associated with vascular impairment and heart remodeling of a similar magnitude. These conditions have additive effects and direct influences on arterial stiffness and heart structure, suggesting the potential harmful effects for cardiovascular diseases, including atrial fibrillation and heart failure progression.

Abbreviations: AHI = apnea-hypopnea index; BMI = body mass index; IVST = interventricular septal thickness; LAD = left atrial diameter; LV = left ventricular; LVEDD = left ventricular end-diastolic internal dimension; LVPWT = left ventricular posterior wall thickness; OSA = obstructive sleep apnea; PWV = pulse-wave velocity

This study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and the E. J. Zerbini Foundation.

The authors have no conflicts of interest to disclose.

Table Graphic Jump Location
Table 1. Patient Characteristics*
* 

Values are presented as mean ± SEM or %.

 

Different from control subjects and OSA groups (p < 0.001).

 

Different from control subjects and hypertension groups (p < 0.001). The remained variables were not significant (p < 0.05).

Figure Jump LinkFigure 1. PWV after adjustments for systolic BP in control subjects, normotensive OSA patients, hypertensive subjects without OSA (hypertension [HTN]), and OSA patients with hypertension (OSA + HTN). Data are shown as mean ± SEM. *p < 0.0001 vs control subjects; **p < 0.01 vs control subjects; ***p < 0.01 vs OSA and hypertension groups.Grahic Jump Location
Figure Jump LinkFigure 2. Echocardiographic parameters of the four groups: LAD (top left, A); LVEDD (top right, B); IVST (center left, C); LVPWT (center right, D); LV mass index (bottom left, E); and LV hypertrophy (bottom right, F). Data are shown as mean (± SEM). *p < 0.05; **p < 0.0001. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location
Figure Jump LinkFigure 3. Correlations between LV mass index and PWV in the four groups. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location

We are very grateful to Professor Robert Skomro for his suggestions and critical review of the manuscript.

Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force.Sleep1999;22,667-689. [PubMed]
 
Peppard, PE, Young, T, Palta, M, et al Prospective study of the association between sleep-disordered breathing and hypertension.N Engl J Med2000;342,1378-1384. [PubMed] [CrossRef]
 
Drager, LF, Pereira, AC, Barreto-Filho, JA, et al Phenotypic characteristics associated with hypertension in patients with obstructive sleep apnea.J Hum Hypertens2006;20,523-528. [PubMed]
 
Reichmuth, KJ, Austin, D, Skatrud, JB, et al Association of sleep apnea and type II diabetes: a population-based study.Am J Respir Crit Care Med2005;172,1590-1595. [PubMed]
 
Young, T, Peppard, P, Palta, M, et al Population-based study of sleep-disordered breathing as a risk factor for hypertension.Arch Intern Med1997;157,1746-1752. [PubMed]
 
Shahar, E, Whitney, CW, Redline, S, et al Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study.Am J Respir Crit Care Med2001;163,19-25. [PubMed]
 
Wolk, R, Kara, T, Somers, VK Sleep-disordered breathing and cardiovascular disease.Circulation2003;108,9-12. [PubMed]
 
Drager, LF, Bortolotto, LA, Lorenzi, MC, et al Early signs of atherosclerosis in obstructive sleep apnea.Am J Respir Crit Care Med2005;172,613-618. [PubMed]
 
van Popele, NM, Grobbee, DE, Bots, ML, et al Association between arterial stiffness and atherosclerosis: the Rotterdam Study.Stroke2001;32,454-460. [PubMed]
 
Mattace-Raso, FU, van der Cammen, TJ, Hofman, A, et al Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study.Circulation2006;113,657-663. [PubMed]
 
Willum-Hansen, T, Staessen, JA, Torp-Pedersen, C, et al Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population.Circulation2006;113,664-670. [PubMed]
 
Belz, GG Elastic properties and Windkessel function of the human aorta.Cardiovasc Drugs Ther1995;9,73-83. [PubMed]
 
Nichols, WW Clinical measurement of arterial stiffness obtained from noninvasive pressure waveforms.Am J Hypertens2005;18,3S-10S. [PubMed]
 
Weber, T, Auer, J, O’Rourke, MF, et al Arterial stiffness, wave reflections, and the risk of coronary artery disease.Circulation2004;109,184-189. [PubMed]
 
Noda, A, Okada, T, Yasuma, F, et al Cardiac hypertrophy in obstructive sleep apnea syndrome.Chest1995;107,1538-1544. [PubMed]
 
Hedner, J, Ejnell, H, Caidahl, K Left ventricular hypertrophy independent of hypertension in patients with obstructive sleep apnea.J Hypertens1990;8,941-946. [PubMed]
 
Shivalkar, B, Van de Heyning, C, Kerremans, M, et al Obstructive sleep apnea syndrome: more insights on structural and functional cardiac alterations, and the effects of treatment with continuous positive airway pressure.J Am Coll Cardiol2006;47,1433-1439. [PubMed]
 
Folkow, B Physiological aspects of primary hypertension.Physiol Rev1982;62,347-504. [PubMed]
 
Kazzam, E, Ghurbana, BA, Obineche, EN, et al Hypertension–still an important cause of heart failure?J Hum Hypertens2005;19,267-275. [PubMed]
 
de Simone, G, Kitzman, DW, Chinali, M, et al Left ventricular concentric geometry is associated with impaired relaxation in hypertension: the HyperGEN study.Eur Heart J2005;26,1039-1045. [PubMed]
 
Millman, RP, Redline, S, Carlisle, CC, et al Daytime hypertension in obstructive sleep apnea: prevalence and contributing risk factors.Chest1991;99,861-866. [PubMed]
 
Young, T, Peppard, PE, Gottlieb, DJ Epidemiology of obstructive sleep apnea: a population health perspective.Am J Respir Crit Care Med2002;165,1217-1239. [PubMed]
 
Silverberg, DS, Oksenberg, A, Iaina, A Sleep related breathing disorders are common contributing factors to the production of essential hypertension but are neglected, underdiagnosed, and undertreated.Am J Hypertens1997;10,1319-1325. [PubMed]
 
Baguet, JP, Hammer, L, Levy, P, et al Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients.J Hypertens2005;23,521-527. [PubMed]
 
Logan, AG, Perlikowski, SM, Mente, A, et al High prevalence of unrecognized sleep apnea in drug-resistant hypertension.J Hypertens2001;19,2271-2277. [PubMed]
 
Chobanian, AV, Bakris, GL, Black, HR, et al Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: national Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee: seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.Hypertension2003;42,1206-1252. [PubMed]
 
Imholz, BP, Langewouters, GJ, van Montfrans, GA, et al Feasibility of ambulatory, continuous 24-hour finger arterial pressure recording.Hypertension1993;21,65-73. [PubMed]
 
Bortolotto, LA, Blacher, J, Kondo, T, et al Assessment of vascular aging and atherosclerosis in hypertensive subjects: second derivative of photoplethysmogram versus pulse wave velocity.Am J Hypertens2000;13,165-171. [PubMed]
 
Bortolotto, LA, Safar, ME, Billaud, E, et al Plasma homocysteine, aortic stiffness, and renal function in hypertensive patients.Hypertension1999;34,837-842. [PubMed]
 
Asmar, R, Benetos, A, Topouchian, J, et al Assessment of arterial distensibility by automatic pulse wave velocity measurement: validation and clinical application studies.Hypertension1995;26,485-490. [PubMed]
 
Lang, RM, Bierig, M, Devereux, RB, et al American Society of Echocardiography’s Nomenclature and Standards Committee; Task Force on Chamber Quantification; American College of Cardiology Echocardiography Committee; American Heart Association; European Association of Echocardiography, European Society of Cardiology: recommendations for chamber quantification.Eur J Echocardiogr2006;7,79-108. [PubMed]
 
Devereux, RB Detection of left ventricular hypertrophy by M-mode echocardiography: anatomic validation, standardization, and comparison to other methods.Hypertension1987;9,II19-II26. [PubMed]
 
Wang, YX, Fitch, RM Vascular stiffness: measurements, mechanisms and implications.Curr Vasc Pharmacol2004;2,379-384. [PubMed]
 
Minoguchi, K, Yokoe, T, Tazaki, T, et al Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea.Am J Respir Crit Care Med2005;172,625-630. [PubMed]
 
Vaitkevicius, PV, Fleg, JL, Engel, JH, et al Effects of age and aerobic capacity on arterial stiffness in healthy adults.Circulation1993;88,1456-1462. [PubMed]
 
O’Rourke, MF, Staessen, JA, Vlachopoulos, C, et al Clinical applications of arterial stiffness; definitions and reference values.Am J Hypertens2002;15,426-444. [PubMed]
 
Laurent, S, Boutouyrie, P, Asmar, R, et al Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients.Hypertension2001;37,1236-1241. [PubMed]
 
Blacher, J, Guerin, AP, Pannier, B, et al Impact of aortic stiffness on survival in end-stage renal disease.Circulation1999;99,2434-2439. [PubMed]
 
Cloward, TV, Walker, JM, Farney, RJ, et al Left ventricular hypertrophy is a common echocardiographic abnormality in severe obstructive sleep apnea and reverses with nasal continuous positive airway pressure.Chest2003;124,594-601. [PubMed]
 
Usui, K, Parker, JD, Newton, GE, et al Left ventricular structural adaptations to obstructive sleep apnea in dilated cardiomyopathy.Am J Respir Crit Care Med2006;173,1170-1175. [PubMed]
 
Parkash, R, Green, MS, Kerr, CR, et al Canadian Registry of Atrial Fibrillation: the association of left atrial size and occurrence of atrial fibrillation; a prospective cohort study from the Canadian Registry of Atrial Fibrillation.Am Heart J2004;148,649-654. [PubMed]
 
Gami, AS, Pressman, G, Caples, SM, et al Association of atrial fibrillation and obstructive sleep apnea.Circulation2004;110,364-367. [PubMed]
 
Helin, P, Garbarsch, C, Lorenzen, I Effects of intermittent and continuous hypoxia on the aortic wall in rabbits.Atherosclerosis1975;21,325-335. [PubMed]
 
Chen, L, Einbinder, E, Zhang, Q, et al Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats.Am J Respir Crit Care Med2005;172,915-920. [PubMed]
 
Fan, C, Iacobas, DA, Zhou, D, et al Gene expression and phenotypic characterization of mouse heart after chronic constant or intermittent hypoxia.Physiol Genomics2005;22,292-307. [PubMed]
 
Bradley, TD, Floras, JS Sleep apnea and heart failure: part I: obstructive sleep apnea.Circulation2003;107,1671-1678. [PubMed]
 
Izzo, JL, Jr, Gradman, AH Mechanisms and management of hypertensive heart disease: from left ventricular hypertrophy to heart failure.Med Clin North Am2004;88,1257-1271. [PubMed]
 
Arias, MA, Garcia-Rio, F, Alonso-Fernandez, A, et al Obstructive sleep apnea syndrome affects left ventricular diastolic function: effects of nasal continuous positive airway pressure in men.Circulation2005;112,375-383. [PubMed]
 
de Simone, G, Roman, MJ, Koren, MJ, et al Stroke volume/pulse pressure ratio and cardiovascular risk in arterial hypertension.Hypertension1999;33,800-805. [PubMed]
 

Figures

Figure Jump LinkFigure 1. PWV after adjustments for systolic BP in control subjects, normotensive OSA patients, hypertensive subjects without OSA (hypertension [HTN]), and OSA patients with hypertension (OSA + HTN). Data are shown as mean ± SEM. *p < 0.0001 vs control subjects; **p < 0.01 vs control subjects; ***p < 0.01 vs OSA and hypertension groups.Grahic Jump Location
Figure Jump LinkFigure 2. Echocardiographic parameters of the four groups: LAD (top left, A); LVEDD (top right, B); IVST (center left, C); LVPWT (center right, D); LV mass index (bottom left, E); and LV hypertrophy (bottom right, F). Data are shown as mean (± SEM). *p < 0.05; **p < 0.0001. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location
Figure Jump LinkFigure 3. Correlations between LV mass index and PWV in the four groups. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Patient Characteristics*
* 

Values are presented as mean ± SEM or %.

 

Different from control subjects and OSA groups (p < 0.001).

 

Different from control subjects and hypertension groups (p < 0.001). The remained variables were not significant (p < 0.05).

References

Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force.Sleep1999;22,667-689. [PubMed]
 
Peppard, PE, Young, T, Palta, M, et al Prospective study of the association between sleep-disordered breathing and hypertension.N Engl J Med2000;342,1378-1384. [PubMed] [CrossRef]
 
Drager, LF, Pereira, AC, Barreto-Filho, JA, et al Phenotypic characteristics associated with hypertension in patients with obstructive sleep apnea.J Hum Hypertens2006;20,523-528. [PubMed]
 
Reichmuth, KJ, Austin, D, Skatrud, JB, et al Association of sleep apnea and type II diabetes: a population-based study.Am J Respir Crit Care Med2005;172,1590-1595. [PubMed]
 
Young, T, Peppard, P, Palta, M, et al Population-based study of sleep-disordered breathing as a risk factor for hypertension.Arch Intern Med1997;157,1746-1752. [PubMed]
 
Shahar, E, Whitney, CW, Redline, S, et al Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study.Am J Respir Crit Care Med2001;163,19-25. [PubMed]
 
Wolk, R, Kara, T, Somers, VK Sleep-disordered breathing and cardiovascular disease.Circulation2003;108,9-12. [PubMed]
 
Drager, LF, Bortolotto, LA, Lorenzi, MC, et al Early signs of atherosclerosis in obstructive sleep apnea.Am J Respir Crit Care Med2005;172,613-618. [PubMed]
 
van Popele, NM, Grobbee, DE, Bots, ML, et al Association between arterial stiffness and atherosclerosis: the Rotterdam Study.Stroke2001;32,454-460. [PubMed]
 
Mattace-Raso, FU, van der Cammen, TJ, Hofman, A, et al Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study.Circulation2006;113,657-663. [PubMed]
 
Willum-Hansen, T, Staessen, JA, Torp-Pedersen, C, et al Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population.Circulation2006;113,664-670. [PubMed]
 
Belz, GG Elastic properties and Windkessel function of the human aorta.Cardiovasc Drugs Ther1995;9,73-83. [PubMed]
 
Nichols, WW Clinical measurement of arterial stiffness obtained from noninvasive pressure waveforms.Am J Hypertens2005;18,3S-10S. [PubMed]
 
Weber, T, Auer, J, O’Rourke, MF, et al Arterial stiffness, wave reflections, and the risk of coronary artery disease.Circulation2004;109,184-189. [PubMed]
 
Noda, A, Okada, T, Yasuma, F, et al Cardiac hypertrophy in obstructive sleep apnea syndrome.Chest1995;107,1538-1544. [PubMed]
 
Hedner, J, Ejnell, H, Caidahl, K Left ventricular hypertrophy independent of hypertension in patients with obstructive sleep apnea.J Hypertens1990;8,941-946. [PubMed]
 
Shivalkar, B, Van de Heyning, C, Kerremans, M, et al Obstructive sleep apnea syndrome: more insights on structural and functional cardiac alterations, and the effects of treatment with continuous positive airway pressure.J Am Coll Cardiol2006;47,1433-1439. [PubMed]
 
Folkow, B Physiological aspects of primary hypertension.Physiol Rev1982;62,347-504. [PubMed]
 
Kazzam, E, Ghurbana, BA, Obineche, EN, et al Hypertension–still an important cause of heart failure?J Hum Hypertens2005;19,267-275. [PubMed]
 
de Simone, G, Kitzman, DW, Chinali, M, et al Left ventricular concentric geometry is associated with impaired relaxation in hypertension: the HyperGEN study.Eur Heart J2005;26,1039-1045. [PubMed]
 
Millman, RP, Redline, S, Carlisle, CC, et al Daytime hypertension in obstructive sleep apnea: prevalence and contributing risk factors.Chest1991;99,861-866. [PubMed]
 
Young, T, Peppard, PE, Gottlieb, DJ Epidemiology of obstructive sleep apnea: a population health perspective.Am J Respir Crit Care Med2002;165,1217-1239. [PubMed]
 
Silverberg, DS, Oksenberg, A, Iaina, A Sleep related breathing disorders are common contributing factors to the production of essential hypertension but are neglected, underdiagnosed, and undertreated.Am J Hypertens1997;10,1319-1325. [PubMed]
 
Baguet, JP, Hammer, L, Levy, P, et al Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients.J Hypertens2005;23,521-527. [PubMed]
 
Logan, AG, Perlikowski, SM, Mente, A, et al High prevalence of unrecognized sleep apnea in drug-resistant hypertension.J Hypertens2001;19,2271-2277. [PubMed]
 
Chobanian, AV, Bakris, GL, Black, HR, et al Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: national Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee: seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.Hypertension2003;42,1206-1252. [PubMed]
 
Imholz, BP, Langewouters, GJ, van Montfrans, GA, et al Feasibility of ambulatory, continuous 24-hour finger arterial pressure recording.Hypertension1993;21,65-73. [PubMed]
 
Bortolotto, LA, Blacher, J, Kondo, T, et al Assessment of vascular aging and atherosclerosis in hypertensive subjects: second derivative of photoplethysmogram versus pulse wave velocity.Am J Hypertens2000;13,165-171. [PubMed]
 
Bortolotto, LA, Safar, ME, Billaud, E, et al Plasma homocysteine, aortic stiffness, and renal function in hypertensive patients.Hypertension1999;34,837-842. [PubMed]
 
Asmar, R, Benetos, A, Topouchian, J, et al Assessment of arterial distensibility by automatic pulse wave velocity measurement: validation and clinical application studies.Hypertension1995;26,485-490. [PubMed]
 
Lang, RM, Bierig, M, Devereux, RB, et al American Society of Echocardiography’s Nomenclature and Standards Committee; Task Force on Chamber Quantification; American College of Cardiology Echocardiography Committee; American Heart Association; European Association of Echocardiography, European Society of Cardiology: recommendations for chamber quantification.Eur J Echocardiogr2006;7,79-108. [PubMed]
 
Devereux, RB Detection of left ventricular hypertrophy by M-mode echocardiography: anatomic validation, standardization, and comparison to other methods.Hypertension1987;9,II19-II26. [PubMed]
 
Wang, YX, Fitch, RM Vascular stiffness: measurements, mechanisms and implications.Curr Vasc Pharmacol2004;2,379-384. [PubMed]
 
Minoguchi, K, Yokoe, T, Tazaki, T, et al Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea.Am J Respir Crit Care Med2005;172,625-630. [PubMed]
 
Vaitkevicius, PV, Fleg, JL, Engel, JH, et al Effects of age and aerobic capacity on arterial stiffness in healthy adults.Circulation1993;88,1456-1462. [PubMed]
 
O’Rourke, MF, Staessen, JA, Vlachopoulos, C, et al Clinical applications of arterial stiffness; definitions and reference values.Am J Hypertens2002;15,426-444. [PubMed]
 
Laurent, S, Boutouyrie, P, Asmar, R, et al Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients.Hypertension2001;37,1236-1241. [PubMed]
 
Blacher, J, Guerin, AP, Pannier, B, et al Impact of aortic stiffness on survival in end-stage renal disease.Circulation1999;99,2434-2439. [PubMed]
 
Cloward, TV, Walker, JM, Farney, RJ, et al Left ventricular hypertrophy is a common echocardiographic abnormality in severe obstructive sleep apnea and reverses with nasal continuous positive airway pressure.Chest2003;124,594-601. [PubMed]
 
Usui, K, Parker, JD, Newton, GE, et al Left ventricular structural adaptations to obstructive sleep apnea in dilated cardiomyopathy.Am J Respir Crit Care Med2006;173,1170-1175. [PubMed]
 
Parkash, R, Green, MS, Kerr, CR, et al Canadian Registry of Atrial Fibrillation: the association of left atrial size and occurrence of atrial fibrillation; a prospective cohort study from the Canadian Registry of Atrial Fibrillation.Am Heart J2004;148,649-654. [PubMed]
 
Gami, AS, Pressman, G, Caples, SM, et al Association of atrial fibrillation and obstructive sleep apnea.Circulation2004;110,364-367. [PubMed]
 
Helin, P, Garbarsch, C, Lorenzen, I Effects of intermittent and continuous hypoxia on the aortic wall in rabbits.Atherosclerosis1975;21,325-335. [PubMed]
 
Chen, L, Einbinder, E, Zhang, Q, et al Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats.Am J Respir Crit Care Med2005;172,915-920. [PubMed]
 
Fan, C, Iacobas, DA, Zhou, D, et al Gene expression and phenotypic characterization of mouse heart after chronic constant or intermittent hypoxia.Physiol Genomics2005;22,292-307. [PubMed]
 
Bradley, TD, Floras, JS Sleep apnea and heart failure: part I: obstructive sleep apnea.Circulation2003;107,1671-1678. [PubMed]
 
Izzo, JL, Jr, Gradman, AH Mechanisms and management of hypertensive heart disease: from left ventricular hypertrophy to heart failure.Med Clin North Am2004;88,1257-1271. [PubMed]
 
Arias, MA, Garcia-Rio, F, Alonso-Fernandez, A, et al Obstructive sleep apnea syndrome affects left ventricular diastolic function: effects of nasal continuous positive airway pressure in men.Circulation2005;112,375-383. [PubMed]
 
de Simone, G, Roman, MJ, Koren, MJ, et al Stroke volume/pulse pressure ratio and cardiovascular risk in arterial hypertension.Hypertension1999;33,800-805. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543