High Blood Press Cardiovasc Prev DOI 10.1007/s40292-015-0088-1
ORIGINAL ARTICLE
Evaluation of Blood Pressure Control in an Obstructive Sleep Apnea Population Followed in Cardiology Pascal Delsart1 • Marc Takla1 • Philippe Marboeuf2 • Gonzague Claisse1 • Natalia Kpogbemabou1 • Remy Lubret3 • Medhi Hattabi4 • Claire Mounier-Vehier1
Received: 7 March 2015 / Accepted: 9 April 2015 Ó Springer International Publishing Switzerland 2015
Abstract Objective Obstructive sleep apnea (OSA) is the most common factor involved in uncontrolled blood pressure (BP). Management of OSA is part of cardiologist work. We have few data on BP control in a population of OSA followed by cardiologists. Aim We evaluated the prevalence of effective BP control using ambulatory measurement in a population of patients followed in cardiology. Methods Data from 69 OSA patients treated for more than 6 months by continuous positive airway pressure (CPAP) were collected prospectively from March 2012 until December 2012. These patients were divided into 2 groups according to the results of 24-h ambulatory BP monitoring (ABPM). Controlled BP was defined as a 24 h BP \130/80 mmHg. Results All patients were hypertensive. 44 patients (63 %) had uncontrolled hypertension (HTN). The onset of OSA (p = 0.01) and persistent daytime sleepiness appeared as predictors of uncontrolled BP. Systolic BP (SBP) during consultation and all the ABPM variables were higher in uncontrolled BP patients. Uncontrolled BP was
& Pascal Delsart [email protected] 1
Service de me´decine vasculaire et Hypertension arte´rielle, Hoˆpital Cardiologique, CHRU Lille, Boulevard Pr Leclercq, 59037 Lille Cedex, France
2
Cabinet Magellan a` He´nin-Beaumont, He´nin-Beaumont, France
3
Hoˆpital Duchene a` Boulogne-sur-mer, Boulogne-sur-mer, France
4
Cabinet de Cardiologie de Villeuneuve d’Ascq, Villeuneuve d’Ascq, France
associated with greater left ventricular mass (p = 0.02) and greater diameter of the ascending aorta (p = 0.04). Conclusion Control of HTN should be evaluated in all OSA patients, using ABPM. The onset of OSA and high SBP during consultation are both factors associated with uncontrolled BP in this population. Repeating ABPM should be of interest for the follow up of these patients. Keywords Sleep apnea Ambulatory monitoring Blood pressure control
1 Introduction Optimization of cardiovascular risk needs a joint management of cardiovascular risk factors and pulmonary disease as chronic obstructive pulmonary disease and obstructive sleep apnea (OSA) [1]. The relationship between OSA and arterial hypertension (HTN) is now well established. OSA is present in 35 % of hypertensives and 80 % of patients with resistant HTN are apneic [2]. All patients carriers of OSA should be screened for HTN, since OSA is an independent risk factor for the development of HTN [3].We know that the link between these two diseases is of ‘‘dose response’’ type. Severe OSA is associated with both higher prevalence of HTN and the severity of sleep disorders is linearly associated with systolic and diastolic BP [4]. Although OSA is not yet clearly recognized as being an independent cardiovascular risk factor, numerous studies have shown that OSA increases the occurrence of cardiac and cerebral events [5]. Therefore, the management of OSA by the cardiologist is very important. It appears as an additional risk factor to take into consideration in the cardiological consultation. The use of ambulatory BP monitoring (ABPM) is the cornerstone in the management
P. Delsart et al.
of HTN. In OSA, the increase in BP is often nocturnal and therefore escapes the consultation data. Despite the high prevalence of OSA in the population of patients followed in cardiology, data on effective BP control and its predictors are quite rare. It seemed interesting to evaluate the predictors of BP control using ambulatory measurements.
2.3 OSA Data The onset of CPAP and duration of CPAP use were collected. All patients were asked about the presence of insomnia and persistent daytime sleepiness. No standardized sleepiness scale was used. 2.4 Laboratory Data
2 Methods Data were prospectively collected by 7 cardiologists consecutively from March 2012 to December 2012. OSA patients were included during follow-up consultation. This study was designed for a population of stable patients, defined as follows: the patient is treated by continuous positive airway pressure (CPAP) for more than 6 months; the patient has not been hospitalized for an acute cardiovascular event or acute respiratory disease in the last 6 months. After analyzing the data according to 24 h ABPM, the population was divided in 2 groups: Group 1 consisted of patients who had a controlled 24 h BP (BP level below 130/80 mmHg) and group 2 consisted of patients with uncontrolled 24 h BP. 2.1 Clinical Data Cardiovascular history was defined by previous documented atrial fibrillation, stroke, hospitalization for heart failure, coronary artery disease (acute coronary syndrome, myocardial revascularization), C50 % carotid stenosis, peripheral arterial disease (peripheral vascular intervention, lower extremity arterial revascularization), abdominal aortic aneurysm [30 mm). The cardiovascular risk factors (smoking status, dyslipidemia, HTN, type 2 diabetes mellitus, family history of premature cardiovascular disease) and the height, weight, body mass index and waist circumference were collected. A patient was considered as active smoker if present smoking or stopped for less than 3 years. 2.2 BP Data BP was taken during consultation after 10 min of sitting rest with a size-adapted cuff, using an electronic device (Data scope Acutor Plus deviceÒ). The average of 3 measurements was used for analysis. ABPM was performed in all patients, with a cuff adapted (Spacelabs Medical 90207Ò). BP measurement was made of every 15 min. The daytime BP was measured between 6 am and 22 pm and the nighttime BP was measured between 22 p.m. and 6 a.m. The dipping status was defined as a drop in BP over 10 % between the average daytime BP and the average nighttime BP for the systolic and/or the diastolic BP [6].
Renal function was assessed by glomerular filtration rate according to the MDRD formula [7]. Each patient received a total lipid profile including LDL, HDL, triglycerides, and fasting glucose level. 2.5 Antihypertensive Drugs For each patient, data for antihypertensive drugs classes were collected, including: angiotensin converting enzyme (ACE) inhibitors, Angiotensin II receptor blockers (ARBs), beta blockers, calcium channel blockers, thiazide diuretics, aldosterone antagonists, centrally acting drugs, alpha adrenergic blockers. The number of antihypertensive drugs was also identified for each patient as defining a score of antihypertensive treatment. 2.6 Electrocardiogram Data For each patient, the electrocardiogram was analyzed. It was performed at the time of the cardiologist consultation’, ie at least 6 months after CPAP therapy. Information about sinus rhythm and left ventricular hypertrophy were collected [8]. Left ventricular hypertrophy is defined by Sokolow-Lyon index [35 mm. 2.7 Echocardiographic Data The following echocardiographic data were collected: left ventricular ejection fraction, left ventricular mass (g/m2), left atrium area and diameter, and diameter of the ascending aorta. The echocardiogram was performed at the time of the cardiologist consultation’, ie at least 6 months after CPAP therapy.
3 Statistical Method Statistical analyzes were made using GraphPad SoftwareÒ. Continuous variables are expressed as mean ± standard deviation. Categorical data are expressed as a percentage. Comparison of two samples was made by non parametric tests. P \ 0.05 was retained as significant for all the tests.
Evaluation of Blood Pressure Control
The aim of our study was to evaluate the BP control in an OSA population having a regular follow up in cardiology. 94 % of patients were hypertensive in our work, ie the patients were under antihypertensive medication at the
inclusion or they have a clinical casual BP upper than 140/90 mmHg at rest without drug. Our study showed that around two thirds of the patients were not controlled for BP. Controlled BP has long been recognized as a factor in reducing mortality and cardiovascular morbidity (either primary or secondary prevention). The control of cardiovascular risk factors is a priority in the follow up patients. HTN control is unfortunately too low, around 50 % of patients in France (French League Against Hypertension Survey). Among the factors often implicated in uncontrolled BP, two are major: poor therapeutic compliance and OSA [9]. CPAP treatment is efficacy for both improving the quality of life and decreasing cardiovascular morbidity and mortality [10]. Although, it seems to have a moderate effect on lowering BP, except in cases of severe HTN or severe OSA [11, 12]. In this population, there is also a high prevalence of other factors recognized as responsible for uncontrolled BP, namely diabetes and abdominal obesity. There is no difference regarding the dipping pattern between the two groups. The vascular complications of OSA may also explain uncontrolled BP. Indeed, OSA promotes the development of microangiopathic and macroangiopathic lesions [13, 14]. We found a higher left ventricular mass in uncontrolled hypertensive as previously described [15, 16]. The severity of left ventricular hypertrophy is correlated with transient nocturnal oxygen desaturation. One study showed a significant reduction of left ventricular hypertrophy after 6 months of treatment with CPAP. We also found a significant difference in the diameter of the ascending aorta between the two groups. It was previously shown that OSA could favor the development of ascending aortic aneurysm, the main mechanism being the
Table 1 Characteristics of the population
Clinical and demographic data
Group 1 (controlled BP) n = 25
Group 2 (uncontrolled BP) n = 44
p
Age (years) Male/female (n)
56.4 ± 8.7 18/7
58.8 ± 8.9 37/7
0.2 0.2
BMI (kg/m2)
33.4 ± 6.2
33.4 ± 7.4
0.9
4 Results Data from 69 patients were collected. Sixty-four patients intake an anti hypertensive drug at the inclusion. Among the five patients without any anti hypertensive drug, 4 patients were not hypertensive defined as a clinical casual BP under 140 mmHg for the systolic and under 90 mmHg for the diastolic at rest. 2 patients on the four free of drug had both clinical and 24-h ambulatory BP value in the normal range. In the entire population, 44 patients (63 %) have uncontrolled BP (systolic BP [130 mmHg and/or diastolic BP [80 mmHg on 24-h ABPM). Among baseline characteristics, BP control is not correlated with age, gender or BMI (Table 1). None other usual cardiovascular risk factor was associated with BP control. Patients previously hospitalized for heart failure had a better BP control. The onset of CPAP use was statistically higher in uncontrolled BP patients (Table 2). We noted no difference between the two groups for the different therapeutic classes used in each group (Table 3). The uncontrolled BP group was associated with a greater left ventricular mass (p = 0.02), a greater diameter of the ascending aorta (p = 0.04), a higher HDL-cholesterol level (p = 0.03) (Table 4). Systolic BP during consultation and all the ABPM variables were higher in group 2 (Table 5).
5 Discussion
Abdominal circumference (cm)
121.1 ± 19.2
116 ± 25.6
0.38
Active smoker
6 (24 %)
11 (25 %)
0.9
Dyslipidemia
11 (60 %)
25 (56.8 %)
0.8
HTN
25 (100 %)
44 (100 %)
0.2
Type 2 diabetes mellitus
9 (36 %)
21 (47.7 %)
0.3
Family history of CV disease
6 (25 %)
7 (15.9 %)
0.4
Atrial fibrillation
1 (4 %)
4 (9 %)
0.4
Stroke
2 (8 %)
4 (9 %)
0.8
CAD
12 (48 %)
22 (48 %)
0.8
PAD
4 (16 %)
8 (18 %)
0.8
BMI body mass index, BP blood pressure, CAD coronary arterial disease, CV Cardiovascular, HTN hypertension, PAD peripheral arterial disease
P. Delsart et al. Table 2 OSA data
OSA
Group 1 (controlled BP) n = 25
Group 2 (uncontolled BP) n = 44
p
Onset of CPAP use (years)
3.6 ± 3.27
6.3 ± 5.06
0.01
Duration of CPAP use (hours/night)
6.7 ± 1.4
6.8 ± 1.6
0.8
Insomnia
3 (12 %)
12 (27 %)
0.14
Daytime sleepiness
2 (8 %)
11 (25 %)
0.08
BP blood pressure, CPAP continuous positive airway pressure, OSA obstructive sleep apnea
Table 3 Therapeutic data
Antihypertensive drugs
Group 1 (controlled BP) n = 25
Group 2 (uncontrolled BP) n = 44
p
ACE inhbitors or ARBs
21 (84 %)
40 (90 %)
0.3
Beta blockers
17 (68 %)
31 (70 %)
0.8
Calcium channel blockers
11 (44 %)
25 (56 %)
0.3
Thiazide diuretics
7 (28 %)
19 (43 %)
0.2
Aldosterone antagonists Centrally acting drugs
4 (16 %) 1 (4 %)
12 (27 %) 5 (11 %)
0.3 0.3
Alpha adrenergic blockers
2 (8 %)
0 (0 %)
0.05
Antihypertensive score
2.56 ± 1.3
2.95 ? 1.4
0.2
VKA
1 (4 %)
5 (11 %)
0.6
Statin
12 (48 %)
27 (61 %)
0.3
Antiplatelet therapy
12 (48 %)
20 (44 %)
0.8
ACE inhibitors angiotensin converting enzyme inhibitors, ARBs angiotensin II receptor blockers, BP blood pressure, VKA vitamin K antagonists
Table 4 Laboratory and echocardiographic data
Laboratory and ultrasonographic data Creatinine (mg/l)
Group 1 (controlled BP) n = 25 9.1 ± 3.2
2
Gfr (ml/min/1.73 m ) Fasting glucose level (g/l)
Group 2 (uncontrolled BP) n = 44
p
10.4 ± 4.3
0.19
96 ± 21
87 ± 29
0.18
1.07 ± 0.2
1.21 ± 0.46
0.13
HDL-cholesterol (g/l)
0.46 ± 0.13
0.40 ± 0.08
0.03
LDL-cholesterol (g/l)
1.02 ± 0.35
1.14 ± 0.36
0.19
Triglyceridemia (g/l) Echocardiographic data
1.38 ± 0.47
1.72 ± 1.14
0.15 1.5
LVEF (%)
56 ± 10
59 ± 8
LA area (cm2)
22 ± 4
22 ± 5
0.8
Ascending aorta diameter (mm)
31 ± 3.7
34 ± 4.6
0.04
LV mass (g/m2)
83 ± 13
92 ± 16
0.02
BP blood pressure, Gfr glomerular filtration rate, LA left atrium, LV left ventricular, LVEF left ventricular ejection fraction
repetition of transmural pressure related with obstructive events [17, 18]. Severe OSA may be a factor of the rapid expansion of the thoracic aortic aneurysm. We did not found a significant difference in the antihypertensive drugs between the 2 groups. Some studies have suggested that the prescription of beta blockers may be helpful in OSA patients. In our study, the distribution of beta-blockers was homogeneous in both groups. The
cardiometabolic effects of CPAP use has already been described in obese males with OSA [19]. In this work, the HDL-cholesterol level was significantly higher in the BP control group. A population based study found a small improvement in HDL cholesterol after 6 months of CPAP therapy [20]. The magnitude of cholesterol change with CPAP was more evident in patients with abnormal initial value and in patients with good compliance.
Evaluation of Blood Pressure Control Table 5 Blood pressure data (clinic and ABPM)
Data on hypertension
Group 1 (controlled BP) n = 25
Group 2 (uncontrolled BP) n = 44
p
Clinic SBP (mmHg)
129 ± 14
141 ± 6
0.004
Clinic DBP (mmHg)
79 ± 9
80 ± 10
0.5
Clinic HR (bpm)
74 ± 14
74 ± 14
0.8
24-h SBP (mmHg)
119 ± 7
143 ± 14
0.0001
24-h DBP (mmHg)
72 ± 5
83 ± 10
0.0001
24-h HR (bpm)
72 ± 10
73 ± 14
0.7
24-h mean BP (mmHg)
88 ± 5
102 ± 11
0.0001
Dipping n, (%)
15 (60)
27 (61)
0.9
Daytime SBP (mmHg)
124 ± 8
147 ± 16
0.0001
Daytime DBP (mmHg)
76 ± 7
86 ± 12
0.0004
Daytime HR (bpm) Daytime mean BP (mmHg)
75 ± 11 92 ± 7
76 ± 12 106 ± 12
0.9 0.0001
Nighttime SBP (mmHg)
108 ± 7
132 ± 15
0.0001
Nighttime DBP (mmHg)
64 ± 5
75 ± 10
0.0001
Nighttime HR (bpm)
66 ± 9
66 ± 11
0.8
Nighttime mean BP (mmHg)
80 ± 5
94 ± 10
0.0001
BP blood pressure, DBP diastolic blood pressure, SBP systolic blood pressure, HR heart rate
6 Limits The limitations of our study include its small sample size with a limited statistical power of our assumption. The data of OSA were collected by patients’ interview during a consultation with a cardiologist.
7 Conclusion The causal relationship between OSA and HTN is well established. Screening of HTN should be made in all OSA using ABPM. BP control was not achieved in two thirds of OSA hypertensive patients. A long history of OSA is a predictor of uncontrolled BP in this population. Conflict of interest The authors have no conflict of interest to declare.
References 1. Ferri C. Strategies for reducing the risk of cardiovascular disease in patients with chronic obstructive pulmonary disease. High Blood Press Cardiovasc Prev. 2015. doi:10.1007/s40292-0150078-3. [Epub ahead of print]. 2. Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC, Amodeo C, Bortolotto LA, Krieger EM, Bradley TD, Lorenzi-Filho G. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58(5):811–7. doi:10.1161/ HYPERTENSIONAHA.111.179788.
3. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378–84. 4. Grote L, Hedner J, Peter JH. Sleep-related breathing disorder is an independent risk factor for uncontrolled hypertension. J Hypertens. 2000;18(6):679–85. 5. Phillips B. Sleep-disordered breathing and cardiovascular disease. Sleep Med Rev. 2005;9(2):131–40. 6. Loredo JS, Ancoli-Israel S, Dimsdale JE. Sleep quality and blood pressure dipping in obstructive sleep apnea. Am J Hypertens. 2001;14(9 Pt 1):887–92. 7. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461–70. 8. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John Sutton M, Stewart W; 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 Echocardiogr. 2006;7(2):79–108. 9. De Geest S, Sabate´ E. Adherence to long-term therapies: evidence for action. Eur J Cardiovasc Nurs. 2003;2(4):323. 10. Milleron O, Pillie`re R, Foucher A, de Roquefeuil F, Aegerter P, Jondeau G, Raffestin BG, Dubourg O. Benefits of obstructive sleep apnoea treatment in coronary artery disease: a long-term follow-up study. Eur Heart J. 2004;25(9):728–34. 11. Haentjens P, Van Meerhaeghe A, Moscariello A, De Weerdt S, Poppe K, Dupont A, Velkeniers B. The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med. 2007;167(8):757–64.
P. Delsart et al. 12. Logan AG, Tkacova R, Perlikowski SM, Leung RS, Tisler A, Floras JS, Bradley TD. Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex. Eur Respir J. 2003;21(2):241–7. 13. Tanriverdi H, Evrengul H, Kaftan A, Kara CO, Kuru O, Tanriverdi S, Ozkurt S, Semiz E. Effect of obstructive sleep apnea on aortic elastic parameters: relationship to left ventricular mass and function. Circ J. 2006;70(6):737–43. 14. Tanriverdi H, Evrengul H, Kara CO, Kuru O, Tanriverdi S, Ozkurt S, Kaftan A, Kilic M. Aortic stiffness, flow-mediated dilatation and carotid intima-media thickness in obstructive sleep apnea: non-invasive indicators of atherosclerosis. Respiration. 2006;73(6):741–50. 15. Suzuki T, Nakano H, Maekawa J, Okamoto Y, Ohnishi Y, Yamauchi M, Kimura H. Obstructive sleep apnea and carotid-artery intima-media thickness. Sleep. 2004;27(1):129–33. 16. Tavil Y, Kanbay A, Sen N, Ulukavak Ciftc¸i T, Abaci A, Yalc¸in MR, Ko¨ktu¨rk O, Cengel A. The relationship between aortic stiffness and cardiac function in patients with obstructive sleep apnea, independently from systemic hypertension. J Am Soc Echocardiogr. 2007;20(4):366–72.
17. Cicek D, Lakadamyali H, Yag˘basan BD, Sapmaz I, Mu¨derrisog˘lu H. Obstructive sleep apnoea and its association with left ventricular function and aortic root parameters in newly diagnosed, untreated patients: a prospective study. J Int Med Res. 2011;39(6):2228–38. 18. Sto¨whas AC, Namdar M, Biaggi P, Russi EW, Bloch KE, Stradling JR, Kohler M. The effect of simulated obstructive apnea and hypopnea on aortic diameter and BP. Chest. 2011;140(3):675–80. doi:10.1378/chest.10-2799. 19. Kraiczi H, Hedner J, Peker Y, Grote L. Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide, and losartan for antihypertensive treatment in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2000;161(5):1423–8. 20. Steiropoulos P, Tsara V, Nena E, Fitili C, Kataropoulou M, Froudarakis M, Christaki P, Bouros D. Effect of continuous positive airway pressure treatment on serum cardiovascular risk factors in patients with obstructive sleep apnea-hypopnea syndrome. Chest. 2007;132(3):843–51.
ORIGINAL ARTICLE
Evaluation of Blood Pressure Control in an Obstructive Sleep Apnea Population Followed in Cardiology Pascal Delsart1 • Marc Takla1 • Philippe Marboeuf2 • Gonzague Claisse1 • Natalia Kpogbemabou1 • Remy Lubret3 • Medhi Hattabi4 • Claire Mounier-Vehier1
Received: 7 March 2015 / Accepted: 9 April 2015 Ó Springer International Publishing Switzerland 2015
Abstract Objective Obstructive sleep apnea (OSA) is the most common factor involved in uncontrolled blood pressure (BP). Management of OSA is part of cardiologist work. We have few data on BP control in a population of OSA followed by cardiologists. Aim We evaluated the prevalence of effective BP control using ambulatory measurement in a population of patients followed in cardiology. Methods Data from 69 OSA patients treated for more than 6 months by continuous positive airway pressure (CPAP) were collected prospectively from March 2012 until December 2012. These patients were divided into 2 groups according to the results of 24-h ambulatory BP monitoring (ABPM). Controlled BP was defined as a 24 h BP \130/80 mmHg. Results All patients were hypertensive. 44 patients (63 %) had uncontrolled hypertension (HTN). The onset of OSA (p = 0.01) and persistent daytime sleepiness appeared as predictors of uncontrolled BP. Systolic BP (SBP) during consultation and all the ABPM variables were higher in uncontrolled BP patients. Uncontrolled BP was
& Pascal Delsart [email protected] 1
Service de me´decine vasculaire et Hypertension arte´rielle, Hoˆpital Cardiologique, CHRU Lille, Boulevard Pr Leclercq, 59037 Lille Cedex, France
2
Cabinet Magellan a` He´nin-Beaumont, He´nin-Beaumont, France
3
Hoˆpital Duchene a` Boulogne-sur-mer, Boulogne-sur-mer, France
4
Cabinet de Cardiologie de Villeuneuve d’Ascq, Villeuneuve d’Ascq, France
associated with greater left ventricular mass (p = 0.02) and greater diameter of the ascending aorta (p = 0.04). Conclusion Control of HTN should be evaluated in all OSA patients, using ABPM. The onset of OSA and high SBP during consultation are both factors associated with uncontrolled BP in this population. Repeating ABPM should be of interest for the follow up of these patients. Keywords Sleep apnea Ambulatory monitoring Blood pressure control
1 Introduction Optimization of cardiovascular risk needs a joint management of cardiovascular risk factors and pulmonary disease as chronic obstructive pulmonary disease and obstructive sleep apnea (OSA) [1]. The relationship between OSA and arterial hypertension (HTN) is now well established. OSA is present in 35 % of hypertensives and 80 % of patients with resistant HTN are apneic [2]. All patients carriers of OSA should be screened for HTN, since OSA is an independent risk factor for the development of HTN [3].We know that the link between these two diseases is of ‘‘dose response’’ type. Severe OSA is associated with both higher prevalence of HTN and the severity of sleep disorders is linearly associated with systolic and diastolic BP [4]. Although OSA is not yet clearly recognized as being an independent cardiovascular risk factor, numerous studies have shown that OSA increases the occurrence of cardiac and cerebral events [5]. Therefore, the management of OSA by the cardiologist is very important. It appears as an additional risk factor to take into consideration in the cardiological consultation. The use of ambulatory BP monitoring (ABPM) is the cornerstone in the management
P. Delsart et al.
of HTN. In OSA, the increase in BP is often nocturnal and therefore escapes the consultation data. Despite the high prevalence of OSA in the population of patients followed in cardiology, data on effective BP control and its predictors are quite rare. It seemed interesting to evaluate the predictors of BP control using ambulatory measurements.
2.3 OSA Data The onset of CPAP and duration of CPAP use were collected. All patients were asked about the presence of insomnia and persistent daytime sleepiness. No standardized sleepiness scale was used. 2.4 Laboratory Data
2 Methods Data were prospectively collected by 7 cardiologists consecutively from March 2012 to December 2012. OSA patients were included during follow-up consultation. This study was designed for a population of stable patients, defined as follows: the patient is treated by continuous positive airway pressure (CPAP) for more than 6 months; the patient has not been hospitalized for an acute cardiovascular event or acute respiratory disease in the last 6 months. After analyzing the data according to 24 h ABPM, the population was divided in 2 groups: Group 1 consisted of patients who had a controlled 24 h BP (BP level below 130/80 mmHg) and group 2 consisted of patients with uncontrolled 24 h BP. 2.1 Clinical Data Cardiovascular history was defined by previous documented atrial fibrillation, stroke, hospitalization for heart failure, coronary artery disease (acute coronary syndrome, myocardial revascularization), C50 % carotid stenosis, peripheral arterial disease (peripheral vascular intervention, lower extremity arterial revascularization), abdominal aortic aneurysm [30 mm). The cardiovascular risk factors (smoking status, dyslipidemia, HTN, type 2 diabetes mellitus, family history of premature cardiovascular disease) and the height, weight, body mass index and waist circumference were collected. A patient was considered as active smoker if present smoking or stopped for less than 3 years. 2.2 BP Data BP was taken during consultation after 10 min of sitting rest with a size-adapted cuff, using an electronic device (Data scope Acutor Plus deviceÒ). The average of 3 measurements was used for analysis. ABPM was performed in all patients, with a cuff adapted (Spacelabs Medical 90207Ò). BP measurement was made of every 15 min. The daytime BP was measured between 6 am and 22 pm and the nighttime BP was measured between 22 p.m. and 6 a.m. The dipping status was defined as a drop in BP over 10 % between the average daytime BP and the average nighttime BP for the systolic and/or the diastolic BP [6].
Renal function was assessed by glomerular filtration rate according to the MDRD formula [7]. Each patient received a total lipid profile including LDL, HDL, triglycerides, and fasting glucose level. 2.5 Antihypertensive Drugs For each patient, data for antihypertensive drugs classes were collected, including: angiotensin converting enzyme (ACE) inhibitors, Angiotensin II receptor blockers (ARBs), beta blockers, calcium channel blockers, thiazide diuretics, aldosterone antagonists, centrally acting drugs, alpha adrenergic blockers. The number of antihypertensive drugs was also identified for each patient as defining a score of antihypertensive treatment. 2.6 Electrocardiogram Data For each patient, the electrocardiogram was analyzed. It was performed at the time of the cardiologist consultation’, ie at least 6 months after CPAP therapy. Information about sinus rhythm and left ventricular hypertrophy were collected [8]. Left ventricular hypertrophy is defined by Sokolow-Lyon index [35 mm. 2.7 Echocardiographic Data The following echocardiographic data were collected: left ventricular ejection fraction, left ventricular mass (g/m2), left atrium area and diameter, and diameter of the ascending aorta. The echocardiogram was performed at the time of the cardiologist consultation’, ie at least 6 months after CPAP therapy.
3 Statistical Method Statistical analyzes were made using GraphPad SoftwareÒ. Continuous variables are expressed as mean ± standard deviation. Categorical data are expressed as a percentage. Comparison of two samples was made by non parametric tests. P \ 0.05 was retained as significant for all the tests.
Evaluation of Blood Pressure Control
The aim of our study was to evaluate the BP control in an OSA population having a regular follow up in cardiology. 94 % of patients were hypertensive in our work, ie the patients were under antihypertensive medication at the
inclusion or they have a clinical casual BP upper than 140/90 mmHg at rest without drug. Our study showed that around two thirds of the patients were not controlled for BP. Controlled BP has long been recognized as a factor in reducing mortality and cardiovascular morbidity (either primary or secondary prevention). The control of cardiovascular risk factors is a priority in the follow up patients. HTN control is unfortunately too low, around 50 % of patients in France (French League Against Hypertension Survey). Among the factors often implicated in uncontrolled BP, two are major: poor therapeutic compliance and OSA [9]. CPAP treatment is efficacy for both improving the quality of life and decreasing cardiovascular morbidity and mortality [10]. Although, it seems to have a moderate effect on lowering BP, except in cases of severe HTN or severe OSA [11, 12]. In this population, there is also a high prevalence of other factors recognized as responsible for uncontrolled BP, namely diabetes and abdominal obesity. There is no difference regarding the dipping pattern between the two groups. The vascular complications of OSA may also explain uncontrolled BP. Indeed, OSA promotes the development of microangiopathic and macroangiopathic lesions [13, 14]. We found a higher left ventricular mass in uncontrolled hypertensive as previously described [15, 16]. The severity of left ventricular hypertrophy is correlated with transient nocturnal oxygen desaturation. One study showed a significant reduction of left ventricular hypertrophy after 6 months of treatment with CPAP. We also found a significant difference in the diameter of the ascending aorta between the two groups. It was previously shown that OSA could favor the development of ascending aortic aneurysm, the main mechanism being the
Table 1 Characteristics of the population
Clinical and demographic data
Group 1 (controlled BP) n = 25
Group 2 (uncontrolled BP) n = 44
p
Age (years) Male/female (n)
56.4 ± 8.7 18/7
58.8 ± 8.9 37/7
0.2 0.2
BMI (kg/m2)
33.4 ± 6.2
33.4 ± 7.4
0.9
4 Results Data from 69 patients were collected. Sixty-four patients intake an anti hypertensive drug at the inclusion. Among the five patients without any anti hypertensive drug, 4 patients were not hypertensive defined as a clinical casual BP under 140 mmHg for the systolic and under 90 mmHg for the diastolic at rest. 2 patients on the four free of drug had both clinical and 24-h ambulatory BP value in the normal range. In the entire population, 44 patients (63 %) have uncontrolled BP (systolic BP [130 mmHg and/or diastolic BP [80 mmHg on 24-h ABPM). Among baseline characteristics, BP control is not correlated with age, gender or BMI (Table 1). None other usual cardiovascular risk factor was associated with BP control. Patients previously hospitalized for heart failure had a better BP control. The onset of CPAP use was statistically higher in uncontrolled BP patients (Table 2). We noted no difference between the two groups for the different therapeutic classes used in each group (Table 3). The uncontrolled BP group was associated with a greater left ventricular mass (p = 0.02), a greater diameter of the ascending aorta (p = 0.04), a higher HDL-cholesterol level (p = 0.03) (Table 4). Systolic BP during consultation and all the ABPM variables were higher in group 2 (Table 5).
5 Discussion
Abdominal circumference (cm)
121.1 ± 19.2
116 ± 25.6
0.38
Active smoker
6 (24 %)
11 (25 %)
0.9
Dyslipidemia
11 (60 %)
25 (56.8 %)
0.8
HTN
25 (100 %)
44 (100 %)
0.2
Type 2 diabetes mellitus
9 (36 %)
21 (47.7 %)
0.3
Family history of CV disease
6 (25 %)
7 (15.9 %)
0.4
Atrial fibrillation
1 (4 %)
4 (9 %)
0.4
Stroke
2 (8 %)
4 (9 %)
0.8
CAD
12 (48 %)
22 (48 %)
0.8
PAD
4 (16 %)
8 (18 %)
0.8
BMI body mass index, BP blood pressure, CAD coronary arterial disease, CV Cardiovascular, HTN hypertension, PAD peripheral arterial disease
P. Delsart et al. Table 2 OSA data
OSA
Group 1 (controlled BP) n = 25
Group 2 (uncontolled BP) n = 44
p
Onset of CPAP use (years)
3.6 ± 3.27
6.3 ± 5.06
0.01
Duration of CPAP use (hours/night)
6.7 ± 1.4
6.8 ± 1.6
0.8
Insomnia
3 (12 %)
12 (27 %)
0.14
Daytime sleepiness
2 (8 %)
11 (25 %)
0.08
BP blood pressure, CPAP continuous positive airway pressure, OSA obstructive sleep apnea
Table 3 Therapeutic data
Antihypertensive drugs
Group 1 (controlled BP) n = 25
Group 2 (uncontrolled BP) n = 44
p
ACE inhbitors or ARBs
21 (84 %)
40 (90 %)
0.3
Beta blockers
17 (68 %)
31 (70 %)
0.8
Calcium channel blockers
11 (44 %)
25 (56 %)
0.3
Thiazide diuretics
7 (28 %)
19 (43 %)
0.2
Aldosterone antagonists Centrally acting drugs
4 (16 %) 1 (4 %)
12 (27 %) 5 (11 %)
0.3 0.3
Alpha adrenergic blockers
2 (8 %)
0 (0 %)
0.05
Antihypertensive score
2.56 ± 1.3
2.95 ? 1.4
0.2
VKA
1 (4 %)
5 (11 %)
0.6
Statin
12 (48 %)
27 (61 %)
0.3
Antiplatelet therapy
12 (48 %)
20 (44 %)
0.8
ACE inhibitors angiotensin converting enzyme inhibitors, ARBs angiotensin II receptor blockers, BP blood pressure, VKA vitamin K antagonists
Table 4 Laboratory and echocardiographic data
Laboratory and ultrasonographic data Creatinine (mg/l)
Group 1 (controlled BP) n = 25 9.1 ± 3.2
2
Gfr (ml/min/1.73 m ) Fasting glucose level (g/l)
Group 2 (uncontrolled BP) n = 44
p
10.4 ± 4.3
0.19
96 ± 21
87 ± 29
0.18
1.07 ± 0.2
1.21 ± 0.46
0.13
HDL-cholesterol (g/l)
0.46 ± 0.13
0.40 ± 0.08
0.03
LDL-cholesterol (g/l)
1.02 ± 0.35
1.14 ± 0.36
0.19
Triglyceridemia (g/l) Echocardiographic data
1.38 ± 0.47
1.72 ± 1.14
0.15 1.5
LVEF (%)
56 ± 10
59 ± 8
LA area (cm2)
22 ± 4
22 ± 5
0.8
Ascending aorta diameter (mm)
31 ± 3.7
34 ± 4.6
0.04
LV mass (g/m2)
83 ± 13
92 ± 16
0.02
BP blood pressure, Gfr glomerular filtration rate, LA left atrium, LV left ventricular, LVEF left ventricular ejection fraction
repetition of transmural pressure related with obstructive events [17, 18]. Severe OSA may be a factor of the rapid expansion of the thoracic aortic aneurysm. We did not found a significant difference in the antihypertensive drugs between the 2 groups. Some studies have suggested that the prescription of beta blockers may be helpful in OSA patients. In our study, the distribution of beta-blockers was homogeneous in both groups. The
cardiometabolic effects of CPAP use has already been described in obese males with OSA [19]. In this work, the HDL-cholesterol level was significantly higher in the BP control group. A population based study found a small improvement in HDL cholesterol after 6 months of CPAP therapy [20]. The magnitude of cholesterol change with CPAP was more evident in patients with abnormal initial value and in patients with good compliance.
Evaluation of Blood Pressure Control Table 5 Blood pressure data (clinic and ABPM)
Data on hypertension
Group 1 (controlled BP) n = 25
Group 2 (uncontrolled BP) n = 44
p
Clinic SBP (mmHg)
129 ± 14
141 ± 6
0.004
Clinic DBP (mmHg)
79 ± 9
80 ± 10
0.5
Clinic HR (bpm)
74 ± 14
74 ± 14
0.8
24-h SBP (mmHg)
119 ± 7
143 ± 14
0.0001
24-h DBP (mmHg)
72 ± 5
83 ± 10
0.0001
24-h HR (bpm)
72 ± 10
73 ± 14
0.7
24-h mean BP (mmHg)
88 ± 5
102 ± 11
0.0001
Dipping n, (%)
15 (60)
27 (61)
0.9
Daytime SBP (mmHg)
124 ± 8
147 ± 16
0.0001
Daytime DBP (mmHg)
76 ± 7
86 ± 12
0.0004
Daytime HR (bpm) Daytime mean BP (mmHg)
75 ± 11 92 ± 7
76 ± 12 106 ± 12
0.9 0.0001
Nighttime SBP (mmHg)
108 ± 7
132 ± 15
0.0001
Nighttime DBP (mmHg)
64 ± 5
75 ± 10
0.0001
Nighttime HR (bpm)
66 ± 9
66 ± 11
0.8
Nighttime mean BP (mmHg)
80 ± 5
94 ± 10
0.0001
BP blood pressure, DBP diastolic blood pressure, SBP systolic blood pressure, HR heart rate
6 Limits The limitations of our study include its small sample size with a limited statistical power of our assumption. The data of OSA were collected by patients’ interview during a consultation with a cardiologist.
7 Conclusion The causal relationship between OSA and HTN is well established. Screening of HTN should be made in all OSA using ABPM. BP control was not achieved in two thirds of OSA hypertensive patients. A long history of OSA is a predictor of uncontrolled BP in this population. Conflict of interest The authors have no conflict of interest to declare.
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