OSA (obstructive sleep apnoea) stimulates sympathetic nervous activity and elevates resting HR (heart rate) and BP (blood pressure). In the present study in a cohort of 309 untreated OSA patients, the resting HR and BP during the daytime were correlated with AHI (apnoea/hypopnea index) and compared with patients with R389R (n=162), R389G (n=125) and G389G (n=22) genotypes of the β1-adrenoreceptor R389G polymorphism. We analysed the impact of the genotype on the decline of HR and BP in a subgroup of 148 patients (R389R, n=86; R389G, n=54; G389G, n=8) during a 6-month follow-up period under CPAP (continuous positive airway pressure) therapy during which cardiovascular medication remained unchanged. In untreated OSA patients, we found an independent relationship between AHI and resting HR (β=0.096, P<0.001), systolic BP (β=0.09, P=0.021) and diastolic BP (β=0.059, P=0.016). The resting HR/BP, however, did not differ among carriers with the R389R, R389G and G389G genotypes. CPAP therapy significantly reduced HR [−2.5 (−1.1 to −4.0) beats/min; values are mean difference (95% confidence intervals)] and diastolic BP [−3.2 (−1.5 to −5.0) mmHg]. The decline in HR was more significantly pronounced in the R389R group compared with the Gly389 carriers [−4.1 (−2.3 to −5.9) beats/min (P<0.001) compared with −0.2 (2.1 to −2.6) beats/min (P=0.854) respectively; Student's t test between groups, P=0.008]. Diastolic BP was decreased significantly (P<0.001) only in Gly389 carriers (R389G or G389G) compared with R389R carriers [−5.0 (−2.3 to −7.6) mmHg compared with −2.0 (0.4 to −4.3) mmHg respectively]. ANOVA revealed a significant difference (P=0.023) in HR reduction between the three genotypes [−4.1 (±8.4) beats/min for R389R, −0.5 (±9.3) beats/min for R389G and +1.9 (±7.2) beats/min for G389G]. In conclusion, although the R389G polymorphism of the β1-adrenoceptor gene did not influence resting HR or BP in untreated OSA patients, it may modify the beneficial effects of CPAP therapy on these parameters.

INTRODUCTION

Patients with OSA (obstructive sleep apnoea) show increased sympathetic nervous activity during the day and night in response to the repetitive decline of arterial blood O2 saturation during sleep [14]. It is likely that this phenomenon contributes to the increased risk of cardiovascular diseases and complications in OSA patients [5,6].

The β1-adrenoceptor is expressed in heart and kidney and is activated by circulating adrenaline (epinephrine) as well as by noradrenaline (norepinephrine) released from sympathetic nerves at the neuroeffector junction. β1-Adrenoreceptors, which couple to Gs-proteins, stimulate adenylate cyclase and increase intracellular cAMP. This leads to increased inotropy and chronotropy in the heart and, furthermore, stimulates renin release from juxtaglomerular cells in the kidney. Mason and co-workers [7] characterized a ‘gain-of-function’ polymorphism of the β1-adrenoceptor gene, which leads to an exchange of glycine with arginine at position 389. The polymorphism is localized within the Gs-coupling domain of this receptor. The Arg389 receptor phenotype has a much greater ability to couple to adenylate cyclase than the Gly389 receptor phenotype [7]. Subsequent studies revealed that the Arg389 allele is relatively common, with a prevalence of 71–78% in Caucasian and Chinese subjects and 58% in African–Americans [8]. However, the functional relevance in vivo remains unclear, in particular whether the Arg389 allele contributes to common cardiovascular disorders such as congestive heart failure and coronary heart disease [8].

The aim of the present study was therefore to investigate whether the Arg389 β1-adrenoceptor phenotype modifies HR (heart rate) or BP (blood pressure) in patients with moderate-to-severe OSA. In a subgroup of OSA patients, we evaluated the effect of CPAP (continuous positive airway pressure) therapy on these cardiovascular parameters and analysed whether the responses observed were modulated by this gain-of-function polymorphism.

METHODS

Patients

Patients were consecutively enrolled from 1999–2001 in the sleep laboratory of the Marienhospital Herne (Ruhr University Bochum, Bochum, Germany). Inclusion criteria were diagnosis of OSA and indication for CPAP therapy. Patients with OSA were treated with CPAP when AHI (apnoea/hypopnea index) was >10 events/h or when AHI was between 5 and 10 events/h combined with typical clinical symptoms, such as daytime tiredness. Patients on β-blocker medication were excluded. A total of 309 patients were included in this study.

After written consent for participation, clinical data relating to the cardiovascular risk profile from the time of initial diagnosis were collected. Patient data included results of the polysomnographies, documented diagnoses of further diseases, such as hypertension or diabetes, and medication. These data were controlled by a standardized patient's questionnaire at the time of written consent that included questions about lifestyle habits in addition to a complete patient history. HR and BP were measured three times a day (08:00, 14:00 and 19:00 hours) for 1 min during the hospital visits for polysomnography by palpitation (1 min) and the Riva Rocci method. Patients were rested for at least 10 min before measurements were performed. The measurements were carried out by the nurses/technical assistants in the sleep laboratory, who were introduced to the procedures but were blinded to the purpose of the study. The means of three measurements were used for further calculations.

Diagnosis of hypertension was established if patients were either on antihypertensive drugs or if the mean of three measurements of SBP (systolic BP) was ≥140 mmHg or DBP (diastolic BP) was ≥90 mmHg.

The study protocol was approved by the Local Ethics Committee at Ruhr University Bochum, Bochum, Germany.

Polysomnography

All patients underwent overnight polysomnography (Somnostar 4100; SensorMedics), according to a standardized protocol [9]. Patients were monitored with continuous polygraphic recording from surface leads for electroencephalography (C3/A1 and C4/A2), bilateral electro-oculography, submental and leg electromyography, electrocardiography, oxyhaemoglobin saturation (finger pulse oxymetry), chest and abdominal excursion (inductance plethysmography), nasal and oral airflow from non-invasive sensors, body position, tracheal sounds (microphone) and thoracic and abdominal respiratory movement (inductance plethysmography). Recordings were supervised continuously by a technician in order to ensure that the transducers and lead wires permitted normal positional changes during sleep. Sleeping and awakening times were both at the discretion of subjects. Polysomnography was determined after final waking. Recordings were scored in 30 s periods for sleep, breathing and oxygenation. Breathing events during sleep were defined as abnormal if either complete cessation of airflow lasting ≥10 s was observed (apnoea) or respiratory airflow of ≥50% of the tidal volume lasting ≥10 s was reduced (hypopnoea). Obstructive apnoea was defined as absence of tidal volume in the presence of paradoxical chest or abdominal wall motion. The average number of episodes of apnoea and hypopnea/h of sleep (AHI) was calculated. When AHI was ≥5 events/h, associated with typical clinical features, OSA syndrome was diagnosed. Sleep was staged manually using the methods described by Rechtschaffen and Kales [10]. Patients who had central sleep apnoea were excluded from the study.

Follow-up during CPAP therapy

Patients who were treated with CPAP therapy were re-evaluated by polysomnography after 6 months. A subgroup of 148 patients was identified who tolerated CPAP therapy and in whom cardiovascular medication was kept constant during the initial visit and the first follow-up re-evaluation 6 months later. This subgroup was analysed regarding the impact of CPAP therapy on BP and HR.

Genotyping

Peripheral blood samples from the patients were obtained with their informed consent. Primers were synthesized in order to amplify the 522 bp fragment in which the R389G polymorphism was at position 159: 5′-CGCTCTGCTGGCTGCCCTTCTTCC-3′ (sense) and 5′-TGGGCTTCGAGTCCTGCTATC-3′ (antisense).

PCR was carried out in a final volume of 10 μl with 50 ng of DNA, 200 μM dNTP and 1 unit of Taq polymerase. PCR cycling started with initial denaturation for 5 min at 94 °C. The annealing temperature of the first cycle was 61 °C, second cycle was 58 °C and the remaining 26 cycles were 55 °C. The annealing time was 1 min. Extension was performed at 72 °C for 1 min (final extension, 5 min). The PCR fragment was treated with the restriction endonuclease Mva1 (EcoR11) which fails to digest the Arg389 allele because of the G→C transition. Digested DNA was electrophoresed on 1.5% (w/v) agarose gels. The restriction fragments of the Arg389 allele were 311, 84, 58, 45 and 24 bp long. The Gly389 allele harbours an additional restriction site so that the 311 bp fragment is digested into 135 and 176 bp fragments (Figure 1).

Allele-specific restriction of β1-adrenoceptor genotype polymorphisms

Figure 1
Allele-specific restriction of β1-adrenoceptor genotype polymorphisms

The 311 bp fragment is digested by MvaI into 176 and 135 bp fragments in the presence of the G allele. CC, R389R; GG, G389G; and CG, R389G. M, molecular-mass marker.

Figure 1
Allele-specific restriction of β1-adrenoceptor genotype polymorphisms

The 311 bp fragment is digested by MvaI into 176 and 135 bp fragments in the presence of the G allele. CC, R389R; GG, G389G; and CG, R389G. M, molecular-mass marker.

Statistical analysis

Demographic characteristics of the OSA patients were compared with the different genotypes by using a 2×2 contingency table and χ2 test, and were considered significantly different if the P values were <0.05. Mean values of numeric variables were compared for each genotype by ANOVA. The homogeneity of the variances was confirmed by the Levene test. A multivariate linear/logistic regression model was established to investigate an independent influence of the severity of OSA (represented by AHI) and the R389G polymorphism on BP, HR and the prevalence of hypertension.

In the follow-up cohort of 148 patients, the number of Gly389 homozygotes was small (n=8). Therefore, in an additional model, patients with R389G and G389G genotypes were combined into one group. Differences between the two genotype groups [R389R and (R389G+G389G)] were calculated by Student's t-test.

RESULTS

Association between AHI and BP/HR before CPAP therapy

Table 1 summarizes the polysomnographic and demographic findings in the different genotypes. Arterial hypertension was diagnosed in 167 (54%) patients.

Table 1
Demographics of the different genotypes of the β1-adrenergic receptor R389G polymorphism

Values are means±S.D., or n (%). No significant difference was observed between the genotypes.

Genotype
R389RR389GG389G
n 162 125 22 
HR (beats/min) 77.8±9.8 77.1±9.2 77.4±9.5 
Mean SBP (mmHg) 131.0±16.6 128.5±13.8 128.3±14.4 
Mean SBP (mmHg) 80.1±9.5 78.9±8.5 79.2±8.8 
Mean age (years) 54.5±11.0 54.0±9.8 55.3±11.5 
Gender (female) 24 (14.8) 22 (17.6) 6 (27.3) 
Mean BMI (kg/m230.9±5.4 30.9±5.9 30.9±6.7 
Results of polysomnography    
 Mean AHI (events/h) 29.4±21.7 29.7±24.7 24.7±22.9 
 Mean O2 saturation (%) 92.6±3.2 91.6±4.7 91.8±2.5 
 Mean maximum O2 desaturation (%) 80.3±10.6 80.9±9.4 83.6±6.8 
Cardiovascular history (n   
 Arterial hypertension 87 (53.7) 68 (54.4) 12 (54.5) 
 Type II diabetes mellitus 25 (15.4) 18 (14.4) 1 (4.5) 
 Coronary artery disease 24 (14.8) 11 (8.8) 1 (4.5) 
 Myocardial infarction 4 (2.5) 1 (0.8) 0 (0) 
Genotype
R389RR389GG389G
n 162 125 22 
HR (beats/min) 77.8±9.8 77.1±9.2 77.4±9.5 
Mean SBP (mmHg) 131.0±16.6 128.5±13.8 128.3±14.4 
Mean SBP (mmHg) 80.1±9.5 78.9±8.5 79.2±8.8 
Mean age (years) 54.5±11.0 54.0±9.8 55.3±11.5 
Gender (female) 24 (14.8) 22 (17.6) 6 (27.3) 
Mean BMI (kg/m230.9±5.4 30.9±5.9 30.9±6.7 
Results of polysomnography    
 Mean AHI (events/h) 29.4±21.7 29.7±24.7 24.7±22.9 
 Mean O2 saturation (%) 92.6±3.2 91.6±4.7 91.8±2.5 
 Mean maximum O2 desaturation (%) 80.3±10.6 80.9±9.4 83.6±6.8 
Cardiovascular history (n   
 Arterial hypertension 87 (53.7) 68 (54.4) 12 (54.5) 
 Type II diabetes mellitus 25 (15.4) 18 (14.4) 1 (4.5) 
 Coronary artery disease 24 (14.8) 11 (8.8) 1 (4.5) 
 Myocardial infarction 4 (2.5) 1 (0.8) 0 (0) 

Antihypertensive medication consisted of ACE (angiotensin-converting enzyme) inhibitors/AT (type 1 angiotensin II) receptor antagonists (n=79; 25.6% of the full cohort), diuretics (n=42; 13.6% of the full cohort), calcium channel blockers (n=57; 18.4% of the full cohort), nitrates (n=23; 7.4% of the full cohort), central antihypertensive drugs (n=7; 2.3% of the full cohort) and α-adrenoceptor antagonist (n=1; 0.3% of the full cohort). No patient received β-blockers.

The Levene test revealed a high degree of homogeneity between the variances of the numeric variables when compared between the different genotypes (results not shown).

There were no significant differences in the genotype subgroups regarding antihypertensive medication, age, gender and average AHI levels before therapy as well as cardiovascular history. Furthermore, no difference in BP and HR was detected.

In a multivariate regression model (age, gender, BMI, AHI and R389G), a significant and independent relationship between the severity of OSA (AHI) and BP, HR or the prevalence of hypertension was evident, whereas the β1-adrenoceptor R389G polymorphism did not influence these phenotypes (Table 2).

Table 2
Influence of AHI and the β1-adrenergic receptor R389G polymorphism on HR and BP

A multivariate regression model was used that was adjusted for age, BMI and gender. ADRB1, β1-adrenergic receptor.

HRSBPDBPHypertension
βP valueβP valueβP valuelogP value
AHI 0.096 <0.001 0.090 0.021 0.059 0.016 0.02 0.004 
ADRB1 R389G 0.522 0.544 1.94 0.148 0.556 0.504 0.024 0.911 
HRSBPDBPHypertension
βP valueβP valueβP valuelogP value
AHI 0.096 <0.001 0.090 0.021 0.059 0.016 0.02 0.004 
ADRB1 R389G 0.522 0.544 1.94 0.148 0.556 0.504 0.024 0.911 

Follow-up during CPAP therapy

In a subgroup of 148 patients in whom the medication was kept unchanged during a 6 month period of follow-up, CPAP therapy decreased the mean AHI effectively from 31.0 events/h at baseline to 2.3 events/h (P<0.001; Table 3). No significant change in the BMI (body mass index) was observed (P=0.283).

Table 3
Change of BP and HR after 6 months of CPAP therapy in the follow-up cohort (n=148) and in the subgroups with different R389G genotypes

Values are means±S.D. Full cohort of patients, n=148; R389R subgroup, n=86; G389G or R389G subgroup, n=62. CI, confidence interval.

CPAP therapy
BaselineAfter 6 monthsMean difference (95% CI)P value
Mean AHI (events/h) 31.0±21.3 2.3±2.4 −28.7 (−25.3 to −32.2) <0.001 
Mean BMI (kg/m231.3±5.7 31.1±5.4 −0.2 (0.1 to −0.5) 0.283 
Mean SBP (mmHg)     
 Full cohort 129.7±14.3 128.2±15.6 −1.4 (0.8 to −3.8) 0.201 
  R389R subgroup 129.5±14.6 129.2±15.8 −0.3 (2.6 to −3.2) 0.830 
  G389G or R389G subgroup 129.3±13.9 126.8±15.3 −3.1 (−0.5 to −6.8) 0.097 
Mean DBP (mmHg)     
 Full cohort 80.2±9.2 77.0±9.5 −3.2 (−1.5 to −5.0) <0.001 
  R389R subgroup 79.9±8.5 77.9±9.3 −2.0 (0.4 to −4.3) 0.095 
  G389G or R389G subgroup 80.6±9.0 75.6±9.3 −5.0 (−2.3 to −7.6) <0.001 
Mean HR (beats/min)     
 Full cohort 78.2±8.7 75.7±8.0 −2.5 (−1.1 to −4.0) 0.001 
  R389R subgroup 79.9±8.5 75.7±8.5 −4.1 (−2.3 to −5.9) <0.001 
  G389G or R389G subgroup 75.9±8.4 75.7±7.2 −0.2 (2.1 to −2.6) 0.854 
CPAP therapy
BaselineAfter 6 monthsMean difference (95% CI)P value
Mean AHI (events/h) 31.0±21.3 2.3±2.4 −28.7 (−25.3 to −32.2) <0.001 
Mean BMI (kg/m231.3±5.7 31.1±5.4 −0.2 (0.1 to −0.5) 0.283 
Mean SBP (mmHg)     
 Full cohort 129.7±14.3 128.2±15.6 −1.4 (0.8 to −3.8) 0.201 
  R389R subgroup 129.5±14.6 129.2±15.8 −0.3 (2.6 to −3.2) 0.830 
  G389G or R389G subgroup 129.3±13.9 126.8±15.3 −3.1 (−0.5 to −6.8) 0.097 
Mean DBP (mmHg)     
 Full cohort 80.2±9.2 77.0±9.5 −3.2 (−1.5 to −5.0) <0.001 
  R389R subgroup 79.9±8.5 77.9±9.3 −2.0 (0.4 to −4.3) 0.095 
  G389G or R389G subgroup 80.6±9.0 75.6±9.3 −5.0 (−2.3 to −7.6) <0.001 
Mean HR (beats/min)     
 Full cohort 78.2±8.7 75.7±8.0 −2.5 (−1.1 to −4.0) 0.001 
  R389R subgroup 79.9±8.5 75.7±8.5 −4.1 (−2.3 to −5.9) <0.001 
  G389G or R389G subgroup 75.9±8.4 75.7±7.2 −0.2 (2.1 to −2.6) 0.854 

As shown in Table 3, CPAP therapy significantly decreased HR (P=0.01) and DBP (P<0.01), although the reduction in SBP was not significant (P<0.201). The decline of HR after CPAP was more significantly pronounced in the R389R group (P<0.001) compared with Gly389 carriers (P=0.854; Table 3; P=0.008 for the difference between the groups, as determined by Student's t test). DBP was decreased significantly (P<0.001) only in Gly389 carriers (R389G or G389G) compared with R389R carriers (0.095; Table 3; P=0.09 for the difference between groups, as determined by Student's t test). Reduction in SBP also tended to be greater in Gly389 carriers, but the reduction and difference between the groups were not significant (Table 3).

When the reduction in SBP, DBP and HR between the three genotypes was evaluated (Figure 2), ANOVA revealed a significant difference only in the reduction of HR between the three genotypes.

Effect on SBP, DBP and HR after CPAP therapy in OSA patients

Figure 2
Effect on SBP, DBP and HR after CPAP therapy in OSA patients

Box plots (median and distribution) are shown of the changes in BP and HR after CPAP therapy in OSA patients with different β1-adrenoceptor genotypes. bpm, beats/min.

Figure 2
Effect on SBP, DBP and HR after CPAP therapy in OSA patients

Box plots (median and distribution) are shown of the changes in BP and HR after CPAP therapy in OSA patients with different β1-adrenoceptor genotypes. bpm, beats/min.

DISCUSSION

β-Adrenoceptors in general and the β1-adrenoceptor subtype in particular are important mediators of the sympathetic nervous system and control several cardiovascular parameters. In the heart, β1-adrenoceptor activation increases cardiac chronotropy and inotropy. Moreover, activation of β1-adrenoceptors in the kidney stimulates renin release and thus contributes to high BP. The gene encoding the β1-adrenoceptor has at least 18 SNPs (single nucleotide polymorphisms) [8] and much interest has been focused on the R389G polymorphism. It has been demonstrated in in vitro studies that isoprenaline stimulates cAMP levels in CHW-1102 cells homozygous for R389R to a greater extent than in CHW-cells homozygous for G389G, which suggests a gain-of-function for the Arg389 β1-adrenoceptor subtype [7]. This gain-offunction may be attributable to increased coupling of the Arg389 receptor genotype to the Gs-protein [7]. Accordingly, a recent study using right atrial appendage tissue obtained during cardiac surgery revealed higher tissue cAMP levels as well as a greater inotropic response to noradrenaline in R389R compared with G389G patients [11].

Subsequent in vivo studies, however, revealed differing results concerning the pathophysiological consequences of the R389G polymorphism [8]. In particular, the association of the R389G polymorphism with HR and BP has been inconsistent. Although Bengtsson et al. [12] detected a significantly higher odds ratio (1.9) for the prevalence of arterial hypertension and DBP and HR in R389R homozygotes, Ranade et al. [13] could not detect any of these effects in a large sample of more than 1000 individuals of Chinese and Japanese descent. In contrast, individuals with G389G genotype tended to have a higher SBP and DBP [13]. In line with this, Buscher et al. [14] failed to observe differences in exercise-induced HR responses and plasma renin activity between homozygote G389G and R389R carriers.

Furthermore, haemodynamic responses (HR, BP and coronary flow) to intravenous adrenaline did not differ between carriers of the Gly389 and Arg389 genotypes [15].

In the present study, we investigated a large cohort of patients with moderate-to-severe OSA. These patients have a high prevalence of obesity and hypertension, and are at increased risk for cardiovascular complications [16,17]. Much evidence has been presented that this increased risk is associated with an increased sympathetic nervous activity [14]. Consequent CPAP therapy reduces this sympathetic overactivity. Initial studies suggest that CPAP therapy has beneficial effects on cardiovascular risk profile and improves clinical outcome in these patients [18,19]. In agreement with this concept, we noted a strong correlation between the severity of OSA (as measured by AHI) and resting BP, prevalence of hypertension and resting HR. We observed further that during effective CPAP therapy AHI, HR, DBP and, to a lesser degree, SBP decreased.

HR modulation in OSA patients is mediated via vagal withdrawal. In addition it is feasible that stimulation of cardiac β1-adrenoceptors due to higher levels of neuronally released noradrenaline contributes to HR elevation. In line with this, higher plasma levels of noradrenaline contribute to high BP in OSA patients due to vascular α-adrenoceptor-mediated vasoconstriction. Since the sympathetic nervous system also controls renin release, it is not surprising that renin and angiotensin levels were shown to be higher in OSA patients. Furthermore, CPAP therapy reduces the elevated plasma levels of these hormones [20]. Thus we hypothesized that the proposed gain-of-function R389G polymorphism may influence HR and BP in OSA patients. To our disappointment, the R389R polymorphism was not associated with higher resting HR and BP in untreated OSA patients. This finding could be interpreted as further evidence that the R389G polymorphism of the β1-adrenoceptor gene has only minor relevance in vivo.

The fact that we could not show any difference of resting HR and BP in untreated OSA patients may be determined by the limited number of patients analysed. An alternative explanation is that a cross-sectional analysis of a multifactorially influenced parameter such as HR and BP is less powerful than a follow-up observation of a response to a certain treatment, such as CPAP therapy. To test this possibility, a subgroup of patients, whose medication was kept unchanged during 6 months of CPAP therapy was identified. Since the number of G389G homozygotes was small (n=8) we performed an analysis by pooling homozygous and heterozygous Gly389 carriers. In this subgroup of CPAP-treated OSA patients with unchanged antihypertensive medication (n=148), a significantly greater reduction of HR following CPAP therapy was observed in homozygous R389R carriers. Further statistical evaluation of the three individual genotypes (R389R, R389G and G389G) by ANOVA revealed significant differences in heart responses between groups (Table 3 and Figure 2). As one might expect, there was a rank order of genotypes for the observed HR decreases following CPAP therapy (R389R>R389G>G389G).

Surprisingly, the BP response to CPAP in the follow-up cohort pointed in the opposite direction. Carriers of the Gly389 (homozygotes and heterozygotes) exhibited a greater and significant decrease in DBP and SBP during CPAP therapy. However, differences in the BP-lowering effects of CPAP therapy between the genotype groups (R389R, R389G and G389G) did not reach statistical significance.

The reason for this differential influence of the R389G polymorphism on HR and BP in untreated and treated OSA patients is unclear. In the present study, carriers of the Gly389 variant had a larger BP fall than carriers of the Arg389 variant (homozygotes), but in contrast a significant decrease in HR was observed only in Arg389 homozygotes. One possible explanation is that the arterial baroreceptor reflex counteracted the expected fall in HR in Gly389 carriers. However, we do not know why there was a larger BP effect of CPAP therapy in Gly389 carriers, but it may involve medullary β1-adrenoceptors resulting in a greater fall in central sympathetic outflow in that group.

On the other hand, the better signal transduction of the Arg389 variant [7] may be responsible for the greater HR decrease in this group, which could be interpreted as a consequence of a sudden reduction in sympathetic overactivity following CPAP therapy.

In summary, we could not detect a modification of resting HR and BP by the R389G polymorphism of the β1-adrenoceptor gene in untreated OSA patients. Nevertheless, the R389G polymorphism of the β1-adrenoceptor appears to have an impact on HR and BP response to CPAP therapy. There are, however, several limitations of our study. First, it was not designed to dissect the differing influence of the R389G polymorphism on HR and BP. Secondly, although HR and BP measurements were performed in line with previous studies [12,13], our investigation is limited by comparatively few measurements per patient. Future studies are necessary utilizing 24 h HR and BP measurements before a final conclusion can be drawn.

Abbreviations

     
  • AHI

    apnoea/hypopnea index

  •  
  • BP

    blood pressure

  •  
  • BMI

    body mass index

  •  
  • CPAP

    continuous positive airway pressure

  •  
  • DBP

    diastolic BP

  •  
  • HR

    heart rate

  •  
  • OSA

    obstructive sleep apnoea

  •  
  • SBP

    systolic BP

This study was supported by FoRUM (Forschungsförderung der Ruhr-Universität Bochum, Medizinische Fakultät).

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