325Patients with OSAS were also found to have increased plasma angiotensin II
levels. Moreover, treatment of OSAS with CPAP significantly decreased plasma
renin and angiotensin II levels in parallel to reductions in BP [ 28 ]. In several other
studies, increased inflammation and oxidative stress were shown to reduce nitric
oxide (NO) levels leading to impaired vasodilatation in patients with OSAS, and
CPAP treatment reversed NO levels [ 29 , 30 ]. In the other study, both serum endo-
thelin levels and BP were significantly reduced after CPAP therapy [ 31 ].
Importance of SNS overactivity has been clearly shown in OSAS-induced HT. In
animal experiments, chronic hypoxemia due to OSAS was shown to induce SNS
activity which in turn activated RAAS and increased vascular resistance leading to
hypertension [ 32 ]. However recent findings suggested that SNS overactivity could
cause OSAS. In a renal denervation study, central SNS outflow and BP were signifi-
cantly decreased and OSAS was improved with denervation treatment [ 33 ]. In
another words, SNS overactivity might be the trigger for both RH and OSAS.
Increased arterial stiffness is a well-known risk factor for HT and it may also
play a role in OSAS-induced HT [ 34 , 35 ]. In several studies performed on patients
with severe OSAS, CPAP treatment was found to significantly decrease arterial
stiffness in 4 weeks [ 36 , 37 ]. In contrary, in the study by Jones et al. [ 38 ], arterial
stiffness was not affected after 12 weeks of CPAP treatment. However, in a recent
meta-analysis, significant improvements were found in all parameters of arterial
stiffness after CPAP treatment [ 39 ].
A part of the strong relationship between OSAS and HT may also be explained by
common risk factors such as obesity. Obesity may induce HT by the way of RAAS acti-
vation, impaired sodium excretion, and increased SNS activity in patients with OSAS.
Role of Continuous Positive Airway Pressure (CPAP)
for the Treatment of Hypertension (HT) in OSAS
The contributive effect of OSAS on HT has been clearly demonstrated in the previous
studies. However, there are conflicting results about the role of CPAP on the treat-
ment of hypertension. Controversies on these results may stem from multiple issues
including differences in study designs, degree of OSAS and CPAP compliances,
treatment durations and accuracy, and methods of BP measurements.
In a prospective, multicenter randomized controlled trial (RCT), 194 patients
with OSAS and RH were randomized to two groups as CPAP group or no therapy
group [ 40 ]. After a 12-week follow-up period, significant decrease in 24-h mean BP
(3.1; 95% confidence interval, 0.6–5.6 mmHg) and 24-h diastolic BP (3.2; 95%con-
fidence interval, 1.0–5.4) were observed in the CPAP group. Furthermore, nocturnal
BP dip was evident in the CPAP group.
In another randomized prospective trial performed on patients with OSAS and
RH with a 3-month follow-up period, CPAP treatment significantly reduced 24-h
BP. Moreover number of patients with a dipping pattern significantly increased in
20 The Effect of CPAP Therapy on Resistant Hypertension in Obstructive Sleep...