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Study [ 7 ], patients with moderate-to-severe OSAS were found to have 3.2-fold
increased odds of developing HT relative to subjects without OSAS in 4 years of
follow-up period. In another large prospective cohort study, untreated OSAS
patients including patients who were non-adherent to continuous positive airway
pressure (CPAP) or refused CPAP treatment were all associated with increased
risk for incident hypertension [ 12 ]. However, in contrary to these results, no
increased risk of incident HT could be found in Sleep Heart Health Study at 5 years
of follow- up period [ 13 ].
HT associated with OSAS tends to be resistant, nocturnal, and non-dipper [ 14 ,
15 ]. Prevalence of OSAS in patients with resistant hypertension (RH) has been
reported to be around 64–83% [ 16 , 17 ]. In a study performed on patients with RH,
96% of the male and 65% of the female patients had significant OSAS [ 16 ]. Indeed,
OSAS has been regarded as the most common secondary cause of RH [ 17 ].
Non-dipping pattern of HT is associated with increased risk of cardiovascular
events [ 18 ], end-organ damage, and less favorable outcomes [ 19 ]. Non-dipping HT
is very frequent in patients with OSAS. In untreated patients with mild to severe
OSAS, prevalence of non-dipping has been reported to be 84% [ 20 ].
OSAS, HT, and chronic kidney disease (CKD) are closely related to each other.
HT is well established to be a major etiological factor for the development and pro-
gression of CKD [ 21 ]. Treatment of HT is shown to decrease the rate of kidney
dysfunction [ 22 ]. In a study performed on CKD and non-CKD subjects, RH and
severe OSAS were found to be more prevalent in patients with advanced kidney
disease [ 23 ]. Furthermore, patients with end-stage renal disease with severe OSAS
were found to have seven times higher risk to have RH. A direct reciprocal associa-
tion between OSAS and CKD has also been hypothesized; CKD may increase the
risk of OSAS and OSAS may accelerate the progression to end-stage renal disease
(ESRD). OSAS was found to be present in 50–70% of patients with ESRD [ 24 ].
Pathophysiology of HT in OSAS
Many pathophysiological mechanisms have been proposed for the development of
HT in patients with OSAS such as increased renin-angiotensin-aldosterone system
(RAAS) activity, sympathetic nervous system (SNS) activity, increased inflamma-
tion and oxidative stress, increased endothelin release, endothelial dysfunction, and
arterial stiffness.
RAAS is the principal pathway in the regulation of BP and thus the overactivity
of RAAS is shown to be the main inciting event in HT. Patients with OSAS were
shown to have increased serum aldosterone levels [ 25 ] and 24-h urinary excretion of
aldosterone [ 26 ]. Furthermore, plasma aldosterone levels were found to be directly
associated with the severity of OSAS in patients with resistant HT [ 25 ]. Aldosterone
may contribute to the pathogenesis of OSAS by the way of renal sodium retention
leading increased airway resistance due to parapharyngeal edema. Supporting this
hypothesis, treatment with aldosterone antagonists has been shown to improve
OSAS in patients with RH [ 27 ].
A. Özkök et al.