Sleep Apnea: Secondary Cause or Risk Factor for Hypertension?


Costas G. Thomopoulos, MD, 8, L. Mpellou str. Nea Filothei, Athens 11524, Greece

According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7)1 and the European Society of Cardiology/European Society of Hypertension 20072 guidelines for the management of hypertension, obstructive sleep apnea (OSA) is considered an identifiable cause of hypertension and constitutes the more frequent cause of resistant hypertension. However, both sleep history evaluation and high clinical suspicion assessment for OSA are underestimated or even ignored in usual clinical practice. OSA diagnosis in hypertensive patients may not only steer us towards the appropriate strategy for controlling blood pressure (BP) levels effectively, but it identifies a group of patients with heighten risk beyond the traditional risk factors.3 Observational and experimental evidence suggests that OSA may extend cardiometabolic risk burden by its independent association with coronary artery disease, stroke, arrhythmias, heart failure, and cardiovascular mortality, while obesity and abnormalities in glucose metabolism represent an adverse pairing that is frequently clustered with OSA.4

The obesity epidemic has prompted the recognition of an interaction between OSA and increased BP. Hypertension is a complex disease with a mosaic of interactive etiologies, such as age, sex, nutrition, environment, stress, obesity, and genetics. Along the same lines, the prevalence of OSA increases with age and excess adiposity, while male sex, familiar aggregation, and genetic predisposition are common in the OSA phenotype. Further risk factors associated with OSA and hypertension are smoking, alcohol consumption, hypothyroidism, and polycystic ovary syndrome, while pregnancy may be accompanied by either OSA or hypertension or even their combination.5 This etiologic partnership between hypertension and OSA indicates that these two conditions are associated more commonly than would be expected by chance alone. In these lines, we should take into account some considerations in order to validate or reject the guidelines-oriented belief that OSA resembles a cause of secondary hypertension.

Is OSA a Secondary Cause of Hypertension?

In OSA patients a percentage of 60% are hypertensive, whereas among hypertensive patients only 20% are affected by OSA.3 Therefore, it is logical that not all patients with OSA develop hypertension, although it should be acknowledged that the increasing severity of sleep-disordered breathing, as assessed by apnea/hypopnea index, even within the normal range, constitutes a risk factor for the future development of hypertension over 4 years after adjustment for body size.6 Additionally, obesity generally anticipates the development of OSA and as such, it is difficult to determine etiologic association between OSA and hypertension beyond obesity by statistical means only. It would be interesting to know whether normoweight compared with either overweight or obese patients with OSA are prone to develop hypertension in the future and whether early treatment of OSA is reflected in a buffering effect on hypertension incidence.

The traditional causes of hypertension (ie, renal parenchymal disease, renal artery stenosis, primary aldosteronism, hypothyroidism, implementation of drugs with hypertensive effects, and aorta coartation) increase BP levels in all ages, including the elderly, and hypertension is developed along with the natural history of the secondary cause. By contrast, the severity of sleep-disordered breathing demonstrated no association with hypertension in patients older than 60 years, whereas repetitive nocturnal episodes of the upper airway collapse were correlated with systolic/diastolic hypertension only in patients younger than 60 years.7 Consequently, the clinical designation of OSA as a secondary cause of hypertension may be at least questionable because it is strongly limited by age.

It is known from both meta-analyses8–11 and well-designed prospective studies12,13 that the effect of continuous positive airway pressure (CPAP) therapy is marginally beneficial in reducing both clinic and ambulatory BP levels in hypertensive patients with OSA. Additionally, OSA patients with mild forms of hypertension and OSA patients without hypertension (ie, with prehypertensive BP levels) demonstrated no reductions in BP.3 More specifically, the potential impact of effective CPAP therapy on BP levels is restrained in some millimeters decline for both systolic and diastolic BP (≈2–6 mm Hg/2–3 mm Hg, respectively) as compared with conventional or sham-CPAP therapy. BP reduction was more prominent in patients with daytime symptoms (sleepy snorers) as compared with nonsleepy snorers, suggesting that sleepiness might be the triggering factor in the hypertension-mediated effects of OSA.12,14 The overall evidence so far indicates that CPAP therapy has variable and mild effects on BP levels, further weakening the concept that OSA resembles a secondary cause of hypertension.

By moving the above discussion in the context of resistant hypertension, OSA should be seen as a potent contributing factor of resistance and CPAP treatment is effective in producing satisfactory BP reductions.15 Recent work from Brazil16 evaluating the comparative prevalence of different causes of resistant hypertension demonstrated that OSA is the most prevalent cause (63% of the participants) and essential hypertension underlies the 34% of resistant hypertensive patients. Although the latter study highlighted the important contribution of OSA in the resistant hypertensive phenotype, based on the considerations of the present paper, we should translate the results differently by stating that essential hypertension complicated by OSA as compared with essential hypertension without OSA is almost 2-fold more prevalent in patients with resistant hypertension. This finding is concordant with previous evidence suggesting that the duo of OSA and hypertension as compared with hypertension alone in middle-aged patients is associated with a more deteriorated vascular pattern, qualifying OSA as an accelerator of vascular damage in hypertension.17–19

Our Point of View

At present, the authors believe that OSA should no longer be considered a cause of secondary hypertension. OSA accompanies many cases of essential hypertension and strongly determines difficult-to-treat or resistant hypertension phenotype. Well-designed prospective studies in early ages, recruiting OSA patients with different body size burden are needed in order to confirm or exclude any etiologic association between these conditions. The qualification of secondary hypertension should be strictly limited in its traditional definition, involving causes that anticipate hypertension development, and their treatment should be associated with substantial BP reduction and ongoing pharmacotherapy attenuation. In our view, the new guidelines for the management of hypertension should focus on this particular issue and OSA should be seen as a risk factor and not a cause of essential hypertension.


Acknowledgments and disclosures: None.