Increased Dietary Sodium Is Related to Severity of Obstructive Sleep Apnea in Patients With Resistant Hypertension and Hyperaldosteronism

doi:10.1378/chest.12-0802

Chest

Volume 143, Issue 4, April 2013, Pages 978-983

https://doi.org/10.1378/chest.12-0802 Get rights and content

Background

Obstructive sleep apnea (OSA) is a strong and independent risk factor for the development of hypertension, particularly resistant hypertension, and cardiovascular diseases. Patients with resistant hypertension have a high prevalence of OSA in association with elevated aldosterone levels, high salt intake, and salt-sensitive BP. The objective of this study was to determine whether dietary salt and aldosterone are associated with severity of OSA in patients with resistant hypertension.

Methods

Ninety-seven patients with resistant hypertension were prospectively evaluated by overnight polysomnography and 24-h urinary sodium and aldosterone levels while maintaining their usual diet. Hyperaldosteronism was defined as a plasma renin activity of < 1 ng/mL/h and urinary aldosterone level of ≥ 12 μg/24 h.

Results

Overall, patients' mean clinic BP was 156.3 ± 22.4/88.9 ± 13.3 mm Hg while taking an average of 4.3 ± 1.1 antihypertensive medications. Prevalence of OSA was 77.3%. Twenty-eight (28.9%) patients had hyperaldosteronism. Urinary sodium level was an independent predictor of severity of OSA only in patients with hyperaldosteronism.

Conclusions

The findings suggest that dietary salt is related to the severity of OSA in patients with resistant hypertension and hyperaldosteronism. The results support dietary salt restriction as a treatment strategy for reduction of OSA severity in these patients.

Section snippets

Patients

Consecutive patients with resistant hypertension referred to The University of Alabama at Birmingham Hypertension Clinic were evaluated prospectively. The protocol was approved by the university's Institutional Review Board for Human Use (IRB number F080821013), and all patients provided written informed consent before study participation.

Resistant hypertension was defined as uncontrolled hypertension (> 140/90 mm Hg) determined at two or more clinic visits despite the use of three or more

Results

In total, 97 patients with resistant hypertension were evaluated. Overall, 47.4% were men, 48.5% were black, the mean age was 55.2 ± 9.0 years, and the mean office BP was 156.3 ± 22.4/88.9 ± 13.3 mm Hg (Table 1). Patients took an average of 4.3 ± 1.1 antihypertensive medications, which included angiotensin-converting enzyme inhibitors (61.2%), angiotensin receptor blockers (57.3%), calcium channel blockers (76.7%), β-blockers (77.7%), and diuretics (91.3%). None of the patients were taking

Discussion

To our knowledge, this study is the first to demonstrate in a hypertensive cohort that dietary salt and aldosterone are associated with severity of OSA. UNa, which could be used for the estimation of dietary salt intake, was positively correlated with AHI in patients with resistant hypertension and hyperaldosteronism. The study also confirms that OSA is highly prevalent among patients with resistant hypertension. In a recent prospective analysis of 125 patients with resistant hypertension, OSA

Acknowledgments

Author contributions: Dr Calhoun had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Pimenta: contributed to the study conception and design; data acquisition, analysis, and interpretation; statistical analysis; and drafting of the manuscript.

Dr Stowasser: contributed to the data interpretation and critical revision of the manuscript for important intellectual content.

Dr Gordon: contributed to the

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Cited by (62)

Resistant Hypertension
2023, Hypertension: A Companion to Braunwald's Heart Disease
Resistant hypertension (RHTN) is defined as the failure to lower blood pressure (BP) values to the target value despite appropriate treatment with optimal doses of at least three antihypertensive drugs including a renin-angiotensin system (RAS) blocker, a long-acting calcium channel blocker (CCB), and a thiazide (or thiazide-like) diuretic. Pseudoresistance should be excluded by 24-hour ambulatory or home BP monitoring and nonadherence to medications at best by drug monitoring. RHTN management combines lifestyle changes, the discontinuation of interfering substances, the reinforcement of sodium depletion, and the sequential addition of antihypertensive drugs to the initial triple therapy (diuretic, RAS blocker, and CCB), including spironolactone as a fourth-line treatment, followed by sequential sympathetic nervous system blockade. New pharmacologic treatments targeting new pathways and device-based approaches aiming to decrease sympathetic tone, including renal denervation and baroreceptor stimulation, are currently being developed.
Overall diet quality and proinflammatory diet in relation to risk of obstructive sleep apnea in 3 prospective US cohorts
2022, American Journal of Clinical Nutrition
Inflammation-related mechanisms may be important in the development of obstructive sleep apnea (OSA), and diet plays a crucial role in modulating inflammation. Current epidemiologic evidence for the associations between dietary patterns and OSA risk is limited to cross-sectional studies.
We investigated prospectively the associations of overall diet quality and proinflammatory diet with OSA risk.
We followed 145,801 participants in the Nurses’ Health Study (NHS) (2002–2012), NHS II (1995–2013), and Health Professionals Follow-up Study (1996–2012). Alternative Healthy Eating Index 2010 (AHEI) and Empirical Dietary Inflammatory Pattern (EDIP) scores were calculated based on validated FFQs administered every 4 y. Cox models were used to estimate HRs and 95% CIs.
We documented 8856 incident OSA cases during follow-up. In pooled analyses adjusted for potential confounders, higher diet quality (higher AHEI scores) was associated with lower OSA risk (HR comparing the highest with the lowest quintile of AHEI: 0.76; 95% CI: 0.71, 0.82; P-trend < 0.001), and higher dietary inflammatory potential (higher EDIP scores) was associated with significantly increased risk (HR comparing the highest with the lowest quintile of EDIP: 1.94; 95% CI: 1.81, 2.08; P-trend < 0.001). Additional adjustment for metabolic factors attenuated both associations. The association with AHEI score was no longer statistically significant (comparable HR: 0.98; 95% CI: 0.91, 1.05; P-trend = 0.54), whereas the association with EDIP score remained statistically significant (comparable HR: 1.31; 95% CI: 1.22, 1.41; P-trend < 0.001).
A healthier diet, particularly one with anti-inflammatory potential, was associated with lower OSA risk.
The 2020 Italian Society of Arterial Hypertension (SIIA) practical guidelines for the management of primary aldosteronism
2020, International Journal of Cardiology: Hypertension
Citation Excerpt :
Prospective studies of patients with resistant hypertension showed a 77% prevalence of OSA; moreover, 29% of them also had PA [116], thus suggesting that both OSA and PA often coexist in these patients. As 24-h urinary sodium level was an independent predictor of severity of OSA in PA patients, aldosterone-driven salt and fluid retention might have a play in the development of OSA in resistant patients; moreover, dietary salt restriction could be a treatment strategy for reduction of OSA severity in such patients [117]. Arterial hypertension is a major risk factor for atrial fibrillation (AF) and between 50% and 90% of AF patients have hypertension [118–122].
Considering the amount of novel knowledge generated in the last five years, a team of experienced hypertensionlogists was assembled to furnish updated clinical practice guidelines for the management of primary aldosteronism.
To identify the most relevant studies, the authors utilized a systematic literature review in international databases by applying the PICO strategy, and then they were required to make use of only those meeting predefined quality criteria. For studies of diagnostic tests, only those that fulfilled the Standards for Reporting of Diagnostic Accuracy recommendations were considered.
Each section was jointly prepared by at least two co-authors, who provided Class of Recommendation and Level of Evidence following the American Heart Association methodology. The guidelines were sponsored by the Italian Society of Arterial Hypertension and underwent two rounds of revision, eventually reexamined by an External Committee. They were presented and thoroughly discussed in two face-to-face meetings with all co-authors and then presented on occasion of the 36th Italian Society of Arterial Hypertension meeting in order to gather further feedbacks by all members. The text amended according to these feedbacks was subjected to a further peer review.
After this process, substantial updated information was generated, which could simplify the diagnosis of primary aldosteronism and assist practicing physicians in optimizing treatment and follow-up of patients with one of the most common curable causes of arterial hypertension.
Plasma xanthine oxidase activity is related to increased sodium and left ventricular hypertrophy in resistant hypertension
2019, Free Radical Biology and Medicine
Citation Excerpt :
We previously reported that despite a decrease in LV mass and systolic blood pressure, there is no improvement in LV diastolic function in 35 patients with RHTN who remained on a high-salt diet. [29,31]. Pimenta et al. have shown that in RHTN patients with high urinary aldosterone, the extent of LV hypertrophy [13], urinary protein excretion [35], and severity of sleep apnea [36] increase progressively across urinary sodium groups. Taken together, these human and numerous animal studies highlight the interdependence of aldosterone and dietary sodium in relation to target organ damage. [37].
The extra-renal effects of aldosterone on left ventricular (LV) structure and function are exacerbated by increased dietary sodium in persons with hypertension. Previous studies demonstrated endothelial dysfunction and increased oxidative stress with high salt diet in normotensive salt-resistant subjects. We hypothesized that increased xanthine oxidase (XO), a product of endothelial cells, is related to 24-h urinary sodium and to LV hypertrophy and function in patients with resistant hypertension (RHTN).
The study group included persons with RHTN (n = 91), defined as a blood pressure > 140/90 mmHg on ≥ 3 medications at pharmacologically effective doses. Plasma XO activity and 24-h urine were collected, and cardiac magnetic resonance imaging (MRI) was performed to assess LV function and morphology. Sixty-seven normotensive persons on no cardiovascular medications served as controls. A subset of RHTN (n = 19) received spironolactone without salt restriction for six months with follow-up XO activity measurements and MRI analyses.
XO activity was increased two-fold in RHTN vs. normal and was positively correlated with LV mass, LV diastolic function, and 24-h urinary sodium. In RHTN patients receiving spironolactone without salt restriction, LV mass decreased, but LV diastolic function and XO activity did not improve. Baseline urinary sodium was positively associated with rate of change of LV mass to volume ratio and the LV E/A ratio.
These results demonstrate a potential role of endothelium-derived oxidative stress and excess dietary salt in the pathophysiology of LV hypertrophy and diastolic dysfunction in persons with RHTN unaffected by the addition of spironolactone.
Targeting volume overload and overnight rostral fluid shift: A new perspective to treat sleep apnea
2018, Sleep Medicine Reviews
Citation Excerpt :
More recently, high-salt intake has been implicated in the pathogenesis of OSA. In patients with resistant hypertension and primary aldosteronism, the AHI directly correlated with urine sodium excretion, which is a marker of salt intake [77]. Similarly, an observational study of patients with HF demonstrated that patients with OSA had a higher sodium intake, as measured by a food diary, than patients without OSA, and the AHI directly correlated with sodium intake, which suggests that OSA is associated with fluid overload secondary to the high sodium intake [78].
Sleep apnea is a common condition associated with increased morbidity and mortality. Continuous positive airway pressure and oral appliances are efficient for treating sleep apnea; however, they are often poorly tolerated. Therefore, alternative therapies are needed. Overnight rostral fluid shift has been implicated in the pathogenesis of sleep apnea, particularly in conditions associated with fluid overload. Fluid shift predisposes to both obstructive and central sleep apnea, with the type of sleep apnea being related to whether the fluid shifts from the legs into the neck or chest, respectively. The amount of fluid that shifts from the legs to the upper part of the body at night is correlated with the severity of sleep apnea. As a result of this observation, it has been suggested that the prevention of overnight fluid shift may reduce sleep apnea severity. It has recently been shown that interventions targeting fluid overload and daytime fluid accumulation in the legs consistently attenuate nocturnal fluid shift and sleep apnea, as greater reductions in fluid shift are correlated with greater reductions in sleep apnea severity. This review will focus on interventions that counteract fluid shift, such as diuretics, ultrafiltration/dialysis, physical activity, compression stockings and salt/fluid restriction, which have been shown to have efficacy in reducing sleep apnea severity.
Resistant Hypertension
2018, Hypertension: A Companion to Braunwald's Heart Disease

View all citing articles on Scopus

Funding/Support: This work was supported by National Heart, Lung, and Blood Institute [Grants HL075614 and SCCOR P50 HL077100 (to Dr Calhoun)] and National Institutes of Health National Center for Research Resources [Grant 5UL1 RR025777-04].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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Chest

Original ResearchSleep DisordersIncreased Dietary Sodium Is Related to Severity of Obstructive Sleep Apnea in Patients With Resistant Hypertension and Hyperaldosteronism

Background

Methods

Results

Conclusions

Section snippets

Patients

Results

Discussion

Acknowledgments

Am Heart J

Chest

Chest

Lancet

Prog Cardiovasc Dis

Chest

J Am Coll Cardiol

Am J Hypertens

Prospective study of the association between sleep-disordered breathing and hypertension

N Engl J Med

Sleep-related breathing disorder is an independent risk factor for systemic hypertension

Am J Respir Crit Care Med

Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study

JAMA

Epidemiology of obstructive sleep apnea: a population health perspective

Am J Respir Crit Care Med

Circulation

Hypertension, erectile dysfunction, and occult sleep apnea

Sleep

Sleep apnea and hypertension: interactions and implications for management

Hypertension

The prevalence of obstructive sleep apnea in hypertensives

Am J Respir Crit Care Med

Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension

Hypertension

High prevalence of unrecognized sleep apnoea in drug-resistant hypertension

J Hypertens

Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion

BMJ

Original Research
Sleep Disorders
Increased Dietary Sodium Is Related to Severity of Obstructive Sleep Apnea in Patients With Resistant Hypertension and Hyperaldosteronism