Evidence map›Paper›PMID 38822391›Full record

ArticleClinical hypertension2024

Sympathetic overactivity and nocturnal diuresis in obstructive sleep apnea alter the response to hypertension therapy.

Michael G Ziegler, Milos Milic, Joel E Dimsdale, Paul J Mills

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical hypertension, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02699125 (A Placebo Controlled Double Blinded Crossover Study of the Antihypertensive Efficacy of Guanfacine vs Hydrochlorothiazide in Obstructive Sleep Apnea), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02699125 phase4completednot on this map

A Placebo Controlled Double Blinded Crossover Study of the Antihypertensive Efficacy of Guanfacine vs Hydrochlorothiazide in Obstructive Sleep Apnea (OSA) Associated Hypertension

TypeinterventionalSponsorUniversity of California, San DiegoRan2015 to 2016Enrolled41ConditionsObstructive Sleep ApneaArmsGuanfacine, Hydrochlorothiazide
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Overcoming variable response in renal denervation: Key strategies for reliable clinical implementation.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Review
  3. Review
  4. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Michael G ZieglerDepartment of Medicine, Division of Nephrology and Hypertension, University of California San Diego, UCSD Medical Center, 200 W. Arbor Drive, San Diego, CA, 92103- 8341, USA.
Milos MilicDepartment of Medicine, Division of Nephrology and Hypertension, University of California San Diego, UCSD Medical Center, 200 W. Arbor Drive, San Diego, CA, 92103- 8341, USA. mmilic@ucsd.edu.
Joel E DimsdaleDepartment of Psychiatry, University of California San Diego, UCSD Medical Center, 200 W. Arbor Drive, San Diego, CA, 92103-8341, USA.
Paul J MillsDepartment of Family Medicine and Public Health, University of California San Diego, UCSD Medical Center, 200 W. Arbor Drive, San Diego, CA, 92103-8341, USA.

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
ZOVIRAX CREAM TO TREAT HERPES LABIALIS IN ADOLESCENTSM01RR000827 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAAS, RICHARD H · 1985 to 2010
$74.3M
STRESS PHYSIOLOGY, DIETARY SALT, AND HYPERTENSIONR01HL036005 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIMSDALE, JOEL E · 1985 to 2010
$5.1M
SLEEP APNEA &HYPERTENSION--ROLE OF SYMP NERVOUS SYSTEMR01HL044915 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIMSDALE, JOEL E · 1991 to 2008
$4.7M
NCATS NIH HHS UL1 TR001442NCRR NIH HHS M01 RR000827NHLBI NIH HHS R01 HL036005NHLBI NIH HHS R01 HL044915NIH HHS M01 RR00827, UL1TR001442, HL44915 and HL36005.
6 · The paper itself

Abstract

backgroundObstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy. METHODS AND

resultsForty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal.

conclusionsOSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea.

trial registrationNCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125 .

Indexed as

Ambulatory blood pressureBaroreflexFlow mediated dilationGuanfacineHeart rate variabilityHydrochlorothiazideNorepinephrine

Identifiers

PMID38822391
PMCPMC11143623

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.