The purpose of the study is to test the hypothesis that persistent fluid retention and high
sympathetic output contributes to the development of refractory hypertension (HTN). The
investigators will determine, in a cross-over assessment of high and low salt diets, if
dietary sodium restriction reduces 24-hr ambulatory BP in patients with refractory HTN.
Moreover, the investigators will determine if dietary sodium restriction lessens the severity
of obstructive sleep apnea (OSA) in patients with refractory HTN.
We are proposing a unique phenotype of antihypertensive treatment failure that we refer to as
refractory HTN. We have come to feel that while resistant (RHTN) represents a broad phenotype
with multiple and overlapping etiologies of treatment resistance, there is a unique subset of
patients who never achieve BP control in spite of maximal therapy. In a recently published
retrospective analysis of our clinic experience, we found that patients with refractory HTN
comprised about 10% of patients referred to us for RHTN.
A large number of intervention studies have verified the benefit of dietary salt restriction
to reduce BP. We made such an assessment in a prospective, randomized, cross-over comparison
of high- and low salt diets in 12 patients with confirmed RHTN. The average reduction in BP
going from high to the low salt diet was 23/10 mmHg in the clinic and 20/10 mmHg during 24-hr
ambulatory BP monitoring. These dramatic results demonstrated that patients with RHTN are
exquisitely salt-sensitive and highlight the degree of BP reduction that can be accomplished
with meaningful salt restriction. However, we are proposing the novel hypothesis that
refractory HTN is mechanistically unique from RHTN in that it is not secondary to
recalcitrant fluid retention.
Determining an association between dietary salt restriction and severity of obstructive sleep
apnea (OSA) would potentially help us to find new therapies guided towards achieving better
control of BP in patients with refractory HTN. We will investigate the effect of dietary salt
intake on severity of OSA vascular function in patients with refractory HTN by doing vascular
studies (pulse wave analysis/velocity, calculating thoracic impedance)).
- Adult subjects ≥ 19 years of age
- Refractory hypertension defined as office BP > 140/90 that is uncontrolled with at
least 5 different classes of antihypertensive medications
- Self-reported adherence >80% with prescribed antihypertensive medications
- Severe hypertension (office BP >160/100 mm Hg)
- History of congestive heart failure (ejection fraction of <40%)
- Chronic kidney disease (creatinine clearance <60 ml/min)
- History of cardiovascular disease (stroke, TIA, myocardial infarction, or
- White coat hypertension defined as office BP >140/90 mm Hg and ambulatory daytime BP
<135/85 mm Hg
- Pregnant or nursing women