Effect of Dietary Sodium Intake on Vascular Endothelium

Postural Tachycardia Syndrome (POTS) Clinical Trial

Official title:

A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01550315
• Other study ID #: 111577
• Secondary ID: R01HL102387
• Status: Completed
• Phase: N/A
• Start date: April 2012
• Est. completion date: September 2021

Study information

• Verified date: December 2021
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will test the hypothesis that markers of vascular endothelial dysfunction will be exaggerated acutely with an extreme high sodium diet compared to an extreme low-sodium diet. The investigators will compare patients with postural orthostatic tachycardia (POTS) to healthy control subjects.

Description:

The study will involve a crossover design in which each subject will be assessed (as below) while on a very low-sodium (10 mEq/day) diet compared with a very high-sodium diet. These acute dietary interventions will be part of the parent study ("Dietary Salt in Postural Tachcyardia Syndrome" funded by R01 HL102387) for 4-5 days at the time of the study. Dietary success will be assessed using a 24h urine for sodium and creatinine as a part of the parent study.

Blood will be drawn and collected in a fasting state for future assay and analysis of the following tests:

• Glucose, Insulin (glucose impairment, insulin resistance)

• Fasting lipid profile

• C-Reactive Protein (hsCRP) (inflammatory state)

• Inflammatory cytokines (inflammatory state)

• aliquots (future analysis)

Pulsitile Arterial Tonometry (PAT) Protocol Calf Blood Flow in Reactive Hyperemia (CBF-RH) - venous occlusion plethysmography Evaluation of Forearm-Mediated Dilation

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: September 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Subjects will be enrolled in the parent study "Dietary Salt in Postural Tachcyardia Syndrome" funded by R01 HL102387 Postural Tachycardia Syndrome

• Diagnosed with postural tachycardia syndrome by the Vanderbilt Autonomic Dysfunction Center

• Subjects will be enrolled in the parent study "Dietary Salt in Postural Tachcyardia Syndrome" funded by R01 HL102387

• Postural Tachycardia Syndrome

• Diagnosed with postural tachycardia syndrome by the Vanderbilt Autonomic Dysfunction Center

• Increase in heart rate =30 beats/min with position change from supine to standing (10 minutes)

• Chronic symptoms consistent with POTS that are worse when upright and get better with recumbence Control Subjects

• Healthy, non-obese, non-smokers without orthostatic tachycardia

• Selected to match profiles of POTS patients (gender, age)

• Not using vasoactive medication

• Age between 18-60 years

• Male and female subjects are eligible.

• Able and willing to provide informed consent

Exclusion Criteria:

• Overt cause for postural tachycardia (such as acute dehydration)

• Inability to give, or withdrawal of, informed consent

• Pregnant

• Other factors which in the investigator's opinion would prevent the subject from completing the protocol.

Related Conditions & MeSH terms

• Postural Orthostatic Tachycardia Syndrome
• Postural Tachycardia Syndrome (POTS)
• Tachycardia

Intervention

Procedure:
• Pulsitile Arterial Tonometry (PAT) Protocol
A blood pressure cuff will be placed on one upper arm (study arm; non-dominant), while the contralateral arm will serve as a control (control arm). RH-PAT probes will be placed on one finger (finger II, III, or IV) of each hand (same finger on both hands). The fingers on either side of the one with the probe will be separated using soft sponge rings. Continuous recording of pulsatile blood volume responses from both hands will be initiated. After a 10-min equilibration period, the blood pressure cuff on the study arm will be inflated to 60 mm Hg above systolic pressure for 5 min. The cuff will then be deflated to induce reactive hyperemia, PAT recording will be stopped.

Device:
• Calf Blood Flow in Reactive Hyperemia (CBF-RH)
Calf blood flow (CBF) will be determined using venous occlusion plethysmography and calibrated mercury strain-gauges during reactive hyperemia after a 5 min of ischemia of the distal limb. Strain-gauges will be applied to the widest part of the non-dominant calf (~10 cm below patella). Participants will remain quietly supine for 10 min with legs elevated on foam pads above the right atrium to achieve stable baseline measurements of CBF. The venous occlusion cuff is inflated for 4 seconds at 8 seconds intervals, while monitoring the change in resistance in the system, pressure inside the measuring cuff, and 5-10 determinations are performed
• Evaluation of Forearm-Mediated Dilation
The arm will be kept extended and immobilized at heart level. Brachial artery diameter will be measured using a high resolution ultrasonography using a linear array probe with a 5 to 17 MHz frequency range. The brachial artery will be imaged in longitudinal sections, 5-10 cm proximal to placement of an occlusion cuff in the dominant forearm just below the antecubital fossa. The probe will be held with a stereotaxic holder with micrometer movement capabilities.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (3)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (25)

Al Suwaidi J, Higano ST, Holmes DR Jr, Lennon R, Lerman A. Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries. J Am Coll Cardiol. 2001 May;37(6):1523-8. — View Citation

Appel LJ, Frohlich ED, Hall JE, Pearson TA, Sacco RL, Seals DR, Sacks FM, Smith SC Jr, Vafiadis DK, Van Horn LV. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke: a call to action from the American Heart Association. Circulation. 2011 Mar 15;123(10):1138-43. doi: 10.1161/CIR.0b013e31820d0793. Epub 2011 Jan 13. — View Citation

Böger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, Blaschke TF, Cooke JP. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation. 1998 Nov 3;98(18):1842-7. — View Citation

Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman A. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004 Dec 7;44(11):2137-41. — View Citation

Centers for Disease Control and Prevention (CDC). Vital signs: prevalence, treatment, and control of hypertension--United States, 1999-2002 and 2005-2008. MMWR Morb Mortal Wkly Rep. 2011 Feb 4;60(4):103-8. — View Citation

Clarkson P, Celermajer DS, Powe AJ, Donald AE, Henry RM, Deanfield JE. Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease. Circulation. 1997 Nov 18;96(10):3378-83. — View Citation

Dakak N, Husain S, Mulcahy D, Andrews NP, Panza JA, Waclawiw M, Schenke W, Quyyumi AA. Contribution of nitric oxide to reactive hyperemia: impact of endothelial dysfunction. Hypertension. 1998 Jul;32(1):9-15. — View Citation

Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ; Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005 Jan;23(1):7-17. Review. — View Citation

Dishy V, Sofowora GG, Imamura H, Nishimi Y, Xie HG, Wood AJ, Stein CM. Nitric oxide production decreases after salt loading but is not related to blood pressure changes or nitric oxide-mediated vascular responses. J Hypertens. 2003 Jan;21(1):153-7. — View Citation

Fujiwara N, Osanai T, Kamada T, Katoh T, Takahashi K, Okumura K. Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension : modulation of nitric oxide synthesis by salt intake. Circulation. 2000 Feb 29;101(8):856-61. — View Citation

Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Kajiyama G, Oshima T. A noninvasive measurement of reactive hyperemia that can be used to assess resistance artery endothelial function in humans. Am J Cardiol. 2001 Jan 1;87(1):121-5, A9. — View Citation

Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP, Karas RH, Udelson JE. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003 Jul;146(1):168-74. — View Citation

Landmesser U, Merten R, Spiekermann S, Büttner K, Drexler H, Hornig B. Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation. 2000 May 16;101(19):2264-70. — View Citation

Mangin EL Jr, Kugiyama K, Nguy JH, Kerns SA, Henry PD. Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta. Circ Res. 1993 Jan;72(1):161-6. — View Citation

MENEELY GR, BALL CO. Experimental epidemiology of chronic sodium chloride toxicity and the protective effect of potassium chloride. Am J Med. 1958 Nov;25(5):713-25. — View Citation

Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA. Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev. 2005 Apr;85(2):679-715. Review. — View Citation

Meredith IT, Currie KE, Anderson TJ, Roddy MA, Ganz P, Creager MA. Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide. Am J Physiol. 1996 Apr;270(4 Pt 2):H1435-40. — View Citation

Nohria A, Gerhard-Herman M, Creager MA, Hurley S, Mitra D, Ganz P. Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. J Appl Physiol (1985). 2006 Aug;101(2):545-8. Epub 2006 Apr 13. — View Citation

Noon JP, Haynes WG, Webb DJ, Shore AC. Local inhibition of nitric oxide generation in man reduces blood flow in finger pulp but not in hand dorsum skin. J Physiol. 1996 Jan 15;490 ( Pt 2):501-8. — View Citation

Quyyumi AA, Dakak N, Andrews NP, Husain S, Arora S, Gilligan DM, Panza JA, Cannon RO 3rd. Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis. J Clin Invest. 1995 Apr;95(4):1747-55. — View Citation

Rozanski A, Qureshi E, Bauman M, Reed G, Pillar G, Diamond GA. Peripheral arterial responses to treadmill exercise among healthy subjects and atherosclerotic patients. Circulation. 2001 Apr 24;103(16):2084-9. — View Citation

Strazzullo P, D'Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ. 2009 Nov 24;339:b4567. doi: 10.1136/bmj.b4567. Review. — View Citation

Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H2-12. doi: 10.1152/ajpheart.00471.2010. Epub 2010 Oct 15. Review. — View Citation

Vergnani L, Hatrik S, Ricci F, Passaro A, Manzoli N, Zuliani G, Brovkovych V, Fellin R, Malinski T. Effect of native and oxidized low-density lipoprotein on endothelial nitric oxide and superoxide production : key role of L-arginine availability. Circulation. 2000 Mar 21;101(11):1261-6. — View Citation

Wilkinson IB, Qasem A, McEniery CM, Webb DJ, Avolio AP, Cockcroft JR. Nitric oxide regulates local arterial distensibility in vivo. Circulation. 2002 Jan 15;105(2):213-7. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FMD (% Change)	The primary analysis will involve a non-parametric, paired, Signed Rank test of flow mediated dilation (FMD) between all subjects (POTS & control subjects) on the high sodium diet vs low sodium diet	FMD was assessed on the morning of day 7, after 6 days of being on either a high salt diet or a low salt diet.