Vitamin K Status and Markers of Vascular Function in Patients With and Without Postural Hypotension (VITKOH)

Postural hypotension is common in older people, leading to falls, decline in function, and dependence. Available treatments have limited efficacy and tolerability; novel approaches to treatment are therefore needed. Decreased vascular health, stiffening of the arteries and consequent decreased vascular reactivity are thought to contribute to postural hypotension and are therefore therapeutic targets.

Recent trial evidence has suggested that vitamin K may exert beneficial effects on vascular health particularly in respect to inhibiting calcification. Calcification increases vascular stiffness, decreases compliance and thus decreases the ability of blood vessels to autoregulate blood pressure and flow - which could contribute to postural drops in blood pressure. Worsened vascular health could also impact adversely on baroceptor function, which is needed for blood pressure autoregulation and which is disrupted in patients with orthostatic hypotension.

Vitamin K intake is below recommended daily intake in 60% of adults in the UK. In animals, vitamin K supplementation may be able to reverse calcification of arteries, and in humans Vitamin K has been shown to arrest decline in carotid artery elasticity compared to placebo. High levels of circulating vitamin K were also associated with lower levels of CRP in the Framingham cohort, suggesting a possible role in the suppression of chronic inflammation that is known to accompany vascular disease. The recent ECKO study suggested that vitamin K may reduce falls and fractures; an intriguing question that follows on from this is whether this could be due to beneficial effects on vascular health and postural hypotension, leading to less dizziness and reduced falls.

This cross-sectional comparative study aims to find whether there is a difference in the vitamin K status of patients with postural hypotension compared to those without postural hypotension and whether differences in vitamin K status are associated with other markers of vascular function in patients with and without postural hypotension. This could potentially lead to new treatments for the condition for which there is currently little of proven benefit.

Study Overview

• Status: Completed
• Conditions: Orthostatic Hypotension
• Intervention / Treatment: Other: Vitamin K status

• Study Type: Observational
• Enrollment (Actual): 49

Contacts and Locations

Study Locations

• United Kingdom
  • Angus
    • Dundee, Angus, United Kingdom, DD1 9SY
      • Univeristy of Dundee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Aged 65 years or older, not on warfarin, able to stand unaided, able to give informed consent.

Description

Inclusion Criteria:

• 65 years or older
• For postural hypotension group: >20mmHg systolic BP drop or >10mmHg diastolic BP drop on standing, and syncopal symptoms on standing.
• For control group: no fall in BP or <20mmHg systolic BP drop and <10mmHg diastolic BP drop on standing, and no syncopal symptoms on standing. No previous diagnosis of orthostatic hypotension.

Exclusion Criteria:

• On warfarin
• Unable to consent
• Unable to stand unaided

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Orthostatic Hypotension; >20mmHg systolic BP drop or >10mmHg diastolic BP drop on standing, and syncopal symptoms on standing	Other: Vitamin K status; Vitamin K status indicated by desphospho-uncarboxylated matrix Gla protein level
Control; No fall in BP or <20mmHg systolic BP drop and <10mmHg diastolic BP drop on standing, and no syncopal symptoms on standing	Other: Vitamin K status; Vitamin K status indicated by desphospho-uncarboxylated matrix Gla protein level

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum non-phosphorylated, non-carboxylated Matrix Gla Protein	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin K1 Level		Day 1
Vitamin D		Day 1
Flow mediated dilatation	Measure of endothelial function	Day 1
Pulse wave velocity	Measure of arterial stiffness and reflectivity	Day 1
Carotid intima media thickness		Day 1
Pulse wave augmentation index	Measure of arterial stiffness and refelctivity	Day 1

Collaborators and Investigators

• Sponsor: University of Dundee
• Collaborators: British Geriatrics Society

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: July 20, 2015
• First Submitted That Met QC Criteria: July 21, 2015
• First Posted (Estimate): July 22, 2015

Study Record Updates

• Last Update Posted (Estimate): July 24, 2015
• Last Update Submitted That Met QC Criteria: July 23, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Orthostatic hypotension; Vitamin K
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Hypotension; Hypotension, Orthostatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Micronutrients; Vitamins; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K
• Other Study ID Numbers: 2011CV14