Clinical trial NCT00331370: Hypertension Related Damage to the Microcirculation in South Asian: Emergence, Predictive Power and Reversibility
Official title: Hypertension Related Damage to the Microcirculation in South Asian: Emergence,Predictive Power and Reversibility
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypertension
Diabetes
Cardiovascular Disease
Retinopathy
Lead sponsor: Aga Khan University
Sponsor class: OTHER
Collaborators: name: Imperial College London
First posted: 2006-05-31
Enrollment: 2880
Sex: ALL
Minimum age (years): 9
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: Damage to very small blood vessels is a consequence, but can also precede high blood pressure. Such damage, measured by disturbances in the vessels in the retina (back of the eye) is a strong predictor of heart disease and stroke. South Asian people have one of the highest rates of hypertension in the world (30% in adults). In Pakistan, this is usually severe, undetected and untreated. The Wellcome Trust has already funded a study of blood pressure control in adults and children in this population. We propose a substudy, taking photographs of the retina and making measurements of the vessels, to determine whether such blood pressure related changes occur at an early age in young children with a family history of high blood pressure compared to those without, whether such changes predict an increase in blood pressure over time, and whether, in adults, such changes can be reversed by blood pressure treatment. The hypothesis of our study is: young offspring of South Asian people with hypertension have a disturbed microcirculation, as assessed by abnormalities of retinal vessels, compared to offspring of normotensive parents. Our 2nd hypothesis is: Abnormal retinal vascular geometry will improve proportionately to achieved reductions in BP.

Detailed description: Background

The role of the microcirculation is increasingly being recognized in the etiopathogenesis of cardiovascular disease. Delays in this recognition are in part due to the difficulty of studying the microcirculation non-invasively, in large numbers of individuals. Retinal vessels provide an easily accessible "window" to the microcirculation. Abnormalities of the retinal vasculature have been shown to be associated with cardiovascular risk factors and all cause mortality. Non-invasive assessment of the retinal circulation presents a valuable opportunity to study the structure and function of the microvasculature

Aims of the project

To compare geometry of retinal microvasculature of 1) hypertensive vs normotensive adults, 2) children aged 10 to 14 years of hypertensive parent (test group) versus normotensive parent (control group), and, 3) to assess the impact of blood pressure lowering on these changes over 2 years.

Primary outcome would be abnormal retinal geometry defined as the composite outcome of a) abnormal arteriolar length: diameter ratios (a measure of relative arteriolar narrowing), b) narrowed branching angles (an indicator of arteriolar rarefaction), or c) disturbed junction exponents (a marker of endothelial dysfunction.

Significance of the study

If successful, this work could be extended to address future questions, including the predictive value of these abnormalities for development of diabetes and hypertension as well as CVD; to explore further the role of microvascular disturbances in disease etiology, and to assess the impact of drug therapy on these abnormalities and their relationship to outcomes in the South Asian population

Eligibility criteria: Inclusion Criteria:

All subjects aged 9 years or over residing in randomly selected communities

Exclusion Criteria:

Pregnancy

Those who have severe co-morbid conditions

Patients with known history of glaucoma will be excluded from our study because instillation of mydriatic drops was thought to be hazardous for them.

Primary outcomes:
measure: Primary outcome would be abnormal retinal geometry defined as the composite outcome of a) abnormal arteriolar length: diameter, b) narrowed branching angles, or c) disturbed junction exponents.
Secondary outcomes:
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Aga Khan University
state: Sindh
Study officials:
affiliation: Aga Khan University
name: Tazeen H Jafar, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Nish Chaturvedi, MD, MFPHM
role: STUDY_CHAIR
affiliation: Imperial College London
name: Alun Hughes, MD, Phd
role: STUDY_CHAIR
affiliation: Aga Khan University
name: Juanita Hatcher, Phd, MSc
role: STUDY_CHAIR
affiliation: Imperial College London
name: Simon Thom, MD, FRCP
role: STUDY_CHAIR
affiliation: Aga Khan University
name: Khabir Ahmad, MD, MSc
role: STUDY_CHAIR
affiliation: Aga Khan University
name: Muhammad Saleem Khan, MSc Epi&Bio
role: STUDY_CHAIR
References: