Genetic Analysis of African-Americans With High Blood Pressure

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00353925
First received: July 18, 2006
Last updated: March 5, 2008
Last verified: December 2007
  Purpose

The purpose of this study is to learn if kinase, a protein found in the heart, contributes to thickening of the heart muscle in people with high blood pressure.

A protein called myosin causes the heart to contract and relax. It is thought that kinase changes myosin to make it work better at different heart rates. This study will try to determine if, in some people with high blood pressure, the different forms of this protein cause changes in the heart. If the protein affects the size of the heart, it might be possible to use it to improve heart function after an injury, such as a heart attack.

African-Americans with high blood pressure will be eligible for this study. Current data show that of almost 900 multi-ethnic individuals, the particular form of kinase under study in this project is found exclusively in the African-American population. Study participants will have two tubes of blood drawn for DNA testing to determine what form of kinase is present. An electrocardiogram will also be done if a recent one is not available. Some people may also have an echocardiogram, an ultrasound test to image the heart.


Condition
Hypertension

Study Type: Observational
Official Title: Genetic Analysis of African-American Hypertensives

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 1000
Study Start Date: October 1999
Estimated Study Completion Date: December 2007
Detailed Description:

Genetic and in vitro mechanical studies in our laboratory have suggested that the perturbations in the phosphorylation of the cardiac myosin regulatory light chain (RLC) can modulate cardiac function and produce a compensatory hypertrophic response. We have cloned a novel human cardiac kinase (MLCK) that targets the cardiac RLC and identified a common allele unique to the African-American population. The purpose of this protocol is to evaluate a large group of African-American individuals with hypertension and/or cardiac disease, a portion of who will possess this allele. It is well documented that hypertensive African-Americans have an increased prevalence of left ventricular hypertrophy (LVH). We expect that, in this population of hypertensive individuals, we will find an increased left ventricular mass in individuals who are heterozygous or homozygous for this kinase allele.

In this study, patients with the allele can be matched to others in the cohort without the allele and evaluated by echocardiography and cardiac MRI to evaluate cardiac function and chamber size. In addition, metabolic stress testing will be performed to assess the implications of this allele on clinical performance. Another group of 75 Afro-Americans with dilated cardiomyopathy will be referred from local heart failure clinics and evaluated in a similar fashion. Allele prevalence and associated cardiac findings will also be compared with hypertensive patients matched for age and gender. In a parallel experiment, mice over-expressing this kinase, are being generated and will provide us with tissue samples with which to pursue the biophysical basis of the mechanical changes in muscle function.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Inclusion Criteria (Main Cohort):

Afro-American patients with a history of hypertension

Age greater than or equal to 21 years old

Presence of the kinase allele (homo or heterozygous)

Ability to give informed consent.

Inclusion Criteria (Myopathy Cohort):

All of the above as well as:

Left ventricular ejection fraction of less than 35% by any imaging technique.

EXCLUSION CRITERIA

For subjects with Kinase Allele:

There will be no exclusion criteria. Patients will be evaluated even if they are only able to participate in part of the study.

For Subjects without the kinase allele and Myopathy Cohort:

History of myocardial infarction

History of significant valve disease

History of primary hyperthropic or infiltrative cardiomyopathy

History of rheumatic heart disease

Chronic atrial arrhythmia, bundle branch block intraventricular conduction defect or definite myocardial infarction on EKG

Inability to perform a metabolic stress test

Inability to perform a cMRI

Poor echocardiographic windows precluding accurate analysis

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00353925

Locations
United States, Maryland
University of Maryland, Baltimore
Baltimore, Maryland, United States, 21201-1595
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00353925     History of Changes
Other Study ID Numbers: 000003, 00-H-0003
Study First Received: July 18, 2006
Last Updated: March 5, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Hypertrophy
LVH
Cardiac
Blood Pressure
Papillary Muscle

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 17, 2014