Understanding the Genetic Basis of Atherosclerosis and Peripheral Arterial Disease (GenePAD)

The Genetic Determinants of Peripheral Arterial Disease

Atherosclerosis, a condition in which fatty deposits build up along the inner walls of arteries, can occur throughout the body. The purpose of this study is to examine the possible genetic differences that may influence where atherosclerosis occurs.

Study Overview

• Status: Completed
• Conditions: Peripheral Vascular Diseases

Detailed Description

Plaque build-up caused by atherosclerosis increases the risk of blood clots, heart attack, and stroke. Blockages of plaque can occur in different areas of the body. PAD, a circulatory disorder in which blockages occur in the peripheral arteries, is one manifestation of atherosclerosis. Individuals with PAD experience reduced blood flow to the legs, which may cause leg pain while walking. Coronary artery disease (CAD), in which plaque builds up in arteries leading to the heart, is another atherosclerosis-related condition. Individuals with PAD and CAD have similar atherosclerosis risk factors, but it remains unknown why some individuals develop one disease and not the other. Genetic differences may influence where atherosclerosis develops. The goal of the study is to identify genetic variations that may cause inherited differences in plaque distribution.

This study will enroll individuals with PAD who have been referred by their doctor for a coronary angiogram to confirm the presence of CAD. A control group composed of individuals who do not have PAD, but have similar risk factors for atherosclerosis, will also be enrolled. All participants will attend one study visit. They will undergo a coronary angiogram, a procedure in which a special dye is inserted intravenously into an artery of the heart. X-rays will be taken to document how blood flows through the artery. Questionnaires assessing quality of life, exercise habits, tobacco exposure, and family medical history will be completed. Participants will also undergo blood pressure measurements and blood collection for genetic analysis. Yearly follow-up phone calls will occur for 5 years to document any hospitalizations.

• Study Type: Observational
• Enrollment (Actual): 1789

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • New York
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects are recruited from individuals undergoing elective coronary angiography for suspected CAD at Stanford University or Mount Sinai Medical Centers.

Description

Inclusion Criteria:

• Hemodynamically significant PAD, as documented by an ankle-brachial index less than 0.9; control group participants will not have PAD
• Received a referral for an elective coronary angiogram
• Suspected CAD

Exclusion Criteria:

• History of radiation treatment
• History of organ transplant
• History of viral diseases (i.e. HIV, hepatitis)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
1; Subjects with no hemodynamically significant disease (NHSD) of the coronary or peripheral arteries
2; Subjects with coronary artery disease only
3; Subjects with both coronary artery disease and peripheral arterial disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identifying genetic variations that may cause inherited differences in plaque distribution	Measured at participants' study visit

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: John P. Cooke, MD, PhD, Stanford University

Publications and helpful links

General Publications

• Flores AM, Schuler A, Eberhard AV, Olin JW, Cooke JP, Leeper NJ, Shah NH, Ross EG. Unsupervised Learning for Automated Detection of Coronary Artery Disease Subgroups. J Am Heart Assoc. 2021 Dec 7;10(23):e021976. doi: 10.1161/JAHA.121.021976. Epub 2021 Nov 30.
• Sadrzadeh Rafie AH, Stefanick ML, Sims ST, Phan T, Higgins M, Gabriel A, Assimes T, Narasimhan B, Nead KT, Myers J, Olin J, Cooke JP. Sex differences in the prevalence of peripheral artery disease in patients undergoing coronary catheterization. Vasc Med. 2010 Dec;15(6):443-50. doi: 10.1177/1358863X10388345.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: September 22, 2006
• First Submitted That Met QC Criteria: September 22, 2006
• First Posted (Estimate): September 25, 2006

Study Record Updates

• Last Update Posted (Estimate): May 28, 2015
• Last Update Submitted That Met QC Criteria: May 27, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Atherosclerosis; Peripheral Arterial Disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Atherosclerosis
• Other Study ID Numbers: 1361; R01HL075774 (U.S. NIH Grant/Contract)