Extremes of Coronary Artery Disease and Normality:CAD Extremes

Summary

In the field of cardiovascular medicine, there are two differing groups of patients that remain puzzling to clinicians: patients who are not expected to have coronary artery disease (CAD) yet are diagnosed with significant CAD; and those who are have multiple risk factors for CAD but do not have CAD. Bats exhibit unique phenotypes including long lifespans and likely reduced atherosclerosis. Prior work has identified multiple molecular mechanisms of suppressing the activation of inflammasomes, causally linked to atherosclerosis. The investigators hypothesize there are different molecular markers that confer protection or increased risk for CAD, some of which may be similar to bats. Thus, the aim of this study is to identify molecular markers that contribute to or are protective against acute coronary syndrome (ACS) through analyzing the genetics, peripheral blood and atherosclerotic samples from both extreme patient groups using single-cell RNA sequencing and multi-omics approach. In addition, novel anti-atherosclerotic mechanisms and factors from bat studies will be assessed in the human samples. Identification of novel targets that prevent or cause CAD has the potential to aid in the early identification of high-risk patients and development of new therapeutics to combat this growing epidemic. To conduct this study, patients who have undergone a coronary angiogram or a CT coronary angiogram that fall into the both extremes will be recruited and blood samples will be taken for the above analysis. These will be compared to a group of controls (low risk without disease and high risk with disease).

Eligibility

Inclusion Criteria:

Group 1:

1. Evidence of significant CAD a. Coronary angiogram or CT coronary angiogram with documented stenosis \>=50% in left main or \>=70% in major epicardial vessel or major branches (LAD, LCX, RCA)

   AND all of the following
2. Age \</= 45 for males and \</= 50 for females
3. Absence of diabetes mellitus
4. Absence of tobacco use
5. No prior CVA or PAD

Group 2

1. Evidence of significant CAD

   1. Coronary angiogram or CT coronary angiogram with documented stenosis \>=50% in left main or \>=70% in major epicardial vessel or major branches (LAD, LCX, RCA)

   AND all of the following
2. Age \</= 45 for males and \</= 50 for females
3. Absence of diabetes mellitus
4. Absence of tobacco use
5. No prior CVA or PAD

Group 3 1. Evidence of significant CAD with one of the following:

1. age\>65
2. Diabetes mellitus
3. End Stage Renal Failure (ESRF)
4. Framingham risk score \>10%

Group 4

1\. No evidence of significant CAD and all of the following

1. Age \<55 for males, \<65 for females
2. Absence of diabetes mellitus
3. Absence of CKD
4. Absence of tobacco use

Exclusion Criteria:

1. Prior history of cancer (excludes pre-cancerous lesions)
2. Expected life expectancy less than 1 year
3. Known autoimmune disease
4. Psychiatric illness
5. Chronic lung disease requiring long term medications or oxygen
6. Chronic infective disease, including tuberculosis, hepatitis B and C; and HIV
7. Inability to comply with study protocol
8. Any other acute or chronic medical or physical condition deemed by the investigator to affect study outcomes

Conditions2

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