Psoriasis and Risk of Coronary Artery Disease: Detection of Early Atherosclerosis

1. Psoriasis and Risk of Coronary Artery Disease: Detection of Early Atherosclerosis Eric H. Yang, MD, FACC Assistant Professor of Medicine Director of the Coronary Care Unit Interventional Cardiology University of North Carolina at Chapel Hill

2. Case 35 year old white male with psoriasis. PASI score 52 Being evaluated for systemic therapy.

4. Outline Background Invasive Detection of CAD Non-Invasive Detection of Early CAD Surrogate Biomarkers Endothelial Function

5. �Great Advances in Cardiovascular Medicine� Pharmacology: Beta Blockers, ACEI, Statins, Thrombolytics Coronary Interventions: Angioplasty, Stents, Distal Protection Devices Prevention: Smoking Cessation, Cardiac Rehab

6. This slide illustrates the leading causes of death for all males and females for 2002, which underscores the magnitude of the problem of cardiovascular disease. Among both men and women, the deaths from total cardiovascular disease was almost greater than those from all other causes combined. Any impact we can make to improve the incidence of adverse cardiovascular outcomes will have an enormous effect on public health.This slide illustrates the leading causes of death for all males and females for 2002, which underscores the magnitude of the problem of cardiovascular disease. Among both men and women, the deaths from total cardiovascular disease was almost greater than those from all other causes combined. Any impact we can make to improve the incidence of adverse cardiovascular outcomes will have an enormous effect on public health.

7. Epidemiology 1.7 Million Americans per year suffer from a AMI, 290,000 of which are STEMI. It is estimated that the number of years of life lost due to an AMI is 14.2 years. The direct and indirect cost of myocardial infarction to the American Society is billions of dollars per year. 12% of those who make it to a hospital will die from their STEMI.

8. �Whatcha Talkin Bout Willis?� Psoriasis and CAD: Epidemiological Data

9. General Practice Research Database (GPRD) 8 Million UK residents with > 35 million years of follow up. Gelfand Study: Divided population into 3 Groups: Mild Psoriasis: Not on Systemic Therapy (N = 127,139) Severe Psoriasis: On systemic Therapy (N=3837) Matched Controls: N= 556,955

10. Mild PsoriasisMultivariate Cox Proportional Hazard of MI

11. Severe PsoriasisMultivariate Cox Proportional Hazard of MI

12. Adjusted Relative Risk of MIBased on Patient Age

13. Swedish Inpatient Registry National Database of all Inpatient Admissions/Discharges in Sweden since 1947. Mallbris et. al. selected 8991 patients hospitalized for psoriasis. Compared Cardiovascular Mortality to general population

14. Inverted Risk for Age

15. Summary Psoriasis appears to be an independent risk factor for CAD. The risk is greatest in those with severe psoriasis. There is an �Inverted Risk for Age�, that is, psoriasis is a greater risk factor for CAD in the younger population.

16. �Ok. We Have a Problem, But What Do We Do About it?� Therapy and Prevention

17. Associated Conventional Risk Factors

18. Conventional Risks Blood Pressure Control Smoking Cessation Aggressive Lipid Therapy Glucose Control

19. Disease Specific Therapy Does disease specific therapy for psoriasis reduce the risk for future cardiac events? No current large scale trials investigating this question. In order to study effect of disease specific therapy on cardiac risk, we need a method for detecting early CAD.

20. Ideal Test Low risk and cost to patient Easy to perform in serial fashion Reliable predictor of future cardiac events.

21. Invasive Assessment of CAD

22. Coronary Angiography �Gold Standard� Limited ability to detect early phases of atherosclerosis. Invasive

23. Intravascular Ultrasound Small ultrasound probe that is placed intracoronary via a guiding catheter and wire. Allows �look inside� vessel. Able to detect and quantify amount of early atherosclerotic disease. Modality used in statin trials investigating plaque regression with therapy. Requires advance skill set to perform. More Invasive than coronary angiography.

24. Summary Coronary angiography is of limited technical and practical use in detecting early atherosclerosis. IVUS can both detect and quantify amount of CAD in the early stages of atherosclerosis. It�s use for routine clinical early detection is limited by it�s invasive nature.

25. Non-Invasive Imaging

26. CT Angiography Uses CT technology to perform �coronary angiogram� non-invasively. Sensitivity �ok� for large vessels with significant stenosis. Poor resolution in small vessels and unable to detect early disease. Significant radiation and contrast dye exposure limits use for serial studies.

27. Coronary Calcium Based on theory that coronary atherosclerosis is associated with calcification of vessels. Detection method requires less radiation than CT angio. No contrast dye needed

28. Risk Adjusted Hazard Ratios for Coronary Event based on Age and Coronary Calcium Score

29. Summary CT angiography is of limited use in detecting early disease due its limited spatial resolution. Coronary Calcium scoring may be practical for early detection.

30. Biomarkers �Can we predict events by charting levels of stuff?�

31. CRP Coronary atherosclerosis is believed to be a chronic inflammatory disease. The role of CRP in the mechanism of CAD is unknown. It may be directly involved in the mechanism or a bystander.

32. CRP and CAD

33. CRP in a Population Based Study

34. Lipoprotein-Associated Phospholipase A2 Lp-PLA2 �.NOT Lp(a) Member of the phospholipase A2 family of enzymes. Produced by macrophages, T lymphocytes, and mast cells. Hydrolyzes the sn2 ester bond in phospholipids whose fatty acid moiety has been shortened or altered by oxidation to yield oxidized fatty acid and lysophosphatidylcholine. These metabolites have proinflammatory properties16, and lysophosphatidylcholine has been shown to have adverse effects on endothelial function. JACC 2008;51(9) 913 JACC 2008;51(9) 913

35. Lp-PLA2 Adverse Cardiac Events

36. Long Term Longitudinal Population Based Study

37. Lp-PLA2: Coronary Endothelial Dysfunction ( N=172)

38. Summary Many biomarkers exists. CRP has been shown to be predictive of future events. It is however affected by numerous other factors. LP-PLA2 has been shown to be predictive of future cardiac events. It may also be directly involved in causing endothelial dysfunction.

39. Endothelial Dysfunction �Is this the cause of everything that is wrong with me?�

40. Coronary Endothelium Function Regulation and prevention of thrombosis. Regulation of vasomotor tone and coronary blood flow.

41. Clinical Consequences of Endothelial Dysfunction Coronary Endothelial Dysfunction is clearly associated with adverse cardiac events. May be considered a marker for early CAD

42. Endothelial DysfunctionIn Patients with Psoriasis

43. Assessment of Endothelial Function Invasive Brachial Flow Mediated Dilation Peripheral Artery Tone

44. Endothelial Function Protocol

45. Brachial Flow Mediated Dilation Measure Brachial Flow at rest and after occlusion. Correlates with future cardiac events. Non-invasive Technically demanding

46. Peripheral Artery Tone Non-Invasive Less Technically Demanding than Brachial flow. Correlates with invasive coronary endothelial functional assessment.

47. Summary Endothelial dysfunction occurs during the early stages of CAD. Assessment of endothelial function can be used as a method to detect early disease progression and regression. Invasive and Non-invasive methods exist.

48. Conclusion Severe psoriasis is associated with an increased risk of CAD. The risk is highest in younger patients. Future studies are needed to determine if systemic therapy reduces this risk. These studies should included biomarkers and assessment of endothelial function.