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Nagi Abdalla
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   Eicosapentaenoic acid (EPA):
     polyunsaturated fatty acid derived from the omega-3 family
     Sources: marine and plant oils
     benefits were discovered in the 1970s by researchers studying the
      Greenland Inuit Tribe..
   Treating depression, when used with
conventional antidepressants.

   wound healing, when used with RNA
and L-arginine following surgery.

  Treating borderline personality
disorder, a mood disorder.

  Reducing the risk of heart
attack, stroke, and other cardiovascular
problems in people with heart disease.

   Psoriasis.
Watkins et al. Nature Reviews Genetics advance online publication;
published online 07 February 2006 | doi:10.1038/nrg1805
   Previous studies on EPA:
     (Eicosapentaenoic acid and prevention of thrombosis and
      atherosclerosis) Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR.
     (Omega-3 dietary supplements and the risk of cardiovascular events: A
      systematic review) Marik PE, Varon J.
     (Omega-3 polyunsaturated fatty acids and cardiovascular diseases)
      Lavie CJ, Milani RV, Mehra MR, Ventura HO.
   About ACS:
     A major cause is disruption of vulnerable plaques and thrombosis
     Plaque vulnerablility is determened by: Fibrous cap thickness and the
      yellow color grade
     Plaque rupture and thrombosis is the mecahnism of ACS in more than
      90% of cases
   Aim of this study:
     Association between the serum EPA/AA ratio and plaque vulnerability
      evaluated by coronary angioscopy.
 54 patients underwent PCI and coronary angiography
examination (16 with ACS + 38 with stable angina)

   Patients with stable angina were divided into 2 groups:
     ↓ EPA/AA ratio (n=19, EPA/AA ratio <0.37 [median])
     ↑ EPA/AA ratio (n=19, EPA/AA ratio ≥0.37 [median])

Fasting blood samples were collected and serum PUFA
measurements were acquired using Gas-Chromatography

No patients in the present study were taking the purified
EPA drug, ethyl eicosapentate.
 PCI was done by routine
procedures and An
angioscopic examination
was performed to evaluate
the plaque lesion.

 Clinical characteristics of
plaques color were
identified and
differentiated from
thrombus features.
   Statistical tools used in this study:
     Data presentation  mean±SD
     Comparison between low and high groups unpaired Student’s t-test
     Factors associated with grade 3 yellow plaque and different levels of
      PUFAs  Multivariate stepwise logistic regression analysis
     Data from patients with ACS were used as reference
     Software used  SPSS II
 EPA,EPA/AA,DHA
were comparable
between high and low
ratio groups
 Number of detected
plaques was not
comparable but the degree
of yellow color was
significantly higher in low
ratio group than in high
ratio group

 Number of thrombotic
plaques were comparable
between the 2 Stable
angina groups
•Multivariate analysis was
done after including all lipid
levels and showed:

The maximum color grade
had a weak but significant
correlation with EPA.

serum EPA level was
significantly associated with
the presence of grade-3 yellow
plaques
 This study evaluated EPA/AA ratio in patients with
coronary plaque vulnerability using :
     Maximum color grade
     Number of already thrombogenic/disrupted yellow plaques
      as comparison factors,
in order to associate the findings with different types of
Coronary Heart diseases
 2 main findings were discussed:
     Association between high and low ratio stable angina patients
     Association between low ratio patients and ACS patients
 Other Studies on the effect of EPA therapy and antiplatelet
therapy:
     EPA therapy reduces serum LDL and C-reactive protein
     EPA has an anti-inflammatory effect that protects against
      atherosclerotic disease

   This study had showed:
     among the majority of patients with stable angina on aspirin and low LDL
       patients with the lower ratio had higher plaque vulnerability..

     Therefore, EPA therapy might contribute to the stabilization of coronary
      plaques and prevention of cardiovascular events through mechanisms
      different from statins or anti-platelet therapy.

 Other studies have shown the relation between serum
EPA and atherosclerosis but this is the first study to show
the relation between EPA/AA ratio and the level of plaque
vulnerability.
 Multivariate analysis was done in this study after including markers
of lipid and inflammation profiles:
         (AA,EPA,DHA,LDL,HDL,CRP)
And revealed that:
         “low serum EPA level was significantly associated with the presence of
grade-3 yellow plaques  which are regarded as vulnerable plaques and compatible
with thin-cap fibroatheroma.”
   It should be noted that:
     The correlation between [color grade] and the [EPA/AA ratio] was weak, due to:
       the lack of healthy patients who had low maximum color grade and a high EPA/AA ratio in
        this study.
       maximum color grade is determined by multiple factors.
     LDL was not associated with color grade because it was controlled by statin
      treatment.

 In another study: statin was found to reduce color grade of the
plaques but not associated with LDL levels
 Since low serum EPA level and a low EPA/AA ratio would be
associated with high coronary plaque vulnerability EPA therapy
might reduce cardiovascular events by stabilizing coronary plaques.
   Small number of patients were enrolled in this study

 there is a need to enroll healthy stable angina patients
with a low maximum color grade and a high EPA/AA ratio
and did not undergo PCI in order to strengthen this
conclusion.

 Evaluation of thrombus formation at the stent (as a
complication of PCI) was not done in order to minimize
the effect of this invasive procedure on the patient.
      Also not all coronary arteries were evaluated for
the same reason.
Low serum EPA level and a low EPA/AA ratio were
associated with the high vulnerability of coronary
                    plaques.
Thank you for listening

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Relationship Between Coronary Plaque Vulnerability and Serum n-3/n-6 Polyunsaturated Fatty Acid Ratio

  • 1. Nagi Abdalla 엠네기
  • 2.
  • 3. Eicosapentaenoic acid (EPA):  polyunsaturated fatty acid derived from the omega-3 family  Sources: marine and plant oils  benefits were discovered in the 1970s by researchers studying the Greenland Inuit Tribe..
  • 4. Treating depression, when used with conventional antidepressants.  wound healing, when used with RNA and L-arginine following surgery.  Treating borderline personality disorder, a mood disorder.  Reducing the risk of heart attack, stroke, and other cardiovascular problems in people with heart disease.  Psoriasis.
  • 5. Watkins et al. Nature Reviews Genetics advance online publication; published online 07 February 2006 | doi:10.1038/nrg1805
  • 6. Previous studies on EPA:  (Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis) Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR.  (Omega-3 dietary supplements and the risk of cardiovascular events: A systematic review) Marik PE, Varon J.  (Omega-3 polyunsaturated fatty acids and cardiovascular diseases) Lavie CJ, Milani RV, Mehra MR, Ventura HO.  About ACS:  A major cause is disruption of vulnerable plaques and thrombosis  Plaque vulnerablility is determened by: Fibrous cap thickness and the yellow color grade  Plaque rupture and thrombosis is the mecahnism of ACS in more than 90% of cases  Aim of this study:  Association between the serum EPA/AA ratio and plaque vulnerability evaluated by coronary angioscopy.
  • 7.
  • 8.  54 patients underwent PCI and coronary angiography examination (16 with ACS + 38 with stable angina)  Patients with stable angina were divided into 2 groups:  ↓ EPA/AA ratio (n=19, EPA/AA ratio <0.37 [median])  ↑ EPA/AA ratio (n=19, EPA/AA ratio ≥0.37 [median]) Fasting blood samples were collected and serum PUFA measurements were acquired using Gas-Chromatography No patients in the present study were taking the purified EPA drug, ethyl eicosapentate.
  • 9.
  • 10.  PCI was done by routine procedures and An angioscopic examination was performed to evaluate the plaque lesion.  Clinical characteristics of plaques color were identified and differentiated from thrombus features.
  • 11. Statistical tools used in this study:  Data presentation  mean±SD  Comparison between low and high groups unpaired Student’s t-test  Factors associated with grade 3 yellow plaque and different levels of PUFAs  Multivariate stepwise logistic regression analysis  Data from patients with ACS were used as reference  Software used  SPSS II
  • 12.
  • 13.  EPA,EPA/AA,DHA were comparable between high and low ratio groups
  • 14.  Number of detected plaques was not comparable but the degree of yellow color was significantly higher in low ratio group than in high ratio group  Number of thrombotic plaques were comparable between the 2 Stable angina groups
  • 15. •Multivariate analysis was done after including all lipid levels and showed: The maximum color grade had a weak but significant correlation with EPA. serum EPA level was significantly associated with the presence of grade-3 yellow plaques
  • 16.
  • 17.  This study evaluated EPA/AA ratio in patients with coronary plaque vulnerability using :  Maximum color grade  Number of already thrombogenic/disrupted yellow plaques as comparison factors, in order to associate the findings with different types of Coronary Heart diseases  2 main findings were discussed:  Association between high and low ratio stable angina patients  Association between low ratio patients and ACS patients
  • 18.  Other Studies on the effect of EPA therapy and antiplatelet therapy:  EPA therapy reduces serum LDL and C-reactive protein  EPA has an anti-inflammatory effect that protects against atherosclerotic disease  This study had showed:  among the majority of patients with stable angina on aspirin and low LDL  patients with the lower ratio had higher plaque vulnerability..  Therefore, EPA therapy might contribute to the stabilization of coronary plaques and prevention of cardiovascular events through mechanisms different from statins or anti-platelet therapy.  Other studies have shown the relation between serum EPA and atherosclerosis but this is the first study to show the relation between EPA/AA ratio and the level of plaque vulnerability.
  • 19.  Multivariate analysis was done in this study after including markers of lipid and inflammation profiles: (AA,EPA,DHA,LDL,HDL,CRP) And revealed that: “low serum EPA level was significantly associated with the presence of grade-3 yellow plaques  which are regarded as vulnerable plaques and compatible with thin-cap fibroatheroma.”  It should be noted that:  The correlation between [color grade] and the [EPA/AA ratio] was weak, due to:  the lack of healthy patients who had low maximum color grade and a high EPA/AA ratio in this study.  maximum color grade is determined by multiple factors.  LDL was not associated with color grade because it was controlled by statin treatment.  In another study: statin was found to reduce color grade of the plaques but not associated with LDL levels  Since low serum EPA level and a low EPA/AA ratio would be associated with high coronary plaque vulnerability EPA therapy might reduce cardiovascular events by stabilizing coronary plaques.
  • 20. Small number of patients were enrolled in this study  there is a need to enroll healthy stable angina patients with a low maximum color grade and a high EPA/AA ratio and did not undergo PCI in order to strengthen this conclusion.  Evaluation of thrombus formation at the stent (as a complication of PCI) was not done in order to minimize the effect of this invasive procedure on the patient. Also not all coronary arteries were evaluated for the same reason.
  • 21. Low serum EPA level and a low EPA/AA ratio were associated with the high vulnerability of coronary plaques.
  • 22. Thank you for listening