Plasma concentration of tnf and risk of recurrent coronary events
Download
1 / 32

Plasma Concentration of TNF- and Risk of Recurrent Coronary Events - PowerPoint PPT Presentation


  • 117 Views
  • Uploaded on

Plasma Concentration of TNF-  and Risk of Recurrent Coronary Events. 2.5 2.0 1.5 1.0. Relative Risk. 0–2.47 (1 st –50 th ). 2.48–3.05 (51 st –75 th ). 3.06–4.17 (76 th –95 th ). 4.18+ (>95 th ). TNF-  Concentration, pg/mL (percentile of control distribution).

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Plasma Concentration of TNF- and Risk of Recurrent Coronary Events' - kiona


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Plasma concentration of tnf and risk of recurrent coronary events l.jpg
Plasma Concentration of TNF- and Risk of Recurrent Coronary Events

2.5

2.0

1.5

1.0

Relative Risk

0–2.47(1st–50th)

2.48–3.05(51st–75th)

3.06–4.17(76th–95th)

4.18+(>95th)

TNF- Concentration, pg/mL (percentile of control distribution)


Predictive value of crp and other inflammatory markers ldl 130 mg dl l.jpg
Predictive Value of CRP and Other Inflammatory Markers: LDL <130 mg/dL

4

3

2

1

hs-CRP

SAA

Relative Risk of FutureCoronary Events

IL-6

sICAM-1

1

2

3

4

Quartile of Inflammatory Marker


Slide3 l.jpg
Age-Adjusted Correlation Coefficients for hs-CRP Levels and Lipid Parameters over a 5-Year Follow-up Period





Hs crp aspirin and risks of future mi physicians health study l.jpg
hs-CRP, Aspirin, and Risks of Future MI: by preventive therapies?Physicians' Health Study

Aspirin

Placebo

Relative Risk of MI

1

2

3

4

Quartile of C-Reactive Protein


Low dose aspirin reduces thromboxane b 2 but not crp l.jpg
Low-Dose Aspirin Reduces Thromboxane B by preventive therapies?2 but not CRP

140

120

100

80

60

40

20

0

140

120

100

80

60

40

20

0

28 Days

31 Days

Serum CRP (% of Baseline)

Serum Thromboxane (% of Baseline)

* p<0.001

* *

Placebo(n=11)

ASA 81 mg qd(n=13)

Placebo(n=11)

ASA 81 mg qd(n=13)


Slide9 l.jpg
Reduction of Proinflammatory Cytokines and CRP with Higher-Dose Aspirin in Patients with Chronic Stable Angina


Elevated crp levels in obesity nhanes 1988 1994 l.jpg
Elevated CRP Levels in Obesity: Higher-Dose Aspirin in Patients with Chronic Stable AnginaNHANES 1988-1994

Percent with CRP 0.22 mg/dL

Normal

Overweight

Obese


Effects of weight loss on crp concentrations in obese healthy women l.jpg
Effects of Weight Loss on CRP Higher-Dose Aspirin in Patients with Chronic Stable AnginaConcentrations in Obese Healthy Women

  • 83 women (mean BMI 33.8, range 28.2-43.8 kg/m2) placed on very low fat, energy-restricted diet (6.0 MJ, 15% fat) for 12 weeks

  • Baseline CRP positively associated with BMI (r=0.281, p=0.01)

  • CRP reduced by 26% (p<0.001)

  • Average weight loss 7.9 kg, associated with change in CRP

  • Change in CRP correlated with change in TC (r=0.240, p=0.03) but not changes in LDL-C, HDL-C, or glucose

  • At 12 weeks, CRP concentration highly correlated with TG (r=0.287, p=0.009), but not with other lipids or glucose


Effects of weight loss in obese women on il 6 tnf and crp l.jpg
Effects of Weight Loss in Obese Women on IL-6, TNF- Higher-Dose Aspirin in Patients with Chronic Stable Angina, and CRP

Before diet

After very low calorie diet(mean BMI reduction 2.1 kg/m2; mean reduction in body fat mass 4 kg)

p=0.05

p=0.14

p=0.6

mg/L

pg/mL

IL-6

TNF-

CRP


Effects of n 3 fatty acid therapy on lipids and scams l.jpg
Effects of n-3 Fatty Acid Therapy on Lipids and sCAMs Higher-Dose Aspirin in Patients with Chronic Stable Angina

TG

TC

sICAM-1

sE-selectin

*

*

*

Percent Change

All Patients

* p<0.05

DM Patients

*


Effect of hrt on hs crp the pepi study l.jpg
Effect of HRT on hs-CRP: Higher-Dose Aspirin in Patients with Chronic Stable Anginathe PEPI Study

3.0

2.0

1.0

CEE + MPA cyclic

CEE + MPA continuous

CEE + MP

CEE

hs-CRP (mg/dL)

Placebo

0

12

36

Months


Hs crp and relative risk of recurrent coronary events care l.jpg
hs-CRP and Relative Risk of Recurrent Coronary Events: Higher-Dose Aspirin in Patients with Chronic Stable AnginaCARE

P Trend = 0.044

P=0.02

Relative Risk

1<0.12

20.12-0.20

30.21-0.37

40.38-0.66

5>0.66

Quintile of hs-CRP (range, mg/dL)


Inflammation pravastatin and relative risk of recurrent coronary events care l.jpg
Inflammation, Pravastatin, and Relative Risk of Recurrent Coronary Events: CARE

P Trend = 0.005

Relative Risk

Pravastatin

Placebo

Pravastatin

Placebo

Inflammation Absent

Inflammation Present


Baseline lipid levels in patients with and without inflammation care l.jpg
Baseline Lipid Levels in Patients with and without Inflammation: CARE

250

200

150

100

50

0

Inflammation absent

Inflammation present

Mean Baseline (mg/dL)

TC

LDL-C

HDL-C

TG


Long term effect of pravastatin on hs crp care placebo and pravastatin groups l.jpg
Long-Term Effect of Pravastatin on hs-CRP: Inflammation: CARE Placebo and Pravastatin Groups

Placebo

0.25

0.24

0.23

0.22

0.21

0.20

0.19

0.18

–21.6%

(P=0.007)

Median hs-CRPConcentration (mg/dL)

Pravastatin

Baseline

5 Years


Change in hs crp concentration over 5 years care subgroup analyses l.jpg
Change in hs-CRP Concentration Over 5 Years: Inflammation: CARE Subgroup Analyses

Placebo

Pravastatin

All Subjects

Age >60 years

Age <60 years

BMI >27 kg/m2

BMI <27 kg/m2

Smokers

Nonsmokers

SBP >128 mm Hg

SBP <128 mm Hg

DBP >78 mm Hg

DBP <78 mm Hg

LDL-C >138 mg/dL

LDL-C <138 mg/dL

HDL-C >35 mg/dL

HDL-C <35 mg/dL

Triglycerides >160 mg/dL

Triglycerides <160 mg/dL

-0.2

-0.1

0

0.1

0.2

0.3

Change in hs-CRP over 5 Years (mg/dL)

Click for larger picture


Change in hs crp according to observed changes in ldl c care placebo and pravastatin groups l.jpg
Change in hs-CRP according to Observed Changes in LDL-C: Inflammation: CARE Placebo and Pravastatin Groups

0.15

Placebo

0.10

Pravastatin

0.05

Change in hs-CRP (mg/dL)

0

-0.05

-0.10

-0.15

Decrease

0–25

Decrease

25–50

Decrease

50–75

Decrease

>75

Increase

0–25

Change in LDL-C (mg/dL)


Slide21 l.jpg
CRP in Combination with LDL-C as a Method to Target Statin Therapy in Primary Prevention: AFCAPS/TexCAPS

Event Rate

Median LDL-C = 149.1 mg/dLMedian CRP = 0.16 mg/dL


Statin therapy lipid levels crp and survival among patients with severe coronary artery disease l.jpg
Statin Therapy, Lipid Levels, CRP, and Survival Among Patients with Severe Coronary Artery Disease

P Trend <0.0001

P Trend = 0.94

Mortality (%)

Medium

High

Low

Medium

High

Low

CRP Tertiles Statins

CRP TertilesNo Statins


Effect of statin therapy on hs crp levels at 6 weeks l.jpg

* Patients with Severe Coronary Artery Disease

*

*

Effect of Statin Therapy on hs-CRP Levels at 6 Weeks

6

5

4

3

2

1

0

*p<0.025 vs. Baseline

hs-CRP (mg/L)

Baseline

Prava(40 mg/d)

Simva(20 mg/d)

Atorva(10 mg/d)


Effect of pravastatin on crp levels in primary and secondary prevention prince l.jpg

12 weeks Patients with Severe Coronary Artery Diseasevs. baseline

24 weeksvs. baseline

24 weeks ITTvs. placebo

Effect of Pravastatin on CRP Levels in Primary and Secondary Prevention: PRINCE

Primary Prevention

Secondary Prevention

Change in CRP, %

*

**p<.005vs. baseline

*p<.001vs. baseline

**

*

**

*


Slide25 l.jpg
Effect of Bezafibrate with and without Fluvastatin on Plasma Fibrinogen, PAI-1, and CRP in Patients with CAD and Mixed Hyperlipidemia

Fibrinogen

PAI-1

CRP

n:

81

80

74

Change at 24 weeks, %

70

72

63

83

80

75

*

P<0.05 vs. baseline

*

*

Beza 400 mg/d+ fluva 20 mg/d

Beza 400 mg/d+ fluva 40 mg/d

Beza 400 mg/d


Slide26 l.jpg
CRP in Combination with TC:HDL-C Ratio as a Method to Target Statin Therapy in Primary Prevention: AFCAPS/TexCAPS

Event Rate

Median TC:HDL-C = 5.96Median CRP = 0.16 mg/dL


Slide27 l.jpg
Effect of Gemfibrozil and Ciprofibrate on Plasma Fibrinogen and CRP Levels in Patients with Primary Hypercholesterolemia

Pretreatment

12 Weeks

*p<0.005 vs. pretreatment level

*

*

CRP, mg/L

Fibrinogen, g/L

Gemfibrozil600 mg bid(n=51)

Ciprofibrate100 mg/d(n=48)

Gemfibrozil600 mg bid(n=51)

Ciprofibrate100 mg/d(n=48)


Hs crp potential clinical applications l.jpg
hs-CRP: Potential Clinical Applications and CRP Levels in Patients with Primary Hypercholesterolemia

  • Adjunct to lipid screening in the detection of individuals at high risk for coronary artery disease

  • Method to better target statin therapy in the setting of primary prevention

  • Potential prognostic value in acute coronary syndromes

    Inflammation is likely to represent a new target for both the treatment and prevention of acute myocardial infarction


Summary l.jpg
Summary and CRP Levels in Patients with Primary Hypercholesterolemia

  • Lifestyle modification and some pharmacotherapies (full-dose ASA, statins) lower hs-CRP

  • Lipid-modifying therapies with oral estrogens and fibrates are not associated with reduction in hs-CRP

  • Individuals with high levels of hs-CRP are at increased risk for CHD events and benefit from ASA and statins


Infection and chd is there a connection l.jpg
Infection and CHD - is there a connection? and CRP Levels in Patients with Primary Hypercholesterolemia

  • Local or systemic infections resulting from gram negative bacteria such as Chlamydia pneumoniae and Helicobacter pylori, including cytomegalovirus (CMV) have been implicated in atheroscelosis

  • While several case control studies have shown increased titers of C.pneumoniae and H. Pylori in those with vs. without CHD, convincing evidence from prospective studies is lacking.


Prospective studies of chd and infectious pathogens l.jpg
Prospective Studies of CHD and Infectious Pathogens and CRP Levels in Patients with Primary Hypercholesterolemia

  • Physician’s Health Study (nested case-control) shows RR 1.1 (0.8-1.5) for C. Pneumoniae, 0.94 (0.7-1.2) for cytomegalovirus, and 0.72 (0.6-0.9) for Herpes simplex virus.

  • H. pylori also shows mixed results. Whincup showed a nonsignificant 1.3 OR when adjusted for other risk factors, the large ARIC study showed no relation, and the Caerphilly Prospective study showed RR=1.05 in 1796 men followed 14 years.


Infectious agents and the future l.jpg
Infectious Agents and the Future and CRP Levels in Patients with Primary Hypercholesterolemia

  • Individuals with greater infectious burdens may be at greater risk, because they are older, have poorer health habits, less access to care.

  • Observed associations often may be due to selection biases or confounding from age and other factors

  • Prospective clinical trials under way examining role of certain antibiotics such as azithromycin on reduction of recurrent events in CHD patients.

  • Until these data are available, no role for measurement or treatment of infectious burden.


ad