Inflammation and Cardiovascular Disease: Role of Fibrinogen, CRP, and Other Markers, Slides of Public Health

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Inflammation and CHD docsity.com

Thrombosis, Inflammation, and Infection ^ Many persons experiencing cardiovascularevents often do not have well-recognizedstandard risk factors such as elevatedcholesterol or hypertension. ^ Thrombosis, local or systemic inflammation,and chronic infection may play importantroles in the initiation and progression of CHD docsity.com

Total Cholesterol Distribution: CHD vs Non-CHD Population^ 35% of CHDOccurs in Peoplewith TC<200mg/dL

150 200^ Total Cholesterol (mg/dL) No CHD CHD^250

Framingham Heart Study—26-Year Follow-up docsity.com

Inflammation and Atherosclerosis ^ Inflammation may determine plaque stability-^ Unstable plaques have increased leukocyticinfiltrates-^ T cells, macrophages predominate rupture sites-^ Cytokines and metalloproteinases influence bothstabilityand degradation of the fibrous cap ^ Lipid lowering may reduce plaque inflammation-^ Decreased macrophage number-^ Decreased expression of collagenolytic enzymes(MMP-1)-^ Increased interstitial collagen-^ Decreased expression of E-selectin-^ Reduced calcium deposition docsity.com

Evaluating Novel Risk Factors for CAD ^ Consistency ofprospective data ^ Strength ofassociation ^ Independence ofassociation ^ Improve predictivevalue ^ Standardized measure

^ Low variability ^ Highreproducibility ^ Biologicplausibility ^ Low cost ^ Modifiable

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Biomarkers for Venous and ArterialThrombosis

hs-CRP / SAA / IL-6 / TNF

Lp(a)

Platelet function

PAI-1: ag

tPA: ag

vWF: ag

Factor VII

Fibrinogen

ArterialVenous

Parameter docsity.com

Thrombosis and Cardiovascular Risk ^ Thrombus formation is a crucial factor in theprecipitation of unstable angina or myocardialinfarction, as well as occlusion during or followingangioplasty. ^ Often preceded by platelet aggregation and activationof the coagulation system. ^ A thrombus may develop at sites of only mild tomoderate coronary stenosis.

The majority of coronary events occur where there is less than 70%stenosis.  Occlusive coronary thrombosis plays a role in over80% of myocardial infarctions and about 95% ofsudden death victims.docsity.com

Fibrinogen and Atherosclerosis^ ^ Promotes atherosclerosis^ ^ Essential component of platelet aggregation^ ^ Relates to fibrin deposited and the size of the clot^ ^ Increases plasma viscosity^ ^ May also have a proinflammatory role^ ^ Measurement of fibrinogen, incl. Test variability,remains difficult.^ ^ No known therapies to selectively lower fibrinogenlevels in order to test efficacy in CHD riskreduction via clinical trials.docsity.com

Fibrinogen and CHD Risk Factors ^ Fibrinogen levels increase with age and bodymass index, and higher cholesterol levels ^ Smoking can reversibly elevated fibrinogen levels,and cessation of smoking can lower fibrinogen. ^ Those who exercise, eat vegetarian diets, andconsume alcohol have lower levels.

Exercise may

also lower fibrinogen and plasma viscosity.  Studies also^ show statin-fibrate combinations(simvastatin-ciprofibrate) and estrogen therapy tolower fibrinogen.docsity.com

Other Thrombotic Factors and CHD ^ Mixed reports of coagulation factor VIIc incardiovascular disease.

PROCAM study showed

no association with CHD events, CHS also showedno relation to subclinical CVD.  Endogenous tissue-type plasminogen activator(tPA) shown in some studies to relate to increasedcardiovascular risk--Physician’s Health Studyshowed RR for MI 2.8, stroke 3.5 in those in 5thvs. 1st quintile of tPA.  Plasminogen activitor inhibitor type 1 (PAI-1)shown associated with increased cardiovascularrisk, esp in diabetic patients.docsity.com

Aspirin and Cardiovascular Risk:

Clinical

Trial Evidence for Secondary Prevention ^ Antiplatelet Trialists Collaboration of 54,000patients with cardiovascular disease (10trials post-MI) showed 31% reduction in MI,42% reduction in stroke, 13% reduction intotal vascular mortality ^ International Study of Infarct Survival of17,187 pts w/evolving MI showed 49%reduction in reinfarction, 26% reduction innonfatal stroke, and 23% reduction in totalvascular mortality docsity.com

Antiplatelet Therapy:

AHA

Recommendations  Aspirin is clearly recommended in secondaryprevention.^ Provides additional benefit in conjunctionwith thrombolytic therapy.

Clopidogrel may be an option in aspirin-intolerant patients.  Aspirin is not recommended for primary prevention inthose free of CHD and younger than 50 years old.  Aspirin may be considered in those over age 50 withadditional risk factors, free of contraindications, andmay benefit those with hypertension, diabetes, andcigarette smoking.  American Diabetes Association recommends aspirin indiabetics with at least one other CHD risk factor.docsity.com

Risk Factors for Future CardiovascularEvents:^ WHS Lipoprotein(a)HomocysteineIL-6TCLDL-CsICAM-1SAAApo BTC:HDL-Chs-CRPhs-CRP + TC:HDL-C^0 1.0^ 2.0^ Relative Risk of Future Cardiovascular Events

4.0^ 6. docsity.com

CRP vs hs-CRP^ ^ CRP is an acute-phase protein produced by the liver inresponse to cytokine production (IL-6, IL-1, tumornecrosis factor) during tissue injury, inflammation, orinfection.^ ^ Standard CRP tests determine levels which areincreased up to 1,000-fold in response to infection ortissue destruction, but cannot adequately assess thenormal range^ ^ High-sensitivity CRP (hs-CRP) assays (i.e. DadeBehring) detect levels of CRP within the normal range,levels proven to predict future cardiovascular events.docsity.com