Pathophysiology and Risk Factors Pathophysiology and Risk Factors of Coronary Artery Diseaseof Coronary Artery Disease

Cardiac Wellness Institute of Calgary

Updated May 2010

OverviewOverview Cardiovascular DiseasesCardiovascular Diseases Atherogenesis and response to Injury Atherogenesis and response to Injury

(Endothelial Dysfunction) (Endothelial Dysfunction) Manifestations and Diagnosis of CADManifestations and Diagnosis of CAD Treatment of CADTreatment of CAD Risk Factors Contributing to CADRisk Factors Contributing to CAD

– Modifiable vs Non-modifiableModifiable vs Non-modifiable

Cardiovascular DiseasesCardiovascular Diseases ArteriosclerosisArteriosclerosis – loss of elasticity of the – loss of elasticity of the

arteries; thickening and hardening of artery arteries; thickening and hardening of artery walls. walls.

AtherosclerosisAtherosclerosis – process where fatty material – process where fatty material is deposited along walls of arteries. This is deposited along walls of arteries. This material thickens, hardens, and can eventually material thickens, hardens, and can eventually block the artery. Atherosclerosis is just one type block the artery. Atherosclerosis is just one type of Arteriosclerosis. of Arteriosclerosis.

Our understanding of the development and Our understanding of the development and progression of atherosclerosis (atherogenesis) progression of atherosclerosis (atherogenesis) is still incompleteis still incomplete

Vascular AnatomyVascular Anatomy EndotheliumEndothelium: barrier between blood and : barrier between blood and

arterial wallarterial wall

3 layers in arterial wall:3 layers in arterial wall:

– Tunica IntimaTunica Intima - connective tissue; where lesions - connective tissue; where lesions formform

– Tunica MediaTunica Media - smooth muscle - smooth muscle

advanced atherosclerosis characterized by proliferation of advanced atherosclerosis characterized by proliferation of smooth muscle cells heresmooth muscle cells here

– Tunica AdventitiaTunica Adventitia - connective tissue; highly - connective tissue; highly vascularized to provide nutrientsvascularized to provide nutrients

Endothelial Endothelial FunctionFunction

Regulates vasomotionRegulates vasomotion Regulates thrombosisRegulates thrombosis Regulates transport of Regulates transport of

substances to and from substances to and from vascular spacevascular space

Regulates growth and Regulates growth and apoptosisapoptosis of vascular of vascular wallwall

Regulates LDL Regulates LDL oxidationoxidation

Inadequate vasodilationInadequate vasodilation ProthromboticProthrombotic Altered permeabilityAltered permeability Increased secretion of Increased secretion of

growth factorsgrowth factors Increased oxidation of Increased oxidation of

LDLLDL

Endothelial Endothelial DysfunctionDysfunction

Atherogenesis Atherogenesis Response to InjuryResponse to Injury

Arterial InjuryArterial Injury – Can result from smoke, hypertension, cholesterol, Can result from smoke, hypertension, cholesterol,

glycated substances, vasoconstriction, homocysteine glycated substances, vasoconstriction, homocysteine or infectious agentsor infectious agents

– Normal endothelial function is not repaired by Normal endothelial function is not repaired by inherent mechanismsinherent mechanisms

Endothelial Dysfunction and Inflammatory Endothelial Dysfunction and Inflammatory ResponseResponse– Arterial homoeostasis is altered by injury, results in Arterial homoeostasis is altered by injury, results in

inflammatory responseinflammatory response– Increased adhesiveness endothelial cells lose Increased adhesiveness endothelial cells lose

selective permeabilityselective permeability

AtherogenesisAtherogenesis Platelet aggregationPlatelet aggregation

– Platelets adhere to damaged endothelium and form Platelets adhere to damaged endothelium and form small blood clots on vessel wall (mural thrombi)small blood clots on vessel wall (mural thrombi)

– Release growth factors and vasoconstrictor Release growth factors and vasoconstrictor substancessubstances

– Can cause obstruction to blood flowCan cause obstruction to blood flow

AtherogenesisAtherogenesis LDL oxidationLDL oxidation

– Excess oxidized LDL particles accumulate in arterial Excess oxidized LDL particles accumulate in arterial wall, attracting monocytes and other cells into intimawall, attracting monocytes and other cells into intima

– Monocytes mature into macrophages and cause Monocytes mature into macrophages and cause proliferation of smooth muscle cells and promote proliferation of smooth muscle cells and promote uptake of more lipids, particularly LDLuptake of more lipids, particularly LDL

– These cells move from the media to the intima, These cells move from the media to the intima, becoming becoming foam cellsfoam cells, producing fatty streaks or , producing fatty streaks or lesionslesions

– Continued release of vasoactive substances and Continued release of vasoactive substances and growth factorsgrowth factors

AtherogenesisAtherogenesis Foam cellsFoam cells

– Release cholesterol into extracellular spaceRelease cholesterol into extracellular space

Fatty streaksFatty streaks– Earliest visually detectable lesion of atherosclerosisEarliest visually detectable lesion of atherosclerosis

– As the process continues, smooth muscle cells As the process continues, smooth muscle cells accumulate in the intima and form a fibrous plaque accumulate in the intima and form a fibrous plaque

Response to InjuryResponse to Injury Fibromuscular plaqueFibromuscular plaque

– With continued accumulation, lesion progresses in With continued accumulation, lesion progresses in size and appearance to Fibromuscular plaque with size and appearance to Fibromuscular plaque with an Atheroma (cholesterol core)an Atheroma (cholesterol core)

RemodelingRemodeling– Outward growth of artery & increased lumen sizeOutward growth of artery & increased lumen size

– Lumen size increases to compensate for Lumen size increases to compensate for atherosclerotic plaqueatherosclerotic plaque

– If plaque bulk continues to increase, lumen diameter If plaque bulk continues to increase, lumen diameter is decreased and blood flow obstruction occursis decreased and blood flow obstruction occurs

AtherogenesisAtherogenesis Plaque rupture, thrombus formation, Plaque rupture, thrombus formation,

incorporationincorporation– Layered appearance to lesion and increased plaque Layered appearance to lesion and increased plaque

progressionprogression– Rupture may result from local stress or chemical Rupture may result from local stress or chemical

factors and exposes contents or lesion to bloodfactors and exposes contents or lesion to blood– Plaques that are most vulnerable to rupture typically Plaques that are most vulnerable to rupture typically

have a large lipid core, thinned fibrous cap, and have a large lipid core, thinned fibrous cap, and outward remodeling of arterial wall outward remodeling of arterial wall

Advanced Atherosclerotic PlaqueAdvanced Atherosclerotic Plaque

Progression of AtherosclerosisProgression of Atherosclerosis

IntimaMedia

Core ofextracellular

lipid

Fibrous thickening

Thrombus fissure & hemtoma

Type VI (Complicated lesion)

Type V(Fibroatheroma)

Type IV (Atheroma)

Type III (Preatheroma) Type II (Lesion) Coronary artery atlesion-prone location

Small pools ofextracellular

lipid

Macrophagefoam cells

Adaptive thickening

(smooth muscle)

Adapted from Stary in Fuster et al (eds). Atherosclerosis and Coronary Artery Disease 1996.

AtherogenesisAtherogenesis Does not occur in a predictable linear pattern Does not occur in a predictable linear pattern Some lesions develop slowly and are stable for Some lesions develop slowly and are stable for

long periods of time, others develop quickly long periods of time, others develop quickly Partial regression of fatty, soft lesions is Partial regression of fatty, soft lesions is

possible with aggressive risk reductionpossible with aggressive risk reduction Endothelial dysfunction can be reversed Endothelial dysfunction can be reversed

– Exercise, dietary fat intake control, decreasing Exercise, dietary fat intake control, decreasing stress, maintaining optimal blood pressure and stress, maintaining optimal blood pressure and blood glucose levelsblood glucose levels

Manifestations of Manifestations of AtherosclerosisAtherosclerosis

The HeartThe Heart– Myocardial IschemiaMyocardial Ischemia

– AnginaAngina

– Myocardial InfarctionMyocardial Infarction

BrainBrain LegsLegs

Manifestations of Manifestations of AtherosclerosisAtherosclerosis

Myocardial Ischemia – Myocardial Ischemia – ischemic cascadeischemic cascade LV stiffening & decreased diastolic filling (diastolic LV stiffening & decreased diastolic filling (diastolic

dysfunction)dysfunction) Impaired LV systolic emptyingImpaired LV systolic emptying ECG changes associated with altered repolarization ECG changes associated with altered repolarization Angina Pectoris – transient, referred cardiac pain Angina Pectoris – transient, referred cardiac pain

resulting from ischemiaresulting from ischemia

Manifestations of Manifestations of AtherosclerosisAtherosclerosis

Angina – Angina – Types:Types: Silent ischemia:Silent ischemia: no painno pain Anginal Equivalent:Anginal Equivalent: shortness of breath, diaphoresis shortness of breath, diaphoresis

etc.etc. Typical Angina:Typical Angina: occurs with exertion, emotions & occurs with exertion, emotions &

relieved with rest or NTGrelieved with rest or NTG Atypical Angina:Atypical Angina: similar symptoms, but no exertion similar symptoms, but no exertion

etcetc Stable Angina:Stable Angina: reproducible, predictablereproducible, predictable Unstable Angina:Unstable Angina: new onset, increased freq, new onset, increased freq,

intensity, duration, or occurs at restintensity, duration, or occurs at rest

Manifestations of Manifestations of AtherosclerosisAtherosclerosis

Myocardial InfarctionMyocardial Infarction Diagnosis:Diagnosis: 2 of 3 criteria: 2 of 3 criteria:

1) Chest pain > 30 minutes1) Chest pain > 30 minutes

2) ECG – Q waves / ST segment elevation/ T wave 2) ECG – Q waves / ST segment elevation/ T wave inversioninversion

3) Cardiac enzymes: 3) Cardiac enzymes: Creatine phosphokinase (CK) Normal = 0-195Creatine phosphokinase (CK) Normal = 0-195 Troponin T – Normal < 0.03Troponin T – Normal < 0.03

Manifestations of Manifestations of AtherosclerosisAtherosclerosis

Myocardial Infarction Myocardial Infarction Signs & SymptomsSigns & Symptoms::

– Angina, GI upset, Dyspnea, Diaphoresis, SyncopeAngina, GI upset, Dyspnea, Diaphoresis, Syncope Treatment:Treatment:

– Relieve symptoms (nitroglycerin, painkillers)Relieve symptoms (nitroglycerin, painkillers)– ReperfusionReperfusion

Manifestations of Manifestations of AtherosclerosisAtherosclerosis

Myocardial InfarctionMyocardial Infarction STEMI vs. NSTEMI: STEMI vs. NSTEMI:

– ST Elevation MI – ST elevation of 1 mm or more in ST Elevation MI – ST elevation of 1 mm or more in contiguous leads or new LBBBcontiguous leads or new LBBB

– Non-ST Elevation MI – ST depression or T wave Non-ST Elevation MI – ST depression or T wave inversion lasting greater than or equal to 24 hoursinversion lasting greater than or equal to 24 hours

Manifestation of Manifestation of AtherosclerosisAtherosclerosis

BrainBrain– Transient ischemic attack (TIA)Transient ischemic attack (TIA)

– Cerebrovascular accident (stroke)Cerebrovascular accident (stroke)

LegsLegs– Intermittent claudicationIntermittent claudication

Diagnosis of Coronary Diagnosis of Coronary Artery Artery

DiseaseDisease

Graded Exercise Test (GXT)Graded Exercise Test (GXT)Used to assess...Used to assess...

IschemiaIschemia– ST segment changesST segment changes

– ArrhythmiaArrhythmia

Functional CapacityFunctional Capacity– MET’sMET’s

Efficacy of medical or surgical Efficacy of medical or surgical interventionintervention

Myocardial Perfusion Imaging Myocardial Perfusion Imaging (Thallium scan)(Thallium scan)

Used to assess...Used to assess... IschemiaIschemia Ventricular FunctionVentricular Function

– Ejection FractionEjection Fraction

Myocardial ViabilityMyocardial Viability– Reversible vs non-reversibleReversible vs non-reversible

EchocardiographyEchocardiographyUsed to assess...Used to assess...

Myocardial StructuresMyocardial Structures– MR, TR, ARMR, TR, AR

Ventricular FunctionVentricular Function– EFEF

– Wall motion abnormalitiesWall motion abnormalities

EffusionsEffusions ThrombusThrombus IschemiaIschemia

Cardiac AngiographyCardiac AngiographyUsed to assess...Used to assess...

Coronary arteriesCoronary arteries Pressures within cardiac chambersPressures within cardiac chambers Valve functionValve function Ventricular functionVentricular function

Interventions and Interventions and Treatment of Coronary Treatment of Coronary

Artery DiseaseArtery Disease

No Cure!!!No Cure!!!

Risk Factor ModificationRisk Factor Modification

Treat to TargetTreat to Target

Medical ManagementMedical ManagementBalancing the Supply and Demand EquationBalancing the Supply and Demand Equation

Lower the DemandLower the Demand Beta BlockersBeta Blockers

Decrease contractilityDecrease contractility Decrease heart rateDecrease heart rate

NitratesNitrates Decrease preloadDecrease preload

Calcium Channel Calcium Channel BlockersBlockers Decrease preloadDecrease preload

Increase the SupplyIncrease the Supply Beta BlockersBeta Blockers

Increase diastoleIncrease diastole

NitratesNitrates Increase collateral Increase collateral

circulationcirculation

Calcium Channel Calcium Channel BlockersBlockers Decrease vascular Decrease vascular

resistanceresistance

Percutaneous Coronary Percutaneous Coronary Intervention (PCI)Intervention (PCI)

Indications for Angioplasty (+/- stenting)Indications for Angioplasty (+/- stenting) Electively for chronic stable anginaElectively for chronic stable angina Urgently for unstable anginaUrgently for unstable angina Emergently for myocardial infarctionEmergently for myocardial infarction 1 or 2 vessel disease1 or 2 vessel disease NEVERNEVER for left main disease for left main disease

Coronary Artery Bypass Graft Coronary Artery Bypass Graft Surgery (CABG)Surgery (CABG)

IndicationsIndications Left main disease > 50 %Left main disease > 50 % Proximal 3 vessel diseaseProximal 3 vessel disease Multivessel disease with left ventricular Multivessel disease with left ventricular

dysfunctiondysfunction Lifestyle limiting angina unresponsive to Lifestyle limiting angina unresponsive to

medical therapy or PCImedical therapy or PCI

Risk Factors for Coronary Risk Factors for Coronary Artery DiseaseArtery Disease

Non-modifiable and ModifiableNon-modifiable and Modifiable

Non-Modifiable Risk FactorsNon-Modifiable Risk Factors Family HistoryFamily History

– Twice the risk of MI if one first-degree relative with MITwice the risk of MI if one first-degree relative with MI– Triple the risk of MI if 2+ first-degree relatives with MITriple the risk of MI if 2+ first-degree relatives with MI– Risk is strongest if MI occurred at age 55 or lessRisk is strongest if MI occurred at age 55 or less

Advancing AgeAdvancing Age– Risk of CAD Increases as we get olderRisk of CAD Increases as we get older

GenderGender– Men are at risk at an earlier age than womenMen are at risk at an earlier age than women– Women’s risk of heart disease increases after Women’s risk of heart disease increases after

menopause and soon equals men’smenopause and soon equals men’s

Modifiable Risk FactorsModifiable Risk Factors Tobacco SmokingTobacco Smoking DyslipidemiaDyslipidemia HypertensionHypertension ObesityObesity Sedentary LifestyleSedentary Lifestyle DiabetesDiabetes Emerging Risk FactorsEmerging Risk Factors

Tobacco SmokingTobacco Smoking The MOST preventable risk factorThe MOST preventable risk factor Smokers have 2 to 5 times the risk of CAD as Smokers have 2 to 5 times the risk of CAD as

nonsmokersnonsmokers Risk factor if one is currently smoking, has quit Risk factor if one is currently smoking, has quit

within the past 6 months, or has exposure to within the past 6 months, or has exposure to environmental tobacco smokeenvironmental tobacco smoke

Tobacco SmokingTobacco Smoking Increase workload to heartIncrease workload to heart

– Increased HR and BPIncreased HR and BP Endothelial dysfunctionEndothelial dysfunction

– Increased vasoconstrictionIncreased vasoconstriction– Decreased HDLDecreased HDL– Increased LDL and TriglyceridesIncreased LDL and Triglycerides– Increased LDL oxidationIncreased LDL oxidation– Increased platelet aggregationIncreased platelet aggregation– Decreased ODecreased O2 2 carrying capacity of red blood cellscarrying capacity of red blood cells

DyslipidemiaDyslipidemia 2 main types of lipids:2 main types of lipids:

– CholesterolCholesterol

– Triglycerides (TGs)Triglycerides (TGs)

Lipids are an essential component of healthy Lipids are an essential component of healthy body functioning, including:body functioning, including:

– Structural component of cell wallsStructural component of cell walls

– HormonesHormones

– Energy sourceEnergy source

DyslipidemiaDyslipidemia Much research to support the link between Much research to support the link between

abnormal serum lipid levels and CADabnormal serum lipid levels and CAD

LDL = LDL = risk of CAD risk of CAD

HDL = HDL = risk of CAD risk of CAD

TGs = TGs = risk of CAD risk of CAD

DyslipidemiaDyslipidemia Abnormal lipid levels are known to be the basis Abnormal lipid levels are known to be the basis

of the atherosclerotic processof the atherosclerotic process Endothelial DysfunctionEndothelial Dysfunction

– Elevated cholesterol levelsElevated cholesterol levels

Reduce vasodilationReduce vasodilation

Increase thrombosisIncrease thrombosis

– Elevated triglyceride levelsElevated triglyceride levels Mechanism is unclear Mechanism is unclear

Lipid Targets for CADLipid Targets for CAD

2009 Canadian Cholesterol Guidelines 2009 Canadian Cholesterol Guidelines

Primary Targets:Primary Targets: LDL-C < 2.0mmol/L or 50% reduction LDL-C < 2.0mmol/L or 50% reduction AlternateAlternate: Apolipoprotein B < 0.80 g/L: Apolipoprotein B < 0.80 g/L

Can J Cardiol 2009; 25(10): 567-579.

Lipid Targets for CADLipid Targets for CAD

2009 Canadian Cholesterol Guidelines 2009 Canadian Cholesterol Guidelines

Secondary Targets:Secondary Targets: (once LDL cholesterol is at goal)(once LDL cholesterol is at goal) Total Cholestrol to High-Density Lipoprotein (HDL) Total Cholestrol to High-Density Lipoprotein (HDL)

cholesterol ratio less than 4.0cholesterol ratio less than 4.0 Non HDL cholesterol < 3.5 mmol/LNon HDL cholesterol < 3.5 mmol/L Triglycerides < 1.7 mmol/LTriglycerides < 1.7 mmol/L Apolipoprotein B to apolipoprotein AI ratio < 0.8Apolipoprotein B to apolipoprotein AI ratio < 0.8 High-sensitivity C-reactive protein (CPR) < 2 mg/LHigh-sensitivity C-reactive protein (CPR) < 2 mg/L

Can J Cardiol 2009; 25(10): 567-579.

HypertensionHypertension Primary risk factor for CADPrimary risk factor for CAD Hypertension is associated with three to four times Hypertension is associated with three to four times

increased risk for CAD, MI and CVA & PVDincreased risk for CAD, MI and CVA & PVD Hypertension as a precursor or consequence of Hypertension as a precursor or consequence of

endothelial dysfunction?endothelial dysfunction?– Vasoconstriction (increases SBP)Vasoconstriction (increases SBP)– Vascular wall injuryVascular wall injury

Increased platelet aggregationIncreased platelet aggregation

– myocardiummyocardium increased wall stressincreased wall stress increased myocardial Oincreased myocardial O22 demand demand

Blood Pressure TargetsBlood Pressure Targets

ACSM GuidelinesACSM GuidelinesOptimalOptimal 120 / <80* 120 / <80*

NormalNormal 120-129 / 80-84*120-129 / 80-84*

High Normal High Normal 130-139 / 85-89*130-139 / 85-89*

HypertensionHypertension >140 / >90*>140 / >90*

*All units in mmHg*All units in mmHg

Blood Pressure TargetsBlood Pressure Targets

2010 Canadian Hypertension Guidelines 2010 Canadian Hypertension Guidelines Non-DiabeticsNon-Diabetics

<140/90 mmHg<140/90 mmHg

Diabetics or persons with chronic kidney Diabetics or persons with chronic kidney diseasedisease

<130/80 mmHg<130/80 mmHg

ObesityObesity The risk for CVD is greater in person’s with The risk for CVD is greater in person’s with

central (android) obesity than those with central (android) obesity than those with peripheral (gynoid) obesity peripheral (gynoid) obesity

Obesity is often associated with …Obesity is often associated with …

– DiabetesDiabetes

– HypertensionHypertension

– DyslipidemiaDyslipidemia

– InactivityInactivity

ObesityObesity Body Mass Index (BMI)Body Mass Index (BMI)

Measured in Kg/mMeasured in Kg/m22

ACSM BMI TargetsACSM BMI TargetsUnderweightUnderweight <18.5<18.5NormalNormal 18.5-24.918.5-24.9OverweightOverweight 25.0-29.925.0-29.9ObeseObese >30>30

ObesityObesity Waist CircumferenceWaist Circumference

ACSM Waist Circumference TargetsACSM Waist Circumference Targets

MenMen < 102 cm< 102 cm

WomenWomen < 88 cm< 88 cm

Sedentary LifestyleSedentary Lifestyle Lower fitness level is associated with increased Lower fitness level is associated with increased

risk of CAD in men and womenrisk of CAD in men and women

The relative risk of CAD associated with The relative risk of CAD associated with physical inactivity is comparable to that physical inactivity is comparable to that observed for cigarette smoking, observed for cigarette smoking, hypercholesterolemia and hypertensionhypercholesterolemia and hypertension

Persons who are physically inactive after a Persons who are physically inactive after a heart attack have significantly high mortality heart attack have significantly high mortality rates than active individuals rates than active individuals

Sedentary LifestyleSedentary LifestylePhysical Physical activityactivity reduces the risk of reduces the risk of CAD CAD through:through:

Improved balance between myocardial OImproved balance between myocardial O22 supply and supply and demanddemand

Decreased platelet aggregationDecreased platelet aggregation Decreased susceptibility to malignant ventricular Decreased susceptibility to malignant ventricular

arrhythmiasarrhythmias Improved endothelial toneImproved endothelial tone Beneficial effect on other CAD risk factors (ie. diabetes, Beneficial effect on other CAD risk factors (ie. diabetes,

dyslipidemia, hypertension, obesity, stress)dyslipidemia, hypertension, obesity, stress)

DiabetesDiabetes People with diabetes have 2 to 7 times People with diabetes have 2 to 7 times

increased risk of developing CAD than people increased risk of developing CAD than people without diabeteswithout diabetes

Mechanism of atherosclerosis is unclearMechanism of atherosclerosis is unclear– Endothelial damageEndothelial damage

Increased platelet aggregationIncreased platelet aggregation Insulin promotes synthesis of lipids and uptake of lipids by Insulin promotes synthesis of lipids and uptake of lipids by

smooth musclesmooth muscle

Excess sugar in vessels damages the lining Excess sugar in vessels damages the lining making it vulnerable to plaques and clotsmaking it vulnerable to plaques and clots

DiabetesDiabetesCareful control of blood sugar levels reduces the Careful control of blood sugar levels reduces the

risk of developing the complications of diabetesrisk of developing the complications of diabetes

Targets for diabetic controlTargets for diabetic control

ACSMACSMFBG <200 mg/dLFBG <200 mg/dL

2 hr pc BS <200mg/dL2 hr pc BS <200mg/dL

CanadianCanadianFBG 4-7 mmol/LFBG 4-7 mmol/L

2 hr pc BS 5-11 mmol/L2 hr pc BS 5-11 mmol/L

HgbA1C <0.07HgbA1C <0.07

StressStress Psychosocial factors associated with CAD risk:Psychosocial factors associated with CAD risk:

– Type A personalityType A personality

– Hostility/AngerHostility/Anger

– Depression/AnxietyDepression/Anxiety

3 to 4 times increased risk of death in first year 3 to 4 times increased risk of death in first year following MIfollowing MI

StressStress (Canadian)(Canadian)

Influence CAD risk via 2 main mechanisms:Influence CAD risk via 2 main mechanisms: Catacholamine releaseCatacholamine release

– increased BPincreased BP– increased HRincreased HR– vasoconstrictionvasoconstriction

– increased Oincreased O2 2 demanddemand

Decreased adherence to lifestyle Decreased adherence to lifestyle modification recommendationsmodification recommendations

Atherogenic DietAtherogenic Diet Diets high in fruits, vegetables, whole grains Diets high in fruits, vegetables, whole grains

and unsaturated fatty acids have lower risk for and unsaturated fatty acids have lower risk for CAD CAD

This influence goes beyond what is explained This influence goes beyond what is explained by other risk factors that may be related to diet.by other risk factors that may be related to diet.

Emerging Risk FactorsEmerging Risk Factors Nontraditional factors that are associated with Nontraditional factors that are associated with

increased risk of CVD, but a causal link has not yet increased risk of CVD, but a causal link has not yet been proved with certaintybeen proved with certainty

– Poor oral healthPoor oral health

– Dietary trans fat intakeDietary trans fat intake

– HomocysteineHomocysteine

– Lipoprotein ALipoprotein A

– Infectious agentsInfectious agents

– Adhesion moleculesAdhesion molecules

– CytokinesCytokines

– FibrogenFibrogen

– High sensitive C-High sensitive C-reactive proteinreactive protein