Coronary Heart Diseases (Ischemic heart diseases)Coronary Heart Diseases (Ischemic heart diseases)

Definition:Definition: “impairment of heart function due to inadequate blood “impairment of heart function due to inadequate blood flow to the heart compared to its needs, caused by flow to the heart compared to its needs, caused by obstructive changes in the coronary circulation to the obstructive changes in the coronary circulation to the heart”heart”

WHO→ CHD, CAD or IHD is our modern epidemic or WHO→ CHD, CAD or IHD is our modern epidemic or the emerging epidemic.the emerging epidemic.

IHD is first leading cause of IHD is first leading cause of Death in the WorldDeath in the World . .

The lumen of a coronary artery can be narrowed when a The lumen of a coronary artery can be narrowed when a segment of the wall thickens segment of the wall thickens (stenosis)(stenosis). .

Coronary Atherosclerosis: Coronary Atherosclerosis: This process of arteries thickening and narrowing is This process of arteries thickening and narrowing is brought about by two linked processes called brought about by two linked processes called atherogenesisatherogenesis and and thrombogenesisthrombogenesis

..

Atherogenesis:Atherogenesis: Is the formation of atherosclerotic plaque Is the formation of atherosclerotic plaque (atheroma) (atheroma) in in the internal layer of the wall of the artery.the internal layer of the wall of the artery. Thrombogenesis:Thrombogenesis: Is the formation of a blood clot Is the formation of a blood clot (thrombus) (thrombus) in a vessel byin a vessel bythrombocytes circulating in the blood on atheromatous thrombocytes circulating in the blood on atheromatous plaqueplaque..

Atherogenesis:Atherogenesis: Is the formation of atherosclerotic plaque Is the formation of atherosclerotic plaque (atheroma) (atheroma) in in the internal layer of the wall of the artery.the internal layer of the wall of the artery.

Atherogenesis starts with fatty deposits. Fibrous tissue Atherogenesis starts with fatty deposits. Fibrous tissue then grows around a fatty deposit creating an then grows around a fatty deposit creating an atherosclerotic plaque, which protrudes into the lumen of atherosclerotic plaque, which protrudes into the lumen of the artery narrowing itthe artery narrowing it..

Atherogenesis:Atherogenesis: Is the formation of atherosclerotic plaque Is the formation of atherosclerotic plaque (atheroma) (atheroma) in in the internal layer of the wall of the artery.the internal layer of the wall of the artery.

Plaques vary in shape, size and composition, even in Plaques vary in shape, size and composition, even in the same person and they are of 2 main types:the same person and they are of 2 main types:

1. Stable: 1. Stable: Atherosclerotic plaque contains little fat Atherosclerotic plaque contains little fat (cholesterol) and have a thick fibrous shell.(cholesterol) and have a thick fibrous shell.

2. Unstable: 2. Unstable: Atherosclerotic plaque Atherosclerotic plaque contains huge fat (cholesterol) and contains huge fat (cholesterol) and have a thin fibrous shellhave a thin fibrous shell..

Thrombogenesis:Thrombogenesis: Is the formation of a blood clot Is the formation of a blood clot (thrombus) (thrombus) in a vessel byin a vessel bythrombocytes circulating in the blood on atheromatous thrombocytes circulating in the blood on atheromatous plaque.plaque. When a plaque full of cholesterol When a plaque full of cholesterol ulceratesulcerates or or desquamatesdesquamates, it releases the cholesterol content and , it releases the cholesterol content and various fragments of the plaque to the circulation. various fragments of the plaque to the circulation.

This triggers the formation of a This triggers the formation of a blood clot blood clot by by thrombocytes circulating in the blood, which leads to thrombocytes circulating in the blood, which leads to varying degrees of obstruction of the lumenvarying degrees of obstruction of the lumen..

Atherosclerosis can affect one or all coronary arteries Atherosclerosis can affect one or all coronary arteries and their branches. This process can be diffused or and their branches. This process can be diffused or localized to a varying degree.localized to a varying degree. Atherogenesis is Atherogenesis is slowslow (it may take up to 20–30 years) (it may take up to 20–30 years) from the first fatty streaks before the coronary arteries from the first fatty streaks before the coronary arteries are critically narrowed, are critically narrowed, whereas thrombogenesis may be whereas thrombogenesis may be quite rapidquite rapid..

Clinical manifestations of coronary atherosclerosisClinical manifestations of coronary atherosclerosis

Usually develop when the coronary arteries are Usually develop when the coronary arteries are narrowed at least by narrowed at least by 75%75%. .

1. Chest pain (angina pectoris ”stable or unstable”).1. Chest pain (angina pectoris ”stable or unstable”).2. Heart attack (myocardial infarction).2. Heart attack (myocardial infarction).3. Arrhythmia of any kinds. 3. Arrhythmia of any kinds. 4. Sudden cardiac death. 4. Sudden cardiac death. 5. Congestive heart failure5. Congestive heart failure..

Irreversible damage to the cells may occur in about 40 Irreversible damage to the cells may occur in about 40 minutes. minutes. The dead heart muscle cells cannot be replaced by The dead heart muscle cells cannot be replaced by new muscle cells (specialized). new muscle cells (specialized). They are replaced by scar tissue, which is less elastic They are replaced by scar tissue, which is less elastic and does not contract as the muscle leading to many and does not contract as the muscle leading to many complications.complications.

Inflammatory markers in atherosclerosis:Inflammatory markers in atherosclerosis:

1. Pro-inflammatory cytokines (1. Pro-inflammatory cytokines (IL-1BIL-1B, , TNF-alphaTNF-alpha))2. Messenger cytokine (2. Messenger cytokine (IL-6IL-6).).

3. 3. CRPCRP as a prognostic factor and a predictor for as a prognostic factor and a predictor for treatment efficacytreatment efficacy..

The role of infection:The role of infection:

Certain infectious agents have been implicated based on Certain infectious agents have been implicated based on their isolation from the atheromatous plaques or on the their isolation from the atheromatous plaques or on the presence of positive serology findings for organisms presence of positive serology findings for organisms such as such as 1. 1. C pneumoniae, C pneumoniae, 2. Helicobacter pylori,2. Helicobacter pylori, 3. Herpes simplex virus, 3. Herpes simplex virus,

4. Cytomegalovirus4. Cytomegalovirus . .

Causes of Causes of deathdeath in men and women in men and women

European cardiovascular disease statistics, 2008European cardiovascular disease statistics, 2008

DiseasesMen(%) Women(%)

CAD2122

Stroke1117

Other CVD1115

Cancer2117) breast 3(%

Respiratory76

Injuries-Poisonning

125

Other1718

Annually, approximately 1.5 (0.5%) million Americans Annually, approximately 1.5 (0.5%) million Americans have an AMI, a third of whom die (0.16%).have an AMI, a third of whom die (0.16%).

The survivors of MI have a poor prognosis, carrying a The survivors of MI have a poor prognosis, carrying a 1.5- to 15-fold higher risk of mortality and morbidity than 1.5- to 15-fold higher risk of mortality and morbidity than the rest of the population. the rest of the population.

Risk factors:Risk factors:

The cause of atherosclerosis is not known. The cause of atherosclerosis is not known.

Risk factors can be divided into those that cannot be Risk factors can be divided into those that cannot be changed (changed (unmodifiableunmodifiable; namely age, sex, race and ; namely age, sex, race and family history) and those that can be (family history) and those that can be (modifiedmodified; or ; or managed (such obesity and alcohol consumption).managed (such obesity and alcohol consumption).

Risk factors multiply each other’s effect of increasing the Risk factors multiply each other’s effect of increasing the risk of CHD (risk of CHD (multiplicativemultiplicative not additive) not additive)..

Multiplicative and exponential:Multiplicative and exponential:The negative impact of more than one risk factor is not The negative impact of more than one risk factor is not arithmetic but exponential. It can be quantified as arithmetic but exponential. It can be quantified as follows:follows:• The presence of one risk factor implies that the • The presence of one risk factor implies that the atherogenic risk is 1 on a relative scale. atherogenic risk is 1 on a relative scale.

• The presence of three risk factors implies that the • The presence of three risk factors implies that the relative atherogenic risk is 9 and not 3, because the risk relative atherogenic risk is 9 and not 3, because the risk does not grow arithmetically (1 + 1 + 1= 3) but does not grow arithmetically (1 + 1 + 1= 3) but exponentially (3 times 3 = 9).exponentially (3 times 3 = 9).

Conversely, eliminating two of three risk factors would Conversely, eliminating two of three risk factors would reduce the relative atherogenic risk from 9 to 1reduce the relative atherogenic risk from 9 to 1..

Un-modifiable risk factors:Un-modifiable risk factors:

Age:Age:40-45 for men40-45 for men50-55 for women.50-55 for women.

Sex:Sex: At all age men > womenAt all age men > womenThere is about a decade difference in incidence.There is about a decade difference in incidence.

Family history:Family history:Close or primary relatives.Close or primary relatives.Especially premature atherosclerosis.Especially premature atherosclerosis.

Race:Race:Till now there is no clear data established CHD stateTill now there is no clear data established CHD state . .

Modifiable risk factors:Modifiable risk factors:

Dyslipedemia:Dyslipedemia:↑ LDL↑ LDL↑ VLDL↑ VLDL↑ TG↑ TG↑ Cholesterol↑ Cholesterol↓ HDL↓ HDL

Smoking:Smoking:Very strong evidenceVery strong evidenceDose-response relationshipDose-response relationship2-4 times risk2-4 times riskPassive smokers also at large riskPassive smokers also at large riskMultiplicative effects by acting on other risk factorsMultiplicative effects by acting on other risk factors

Modifiable risk factors:Modifiable risk factors: Hypertension:Hypertension:Well established risk factorWell established risk factorBoth systolic and diastolic hypertensionBoth systolic and diastolic hypertension

Obesity:Obesity:Central obesity more harmful than general obesityCentral obesity more harmful than general obesityBMI > 25 (pre-obese) and > 30 (obese)BMI > 25 (pre-obese) and > 30 (obese)WHR > 1 for men and WHR > 0.85 fro womenWHR > 1 for men and WHR > 0.85 fro womenWaist > 40 inch for men and Waist > 35 inch for womenWaist > 40 inch for men and Waist > 35 inch for women..

Modifiable risk factors:Modifiable risk factors:

Diabetes:Diabetes:Both types IDDM and NIDDMBoth types IDDM and NIDDMRisk equivalent to established CHDRisk equivalent to established CHDIt causes and accelerates atherosclerosisIt causes and accelerates atherosclerosisDo not forget “silent MI”.Do not forget “silent MI”.

Sedentary life:Sedentary life:Because physical activity improves lipid profiles, ↓ BP, Because physical activity improves lipid profiles, ↓ BP, controls body weight, controls serum glucose, copes controls body weight, controls serum glucose, copes with stress.with stress.At least 30 min exercise (moderate) / day for 4-5 times / At least 30 min exercise (moderate) / day for 4-5 times /

weekweek . .

Modifiable risk factors:Modifiable risk factors: Metabolic Syndrome:Metabolic Syndrome:A cluster of Most established heart attack risk factors A cluster of Most established heart attack risk factors including:including:- Diabetes or insulin resistant (± glucose intolerance), +- Diabetes or insulin resistant (± glucose intolerance), +- Raised blood pressure, + - Raised blood pressure, + - Atherogenic dyslipidemia, + - Atherogenic dyslipidemia, + - Abdominal obesity, + - Abdominal obesity, + - Pro-thrombotic (± pro-inflammatory state)- Pro-thrombotic (± pro-inflammatory state)* Main target for intervention.* Main target for intervention.

Personality type APersonality type A

Dependent / Emerging / Novel Risk Factors: Dependent / Emerging / Novel Risk Factors: •↑ Homocysteine.•↑ Homocysteine.•↑ Lp (a).•↑ Lp (a).•Abnormalities in blood coagulation:•Abnormalities in blood coagulation:– ↑ Plasma fibrinogen.– ↑ Plasma fibrinogen.– ↑ Coagulation factors: V, VII, VIII.– ↑ Coagulation factors: V, VII, VIII.– Platelets abnormalities.– Platelets abnormalities.– Impaired fibrinolysis. – Impaired fibrinolysis. •Inflammatory markers:•Inflammatory markers:– C-Reactive protein.– C-Reactive protein.– Interlukin.– Interlukin.•Short stature.•Short stature.•Impaired glucose tolerance.•Impaired glucose tolerance.•Increased oxidative stress.•Increased oxidative stress.•Stress.•Stress.•Tachycardia.•Tachycardia.•Ethnic group.•Ethnic group.•S. creatinine.•S. creatinine.

Ultra-novel risk factors:Ultra-novel risk factors:• Plasma Myeloperoxidase.• Plasma Myeloperoxidase.• Red Cell Glutathione Peroxidase 1 activity• Red Cell Glutathione Peroxidase 1 activity..

The French paradox: The French paradox: is partly explained by co-eating of is partly explained by co-eating of antioxidatives plants, with its possible HDL-raising antioxidatives plants, with its possible HDL-raising benefit.benefit.

The Mediterranean diet:The Mediterranean diet: which includes predominant which includes predominant use of monounsaturated fatty acids, such as olive oil or use of monounsaturated fatty acids, such as olive oil or canola oil, which are less atherogenic. canola oil, which are less atherogenic.

The Eskimos: The Eskimos: have been found to have a lower have been found to have a lower prevalence of CAD as a result of consuming fish oils prevalence of CAD as a result of consuming fish oils containing omega-3 fatty acidscontaining omega-3 fatty acids..

Prevention:Prevention:

1. Primary: 1. Primary: By eliminating or reducing established risk By eliminating or reducing established risk factors (such as stop smoking and decrease weight) factors (such as stop smoking and decrease weight) 2. Secondary: 2. Secondary: Good treatment of established case MI to Good treatment of established case MI to reduce complication.reduce complication.3. Tertiary: 3. Tertiary: Rehabilitation of established case of MI to Rehabilitation of established case of MI to return to normal life.return to normal life.4. Primordial: 4. Primordial: Prevention of risk factor before its Prevention of risk factor before its development (such as healthy diets for baby).development (such as healthy diets for baby).

Strategies for prevention:Strategies for prevention:

1. Population strategies.1. Population strategies.2. High risk strategies2. High risk strategies..

The assessment of overall cardiovascular (CV) risk is a The assessment of overall cardiovascular (CV) risk is a valuable and accepted means of identifying patients who valuable and accepted means of identifying patients who are likely to benefit most from intervention.are likely to benefit most from intervention. Risk elimination is central to the management of CV Risk elimination is central to the management of CV disease.disease.

Data from large epidemiological cohort studies have Data from large epidemiological cohort studies have provided the raw data used to evaluate the contribution provided the raw data used to evaluate the contribution of individual CV risk factors.of individual CV risk factors.

Usually, they use Usually, they use 10 years risk 10 years risk (prediction) of large (prediction) of large CV events (such CV events (such MIMI) for certain person, given as) for certain person, given as %%..

GLOBAL RISK ASSESSMENT SCORING SYSTEMSGLOBAL RISK ASSESSMENT SCORING SYSTEMS

• FRAMINGHAM Scoring System (USA).• FRAMINGHAM Scoring System (USA).

• PROCAM Scoring System (Germany).• PROCAM Scoring System (Germany).

• SCORE Project (European). • SCORE Project (European).

• INDIANA Project (Latin Americans).• INDIANA Project (Latin Americans).

• Australian Scoring System (Australia).• Australian Scoring System (Australia).

EtcEtc . .

Example: Example: Peter has a 5% global risk of CV event, this Peter has a 5% global risk of CV event, this means, 100 persons, like Peter, 5 of them will get major means, 100 persons, like Peter, 5 of them will get major CV event (like MI) within subsequent 10 years.CV event (like MI) within subsequent 10 years.

Classification of risk and action:Classification of risk and action:

0-1 0-1 (risk factors) → no scoring. (risk factors) → no scoring.

Multiple (risk factors) Multiple (risk factors) → scoring , → Assessment of 10 years → scoring , → Assessment of 10 years risk for CHDrisk for CHD

< 10% (low)< 10% (low)

10-20% (moderate)10-20% (moderate)

> 20% (high)> 20% (high)

IMPLICATIONS:IMPLICATIONS: • Identification of high risk individuals.• Identification of high risk individuals.

• Intensive Life Style Modification.• Intensive Life Style Modification.

• Initiation of pharmacologic Intervention.• Initiation of pharmacologic Intervention.

• Extent of risk factors correction.• Extent of risk factors correction.

• Indications for non-invasive testing• Indications for non-invasive testing..

HIGH RISK INDIVIDUAL:HIGH RISK INDIVIDUAL:

1. Probability of Developing a Fatal or Nonfatal MI 1. Probability of Developing a Fatal or Nonfatal MI =>20% in next 10 years.=>20% in next 10 years.

: : 2. CHD Risk Equivalent2. CHD Risk Equivalent

• Three or more major risk factors.• Three or more major risk factors.• High risk score.• High risk score.• Established –clinical atherosclerotic disease.• Established –clinical atherosclerotic disease.• Very high level single risk factor• Very high level single risk factor

Metabolic syndromeMetabolic syndrome.. ••

Statins for primary prevention:Statins for primary prevention:

1. Statins produce 30% reduction in major coronary 1. Statins produce 30% reduction in major coronary events for primary prevention.events for primary prevention.

2. More evidence for men than women.2. More evidence for men than women. 3. Moderate dose statin may be most efficient.3. Moderate dose statin may be most efficient.

4. Treatment according to scoring system.4. Treatment according to scoring system.

Brugts et al BMJ 2009; 338: 2376Brugts et al BMJ 2009; 338: 2376--

Aspirin for primary prevention of CHD events in men:Aspirin for primary prevention of CHD events in men:

• Aspirin reduces relative risk of CHD events (nonfatal MI) in men • Aspirin reduces relative risk of CHD events (nonfatal MI) in men by by 23%23%..

• Aspirin causes gastrointestinal bleeding in • Aspirin causes gastrointestinal bleeding in 1-5 of 1000 users 1-5 of 1000 users over 5 yearsover 5 years..

• Aspirin may also cause bleeding strokes in • Aspirin may also cause bleeding strokes in 1 of 1000 users over 1 of 1000 users over 5 years5 years..

• Determining benefit / harm ratio requires estimate of underlying • Determining benefit / harm ratio requires estimate of underlying CHD risk.CHD risk.

ATT Collaboration Lancet 2009; 373: 1849-60 Pignone et al Annals Internal Medicine ATT Collaboration Lancet 2009; 373: 1849-60 Pignone et al Annals Internal Medicine 2002; 136: 161-722002; 136: 161-72

Effects of aspirin in 1000 men over 5 yearEffects of aspirin in 1000 men over 5 year

Events2.5% risk of

CHD in 5 y

5% risk of

CHD in 5 y

10% risk of

CHD in 5 y

MI prevented

61228

GIT Bleed3-53-53-5

Stroke Bleed

111

WHAT TO DOWHAT TO DO???????????????? ????????????????

Treatment ThresholdTreatment Threshold

10 years CVD riskTreatment

< 5%No treatment

5-10%Statin

10- 15%Consider

Statin + Aspirin

<15%

Statin + Aspirin

QuestionsQuestions? … ? …