Coronary Heart Diseases (Ischemic heart diseases)Definition: “impairment of heart function due to inadequate blood flow to the heart compared to its needs, caused by obstructive changes in the coronary circulation to the heart”WHO→ CHD, CAD or IHD is our modern epidemic or the emerging epidemic. IHD is first leading cause of Death in the World.
The lumen of a coronary artery can be narrowed when a segment of the wall thickens (stenosis). Coronary Atherosclerosis: This process of arteries thickening and narrowing is brought about by two linked processes called atherogenesis and thrombogenesis .
Atherogenesis: Is the formation of atherosclerotic plaque (atheroma) in the internal layer of the wall of the artery. Thrombogenesis: Is the formation of a blood clot (thrombus) in a vessel by thrombocytes circulating in the blood on atheromatous plaque.
Atherogenesis: Is the formation of atherosclerotic plaque (atheroma) in the internal layer of the wall of the artery. Atherogenesis starts with fatty deposits. Fibrous tissue then grows around a fatty deposit creating an atherosclerotic plaque, which protrudes into the lumen of the artery narrowing it.
Atherogenesis: Is the formation of atherosclerotic plaque (atheroma) in the internal layer of the wall of the artery. Plaques vary in shape, size and composition, even in the same person and they are of 2 main types: 1. Stable: Atherosclerotic plaque contains little fat (cholesterol) and have a thick fibrous shell. 2. Unstable: Atherosclerotic plaque contains huge fat (cholesterol) and have a thin fibrous shell.
Thrombogenesis: Is the formation of a blood clot (thrombus) in a vessel by thrombocytes circulating in the blood on atheromatous plaque. When a plaque full of cholesterol ulcerates or desquamates, it releases the cholesterol content and various fragments of the plaque to the circulation. This triggers the formation of a blood clot by thrombocytes circulating in the blood, which leads to varying degrees of obstruction of the lumen.
Atherosclerosis can affect one or all coronary arteries and their branches. This process can be diffused or localized to a varying degree. Atherogenesis is slow (it may take up to 20–30 years) from the first fatty streaks before the coronary arteries are critically narrowed, whereas thrombogenesis may be quite rapid.
Clinical manifestations of coronary atherosclerosisUsually develop when the coronary arteries are narrowed at least by 75%. 1. Chest pain (angina pectoris ”stable or unstable”).2. Heart attack (myocardial infarction).3. Arrhythmia of any kinds. 4. Sudden cardiac death. 5. Congestive heart failure.
Irreversible damage to the cells may occur in about 40 minutes. The dead heart muscle cells cannot be replaced by new muscle cells (specialized). They are replaced by scar tissue, which is less elastic and does not contract as the muscle leading to many complications.
Inflammatory markers in atherosclerosis: 1. Pro-inflammatory cytokines (IL-1B, TNF-alpha) 2. Messenger cytokine (IL-6). 3. CRP as a prognostic factor and a predictor for treatment efficacy.
The role of infection: Certain infectious agents have been implicated based on their isolation from the atheromatous plaques or on the presence of positive serology findings for organisms such as 1. C pneumoniae, 2. Helicobacter pylori, 3. Herpes simplex virus, 4. Cytomegalovirus.
Causes of death in men and women
European cardiovascular disease statistics, 2008Diseases
Men (%)
Women (%)
CAD
21
22
Stroke
11
17
Other CVD
11
15
Cancer
21
17 (breast 3 %)
Respiratory
7
6
Injuries-Poisonning
12
5
Other
17
18
Annually, approximately 1.5 (0.5%) million Americans have an AMI, a third of whom die (0.16%). The survivors of MI have a poor prognosis, carrying a 1.5- to 15-fold higher risk of mortality and morbidity than the rest of the population.
Risk factors:The cause of atherosclerosis is not known. Risk factors can be divided into those that cannot be changed (unmodifiable; namely age, sex, race and family history) and those that can be (modified; or managed (such obesity and alcohol consumption).Risk factors multiply each other’s effect of increasing the risk of CHD (multiplicative not additive).
Multiplicative and exponential:The negative impact of more than one risk factor is not arithmetic but exponential. It can be quantified as follows:• The presence of one risk factor implies that the atherogenic risk is 1 on a relative scale. • The presence of three risk factors implies that the relative atherogenic risk is 9 and not 3, because the risk does not grow arithmetically (1 + 1 + 1= 3) but exponentially (3 times 3 = 9).Conversely, eliminating two of three risk factors would reduce the relative atherogenic risk from 9 to 1.
Un-modifiable risk factors: Age: 40-45 for men 50-55 for women. Sex: At all age men > women There is about a decade difference in incidence. Family history: Close or primary relatives. Especially premature atherosclerosis. Race: Till now there is no clear data established CHD state.
Modifiable risk factors:Dyslipedemia:↑ LDL↑ VLDL↑ TG↑ Cholesterol↓ HDLSmoking:Very strong evidenceDose-response relationship2-4 times riskPassive smokers also at large riskMultiplicative effects by acting on other risk factors
Modifiable risk factors: Hypertension: Well established risk factor Both systolic and diastolic hypertension Obesity: Central obesity more harmful than general obesity BMI > 25 (pre-obese) and > 30 (obese) WHR > 1 for men and WHR > 0.85 fro women Waist > 40 inch for men and Waist > 35 inch for women.
Modifiable risk factors: Diabetes:Both types IDDM and NIDDMRisk equivalent to established CHDIt causes and accelerates atherosclerosisDo not forget “silent MI”.Sedentary life:Because physical activity improves lipid profiles, ↓ BP, controls body weight, controls serum glucose, copes with stress.At least 30 min exercise (moderate) / day for 4-5 times / week.
Dependent / Emerging / Novel Risk Factors: •↑ Homocysteine.•↑ Lp (a).•Abnormalities in blood coagulation:– ↑ Plasma fibrinogen.– ↑ Coagulation factors: V, VII, VIII.– Platelets abnormalities.– Impaired fibrinolysis. •Inflammatory markers:– C-Reactive protein.– Interlukin.•Short stature.•Impaired glucose tolerance.•Increased oxidative stress.•Stress.•Tachycardia.•Ethnic group.•S. creatinine.Ultra-novel risk factors:• Plasma Myeloperoxidase.• Red Cell Glutathione Peroxidase 1 activity.
The French paradox: is partly explained by co-eating of antioxidatives plants, with its possible HDL-raising benefit. The Mediterranean diet: which includes predominant use of monounsaturated fatty acids, such as olive oil or canola oil, which are less atherogenic. The Eskimos: have been found to have a lower prevalence of CAD as a result of consuming fish oils containing omega-3 fatty acids.
Prevention: 1. Primary: By eliminating or reducing established risk factors (such as stop smoking and decrease weight) 2. Secondary: Good treatment of established case MI to reduce complication. 3. Tertiary: Rehabilitation of established case of MI to return to normal life. 4. Primordial: Prevention of risk factor before its development (such as healthy diets for baby). Strategies for prevention: 1. Population strategies. 2. High risk strategies.
The assessment of overall cardiovascular (CV) risk is a valuable and accepted means of identifying patients who are likely to benefit most from intervention. Risk elimination is central to the management of CV disease. Data from large epidemiological cohort studies have provided the raw data used to evaluate the contribution of individual CV risk factors. Usually, they use 10 years risk (prediction) of large CV events (such MI) for certain person, given as %.
GLOBAL RISK ASSESSMENT SCORING SYSTEMS• FRAMINGHAM Scoring System (USA).• PROCAM Scoring System (Germany).• SCORE Project (European). • INDIANA Project (Latin Americans).• Australian Scoring System (Australia).Etc.
Example: Peter has a 5% global risk of CV event, this means, 100 persons, like Peter, 5 of them will get major CV event (like MI) within subsequent 10 years.Classification of risk and action:0-1 (risk factors) → no scoring.Multiple (risk factors) → scoring , → Assessment of 10 years risk for CHD< 10% (low)10-20% (moderate)> 20% (high)
IMPLICATIONS: • Identification of high risk individuals.• Intensive Life Style Modification.• Initiation of pharmacologic Intervention.• Extent of risk factors correction.• Indications for non-invasive testing.
HIGH RISK INDIVIDUAL: 1. Probability of Developing a Fatal or Nonfatal MI =>20% in next 10 years.: 2. CHD Risk Equivalent• Three or more major risk factors.• High risk score.• Established –clinical atherosclerotic disease.• Very high level single risk factorMetabolic syndrome. •
Statins for primary prevention: 1. Statins produce 30% reduction in major coronary events for primary prevention. 2. More evidence for men than women. 3. Moderate dose statin may be most efficient. 4. Treatment according to scoring system. Brugts et al BMJ 2009; 338: 2376-
Aspirin for primary prevention of CHD events in men:• Aspirin reduces relative risk of CHD events (nonfatal MI) in men by 23%.• Aspirin causes gastrointestinal bleeding in 1-5 of 1000 users over 5 years.• Aspirin may also cause bleeding strokes in 1 of 1000 users over 5 years.• Determining benefit / harm ratio requires estimate of underlying CHD risk.ATT Collaboration Lancet 2009; 373: 1849-60 Pignone et al Annals Internal Medicine 2002; 136: 161-72
Effects of aspirin in 1000 men over 5 year
10% risk of CHD in 5 y5% risk of CHD in 5 y
2.5% risk of CHD in 5 y
Events
28
12
6
MI prevented
3-5
3-5
3-5
GIT Bleed
1
1
1
Stroke Bleed
WHAT TO DO ????????????????
Treatment ThresholdTreatment
10 years CVD risk
No treatment
< 5%
Statin
5-10%
Consider Statin + Aspirin
10- 15%
Statin + Aspirin
> 15%