Coronary Artery Disease
Atherosclerosis is the leading cause of death and disability in the developed and developing world Clinical manifestations depend on the particular vascular bed affected Coronary vasculature angina, MI, sudden death Cerebral TIA, stroke Peripheral claudication, gangrene Renal hypertensionEpidemiology Risk factors Pathogenesis Spectrum Prevention
EpidemiologyThe three major clinical manifestations of atherosclerotic CVD are: CHD CVA PVD
Disease impact: In 1997, more than 5mn Americans had CVD Currently one in five American has some form of CVD Each year 1mn deaths are due to CVD (42% of all deaths!) One-sixth of CVD deaths are in persons <65 yrs of age Annually 1.5mn Americans have MI 0.5mn die from CHD 0.5mn have stroke 0.15mn die from stroke
Death rates from CHD has decreased by 40% since 1968 CVD still remains the leading cause of death in developed nations CHD & stroke are the 2nd and 3rd leading causes of mortality even in the developing regions
Pathophysiology
CADis almost always due Atherosclerosis Occasionally, other such as aortitis, polyarteritisAtherosclerosis is a progressive inflammatory disorder of the arterial wall that is characterised by focal lipidrich deposits of atheroma.Development of lesions, starting in childhood, progress through phases, caused by injury to intima of arteryPhase I : fatty streaks – do not obstruct flowPhase II: fibrous plaque- elevated lesion protruding into lumen obstructs flow to varying degreesPhase III: complicated lesions – partially or totally occlude lumenEarly atherosclerosis(Fatty streaks )tend to occur at sites of altered arterial shear stress, such as bifurcations.They develop when inflammatory cells, predominantly monocytes, bind to receptors expressed by endothelial cells, migrate into the intima, take up oxidised low-density lipoprotein (LDL)particles and become lipid-laden macrophages or foam cells. In response to cytokines and growth factors produced by activated macrophages, smooth muscle cells migrate from the media of the arterial wall into the intima, and change from a contractile to a repair phenotype in an attempt to stabilise the atherosclerotic lesion. Advanced lesion Vulnerable plaques Stable plaques Thin fibrous cap Thick cap Large lipid core Dense extracellular matrix High macrophage content Less lipid rich core
Concept of “Risk factors” for CAD evolved from prospectiveepidemiological studies in US and Europe whichdemonstrated consistent association among characteristics observed at one point of time in apparently healthy individuals and subsequent incidence of CAD in these patients.But, presence of a risk factor does not necessarily imply a direct causal relationship.
Non-modifiable risk factorsAge: death from CAD with ageSexFamily historyRace: afro-Americans have = 45% > hypertension than Caucasians Risk factors
Coronary Artery Disease
Modifiable Risk FactorsCigarette smoking: 2X increased risk for CADHTN: damages blood vessels leading to plaque formation and atherosclerosisHyperlipidemia: CAD and atherosclerosis by causing build up in artery wallsPhysical Inactivity: risk of CAD 2XDiabetes: risk 2X in men; 3X in womenObesityStress : increased catecholamine release; sympathetic responseDyslipidemia
Better term than hyperlipidemia as it includes the risk of having low HDL Serum total cholesterol (TC) is a composite of: LDL cholesterol- directly related to CVD HDL cholesterol- inversely related to CVD VLDL cholesterol- related to CVD in patients with DM and low HDL Best single predictor for CVD risk is TC/HDL ratio. Ideal ratio is <3, intermediate 3-5, high risk >5 This ratio is also the best predictor of treatment benefitsHypertension
Potent risk factor for all CVD and dominant risk factor for stroke. Graded relationship between level of BP and outcomes. SBP rises with age, whereas DBP plateaus in the late middle life and decreases somewhat then.Trials for isolated systolic hypertension have shown benefits for both stroke and CHD
Systolic and diastolic hypertension increase the RR for CVDby 1.6 timesFor combined Systolic and diastolic HTN the RR is 2.0The risk for CVD is increased even in individuals with “high normal BP” (130-39/85-89 mm Hg)Smoking
This habit increases the risk of vascular outcomes by 2 fold. Both, regular and filter cigarettes have same adverse effects. Low tar/low nicotine products have not been shown to reduce the risk Unlike other modifiable risk factors, cigarette smoking can be eliminated entirely Benefits of quitting smoking are dramatic. Risk in ex-smokers falls to near non-smoking levels in 2 yrs.
Obesity
It contributes independently to CVD risk and also aggravates known CVD risk factors. Measures of obesity include: BMI Waist: hip ratio.Diabetes Mellitus
Patients with either type I or type II diabetes have increased risk for CVD Risk of CHD is increased 2-fold in young men and 3-fold in young women with type 2 diabetes Type II diabetics have one or more metabolic abnormalities (hypertriglyceridemia, low HDL, hypertension) They may also have normal LDL levels but LDL particles are dense and small thus being more atherogenicSpectrum of coronary artery disease -Silent ischemia -Chronic stable angina -Acute coronary syndromes Unstable angina NSTEMI STEMI -Heart failure -Arrhythmia -Sudden death
Chronic stable angina
Angina pectoris is the clinical syndrome caused by transient myocardial ischaemia. It may occur whenever there is an imbalance between myocardial oxygen supply and demand. Coronary atheroma is by far the most common cause of angina.Chronic stable angina
Chest discomfort caused by transient myocardial ischemia without cell deathUsually brought on by physical or emotional stress and promptly relieved by rest.Precipitated by 4 “E’s”Extreme emotionExtreme temperatureExcessive eatingExerciseCoronary atheroma is by far the most common cause of angina.Physical examination is frequently unremarkable.Investigations
Resting ECG often normal. Exercise ECG. Myocardial perfusion scanning. Stress echocardiography. Coronary arteriographyManagement
Risk factors modification such as smoking, hypertension and hyperlipidaemia. Drugs Antiplatelet therapy Low-dose aspirin reduces the risk of adverse events such as MI and should be prescribed for all patients with coronary artery disease indefinitely .Clopidogrel (75 mg daily) is an equally effective. Anti-anginal drug treatment Nitrates Beta-blockersCalcium channel antagonists Potassium channel activators Invasive treatment Percutaneous coronary intervention PCI. CABG
Acute coronary syndrome
Acute coronary syndrome is a term that encompasses both unstable angina and myocardial infarction (MI). It is characterised by new-onset or rapidly worsening angina (crescendo angina), angina on minimal exertion or angina at rest in the absence of myocardial damage. In contrast, MI occurs when symptoms occur at rest and there is evidence of myocardial necrosis, as demonstratedby an elevation in cardiac troponin or creatinekinase-MB isoenzym.Acute myocardial infarction (AMI) One of the most common diagnosis in hospitalized patients in industrialized nations Mortality of acute MI is 30% and one-half of these deaths occur before hospitalization Mortality after admission has decreased by 30% in last 2 decades 1
Pathophysiology AMI results when thrombus (occlusive/nonocclusive) develops at the site of ruptured plaque
Vulnerable plaque Rupture
Coagulation cascade platelet adhesion, activation activation,aggregation
Fibrin and platelet clot Coronary occlusion MI
Presentation:Chest pain- most common, similar to anginal pain butmore severe and prolongeddescribed as severe, crushing/squeezing/pressure‘worst pain’ everChest pain may be absent in pts with DM or in elderlyAtypical presentations:confusion, syncope, profound wkness, arrhythmia
Differential diagnosis: Pericarditis Pulmonary embolism Pneumothorax Aortic dissection Esophageal spasm
Examination: Anxiety, pallor, restlessness Substernal chest pain with diaphoresis is strongly suggestive of AMI Those with anterior MI may have sympathetic overactivity whereas those with inferior MI may have para- sympathetic overactivity S3/S4 Transient systolic murmur due to dysfunction of mitral apparatus leading to mitral regurgitation
Laboratory findings: EKG specific but insensitive tool for diagnosis of myocardial ischemia Total occlusion of infarct related artery leads to ST elevation (STEMI) and subsequent evolution of Q waves Partial occlusion/early recanalization/rich collaterals leads to NSTEMI (non-ST elevation MI)
Serum cardiac markers: Released into the circulation from necrotic heart muscle CK (creatine kinase) rises 4-8 hrs after onset of MI and normalize by 48-72 hrs not specific for myocardial necrosis MB isoenzyme of CK is more specific Cardiac specific troponins: more sensitive and specific than CK and CKMB for identification of myocardial necrosis Myoglobin- first serum marker to rise after MI, but lacks specificity.
Cardiac Enzymes
Cardiac imaging 2D echocardiography reveals regional wall motion abnormality also useful to identify mechanical complications of MI Radionuclide imaging used infrequently in the diagnosis of acute MI mainly used to risk stratify patients with CHDManagement Prehospital care: Major elements include Recognition of symptoms by the patient and prompt medical attention Rapid deployment of EMS capable of resuscitation and defibrillation Expeditious implementation of reperfusion
Goals of Initial management in ED Control of cardiac pain Rapid identification of patients suitable for reperfusion Triage of low risk patients for subsequent care Avoiding inappropriate discharge of patients with MI
Initial management Focused history and Focused examiation Reaassurance Enssure IV acess + Basic investigaions Aspirin: 160-325 mg chewable aspirin + Clopidogril Oxygen by nasal cannula if hypoxemia is present Sublingual nitroglycerine followed by IV infusion if needed Intravenous betablockers (decrease myocardial oxygen demand, control chest pain and reduce mortality) Morphine for pain relief (given IV in small doses)+ Metelopromide Monitor 12 Leads ECG Consider Reperfusion
Reperfusion therapy
Primary percutaneous coronary intervention (PCI). Thrombolysis.STEMI
ASA, beta blockers, antithrombin therapy<12 hrs >12 hrs
Eligible for Lytic therapy
Lytic C/I
Not a candidate For reperfusion
Persistent symptoms
Thrombolysis Primary PCI no yes
Other medical therapy Consider reperfusion (ACEI, nitrates, beta blockers, antiplatelets, antithrombin,statins)
Time is muscle
Complications of acute coronary syndromeArrhythmias VF,AF, BRADYCARDIA Ischaemia Acute circulatory failure Pericarditis Mechanical complications Embolism Impaired ventricular function HF Ventricular aneurysm
Unstable angina/NSTEMI Aspirin, anticoagulants, nitrates, GP IIb-IIIa antagonist Betablockers(calcium channel blockers) Assess clinical status
High risk/unstable Stable
(Recurrent ischemia, LV dysfunction Widespread EKG changes, positive enzyme markers)
Cardiac catheterization Severe ischemia
Revascularization (PCI/CABG) Medical therapy
Stress test
yes
no