PATHOPHYSIOLOGY OF CARDIOVASCULAR DISEASE CVD

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PATHOPHYSIOLOGY OF CARDIOVASCULAR DISEASE (CVD)

• leading cause of death in the U.S. for men and
  women
• 42 of all deaths (1 out every 2.4 deaths)
• an average of one death every 33 seconds

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CARDIOVASCULAR DISEASE

• claims as many lives as the other top 8 causes of
  death combined
• 1/6th are under age 65
• From 1984 -1994 CVD deaths declined 22 (although
  the actual number of deaths dropped only 3)

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CARDIOVASCULAR DISEASE

• includes
• coronary artery disease
• stroke
• hypertension
• congenital heart disease
• valvular heart disease
• rheumatic heart disease
• arrhythmias

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CARDIOVASCULAR DISEASE

• Coronary Artery Disease (CAD) or Coronary Heart
  disease (CHD)
• single leading cause of death in the U.S. (20 of
  all deaths)
• May result in
• angina pectoris
• myocardial infarction
• sudden cardiac death
• congestive heart failure
• KEY TERMS Pg 412 Resource Manual

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Myocardial Infarction

• 1.5 million myocardial infarctions (MIs) per
  year
• 500,000 fatal
• 250,000 die within an hour of onset (sudden MI)

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Myocardial Infarction

• 13.5 million alive today with history of MI
• 5 of MI in people under 40 years old
• 45 under 65 years old
• In 48 of men and 63 of women who died suddenly
  of MI, there were no previous symptoms

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Coronary Heart Disease

• atherosclerosis
• progressive build-up of plaque on the inside of
  the artery wall
• large arteries
• arteriosclerosis
• hardening of the arteries
• thickening of arterial wall
• loss of elastic tissue

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Coronary Heart Disease

• Causes of Atherosclerosis
• Risk factors - increase the probability of
  developing the disease
• Primary or major risk factors (pg 415)
• hypertension
• dyslipidemia
• cigarette smoking
• physical inactivity
• obesity

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Coronary Heart Disease

• Secondary risk factors
• diabetes
• personality type / stress
• family history of CHD
• age
• gender
• race

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Coronary Heart Disease

• Risk factors
• Key Terms pg 96 Resource Manual
• Other classification scheme Box 5-1 pg 97
• Lipid classification
• Box 5-2 pg 98-100
• Blood pressure pg 103
• Obesity pg 104
• Emerging risk factors
• Framingham Risk Assessment

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Coronary Arteries

• Normal coronary arteries
• left main
• left anterior descending (LAD)
• circumflex
• right coronary artery
• posterior descending artery (PDA)

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Process of Atherosclerosis

• Atherosclerosis - lesions of the large and
  medium-sized arteries with deposits in the intima
  of yellowish plaques containing cholesterol,
  lipoid material , and lipophages
• 3 stages of development
• Intimal thickening- reversible
• Fatty streaks - reversible
• Fibrous plaques - irreversible (at least for the
  most part)

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Process of Atherosclerosis

• Endothelium or endothelial layer (figure 29-1 pg
  412)
• lines inside of arterial walls
• in direct contact with blood
• controls passage of substances from blood into
  arterial wall
• Anti-thrombotic inhibit blood clots

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Process of Atherosclerosis

• Endothelial Cells
• Produce several vasoactive substances
• Prostacyclin - vasodilator antithrombotic
• Endothelial derived relaxing factor (EDRF) or
  nitric oxide - inactivates platelets inhibits
  smooth muscle cell migration and proliferation

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Process of Atherosclerosis

• Endothelial Cells
• under normal conditions - protect against the
  development of atherosclerosis
• when damaged - play a major role in its
  development
• Box 29-1 pg 413 - causes of endothelial injury

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Process of Atherosclerosis

• layers of the artery
• intima
• media
• adventitia - contain collagen, elastin, and
  fibroblasts contain the vasa vasorum small
  blood vessels

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Process of Atherosclerosis

• Smooth muscle cells
• located primarily in the medial layer
• contractile
• synthetic
• sensitive to growth promoting factors(prolifitive
  ) and migrating factors

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Process of Atherosclerosis

• Platelets
• tiny cells in the blood stream that repair
  holes in the arterial wall (intima)
• platelet plug prevents blood loss
• prothrombotic - clot forming
• Monocytes and Macrophages
• cells of the immune system
• activated at sites of arterial injury

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Process of Atherosclerosis

• Fibroblasts
• type of connective tissue
• in response to growth factors, migrate from the
  media to intima and synthesize fibrous tissue
  (along with smooth muscles)
• Foam Cells
• cells formed from other cells such as
  macrophages which release cholesterol into the
  extracellular space giving rise to fatty streaks

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Process of Coronary Artery Disease

• Injury hypothesis of CAD
• endothelial disruption is the first step in a
  series of events
• risk factors may be involved in causing the
  initial injury
• Box 29-1 pg 413 Resource Manual - list of
  factors that may result in endothelial injury
• Inflammatory response Box 29-2 pg 413

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Process of Coronary Artery Disease

• Following endothelial injury, a number of
  pathologic events occur which often lead to
  narrowing of the arterial lumen diameter
• Endothelial disruption can lead to
• mitogenic effects - growth of tissues /cells
• chemotactic effects - migration of cells
• Injury hypothesis of CAD
• figure 29.2 Resource Manual

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Process of Coronary Artery Disease

• Relationship of cardiovascular disease risk
  factors to the Injury hypothesis
• tobacco use - Box 29-3 pg 415
• diabetes - Box 29-4 pg 415
• hypertension
• dyslipidemia

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Process of Atherosclerosis

• progression of atherosclerosis is non-linear
• some lesions are stable over many years
• some progress rapidly within months
• Rupture of Fissuring of plaques
• from turbulent flow or chemical factors
• may lead to mural thrombi (platelet aggregation)
  of varying sizes at these sites
• Thrombi may be incorporated into the plaque
  during this process

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Process of Atherosclerosis

• Coronary atherosclerosis can occur diffusely
  (long length of artery) with occasional discrete,
  localized areas of more pronounced narrowing of
  the vessel lumen that may produce obstruction of
  blood flow.
• Non-atherosclerotic coronary obstructions
• Coronary vasospasm
• Intracoronary thrombus

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Atherosclerotic Plaques

• Described as percent occlusion or percent
  stenosis
• Example 90 stenosis of the LAD
• Obstructive coronary atherosclerosis is used to
  describe CAD that is severe enough to reduce
  blood flow
• Severity of coronary atherosclerosis is detected
  using coronary angiography
• coronary angiogram

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Atherosclerotic Plaques

• Regression of CAD using non-invasive
  interventions
• Diet
• Exercise
• Medications

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Treatment Options for CAD

• Revascularization Procedures
• Percutaneous Transluminal Coronary Angioplasty
  (PTCA)
• Coronary Artery Bypass Surgery (CABS) or Coronary
  Artery Bypass Graft (CABG) surgery
• Coronary Atherectomy and Rotablator
• Laser Angioplasty

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• Percutaneous Transluminal Coronary
  Angioplasty (PTCA)

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Coronary Obstructions After Cardiac Interventions

• Restenosis - reocclussion of obstructive lesion
• Tend not to be as lipid rich as original plaque
  and are highly related to thrombosis
• Approximately 35 at 5 years from original CABS
• Approximately 45 at 6 months for PTCA
• Restenosis rate reduced using coronary stents
  after PTCA

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Progression of Atherosclerosis

• Rate of progression is highly related to number
  and severity of risk factors
• Native vessels
• Saphenous vein grafts
• Internal mammary grafts
• After PTCA and other interventions

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Exercise and Atherosclerosis

• Independently reduces risk of CAD
• Slows rate of progression by acting on other risk
  factors
• Increases fibrinolytic activity
• May stimulate the formation of collateral vessels
  when one or more obstructive lesions are present

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Manifestations of Coronary Atherosclerosis
Coronary Blood Flow

• heart - completely aerobic organ
• coronary blood flow myocardial oxygen supply
• oxygen requirements of the myocardium
  myocardial oxygen demand
• at rest, myocardium extracts 85 or more of
  oxygen from blood
• exercise 5-6 fold increase in coronary blood flow

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Coronary Blood Flow

• Normal conditions coronary supply is closely
  regulated to myocardial O2 demand
• auto regulation
• factors of myocardial oxygen demand
• heart rate
• stroke volume
• cardiac output
• systolic blood pressure
• total peripheral resistance

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Coronary Blood Flow

• Determined by arterial pressure and vascular
  resistance
• intramyocardial pressure also affects coronary
  flow
• systole vs. diastole (figure 29.5 pg 417 Resource
  Manual)
• reduction of luminal diameter reduces flow
• luminal area obstruction of 75 causes blood
  flow reduction at rest
• hemodynamically significant lesion

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Coronary Blood Flow

• Atherosclerotic arteries have limited ability to
  vasodilate
• Atherosclerotic arteries are deficient in EDRF
  (nitric oxide) which increase likelihood of a
  mural thrombus

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Myocardial Ischemia

• coronary blood flow does not adequately meet
  myocardial oxygen demand
• results in progressive abnormalities in cardiac
  function ischemic cascade
• stiffening of the left ventricle
• results in decreased diastolic filling (diastolic
  dysfunction)
• impaired systolic emptying
• hypokinesis, akinesis, dyskinesis

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Myocardial Ischemia

• Systolic impairment demonstrated by
• segmental wall motion abnormalities
• reduction in left ventricular ejection fraction
• reduced stroke volume
• echocardiogram
• stress echo

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Myocardial Ischemia

• EKG changes
• ST segment depression
• ST segment elevation
• T wave inversion
• ventricular arrhythmias

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Myocardial Ischemia

• reversible
• no permanent cardiac damage
• prolonged ischemia
• irreversible damage may occur necrosis of
  myocardial tissue (myocardial infarction)

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Angina Pectoris

• heart pain due to myocardial ischemia
• characteristics of typical or classic
• pressure, tightness, squeezing, heaviness, or
  choking
• radiates down left arm, back, and/or jaw
• occurs with physical activity, emotional stress,
  cold weather, heavy meals
• last few minutes or until activity ceases

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Myocardial Ischemia

• angina pectoris
• relieved with rest
• nitroglycerin
• stable angina
• atypical angina
• unstable angina
• Prinzmetals angina

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STABLE CAD

• Presence of hemodynamicaly significant lesion(s)
• anatomically stable lesions that result in
• predictable, reproducible ischemia and/or angina

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Myocardial Infarction

• Result of severe, prolonged (60 min) ischemia in
  the presence or absence of angina
• irreversible heart muscle damage - necrosis
• MI can occur in lesions with less than 50
  stenosis
• rupture prone plaques
• explains why many persons who experience MI do
  not report a history of angina before infarction

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Acute MI

• Thickness of walls affected
• transmural infarction - Q wave
• subendocardial infarction - non Q wave
• Location of wall
• anterior,posterior, lateral, anterolateral,
  inferior, septal
• Location by ECG (Table 29.1 pg 420)

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Acute Myocardial Infarction

• Location of obstructive lesion
• determines wall(s) affected
• proximal vs. distal occlusion

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Diagnosis of Acute MI

• Symptoms
• ECG
• figure 27.4 Resource Manual
• evaluation of cardiac enzymes
• page 235 Resource Manual
• lactate dehydrogenase (LDH)
• Creatinine phosphokinase (CK)
• CK-MB elevated in first 24 hrs

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Treatment of MI

• Early reperfusion
• streptokinase or tissue plasminogen activator
  (tpa)
• rescue angioplasty
• emergent CABS
• nitroglycerine
• beta blockers

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Post-Myocardial Infarction

• Necrosis, scarring during first 6-12 weeks
• Infarct dilation and remolding - thinning of
  ventricular wall and enlargement of cardiac
  chambers
• may develop congestive heart failure

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Myocardial Infarction

• Characteristics associated with higher risk of
  reinfarction and death
• EF
• ischemia during low intensity exercise
• poor exercise capacity (
• complex ventricular arrhythmias