A. Types of Vascular Disease

1. Arterial Disease [1]
   1. Atherosclerosis
   2. Thrombosis and/or Embolism (thromboembolism)
   3. Aneurysm
   4. Arteriovenous malformation (AVM)
   5. Hemostasis (capillary beds)
   6. Restenosis [18]
   7. Hypertension [19]
   8. Arterial ulceration
2. Venous Disease
   1. Thrombosis: deep vein, superficial vein
   2. Septic thrombophlebitis
   3. Chronic venous diseasincluding vericose veins, skin changes, venous ulceration [21]
3. Autoimmune vasculitis
   1. Vasculitis, systemic
   2. Vasculitis, focal (very uncommon)
4. Atherosclerotic Disease
   1. Cardiovascular Disease (CVD) [2]
   2. Stable Angina
      1. Unstable (Rest) Angina
      2. Non-Q Wave / Non-ST elevation (typically partial thickness) Myocardial Infarction (MI)
      3. ST elevation / Q-Wave (typically transmural) MI (STEMI)
   3. Sudden Cardiac Death (SCD) - usually arrhythmic secondary to acute ischemia
      1. Acute Coronary Syndromes (ACS) include unstable angina and any type of MI
      2. Coronary restenosis
   4. Cerebrovascular Disease
   5. Presence of Apo E4 genotype may be synergistic for vascular dementia [6]
      1. Chronic hypertension (HTN) may increase risk of dementia
      2. Treatment of systolic HTN in elderly reduces dementia incidence [17]
   6. Renovascular Disease
   7. Hypertensive
      1. Normotensive
      2. Renal artery stenosis and fibromuscular dysplasia
      3. Progressive Renal Failure (~10% of chronic renal failure patients)
   8. Peripheral Arterial (Vascular) Disease (PAD)
5. Thromboembolic Disease
   1. Atherosclerosis - plaque rupture acute coronary syndromes
   2. Cholesterol emboli
   3. Coagulopathy
6. Metabolic Syndrome (Insulin Resistance Syndromes) [2]
   1. Insulin Resistance (required)
   2. Hyperinsulinemia
   3. Diabetes Mellitus Type 2
   4. Obesity
   5. Hypertension
   6. Dyslipidemias: increased small, dense LDL, reduced HDL, increased triglycerides
   7. Endothelial dysfunction and atherosclerosis are major components
   8. Hypertension, atherosclerosis and diabetes can contribute to cognitive decline, particularly in the presence of Apo E4 [6]
7. Diabetic Vascular Disease
   1. Proliferation of microvasculature
   2. Arteriovenous shunting
   3. Capillary Leakage
   4. Basement Membrane damage
   5. Proliferative diabeteic retinopathy
   6. Increased production of angiogenic hormones (VEGF, FGF, others)
8. Sudden Cardiac Death (SCD) [11]
   1. Atherogenesis and dyslipidemias associated with SCD
   2. Proinflammatory and prothrombotic factors exert pro-arrhythmic effects
   3. Possible that agents which reduce harmful lipids and/or inflammation will reduce SCD
9. AVM [12]
   1. Arteriovenous shunting through tortuous vessels
   2. Connection of feeding arteries to draining veins without intervening capillaries
   3. Arterial and venous elements both have hypertrophy
   4. Likely formed during 80mm stage of embryonic development
   5. Prevalence of cerebral AVMs is ~0.01%
   6. AVMs also found in gastrointestinal (GI) tract, liver, other areas
   7. Main risk of AVM are related to bleeding
   8. In CNS, present with hemorrhage, seizures, pain
   9. GI AVM usually present with bleeding
10. Hemangioma - benign soft tissue tumor of abnormal endothelial proliferation [14]
11. Pre-eclampsia and eclampsia [16]
12. Genetic Disease
    1. Marfan Syndrome
    2. Ehlers-Danlos Syndrome
    3. Osler-Weber-Rendu Syndrome

B. Event Rates for Acute Vascular Diseases

1. Prospective study in 91,106 persons in Oxfordshire UK 2002-05 [20]
   1. 2024 acute vascular events occurred in 1657 individuals
   2. Cerebrovascular disease (CVD) 45% / 918: 618 strokes, 300 TIAs
   3. CAD 42% / 856: 159 ST-elevation MI, 316 non-ST MI, 281 USA, 163 SCD
   4. PAD 9% / 188: 43 aortic, 53 embolic visceral and limb ischemia, 92 critical limb ischemia
   5. 62 unclassifiable deaths
   6. Relative incidence of cerebrovascular compared with coronary events ~1.2
   7. Steep rise in event rates with age in all categories
2. REACH Study [9]
   1. Prostpective Study of 68,236 patients for 1 year followup
   2. Overall risk of cardiovascular (CV) events ~4% in 1 year for established atherosclerosis
   3. With multiple CV risk factors, risk of CV events in 1 year ~2%
   4. With established cerebrovascular disease (CVD), 1 year CV event rate 6%

C. Risk Factors in Adults

1. Genetic Predisposition
   1. Multiple contributions, generally poorly characterized
   2. Assess Family History
   3. Many genetic contributions to clotting abnormalities
2. Smoking Cigarettes [15]
   1. Increases levels of C-reactive protein (CRP), an inflammatory marker
   2. Increases levels of fibrinogen and homocysteine which promote clotting
3. Hypercholesterolemia
   1. Primary Disease
   2. Nephrotic Syndrome
   3. Familial Disease
4. Diabetes Mellitus
5. Obesity
6. Rheumatologic Syndromes
   1. Raynaud's Disease
   2. Systemic Vasculitis
   3. Anticardiolipin Syndrome (anti-endothelial Abs)
7. Glucocorticoid Therapy - may exacerbate disease
8. Homocysteine [1,13]
   1. Hyperhomocystenemia and homocystinuria associated with vascular disease
   2. Reduction of homocysteine levels associated with improved endothelial function
9. Estrogen Receptor (ER) Alpha Polymorphisms [5]
   1. ER alpha T>C polymorphism associated with increased CVD risk
   2. ER alpha CC genotype odds ratio for major CVD 2.0 versus CT or TT genotype
   3. CC genotype odds ratio for myocardial infarction 3.0 versus other genotypes
10. Hypercoagulability
11. Elevated serum uric acid levels [8]
12. Cocaine (and other stimulant) Abuse
13. Exercise Reduces Risk
    1. Improves coronary endothelial function even in patients with atherosclerosis [7]
    2. Improves glycemic control and blood pressure

D. Assessment of Vascular Disease

1. Symptoms of Vascular Insufficiency
   1. Cool, blue extremities
   2. Claudication - pain in an extremity which gets better with rest
   3. Chest Pain, especially on exertion
   4. Ulcers - especially lower extremities
2. Signs
   1. Decrease in palpation of pulses - cannot detect collateral flow
   2. Carotid or other Bruits - very unreliable
   3. Appearance of extremities, hypersensitivity
   4. Diabetic retinopathy changes - microaneurysms seen in early disease
3. Non-Invasive Diagnostic Tests
   1. Doppler-Ultrasound - very sensitive and specific
   2. Excellent for diagnosis peripheral arterial (vascular) disease, carotid disease
   3. Undergoing development for coronary disease
   4. Ultrasonographic examination of carotid arteries is a good predictor for diffuse disease
   5. Carotid intimal or medial thickening is risk factor for heart attack and stroke [4]
   6. Magnetic Resonance Angiography - excellent and safe for cerebral and abdominal disease
   7. CT Angiography - good for aortic disease in thorax or abdomen
   8. Transesophageal Echocardiography - excellent in setting of subacute thoracic dissection
4. Vascular Ultrasound
   1. Assessment of internal carotid is sensitive and predicts diffuse disease
   2. Vascular ultrasound determination of intimal:medial thickness (IMT) is very useful
   3. IMT increases of 30µm per year associated with >2 fold risk for cardiac disease [10]
   4. Carotid IMT should be used in all studies evaluating atherosclerotic risks and therapies
5. Invasive Testing
   1. Angiography is usually gold standard
   2. Risk of peripheral embolism, stroke, from angiography is not insignificant
   3. Arterial Pressure Tracing (transduced signal) may be helpful

E. Preoperative Cardiac Assessment

1. Usual practice is cariac evaluation prior to non-cardiac vascular surgery
2. Likely that coronary angiography should be reserved for patients with high surgical risk
3. If coronary angiography shows inoperable disease, then vascular surgery should probably be canceled
4. If vascular surgery was very risky, then angiography can help with assessment

References

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