Download Inflammation is the basis for cardiovascular

Example: Advanced Clinical Foundations Modules
Inflammation is the basis for cardiovascular disease
Cardiovascular Overview: The Deadliest Disease
Cardiovascular Disease kills more New Zealanders a year than any other cause
41% of all New Zealanders are killed my cardiovascular disease
28% deaths result from all Cancers
Cardiovascular Risk Factors (Based on the Framingham Study)
Symptomatic disease
previous angina, MI, PTCA, CHF, TIA, CVA, PVD
impaired renal function or left ventricular hypertrophy
Major Risk Factors
age
male gender
cigarette smoking
hypertension
increased total cholesterol
diabetes
Other Risk Factors
family history of early CHD (early MI)
physical inactivity
obesity
Atherogenesis – Atherosclerosis from beginning
Old Thought – Atherosclerosis was due to a mechanical cause, similar to a corroded pipe. Increased
lipids ► cause deposits ► result in clogged arteries
New Knowledge - It appears that an inflammatory reaction is the basis of the pathology. Cholesterol
plays a role, but it is not always elevated in people with cardiovascular disease
Atherosclerosis Treatment
Cardiac and Vascular Protective
Antiplatelet Therapy
Statin (regardless of LDL)
ACE Inhibitor (regardless of BP status)
Beta Blocker (regardless of BP status)
Smoking Cessation
Exercise
Hemodynamic/Metabolic Protection
Blood Pressure Control (BP <140/90; DM BP <130/80)
Lipid Control
Diabetes Control (HgA1c <7%)
Genesis of atherosclerosis
A blood-borne irritant, such as homocysteine (derived from the protein in our diets), produces toxins on
contact with plasma, and those toxins injure the arterial wall. Fatty substances (LDL - low density
lipoprotein) cholesterol infiltrates the arterial intima (inner layer) at the points of intimal injury.
Advanced Cardiovascular Clinical Reasoning
© Equinox Health Ltd. 2010
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Example: Advanced Clinical Foundations Modules
Role of LDL in Atherogenesis
LDL readily enters the artery wall with the help of apolipid B (APOB). High levels of APOB are
associated with increased plaque formation. Once the LDL enters the artery wall (the intima) it is
oxidized and modified. The modified LDL is proinflammatory.
Endothelial Cell Role in Atherogenesis
Endothelial cells have antithrombogenic properties and produce vasodilators and vasoconstrictors.
Disruption of the endothelium may cause plaque instability and fissuring which lead to MI.
Endothelial cells release potent vasodilator known as Endothelial-derived Relaxing Factor (EDRF)
was found to be nitric oxide (it is still under debate if there are others types of EDRF), which is
protective. Atherosclerosis replaces EDRF-producing endothelial cells
Endothelins are major vasoconstrictors produced by endothelial cells and are elevated in
atherosclerosis, MI, CHF and hypertension (HTN). There are many causes of endothelium and
disruption and inflammation. These include hyperlipidemia, hyperglycaemia, abdominal obesity, and
possibly bacterial or viral infection.
Genesis of atherosclerosis
Monocytes (circulating immune cells) rush to the site of injury, burrow into the blood vessel walls,
mature into macrophages ("big eaters"), gorge themselves on oxidized fatty substances (lipid
peroxidation) and die, causing inflammation
Fatty streaks form inside the large- and medium-size arteries, often at stress points and where
branching occurs or where the wall is already damaged.
These deposits thicken, forming an atheroma (a hard mass of fatty tissue) that gradually erodes the
wall, narrows the arterial pathway and impairs the flow of blood. An atheroma builds up to form a harder
mass called plaque.
The fibrous cap of the plaque contains smooth muscle cells, collagen, and intra and extracellular lipids.
The lipid-filled "foam cells" are believed to be either monocytes or modified smooth muscle cells. The
necrotic core contains cell debris, cholesterol esters and crystals, and calcium.
Coronary Heart Disease (CHD)
Atherosclerosis can cause disease of the coronary vessels which can cause angina, myocardial
infarction, dysrhythmias, conduction defects, heart failure and sudden death. However, CHD is often a
silent disorder because at least 75% of the vessel lumen must be occluded before there is a significant
reduction in blood flow.
Acute MI is usually precipitated by disruption of an atherosclerotic plaque.
Emerging Risk Coronary Heart Disease Risk Factors
Apolipoprotein B (ApoB): This is the major protein associated with LDL-C, very low density
lipoprotein(VLDL) and intermediate density lipoprotein (IDL). ApoB is a good predictor of risk and may
be more widely used as assays become standardised.
LDL-C Particle Size: Small LDL-C particle size promotes atherogenicity. Triglyceride levels over 1.7
mmol/L are a useful surrogate measure for small dense LDL-C.
Advanced Cardiovascular Clinical Reasoning
© Equinox Health Ltd. 2010
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Example: Advanced Clinical Foundations Modules
Urinary Albumin/Microalbuminuria: Marker for generalised endothelial damage and urinary albumin
excretion correlates with atherosclerotic arterial disease. Microalbuminuria may indicate vascular
damage, especially in people with elevated blood pressure, Further data on the effectiveness of
interventions in reducing albumin excretion and its impact on cardiovascular outcomes is required
before routine measurement can be recommended. However, there is increased risk of cardiovascular
events in people with diabetes and microalbuminuria often precedes renal nephropathy.
C-Reactive Protein: Discovered in 1929 and is a non-specific marker of inflammation. It is produced
in liver in response to Interluken-6 (IL-6) which is released in areas of inflammation. Endolethial cell
lining of vessels also produce inflammatory mediators. Levels: 0.1 to 1.0, <1.0 good, >3.0 may
indicate inflammation But, it isn’t very specific – rheumatoid arthritis may not have elevated CRP levels.
Elevated levels of C-Reactive protein are also correlated with:
Total Mortality
Heart Attack
Stroke
Sudden Cardiac Death
Type II Diabetes
Metabolic Syndrome
Body Mass Index
Depression
Heavy Drinking
No Alcohol Drinking
Post-Menopause hormone replacement
Cigarette Smoking
Age
Weight
Anger/Hostility
Decreased C-Reactive protein levels are associated with:
Weight Loss
Drinking in Moderation
Statins (with or without elevated cholesterol levels)
Exercise
There is no correlation with C-Reactive protein levels with these factors:
Cancer
Cholesterol
Many MI occur in people without significant risk factors
Understanding C-reactive protein helps guide us to the most important health promotion activities for
patients.
Eat a diet high in polyunsaturated oils (including fish)
Maintain a desirable weight
Increase physical activity
Decrease stress
Free Radicals: Oxidative stress is caused by the build-up of free radicals which are a by product of
oxygen metabolism by mitochondria. These free radicals are highly reactive oxygen molecules that
damage DNA, proteins, and lipids and promote the turning on of genes that cause cell death.
Anti-Inflammation Diet: Important to reduce high glycaemic foods because the they raise CRP, as
well as omega-6 oils found in corn and soybean oil. It is well known that it is also important to reduce
Advanced Cardiovascular Clinical Reasoning
© Equinox Health Ltd. 2010
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Example: Advanced Clinical Foundations Modules
trans-fatty acids and fried foods. Animal proteins contain arachidonic acid, which the body uses to
produce pro-inflammatory prostaglandins.
Anti-Inflammation Diets such as the Mediterranean diet and the DASH diet promote eating whole,
unprocessed plant foods with plenty of colour and variety. Antioxidants like beta-carotene (found in
squash, carrots, and spinach), lycopene (found in tomatoes), and vitamin C (found in broccoli and
citrus) are thought to "sweep up" the free radicals. Other foods such as ginger, garlic, onion, turmeric,
and rosemary have strong anti-inflammatory properties. Blueberries, cherries, and blackberries are rich
in anti-inflammatory flavonoid compounds and omega-3 fatty acids found in wild salmon, herring,
flaxseed, and walnuts also have anti-inflammatory qualities.
Exercise: an active body revs up production of antioxidants, which "vacuum" the free radicals.
However, overly strenuous or weekend-warrior-type exercise can actually boost inflammation levels. In
one study, six months of exercising for an average of 2.5 hours a week, people with a known risk of
heart disease had a 35% reduction in CRP levels
Visceral Fat: It used to be thought of as an inert storage area, but now we known as a dynamic,
chemical producing area.
Risk for the Insulin Resistance Syndrome
BMI ≥25 kg/m2 or waist circumference M >100
cm, F >90 cm
Sedentary lifestyle
Age >40 years
Non-Caucasian ethnicity
Family history of
Type II Diabetes
Hypertension
Cardiovascular Disease
History of glucose intolerance or gestational
diabetes
Personal diagnosis of
Hypertension
High Triglycerides
low HDL
Cardiovascular Disease
Acanthosis nigricans
Polycystic ovarian syndrome (PCOS))
Advanced Cardiovascular Clinical Reasoning
© Equinox Health Ltd. 2010
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