Cardiovascular disease Flashcards
(33 cards)
Cardiovascular disease (CVD)
diseases and injuries of the heart and blood vessels (in the heart, brain and throughout the body)
Atherosclerosis
build up of plaque in arteries, narrowing arteries and limiting blood flow
Coronary heart disease
build up of plaque in coronary arteries, which may lead to heart attack
Heart attack
Myocardial infarction: loss of blood flow to the heart
What causes artherosclerosis?
LDL “bad cholesterol” transport cholesterol to cells. If LDL is not taken by cells - keeps circulating in blood. The longer LDL circulates in blood, the more likely it is oxidized (becomes heavy;micro-injury accumulates)
- uptake by macrophage
- foam cell formation
- fatty plaques
- atherosclerosis
Development of atherosclerosis
- Arterial endothelial cell injury
- Entry of LDL cholesterol and phagocytic cells
- Phagocytes engorges LDL -> Foam cells
- Formation of fatty plaques; narrowing of blood vessel (MI); Rapture (Thrombus)
Un-modifiable risk factors
Age
Biological sex (male>female)
Family history
Ethnicity
Modifiable risk factors
High blood cholesterol
High blood pressure
Diabetes
Overweight/obesity
Excessive alcohol use
Physical inactivity
Smoking
Stress
“Unhealthy” diet (Poor diet)
Classic Diet-Heart Hypothesis
Dietary characterisitics: highly saturated fat, high cholesterol, low PUFA
Elevated serum cholesterol
Atheromatous plaque
Coronary arteries narrow
Myocardial infraction
What is the history of “Diet-heart” hypothesis from early studies in animal studies?
- Dietary cholesterol is transported in bloodstream
- Cholesterol deposits in arteries supplying heart can lead to heart attack
- Coronary heart disease identified as early as 1930
Measuring Serum Cholesterol
Lipid profile: Blood test FASTING state that report:
Total cholesterol
LDL cholesterol
HDL cholesterol
Triacylglycerols
Ratio of total cholesterol/HDL cholesterol or LDL/HDL appears to be most predictive of CHD risk
Main apolipoproteins:
HDL - apoA
LDL - apoB
- HDL is higher than LDL
Ratio of apoB/apoA also used
Looking at ratios is of greater validity and significance in clinical diagnostic
than measuring total cholesterol only
Dietary Fat & Serum Cholesterol
Dietary cholesterol does not seem to have a major influence on serum cholesterol
Dietary fat does seem to modify serum cholesterol
* Replacing saturated fats or carbohydrate with monounsaturated or polyunsaturated fats (PUFA) decreases total cholesterol to HDL cholesterol ratio
Based on the previous figure, from Micha & Mozzafarian 2010, replacing carbohydrate with which fatty acid would be predicted to give the least favorable serum cholesterol profile (i.e. which would be predicted to be the worst for CHD risk?)
A) Saturated
B) Monounsaturated
C) Polyunsaturated
D) Trans
D) Trans
What are the current recommendations for dietary cholesterol?
Dietary Reference Intakes:
* Minimize intakes of saturated and trans fats
* AMDR: n-6 PUFA 5-10% energy
* AMDR: n-3 PUFA 0.6-1.2% energy
No recommendations for MUFA
AMDR: Fat = 20-35% energy
Why is epidemiological studies evidence conflicting?
Epidemiological studies are difficult to interpret
* Difficult to separate effects of nutrients from dietary patterns or lifestyle factors
* Studies may be done on secondary prevention
* Difficulties in conducting “good” observational and experimental nutrition studies
What replaces saturated fat is important!
What is the latest evidence?
- Lowered intake of dietary saturated fat and replacement with polyunsaturated vegetable oil reduced CVD by ≈30% (RCTs)
- Benefits from lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat (prospective cohort studies)
- NO benefits: replacement of saturated fat with mostly refined carbohydrates and sugars (clinical trials)
Is the “Diet-Heart” Hypothesis too simplistic?
Most inter-individual variation in serum cholesterol is NOT related to dietary fat/cholesterol intake.
Factors other than blood cholesterol are important in the etiology of CHD
- types of fats replaced SF matters
Lipoproteins (a)
-similar to LDL particle with covalently linked glycoprotein: apolipoprotein(a)
- may have prothrombotic (blood clotting) properties in addition to atherosclerotic properties of LDL
- appears to be positively correlated with CHD risk
What are dietary factors that may influence CHD?
- Saturated fats/PUFA/n-3 fatty acids (fish oils)
- Glycemic index
- Whole grains/Fiber
- Anti-oxidants
- Phytochemicals
- Vitamin D
- Magnesium
- Alcohol
- B vitamins- folate, B6, B12
Omega-3 Fatty Acids
- Hypothesis generated from observation of
lower rates of CHD in populations with very high intake of fish such as Greenland & Japan
Possible mechanisms: - Effects on blood lipids (triacylglycerol lowering)
- Anti-arrhythmic effects
- Anti (less)-inflammatory effects
- Anti-thrombotic effects
Fiber
- May reduce serum cholesterol by binding to bile acids in the gut
- Major pathway of cholesterol excretion in the body; to produce new ble need CH from blood
- May also improve glycemic control, insulin resistance and weight control
- Whole grains: source of fiber,
phytochemicals, magnesium.
Anti-Oxidants
- Eg. Vit E, Vit C, beta-carotene, selenium
- Hypothesis that anti-oxidants may protect the arterial wall and prevent LDL oxidation
- Oxidation of LDL particles is an important step in progression of atherosclerosis
Phytochemical
E.g. Flavonoids, stilbenoids, and others
* Have anti-oxidant properties
* Stilbenoids (e.g., resveratrol from grapes and pterostilbene from blueberries) modify gene expression through epigenetic mechanisms which may explain their anti-oxidant and anti-inflammatory properties
Vitamin D
Low vit D associated with higher risk for CHD:
* Decreasing inflammation
* Endothelial function
* Reducing vascular stiffness
Possible mechanisms:
* Vitamin D receptor (VDR) and VDR responsive elements in DNA
* Regulation of gene expression
* Epigenetic mechanisms
