MNT 2 - Exam #1 (Part 2) Flashcards
What is Atherosclerosis?
-Thickening of the blood vessel walls caused by presence of plaque (AS);
-Begins as fatty, fibrous growth which may calcify over time
— Incompletely understood process;
— Involves endothelial cells, smooth muscle cells, platelets, and leukocytes;
— Begins as a response to endothelial lining injury that results in an inflammatory process;
— AS occudes lumen of blood vessels = ischemia
What can Atherosclerosis lead to?
This can lead to an infarct =
- Myocardial Infarction (MI)/ CAD
- CVA
- Peripheral vascular disease (PVD)
- CHF
What studies have greatly contributed to the epidemiological study of CVD?
- Framingham Study
- National Health and Nutrition Examination (NHANES) Surveys
- National Cholesterol Education Program (NCEP)
What are the risk factors for Atherosclerosis?
- Family history
- Age and gender
- Obesity
- Dyslipidemia
- Hypertension (can initiate AS lesion/ cause plaque to rupture)
- Physical inactivity
- Atherogenic diet
- Diabetes mellitus
- Impaired fasting glucose and metabolic syndrome
- Cigarette smoke
- Sleep Apnea
What was the MRFIT study?
(Multiple Risk Factor Intervention Trial);
- 366,000 men & women;
- Compared mortality rates for “low risk” vs “high risk” individuals
MRFIT “Low Risk”
(ABSENCE of risk factors)
- serum chol. </equal to: 120/80mmHg
- Non-cigarette smokers
MRFIT “High Risk”
(WITH risk factors);
- serum chol. >200;
- BP> 120/80mmHG;
- Smokers
What was the Nurses’ Health Study?
- 84,129 women;
- Identified 5 healthy lifestyle factors
1. No cigarettes
2. ½ glass wine/day
3. 30 mins. or more/day mod./vigorous P.A.
4. BMI< 25
5. Diet with:
6. lower Trans fats & glycemic load,
7. Higher cereal fiber, omega 3’s,folate, and P/S ratio
What were the results of the Nurses Health Study?
- 14 year period =
- 3 healthy factors present: risk of CHD reduced by 57%;
- 4 healthy factors present: risk reduced by 66%;
- 5 healthy factors present: risk reduced by 83%
What defines Obesity?
- Major Risk Factor of so many diseases!;
- BMI = >29.9
- Waist Circumference (40 men, 35 women);
- *NCEP Adult treatment panel III (ATPIII) identified waist girth alone as suitable identifier of risk
What other Atherosclerosis risk factors are associated with Obesity?
- Dyslipidemia
- HTN
- Physical Inactivity
- Diabetes
What does a LOW level of Adiponectin predict?
- Hypertension
- Myocardial infarction
- Coronary dysfunction
- All related to high levels of LEPTIN;
- *Adiponectin DECREASES with decreased adipose tissue
How is HTN a risk factor for atherosclerosis?
[HTN = CV condition & risk factor for other forms of CVD]
- Mechanism =
1. Increased pressure against endothelium can cause initial lesion;
2. Changes in pressure can cause established plaque to rupture leading to an event such as infarct or proliferation of plaque; - Site = Force of BP amplified where vessels branch b/c obstructive plaque is more common in these areas
How does BP related to Atherosclerosis?
Elevated Blood Pressure/Hypertension Remains One of the Most Important Multipliers for Cardiovascular Risk:
What is a BP of >140/90mmHG associated with?
- 69% of first myocardial infarctions;
- 74% of cases of coronary heart disease;
- 77% of first strokes;
- 91% of cases of heart failure;
- 277,000 deaths in 2003;
- $63.5 billion annually (direct/indirect)
How is Physical Inactivity related to Atherosclerosis?
Impact of Physical Inactivity on CVD risk similar to: impact of dyslipidemia, HTN, cigarettes
What are the BENEFIT of ACTIVITY?
- Decreases BP;
- Decreases TAG;
- Increases HDL cholesterol → HAS NOT show to reduce LDL cholesterol or total cholesterol → ONLY raises good, doesn’t lower the bad;
- Improves endothelial function;
- Decreases platelet aggregation;
- Helps with weight reduction
Risk for Death related to Fit vs. Unfit MEN:
- Normal Weight – Unfit 3.1X greater risk;
- Overweight – Unfit 4.5X greater risk (fit 1.5X);
- Obese – Unfit 5X greater risk (fit 1.6X)
What were the results of the Nurse’s health study and Fit vs. Unfit Women?
1. Normal Weight — Less than 1hr PA = 2.9X — 1-3.5hr/wk PA = 1.6X — More than 3.5hr/wk PA = 1X 2. Overweight — Less than 1hr PA = 4.3X — 1-3.5hr/wk PA = 2.1X — More than 3.5hr/wk PA = 1.5X 3. Obese — Less than 1hr PA = 4.7X — 1-3.5hr/wk PA = 2.5X — More than 3.5hr/wk PA = 1.9X
How do glucose abnormalities related to Atherosclerosis?
— Impaired fasting glucose associated with increased risk of CVD mortality; IFG = plasma glu of 110-125mg/dL;
— CVD Mortality risk with Diabetes:
-CAD = most common cause of death for patients with DM
-Individuals with type 1 and 2 DM have 2-4 times greater CVD mortality risk than non diabetics
What are the Metabolic Risk Factors?
- Abdominal obesity – waist cir. >40in. Men/ 35in. women;
- Insulin resistance – FBG>/=100mg/dL or previously diagnosed T2DM;
- Dyslipidemia – any abnormalities in a lipid panel;
- TAG >/= 150mg/dL;
- HDL cholesterol < 40mg/dL men; < 50mg/dL women;
- HTN – BP >/= 130/85 mmHg or previously dx’s HTN;
- Prothrombotic state = abnormality in blood coagulated
What is the NCEP Definition of Metabolic Syndrome?
(National Cholesterol Education Program);
-Individual has 3 metabolic risk factors
What else is seen elevated with Metabolic Syndrome?
-Higher CRP seen w/ Metabolic syndrome);
→ CRP (C-reactive protein) is an acute phase reactant, a protein made by the liver and released into the bloodstream within a few hours after tissue injury, the start of an infection, or other cause of inflammation
What is the mechanisms for vascular injury in DM?
(Metabolic syndrome);
-Dyslipidemia = low HDL; high Triglycerides;
-Hypertension;
-Obesity;
-Hyperglycemia
= Increased Free Fatty Acids cause endothelial dysfunction and are PRO-inflammatory
= Oxidative Stress is increased by multiple cardiovascular risk factors
How are LESIONS in the arteries formed?
- Damage to endothelial layer = inflammatory process = attracts platelets;
- Platelets attach to endothelium and form small Clot (mural thrombus);
- Platelets adhere to subendothelial surface & secrete Adenosine diphoshate (ADP) and platelet derived growth factor (PDGF).
What are the effects of ADP and PDGF?
- ADP and PDGF respectively promote platelet aggregation and attract monocytes, smooth muscle cells, and other cells.;
- Net result: increase in collagen and other fibrous growth;
- Plaque increases in size causing artery to EXPAND outward
Stage 1 of Plaque Progression
-Monocytes (phagocytic WBCs) circulate in bloodstream and respond to injury in artery wall
Stage 2 of Plaque Progression
- Monocytes slip under blood vessel cell and engulf LDL cholesterol making FOAM CELLS;
- Thin layer of foam cells develops = FATTY STREAK
Stage 3 of Plaque Progression
- Fatty streak thickens and forms plaque that accumulates more lipids, smooth muscle cells, collagen, and debris;
- If artery expands to accomodate thickening plaque, and contains a large lipid core with a fibrous coating, it is vulnerable to rupture and thrombosis
What are the classes of Lipoprotiens?
- Chylomicrons, VLDL, and their catabolic remnants;
- LDL;
- HDL
What are Chylomicrons, VLDL, and their catabolic remnants?
- > 30mn (largest)
- Potentially PRO-inflammatory
What are LDLs?
- 20-22nm;
- Potentially PRO-inflammatory
What are HDLs?
→ GOOD cholesterol;
- 9-15nm;
- Potentially ANTI-inflammatory
How do LDLs cause inflammation in the arteries?
- LDL enter artery wall and can be modified;
1. LDL leaves lumen and enters the intima of the artery;
2. Oxidation of Lipids and ApoB;
3. Hydrolysis of Phosphatifylcholin to Lysophospahatidylcholine;
4. Aggregation;
5. Other modifications = - MODIFIED LDLs — modified LDLs are PROinflammatory
What is the Intima?
- The tunica intima (“inner coat”), or intima for short, is the innermost tunica (layer) of an artery or vein.;
- It is made up of one layer of endothelial cells and is supported by an internal elastic lamina;
- The endothelial cells are in direct contact with the blood flow.
How do Monocytes differentiate into Macrophages?
- Monocytes enter the intima;
- MCP-2 attaches to monocyte ;
- Modified LDLs promote the differentiation of monocytes into macrophages
What is the effect of Modified LDLs on the newly formed macrophages?
- Modified LDL Induces Macrophages to Release Cytokines That Stimulate Adhesion Molecule Expression in Endothelial Cells;
- LDL enhances monocytes being taking into the intima, promotes the differentiation of monocytes to macrophages and the development of cytokines → Ultimate formation of foam cells which are the first step of atherosclerosis;
- **If LDLs do NOT become modified, then they do NOT contribute to the oxidation and formation of the foam cells
What is the protective effect of HDLs?
HDL Prevents Formation of Foam Cells =
The HDL inhibits the oxidation of LDL, so there is no enhancement of monocytes turning into macrophages
What are the are the clinical manifestation of Atherosclerosis?
- Asymptomatic = little or no symptoms;
- May progress to ischemic heart disease
What are the procedures that are utilized to treat atherosclerosis?
- PCI (percutaneous coronary intervention) = Balloon tipped catheter inserted in groin and Often involves a stent;
- CABG;
- Medications
What are the drug therapies used for primary prevention of atherosclerosis?
- MHG-CoA reductase inhibitors (statins);
- Bile acid sequestrants;
- Nicotinic acid;
- Fibric acids
What are the side effects or interactions of Statins?
- Side effects = myopathy and increased liver enzymes;
- Food-drug interactions = nausea, dyspepsia, abd pain, constipation, diarrhea, flatulence
What are the side effects or interactions of Bile Acids Sequestrants?
Side effects = gesture distress, constipation, decreased drug absorption;
-Food-drug interactions = decreased absorption of minerals and fat-soluble vitamins;
What are the side effects or interactions of Nicotinic acid (niacin)?
- Side effects = flushing, hyperglycemia, hyperuriecmia (gout), hepatotocxicity;
- Food-drug interactions = dry mouth, N/V, peptic ulcer, dyspepsia, cramps, diarrhea, flatulence
What are the side effects or interactions of Fibric acids?
- Side effects = Gallstones, myopathy;
- Food-drug interactions = N/V constipation, flatulence
What are the clinical effects of atherosclerotic drugs?
These drugs can lower cholesterol MUCH more than medications!! Statin drug may truly be necessary to controlling cholesterol levels depending on the individual. → Sometimes diet will be enough, but should still be followed to not exacerbate
What are the ATP III Guidelines?
(Adult Treatment Panel);
- Developed by National Cholesterol Education Program (NCEP);
- Treat patients with CHD;
- Focus on prevention of CHD in those with multiple risk factors;
- LDL cholesterol- primary target of therapy
What are the Step of the ATP III?
- Obtain Lipid Profile;
- Identify clinical atheroslerotic dx = high risk for CHD events (CHD risk equivalents);
- Identify Other Major Risk Factors that modify LDL Goals;
- LDL Goals based on Risk Assessment;
- Determine Risk Category;
- Initiate TLC if LDL above goal
What are the levels of LDL cholesterol?
-Optimal - 190
What are the levels of Total Cholesterol?
-Desirable = 240
What are the levels of HDL cholesterol?
-Low = /= 60 (NEGATIVE risk factor = removes one risk factor from the total count)
What are the identified atherosclerotic diagnosis?
- High risk for CHD events (CHD risk equivalents) =
1. Clinical CHD → Check the chart, would be diagnosed by an MD;
2. Symptomatic carotid artery disease;
3. Peripheral artery disease;
4. Abdominal aortic aneurysm – An abdominal aortic aneurysm is an enlarged area in the lower part of the aorta, the major blood vessel that supplies blood to the body; The aorta, about the thickness of a garden hose, runs from your heart through the center of your chest and abdomen.
What are the other major risk factors that modify LDL goal for ATP 3/TLC?
- Cigarette Smoking;
- HTN (BP > 140/90 or on antihypertensive medication);
- Low HDL cholesterol (< 40 mg/dL);
- **An HDL greater than 60 REMOVES one risk factor → Protective factor ;
- Family history of premature CHD = Male: 1st degree relative < 55 years; Female: 1st degree relative < 65 years;
- Age: men > 45 years, women > 55 years
What are the LDL goals based on Risk Assessment for ATP 3/TLC?
- CHD and CHD risk equivalents (highest risk) → LDL goal: < 100 mg/dL = DM would be a risk equivalent;
- Multiple risk factors (+ 2) (those that modify LDL level) → LDL goal: < 130 mg/dL;
- Zero to one risk factor → LDL goal: < 160 mg/dL;
- **very high risk: optional goal: LDL < 70mg/dl (conflicting evidence) → HIGHER the RISK, LOWER the GOAL!!;
- Risk equivalents: other forms of CAD, Diabetes
What determines the Risk Category for ATP 3/TLC?
- Establish LDL goal of therapy ;
- Determine need for TLC (Therapeutic Lifestyle Change diet);
- Determine level for drug consideration
What is the TCL diet?
- Therapeutic Lifestyle Changes (TLC) =
1. Multifaceted lifestyle approach;
2. ↓ in saturated fat and cholesterol;
3. Using plant stanol/sterols and increased intake of soluble fiber ;
4. Weight management;
5. Increased physical activity (at least moderate) → Should expend at least 200 kcal/day from exercise
What are are the main recommendations?
- Fat = 25-35% of total calories;
- Sat. Fat = < 7% kcal;
- CHO = 50-60% kcal;
- Fiber = 30grams;
- Pro = 15% kcals;
- Chol = 200mg/day
* *Fat is more liberal with TLC; Much lower with the DASH (25% total and 6% saturated)
Other TLC Recommendations
- Sodium: < 1% total energy; Add omega 3 Fatty acids: 1g EPA & DHA/d (current lack of conclusive data) ;
* *emphasis on SOLUBLE fiber – insoluble fiber does not effect serum lipids = Oats, flax seed, apples;
* *(Don’t forget weight reduction, physical activity/cardiac rehab.)
How do Plant Sterol esters and stand esters help cholesterol and LDL?
-Plant sterol esters and stanol esters assist in lowering Total Cholesterol and LDL by:
— Inhibiting absorption of dietary cholesterol
—*caution re: use with normocholesterolemic individuals, children and pregnant women: can affect absorption of beta carotene, alpha tocopherol
How does soluble fiber help lower cholesterol?
- Decreases absorption of lipids;
- Binds bile acidsà increased bile acid excretion
Sources of soluble fiber & plant sterol/stanol esters; Tips for consumers; Dietary modifications
- Soluble fiber: fruit, vegetables, oats, soy. (beans required in larger quantity to have similar effect);
- Plant sterol/stanol esters: Benecol or Promise active → NOT recommended for people who do not have cholesterol problems;
- Dietary modifications to decrease SFA/ increase PUFA
How do Triglycerides relate to CHD?
- Elevated TG are also an independent risk factor for CHD;
- Elevated TG most often seen in metabolic syndrome;
- Elevated TG is a secondary goal in ATP III
What factors that increase triglyceride levels?
- Obesity and overweight;
- Physical inactivity;
- Smoking;
- Alcohol intake → Major effect on TG;
- High CHO diets (> 60%) → Major effect on TG;
- Disease states ( ex: type 2 DM) = Elevated blood glucose is often seen along with elevated TGs→ Many times lowering glucose also brings down TGs
What are the ATP 3 classifications of Triglycerides?
- Normal: < 150 mg/dL;
- Borderline-high: 150-199;
- High: 200-499;
- Very High: > 500
What are the ATP 3 treatment guidelines for all TG levels?
-Primary goal for all with elevated TG = achieve the target goal for LDL
What are the ATP 3 treatment guidelines for borderline high TG levels?
-Borderline High TG (150-199 mg/dL) = Emphasize weight reduction and ↑ exercise
What are the ATP 3 treatment guidelines for high TG levels?
-High TG: (200-499 mg/dL) =
— Emphasize wt reduction and exercise;
— Drug therapy may be indicated
What are the ATP 3 treatment guidelines for very high TG levels?
-Very high TG (> 500 mg/dL) =
— Very low fat diets (< 15% of calorie intake);
— Eliminate all alcohol;
— Weight reduction and increased exercise
• Drug therapy
What are the AND Nutr. Care Manual/EAL other guides of elevated TGs?
- Avoid extremes in carbohydrate and fat intake ;
- Limit added sugar as much as possible ;
- Recommend elminitation of concentrated sweets;
- Limit alcohol as much as possible;
- Include at least 30 minutes of moderate physical activity on most days (EAL, 200);
- In addition, supplemental fish oil (2 g to 4 g of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may be used under medical supervision (*Rx from MD. OTC not well regulated)
What are the ATP 3 assessment tools for elevated TGs?
- MEDFICTS assessment tool
- Dietary CAGE questions (Table 13.10);
- REAP (Table 13.11)
Dietary CAGE
C= cheese (full-fat and 2% dairy); A= Animal fats; G = Got it away from home; E = eat high-fat commercial products (candy, pastries, pie, doughnuts, cookies)
What is the REAP assessment tool?
Rapid Eating Assessment for Patients (REAP);
-Standardized questions about certain food consumer per week
What are the main medication recommended by ATP 3 for treating cholesterol/CHD?
HMG CoA Reductase inhibitors = STATINS:
- Atorvastatin (Lipitor)
- Fluvastatin (Lescol)
- Lovastatin (Mevacor)
- Pravastatin (Pravachol)
- Simvastatin (Zocor)
- Rosuvastatin (Crestor)
How do statins work?
- block the production of cholesterol in the liver;
- lower LDL cholesterol (18-55%) and triglycerides (7-30%);
- Some increase in HDL cholesterol (5-15%);
Possible Side effects:
- intestinal distress
- Increased liver enzymes
- muscle tenderness
Nicotinic Acid Medications
Thought to:
- Inhibit lipolysis of adipose tissue
- Inhibit hepatic synthesis of TAG
- lowers LDL cholesterol (5-25%)
- raises HDL cholesterol 15-35%)
- lowers TAG (20-50%)
Side effects = flushing, itching, hyperglycemia
Bile Acid Sequestrants
Where/ How they work/ how they’re taken:
- work inside the intestine,
- bind to bile from the liver and prevent it from being reabsorbed into the circulatory system
Side effects/ food drug interactions:
- constipation, gas and upset stomach
- May decrease absorption of minerals and fat-sol. vitamins
Fibric Acid/Fibrates
How they work:
- reduce the production of triglycerides (decrease TAG 20-50%)
- can increase HDL cholesterol (10-20%)
Side effects/ food drug interactions:
- Gallstones, myopathy
- N/V, constipation, flatulence
