Required Readings Midterm II Flashcards
Any increase in HDL cholesterol reduces CVD risk independently of a decrease in ____
LDL
How does HDL reduce CVD?
RCT and release of NO
Replacing carbohydrates with ___ increased HDL
MUFA
Replacing SFAs with MUFAS reduces ____ and ____
LDL
total-to-HDL ratio
What else does MUFA do?
- Increase HDL
- Decrease TG
- Lower susceptibility of LDL to oxidation
What is the pathophysiology behind MUFA and reducing CVD?
-reduce platelet aggregation
-Increase fibrinolysis
-Increase coagulation time
Ultimately reduce the prothrombotic sate which is characteristic of CVD
Explain the relationship between omega-3 FA and lowering cholesterol
- inhibit endogenous synthesis and esterification
- increase excretion in bile
- increase bile salt synthesis
What else does omega-3 inhibit?
Glucose-6-phosphotase, inhibit glucose originated from glycogenolysis to enter the bloodstream
How is EPA and DHA beneficial for those with hyperTGs?
Lowering VLDL synthesis within the liver
Consuming small amounts of what is associated with a 27% risk reduction of non-fatal heart attacks?
Fish
What are sourced of ALA?
flaxseed, canola oil, soybean oils and small amounts in dark leafy vegetables
Replacing which of the following as the greatest effect on decreasing LDL concentration and the total-to-HDL cholesterol ratio?
a) MUFA
b) PUFA
c) Omega-3 only
d) EPA and DHA only
e) All of the above
b) PUFA
What is the minimum recommendation of PUFA for decreasing CHD events?
6% with a rang of 6-11%
How do oats reduce CVD risk?
Increase LDL receptors, which reduces serum lipids.
What else contains soluble fibre with CVD risk reduction?
Apples
What are some advantages of vegetable-protein rich diets?
- greater satiety, weight loss
- lower plasma TGs
- Reduced BP
- Spare lean mass
- Control of hypertension and atherosclerosis
What do phytosterols do?
Displace cholesterol from absorption in the GI tract, increasing excretion
What is the relationship between polyphenols and CVD?
Antioxidant activity, and inhibiting the endogenous synthesis of cholesterol
What is a powerful flavanol found in foods that exert anti-inflammatory, anti proliferative, and anti-oxidative effects?
Quercetin
What is the relationship between grapes and reducing CVD?
- increase HDL
- reduce total-to-HDL cholesterol
- Improve antioxidant capacity
What is the effect of soybeans?
Inhibit LDL cholesterol oxidation
What is the FDA approve recommendation for soy protein?
25 g of soy protein in a diet low in SFA and cholesterol is a mean to reduce to risk of CVD
What is the effect of cocoa?
Polyphenols in cocoa will reduce oxidation of LDL cholesterol, anti-inflammatory, antioxidant, moderate immune response, enhance vascular function and decrease platelet adhesion.
What else may the antioxidants in cocoa do?
- Alter glycemic response
- Change lipid profile
- Reduce platelet aggregation
- Reduce inflammation
- Reduce BP
What are found in cruciferae vegetables that belong in the bassicaccae family?
-glucosinolates
-polyphenols
-carotenoids
-phytosterols
All anti-inflammatory and antioxidant in nature
Why can nuts added into the diet significantly improve CVD risk?
content of MUFA, PUFA and the presence of high fiber and bioactive molecules.
What is the FDA recommendation on nuts? Why?
- FDA advocates an intake of 42 g/day for cardiovascular health
- Increasing HDL cholesterol and lowering LDL cholesterol
What is one of the most important dietary targets in the prevention of CVD?
Cranberry juice
What are the effects of cranberry juice?
Decrease:
- Dyslipidemia
- Oxidative stress
- Hypertension
- Inflammation
- Endothelial dysfunction
Although cranberry consumption is related to improved lipid profile and endothelia function, what is not mentioned in the literature?
The amounts that must be consumed to achieve the benefits attributed to them
What is the chief bioactive component of turmeric?
Curcumin
What did a recent systematic review and meta-analysis of RCT discover about curcumin and lipid profile?
Did NOT affect total cholesterol, LDL cholesterol, TGs and HDL cholesterol
What are the bioactive ingredients in garlic?
Enzymes (allinase_ and sulfur-rich compounds
How is garlic antiatherogenic?
- Antibacterial
- Antihypertensive
- Antithrombotic
Which vegetable ranks the highest in flavonoids, predominantly containing quercetin?
Onion
What are the effects of cinnamon?
- Weight loss
- Decreased fasting glucose concentrations
- Glycated hemoglobin decreased
What is the last word about cinnamon?
Although positive influences are claimed in most animal models. clinically proven trials remain scarce and contradictory
In summary, what foods have been found to exert a positive impact on human health?
- PUFA and MUFA
- Soluble fibres (oars, psyllium)
- Phytosterols
- Soy protein
- Oilseeds
- Nuts
Which SFA are known for increasing cholesterol?
Lauric (C12)
Myristic (C14)
Palmitic (C16)
Which SFA does not increase cholesterol
Stearic (C18)
What was the rationale in proposing the 7% or less cut-off of SFA intake?
That is all solid fats were isocalorically replaced with oils, totals SFA would be reduced to ~7% of calories
What are most arguments advocating for a low SFA diet based on?
The indisputable LDL-raising effects of SFA
What is the proposed effect of replacing 5% of energy from carbs with SFA?
A 5% increase in LDL cholesterol, and 5% increase in CHD
What is the debate of the CHD lowering effects of foods?
That we are unsure if the diet-induced change in plasma LDL-cholesterol has the same CVD benefit as statin induced change in LDL-cholesterol
What is important to consider about SFA?
Is that they may affect other plasma risk factors in a neutral or even beneficial way
What do most SFA do?
Increase HDL concentrations compared to dietary cabs, therefore has a LITTLE impact on the total cholesterol/HDL-cholesterol ratio
What is a powerful lipid risk factor for CVD?
Total-cholesterol/HDL-cholesterol ratio
What may be superior than measuring HDL cholesterol within the blood?
ApoB protein - which reflects the number of atherogenic particles in the blood, and NOT just LDL
(T/F) Replacing dietary carbohydrates with SFA has a significant impact on APO B concentration
False
What has dietary SFA been shown to do?
- Increase the size of LDL particles compared with other nutrients
- Reduce plasma TG concentrations when comrade to carbs
What did a large multi-centre intervention study suggest regarding the isoenergetic replacement of SFAs with MUFA or carbs?
The replacement has no deleterious effects on insulin sensitivity
What is the recommendation on SFA regarding inflammation?
The impact of SFA on inflammation remains unclear, and further research on this topic is required
What is controversial about the new speculations about SFA with respect to older studies?
That analysis of co-hort studies have shown that for each 5% lower energy intake from SFA replaced by PUFA there was 13% reduction in CHD and 26% reduction in coronary death
In summary, what is the impact of dietary SFA on blood cholesterol?
Impact is indisputable, and the resulting impact on CVD risk is not as straight forwards with data giving place to very discordant interpretation
What is the effect of SFA from cheese?
Cheese consumption may not increase plasma cholesterol concentration compared with butter of equal SFA content
What is higher SFA from meat associated with?
Associated with a higher risk of CVD
What is SFA from butter, plants or mixed sources associated with?
No CVD risk
What is the bottom line on dietary guideline in Canada for the prevention of CVD?
There are currently no harmonized dietary guidelines in Canada for the prevention of CVD`
What are the key components of the portfolio diet?
-Plant sterols
-Viscous fibers
-Plant protein from soy
-Nuts
<7% energy from SFA, and <200 mg cholesterol/day
What sodium intake is necessary and NOT sufficient for the development of primary hypertension?
50-100 mmol
When sodium intake exceeds ____ most people remain normotensive
100 mmol
Isolated populations that eat natural foods have an individual potassium intake that exceeds ___ and a sodium intake of only ____ per day
150 mmol
20-40 mmol
What is the ratio of dietary potassium to dietary sodium in a non-processed diet?
Always >3:1 and usually closer to 10:1
In industrialized nations that eat processed foods will ingest ____ of potassium/day and ____ of sodium/day
30-70 mmol
100-400 mmol
What is the ratio of dietary potassium and sodium in an industrialized populations diet?
<0.4:1
Hypertension affects less than ___ of people on isolated societies but approx ___ of adults in industrialized societies
1%
1/3
The movement of _____ into more urban areas is consistently associated with age-related increases in ____
isolated populations
blood pressure and potassium:sodium ratio
Potassium restriction causes a deficit in cellular potassium that triggers cells to _____ in order to maintain their tonicity and volume
gain sodium
What had a significant, inverse relation with blood pressure in the INTERSALT study?
the urinary potassium:sodium ratio
The urinary potassium:sodium ratio in the INTERSALT study has a stronger statistical relationship than what?
Than either sodium or potassium excretion alone
What diet caused sodium retention and an elevated blood pressure?
Low in potassium and USUAL sodium intake
What intake of potassium supplementation has been concluded to lower systolic blood pressure and diastolic pressure?
> /= 60 mmol/day
What can reduce the need for antihypertensive medication?
Potassium supplementation
In the DASH trial diet, how much did BP reduce compared to the SAD diet?
Both diastolic and systolic BP decreased at a constant level of sodium intake
The potassium content of the diet of fruits and vegetables was more than _____ as high than the SAD diet
twice
What accounted for the observed reduction in BP when comparing the DASH and SAD diets?
The higher potassium:sodium ratio observed in the DASH diet
Define sodium sensitivity
An increase in BP in response to a higher sodium chloride intake than in a baseline diet, and may occur in normotensive and hypertensive subjects
What has dietary potassium been shown to do?
Exert a powerful, dose-dependent inhibitory effect on sodium sensitivity
An increase in dietary potassium can even abolish _____ in both normotensive and hypertensive subjects
sodium sensitivity
Human kidney are poised to _____
conserve sodium and excrete potassium
What is the evolutionary explanation for the function of human kidneys?
Humans usually consumed a sodium poor and potassium rich diet
What is the problem with kidney function and modern day diets?
The sodium-sparing, potassium-excreting mechanism is un-fit for the sodium-rich and potassium-poor modern diet
What contributes to the retention of sodium by the kidneys?
Aldosterone
According to the Framingham Offspring Study, what predisposes normotensive subjects to hypertension?
Aldosterone excess, as defined by higher aldosterone values within a physiological range
When can fecal potassium losses excess urinary losses?
In a low potassium diet, where there is an inadequate conservation of potassium bu the kidneys and the alimentary tract
Despite and excess of sodium what is NOT increased in primary hypertension?
ECF volume
Plasma volume
Blood volume
What is decreased in untreated hypertension? What remains the same?
Skeletal-muscle potassium
Serum potassium
What is negatively correlated with muscle potassium in normotensive and hypertensive subjects?
Systolic and diastolic blood pressure
_____ is increased in primary hypertension because of the stimulation of ____ located on the ____
- Reabsorption of filtered sodium
- Sodium transporters
- Luminal membrane
Where is the bulk of filtered sodium reabsorbed?
By a pivotal luminal transporter, which is sodium-hydrogen exchanger type 3
What activity is increased in hypertension?
Sodium-hydrogen exchanger type 3
Besides hypertension, what else will increase the activity of the sodium-hydrogen transporter?
Potassium depletion
We know that both hypertension AND potassium depletion will increase activity of the sodium-hydrogen transporter - How?
Induction of intracellular acidosis (more hydrogen into the cell) and by stimulating the sympathetic nervous system an the renin-angiotensin system
What endogenous substance is released by the adrenal glands and the brain in response to a high-sodium diet?
Digitalis-like factor
What is the action of the digitalis-like factor?
Mediates sodium retention by increasing the activity and expression of the renal sodium pump
What is the long-term effect of potassium depletion?
Stimulate the activity and the expression of the renal sodium pump, therefore promoting sodium retention
What stimulates the activity and the expression of the renal sodium pump, therefore promoting sodium retention?
Long-term potassium depletion
Release of digitalis-like-factor
What contrasts with the inhibitory effect of potassium depletion and digitalis-like factor on the vascular sodium pump?
Long-term stimulatory effect on the renal sodium pump
What increases the action of the renal sodium pump?
- Potassium depletion
- Excess sodium (via digitalis-like-factor)
- Aldosterone
What increases the action of the sodium hydrogen pump?
Potassium depletion
Potassium depletion —> ? —–> ? —-> Increased activity of the sodium hydrogen pump
Sympathetic activity
Ang II
What occurs in primary aldosteronism?
Potassium administration will augment aldosterone BUT reduced BP, normalizes circulatory reflected of increases SA, corrects baroreceptors hypo-responsiveness
What increases the sodium concentration and decreases the potassium concentration in the INTRAcellular fluid? How?
INHIBITION of the sodium pump of arterial and arteriolar vascular smooth-muscle cells
By
-Release of digitalis-like-factor
-Decreased Potassium
What does increased intracellular sodium stimulate?
Increase calcium into the cells by stimulating the sodium-calcium exchanger
What will depolarize the membrane?
A deficit of potassium in the body or hypokalemia will inhibit the potassium channels (No K+ in, more – inner membrane)
What will decrease the membrane potential?
Inhibition of the sodium pump (More Na+ remains in the cell, more +, more likely to depolarize)
What is defective in primary hypertension?
Endothelium-dependant vasoldialtion
What plays an important role in endothelium-dependent vasodilation?
Homeostasis of sodium and potassium
Explain the mechanism behind increasing dietary potassium and decreasing BP
Will induce the hyper polarization of the endothelial cell through stimulating the the sodium pump and opening of the potassium channels
What does they hyper-polarization of the endothelium due to the increase of dietary potassium do?
Since intracellular sodium decreases, cystolic calcium decreased which in turn promotes vasodilation = DECREASED BP!
What is baroreceptor sensitivity depressed by? What is it restored by?
- Potassium depletion
- Potassium supplementation
What inhibits insulin secretion? What increases insulin sensitivity?
- Potassium depletion
- Potassium infusion and hyperkalemia
What worsen glucose intolerance in T2DM?
Thiazide (diuretic)-induced hypokalemia
What does the IOM recommend in terms of sodium?
65 mmol/day of sodium, or approximately 3.8 g of sodium chloride
What does the IOM recommend in terms of potassium?
120 mmol, or 4.7 g/day which is about twice the current U.S average
What would adoption of the IOMs recommendations cause
Increase dietary potassium:sodium ratio by a factor of 10
What forms of potassium offer larger cellular entry in exchange for sodium an exert greater antihypertensive effects?
Those that do NOT contain chloride - from fruits and vegetables
How often is CV risk assessment recommended for men and women?
Every 5 years between ages of 40 to 75
Who should be screened for dyslipidemias?
Men > 40 y/o, women >40 y/o or post-menopausal or those with certain conditions
What should be included when screening for adults in a comprehensive risk assessment to reduce CVD events?
non-fasted lipid and lipoprotein testing
When should lipid levels be measured fasting?
If TGs > 4.5 mmol/L
What should be used as an alternate target to LDL-C in adults?
non-HDL-C and Apo-B
What are statin indicated conditions?
- Clinical atheroclerosis
- Abdominal aortic aneurysm
- Most DM
- Chronic Kidney disease
- LDL > 5mmol/L
When should statin therapy NOT be administered?
When FRS <10%
When should statin therapy be administered?
When FRS > 20%
What treatment is recommended to reduce CVD ins adults older than 50 y/o with CKD not treated with dialysis or kidney transplant
Statin or statin/ezetimibe combination
Is lipid-lowering therapy recommended in adults with dialysis-dependent CKD?
No
What is Lp(a)
LDL-like particle in which apoB is highly heritabl single-gene
What is the target LDL level to decrease CVD risk and mortality?
<2 mmol/L or > 50% reduction when patients LDL > 5 mmol/L
What dietary recommendations are made surrounding reducing CVD risk?
- Adopt mediterranean diet
- Avoid intake of trans fats and reduce SFA intake
Should omega-3 supplements be recommmneded?
No
Individuals should replace SFA with _____ especially those from mixed ____
PUFA
Omega 3/6
Give some examples of recommended dietary patterns to reduce CVD risk
- Med diet
- Portfolio diet
- DASH diet
- High in nuts
- High in legumes
- High in olive oil
- High in fruits/veg
- High in fibre
What diets are recommended to reduce LDL-C?
- Portfolio diet
- High in nuts
- High in soy protein
- High in plant sterols
- High is viscous soluble fibre
Adults should accumulate at least ____ of moderate-to-vigoruous aerobic PA/week in bouts of _____ or more to reduce CVD risk
150 minutes
10 minutes
How can the maximal CVD risk reduction be achieved?
- Low risk lifestyle
- Healthy body weight
- Healthy diet
- Regular PA
- Moderate alcohol consumption
- Moderate sleep
What drug, when combined with a stating in high risk patients resulted in a significant reduction in clinical events?
Ezetimibe
What drug, when combined with statin therapy for patients who have achieved lipid-targets CANNOT be recommended in light of recent clinical trials?
Niacin
What drug failed to show a benefit on CV outcome when combined with statin therapy in patient with diabetes with or without CAH?
Fibrates (Fenofibrates)
Who may fibrates benefit?
Patients with high TG/Low HDL at baseline
Which drug offers the same LDL-C lowering as ezetimibe and has some glycemic benefits?
Bile Acid Sequestrants
When are PCSK9 inhibitors recommended to lower LDL?
Patients with familial hypercholesterolemia whose LDL-C levels remain above target despite maximal statin therapy, or with those in atherosclerotic CVD
Should patients on statins who are experiencing myalgia take vitamins/minerals/supplements for symptoms?
No
How does the med diet increase survival?
Protective against CHD and complications but also against other chronic diseases, including cancer
What does the med diet reduce?
- Coronary atherosclerosis/thrombosis
- Risk of fatal complications of atherosclerosis and thrombosis
What is an advantage of the med diet?
No side effects unlike drug therapies
What kinds of veg is the med diet characterized by?
Raw, sometimes cooked, seasonal vegetables throughout the year and large amounts of onions, garlic, parsley, rosemary, oregano, thyme and aromatic herbs
Nuts in med diet?
Almonds, hazelnuts but particularly walnuts (rich in ALA)
What are other sources of ALA?
- Purslane
- Animal products fed with ALA-linseed
Grains in med diet?
Preferable whole, fermented with natural leaven and sometimes flavoured with ALA-rich linseed
Fish in med diet?
Fatty fish: anchovy, sardine, mackerel, sea beam, red tuna
What is the main oil used in me?
Olive oil, low in SFA and high in MUFA
What is the major component of a healthy diet?
Low n-6/n-3 ratio
What kind of dairy products are included in the med diet?
Fermented cheese and yoghurt and almost never as milk, butter or cream
What kinds fo animal products are included in the med diet?
ALA rich eggs
Small amount so meat (lean meat, rabbit, chicken, and duck(
What is a major characteristic of the Med diet?
Moderate alcohol drinking, especially during meals - red wine
How many drink of red win/day in associated with a better life expectancy in the general population?
1-2 drinks/day for women
2-4 drinks/day for men
What supported the cause-effect relationship between moderate drinking and better survival?
When long-term abstainers from alcohol began consuming the recommended amount of drinks saw benefits
Moderate drinking results in approximately ___ lower cardiac mortality and a decrease in _____ all-cause mortality
30%
20%
At a biological level, how does alcohol reduce CVD risk?
- reduced platelet function and fibrinogen levels
- Insulin resistance
- Positive interactions with omega-3
Moderate drinking may reduce ____
Sudden cardiac death, which accounts for 65-75% of all cardiac deaths in the population
What may be the most-effective way to prevent both fatal and non-fatal complications of CHD?
Moderate wine drinking
In summary, what is the med diet effective in reducing?
- Coronary atherosclerosis/thrombosis
- Risk of SCD and CHF
What is anemia of chronic diseases?
2nd most common anemia. Development of microcytic RBCs as erythropoiesis is restricted due to inappropriate iron sequestration
What are the 3 mechanism behind development of anemia of chronic disease?
- Slightly shortened RBC survival
- Erythropoiesis impaires
- Iron metabolism altered
Why is RBC survival shortened?
Release of inflammatory cytokines which occur in patients with cancer and infections
What is erythropoiesis impaired?
Decrease in EPO and marrow responsiveness to EPO
Why is iron metabolism altered?
Increased hepcidin, which inhibits iron absorption and recycling leading to iron sequestration
How to diagnose anemia of chronic disease?
- Symptoms and signs of underlying disorder
- CBC, serum iron, ferritin, transferring and reticulocyte count
When should anemia of chronic disease in suspected?
Patients with microcytic or normocytic anemia alongside a choric illness, infection, inflammation or cancer.
How to treat anemia of chronic disease?
Treat the underlying disorder
Acidosis =
blood pH <7.35
Alkalosis =
blood pH > 7.45
How can respiratory acidosis arise?
Pulmonary dyfunction
How can respiratory alkalosis arise?
- Intense exercise
- Anxiety
- Sepsis
What are the 6 easy steps of ABG analysis?
1) Is pH normal?
2) Is CO2 normal?
3) is HCO3 normal?
4) Match CO2 or HCO3 with PH
5) Does the Co2 or the HCO3 go opposite direction of pH?
6) Are pO2 and O2 saturation normal?
