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1
Q

Red yeast rice contains varying amounts of a family of naturally occurring substances called ________ that have HMG CoA reductase inhibitor activity.

A

monacolins

2
Q

What two meds are PCSK9 Inhibitors?

How are they administered?

A

alirocumab and evolocumab

injection or infusion patch pump

3
Q

High Triglycerides are a(n) _____________ risk factor for CAD.

A

INDEPENDENT

4
Q

TG is ________ (inversely/directly) related to HDL.

A

Inversely

**lowering TG should raise HDL.

5
Q

When would you need to monitor ALT in a pt who is on a statin? (7 reasons)

A
  1. Pts >75 yo
  2. pts with multiple comorbidities
  3. renal or hepatic dysfunction
  4. h/o statin in tolerance
  5. muscle disorders
  6. unexplained elevated liver enzymes
  7. pts on meds that can affect statin metabolism
6
Q

LDL becomes elevated when LDL is _______ and then taken up by macrophages lining the ________ ________.

A

oxidized

arterial intima

7
Q

__________ dyslipidemia is non-genetic and can be caused by any of the following: sedentary lifestyle with excessive dietary intake of saturated fat, cholesterol, and trans fats, alcohol overuse, DM, chronic kidney disease, hypothyroidism,
primary biliary cirrhosis and other cholestatic liver diseases

A

Secondary

8
Q

What supplement might you recommend to a pt who recently started statin therapy and is now having muscle pain?

A

CoQEnzyme10

9
Q

If normal ____ and _____ LDL particle, pt is at increased risk for CAD.

A

LDL

HIGH

10
Q

Which two statins are first line?

A

Lipitor (atorvastatin)

Crestor (rosuvastatin)

11
Q

Fibrates are second line for dyslipidemia, but first line for what?

A

First line use to reduce risk of pancreatitis in patients with very high TGs

12
Q

Some pts may not respond to high dose statins and may require adjunct therapy. Which 3 meds would you consider, in order from first line to last line and why?

A
  1. Ezetimibe is the first non-statin medication that should be considered in most pt scenarios. It is safe and tolerable and has demonstrated modest efficacy when added to moderate-dose statin.
  2. Bile acid sequestrants (BAS) may be considered as second-line therapy for patients in whom ezetimibe is not tolerated.
    (Avoid in patients with triglycerides >300 mg/dl)
  3. PCSK9 Inhibitors may be considered if the goals of therapy have not been achieved on maximally tolerated statin and ezetimibe in higher-risk patients with clinical ASCVD or familial hypercholesterolemia.
    **Given the lack of long-term safety and efficacy data
    not recommended for use in primary prevention pts who do not have familial hypercholesterolemia
13
Q

What should do if you suspect a pt cannot tolerate the statin you initially prescribed them?

a. add aspirin to their regimen
b. increase the dose of the statin
c. temporarily stop the statin and then try a different statin
d. tell them to suck it up

A

C.

The approach to suspected statin intolerance:

  • temporary discontinuation of statin therapy
  • lower dosing
  • re-challenge preferably with 2-3 statins of differing metabolic pathways
  • intermittent (1-3x weekly) dosing of long half-life statins
14
Q

Name 3 bile acid sequestrant meds.

A
  1. Cholestyramine and
  2. colestipol: powder form, mixed in drinks 2-3 times a day (Colestipol also has a tablet form)
  3. Colesevelam: newer, less side effects, greater binding affinity to bile acids
15
Q

We see ______ Lp(a) in nephrotic kidney disease, but ______ Lp(a) in dialysis pts.

A

Higher

Lower

16
Q

TRUE OR FALSE?

When initiating a statin, you should start with the max dose and continue if tolerated.

A

True

17
Q

What factors does the 10 yr ASCVD calc look at?

A
Gender
Age   (men >45 and Women >55)
Race
Total Cholesterol
HDL-C <40 mg/dL
Systolic Blood pressure 
Treatment for hypertension
Diagnosis of Diabetes
Smoking history
18
Q

What are some other indications that may require treatment, even if the pt does not fall into one of the 4 benefit groups?

A
  • Primary LDL-C >160
  • Genetic hyperlipidemias
  • Fam Hx
  • hs-CRP >2mg/L
  • CAC score >300 or more
  • ABI <0.9
19
Q

What are some of the benefits of statin medications?

A
  • Possible coronary plaque stabilization (Crestor has a study to prove this in the carotid arteries)
  • Improved endothelial cell function
  • Reduces CRP
  • May be preventing: CHF, osteoporosis, and Alzheimer’s disease
  • Possible anti-inflammatory properties
20
Q

If your pt with dyslipidemia insists on taking Fish Oils for their condition, what would you recommend to them regarding dosing?

A

Fish oil supplements should be taken at doses of ≥3 to 6g/day ofEPA/DHAconcentrate.

In many fish oil supplements, only 30-50% of ingredients are active omega-3 fatty acids, hence the high doses needed

21
Q

True or false? Angiotensin II promotes the development and severity of atherosclerosis, particularly when combined with hyperlipidemia.

A

TRUE
Think about HTN and the role of Angiotensin II.
Angiotensin II may also play a role in the modulation of vascular smooth muscle cell proliferation.

22
Q

Case 5: A 48-year-old man with FH and history of 3-vessel coronary artery bypass surgery 7 years ago sees you now for statin intolerance. The maximum dose of statin that he can tolerate is rosuvastatin 10 mg twice a week. On more frequent dosing he developed shoulder, low back, and thigh aching without weakness and a normal CK level. He had similar symptoms on low doses of simvastatin, atorvastatin and pravastatin.

On rosuvastatin 10 mg twice a week, his most recent LDL–C was 168 mg/dL, triglycerides were 138 mg/dL, and HDL–C was 46 mg/dL.

Which of the following statements is the most correct answer?

a. Ezetimibe has been shown to further reduce ASCVD events when added
to statin therapy. He should continue the rosuvastatin and ezetimibe 10 mg should be added.

b. Gemfibrozil has been shown to reduce ASCVD events when used as
monotherapy in men with coronary heart disease. He should continue the
rosuvastatin and gemfibrozil 600 mg twice daily should be added.

c. Bile acid sequestrants have been shown to reduce ASCVD events when
used as monotherapy in men with primary hypercholesterolemia. He
should continue the rosuvastatin and cholestyramine 4 g packet twice
daily should be added.

d. He should discontinue the rosuvastatin and begin lovastatin 40 mg daily.

A

c. Bile acid sequestrants have been shown to reduce ASCVD events when
used as monotherapy in men with primary hypercholesterolemia. He
should continue the rosuvastatin and cholestyramine 4 g packet twice
daily should be added.

23
Q

Cholesterol esters & triglycerides are ______(soluble/insoluble) in water.

A

Insoluble

24
Q

This lipoprotein is a variation of LDL, but is more atherogenic/ “sticky” than LDL.

A

Lipoprotein A

25
Q

True or false?
Endothelial dysfunction has nothing to do with the traditional risk factors of atherosclerosis (i.e. HTN, DM, tobacco use, etc)

A

FALSE
Endothelial dysfunction is associated with many of the traditional risk factors: hypercholesterolemia, diabetes, hypertension, and tobacco use

26
Q

How do statins work to lower cholesterol levels?

A

Inhibits an early rate limiting step in cholesterol synthesis (HMG-CoA to Mevalonic acid) within the liver

AKA: Reduces cholesterol synthesis in the liver.

Increases production of LDL receptors–> therefore increased removal of LDL from the blood stream

27
Q

LDL’s are ________(small/large), making them _______(highly/not very) atherogenic

A

Small
Highly atherogenic
(Small density LDL’s are even more atherogenic)

28
Q
\_\_\_\_\_\_\_\_\_\_ is a complex process involving:
Endothelial dysfunction
Dyslipidemia
Inflammatory and Immunologic factors
Plaque rupture
Smoking
A

Atherosclerosis

29
Q

True or false?
Evidence clearly shows that ASCVD events are reduced by using the maximum tolerated statin intensity in those groups shown to benefit.

A

TRUE

30
Q

In what two situations would it be necessary to refer pt to a lipid specialist and registered dietician?

A
  • high risk pt with statin intolerance

- patients with familial hypercholesterolemia.

31
Q

How often should you check labs on a pt who you start on a statin?

A
  • Baseline prior to starting
  • Repeat 4 to 12 weeks after starting statin therapy
  • Then every 3 to 12 months as clinically indicated to assess for compliance
32
Q

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are cell surface __________ induced at endothelial sites of inflammation

A

glycoproteins

Adhesion molecules are responsible (in part) for the adherence of leukocytes to endothelium.
“Make things stick.”

33
Q

Serum CRP is the BEST STUDIED of the inflammatory markers. ______ (high/low) CRP is consistently associated with atherosclerotic cardiovascular disease, however its fxn as a causal risk factor has not been established.

A

HIGH/elevated

34
Q

TRUE OR FALSE?
Oxidation of LDL causes changes in vascular tone, induction of growth factors, increased platelet aggregation and the formation of autoantibodies

A

TRUE

35
Q

There are ____ subclasses of LDL’s (all based on density differences).

A

7

Each has own LDL particle number.

36
Q

This type of lipoprotein has a protective effect against atherosclerosis via the “Reverse Cholesterol Transport” system and
Helps clear excess cholesterol from circulation

A

High density lipoprotein

37
Q

What are some common side effects of statins?

A
  • Increased liver enzymes
  • Muscle aches/pains
  • Rhabdomyolosis
38
Q

___ ____ ______ deliver cholesterol to tissues–gonads, adrenals, and rapidly dividing cells. Their coat is made up of ______.

A

Low density lipoproteins

phospholipids & apolipoprotein B-100 (APO-B)

39
Q

Pt’s with ________ _______ _________may have Xanthomas or arcus senalis.. Depending on severity of lipid disorder or extent.

A

Primary (genetic) lipid disorders

40
Q

Which is more common? Total occlusion of an artery due to plaque OR plaque rupture with thrombus?

A

Total occlusion of an artery due to plaque growth is not as common as you would think!
Why? The artery grows in diameter to accommodate the occlusive area.
Plaque rupture with thrombus (blood clot) is the more frequent cause of an AMI or ischemic stroke

41
Q

_______ form when proteins and phospholipids form complexes with cholesterol esters/ triglycerides.

A

Lipoproteins

42
Q

NCEP recommends: Fasting lipid panel every 5 years in all adults age ___ and older.

The ACC/AHA Guidelines and ATP IV recommend screening every 4-6 years in individuals aged __ - ___ years.

A

20 yrs

40-75

43
Q

Low density lipoproteins are removed from the blood stream via the ________; via LDL receptor, but can also be removed via the non-LDL-receptor-mediated- pathway via _________ cells, smooth muscle cells, and macrophages, which leads to plaque growth.

A

Liver

Kupffer

44
Q

Name the 3 layers of blood vessel lining from innermost to outermost.

A

Intima
Media
Adventitia

45
Q

Macrophages that are “lipid laden” are called ____ _____, which bury in the intimal lining of the arteries to eventually form plaque

A

Foam cells

46
Q

________ are the major forms of circulating cholesterol

A

cholesterol esters and triglycerides

47
Q

How many LDL-C levels must be recorded at less than 40mg/dl, before you may decrease a pt’s statin dose?

A

two

48
Q

_________ is an antilipemic agent, that should be considered first when adding to a statin for dyslipidemia. This med should also be used in pts with primary (heterozygous familial and nonfamilial) hyperlipidemia.

A

Ezetimibe (Zetia)

49
Q
Dyslipidemia (Aka: hyperlipidemia or hypercholesterolemia)
 is characterized by:
\_\_\_\_\_\_ LDL
\_\_\_\_\_\_ HDL
\_\_\_\_\_\_ Triglycerides
A

Elevated
Low
Elevated

50
Q

True or false? Bile acid sequestrants May decrease absorption of antihypertensives like thiazides and propranolol.

A

True

51
Q

What are some common side effects of Niacin?

A
  • Cutaneous flushing (recommend taking 162mg ASA 30 mins prior)
  • GI upset (take with a meal)
  • Other: pruritis, acanthosis nigricans, cardiac arrythmias, gout, myopathy (measure liver fxn, uric acid, and glucose levels)
52
Q

When should your pt take their statin? Morning or night? Why?

A

Night.

most cholesterol synthesis happens at night.

53
Q

When would you want to consider a PCSK9 Inhibitor for a pt?

A

If the pt had both high cardiovascular risk and significant, residual LDL-C burden exist, despite maximally tolerated statin therapy plus ezetimibe, then the patient is a good candidate for PCSK9 administration

54
Q

This class of medication stimulates lipoprotein lipase, which inhibits the production of VLDL. Ultimately this med class reduces plasma triglycerides and raises HDL.

A

Fibric Acid Derivatives
(aka: Fibrates)

Examples:
Gemfibrozil (Lopid of Gem-Fibro)
Fenofibrate (Tricor)
Fenofibric acid (Trilipix)

55
Q

______ is a high sensitivity CRP test that is more specific for heart disease versus systemic inflammation.

A

hs-CRP

56
Q

____ _________ is the extracorporeal removal of circulating apo B-containing lipoproteins.
This tx is typically used in individuals with Homozygous Familial Hypercholesterolemia (HoFH), but is also approved for heterozygous FH.

A

LDL Apheresis

  • *FYI–There are multiple apheresis methods:
  • dextran sulphate cellulose adsorption
  • heparin-induced extracorporeal LDL cholesterol precipitation,
  • Immunoadsorption
  • double filtration plasmapheresis of lipoproteins

**VERY EXPENSIVE

57
Q

TRUE OR FALSE?

ALL of the genetic, primary dyslipidemias have a PHYSICAL exam finding.

A

TRUE

58
Q

Elevated levels of LpPLA2 predict a 40 to 400 % increased risk of ____ and _______.

A

MI and stroke

59
Q

What 4 things does a General Fasting Lipid Panel test for?

A

Total Cholesterol, HDL-C, LDL-C, and TG

*Often comes with an HDL to LDL ratio

60
Q

Name 3 contraindications of statins.

A

Pregnancy
Lactation
Active liver disease

61
Q

What are the 4 statin benefit groups? Know what level statin each category would get.

A
  1. Individuals with clinical ASCVD
    (Age < 75 = High-Intensity Statin
    Age > 75 or not candidate for High intensity = Moderate-Intensity Statin)
  2. Individuals w/ primary elevations of LDL-C of 190 or higher
    (High-Intensity Statin, or
    if not a candidate for High intensity–>Moderate-Intensity Statin)
  3. Individuals 40-75 yrs with DM and LDL-C 70-189
    (Moderate Intensity Statin, or
    If >7.5% 10 yr ASCVD risk
    –>High-intensity statin)
  4. Individuals without clinical ASCVD or diabetes who are:
    -40 to 75 years of age
    -with LDL-C 70-189 mg/dL
    -and an estimated 10-year ASCVD risk of 7.5% or higher
    (Moderate to high intensity statin)
62
Q

If TGs are >500 mg/dL, ATP IV guidelines recommend you initiate what treatment? (3 options)

A

omega-3 fatty acids, niacin, or fenofibrate

63
Q

The pooled cohorts calc is only accurate for _________(untreated/treated) dyslipidemia

A

untreated

**Should not be used as a tool to adjust statin therapy

64
Q

Why is HTN bad and a major risk factor for the development of atheroclerosis? Name 3 reasons.

A
  • increases arterial wall tension, potentially leading to disturbed repair processes and aneurysm formation
  • part of “scuffing” up the arterial wall lining, making divets for plaques to deposit
  • Can “pound away” at an atheroma and increase risk of rupture or cause a part to break off and thrombose
65
Q

_________ frequently occur at sites of bends, branches, and bifurcations of coronary arteries

A

Atheromas

**This suggests that altered blood flow can play a role in the development of atherosclerosis.

66
Q

_____ is a non-statin option of medication that at high concentrations will lower VLDL, LDL, and raise HDL. It can also cause some reduction of atheromas.

A

Nicotinic Acid

AKA: Niacin (water soluble Vit B3)

67
Q

Regarding Dyslipidemia:
The USPSTF strongly recommends screening men aged __ and older for lipid disorders.Also, men who are __ - ___ yrs old and at increased risk for CHD, should also be screened.

A

35

20-35

68
Q

Which calculating tool Evaluates a patient’s 10 year risk for ASCVD ? If calculation is ___% or higher, the pt is at high risk for ASCVD in the next 10 yrs.

A

Pooled Cohort Equations Calculator (ACC/AHA CV Risk Calculator in MD Calc)

7.5

69
Q

When would you add a non-statin to a high risk pt’s statin regimen?

A

In high risk pt’s (hx ASCVD or LDL >190) you would consider tx with non-statin if the maximally tolerated statin therapy has not achieved >50% reduction in LDL-C from baseline by their next visit with you.
Statins work pretty quickly, so you should be seeing changes by the time you recheck their levels.

70
Q

CASE 3: A 35-year-old man has a strong family history of premature coronary disease, with both father and brother having an MI before age 55. He is a nonsmoker, nondiabetic and exercises for 150 minutes/week. He has gained 10 lbs since age 18.

BP is 140/90mm Hg
weight is 170 pounds
height is 70 inches
BMI is 24.4
fasting lipid panel: LDL–C is 160 mg/dL, HDL–C 45 mg/dL and triglyceride 100 mg/dL. 
His fasting blood glucose is 92 mg/dL. 

He is on a heart-healthy diet and exercises 150 minutes a
week. He and his wife would like to discuss statin therapy given his strong family history.

Which of the following is likely to be helpful in making a decision regarding statin therapy in this patient?

a. Strong family history of premature ASCVD
b. Coronary calcium score of 300 units or more
c. hs-CRP ≥2.0 mg/L
d. Lifetime risk of ASCVD
e. LDL–C ≥160 mg/dL
f. All of these factors can be considered

A

f. All of these factors can be considered

71
Q

____________ is structurally close to plasminogen and May cause aggravation of the thrombolytic system leading to clot formation.

A

Apoprotein A

72
Q

This conscious habit impairs endothelium-dependent vasodilation (EDV), increases inflammatory markers: CRP, IL-6, and TNF-alpha, increases fibrinogen levels and decreases fibrinolysis, which increases risk of CLOT formation, and increases oxidative modification of LDL.

A

SMOKING

It’s bad, don’t do it! It impacts ALL phases of atheroclerosis.

73
Q

Which lipoprotein metabolism pathway is associated with the synthesis of VLDL by the liver, which then delivers cholesterol and triglycerides to the tissues in fasting state?

A

Endogenous

74
Q

Where are HDL’s made?

A

liver and intestine

75
Q

The ______ layer of the blood vessel is lined with endothelial cells that release nitric oxide.

A

Intima

76
Q

What is the number one treatment used for endothelial dysfunction?

A

STATINS

NOTE: Can be Improved by: correction of hyperlipidemia which increases the bioavailability of nitric oxide HLD tx’d by: diet or by medication
ACE inhibitors
High doses of antioxidants (Vit C, red wine, grapes)

However, clinical benefits of these therapies have only been demonstrated convincingly for statins.

77
Q

Women age __ and up should be screened for dyslipidemia. Women __ - __ and at risk for CHD, should also be screened.

A

45

20-45

78
Q

Metabolism of lipoproteins can take one of two pathways; exogenous or endogenous. Which pathway is the absorption of dietary fat from food which is then distributed to muscle, adipose and the liver?

A

Exogenous

79
Q

Endothelial dysfunction is an initial step in atherosclerosis, and is thought to be caused by ________________________.
This dysfunction is particularly induced by ______ LDL.

A

loss of endothelium-derived nitric oxide

Oxidized

80
Q

Lipoprotein A [Lp(a)] is made of Two components:
LDL-like particle with __________ &
a hydrophilic protein called ___________.

A

Apoprotein B

Apoprotein A

81
Q

Children should be screened for dyslipidemia if they have family history of dyslipidemia or risk factors. What risk factors would make you want to screen a child?

A
  • Early CVD: parent or grandparent with CAD, stroke, or peripheral vascular disease <55 years of age for men, ≤65 years of age for women.
  • Unknown family history
  • Family history of dyslipidemia
  • Children with other risk factors for atherosclerosis including: overweight/obesity, hypertension, cigarette smoking, and type 1 and 2 diabetes mellitus.
82
Q

Adding bile acid sequestrant to statin regimen, reduces MI and CAD deaths in men with _____ cholesterol and ______ TGs

A

high

normal

83
Q

Macrophages that have been modified by oxidized LDL’s, release a variety of _____________ substances.

A

Inflammatory

they also release cytokines and growth factors

84
Q

______ and ________ are two commercially prepared fish oils.

A

Lovaza and Vascepa

85
Q

How does Ezetimibe work in the body?

Ultimately what does it decrease (4 things) and what does it increase (1 thing)?

A

Inhibits absorption of cholesterol at the brush border of the small intestine

Decreases:
Total- C
LDL-C
apo B
TG

Increases:
HDL-C

86
Q

True or false? Cytokines are Anti-inflammatory.

A

False. They are pro-inflammatory

87
Q

HDL’s coats are made of 50% _________, 20% __________, and sub-fractions of HDL2 and HDL3.

A

50% apoprotein (A-1 & A-II)
20% cholesterol

**NOTE: HDL2 may be more protective due to greater cholesterol content, by reversing cholesterol transport.

88
Q

DM is another player in atherosclerosis. Clinical and experimental studies suggest that high levels of _______precede development of arterial disease.

A

Insulin

89
Q

What lab tests would you want to get on your pt before prescribing a statin? (2 recommended, 1 is only if indicated)

A
  • Baseline Fasting lipid panel
  • Baseline ALT

-Creatine Kinase (only if indicated- not rec’d as a routine test)

90
Q

Case 2: A 60-year-old African-American woman has asked whether she should be taking a statin to reduce her risk of stroke, but is worried about the statin causing diabetes. Her mother had diabetes and had a stroke at age 62.

The patient is a nonsmoker and she is on 2 antihypertensive medications.
Blood pressure is 142/88 mm Hg
BMI is 31. 
Her fasting lipid panel reveals:
total cholesterol 200 mg/dL
HDL–C 55 mg/dL
triglyceride 100 mg/dL
LDL–C 125 mg/dL. 
Her fasting blood sugar is 109 mm/dL 
Hemoglobin A1c is 5.9%. 

According to the Pooled Cohort Equation for African-American Women, her estimated 10-year ASCVD risk is 8.7 %.

Which of the following statements is the best answer?
a. She should focus on lifestyle change to improve her risk factors because lifestyle has been shown to reduce ASCVD events more than statin therapy.

b. The risk of progression to diabetes with a statin outweighs any ASCVD risk reduction benefits from statin therapy. The decision about a statin to be deferred.
c. She should start a moderate or high intensity statin.
d. A high-sensitivity C-reactive protein (hs-CRP) >2 would be needed before the decision can be made whether to start a statin.

A

c. She should start a moderate or high intensity statin.

91
Q

True or false? Chronic infection may contribute to the pathogenesis of atherosclerosis.

A

TRUE

How?
Possibly through direct vascular injury and/or induction of a systemic inflammatory state.
Clinical evidence to support this idea is lacking

92
Q

_______ is a lipoprotein-associated, macrophage-secreted enzyme that perpetuates plaque inflammation.

A

LpPLA2 (lipoprotein-associated phospholipase A2)

93
Q

Case 4: A 32-year-old man has gained 35 pounds since he graduated from college and started working as computer programmer. He has never smoked. He has treated hypertension. His father died of an MI at age 73.
He has tried several popular diets to lose weight and lost about 20 pounds each time, but he always regains the weight lost within one year. He bowls once a week.

Weight = 220 lbs and BMI = 32.5
BP = 138/92. 
total cholesterol  = 218 mg/dL
triglycerides = 188 mg/dL 
HDL–C = 40 mg/dL
LDL–C = 138 mg/dL
non HDL–C 178 mg/dL
Fasting glucose = 101 mg/dL. 

Which of the following should be incorporated into your advice for ASCVD risk reduction for him?

a. Refer to a program providing a series of group counseling comprehensive lifestyle change sessions.
b. Start a moderate intensity statin.
c. Try to encourage a diet that will get at least 10-15 pounds off in 6 weeks so he can keep his motivation for weight loss high.
d. Reassure him that by following a strict diet he does not need to increase his physical activity and will be able to maintain his weight over the long haul.
e. Refer for bariatric surgery.

A

c. Try to encourage a diet that will get at least 10-15 pounds off in 6 weeks so he can keep his motivation for weight loss high.

94
Q

___ ____ ________ are second line adjunct therapy and work by binding to bile acids in the intestinal lumen and increasing excretion of bile salts.

A

Bile acid sequestrants

95
Q

Niacin can be used in which type(s) of hyperlipidemia?

A

ALL

96
Q

TRUE OR FALSE?

Evidence shows that increased inflammation = increased risk of atherosclerosis.

A

TRUE