dyslipidemia

Dyslipidemia

Abnormal fats in blood
Elevation of 1+ lipoproteins or reduced HDL-C

Categories of Dyslipidemia lipoproteins

LDL
HDK
TC
TG

Primary Dyslipidemia

genetic/familial
Aka Hypercholesterolemia
Common cause of ASCVD in children

Secondary Dyslipidemia

Other causes

High LDL correlates with

Premature CVD

Heterozygous FH LDL

5-13

Homozygous FH LDL

\>13

What is normal LDL?

2-5

Tx for FH and goal for LDL

Aggressive statin tx
Non pharm
Goal for 50% reduction in LDL

Drugs that cause Dyslipidemia
ABC5D OPR

Amiodarone
Beta blockers
Carbamazepine
Clozapine
CS
Cyclosporine
Contraceptives (oral)
Diuretics (loop and Thiazide)
Ola saline
Phenytoin
Protease inhibitors
Retinoids

Symptoms of Dyslipidemia

Most asymptomatic
Xanthoma/xanthelasma
Corneal arcus
Carotid Bruits

+ve association between

TC or LDL and CAD

invcerse association between

high HDL and lower risk of CAD

relationship between TG and CAD?

none

Screening (age and race)

Age 40+
Women post menopausal or early
High risk pops: Asian, FN

Who to screen (medical conditions)

Aortic aneurysms, Arterial HTN
CKD
COPD
DM
ED
Hx of Dyslipidemia
Signs of Dyslipidemia
Obesity
Inflammatory disease (rheumatoid, lupus)
HIV infection
Pregnancy HTN disorder (GDM, stillbirth, low birthweight, pre term birth)

Modifiable risk factors

Obesity
Diabetes, diet, Dyslipidemia
HTN
Smoking
Alcohol
Psychosocial factor
Physical inactivity

What does the Framingham risk score determine?

10 year rest of CVD events essentially
Determines risk lvl
Tx Rec
Therapeutic targets

The FRS is used for

Primary prevention in those with no CVD

If those have CVD it is

Secondary prevention - high risk people
(MI, stroke, angina, CAD, Sx CABG, aneurysm, PAD)

Those who are considered high risk but no CVD
\**** DC

DM (40+, or those with DM ex for 15+ years that are 30+, micro vascular complications)
CKD (50+ for 3+ months AND eGFR

When is a statin indicated? (Add details)

LDL 5+ (ApoB \>1.45, non HDL \>5.8)
DM pt (\>30y and dx for 15+y or over 40)
CKD (50+ and eGFR

High risk frs

20+ or established CVD

Intermediate risk frs

10-19

Low risk frs

Less than 10

For those that have famHx of premature CVD, how do you calculate FRS

Times 2 for those with family hx in first degree relatives males less than 55 and women less than 65

Screening - what are you looking for in Dyslipidemia?

Fam Hx
Lipid profile
FBG and A1c (if DM un ctrl, can worsen lipid issue)
eGFR
Lipoprotein A

Optional;
ApoB, ACR

LDL gold standard and caveats

Measurement in lab but it's actually calculated, no direct measurement available in AB
Not super accurate (60%) as it is affected by high TG

LDL calculation

LDL \= TC - HDL - (TG/2.2)

If TG is over 4.5

No lab value given for LDL

ApoB dangers

High ApoB doesn't account for size of particles, it calculates total particles for CV risk
So if there is more HDL it would be seen as higher risk than smaller amount of LDL?

What is ApoB

Binds to all lipoproteins - reflects total particles in circulation
Tells you about the total art hero geniecito of lipid profile (best practice)

Why is ApoB and nonHDL used in screening?

ApoB considered best (reflects all particles and not affected by TG)
Non hdl is better than ldl (no extra cost)
Ldl is effected by TG if it is 1.5+

non-HDL

Provides an estimated sum of all atherogenic lipoproteins • Calculation: TC - HDL-C

High TG (hypertriglycericema) caused by

High fat intake (diet)
Excessive etOH
Poor DM ctrl

High TG associated with

Pancreatitis (tx for TG lowering if TG 10+)

Reducing TG reduces CV events?

NO - PROVÉN BY RCTS

Lifestyle modifications for Dyslipidemia (initiate first before Rx tx)
PEDLS

Psych stress management
Exercise 150 min per week
Diet
Limit alcohol 1-2 drink/day
Smoking cessation!!

Low risk FRS

not rec for statin therapy

intermediate risk FRS AND (lab values)

AND LDL \> 3.5 OR non HDL \>4.2 OR ApoB \>1.05

Intermediate risk FRS and \___________ indicate statin tx and healthy behaviour medifications

men\>50 and women\>60 that have ONE additional risk factor: low HDL, IFG, high waist circumference, smoker, HTN

FRS high risk

immediate statin and health behaviour modifications

Diet changes for Dyslipidemia

Calorie restrict
Fibre 30+ g a day
Substitute unsat fats for Saturated or trans fats
More fruits and veggies
Low cholesterol intake

Statin MOA

Upregulate LDL receptors
More removal of and catabolism (breakdown) of LDL
Decrease VLDL (convert to LDL)
Overall reduction in TC, LDL, TG

Statin CI

Liver disease (use lower dose )(and pregnancy, lactation

Statins have most efficacy at

Lowest dose, and doubling statin dose will be \= to 5% decrease in LDL

CI of Statin

Active liver disease (elevation in ALT AST and NASH (Alcohol induced)
Pregnancy and lactation (could cause growth deformation)
Those hypersensitive

Starting dose for statin

Maximum dose or maximally tolerated

When to take statin

Any time not in night though (doesn't matter for crestor and Lipitor

Simvastatin do not recommend,,,

80mg daily - no benefit over 40 and increased risk of myopathy

Pravastatin is the only statin that

Is not metabolized by CYP450

Reduction of MVE with statins

Reduce 1mmol of ldl \= 20-24%

Metabolism of atorvastatin, lovastatin, simvastatin
ALS

CYP3A4

Fluvastatin and rosuvastatin metabolism
FR

Cyp2C9

What can increase statin levels? CYP3A4 INHIBITORS
MGAP

Macrolide antibiotics (-mycin)
Grapefruit
Azole antifungals
Protease inhibitors

What can decrease statin levels?
BRACE

Bosentran
Rifampin
Antacids (take 1 hour before or 2 hr after rosuvastatin with Mg antacids)
Carbamazepine, Phenytoin
Efavirenz

What can drecrease statin metabolism (other drugs)
ACDV

amiodarone
amlodipine
cerapamil
cyclosporine/tacrolimus
diltiazem

General Statin AE
NMED

GI: NVD
mypopathy
elevated liver enzymes
diabetes in those who are prediabetic
nocebo effect

myaligia

muscle pain with CK ≤ ULN

myositis

myalgia with CK \> ULN

Rhabdomyolysis

muscle breakdown with CK \>10x ULN ± serum myoglobin and renal failure

myopathy happens

class effect, possibly dose-related
occurs in first 6 months of therapy
pain in large muscle groups

in mypoathy 40% or more pt will

tolerate another statin

risk factors for myopathy
HI FAD

hx of myalgia with statin, hypothyroidism
renal/hepatic Impairment
female, frame (small body)
advanced age
drug interactions

Rhabdomylysis

Diagnosed by: Myoglobinemia -\> myoglobinuria (darkens urine)
• Can lead to acute renal failure (significant elevation of creatinine and reduction in eGFR)

rhabdomylosis is predicted from

NOT MYALGIAS
dose related probably
increased risk with fibrate combo

should statin be rechallenged if rhabdomyolysis happens?

no unless due to drug interaction

what to monitor for in myopathy

find baseline CK and TSH
no need to monitor if asymptomatic
if symptomatic d/c statin and measure CK (if CK

resume statin after symptomatic myopathy ....

if pt willing and asymptomatic after 6 wks - can be same or alt statin

if CK is < 10x ULN

consider other causes, follow until CK ≤ ULN and patient asymptomatic, then restart different statin or lower dose

muscle biopsies in myopathy

Muscle biopsies have no role - low diagnostic yield

if CK \> 10x ULN

hydrate PRN, follow until CK ≤ ULN and patient asymptomatic, then restart different statin or lower dose (if moderate to severe, consider alternate therapy)

any evidence for Coenzyme Q10?

none but Patients that have a perceived effect (placebo) should not be dissuaded

ALT increase

from statin in first 6 months of therapy, dose related
doesn't predict liver damage or failure

if ALT ≤3x ULN

no routine ALT monitoring required

if if ALT \>3x ULN

d/c statin and reassess in 6-12 weeks

reassessment of ALT after 6-12 weeks: If persistently \>3x ULN

à investigate etiology

reassessment of ALT after 6-12 weeks: If

restart at lower dose or switch statin & reassess in 3-6 weeks

signs of liver failure - d/c statin
Jesus f*kin MALD

Jaundice,
fever,
malaise,
abdominal pain
lethargy,
dark coloured urine

ezetimibe monotherapy

primary prevention of low risk CHD - only if statin intolerant

ezetimibe combination therapy

in moderate severe - will reduce LDL well since statin works in endo pathway, ezetimibe works on exogenous pathway. can also be used to decrease statin dose for statin SE, or used with fibrates

esetimibe AE
GHFAM

GIT disturbances
Headach
fatigue
arthralgia
myalgia

CI ezetimibe

• Combination with statins in patients with active liver disease or unexplained liver enzyme elevation
• Hypersensitivity
• Pregnancy and lactation

drug interactions ezetimibe

• Cyclosporine (increase ezetimibe levels)
• Fibrates (increase ezetimibe levels)
• BAS (decrease ezetimibe levels)

Fibrates MOA

PPARa activators

can increase LDL when TG in VLDL are high

Fibrates - effect on lipids

- decrease VLDL and IDL
- modest decrease LDL
- increase HDL in most patients
increase excretion of hepatic C in bile

Fibrate AE

GIT (indigestion, ab pain, diarrhea)
rash, urticaria, hair loss
myositis (with statins and alcoholics, bad renal function esp )
gallstones esp Clofibrate

Fibrate indications

1st line to reduce TG (in pacreatitis): mix dyslipidemia
pt with severe hyper TGemia \>10
resistant dyslipidemia

Fibrate CI

impaired renal function
pregnant of nursing
gall bladder disease

fibrate interactions

more bleeding (increase anticoagulant dose needed)
decrease metabolism of statins \= toxicity (myalgia, myositis)

Niacin MOA

Inhibits lipolysis (TG) (diacylglycerol acyltransferase-2) in adipose tissue; reduces hepatic TG and VLDL synthesis

Niacin Pharm action

increase HDL

Niacin AE

flushing (can be avoided by taking baby asa 30 min before niacin)
GIT: dyspepsia, NV
reactivate peptic ulcer (take after meal)

Niacin AE high dose

reversive hepatotoxicity
ipair glucose tolerance -\> diabetes
increase uric acid

Niacin indication

Hypercholesterolemia type 2a and 2b or hyper limidemia
hyperTG and low HDL

Niacin CI

gout
peptic ulcer
hepatotoxicity
DM

Niacin reduces LDL by

indicated for combined dyslipidemia • Lowers LDL-C by 20% in combination with statin • Increases HDL-C by 20%

Crystalline niacin (OTC)

Requires titration to develop tolerance to flushing

Extended-release niacin (Niaspan®) (Rx-only)

• Reduced incidence of flushing • Associated with hepatotoxicity

Flush-free niacin (OTC)

• Studied in rabbits
• Contains inositol à no flushing but no absorption (DOESNT WORK ACTUALLY)
• Do NOT recommend as alternative to niacin