Dyslipidemias are disorders of lipoprotein metabolism characterized by increased levels of LDL cholesterol and/or triglycerides or reduced levels of HDL cholesterol. The majority of cases are due to a combination of genetic and lifestyle/medical condition factors. The 2013 ACC/AHA guidelines recommend statin treatment based on four major groups including those with clinical ASCVD or elevated LDL. Management involves dietary modification, weight loss, exercise, and pharmacologic treatment including statins, fibrates, ezetimibe, bile acid sequestrants, and PCSK9 inhibitors.

1. DYSLIPIDMIA
Moderator – Lt Col Tukaram
Presenter – Maj Punita

2. Disorders of lipoprotein metabolism are
collectively referred to as “dyslipidemias.”
INTRODUCTION

3. DYSLIPIDMIAS- CHARACTERIZED BY
 Increased plasma levels of
LDL cholesterol, triglycerides
or both
 Reduced levels of HDL cholesterol

4.  The majority of patients with dyslipidemia
 Combination of genetic predisposition
 Environmental contribution (lifestyle,
medical condition)

5. OVERVIEW OF 2013 ACC/AHA
CHOLESTEROL GUIDELINES
 Goal : Treatment of blood cholesterol to
reduce atherosclerotic cardiovascular risk in
adults, currently the leading cause of death
and disability.

6. FOUR MAJOR STATIN BENEFIT GROUPS
1) Individuals with clinical ASCVD
2) Individuals with LDL >190mg/dl
3) Individuals with DM, 40-75 yo with LDL- 70-
189mg/dl and without clinical ASCVD
4) Individuals without clinical ASCVD or DM
with LDL 70-189mg/dl and estimated 10-year
ASCVD risk >7.5%

8. http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx

9. No recommendations on statin therapy
for patients with NYHA class II-IV or
ESRD on dialysis

10. Intensity of Statin Therapy
*Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice.
There might be a biologic basis for a less-than-average response.
†Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in IDEAL (Pedersen et al).
‡Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is
not recommended by the FDA due to the increased risk of myopathy, including rhabdomyolysis.

11. THE EUROPEAN GUIDELINES ON CVD
PREVENTION IN CLINICAL PRACTICE
 Recommend use of the SCORE system.
 Very high risk
 High risk
 Moderate risk
 Low risk

12. MANAGEMENT

13.  Consumption of less
carbohydrate-rich foods.
 Consumption of dietary
fibre present in legumes,
fruits, vegetables, and
wholegrain cereals (oats,
barley)
 Avoid food with
processed sources of
trans fats
Dietary modification

14.  Fat intake should
predominantly come from
sources of MUFAs and
both n-6 and n-3 PUFAs
 Saturated fat consumption
 < 10% of the total caloric
intake
 < 7% in the presence of
hypercholesterolaemia
Dietary modification

15.  Influences TC and LDL-C
 A decrease in LDL-C concentration of 8
mg/dL is observed for every 10 kg of weight
loss
 Improves insulin sensitivity
 Decreases TG levels
Weight reduction

16.  Intervene in patients with TGs >500 mg/dl in
order to reduce the risk of pancreatitis
 Dietary modification
 Reduce alcohol intake
 Reduce simple carbohydrate intake
 Weight loss
 Regular physical activity
Hypertriglyceridemia

17.  Fibrates
 Agonists of PPARα
 Stimulate LPL activity
 Promote β-oxidation of fatty acids
 S/E : Gallstones, azotemia, myopathy
 Gemfibrozil 600 mg bid
 Fenofibrate 145 mg qd
Hypertriglyceridemia

18.  Omega 3 Fatty Acids (Fish Oils)
 Icosapent ethyl 4 g/d
 Omega-3 acid ethyl esters 4 g/d
 Major side effect is dyspepsia
Hypertriglyceridemia

19.  Nicotinic Acid
 Suppresses lipolysis in the adipocyte
 Effects on the niacin receptor GPR109A
 Third-line agent
 Side effect
cutaneous flushing
Gout in susceptible patients
Dyspepsia
Transaminitis
Hypertriglyceridemia

20. LOW HDL CHOLESTEROL
(HYPOALPHALIPOPROTEINEMIA)
 Men < 40 mg/dl,Women < 50 mg/dl. [3, 4, 5, 6]
 A low HDL cholesterol level
 accelerate the development of atherosclerosis
 impaired reverse cholesterol transport
 Patients may have
 premature coronary heart or peripheral vascular
disease, as well as a
 family history of low HDL cholesterol levels a
 premature CHD.

21.  Management
 weight loss
 smoking cessation
 aerobic exercise
 pharmacologic - niacin and fibrates.

22.  Dietary modification
 Reduce alcohol intake
 Reduce saturated fat, trans fat and cholesterol
 Weight loss
 Regular physical activity
Hypercholesterolemia

23.  A key enzyme in cholesterol biosynthesis
 Increased hepatic LDL receptor activity
 Reduce plasma TGs in a dose-dependent
fashion
 S/E –
Myopathy, transaminitis, dyspepsia,
headaches, fatigue
HMG-CoA Reductase Inhibitors (Statins)

25.  Serum CK levels need not be monitored on a
routine basis
 Serum AST/ALT levels should be checked before
starting therapy, at 2–3 months, and then
annually
 Small % of those taking statins develops
diabetes but Benefits outweigh the increase in
incidence of diabetes
HMG-CoA Reductase Inhibitors (Statins)

26.  Ezetimibe
 Binds directly to and inhibits NPC1L1
(responsible for absorption of cholesterol
from gut)
 Mean reduction in plasma LDL-C is 18%
 Effects on TG and HDL-C levels are
negligible
 S/E- Diarrhoea, URTI, dry cough
Cholesterol Absorption Inhibitors

27.  Bind bile acids in the intestine and promote
their excretion rather than reabsorption
 Major S/E - bloating and constipation
 Drug of choice in children and in women of
childbearing age who are lactating/pregnant
 Cholestyramine 4 g daily
 Colestipol 5 g daily
 Colesevelam 40 g daily
Bile Acid Sequestrants

28.  Proprotein convertase subtilisin/kexin type
9 inhibitor
 If PCSK9 is inhibited
 More LDLRs are recycled and are present
on the surface of cells to remove LDL-
particles from
PCSK9 Inhibitors

30.  Anti-PCSK9 Mabs are injected
subcutaneously, 150 mg once every
fortnightly
 Indications –
 High total CV risk
 Heterozygous Familial
hypercholesterolemia
 statin ‘intolerant’

31. THANK YOU