highlights guidelines based ESC2016 ACE and ACC

2. B Y
M O U S T A F A M O K A R R A B ; M D
A L A Z H A R F A C U L T Y O F M E D I C I N E
C A I R O - E G Y P T
Dyslipidaemia
highlights

3. CVD prevention
 CVD kills >4million people in europe .
 It kills more women than men , although CV death
before the age of 65 ys are mor common in men.
 Prevention is defined as a coordinated set of
actions, at the population level or targeted
at an individual, aimed at eradicating,
eliminating or minimizing the impact of CV
diseases and their related disability.

4.  The importance of CVD prevention remains undisputed
and should be delivered at different levels: (i) in the
general population by promoting healthy lifestyle
behaviour and (ii) at the individual level, in those at
moderate to high risk of CVD or patients with established
CVD, by tackling an unhealthy lifestyle (e.g. poor-quality
diet, physical inactivity, smoking) and by reducing
increased levels of CV risk factors such as increased lipid
or blood pressure levels.
 Prevention is effective in reducing the impact of CVD;
the elimination of health risk behaviors would make it
possible to prevent at least 80% of CVD and even 40% of
cancers, thus providing added value for other chronic
diseases.

6. Defining ASCVD
 Atherosclerotic cardiovascular disease (ASCVD) is
defined as:
 An acute coronary syndrome
 History of myocardial infarction
 Stable or unstable angina
 Coronary or other arterial revascularization
 Stroke, transient ischemic attack
 Or peripheral arterial disease (PAD)

8. Major Atherosclerotic Cardiovascular Disease
Risk Factors
Major risk factors Additional risk factors
Nontraditional risk
factors
Advancing age
⇧ Total serum cholesterol level
⇧ Non–HDL-C
⇧ LDL-C
Low HDL-C
Diabetes mellitus
Hypertension
Stage 3 or 4 chronic kidney disease
Cigarette smoking
Family history of ASCVD
Obesity, abdominal obesity
Family history of hyperlipidemia
⇧ Small, dense LDL-C
⇧ Apo B
⇧ LDL particle concentration
Fasting/postprandial
hypertriglyceridemia
PCOS
Dyslipidemic triad
⇧ Lipoprotein (a)
⇧ Clotting factors
⇧ Inflammation markers
(hsCRP; Lp-PLA2)
⇧ Homocysteine levels
Apo E4 isoform
⇧ Uric acid
⇧ TG-rich remnants
Abbreviations: apo, apolipoprotein; ASCVD, atherosclerotic cardiovascular disease; HDL-C, high-density lipoprotein cholesterol;
hsCRP, highly sensitive C-reactive protein; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; Lp-PLA2,
lipoprotein-associated phospholipase; PCOS, polycystic ovary syndrome.
AACE POSWC. Endocr Pract. 2005;11:126-134; ADA. Diabetes Care. 2017;40(Suppl 1):S1-S135; Brunzell JD, et al. Diabetes Care.
2008;31:811-822; Cromwell WC, et al. J Clin Lipidol. 2007;1:583-592; Einhorn D, et al. Endocr Pract. 2003;9:237-252; Grundy SM, et
al. Circulation. 1998;97:1876-1887; Jellinger P, Handelsman Y, Rosenblit P, et al. Endocr Practice. 2017;23(4):479-497.; Kastelein JJ, et al.
Circulation. 2008;117:3002-3009; NCEP. NIH Publication No. 02-5215. September 2002; Neaton JD, et al. Arch Intern Med.
1992;152:1490-1500; NHLBI. NIH Publication No. 04-5230. August 2004; Stamler J, el al. JAMA. 1986;256:2823-2828; Weiner DE, et
al. J Am Soc Nephrol. 2004;15(5):1307-1315; Yusuf S, et al. Lancet. 2004;364(9438):937-952.

9.  Secondary Prevention ACC/AHH
 All patients with ASCVD
 All patients 40-75 with diabetes
 LDL greater or equal to 190 LDL

14. ASCVD Risk Categories and LDL-C Treatment
Goals
Risk
category
Risk factors/10-year risk
Treatment goals
LDL-C
(mg/dL)
Non-HDL-C
(mg/dL)
Apo B
(mg/dL)
Extreme
risk
– Progressive ASCVD including unstable angina in individuals
after achieving an LDL-C <70 mg/dL
– Established clinical cardiovascular disease in individuals
with DM, stage 3 or 4 CKD, or HeFH
– History of premature ASCVD (<55 male, <65 female)
<55 <80 <70
Very high
risk
– Established or recent hospitalization for ACS, coronary,
carotid or peripheral vascular disease, 10-year risk >20%
– DM or stage 3 or 4 CKD with 1 or more risk factor(s)
– HeFH
<70 <100 <80
High risk
– ≥2 risk factors and 10-year risk 10%-20%
– DM or stage 3 or 4 CKD with no other risk factors <100 <130 <90
Moderate
risk
≤2 risk factors and 10-year risk <10%
<100 <130 <90
Low risk
0 risk factors
<130 <160 NR

16. Question: What are lipid treatment goals?
R35. Treatment goals for dyslipidemia should be
personalized according to levels of risk (Grade A; BEL 1).
R36. For individuals at low risk (i.e., with no risk factors),
an LDL-C goal of less than 130 mg/dL is recommended
(Grade A; BEL 1).
R37. For individuals at moderate risk (i.e., with 2 or fewer
risk factors and a calculated 10-year risk of less than 10%), an
LDL-C goal of less than 100 mg/dL is recommended (Grade
A; BEL 1).
R38. For individuals at high risk (i.e., with an ASCVD equivalent
including diabetes or stage 3 or 4 CKD with no other risk factors, or
individuals with 2 or more risk factors and a 10-year risk of 10%-
20%), an LDL-C goal of less than 100 mg/dL is recommended
(Grade A; BEL 1).
Recommendationsassociatedwiththis
question:
Jellinger P, Handelsman Y, Rosenblit P, et al. Endocr Practice. 2017;23(4):479-497.
Abbreviations: ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; LDL-C, low-density lipoprotein cholesterol.

17. Question: What are lipid treatment goals?
R39. For individuals at very high risk (i.e., with established or recent
hospitalization for ACS; coronary, carotid or peripheral vascular disease;
diabetes or stage 3 or 4 CKD with 1 or more risk factors; a calculated 10-
year risk greater than 20%; or HeFH), an LDL-C goal of less than 70 mg/dL
is recommended (Grade A; BEL 1).
R40. For individuals at extreme risk (i.e., with progressive ASCVD, including
unstable angina that persists after achieving an LDL-C less than 70 mg/dL, or
established clinical ASCVD in individuals with diabetes, stage 3 or 4 CKD,
and/or HeFH, or in individuals with a history of premature ASCVD (<55 years
of age for males or <65 years of age for females), an LDL-C goal of less than 55
mg/dL is recommended (Grade A; BEL 1).
R41. An LDL-C goal of <100 mg/dL is considered “acceptable” for children
and adolescents, with 100 to 129 mg/dL considered “borderline” and 130
mg/dL or greater considered “high” (based on recommendations from the
American Academy of Pediatrics) (Grade D).
Recommendationsassociatedwiththis
question:
Abbreviations: ACS, acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; HeFH. heterozygous
familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol.
Jellinger P, Handelsman Y, Rosenblit P, et al. Endocr Practice. 2017;23(4):479-497.

18. Question: What are lipid treatment goals?
High-Density Lipoprotein Cholesterol
• R42. HDL-C should be greater than 40 mg/dL, but also as high as possible, primarily through
the use of lifestyle interventions (e.g., weight loss, physical activity, and tobacco cessation),
and if risk factors are present (e.g., borderline elevated LDL-C levels, a family history of
premature ASCVD, or a personal history of ASCVD), also through the use of pharmacotherapy
primarily focused on reducing LDL-C (Grade A; BEL 1).
Non–High-Density Lipoprotein Cholesterol
• R43. For most individuals, a non–HDL-C goal (total cholesterol minus HDL-C) 30 mg/dL
higher than the individual’s specific LDL-C goal is recommended (Grade D).
• R44. For individuals at extreme risk, a non-HDL-C goal 25 mg/dL higher than the individual-
specific LDL-C goal is recommended (Grade A; BEL 1).
Apolipoproteins
• R45. For individuals at increased risk of ASCVD, including those with diabetes, an optimal
apo B goal is less than 90 mg/dL, while for individuals with established ASCVD or diabetes
plus 1 or more additional risk factor(s), an optimal apo B goal is less than 80 mg/dL, and for
individuals at extreme risk, an optimal apo B goal is less than 70 mg/dL (Grade A; BEL 1).
Triglycerides
• R46. TG goals of less than 150mg/dL are recommended (Grade A; BEL 1).
Abbreviations: apo, apolipoprotein; ASCVD, atherosclerotic cardiovascular disease; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density
lipoprotein cholesterol; TG, triglycerides.
Jellinger P, Handelsman Y, Rosenblit P, et al. Endocr Practice. 2017;23(4):479-497.

19. Stop smoking, do physical activity, maintain or reduce
body Wight and adjust your BP

33.  Primary Prevention Benefit with Statins 0.4%
absolute risk reduction for all cause mortality and
.43 % of cardiovascular mortality
 244 patients treated for 5 years to prevent one death
 Absolute risk reduction will be proportional to the
20-30 % relative risk reduction with statin in
primary prevention
 Shared decision making is key to appropriate care

34. Primary Prevention in Older Adults
 ACC/AHA Pooled Cohort Equations will always exceed 7.5%.
 No adjustment for quality adjusted life expectancy
 Data limited in over 75 years of age.
 PROSPER trial: pravastatin use 70-82 year old patients,
Showed no benefit on CVD outcomes.
 JUPITER: Justification of Use of Statins in Prevention: An
Intervention Trial Evaluating Rosuvastatin)( high CRP)
Showed primary protection over 70 years of age.
 HOPE-3: Heart Outcomes Prevention Evaluation Showed
use pravastatin was protective.
 Again- Shared decision making is key for primary prevention
in the elderly as well

35.  Compliance is key
 Patients who take less than 80% of their statin dosed
have a 45% relative increase in total mortality
compared with more adherent patients
 Greater mortality than that observed with poor
adherence to other cardiac drugs including
antihypertensive and B –adrenergic blocking
agents.

36.  Reported Side Effects of Statins: Myths and Data
 Diabetes
 Hemorrhagic stroke
 Cognitive decline
 Tendon rupture
 Hepatic injury
 Muscle related symptoms

37.  Familial hypercholesterolemia (FH) is an autosomal
dominant disorder that causes severe elevations in
total cholesterol and low-density lipoprotein
cholesterol (LDLc).
 Xanthomas are noted commonly on the Achilles
tendons and metacarpal phalangeal extensor
tendons of the hands of patients with untreated FH.

39. History
 Children with homozygous FH
 These patients may have symptoms consistent with
ischemic heart disease, peripheral vascular disease,
cerebrovascular disease, or aortic stenosis. Such
symptoms may be confused with conditions that are
more benign unless the diagnosis of homozygous FH is
considered.
 Patients may have articular symptoms such as tendonitis
or arthralgias.
 Patients have a history of unusual skin lesions.
 Parents mostly have Premature CAD and high LDLc

40.  Adults with homozygous FH
 Most patients do not survive beyond age 30 years
unless treated with unusual methods, such as liver
transplantation, LDL apheresis, or ileal bypass
surgery to dramatically lower their LDLc levels.
 Their family history should be positive for severe
hypercholesterolemia and premature CAD in both
parental family lines.

41. Children with heterozygous FH
 Children with heterozygous FH do not have
symptoms related to CHD.
 One parent will have severe hypercholesterolemia
and will probably have either a personal or family
history for early CAD.
 Statistically, because the gene for FH is dominant,
50% of the patient’s siblings will also have
heterozygous FH.

42. Adults with heterozygous FH
 These patients have a long-standing history of severe
hypercholesterolemia dating back to childhood.
 If an acute coronary event has not already occurred,
symptoms consistent with ischemic heart disease are not
uncommon, especially if other cardiovascular risk factors
(especially smoking) are present.
 Past or present symptoms of recurrent Achilles
tendonitis or arthritic complaints may be present.
 Premature CAD and severe hypercholesterolemia are
present in one or more first-degree relatives.
 If carefully questioned, patients with either homozygous
or heterozygous FH may describe first-degree relatives
who had visible tendon xanthomas on their hands.

43. Ferquency
 Based on extrapolations from available data, the
frequency of HeFH can be estimated to be between
1/200 and 1/250, putting the total number of cases
at between 14 and 34 million worldwide.
 The frequency of HoFH is estimated to be 1/160
000–1/300 000.

44. Signs and symptoms
 Homozygous FH
 Signs and symptoms of homozygous FH in children include the
following:
 Symptoms consistent with ischemic heart disease, peripheral vascular
disease, cerebrovascular disease, or aortic stenosis
 Articular symptoms such as tendonitis or arthralgias
 Unusual skin lesions, such as cutaneous xanthomas at birth or by early
childhood (eg, planar xanthomas, tuberous xanthomas; later, tendon
xanthomas)
 Corneal arcus may be present and is sometimes circumferential
 Murmur of aortic stenosis may be present
 Most patients with homozygous FH do not survive adulthood beyond
age 30 years unless treated with unusual methods, such as liver
transplantation, LDL apheresis, or ileal bypass surgery to dramatically
lower their LDLc levels.

45. Heterozygous FH
 Children with heterozygous FH do not have
symptoms related to coronary heart disease (CHD),
and most do not develop tendon xanthomas or
corneal arcus. However, one parent will have severe
hypercholesterolemia and will also probably have
either a personal or family history for premature
CAD.
 Signs and symptoms of heterozygous FH in adults
include the following:
 Long-standing history of severe
hypercholesterolemia dating back to childhood

46.  If no previous acute coronary event, symptoms
consistent with ischemic heart disease, especially in
the presence of other cardiovascular risk factors
(especially smoking)
 Past or present symptoms of recurrent Achilles
tendonitis or arthritic complaints
 If heterozygous FH is left untreated, tendon
xanthomas (Achilles tendons, metacarpophalangeal
[MCP] extensor tendons) will occur by third decade
of life in more than 60% of patients
 Xanthelasmas

47. Diagnosis
 The diagnosis of both homozygous and heterozygous FH
is based primarily on the finding of severe LDLc
elevations in the absence of secondary causes of
hypercholesterolemia.
 A probable diagnosis of heterozygous FH can be made if
the LDLc level is greater than 330 mg/dL or if tendon
xanthomas are present in a patient with an LDLc level
above the 95th percentile. Definitive diagnosis can be
made only with gene or receptor analysis. However, a
substantial increase in serum triglyceride levels should
raise the possibility of another lipid disorder

48.  Testing
 Findings on lipid analysis in patients with FH include the following:
 Homozygous FH: Severely elevated cholesterol levels (total cholesterol
and LDLc levels >600 mg/dL); triglyceride levels within the reference
range
 Heterozygous FH: Elevated LDLc levels commonly greater than 250
mg/dL; in patients younger than 20 years, an LDLc level higher than
200 mg/dL is highly suggestive of heterozygous FH or, possibly,
familial ligand defective apoB-100; in adults, LDLc levels higher than
290-300 mg/dL suggest heterozygous FH
 LDL receptor analysis can be used to identify the specific LDL receptor
defect, and LDL receptor or apoB-100 studies can help distinguish
heterozygous FH from the similar syndrome of familial defective apoB-
100

49.  In August 2013, the European Atherosclerosis Society
(EAS) published a consensus statement for screening and
treatment of heterozygous FH. The recommendations for
screening for heterozygous FH include patients with :
 A family member presenting with diagnosed FH;
 Plasma cholesterol in an adult ≥8mmol/L (≥310 mg/dL);
 Plasma cholesterol in a child ≥6mmol/L (≥230 mg/dL);
 Premature CHD;
 Tendon xanthomas; or
 Sudden premature cardiac death.

50. Management
 The goal of FH treatment is to reduce the risk of
CHD or risk of a CHD-equivalent condition (eg,
carotid artery disease, diabetes, peripheral arterial
disease).

51. Homozygous FH
 Lifestyle changes: Recommended for cardiovascular
benefits .
 High doses of HMG-CoA reductase inhibitors (statins)
combined with bile acid sequestrants, ezetimibe, and
niacin.
 Anti–proprotein convertase subtilisin/kexin type 9 (anti-
PCSK9) monoclonal antibodies (specifically, evolocumab
and alirocumab) can be used as an adjunct to diet and
maximally tolerated statin therapy,
 Estrogen replacement therapy in postmenopausal women
 LDL apheresis for selective removal of lipoproteins that
contain apo-B (when the LDL receptors are absent or
nonfunctional)

52. The following are procedures used in the treatment
of homozygous FH
 Portacaval anastomosis
 Liver transplantation (rarely)
 Investigative therapies for homozygous and
heterozygous FH include probucol, which causes
regression of cutaneous and tendon xanthomas in
patients with both homozygous and heterozygous FH
but no long-term benefits for reduced coronary
atherosclerosis, and gene therapy.

53. Heterozygous FH
 The following are used in the management of heterozygous FH:
 Lifestyle modification, including diet (limited saturated fats, trans fats, and
cholesterol); weight management; aerobic/toning exercises
 HMG-CoA reductase inhibitors (statins) (eg, simvastatin, atorvastatin, or
rosuvastatin), and one or more other LDL lowering medications, or
 Bile acid sequestrants, or
 Ezetimibe, or
 Niacin
 Estrogen replacement therapy in postmenopausal women
 Consider LDL apheresis for the following patients:
 Those with documented CHD whose LDLc level cannot be lowered below 200
mg/dL by conventional therapy
 Those without CHD but who have an LDLc level greater than 300 mg/dL

64.  Main references
 ESC 2016
 EAS_Consensus_on_HoFH.
 American Association of Clinical Endocrinologists
and American College of Endocrinology
Guidelines for Management of
Dyslipidemiaand Prevention of
Cardiovascular Disease

65. S