Transcript Current Dyslipidemia Management Recommendations

Provider Recommendations for Managing
Dyslipidemia: Circa 2016
Harmony and Contrasts with the National Lipid
Association, International Atherosclerosis Society,
European Society of Cardiology and other organizations
Ralph LaForge, MSc, CLS, FNLA
Duke University, Endocrine, Metabolism, & Nutrition Division
CMR Consultants, Durham NC
[email protected]
AGENDA
Key lipids and lipoproteins
ACC/AHA and NLA guideline recommendations
Principle dyslipidemias
Recommendations for lifestyle management
Key Takeaways
Key lipids/lipoproteins for management: Atherogenic lipoproteins (LDL-C,
nonHDL-C), triglycerides, familial hyperlipidemia, high TG – low HDL, and
isolated low HDL-C. Most of these are favorably impacted by therapeutic
lifestyle therapy
Two evidence-based approaches to treat LDL-C (polygenic dyslipidemia):
Treat to target/goal or treat with % statin potency
Therapy intensity, particularly for LDL-C is based not only on the level of
dyslipidemia but also on CVD risk (two approaches here)
Understand choices and responses to pharmacotherapies
Lipids/lipoproteins most responsive to lifestyle therapy
Key Lipids and Lipoproteins
Key Lipid and Lipoprotein Labs
Primary (Tier I)
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TC
LDL
HDL
TG
nonHDL
Secondary (Tier II)
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LDL-P
Apo B
Apo A1
Apo C II & III
CRP
Lp(a)
oxyLDL
LpPla2
Apo E isoforms
Lipoprotein ratios
hs-cTnI
Genotypes
Others
Current Respected Dyslipidemia Guidelines
2013 ACC/AHA Guideline on the Treatment of
Blood Cholesterol to Reduce Atherosclerotic
Cardiovascular Risk in Adults
ACC/AHA and NLA guideline
recommendations
ACC/AHA
NLA
ACC/AHA
A movement away from lab value, the emphasis
on proven medications and the emphasis on
treatment for those with the most to gain are
terrific aspects of the guidelines.
Bob Eckel, MD (ACC/AHA panel member)
“It is important for practicing clinicians to understand that
achieving LDL targets is not precluded by the guidelines.
"In my own clinic, if I think the LDL is not low enough, I'll set
an LDL cholesterol goal under 70 mg/dL,"
"I'm on the guideline committee and we're not setting goals
that aren't evidence based, but I'm setting them in my
own clinic because I believe we need to have a target to
shoot for."
6/2014
Atherosclerotic
Cardiovascular Diseases
(ASCVD)
CHD, stroke, peripheral arterial disease, carotid
artery disease, and other forms of atherosclerotic
vascular disease.
ACC/AHA
ASCVD statin benefit groups
Emphasis on treatment of patient groups in which statins
provide clear net benefit:
(1) Clinical ASCVD (secondary prevention)
(2) LDL–C ≥190 mg/dL
(3) Diabetes, ages 40 to 75 years
(4) 10-year ASCVD risk estimate ≥7.5 percent; aged 40
to 75 years (new risk assessment tool)
ACC/AHA
Statin Benefit Groups Rx
1) Secondary Prevention (clinical ASCVD): Evidence supports high-intensity
statin therapy for this group to maximally lower LDL–C. It does not support the use
of an LDL–C target A
2) LDL-C ≥190 mg/dL: Evaluate causes, esp. FH. Should be treated with statin
therapy (10-year ASCVD risk estimation is not required): Use high-intensity statin
therapy unless contraindicated. B
3) Diabetes: High-intensity statin therapy is reasonable for adults 40 to 75 years
of age with diabetes mellitus with a ≥7.5% estimated 10-year ASCVD risk unless
contraindicated. E
Moderate-intensity statin therapy should be initiated or continued for adults 40 to
75 years of age with diabetes mellitus. A
4) 10-year risk ≥7.5%: Adults 40 to 75 years of age with LDL–C 70 to 189 mg/dL,
without clinical ASCVD* or diabetes and an estimated 10-year ASCVD risk ≥7.5%
should be treated with moderate- to high-intensity statin therapy. A
One omission (ACC/AHA guidelines),
There is no categorical mention of Lifestyle Benefit
Groups with regard to managing LDL-C. i.e., for patients
attempting and motivated to start their therapy with a
systematic intensive lifestyle therapeutic approach.
ACC/AHA
Pooled Cohort Equations
10-year ASCVD risk model*
10-year risk for a first hard ASCVD event
Hard ASCVD defined as nonfatal myocardial infarction or
CHD death, or fatal or nonfatal stroke, over a 10-year
period among people free from ASCVD at the beginning of
the period.
 Applicable to African-American and non-Hispanic white men and women
40 through 79 years of age (ATP III Framingham tool only included Whites)
* The AHA/ACC Work Group added data from ARIC, CHS, CARDIA, and FOS
studies to the Framingham10-year CVD risk prediction equations
ACC/AHA
Pooled Cohort Risk Assessment Equations Predicts 10-year risk for a first
atherosclerotic cardiovascular disease (ASCVD) event
(from ClinCalc.com)
http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx
ACC/AHA
New 10-year Risk calculation specificity
Note that, at present, the risk equations apply most accurately
to non-Hispanic Whites and African Americans.
For other ethnic groups, we recommend use of population
specific equations
These estimates may underestimate the risk for persons from
some race/ethnic groups, especially American Indians, some
Asian Americans (e.g., of south Asian ancestry), and some
Hispanics (e.g., Puerto Ricans), and may overestimate the
risk for others, including some Asian Americans (e.g., of east
Asian ancestry) and some Hispanics (e.g., Mexican
Americans).

Those with diabetes (benefit group 3) and primary
prevention (benefit group 4) require the ACC/AHA 10-year
ASCVD assessment for recommending the intensity of
statin therapy which for Asian Americans, Hispanics (MexAm)
and American Indian/Alaska Natives this risk scoring tool
will be largely inappropriate
ACC/AHA
Journal of Clinical Lipidology (2015) 9, 129–169
NLA Recommendation Differences
Broader look at evidence base
More comprehensive (incl. TG, HDL, Apo B, metsyn,
FH)
Focus on atherogenic lipoprotein targets/goals
Quantitative risk factor scoring
Non-statin therapy options
PCSK9
Principle Dyslipidemias
Principle Dyslipidemias
Atherogenic lipoproteins (Elevated LDL-C & nonHDL-C)
Statin benefit groups & % reduction (ACC/AHA)
LDL targets (NLA, IAS)
Familial hypercholesterolemia (e.g. LDL >190)
Elevated LDL-C and triglycerides
Elevated triglycerides (>500 mg)
Isolated low HDL-C
* High TG – Low HDL (TG/HDL)
Atherogenic Lipoproteins
LDL-C & nonHDL-C
Non HDL-C
0.95
Chylomicrons
VLDL
Density (g/ml)
(ApoB, LDL-P)
IDL
1.006
Chylomicron
Remnants
1.02
LDL
1.06
1.10
HDL2
Lp(a)
HDL3
1.20
5
10
20
40
60
Diameter (nm)
80
1000

An elevated triglyceride concentration confounds the
relationship between LDL-C and ASCVD risk, even in cases
when the triglyceride elevation is borderline, but this appears
to be less of an issue with non–HDL-C.
Non–HDL-C incorporates the triglyceride level
indirectly because the triglyceride concentration is highly
correlated with the concentration of triglyceride-rich
lipoprotein cholesterol
Arterioscler Thromb Vasc Biol. 2008;28:1582-1583
Davidson M Clin Cardio. 2009
NLA 2014
Familial Hypercholesterolemia
LDL-receptor defect
Heterozygous or Homozygous FH
Xanthelasma
Tuberous xanthomas
Eruptive xanthomas
Microscopic view: xanthelasma
(lipid-laden macrophages)
Familial Hyperlipidemia
Adults (>20 years):
LDL cholesterol >190 mg/dL or non-HDL
cholesterol >220 mg/dL;
Children adolescents and young adults (<20 years):
LDL cholesterol ≥160 mg/dL or non-HDL
cholesterol ≥190 mg/dL
Hypertriglyceridemia
Endocrine
Society
2014
Endocrine
Society
2014
Elevated LDL-C and Triglycerides
Familial Combined Hyperlipidemia
Three types:
1. Increased VLDL and LDL
2. Increased VLDL and chylomicron remnants
(remnant removal disease, type III HL) (TG and TC are
often similar in value, eg. 250-300 mg/dl)
3. Very high TG where increase in TC is the result of
the cholesterol in the VLDL and chylomicrons
Buttocks, the shoulders, and the
extensor surfaces of the extremities
Eruptive xanthomas
Feature of very high TG:
e.g., chylomicronemia, FEHTg
Lipemia Retinalis
↑↑TG, VLDL, Chylomicrons
Isolated Low-HDL-C
Hypoalphalipoproteinemia
(low HDL-C, e.g., <30 mg/dL)
25-35 mg/dL Polygenic
5-20 mg/dL Apo A-1 deficiency
ABCA1 mutation (Tangiers disease)
LCAT deficiency (fish eye disease)
LPL deficiency (1/m)
*
Currently there is no evidence that reducing HDL by itself decreases
ASCHD risk
High TG, Low HDL-C
Primarily manifested by:
 HDL-C
(<45 mg/dL)
 Triglycerides
(150 mg/dL ++)
 Non HDL-C (> 160 mg/dL++)
and  Apolipoprotein B
Seen in obesity, metabolic syndrome, and
diabetes
The wide spectrum of
pharmacotherapy
I. Elevated LDL-C
II. Elevated LDL & TG
III. Elevated TG (>500mg/dl)
IV. Isolated low HDL-C *
Statin monotherapy
Niacin
Ezetimibe
PCSK9 inhib.
BAS
Statin-niacin
Statin-ezetimibe
Statin-resin
Statin monotherapy
Statin-niacin
Advicor-Simcor
Statin-n3 fish oil
Statin-fibrate orTLX
Fibrate-ezetimibe
Vytorin-fibrate
Vytorin-niacin
Fibrate or TLX
n3 fish oil Rx
Niacin
Niacin-fish oil
Fibrate-niacin
Fibrate-niacin-FO
Niacin
Fibrate
Niacin-fibrate
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Most responsive lipids and lipoproteins to
therapeutic lifestyle therapy
Cholesterol is a sterol - not a fat

Unlike fatty acids and triglycerides cholesterol
cannot be hydrolyzed to generate ATP-energy
Most Responsive Lab Measures to TLC
1. TG
(acute response)
2. Clincal skinfolds
(subscap, tricep)
3. LDL-P
Non-HDL
Apo B
4. LDL-C
TC
A1C
FPG
* assumptions
(Lange)
Dietary complacency
JAMA Intern Med. Published online April 24, 2014 UCLA/Tokyo/Harvard
NHANES survey 1999 through 2010. N=27, 886 US adults
(non-randomized observational study)
 Statin users were consuming an extra 192 kcal per day in
2009–2010 than they were in 1999–2000, and this could
have contributed to the increase in BMI, which was the
equivalent of a 3- to 5-kg weight gain