Review of the New 2013 ACC/AHA Guidelines on Lipid Management
This presentation is the property of its rightful owner.
Sponsored Links
1 / 109

Review of the New 2013 ACC/AHA Guidelines on Lipid Management K athleen Dively NP Associates In Cardiology Clinical Lipid Specialist FNLA PowerPoint PPT Presentation


  • 98 Views
  • Uploaded on
  • Presentation posted in: General

Review of the New 2013 ACC/AHA Guidelines on Lipid Management K athleen Dively NP Associates In Cardiology Clinical Lipid Specialist FNLA. Objectives. Discuss and review major changes including the lack of target LDL Discuss the role of niacin and ezetimibe

Download Presentation

Review of the New 2013 ACC/AHA Guidelines on Lipid Management K athleen Dively NP Associates In Cardiology Clinical Lipid Specialist FNLA

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

Review of the New 2013 ACC/AHA Guidelines on Lipid ManagementKathleen Dively NPAssociates In CardiologyClinical Lipid SpecialistFNLA


Objectives

Objectives

  • Discuss and review major changes including the lack of target LDL

  • Discuss the role of niacin and ezetimibe

  • Dicuss the role of biomarker ieApoB, CIMT

  • Discuss the use of combination therapy

  • Discuss the use of high dose statin therapy

  • Discuss the management of residual risk


Previous guidelines

Previous Guidelines

  • The first priority of treatment is to treat LDL-C to goal (unless TG is >500)

    • Non-HDL-C should be a secondary treatment target, if LDL-C at goal but TG is ≥200 mg/dL

    • Always screen for residual risk , Look at more than the LDL-C


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

Establish Goals of Therapy based on risk factors & Lab evaluation

Multivariable

Risk Assessment

LDL Management

High Risk

Lifestyle/statin/other

If above goal

CHD/CHD Risk Equiv.

(>20% 10-year risk)

Treatment

Assessment & Goal

LDL-C < 100

(LDL-P < 1000)*

Intermediate Risk

2+ Risk Factors

(10-20% 10-year risk)

Treatment

Assessment & Goal

(LDL-P < 1300)*

LDL-C < 130

Low Risk

Treatment

Assessment & Goal

(LDL-P < 1600)*

LDL-C < 160

0-1 Risk Factors

(0-10% 10 year risk)

*Based on population equivalent cut points

1. Contois JH et al. Clin Chem. 2009;55:407-419

2. Cromwell WC. In: Clinical Challenges in Lipid Disorders.Toth PP, Sica DA, editors. Oxford: Clinical Publishing; 2008.p. 249-59.

3. Cromwell WC, Barringer TA. CurrCardiol Reports 2009;11(6):468-475


Acc aha guideline on the assessment of cardiovascular risk

ACC/AHA Guideline on the Assessment of Cardiovascular Risk

The last NCEP-ATPIII report was delivered in 2001 with an update in 2004. There has been no concensus reached with ATP IV so the 16 member group reconvened under the auspices of the ACC/AHA and were limited to review only level one research.

In response to the 2011 report of the Institute of Medicine on the development of trustworthy clinical guidelines (1), the NHLBI Advisory Council (NHLBAC) recommended that the NHLBI focus specifically on reviewing the highest quality evidence

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Level i evidence

Level I Evidence

  • [This definition,: Evidence obtained from at least one properly designed randomized controlled trial.‎ and therefore considered ( LIKELY reliable )


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease in Adults

There is no evidence to support continued use of specific LDL-C and/or non–high-density lipoprotein cholesterol (non–HDL-C) treatment targets

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease in Adults

The following are no longer considered appropriate strategies: treat to target, lower is best. The new GL recommends: treat to level of ASCVD risk, based upon estimated 10-year or lifetime risk of ASCVD. The guidelines provided no recommendations for initiating or discontinuing statins in NYHA class II-IV ischemic systolic heart failure patients or those on maintenance hemodialysis.

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Acc aha guidelines for 4 classes of statin eligible patients

ACC/AHA Guidelines for 4 Classes of Statin Eligible Patients

Individuals with LDL> 190 mg/dl

Age 40-75 with LDL 70-189mg/dl without ASCVD assess 10 year risk, treat if > 7.5%

Age 40-75 with Diabetes and no ASCVD with LDL-C between 70-189mg/dl

Individuals with clinical ASCVD

No recommendations for CHF or hemodialysis patients.

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Statin eligible

Statin Eligible

  • Estimated that 44% of men

  • 22% of women

  • Under the old guidelines about 15% are eligible


Acc aha guideline on the assessment of cardiovascular risk1

ACC/AHA Guideline on the Assessment of Cardiovascular Risk

  • The contribution to risk assessment for a first ASCVD event using ApoB, CKD, albuminuria, or cardiorespiratory fitness is uncertain at present

  • CIMT is not recommended for routine measurement in clinical practice for risk assessment for a first ASCVD event

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Acc aha guideline on the assessment of cardiovascular risk2

ACC/AHA Guideline on the Assessment of Cardiovascular Risk

  • The use of ezetimibe is no longer recommended as a valid treatment for lipid management.

  • The use of niacin was not addressed

  • The use of fibrates and omega 3s were not addressed

  • The use of combination therapy was not addressed due to lack of clinical evidence.

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Acc aha guideline on the assessment of cardiovascular risk3

ACC/AHA Guideline on the Assessment of Cardiovascular Risk

  • High-intensity statin therapy is defined as a daily dose that lowers LDL-C by ≥50% and moderate-intensity by 30% to <50%. All patients with ASCVD, should receive high-intensity statin therapy; or if not a candidate for high-intensity, should receive moderate-intensity statin therapy.

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Acc aha guideline on the assessment of cardiovascular risk4

ACC/AHA Guideline on the Assessment of Cardiovascular Risk

  • LDL-C ≥190 mg/dl : Should receive high-intensity or moderate-intensity statin therapy.

  • Statin Intolerant: Other cholesterol-lowering agents can be considered to further lower LDL-C.

  • Diabetics with a 10-year ASCVD ≥7.5%: Should receive high-intensity statins and <7.5% moderate-intensity statin therapy.

  • Persons 40-75 years with a ≥7.5% 10-year ASCVD risk: should receive moderate- to high-intensity statin therapy.

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Acc aha guideline on the assessment of cardiovascular risk5

ACC/AHA Guideline on the Assessment of Cardiovascular Risk

To the patients not in the 4 statin groups

Individuals whose 10-year risk is <7.5%

Family history of premature ASCVD,

LDL-C >160 mg/dl,

HS-crp≥2 mg/dl,

Coronary calcium score ≥300 Agatstonunits

ankle-brachial index <0.9

Elevated lifetime risk of ASCVD may be used to enhance the treatment decision making.

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Acc aha guideline on the assessment of cardiovascular risk6

ACC/AHA Guideline on the Assessment of Cardiovascular Risk

Lifestyle modification (i.e., adhering to a heart healthy diet, regular exercise habits, avoidance of tobacco products, and maintenance of a healthy weight) remains a critical component of health promotion and ASCVD risk reduction, both prior to and in concert with the use of cholesterol-lowering drug therapies.

Stone NJ et al. Task Force on Practice Guidelines. Circulation or JACC: on line 2013


Basically all targets have been removed

Basically all targets have been removed

Risk stratification remains, but is much more lenient


Risk stratification statin eligible patients

Risk stratification, Statin eligible patients

  • 10 year risk >7.5%

  • (was > 20%)


Risk factors optimal levels

Risk Factors, optimal levels

  • Total Cholesterol 170mg/dl

  • HDL 50mg/dl

  • Systolic b/p110mmhg


Desk top acc risk calculator

Desk-top ACC Risk Calculator

  • 10 year risk ages 40-79yr

  • Life-time risk ages 20-59yr

  • Pt age 55, non-smoker, TC 213, HDL50, systolic b/p 120 ( untreated), non-diabetic

  • White women 2.1%

  • African American women 3.0%

  • White man 5.3%

  • African American Man 6.1%


Risk assessment calculator no targets of therapy

Risk Assessment Calculator/No targets of therapy


46 year old white male family history of hd

46 year old white male , Family history of HD .


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

  • His 10 year risk with the new calculator was 2%.


Asymptomatic abnormal stress referred for lhc

Asymptomatic, Abnormal stress referred for LHC.

  • 90% proximal LAD

  • Pt was on lipitor and niaspan. Abnormal phytosterol levels.

  • Changed to crestor.

  • LVH by echo. b/p med changed

  • LDLp 1245 (LDLc 75)


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

  • Given the strong evidence that statins reduce risk across the range of LDL levels, the best preventive strategy may be to use the patient’s global cardiovascular risk to determine treatment.

  • The absolute benefit of statins is greatest for those at higher risk—and those at highest risk would tend to benefit most from higher dose or higher potency statins.

  • The benefit diminishes with decreasing risk. A recent analysis of statins for primary prevention showed that a strategy using statins based on patient risk rather than LDL levels can prevent more cardiovascular events while treating fewer people with high dose statins.

BMJ 2010;341:332-333


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

“Clear, compelling evidence supports near-universal empirical statin therapy in patients at high cardiovascular risk (regardless of their natural LDL cholesterol values), but current clinical evidence does not demonstrate that titrating lipid therapy to achieve proposed low LDL cholesterol levels is beneficial or safe.”

Ann Intern Med. 2006;145:520-530


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

Evidenced Based Medicine

  • We conclude that there is clear and compelling evidence that most patients at high risk for cardiovascular disease should be taking at least a moderate dose of a statin if tolerated, even if their natural LDL cholesterol level is low

  • We could find no published high-quality clinical evidence supporting titration of lipid therapy based on proposed LDL cholesterol targets

  • We strongly suggest that those with access to these data conduct further analyses to provide more valid evidence on this important clinical and scientific question

Hayward RA et al. Ann Intern Med. 2006;145:520-530


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

  • The trials of cholesterol lowering treatments tested the effect of fixed doses of drugs, not a strategy of progressively intensifying lipid therapy without regard to strategy to reach specific target ranges

Save a ton of money – No follow up lab tests! No follow up phone calls!

BMJ 2010;341:332-333


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

The first outcome trial ever done using a statin

  • 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 212 – 308 mg/dL on a lipid-lowering diet were randomized to double-blind treatment with simvastatin or placebo

  • Dosage was adjusted, if necessary, at the 12-week and 6-month visits, on the basis of serum total cholesterol at 6 and 18 weeks. The goal of treatment was to reduce serum total cholesterol to 3.0-5.2 mmol/L (115-200 mg/dL)

  • Patients in the simvastatin group whose serum cholesterol was out of range had their dose increased to 40 mg daily, as two 20 mg tablets, or reduced to one 10 mg tablet

Pedersen TR. Lancet 1994;344:1383-1389


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

The Politics of Evidence-Based Medicine

Evidence-based medicine has enabled payers, purchasers, and governmental authorities to use their financial clout to alter the practice of medicine.

Traditionally doctors defined the standard of care. Now, armed with more and better information about medical practices, payers and purchasers can deny payment for medical services that they deem medically unnecessary or ineffective.

In so doing, they redefine standards for appropriate medical practice.

By Marc A. Rodwin, Indiana University Journal of Health Politics, Policy and Law, Vol. 26, No. 2, April 2001

http://www.ahrq.gov/clinic/jhppl/rodwin.htm


Unmet need persistent incidence of chd

Unmet Need: Persistent Incidence of CHD

Framingham Heart Study 26 year f/u, Indicates that Measuring Cholesterol Does Not Tell Us Enough

  • 80% of subjects with cardiac events had lipid levels similar to subjects that were event free

  • 35% of CHD occurs in people with TC<200

20/100

40/100

90/100


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

Should we consider a failure in detection of risk by “standard methods” an appropriate reason to increase the number of statin eligible patients and forfeit our present guidelines?


New acc aha guidelines

New ACC/AHA Guidelines

  • Lipids, there is no longer any support for treating to specific targets

  • Obesity, There is no ideal diet for weight loss

  • Risk Assessment, New calculator for 10 year risk assessment ages 40-75. Ages 20-59 life-time calculator. (my.americanheart.org/cvriskcalculator)

  • Lifestyle, restriction of fat and sodium


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

Steps 2 & 3: Establish Goals of Therapy & Lab evaluation

Multivariable

Risk Assessment

LDL Management

High Risk

Lifestyle/statin/other

If above goal

CHD/CHD Risk Equiv.

(>20% 10-year risk)

Treatment

Assessment & Goal

LDL-C < 100

(LDL-P < 1000)*

Intermediate Risk

2+ Risk Factors

(10-20% 10-year risk)

Treatment

Assessment & Goal

(LDL-P < 1300)*

LDL-C < 130

Low Risk

Treatment

Assessment & Goal

(LDL-P < 1600)*

LDL-C < 160

0-1 Risk Factors

(0-10% 10 year risk)

*Based on population equivalent cut points

1. Contois JH et al. Clin Chem. 2009;55:407-419

2. Cromwell WC. In: Clinical Challenges in Lipid Disorders.Toth PP, Sica DA, editors. Oxford: Clinical Publishing; 2008.p. 249-59.

3. Cromwell WC, Barringer TA. CurrCardiol Reports 2009;11(6):468-475


Potential problems

Potential problems

NO TARGETS OF THERAPY difficult for patient motivation , promotes apathy on the part of the provider

NO ROUTINE LABS difficult for motivation, risk

HIGH DOSE STATIN side effects

HIGH RISK POPULATIONS ischemic CHF, CKD

COMBINATION TX excluded

WIDE SPREAD USE OF STATINS increased costs

ETHNIC SPECIFIC ALGORITHMSnot addressed

INCREASED PAYOR DENIALS considered guidelines for us (not mandates) but do we really have a choice when payors deny


Ezetimibe zetia

Ezetimibe (Zetia)

Bowel absorption inhibitor

Works at the brush border of the small intestine.


Cholesterol torsho

X

Ezetimibe

Cholesterol torsHo

LDLapoB100

Liver

Duodenum

VLDLapoB100

Jejunum

Ileum

CM RemnantapoB48

CM

apoB48

Colon


Niacin effectiveness in reducing events

Niacin effectiveness in reducing events.

  • Fats trial ( Familial hypercholesterolemia ) 78 %

  • Hats trial (HDL atherosclerosis tx) 61 %

  • AFREGS (airforce regression) 53 %

  • Aim High ( no residual risk) 0


Residual risk is not addressed

RESIDUAL RISK IS NOT ADDRESSED

RESIDUAL RISK IS NOT ADDRESSED


Evidence of residual cvd risk

Evidence of Residual CVD Risk

  • 136,905 hospitalizations for (non-CHF) CAD and lipids w/in 24 hrs of admit (at 541 hospitals)

  • Over 50% of patients with LDL-C <100 mg/dL and 17.6% with LDL-C <70 mg/dL

  • For patients without h/o CAD, 72.1% with LDL-C <130 mg/dL and 41.5% with LDL-C <100 mg/dL

Sachdeva A, et al. Am Heart J 2009; 157:111-7.e2.

From AHA’s Get with The Guidelines (GWTG) CAD Program and database; 2000-2006.


Residual cardiovascular risk in major statin trials

Residual Cardiovascular Risk in Major Statin Trials

Patients Experiencing

Major Coronary Events, %

N

4444

9014

4159

20 536

6595

6605

LDL

-35%

-25%

-28%

-29%

-26%

-25%

Secondary

High Risk

Primary

Adapted from Libby PJ, et al. J Am Coll Cardiol, 2005:46:1225-1228.


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

Should we consider a failure in detection of risk by “standard methods” an appropriate reason to increase the number of statin eligible patients and forfeit our present guidelines?


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

NO!


Groups that have come out with position statements in support of lipoprotein testing

Groups that have come out with position statements in support of lipoprotein testing

American Diabetes Association / American College of Cardiology Foundation Consensus Statement [3]

American Association for Clinical Chemistry Lipoproteins & Vascular Diseases Working Group Recommendations [1]

American Association of Clinical Endocrinologists Guidelines for Management of Dyslipidemia [4]

National Lipid Association Expert Recommendations [5]

Canadian Cardiovascular Society Guidelines [6]

ESC/EAS Guidelines for the Management of Dyslipidemia [7]

1] Contois JH ClinChem 2009;55:407-419 2] Otvos et al. J ClinLipidol 2011;5:105-113 3] Brunzell JD et al. j Am CollCardiol 2008;51:1512-1524 4] Jellinger PS et al. EndocrPract 2012;18(suppl 1), 1-78 European Society of Cardiology and European Athrosclerosis society


What s the difference between lipoproteins and cholesterol

What’s the difference between Lipoproteins and Cholesterol ?


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

=

Lipoprotein

=

Cholesterol


Question 1 what causes traffic jams to occur on a highway

Question #1: What causes traffic jams to occur on a highway ?

Number of carsnotthe number of passengers

=


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

POLAR

SURFACE COAT

Phospholipid

Free cholesterol

Apo B

The LDL Particle

NONPOLAR

LIPID CORE

Cholesterol Ester

Triglyceride

LDL-Cholesterol = the weight of the constituent cholesterol within the particle

“LDL” should not imply LDL-Cholesterol


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

Cholesterol Molecules

Apoprotein B-100

Apoprotein B-100

Triglyceride Molecules

Cholesterol Molecules

Triglyceride Molecules

LDL A Particle

LDL B Particle


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

Up to 70%

More Particles

Cholesterol

Balance

LDL-C can vary with particle size

At the same LDL cholesterol, more small LDL vs. large LDL particles present

100 mg/dL

100 mg/dL

Large LDL

Small LDL

Otvos JD et al. Am J Cardiol2002;90(suppl):22i-29i

Cromwell WC et al. J ClinLipidology. 2007;1(6):583-592.


Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

A gradient driven process,LDL particles invade the arterial wall and set in motion the cascade of events that leads to atherosclerosis1,2After adjustment for LDL-P concentration, particle subclass and size do not impact outcomes 3

LDL particle number (LDL-P), as opposed to size, is a key driver of atherogenic plaque formation

Endothelial Cell

Arterial Wall

LDL Particle

Endothelial Gap

1. Fredrickson et al. NEJM 1967; 276: 148

2. Brunzell, et al. Diabetes Care. 2008;4:811-822

3. Ip et al . Ann Intern Med. 2009;150:474-484


Lipoprotein particles

Chylo-

microns

VLDL

IDL

Chylomicron

Remnants

LDL

Triglycerides

(mainly)

LDL

Cholesterol

HDL

HDL

Cholesterol

Lipoprotein Particles

0.95

1.006

Density (g/ml)

1.02

1.06

1.10

1.20

5

10

20

40

60

80

1000

Diameter (nm)


Why alternate measures of ldl quantity are not equivalent

Why Alternate Measures of LDL Quantity are Not Equivalent

  • Concordance:

    • LDL-C and LDL-P “agree” (i.e., are equally high or low)

    • Either LDL measure is an equally good guide to LDL treatment decision-making.

  • Discordance:

    • LDL-C and LDL-P “disagree” (i.e., the values differ, either in their relationship to the normal range or to each other)

    • Which LDL measure should guide clinical decision-making?


  • Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    CHD Event Associations of LDL-P versus LDL-C

    Framingham Offspring Study

    Cromwell WC et al. J ClinLipidology 2007;1(6):583-592.


    Friedwald equation is used to calculate the bad cholesterol ldl

    Friedwald Equation (is used to calculate the bad cholesterol, LDL)

    • LDL Cholesterol=Total chol-(HDL)-(TG/5)

    • It assumes all the TG is carried on VLDL

    • And the TG/CHOL ratio of VLDL is constant at 5:1

    • NOT TRUE when TG>200, DM or metabolic syndrome exist with ^ Chilomycrons, get falsely low HDL and LDL.


    Metabolic syndrome

    MetabolicSyndrome

    • Triglycerides > 150mg/dl

    • FBG > 100 ( or DM)

    • Waist circumference > 35 inches in a women or 40 inches in a man

    • HTN (>130/85 mmHg) or taking B/p medication

    • HDL-C <40mg/dl males or <50mg/dl females

    • NCEP Definition of Metabolic Syndrome 2001 Guidelines


    How nmr lipoprotein analysis works

    How NMR Lipoprotein Analysis works


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    NMR Lipoprotein Analysis

    Lipoprotein subclasses of different size broadcast lipid NMR signals that are naturally distinguishable. The measured amplitudes of these signals provide subclass quantification.

    Jeyarajah EJ et al. Clin Lab Med 2006;26:47-70


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    NMR Measures LDL Particle Number,Not LDL Cholesterol

    Measured LDL-C

    90 mg/dL

    Measured LDL-C

    90 mg/dL

    LDL NMR Signals

    LDL particles 900 nmol/L

    LDL particles

    1600 nmol/L


    Principles for determining appropriate ldl testing guided by landmark publication

    Principles for determining appropriate LDL testing guided by landmark publication

    • Value of the new reference test is best examined in cases of disagreement (discordance) between the new and standard tests.

    • Clinical consequences of disagreements between new and standard test requires a fair “umpire” test.

    • Fair umpire tests include clinical events or disease progression.

    Glasziou P et al. Ann Intern Med 2008;149:816-22.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Multiple Outcome Studies Demonstrate Difference Between LDL-P and LDL-C


    Relationship of ldl particle number with chd outcomes

    Relationship of LDL Particle Number with CHD Outcomes


    Framingham offspring study

    Framingham Offspring Study

    Long-running NIH/NHLBI observational study of residents of Framingham, MA to determine risk factors for future cardiovascular disease (CVD)

    Blood samples obtained in 1988-91 (exam 4)

    Lipids measured by traditional chemical methods

    Lipoprotein particles measured by NMR spectroscopy

    Correlated with CVD occurrence during a 15-year follow up

    3,066 subjects

    431 CVD events (MI, stroke, CHD death, angina, congestive heart failure)

    Discordance defined as either above or below the median for LDL-C and LDL-P

    Cromwell WC et al. J ClinLipidology 2007;1(6):583-592.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    CHD Event Associations of LDL-P versus LDL-C

    Framingham Offspring Study

    Cromwell WC et al. J ClinLipidology 2007;1(6):583-592.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Multi-Ethnic Study of Atherosclerosis (MESA)

    • Large NHLBI observational study of the pathogenesis and progression of subclinical atherosclerosis.

    • N=6,814 asymptomatic men and women free of cardiovascular disease at entry

      • 38% White

      • 28% African-American

      • 22% Hispanic

      • 12% Asian

    • 319 CVD events(MI, CHD death, angina, stroke, stroke death, or other atherosclerotic or CVD death) occurred during 5.5-yr follow-up (n=5598).

    Otvos et al. J ClinLipidol 2011;5:105-13


    Mesa study design

    MESA: Study Design

    • Baseline assessments:

      • LDL particle number (LDL-P) measured by NMR spectroscopy

      • Calculated LDL cholesterol (LDL-C)

      • Carotid intima-media thickness (IMT)

    • Associations of LDL-C and LDL-P with CVD events (prospective) and carotid IMT (cross-sectional) were determined

      • Overall population

      • Concordant subgroup

      • Discordant subgroup

    • Discordance defined as LDL-C and LDL-P levels differing by 12 percentile units, to give equal-sized concordant and discordant subgroups.

    Otvos et al. J ClinLipidol 2011;5:105-13


    Mesa conclusions

    MESA: Conclusions

    • The cholesterol content of LDL particles varies greatly, causing LDL-C in many individuals to over-represent or under-represent LDL particle concentrations.

    • LDL-C and LDL-P were both significantly associated with incident CVD overall.

    • For individuals with concordant levels of LDL-C andLDL-P, both measures of LDL quantity were (as expected) equally predictive of risk.

    • For individuals with discordant levels, only LDL-P was significantly associated with incident CVD.

    • Carotid IMT also tracked with LDL-P rather than LDL-C when these measures were discordant.

    Otvos et al. J ClinLipidol 2011;5:105-13


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    VA-HIT Background

    Purpose:

    Randomized, double-blind trial to determine if increasing low HDL-C will decrease CHD events

    Subjects:

    2531 men with CHD, low HDL-C (31.5 mg/dL), and low LDL-C (111 mg/dL)

    Therapy:

    Gemfibrozil(1.2 g/d) vs. placebo

    Otvos, et al. Circulation 2006;113:1556-63


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    VA-HIT: Principal Results

    Gemfibrozil treatment resulted in a

    22% decrease in nonfatal MI + CHD death

    31% decrease in stroke

    No increase in adverse events

    Otvos, et al. Circulation 2006;113:1556-63


    Va hit trial

    VA Hit Trial

    • Demonstrated that gemfibrozil reduced 5-yr rate of new CHD events.

    • No effect on LDL-C, HDL-C only raised 6%, tri lowered 31%

    • Increased LDL size and decreased LDL particles number (LDL-P)

    • The decrease in particle number was predictive for CHD future events.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    VA-HIT: Alternative Measures of LDL and HDL As Predictors of CHD Events

    HDL

    LDL

    Odds Ratio per 1-SD Increment

    Odds Ratio per 1-SD Decrement

    LDL-C

    Non-HDL-C

    ApoB

    LDL-P*

    HDL-C

    ApoA-1

    HDL-P*

    Adjusted for treatment, age, hypertension, smoking, BMI, and diabetes

    *p<0.001

    Otvos, et al. Circulation 2006;113:1556-63


    Consensus and recommendations

    Consensus and Recommendations


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    2008 ADA/ACC Consensus Statement on Lipoprotein Management in Patients with Cardiometabolic Risk

    “… the cholesterol content of LDL particles varies from person to person and is influenced by metabolic abnormalities such as insulin resistance and hyperglycemia.”

    “Hence, measurement of LDL cholesterol may not accurately reflect the true burden of atherogenic LDL particles, especially in those with the typical lipoprotein abnormalities of cardio-metabolic risk.”

    “Measurements of apoB or LDL particle number by NMR may more closely quantitative the atherogenic lipoprotein load. Some studies suggest that both are better indices of CVD risk than LDL cholesterol or non-HDL cholesterol …”

    Brunzellet al. Diabetes Care. 2008. 31(4): 811-822.


    New guidelines for lipid targets in patients with type ii diabetes

    New Guidelines for Lipid Targets in patients with type II Diabetes

    • ApoB <80mg/dl

    • LDL-p <1000nm/l

      • American Association of clinical endocrinology comprehensive diabetes management 2013 consensus statement


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Recommendations for Using LDL Particle Number Measures as Targets of Therapy

    Garber AJ, et al. EndocrPract 2013;19(Suppl 2):1-48.


    Groups that have come out with position statements in support of lipoprotein testing1

    Groups that have come out with position statements in support of lipoprotein testing

    American Diabetes Association / American College of Cardiology Foundation Consensus Statement [3]

    American Association for Clinical Chemistry Lipoproteins & Vascular Diseases Working Group Recommendations [1]

    American Association of Clinical Endocrinologists Guidelines for Management of Dyslipidemia [4]

    National Lipid Association Expert Recommendations [5]

    Canadian Cardiovascular Society Guidelines [6]

    ESC/EAS Guidelines for the Management of Dyslipidemia [7]

    1] Contois JH ClinChem 2009;55:407-419 2] Otvos et al. J ClinLipidol 2011;5:105-113 3] Brunzell JD et al. j Am CollCardiol 2008;51:1512-1524 4] Jellinger PS et al. EndocrPract 2012;18(suppl 1), 1-78 European Society of Cardiology and European Athrosclerosis society


    Nla expert panel recommendations

    NLA Expert Panel Recommendations


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Recommendations from the NLA Expert Panel on Clinical Utility of Inflammatory Markers and Advanced Lipoprotein Testing

    Measurement for On-Treatment Management Decisions

    Davidson, et al. J ClinLipidol2011;5:338-367.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Recommendations from the NLA Expert Panel

    Unrecognized (and under-treated) LDL particle elevations are common and a significant contributor to the residual risk of many patients with “acceptable” levels of LDL-C.

    When LDL-C and LDL-P levels are discordant (esp. diabetes, metabolic syndrome), risk tracks with LDL-P, not LDL-C.

    LDL-P values should be used to indicate a patient has achieved adequate LDL reduction, because LDL-P is a significant independent predictor of CHD end points.

    Davidson, et al. J ClinLipidol2011;5:338-367.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Approach to Utilization of Lipids and LDL Particle Number in Clinical Practice


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Clinical Cut-points for LDL

    Percentile: 20th 50th 80th

    Optimal

    High

    LDL Cholesterol

    Percent

    of

    Subjects

    Framingham Offspring 1

    70 100 130 160 190 220 250 mg/dL

    LDL Particle Number

    Percent

    of

    Subjects

    MESA 2

    700 1000 1300 1600 1900 2200 2500 nmol/L

    1 Otvos JD, Jayarajah E, Cromwell, WC. Amer J Cardiol2002;90(8A):22i-29i.

    2Otvos JD et al. J ClinLipidol 2011;5:105-33.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Approach to Utilization of Lipids and LDL Particle Number in Clinical Practice

    Step 1: Assess clinical CHD risk

    Step 2: Establish goals of therapy appropriate for degree of clinical risk present (Lipids and LDL Particle Number)

    Step 3: Laboratory evaluation

    Step 4: Consider therapeutic lifestyle changes and medications

    as indicated to achieve targets:

    Primary target: LDL

    Secondary targets: non-HDL and TG

    Step 5:Assess response to therapy and modify intervention as indicated to achieve LDL-P target

    Cromwell WC et al. Lipid and Lipoprotein Disorders: Current Clinical Solutions Baltimore: International Guidelines Center; 2009.


    Risk factors cv disease

    Risk Factors : CV disease

    • Smoking

    • Obesity

    • Sedentary lifestyle

    • HTN

    • Hyperlipidemia

    • Family History of premature heart disease

    • Age , men > 45yrs or women > 55yrs


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Step 1: Assess Clinical Risk (using NCEP ATP-III Guidelines)

    Multivariable

    Risk Assessment

    High Risk

    CHD/CHD Risk Equiv.

    (>20% 10-year risk)**

    Intermediate Risk

    2+ Risk Factors*

    (10-20% 10-year risk)**

    Low Risk

    0-1 Risk Factor*

    (0-10% 10 year risk)**

    *Risk factors are age (>45M;>55W), smoking, hypertension, low HDL-C, family history

    **10-year risk given by age, gender, TC, HDL-C, SBP/hypertension, and smoking

    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Steps 2 & 3: Establish Goals of Therapy & Lab evaluation

    Multivariable

    Risk Assessment

    LDL Management

    High Risk

    Lifestyle/statin/other

    If above goal

    CHD/CHD Risk Equiv.

    (>20% 10-year risk)

    Treatment

    Assessment & Goal

    LDL-C < 100

    (LDL-P < 1000)*

    Intermediate Risk

    2+ Risk Factors

    (10-20% 10-year risk)

    Treatment

    Assessment & Goal

    (LDL-P < 1300)*

    LDL-C < 130

    Low Risk

    Treatment

    Assessment & Goal

    (LDL-P < 1600)*

    LDL-C < 160

    0-1 Risk Factors

    (0-10% 10 year risk)

    *Based on population equivalent cut points

    1. Contois JH et al. Clin Chem. 2009;55:407-419

    2. Cromwell WC. In: Clinical Challenges in Lipid Disorders.Toth PP, Sica DA, editors. Oxford: Clinical Publishing; 2008.p. 249-59.

    3. Cromwell WC, Barringer TA. CurrCardiol Reports 2009;11(6):468-475


    Pharmacologic options for reaching ldl particle number goals step 4

    Pharmacologic Options for Reaching LDL Particle Number Goals Step 4

    Adapted from Rosenson et al. Atherosclerosis. 2010; 213:1-7.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Step 5: Assess Response to Therapy

    If not at Lipid and LDL Particle Number goal – modify therapy and repeat laboratory tests in 3 months

    Following therapeutic changes, repeat laboratory testing every 3 months until goal values for lipid and LDL Particle Number are achieved

    Once at goal – continue therapy and repeat laboratory tests in 1 year

    Cromwell WC, Barringer TA. Curr Cardiol Reports 2009;11(6):468-475.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Contributors to residual risk

    Unrecognized (and under-treated) LDL particle elevations are common and a significant contributor to the residual risk of many patients with “acceptable” levels of LDL-C.

    When LDL-C and LDL-P levels are discordant, risk tracks with LDL-P, not LDL-C, especially in higher risk patients with diabetes and metabolic syndrome.

    LDL-P measurement with findings of discordance between LDL-P and LDL-C yield actionable data for medical decision-making regarding treatment, e.g., statin increase or decrease, combination therapy, etc.


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    The primary objective of this study was

    • To evaluate treatment patterns between patients monitored with LDL-c alone and patients monitored with LDL-c and LDL-p results.

    • The secondary objectives of this study were:

    • To determine the number and type of cardiovascular events and procedures

    • To determine the percentage of patients with LDL control according to NCEP Adult Treatment Panel III Guidelines

    • To determine the percentage of patients with diabetes with A1C control according to ADA


    Inclusion criteria

    Inclusion Criteria

    • Diabetes or metabolic syndrome

    • At least 4 lipid profiles in the 4 years follow-up


    Gender distribution

    Gender Distribution


    Age distribution

    Age Distribution


    Most prevalent comorbid conditions

    Most Prevalent Comorbid Conditions


    Average ldlc in the previous 3 years

    Average LDLc in the Previous 3 Years


    Conclusions

    Conclusions

    • Trending towards decreased CVD events in the group using LDLp to guide therapy.

    • Lower dose statin and more combination tx noted in the group where LDLp guided treatment.


    L tap majority of patients with chd do not reach ncep ldl c targets

    L-TAP: Majority of Patients With CHD Do Not Reach NCEP LDL-C Targets

    25

    n = 4,888

    20

    18

    16.6

    14.4

    15

    13

    11.2

    9.9

    % of

    patients

    9.4

    10

    7.9

    5

    0

    100101-111-121-131-141-151->160

    110120130140150160

    LDL-C (mg/dL) on-treatment

    Pearson TA et al. Arch Intern Med. 2000;160:459-467.

    Other L-TAP data courtesy of TA Pearson.


    Lipid clinic yearly data base retropective analysis

    LIPID CLINIC YEARLY DATA BASE RETROPECTIVE ANALYSIS


    Lipid clinic ldl c goal attainment

    Lipid Clinic LDL-C Goal Attainment


    Overall office ldl goal attainment

    Overall Office LDL Goal Attainment


    Patient case study

    Patient Case Study


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Ms R is a pleasant 55 yr old white female with a history of CAD, hypertension, & hyperlipidemia. She had an MI and stent placement on 2 occasions prior to seeing me. She has been followed at by my Lipid Clinic since October 2000. She has maintained a 10 lb. Weight loss and a low risk NMR profile with diet, exercise and medication. She has had no recurrent events.


    What is mrs r s goal of therapy

    What is Mrs R’s goal of therapy?

    • High risk

    • < 70 LDL -C

    • <700 LDL-P


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Robert Superko

    • Trials have not been designed to address such a strict interpretation but reasonable conclusions, regarding benefit of lipoprotein manipulation, can be made from an abundance of heterogeneous clinical trials

    • A weakness of this strict constructionist approach is that it ignores the very large number of individuals treated with a statin who continue to have a cardiovascular event

    • The new guidelines ignore individuals who continue to have a CHD event despite statin treatment.

    • This is the new guidelines greatest failure in my opinion as such an approach creates the danger of ignoring the traditional pathophysiologic/clinical trial approach to understanding disease and treatments that are in the best interest of the individual patient, and worships at the altar of Randomized Clinical Trial strict interpretation

    http://www.medpagetoday.com 11/14/2013


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    • Although we are enamored of the notion that we live in the world of truth in evidence-based medicine, the real truth is that we know very little.

    • Instead, we understand a great many things with a great deal of probability. For us to practice better medicine and perform superior research, we must all accept this fact.

    • There is no end to science; it is an evolutionary discipline. The best we can do at any moment is be familiar with the totality of the literature and practice medicine based upon its trends as well as our knowledge of human physiology and hard-won clinical experience.

    • In this process, let us be forever vigilant not to slay the intuitive provider.

    Clin. Cardiol. 35, 5, 259–260 (2012)


    Review of the new 2013 acc aha guidelines on lipid management k athleen dively np associates in cardiology clinical lipid specialist fnla

    Parachutes reduce the risk of injury after gravitational challenge, but their effectiveness has not been proved with randomizedcontrolled trials

    In fact our search strategy did not find any randomised controlled trials of the parachute

    We think that everyone might benefit if the most radical protagonists of evidence based medicine organized and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute

    Gordon C S Smith, Jill P Pell BMJ 2003;327:1459–61


    Future updates needed

    Future updates needed

    • 1. Treatment of high triglycerides.

    • 2. Whether on-treatment markers such as apoB, Lp(a), LDL-particles are useful in guiding decisions.

    • 3. Optimal age for starting treatment for reducing lifetime risk of ASCVD.

    • 4. Tx options for ptswith HF, hemodialysis. 5. Long term effects of statin associated new onset diabetes in our patients


    Questions kathleen@dively org www lecturepad org dr thomas dayspring

    [email protected] Thomas Dayspring


  • Login