ada & acc consensus statement lipoprotein management in patients with cardiometabolic risk...

ADA & ACC Consensus Statement ADA & ACC Consensus Statement Lipoprotein Management in Patients Lipoprotein Management in Patients

with Cardiometabolic Riskwith Cardiometabolic Risk

Thomas Dayspring, MD, FACPThomas Dayspring, MD, FACPClinical Assistant Professor of MedicineClinical Assistant Professor of Medicine

University of Medicine and Dentistry of New Jersey University of Medicine and Dentistry of New Jersey New Jersey Medical School New Jersey Medical School

Attending in Medicine: St Joseph’s Regional Medical Center, Attending in Medicine: St Joseph’s Regional Medical Center, Paterson and Wayne, NJPaterson and Wayne, NJ

Diplomate: American Board of Clinical Lipidology Diplomate: American Board of Clinical Lipidology Certified Menopause Clinician: Certified Menopause Clinician: North American Menopause SocietyNorth American Menopause Society

North Jersey Institute of Menopausal Lipidology Wayne, New JerseyNorth Jersey Institute of Menopausal Lipidology Wayne, New Jersey

ADA and ACC Consensus Statement ADA and ACC Consensus Statement on Lipoprotein Management on Lipoprotein Management

Lipoproteins are the particles composed of cholesterol, Lipoproteins are the particles composed of cholesterol, triglycerides, phospholipids and apolipoproteins and they triglycerides, phospholipids and apolipoproteins and they interact with the artery wall and set off the atherosclerotic interact with the artery wall and set off the atherosclerotic cascadecascade

Within each category of lipoproteins, Within each category of lipoproteins, the size, density and the size, density and lipid composition varylipid composition vary

Atherosclerosis results from interactions between modified-Atherosclerosis results from interactions between modified-lipoproteins and monocyte-derived macrophages, lipoproteins and monocyte-derived macrophages, components of innate immunity and cellular elements of the components of innate immunity and cellular elements of the arteryartery

There is a curvilinear relationship between increasing There is a curvilinear relationship between increasing plasma cholesterol and incidence of CVDplasma cholesterol and incidence of CVD

Measurements of cholesterol are indirect estimates of Measurements of cholesterol are indirect estimates of lipoproteins transporting cholesterollipoproteins transporting cholesterol

Brunzell JD, Davidson M, Furberg CD et al. Diabetes Care 2008;31:811-822



Cardiometabolic Risk Cardiometabolic Risk Global Diabetes/CVD RiskGlobal Diabetes/CVD Risk

Overweight/ObesityOverweight/Obesity

Insulin ResistanceInsulin Resistance

GeneticsGenetics AgeAge

Insulin Resistance Insulin Resistance SyndromeSyndrome

LipidsLipids BPBP GlucoseGlucose

Smoking, Smoking, Physical Inactivity, Physical Inactivity, Unhealthy EatingUnhealthy Eating

HypertensionHypertension Inflammation, Inflammation, HypercoagulationHypercoagulation

Age, Race, Gender, Age, Race, Gender, Family HistoryFamily History

Abnormal Lipid MetabolismAbnormal Lipid Metabolism

• LDLLDL

• ApoBApoB

• HDLHDL

• TriglyceridesTriglycerides

??


A plasma level of 25 mg/dL is sufficient to supply peripheral A plasma level of 25 mg/dL is sufficient to supply peripheral cholesterol needscholesterol needs

Individuals with genetic mutations causing low LDL-C avoid Individuals with genetic mutations causing low LDL-C avoid CVD and are free of other abnormalities that might CVD and are free of other abnormalities that might conceivably be linked to very low cholesterol levelsconceivably be linked to very low cholesterol levels

The dyslipoproteinemia of insulin resistance is The dyslipoproteinemia of insulin resistance is characterized by elevated VLDL, lower HDL-C and altered characterized by elevated VLDL, lower HDL-C and altered distributions of all lipoprotein classesdistributions of all lipoprotein classes• Increased VLDL production and decreased clearance causing Increased VLDL production and decreased clearance causing

increased levels of large and intermediate VLDL particlesincreased levels of large and intermediate VLDL particles

• Increased numbers of small, dense LDL particles which are easily Increased numbers of small, dense LDL particles which are easily oxidized, glycated and able to bond to intimal proteoglycansoxidized, glycated and able to bond to intimal proteoglycans



Despite the usefulness of LDL-C for CVD prediction on a Despite the usefulness of LDL-C for CVD prediction on a population level, the measure has limitations for individual population level, the measure has limitations for individual risk assessmentrisk assessment

LDL-C is estimated using the Friedewald Equation, but this LDL-C is estimated using the Friedewald Equation, but this underestimates LDL-C as TG levels increaseunderestimates LDL-C as TG levels increase• LDL-C = TC – [HDL-C + VLDL-C) VLDL-C = TG/5LDL-C = TC – [HDL-C + VLDL-C) VLDL-C = TG/5

However, However, the cholesterol content of LDL particles varies the cholesterol content of LDL particles varies from person to person from person to person and is influenced by insulin and is influenced by insulin resistance and hyperglycemiaresistance and hyperglycemia


Hence, LDL-C may not accurately Hence, LDL-C may not accurately represent atherogenic burden in those represent atherogenic burden in those

with cardiometabolic riskwith cardiometabolic risk


A more accurate way to capture may be to A more accurate way to capture may be to measure LDL measure LDL particles directlyparticles directly using Nuclear Magnetic Resonance (NMR) using Nuclear Magnetic Resonance (NMR)

Cross-sectional and prospective studies show LDL-P is a Cross-sectional and prospective studies show LDL-P is a better discriminator of risk than is LDL-Cbetter discriminator of risk than is LDL-C

• MESA (Multiethnic Study of Atherosclerosis)MESA (Multiethnic Study of Atherosclerosis)• PLAC-1 (Pravastatin Limitation of Atherosclerosis in Coronary Arteries)PLAC-1 (Pravastatin Limitation of Atherosclerosis in Coronary Arteries)• WHS (Women’s Health Study)WHS (Women’s Health Study)• VA-HIT (Veteran’s Affairs HDL Intervention Trial)VA-HIT (Veteran’s Affairs HDL Intervention Trial)• EPIC-Norfolk Population StudyEPIC-Norfolk Population Study• Framingham Offspring StudyFramingham Offspring Study

LDL size can also be measured. The association of small LDL LDL size can also be measured. The association of small LDL and CVD may simply reflect the increased numbers of LDL and CVD may simply reflect the increased numbers of LDL particles in patients with small LDL. particles in patients with small LDL.

Hence it is unclear whether Hence it is unclear whether LDL size adds value to LDL size adds value to measurement of LDL-Pmeasurement of LDL-P



There is little evidence the insulin resistance or diabetes There is little evidence the insulin resistance or diabetes influences Lp(a) concentrations.influences Lp(a) concentrations.

The utility of routine measurement of Lp(a) is unclearThe utility of routine measurement of Lp(a) is unclear More aggressive control of other lipoprotein parameters More aggressive control of other lipoprotein parameters

may be warranted in those with high concentrations of Lp(a)may be warranted in those with high concentrations of Lp(a)


Lipoprotein (a)Lipoprotein (a)


Non HDL-C reflects the concentration of cholesterol within Non HDL-C reflects the concentration of cholesterol within lipoproteins considered atherogenic and adds no expense lipoproteins considered atherogenic and adds no expense and can be calculated from nonfasting specimensand can be calculated from nonfasting specimens

Non-HDL-C = TC – HDL-C or VLDL-C + LDL-CNon-HDL-C = TC – HDL-C or VLDL-C + LDL-C Many studies have demonstrated non-HDL-C is a better Many studies have demonstrated non-HDL-C is a better

predictor of risk than is LDL-Cpredictor of risk than is LDL-C• STRONG Heart StudySTRONG Heart Study

• Physicians Health StudyPhysicians Health Study

• Framingham Cohort and Offspring StudiesFramingham Cohort and Offspring Studies

• Multiple Risk Factor Intervention Trial (Mr FIT )Multiple Risk Factor Intervention Trial (Mr FIT )

• Lipid Research Clinics Prevalence Follow-up Study (LRCF)



Each Chylomicrons, VLDL, IDL, LDL and Lp(a) contains a Each Chylomicrons, VLDL, IDL, LDL and Lp(a) contains a single molecule of apolipoprotein B, making single molecule of apolipoprotein B, making apoB apoB measurement a marker of atherogenic particlesmeasurement a marker of atherogenic particles• Does not require fasting and assay is standardizedDoes not require fasting and assay is standardized

In several epidemiological and post-hoc analyses of clinical In several epidemiological and post-hoc analyses of clinical trials apoB has been a better predictor of risk than LDL-C, trials apoB has been a better predictor of risk than LDL-C, particularly the on-treatment level of LDL-Cparticularly the on-treatment level of LDL-C

Once LDL-C is lowered apoB may be a more effective way to Once LDL-C is lowered apoB may be a more effective way to assess residual CVD risk and to determine the need for assess residual CVD risk and to determine the need for medication adjustmentsmedication adjustments

The The differences between apoB, LDL-C and non-HDL-C are differences between apoB, LDL-C and non-HDL-C are more pronounced in patients with cardiometabolic riskmore pronounced in patients with cardiometabolic risk, , suggesting apoB is a more useful predictor among these suggesting apoB is a more useful predictor among these patientspatients



HDL-C levels are string inverse predictors of CVD events in HDL-C levels are string inverse predictors of CVD events in diabetic and nondiabetic populationsdiabetic and nondiabetic populations

It has been difficult to determine whether raising HDL-C It has been difficult to determine whether raising HDL-C independently reduces CVD events, because all such independently reduces CVD events, because all such interventions also affect concentrations of other lipoproteinsinterventions also affect concentrations of other lipoproteins

Strategies to raise HDL-C remain a promising area of Strategies to raise HDL-C remain a promising area of research that may be particularly valuable in patients with research that may be particularly valuable in patients with cardiometabolic riskcardiometabolic risk

Measurements of HDL subfractions or apoA-I appear to Measurements of HDL subfractions or apoA-I appear to provide little clinical value beyond HDL-Cprovide little clinical value beyond HDL-C



In the fasting state most TG are found in VLDL, so plasma In the fasting state most TG are found in VLDL, so plasma TG are used as a surrogate measure of VLDLTG are used as a surrogate measure of VLDL

TG are a univariate predictor of CVD in many studies but TG are a univariate predictor of CVD in many studies but often not an independent predictor in multivariate analysesoften not an independent predictor in multivariate analyses• This is because TG are linked to HDL and LDL abnormalitiesThis is because TG are linked to HDL and LDL abnormalities

• There are no clinical trial data establishing that lowering TG in There are no clinical trial data establishing that lowering TG in individuals with or without diabetes independently leads to lower individuals with or without diabetes independently leads to lower CVD event rates when one adjusts for HDL-CCVD event rates when one adjusts for HDL-C

Chylomicron remnants may be atherogenic in a manner Chylomicron remnants may be atherogenic in a manner similar to VLDL remnants, but there is little population similar to VLDL remnants, but there is little population based evidence liking chylomicron remnants based evidence liking chylomicron remnants (measurements of which are not available) to CVD(measurements of which are not available) to CVD



HDL-C levels are strong inverse predictors of CVD events HDL-C levels are strong inverse predictors of CVD events in diabetic and nondiabetic populationsin diabetic and nondiabetic populations

It has been difficult to determine whether raising HDL-C It has been difficult to determine whether raising HDL-C independently reduces CVD eventsindependently reduces CVD events, because all such , because all such interventions also affect concentrations of other lipoproteinsinterventions also affect concentrations of other lipoproteins

Strategies to raise HDL-C Strategies to raise HDL-C remain a promising area of remain a promising area of researchresearch that may be particularly valuable in patients with that may be particularly valuable in patients with cardiometabolic riskcardiometabolic risk

Measurements of HDL subfractions or apoA-I appear to Measurements of HDL subfractions or apoA-I appear to provide little clinical value beyond HDL-Cprovide little clinical value beyond HDL-C



Good clinical practice calls for a comprehensive evaluation of Good clinical practice calls for a comprehensive evaluation of current vascular health, factors related to dyslipoproteinemia and current vascular health, factors related to dyslipoproteinemia and other factors affecting global riskother factors affecting global risk• Determine to the extent possible magnitude of future riskDetermine to the extent possible magnitude of future risk• Identify modifiable prognostic risk factorsIdentify modifiable prognostic risk factors• Establish a treatment plan in terms of scope and intensityEstablish a treatment plan in terms of scope and intensity

Subclinical disease may be determined bySubclinical disease may be determined by• Coronary CalcificationCoronary Calcification• Carotid intima-media thicknessCarotid intima-media thickness• Ankle-brachial indexAnkle-brachial index

Other metabolic risk factors include BP, smoking, hyperglycemia, Other metabolic risk factors include BP, smoking, hyperglycemia, diet, inactivity, chronic renal diseasediet, inactivity, chronic renal disease

Family history of premature CAD in siblings is a powerful risk Family history of premature CAD in siblings is a powerful risk predictorpredictor



The independent predictive power and clinical utility of The independent predictive power and clinical utility of C-reactive protein, fibrinogen and homocysteine are still C-reactive protein, fibrinogen and homocysteine are still unclear.unclear.

CRP is often elevated in patients with cardiometabolic risk, CRP is often elevated in patients with cardiometabolic risk, but utility of its measurement in people already known to be but utility of its measurement in people already known to be at risk is unknownat risk is unknown


Other markersOther markers


Dyslipoproteinemia implies the presence of increased Dyslipoproteinemia implies the presence of increased number of atherogenic lipoproteins and/or a reduced number of atherogenic lipoproteins and/or a reduced protective capacity of HDL beyond what is considered protective capacity of HDL beyond what is considered optimaloptimal• It is present when triglycerides are high, HDL-C is low, and/or there It is present when triglycerides are high, HDL-C is low, and/or there

is atherogenic particle excess (such as high LDL-C or small LDL-P)is atherogenic particle excess (such as high LDL-C or small LDL-P)

Lifestyle and pharmacologic therapy should be started Lifestyle and pharmacologic therapy should be started concurrently concurrently in subjects with CVD and those with diabetes in subjects with CVD and those with diabetes and multiple CVD risk factors regardless of baseline LDL-Cand multiple CVD risk factors regardless of baseline LDL-C

Pharmacologic therapy is recommended for moderately Pharmacologic therapy is recommended for moderately high-risk primary prevention patients if LDL-C remains high-risk primary prevention patients if LDL-C remains > 100 after several months of lifestyle changes > 100 after several months of lifestyle changes



For patients who cannot tolerate a statin or the maximum For patients who cannot tolerate a statin or the maximum statin therapy does not achieve treatment goals, other statin therapy does not achieve treatment goals, other LDL-C lowering drugs include ezetimibe, bile-acid LDL-C lowering drugs include ezetimibe, bile-acid sequestrants or niacin. Each of these drugs enhance the sequestrants or niacin. Each of these drugs enhance the LDL-C lowering of statins.LDL-C lowering of statins.• BAS or niacin with statins selectively decrease small LDL particlesBAS or niacin with statins selectively decrease small LDL particles

• BAS used alone can aggravate TGBAS used alone can aggravate TG

NCEP-ATP III established NCEP-ATP III established Non-HDL-CNon-HDL-C as a secondary as a secondary target in those with hypertriglyceridemia or metabolic target in those with hypertriglyceridemia or metabolic syndrome but the use of this measure has not been widely syndrome but the use of this measure has not been widely adoptedadopted

Both LDL-C and Non HDL-C Both LDL-C and Non HDL-C focus on cholesterol which is focus on cholesterol which is only a surrogate given that atherosclerosis is mediated by only a surrogate given that atherosclerosis is mediated by lipoproteinslipoproteins



Measurement of apoB or LDL-P by NMR may more closely Measurement of apoB or LDL-P by NMR may more closely quantitate the atherogenic lipoprotein loadquantitate the atherogenic lipoprotein load

Studies suggest that both are better indices than LDL-C or Studies suggest that both are better indices than LDL-C or non-HDL-C and more reliable indexes of on-treatment non-HDL-C and more reliable indexes of on-treatment residual riskresidual risk• PLAC-1, WHS, AFCAPS-Tex-CAPS, AMORIS, INTER-HEART, PLAC-1, WHS, AFCAPS-Tex-CAPS, AMORIS, INTER-HEART,

4S, LIPID4S, LIPID

Statins lower non-HDL-C more than they lower apoB and Statins lower non-HDL-C more than they lower apoB and several studies show reaching apoB target usually requires several studies show reaching apoB target usually requires more intensive therapy than achieving the equivalent level more intensive therapy than achieving the equivalent level for non-HDL-Cfor non-HDL-C

ApoB and LDL-P appear to be more closely associated with ApoB and LDL-P appear to be more closely associated with cardiometabolic risk factors than LDL-Ccardiometabolic risk factors than LDL-C



When both non-HDL-C and apoB are measured, the two When both non-HDL-C and apoB are measured, the two are highly correlated, but only moderately concordantare highly correlated, but only moderately concordant

At any given level of non-HDL-C there will be wide At any given level of non-HDL-C there will be wide variations of apoB levels and vice versa indicat9ing the variations of apoB levels and vice versa indicat9ing the correlation is of limited value for assessing individual riskcorrelation is of limited value for assessing individual risk• This lack of concordance is particularly marked in patients with This lack of concordance is particularly marked in patients with

elevated triglyceride levelselevated triglyceride levels

The panel concludes that The panel concludes that routine use of non-HDL-C routine use of non-HDL-C constitute a better index than LDL-C for identifying high constitute a better index than LDL-C for identifying high risk patientsrisk patients



LDL-C should not be abandonedLDL-C should not be abandoned• Many years of public and professional education geared towards Many years of public and professional education geared towards

LDL-C has resulted in its successful integration into the fabric of LDL-C has resulted in its successful integration into the fabric of CVD prevention and treatmentCVD prevention and treatment

Non HDL-C should be provided on all laboratory reports Non HDL-C should be provided on all laboratory reports and should also be used to ascertain risk in patients with and should also be used to ascertain risk in patients with low to moderate LDL-C levels (i.e., LDL-C < 130 mg/dL)low to moderate LDL-C levels (i.e., LDL-C < 130 mg/dL)

Measurement of apoB is warranted in patients with Measurement of apoB is warranted in patients with cardiometabolic risk on pharmacologic treatmentcardiometabolic risk on pharmacologic treatment

In particular apoB should be used to guide adjustments to In particular apoB should be used to guide adjustments to therapytherapy

LDL-P as measured by NMR appears equally informative LDL-P as measured by NMR appears equally informative as apoBas apoB



Measurement of apoB is warranted in patients with Measurement of apoB is warranted in patients with cardiometabolic risk on pharmacologic treatmentcardiometabolic risk on pharmacologic treatment

In particular apoB should be used to guide adjustments to In particular apoB should be used to guide adjustments to therapytherapy

LDL-P as measured by NMR appears equally informative LDL-P as measured by NMR appears equally informative as apoBas apoB

The panel recommends that the apoB goal be reachedThe panel recommends that the apoB goal be reached


Particle QuantificationParticle Quantification



Highest-risk patientsHighest-risk patients, including , including those with 1) known CVD or those with 1) known CVD or 2) Diabetes plus one or more 2) Diabetes plus one or more additional CVD risk factoradditional CVD risk factor

High-risk patientsHigh-risk patients, including , including those with 1) no diabetes or those with 1) no diabetes or known clinical CVD but 2 or known clinical CVD but 2 or more additional major CVD more additional major CVD risk factors or 2) Diabetes but risk factors or 2) Diabetes but no other CVD risk factorsno other CVD risk factors

LDL-C LDL-C (mg/dL)(mg/dL)

Non-HDL-C Non-HDL-C (mg/dL)(mg/dL)

ApoB ApoB (mg/dL)(mg/dL)

< 70 < 100 < 80< 70 < 100 < 80

< 100 < 130 < 90< 100 < 130 < 90

TREATMENT GOALSTREATMENT GOALS

Highest-risk patientsHighest-risk patients

• known CVD or known CVD or

• CMR plus one or CMR plus one or more additional more additional CVD risk factorCVD risk factor

High-risk patientsHigh-risk patients

• no CMR or known no CMR or known clinical CVD but 2 clinical CVD but 2 or more additional or more additional major CVD risk major CVD risk factors factors

• CMR but no other CMR but no other CVD risk factorsCVD risk factors

< 70 < 100 < 70 < 100 < 80 < 1000< 80 < 1000

< 100 < 130 < 100 < 130 < 90 < 1300< 90 < 1300

TREATMENT GOALS: LDL-C non-HDL-C TREATMENT GOALS: LDL-C non-HDL-C ApoB LDL-PApoB LDL-P


Elevations of TG and reduced HDL-C are the most common Elevations of TG and reduced HDL-C are the most common abnormalities of the standard lipid panel in subjects with abnormalities of the standard lipid panel in subjects with obesity and insulin resistance-related cardiometabolic riskobesity and insulin resistance-related cardiometabolic risk

It has been difficult to demonstrate that lowering TG is It has been difficult to demonstrate that lowering TG is independently associated with a reduction in CVD eventsindependently associated with a reduction in CVD events

Clinical trial evidence supporting treatment of low HDL-C is Clinical trial evidence supporting treatment of low HDL-C is modest compared with that for LDL-C loweringmodest compared with that for LDL-C lowering

For these reasons NCEP ATP-III recommended non HDL-C For these reasons NCEP ATP-III recommended non HDL-C as a secondary target of treatment with a goal 30 mg/dL as a secondary target of treatment with a goal 30 mg/dL > than the LDL-C goal> than the LDL-C goal

The panel recommends that the apoB goal be reachedThe panel recommends that the apoB goal be reached



The exception to not targeting TG is the relatively small The exception to not targeting TG is the relatively small proportion of patients with severe hypertriglyceridemia in proportion of patients with severe hypertriglyceridemia in whom the initial treatment priority is to reduce the risk of whom the initial treatment priority is to reduce the risk of pancreatitis by combining fat restriction with fibrate, niacin pancreatitis by combining fat restriction with fibrate, niacin or high-dose n-3 FA therapyor high-dose n-3 FA therapy

A statin is the initial drug of choice A statin is the initial drug of choice for the vast majority of for the vast majority of people with cardiometabolic riskpeople with cardiometabolic risk who have high TG who have high TG and low HDL-Cand low HDL-C

In patients on statins who continue to have low HDL-C or In patients on statins who continue to have low HDL-C or elevated non-HDL-C, elevated non-HDL-C, especially if apoB remains elevatedespecially if apoB remains elevated, , combination therapy is recommendedcombination therapy is recommended



The preferred agent to use in combination with a statin is The preferred agent to use in combination with a statin is niacinniacin because there is somewhat better evidence for because there is somewhat better evidence for reduction in CVD events with niacin than there is for fibratesreduction in CVD events with niacin than there is for fibrates

Fibrates have been shown to reduce CVD events in some Fibrates have been shown to reduce CVD events in some studies but not mortalitystudies but not mortality

N-3 fatty acid therapy lowers TG levels at high doses (≥ 4 N-3 fatty acid therapy lowers TG levels at high doses (≥ 4 grams/day) and may be another option to consider to lower grams/day) and may be another option to consider to lower non HDL-C in patients on statin therapy, but CVD outcome non HDL-C in patients on statin therapy, but CVD outcome data are lacking for hypertriglyceridemic patientsdata are lacking for hypertriglyceridemic patients

In diabetic patients, enhanced glycemic control may In diabetic patients, enhanced glycemic control may improve lipid and lipoprotein abnormalities, particularly improve lipid and lipoprotein abnormalities, particularly hypertriglyceridemiahypertriglyceridemia



Niacin decreased CVD in the Coronary Drug Project and Niacin decreased CVD in the Coronary Drug Project and total mortality in an extended follow uptotal mortality in an extended follow up

Niacin in combination with bile-acid sequestrants was Niacin in combination with bile-acid sequestrants was associated with regression of atherosclerosis and CVD associated with regression of atherosclerosis and CVD events in several studiesevents in several studies• FATS, HATS, ARBITER 2, CLASFATS, HATS, ARBITER 2, CLAS

Although niacin has been associated with insulin resistance, Although niacin has been associated with insulin resistance, in diabetes the use of low dose niacin (1500 mg/day) does in diabetes the use of low dose niacin (1500 mg/day) does not significantly increase A1C levelsnot significantly increase A1C levels



In observational studies, In observational studies, low HDL-C is a powerful predictor low HDL-C is a powerful predictor of risk for CVD and remains a risk factor even in patients of risk for CVD and remains a risk factor even in patients with low HDL-Cwith low HDL-C

Because a recent trial with a CETP inhibitor to raise HDL-C Because a recent trial with a CETP inhibitor to raise HDL-C was terminated because of excess CV risk, was terminated because of excess CV risk, it remains it remains unclear if raising HDL-C per se reduces CV riskunclear if raising HDL-C per se reduces CV risk

It may be that by increasing HDL-C by modifying the It may be that by increasing HDL-C by modifying the reverse cholesterol pathway reverse cholesterol pathway may paradoxically increase may paradoxically increase CV riskCV risk, while other mechanisms to increase HDL-C may , while other mechanisms to increase HDL-C may lead to a reduction in risklead to a reduction in risk



Monotherapy with statins, fibrates, niacin and bile acid Monotherapy with statins, fibrates, niacin and bile acid sequestrants have been shown to reduce CV events in sequestrants have been shown to reduce CV events in clinical trials but there is not yet robust evidence for clinical trials but there is not yet robust evidence for incremental benefits or risks of combination therapy incremental benefits or risks of combination therapy compared with those of monotherapycompared with those of monotherapy

Results of on-going and future trials of statin-niacin, statin-Results of on-going and future trials of statin-niacin, statin-fibrate, and statin-n-e fatty acids will answer these fibrate, and statin-n-e fatty acids will answer these questionsquestions

Although statin therapy is highly effective in reducing CVD Although statin therapy is highly effective in reducing CVD risk in primary and secondary prevention, there remain risk in primary and secondary prevention, there remain subsets of patients regarding whom more data are neededsubsets of patients regarding whom more data are needed• These include elderly, chronic kidney disease and young patients These include elderly, chronic kidney disease and young patients

with cardiometabolic riskwith cardiometabolic risk



Patients with cardiometabolic (CMR) risk factors have a Patients with cardiometabolic (CMR) risk factors have a high lifetime risk for CVD. high lifetime risk for CVD.

• They have low HDL-C, increased TG and/or increased They have low HDL-C, increased TG and/or increased numbers of small LDL particlesnumbers of small LDL particles

The panel recommends for patients with CMR riskThe panel recommends for patients with CMR risk

• Statin therapy for the majorityStatin therapy for the majority

• Guide therapy with measurements of apoB and treat Guide therapy with measurements of apoB and treat to apoB goalto apoB goal


SUMMARY SLIDESSUMMARY SLIDES

ADA and ACC Consensus Statement ADA and ACC Consensus Statement In Patients with Cardiometabolic Risk In Patients with Cardiometabolic Risk

Lipoprotein abnormalities are common findings in patients with CMR. Measurement of LDL cholesterol may not accurately reflect the true burden of atherogenic LDL particles, especially in those with typical lipoprotein abnormalities of CMR.

Even with adequate LDL cholesterol lowering, many patients on statin therapy have significant residual CVD risk. Treatment targets and the best approach for CVD risk reduction in this population need to be better defined.

Some have advocated that assessment of other lipoprotein parameters might be more helpful than assessment limited to LDL-C or non-HDL cholesterol in these populations.


SummarySummary


A more accurate way to capture the risk posed by LDL may be to measure the number of LDL particles directly using nuclear magnetic resonance (NMR)

“Many cross-sectional and prospective studies show that LDL particle number is a better discriminator of risk than is LDL cholesterol.”

Measurements of apoB or LDL particle number by NMR may more closely quantitate the atherogenic lipoprotein load.

Some studies suggest that both are better indices of CVD risk than LDL cholesterol or non-HDL cholesterol and more reliable indexes of on-treatment residual CVD risk.


SummarySummary


ApoB and LDL particle number also appear to be more discriminating measures of the adequacy of LDL lowering therapy than are LDL cholesterol or non-HDL cholesterol.”

ApoB and LDL particle concentration also appear to be more closely associated with obesity, diabetes, insulin resistance, and other markers of CMR than LDL cholesterol or non-HDL cholesterol.”


SummarySummary

LIPOSCIENCE PRESS RELEASELIPOSCIENCE PRESS RELEASE

Quantitating Lipoprotein ParticlesQuantitating Lipoprotein Particles

Cardiometabolic Risk (CMR) is associated with Type 2 Diabetes and CVD – obesity, insulin resistance, hyperglycemia and hypertension are risk factors that often cluster together.

ApoB and LDL particle concentration appear to be more closely associated with these markers of CMR than LDL cholesterol or non-HDL cholesterol. • Subsequently, lipoprotein abnormalities are commonly found in

patients with CMR.

According to the consensus statement, ApoB and LDL particle number by NMR appear to be more discriminating measures of the adequacy of LDL lowering therapies than are traditional LDL and HDL cholesterol measures.


The American Diabetes Association (ADA) and the American College of Cardiology (ACC) issued a consensus statement today that states the measurement of LDL particle number by nuclear magnetic resonance (NMR) is one of the more accurate ways to evaluate cardiometabolic risk (CMR).

The study, published in the April issue of Diabetes Care 2008;31:811-822, reinforces that LDL cholesterol may not be the best way to quantify a patient’s risk for cardiovascular disease (CVD).


The NMR LipoProfile® test, developed by LipoScience, Inc., is the only test that quantifies LDL particle number (LDL-P) using Nuclear Magnetic Resonance.

LDL particle information is used by clinicians to monitor the effect of lipid altering interventions, such as statins, in the management of a patient’s cardiovascular health by lowering LDL particle number (LDL-P).

ada & acc consensus statement lipoprotein management in patients with cardiometabolic risk...

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