Morbidity and Mortality Associated with Dyslipidemia
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Transcript of Morbidity and Mortality Associated with Dyslipidemia
By: David Tran, Mercer University, 2013 Pharm.D. CandidatePrececptor: Dr. Ali Rahimi
Morbidity and Mortality Associated with Dyslipidemia
DyslipidemiaAn imbalance of any or all lipid
concentrations in the plasma, including hyperlipidemia, hypertriglyceridemia, and hypercholesterolemia
Puts you at risk of developing heart disease which is the leading cause of death in the United States (~620,000 deaths in 2008)
People of all ages and backgrounds can have high cholesterol
CDC Statistics71 million American adults (33.5%) have high LDL1 out of every 3 adults with high LDL cholesterol
has the condition under controlLess than half of adults with high LDL cholesterol
get treatmentPeople with high total cholesterol have
approximately twice the risk of heart disease as people with optimal levels. A desirable level is lower than 200 mg/dL
The average total cholesterol level for adult Americans is about 200 mg/dL, which is borderline high risk
Hyperlipidemia by Ethnicity (LDL >130 mg/dL)
Race or Ethnic Background
Men (%) Women (%)
Non-hispanic Blacks
34.4 27.7
Mexican Americans
41.9 31.6
Non-hispanic Whites
30.5 32.0
All 32.5 31.0
Lipid GoalsTotal Cholesterol
LDL Triglycerides
HDL
•Desirable <200 mg/dL
•Borderline high200 – 239 mg/dL
• High>240 mg/dL
•Optimal
<100 mg/dL
•Near optimal 100 – 129 mg/dL
• Borderline high130 – 159 mg/dL
• High>160 mg/dL
•Normal <150 mg/dL
•Borderline high150 – 199 mg/dL
•High200 – 499 mg/dL
•Very high>500 mg/dL
•Low<40 mg/dL
•High>60 mg/dL
NCEP/ATP III Recommendations Recommend all adults ≥ 20 years old have
a fasting lipid panel obtained every 5 years
LDL is the primary target
TG should be targeted first if TG are >500 mg/dL
Once LDL goal is achieved, attention should be focused on other parameters (non-HDL cholesterol)
Risk Factors
Age: male >45; female >55Family history: premature CHD in 1st degree
relativeMale <55; female <65
Current cigarette smokingHTN (>140/90 mmHg or on antihypertensive
medications)Low HDL (<40 mg/dL)Abdominal obesity
CHD and CHD Risk EquivalentsEstablished CHDMyocardial ischemiaMICoronary angioplasty
and/or stent placement
CABGPrior unstable angina
CHD Risk EquivalentsCAD
Stroke historyTIACarotid stenosis >50%
Peripheral Artery Disease
Abdominal Aortic Aneurysm
Diabetes Mellitus
Dyslipidemia and Coronary Risk
Continuous, graded relationship between serum total plasma cholesterol concentration and coronary risk
Meta-analysis of 38 primary and secondary prevention trials found that for every 10% reduction in serum cholesterol, CHD mortality would be reduced by 15% and total mortality risk by 11%
High LDL levels associated with an increased incidence of CHD in a large number of studies
Framingham Heart Study found that the risk of myocardial infarction increases by about 25% for every 5 mg/dL decrement below median values
Meta-analysis of prospective population-based studies evaluating the association between serum triglyceride concentration and incidence of cardiovascular disease showed significant risk ratios
Lipid Research Clinics Program found that differences of 30 mg/dL in non-HDL corresponded to 19% and 11% increases in mortality in men and women, respectively
LDL Target GoalsCategory LDL goal LDL goal to
initiate TLCLDL goal to consider drug therapy
CHD or CHD risk equivalents (10 year risk >20%)
<100 mg/dL >100 mg/dL >130 mg/dL
2 or more risk factors (10 year risk 10-20%)
<130 mg/dL >130 mg/dL >130 mg/dL
2 or more risk factors (10 year risk <10%)
<130 mg/dL >130 mg/dL >160 mg/dL
0-1 risk factors <160 mg/dL >160 mg/dL >190 mg/dL
Lipid Synthesis
Lipid Components
LipoproteinsApo-B48 is required for the formation of the
chylomicron and secretion for general circulation
Apo-B100 is required for VLDL assemblyLipoprotein lipase (LPL)- forms free fatty acids
that can be used for energy in the periphery. Also, responsible for the formation of remnants which is taken up by the liver for breakdown into cholesterol
Apo-C2 is responsible for activating LPLApo-E binds to LDL-related protein receptors for
lipids to be taken up into the liver to be broken down into cholesterol and phospholipids
Apolipoprotein BActs as a ligand for LDL receptors in various
cells throughout the body to deliver cholesterolHigh levels of ApoB can lead to plaques that
cause atherosclerosis which can thereby lead to heart disease
ApoB is a marker for CHD riskThe AMORIS study found that measurement of
ApoB improved the prediction of fatal MI at all levels of total cholesterol, LDL, and triglycerides
In multivariate analysis, the concentration of ApoB was more highly significant than LDL in determining outcomes and added predictive power to LDL cholesterol
Apolipoprotein EServes as a transporter of lipoproteins, fat-
soluble vitamins, and cholesterol Variant alleles of ApoE are genetic risk
factors for Alzheimer diseaseDefects in ApoE result in familial
hyperlipidemia which is characterized by increased plasma cholesterol and triglycerides
Cardiovascular biomarker with a positive dose-response association with ischemic stroke
Heart Protection Study
Randomized, placebo-controlled trial of effects of simvastatin and antioxidant vitamins on morbidity and mortality
>20,536 men and women 40–80 yr at increased risk of CHD due to prior disease with total cholesterol >135 mg/dL
Simvastatin 40 mg daily vs placeboDuration of greater than 5 years
Heart Protection StudyPrimary endpoint
The effect of simvastatin on total and cause-specific mortality
Secondary endpointsTreatment effect on CHD morbidity and
mortality in special patient populationsTreatment effect on incidence of cancer,
strokes, major vascular procedures, and other conditions requiring hospitalization
Treatment effect on cause-specific mortality and cancers during longer-term follow-up
Heart Protection Study: Vascular Events by Baseline Disease
Baseline Disease
Simvastatin 40 mg daily (n= 10269)
Placebo (n= 10267)
Previous MI 999 (23.5%) 1250 (29.4%)
Other CHD (non-MI)
460 (18.9%) 591 (24.2%)
No prior CHD•CVD•PVD•Diabetes
574 (16.1%) 172 (18.7%) 327 (24.7%) 276 (13.8%)
744 (20.8%) 212 (23.6%) 420 (30.5%) 367 (18.6%)
All patients 2033 (19.8%) 2585 (25.2%)
Heart Protection Study: Vascular Event by LDL
LDL (mg/dL) Simvastatin 40 mg daily (n=10269)
Placebo (n= 10267)
<100 285 360
100-130 670 881
>130 1087 1365
All patients 2033 2585
References CDC.
Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol. United States, 1999–2002 and 2005–2008. MMWR. 2011;60(4):109–14.
Khan et al. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals. International Journal of Epidemiology. 2013 Apr;42(2):475-492.
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002 Jul 6;360(9326):7-22.
National Institute of Health. Morbidity and Mortality: 2012 Chart Book on Cardiovascular, Lung, and Blood Diseases. Online. 4/16/2013. http://www.nhlbi.nih.gov/resources/docs/2012_ChartBook.pdf
Pereira, Telmo. Dyslipidemia- From Prevention to Treatment: Dyslipidemia and Cardiovascular Risk: Lipid Ratios as Risk Factors for Cardiovascular Disease. Pgs 279-298.
Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–220.
Uptodate. Screening Guidelines for Dyslipidemia. Online. 4/10/2013. http://www.uptodate.com/contents/screening-guidelines-for-dyslipidemia?topidKey=PC%