Morbidity and Mortality Associated
with Dyslipidemia
By: David Tran, Mercer University, 2013 Pharm.D.
Candidate
Prececptor: Dr. Ali Rahimi
Dyslipidemia
 An 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 Statistics
 71 million American adults (33.5%) have high LDL
 1 out of every 3 adults with high LDL cholesterol has the
condition under control
 Less than half of adults with high LDL cholesterol get
treatment
 People 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 Goals
Total
LDL
Cholesterol
•Desirable
<200 mg/dL
•Borderline
high
200 – 239
mg/dL
• High
>240 mg/dL
Triglycerid HDL
es
•Optimal
•Normal
<100 <150 mg/dL
mg/dL
•Borderline
•Near optimal
high
100 – 129
150 – 199
mg/dL
mg/dL
• Borderline
high
•High
130 – 159
200 – 499
mg/dL
mg/dL
• High
>160 mg/dL
•Very high
•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 >55
 Family history: premature CHD in 1st degree relative
 Male <55; female <65
 Current cigarette smoking
 HTN (>140/90 mmHg or on antihypertensive medications)
 Low HDL (<40 mg/dL)
 Abdominal obesity
CHD and CHD Risk Equivalents
Established CHD
CHD Risk Equivalents
 Myocardial ischemia
 CAD
 Stroke history
 TIA
 Carotid stenosis >50%
 MI
 Coronary angioplasty and/or
stent placement
 CABG
 Prior unstable angina
 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 Goals
Category
LDL goal
LDL goal to
initiate TLC
LDL 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
Lipoproteins
 Apo-B48 is required for the formation of the chylomicron




and secretion for general circulation
Apo-B100 is required for VLDL assembly
Lipoprotein 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 LPL
Apo-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 B
 Acts as a ligand for LDL receptors in various cells throughout




the body to deliver cholesterol
High levels of ApoB can lead to plaques that cause
atherosclerosis which can thereby lead to heart disease
ApoB is a marker for CHD risk
The 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 E
 Serves as a transporter of lipoproteins, fat-soluble vitamins,
and cholesterol
 Variant alleles of ApoE are genetic risk factors for Alzheimer
disease
 Defects 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 placebo
 Duration of greater than 5 years
Heart Protection Study
 Primary endpoint
 The effect of simvastatin on total and cause-specific mortality
 Secondary endpoints
 Treatment effect on CHD morbidity and mortality in special
patient populations
 Treatment 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)
Previous MI
999 (23.5%)
Placebo (n=
10267)
Other CHD (nonMI)
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%)
1250 (29.4%)
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
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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%