Documents
Resources
Learning Center
Upload
Plans & pricing Sign in
Sign Out

Lipid_Management_CE

VIEWS: 6 PAGES: 15

									                           Lipid Management
                                            By
Ryan Wargo, Pharm.D.; PGY1 Pharmacy Practice Resident; Physicians Inc. and Ohio Northern
University. Mike Rush, PharmD; Physicians Inc and Kelly Shields, PharmD; Ohio Northern
University.



Objectives

After completion of this activity, the participant should be able to:

   1.   Review the pathophysiology of cholesterol homeostasis
   2.   Identify traditional cardiac risk factors
   3.   Determine appropriate lipid management goals based on current guidelines
   4.   Recommend appropriate therapy for lipid management based on current guidelines
   5.   Recognize the difference between atherosclerotic indicators other than low-density
        lipoprotein (LDL-C) cholesterol



Introduction

Despite advancement in treatment methods, cardiovascular disease (CVD) remains the leading
cause of death in the United States.1 While debate lingers about the utilization of non-traditional
risk factors and risk markers for cardiovascular disease, appropriate management utilizing the
current standard of care can greatly reduce the risk of CVD. As pharmacists we play a major
role by offering therapeutic recommendations based on current guidelines and appropriate
education about emerging risk markers. To be an effective clinician, it is important to
understand what constitutes a cardiac risk factor and the general pathophysiology of cholesterol
homeostasis. The objective of this article is to establish effective management of dyslipidemia
while assessing future trends in patient care.



Pathophysiology

Effective management of dyslipidemia requires a basic understanding of cholesterol homeostasis
and its pathophysiology. Lipids can be divided into two major subtypes, namely cholesterol
esters and triglycerides and each is transported in complexes known as lipoproteins.
Lipoproteins are spherical particles that vary in size and density. The surface makeup of
lipoproteins consists of phospholipids, free cholesterol, and proteins. The lipoprotein core
consists of lipids, triglycerides and cholesterol.2 While several classes of lipoproteins exist; low-
density (LDL), high-density (HDL), and very-low-density (VLDL) make up the majority in
serum. The density of plasma lipoproteins is a correlation between the protein:lipid ratio, overall
size, and apolipoprotein (Apo) content.

Lipoproteins are transported through the body either exogenously or endogenously. The
exogenous system involves the circulation of chylomicrons (large triglyceride-rich particles)
obtained from the diet or intestinal assembly. Chylomicrons serve as transport for fat and fat-
soluble vitamins into the bloodstream and also function to deliver dietary triglycerides to skeletal
muscle and adipose tissue.2 Once in circulation, chylomicrons are degraded by lipoprotein lipase
(LPL) to chylomicron remnants and are eventually taken up by the liver and further metabolized
to aide in the production of HDL, VLDL, and eventually LDL.

The endogenous system is responsible for the transportation of fatty acids and cholesterol in the
form of VLDL, LDL, and HDL. The largest of the lipoproteins, VLDL, is produced in the liver
and is made primarily of triglyceride (TG). Its main role, once discharged into the bloodstream,
is the release of free fatty acids (FFAs) for energy. Eventually, the particle size of VLDL is
reduced to form cholesterol-rich LDL particles. LDL is the focus of current guidelines for lipid
management as it is a primary contributor to atherogenesis and cardiovascular disease. Its
physiological role is transportation of fat-soluble vitamins into tissue space. Lastly, HDL
contains the greatest concentration of cholesterol and is derived from liver and intestinal
synthesis. Its purpose in the endogenous system is to act as a scavenger in the reverse transport
of cholesterol to the liver.

Current Guidelines

The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel III, or ATP III) presents the National Cholesterol
Education Program’s (NCEP) updated recommendations for cholesterol testing and
management.3 The panel focuses on the prevention of coronary heart disease (CHD) through a
clinical approach and bases its recommendations on evidenced based medicine. Current lipid
management strategies are based on these guidelines.

Targets of Therapy

The basic principle of lipid management is the prevention of cardiovascular disease (CVD). As a
result, current preventative strategies recommend treating patients to specific lipid goals and
focus on low-density (LDL-C) cholesterol as the primary target.3,4 These recommendations are
based on trials demonstrating a strong correlation between reduction in LDL-C and a reduced
risk of CHD.5,6,7,8 It is recommended that LDL-C be lowered to each patient’s predetermined
target goal. Recommended targets are based on the principle of primary versus secondary
prevention. Goals of therapy for primary prevention are LDL-C <160 mg/dL for patients with 0
to 1 risk factors and <130 mg/dL for those with ≥2 risk factors and a Framingham risk score of
<20%.3 Secondary prevention consists of patients with established CVD or who have a
documented CVD risk equivalent such as diabetes mellitus (DM), carotid artery disease (CAD),
peripheral artery disease (PAD), abdominal aortic aneurysm (AAA), or a Framingham risk of
≥20%.3 The recommended goal of therapy for secondary prevention is to maintain an LDL-C
level <100 mg/dL. For patients considered at a very high risk for CVD, such as a patient with
DM and CAD concomitantly, the recommendation is to maintain a LDL-C level <70 mg/dL.3,4

The ATP III update has added non-HDL-C as a secondary target of therapy in patients with
elevated triglycerides.4 Non-HDL-C includes intermediate-density lipoprotein and equates to
VLDL + LDL-C. The goal of therapy for non-HDL-C is 30 mg/dL higher than the LDL-C goal
and was added as a secondary target of therapy to take into account the atherogenic potential
associated with remnant lipoproteins in patients with hypertriglyceridemia.4

Risk Stratification

Since the focus of lipid management is prevention, the intensity of risk-reduction therapy should
be tailored to each patient’s absolute risk of CVD development. As mentioned previously, risk
stratification is based on LDL-C levels and identification of accompanying known cardiac risk
factors or CVD risk equivalents. Known cardiac risk factors that modify the LDL-C goal
include: cigarette smoking, hypertension (BP≥140/90 mmHg or patient use of an
antihypertensive medication), low HDL (<40mg/dL), family history of premature CHD (CHD in
male first degree relative <55 years; CHD in female first degree relative <65 years), and age
(men ≥45 years; women ≥55 years). CVD risk equivalents that modify the LDL-C goal include:
clinical manifestations of non-coronary forms of atherosclerotic disease such as PAD, AAA,
CAD, DM, and ≥2 risk factors with a Framingham risk score >20%.4 Framingham risk
assessment estimates the 10-year risk of developing CHD in adults aged 20 and older who do not
have heart disease or diabetes. Risk assessment is based on age, gender, total cholesterol, HDL
cholesterol, smoking, systolic blood pressure and current use of an antihypertensive medication.

Risk stratification is broken into four categories based on the aforementioned cardiac risk factors
and includes: High, moderately high, moderate, and low risk.4 High risk patients maintain a
Framingham score of >20% and include those with CHD or CVD risk equivalents. Moderately
high risk patients maintain a Framingham score of 10-20% and include those with ≥2 risk
factors. Moderate risk patients maintain a Framingham score of <10% and include those with ≥2
risk factors. Lastly, low risk patients include those with 0 to 1 risk factor.4
Coronary Heart Disease Risk Factors
Cigarette smoking
Hypertension (even if treated)
Diabetes mellitus
History of premature CHD (male first degree relative <55 years; CHD in female first degree
relative <65 years)
Age (men ≥45 years; women ≥55 years)
Low HDL-C (<40mg/dL)
*Compiled from NCEP ATP III guidelines. JAMA 2001;285:2486–2497




Risk Category                              Risk Factors
High risk                                  CHD or CVD risk equivalents (Framingham
                                           score >20%)
Moderately high risk                       ≥2 risk factors (Framingham score 10-20%)
Moderate risk                              ≥2 risk factors (Framingham score <10%)
Lower risk                                 0-1 risk factors
*Compiled from NCEP ATP III guidelines. JAMA 2001;285:2486–2497

Treatment

LDL-C lowering therapy is directed toward either therapeutic lifestyle changes (TLC), drug
therapy, or a combination of both. TLC focuses on diet and emphasizes reduction of saturated
fat and cholesterol. While TLC should be tailored to each individual patient, its fundamental
focus is:3

      Reduced intake of saturated fats and cholesterol
      Dietary options that help reduce LDL-C such as plant stanols/sterols and increased fiber
      Weight reduction
      Increased physical activity

While TLC is an effective initial management strategy for a large portion of the population, it
may be necessary to initiate drug therapy due to inadequate reduction or patients with an
extremely elevated baseline LDL-C. While some cholesterol-lowering agents are available over-
the-counter (OTC), most recommended agents still require a prescription. Of the agents utilized
for lipid lowering the most commonly prescribed include: HMG CoA reductase inhibitors
(statins), bile acid sequestrants, nicotinic acid, and fibric acids. Agents should be tailored to each
patient’s individual lipid profile.
Current guidelines establish cut points for the initiation of TLC and drug therapy based on each
patients’ risk stratification and baseline LDL-C level.3,4 For patients with an LDL-C goal of
<100mg/dL, TLC and drug therapy should be initiated at baseline LDL-C levels of ≥100mg/dL
and ≥130 mg/dL respectively.3,4 Patients with an LDL-C goal of <130mg/dL should initiate TLC
at baseline LDL-C levels of ≥130 mg/dL and should initiate drug therapy at baseline LDL-C
levels of ≥130 mg/dL or ≥160 mg/dL if their Framingham score is 10 to 20% or <10%
respectively. For patients with an LDL-C goal of <160 mg/dL, TLC and drug therapy should be
initiated at baseline LDL-C levels of ≥160mg/dL and ≥190 mg/dL respectively.3

When drug therapy becomes necessary, current guidelines recommend an LDL-lowering drug
initially. The initial drug of choice will traditionally be a statin, but alternatives include bile acid
sequestrants or nicotinic acid.3 When recommending initial statin therapy, it is important to take
cost, desired LDL reduction, drug-interactions, renal and hepatic impairment, and adverse event
profile into consideration. Response to therapy should be evaluated at 6 week intervals and
adjusted as necessary. If the goal of therapy has been achieved, the current dose can be
maintained. However, if further LDL reduction is required, therapy can be intensified, either by
increasing the dose of the statin or by combining a statin with a bile acid sequestrant or nicotinic
acid.3 Once the goal for LDL cholesterol has been attained, attention can turn to non-HDL as a
secondary target and other emerging risk factors. Monitoring for response to therapy should be
conducted every 4 to 6 months.3 In high-risk patients with high TG or low HDL, considerations
can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug.4
Drug                          Lipid effects                  Common side effects
Statin                        LDL ↓ 18-55%                   Myopathy
                              HDL ↑ 5-15%                    Increased liver enzymes
                              TG ↓ 7-30%
Bile acid sequestrant         LDL ↓ 15-30%                   Gastrointestinal distress
                              HDL ↑ 3-5%                     Constipation
                              TG     No change or increase   Decreased absorption of other
                                                             drugs
Nicotinic acid                LDL ↓ 5-25%                    Flushing
                              HDL ↑ 15-35%                   Hyperglycemia
                              TG  ↓20-50%                    Hyperuricemia
                                                             Upper GI distress
Fibric acids                  LDL ↓ 20-50%                   Dyspepsia
                              HDL ↑ 10-20%                   Gallstones
                              TG  ↓ 20-50%                   Myopathy

Ezetimibe                   LDL ↓ 19%                     Gastrointestinal distress
                            HDL ↑ 3%                      Myalgia
                            TG ↓ 5%                       URI
Omega-3 fatty acids         LDL ↑ 45%                     Gastrointestinal distress
                            HDL ↑ 9%                      Altered taste sense
                            TG ↓45%
*Compiled from NCEP ATP III guidelines. JAMA 2001;285:2486–2497
       Drug/Dose                                 Percent Change

HMG-CoA                    Dosage         TC     Triglycerides    HDL     LDL

Lescol® (fluvastatin)      20mg qhs      -17%        -12%         +3%     - 22%

                           40mg qhs      -19%        -14%         +4%     - 24%

                           40mg bid      -27%        -18%         +6%     -36%

                           XL 80mg qhs   -25%        -19%         +7%     -35%

Pravachol® (pravastatin)   10mg qhs      - 16%      - 15%         + 7%    - 22%

                           20mg qhs      - 24%      - 11%         + 2%    - 32%

                           40mg qhs      - 25%      - 24%         + 12%   - 34%

                           80mg qhs      -27%          -          +2.8%   -.37%

Zocor® (simvastatin)       5mg qhs       -19%        -12%         +10%    -26%

                           10mg qhs      - 23%      - 15%         +12%    - 30%

                           20mg qhs      - 28%      - 19%         + 8%    - 38%

                           40mg qhs      - 31%      - 18%         + 9%    - 41%

                           80mg qhs      - 36%      - 24%         + 8%    -47%

Lipitor® (atorvastatin)    10mg qd       - 29%      - 19%         + 6%    - 39%

                           20mg qd       - 33%      - 26%         + 9%    - 43%

                           40mg qd       - 37%      - 29%         + 6%    - 50%

                           80mg qd       - 45%      - 37%         + 5%    - 60%

Crestor® (rosuvastatin)    5mg qd        -33%        -35%         +13%    -45%

                           10mg qd       -36%        -10%         +14%    -52%
                          20mg qd         -40%    -23%     +8%     -55%

                          40mg qd         -46%    -28%    +10%     -63%

Miscellaneous             Dosage

Zetia® (ezetimibe)        10mg qd         -13%    -5%      +3%     -19%

Vytorin®                  10/10mg qd      -31%    -23%     +8%     -45%
(simvastatin/ezetimibe)

Vytorin®                  10/20mg qd      -36%    -24%    +10%     -52%

Vytorin®                  10/40mg qd      -39%    -23%     +6%     -55%

Vytorin®                  10/80mg qd      -43%    -31%     +6%     -60%

Advicor®                  500/20mg qd       -       -       -        -
(niacin/lovastatin)

                          750/20mg qd       -       -       -        -

                          1000/20mg qd    - 9%    - 32%   + 20%    - 30%

Niacin                    1gm tid         - 15%   - 50%   + 30%    - 15%

Niaspan®                  500 mg qd       -2%     -5%     +10%      -3%

Niaspan SR                1000 mg qd      -5%     -11%    +15%      -9%

                          1500 mg         -11%    -28%    +22%     -14%
                          (2x750)

                          2000 mg qd      -12%    -35%    +26%     -17%

Lopid® (gemfibrozil)      600mg bid        *      -50%*   + 15%*   - 2%*
(TG>200)

gemfibrozil (TG <200)     600mg bid        *      -30%*   + 10%*   - 15%*

Tricor (fenofibrate)      145mg qd        -17%    -36%    +15%     -20%

Welchol (cholesevelam)    (4x625mg) qd    -7%     +10%     +3      -15%

Lovaza (omega-3)          4x 1g caps qd   -10%    -45%     +9%     +45%
*All values obtained from drug package inserts


Non-traditional Atherosclerotic Indicators

As mentioned previously, CVD remains the leading cause of death in the United States despite
successful management of hyperlipidemia based on current guidelines.1 As a result, numerous
studies have been conducted to objectify and evaluate emerging risk factors associated with
CVD. While there are a vast number of theoretical risk factors, the following are reported with
the most frequency in current literature.

Homocysteine

Homocysteine, a sulfur-containing amino acid formed as a by-product from metabolism of the
essential amino acid methionine. It has no known biological function, but meta-analysis of
studies relating homocysteine to arteriosclerotic vascular disease demonstrate a correlation of
CVD risk and elevated levels of homocysteine.9 Various enzymes metabolize homocysteine and
commonly use B vitamins such as folate, cobalamin (vitamin B12), and pyridoxine (vitamin B6)
as substrates or cofactors.10 Elevated levels of homocysteine exert an atherogenic risk by several
proposed mechanisms, including endothelial dysfunction, alteration of platelet activity, inhibition
of vasodilation, or causing thrombogenisis.11,12 Measurement of plasma homocysteine is
conducted by competitive immunoassay and is best collected in the fasting state to negate
possible elevations from eating.13

Elevated homocysteine levels unaccompanied by other well-established risk factors such as
elevated LDL-C may not increase CVD risk.10 This raises the question “is homocysteine an
independent risk factor for CVD?” There appears to be a consensus on the treatment methods
for reduction of homocysteine levels, but debate lingers on the benefit of reduction on mortality.
Currently, there seems to be support for the treatment of elevated homocysteine (>10 µmol/L) in
patients with other risk factors.11 Since the metabolism of homocysteine is dependent on the
aforementioned B vitamins, treatment recommendations include a modified diet rich in folate-
containing foods or supplemental vitamins containing folic acid, vitamin B12, and vitamin B6.11

C-reactive Protein

C-reactive protein (CRP) is a commonly studied inflammatory marker and its role in CVD
management is highly debated. Inflammation appears to be involved in all stages of
atherosclerosis and therefore the presence of common inflammatory markers as a risk factor for
CVD is reasonable.14 CRP is an acute-phase reactant that is increased during the inflammatory
response to tissue injury or infection.10 Meta-analysis of prospective long-term studies of CRP
and the risk of nonfatal myocardial infarction or death from coronary heart disease demonstrate a
correlation between elevated CRP and CVD risk.10 However, the debate over CRPs role is
whether it is a risk mediator or a risk marker.15

The presence of CRP may add insight to an individual’s risk of CVD, but its use as a global risk
assessment is cautioned for several reasons. Namely, CRP is a nonspecific marker for
inflammation and is often elevated in the presence of inflammatory states (eg, rheumatoid
arthritis, chronic pulmonary disease, and infections) other than atherosclerosis.10 Also, CRP has
a strong correlation with other cardiovascular risk factors such as fibrinogen and its independent
relationship to recurrent cardiovascular events has not been demonstrated.10 For example, in
patients with established vascular disease, fibrinogen, but not CRP, was a significant
independent predictor of recurrent cardiovascular events after adjustment for conventional risk
factors.10, 28

Evidence from recent studies demonstrates that CRP may best be utilized as a risk marker rather
than mediator. Several studies have demonstrated that CRP is closely related to CVD and that
CRP levels may have prognostic value for predicting a cardiovascular event.14-17 However,
evidence of CRP as a cause of CVD is limited and therefore questions exist as to whether
reduction of CRP levels will reduce CVD. A recent study investigating the association of genetic
loci with CRP levels and the risk of CVD assessed whether CRP is in fact a risk factor or
mediator. The study concluded that although CRP levels appear to be elevated in CVD, it does
not seem to be a cause of CVD.18 Based on the data from these trials, the clinical use of CRP
should be as a predictive marker for CVD risk, not as a measure of effectiveness of therapy.10,14

Lp(a)

Lipoprotein(a) (Lp[a]) is a particle found in serum with structural similarities to LDL and
contains apolipoprotein B and the glycoprotein apolipoprotein(a). There are several proposed
mechanisms for Lp(a)s role in atherothrombosis, but its main atherothrombotic effects seem to
be through interference with fribrinolysis of thrombi on plaque surfaces and sites of tissue
injury.10 Epidemiological studies confirm its atherothrombotic effects, but its use as a screening
tool has some limitations.17,19 Strong evidence demonstrating the usefulness of Lp(a) as a cardiac
risk stratification tool in the clinical setting is limited. Also, there is uncertainty about the
applicability of current evidence to intermediate-risk patients and the effects of treatment of
Lp(a) independent of LDL-C. 20

Lp(a) measurement is conducted by enzyme-linked immunosorbent assay (ELISA) and may vary
based on ethnicity.13 Risk stratification based on Lp(a) levels are broken into quartiles. A Lp(a)
level of <20 mg/dL is considered desirable, whereas a level of 20-30 mg/dL is borderline high
risk, 31-50 mg/dL is high risk, and >50mg/dL is very high risk.13
Currently, no highly effective therapy for reduction of Lp(a) concentrations exists. High-dose
nicotinic acid (4gm daily) may be effective, but its tolerability is a major limitation to therapy.10
A recent study determined a mean dose of niacin ER needed for patients to reach the
predetermined Lp(a) goal was 2,819±821 mg/d.21
Small, Dense LDL

LDL size seems to be an important predictor of cardiovascular events and progression of
coronary heart disease.22 Variations of LDL particles can be broken into two separate phenotypes
that differ in size, density, physicochemical composition, metabolic behavior, and atherogenicity.
The phenotype denotations are known as pattern A and pattern B. Pattern A consists of larger,
more buoyant LDL particles, while pattern B consists of smaller, denser LDL particles.22 To
date, prospective epidemiological studies and clinical trials have demonstrated that small, dense
LDL increase the risk of CVD and that perhaps LDL quality may hold more benefit than LDL
quanity.22,23 It is thought small, dense LDL particles are taken up more readily by arterial tissue
and are more susceptible to oxidation than large, more buoyant LDL particles.23,24 There is
question however, that the qualitative assessment of LDL size lacks clinical benefit beyond the
standard quantitative measurement of LDL, TG, and HDL concentrations.

LDL size correlates positively with HDL levels and negatively with TG concentration therefore
patients with metabolic syndrome will often be classified as pattern B.22 It is also common to
observe pattern B in men, postmenopausal women, and in patients with a genetic predisposition,
increased age, or high-carbohydrate diet.23

Based on the aforementioned correlation of LDL size with HDL and TG concentrations,
treatment methods should be directed toward adjustment of the entire lipid profile. As a result,
fibric acids (fenofibrate, gemfibrozil), niacin, and perhaps thiazolidinediones are most effective
at improving the LDL pattern.23, 24,25 While statin therapy will affect the LDL quantity, its effect
on LDL quality is limited. 23, 24,25

Discussion

Current NCEP ATP III guidelines recommend a primary target of treating LDL-C levels to each
patients’ predetermined goal based on the risk stratification mentioned previously.3,4 However, it
has been estimated that up to 50% of all myocardial infarctions and strokes occur in men and
women with LDL levels below the recommended goals.26 As a result, the ATP III update has
recommended more aggressive lipid therapy in patients with “emerging risk factors” for CVD to
allow further risk stratification.4 The emerging risk factors identified by NCEP ATP III are
lipoprotein(a), homocysteine, prothrombotic and proinflammatory factors, impaired fasting
glucose, and evidence of subclinical atherosclerotic disease.3
In the United States, 23 million adults with no history of cardiovascular disease are classified as
intermediate-risk and emerging risk factors might identify those who are actually at high risk.20
However, in order for a risk factor to be useful as a reclassification tool it must meet certain
criteria. A risk factor should be easily and reliably measured, be an independent predictor of
major CHD events, and modifying treatment must be available.10,20 Based on these criteria, it is
of note that universal screening for these emerging risk factors does not add clinical benefit in all
situations.27 Patients with known high-risk for CVD and appropriate treatment will benefit little,
as there is no additional treatment modification available. Also, cost-effectiveness must be
considered. The average cost of a fasting lipid panel including TC, TG, and HFL with a
calculated LDL is $20 to $25, while testing for emerging risk factors can range from $18 to
$100.27

Conclusion

Traditional risk stratification based on NCEP ATP III guidelines should remain the standard of
care for the majority of patients, but individual therapy should be adjusted as necessary. Patients
with an intermediate Framingham risk, a family history of premature CVD without traditional
risk factors, or CVD in the absence of traditional risk factors appear to be of most benefit to
screening of the emerging risk factors mentioned. However, until more information is available
and guidelines are altered, LDL-C reduction should remain the primary target for prevention and
treatment of CVD.

Mini-Case

MR is a 66 yowm with a PMH of HTN, CAD, DM, and dyslipidemia. He presents to the office
for a routine follow-up appointment in no apparent distress and without complaint. His current
medication list includes: lisinopril/HCTZ 20/25mg daily, ASA 81mg daily, metformin 1000mg
twice daily, glipizide 5mg twice daily, and lipitor 80mg daily. The review of systems is
unremarkable and on physical exam MR’s BP is 128/78, pulse is 76, respiratory rate is 16,
temperature is normal, weight is 200 pounds, and height is 68 inches. Recent laboratory results
are as follows:
Lab                                                 Value
TC                                                  175 mg/dL
TG                                                  300 mg/dL
HDL                                                 55 mg/dL
LDL                                                 80 mg/dL
Alc                                                 6.4%
TSH                                                 1.245
    +
Na                                                  140 mmol/L
  +
K                                                   4.2 mmol/L
Cl-                                             100 mmol/L
BUN                                             18 mg/dL
Scr                                             0.9 mg/dL

Questions

Based on MR’s PMH what is his LDL goal?
   A. <160 mg/dL
   B. <100 mg/dL
   C. <130 mg/dL
   D. <70 mg/dL
MR only has one cardiac risk factor (HTN), but has two CHD risk equivalents (DM and CAD).
Therefore, his LDL goal would be <70 mg/dL because he is considered to be at very high risk for
CVD.

Based on MR’s lipid profile, what is the best addition to his current medication regimen?
   A. Gemfibrozil 600mg twice daily
   B. Zetia 10mg daily
   C. Fenofibrate 160mg daily
   D. Fenofibrate 54mg daily
   MR’s LDL is not at goal, but he is currently on the max dose of his statin therapy. Since
   MR’s TG level is also elevated and it does not appear to be related to uncontrolled DM (A1c
   6.4%) or thyroid dysfunction (TSH 1.245). While zetia would be a valid option for further
   LDL reduction, the addition of a fibrate would most likely improve MR’s LDL while lowering
   the TG substantially. Since MR is on lipitor, it would be advised to use fenofibrate over
   gemfibrozil to lessen the risk of myalgias or rhabdomyolysis. Based on MR’s creatinine
   clearance the dose of fenofibrate should be 160mg rather than 54mg daily.

References
   1. Heron M, Hoyert L, Murphy SL, et al. Deaths: Final Data for 2006 [Internet]. Atlanta
      (GA): Centers for Disease Control and Prevention. 2009 Apr 17 [updated 2009 Dec 31;
      reviewed 2009 Mar 6; cited 2010 Jan 5]. Available from:
      http://www.cdc.gov/nchs/FASTATS/deaths.htm.
   2. Talbert Robert L, "Chapter 23. Hyperlipidemia" (Chapter). Joseph T. DiPiro, Robert L.
      Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael Posey:
      Pharmacotherapy: A Pathophysiologic Approach, 7e:
      http://www.accesspharmacy.com/content.aspx?aID=3199458.
   3. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
      Adults. Executive summary of the third report of the National Cholesterol Education
    Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood
    Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486–2497
4. Grundy SM, Cleeman JI, Merz CNB, et al. National Heart, Lung, and Blood Institute;
    American College of Cardiology Foundation; American Heart Association. Implications
    of recent clinical trials for the National Cholesterol Education Program Adult Treatment
    Panel III Guidelines [erratum in Circulation. 2004;110:763]. Circulation. 2004;110:227-
    239.
5. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of
    cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized
    placebo-controlled trial. Lancet. 2002;360(9326):7–22.
6. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, et al. PROSPER study group.
    Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomized
    controlled trial. Prospective Study of Pravastatin in the Elderly at Risk. Lancet.
    2002;360:1623–1630.
7. Sever PS, Dahlof B, Poulter NR, Wedel H, et al. ASCOT investigators. Prevention of
    coronary and stroke events with atorvastatin in hypertensive patients who have average or
    lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac
    Outcomes Trial– Lipid Lowering Arm (ASCOT-LLA): a multicentre randomized
    controlled trial. Lancet. 2003;361:1149–1158.
8. Cannon CP, Braunwald E, McCabe CH, Rader DJ, et al. Pravastatin or Atorvastatin
    Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22
    Investigators. Intensive versus moderate lipid lowering with statins after acute coronary
    syndromes. N Engl J Med. 2004;350:1495–1504.
9. Boushey CJ, Beresford SA, Omenn GS, Lotulsky AG. A quantitative assessment of
    plasma homocysteine as a risk factor for vascular disease. JAMA 1995;274:1049-1057.
10. Hackam DG,Anand SS. Emerging risk factors for atherosclerotic vascular disease: A
    critical review of the evidence. JAMA 2003:290:932-940.
11. Malinow MR, Bostom AG, Krauss RM. Homocysteine, diet and cardiovascular diseases:
    A statement for healthcare professionals from the Nutrition Committee, American Heart
    Association. Circularion.1999;99:178-182.
12. Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk factor for atherosclerosis.
    Ann Pharmacother. 2000;34:57-65.
13. LabCorp Provider. Available at hrrps://wwwJabcorp coml. Accessed December 19, 2009.
14. Pearson TA, Mensah JA, Alexander RW, et al. Markers of inflammation and
    cardiovascular disease. Circulation. 2003;107:499-511.
15. Field KM. Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on
    high-sensitivity C-reactive protein levels. Pharmacotherapy. 2005;25:1365-1377.
16. Torzewski M, Rist C,Mortcnsen RF, et al. C-reactive protein in the arterial intima: Role
    of C-reactive protein receptor -dependent monocyte recruitment in atherogenesis.
    ArterWscler Thromb vase Bioi. 2000;20:2094-2099.
17. Ridker PM, Hennekens CH, Stampfer MJ. A prospective study of lipoprotein(a) and the
    risk of myocardial infarction. JAMA. 1993;270:2195-2199.
18. Elliot P, Chambers JC, Zhang W, et al. Genetic loci associated with C-reactive protein
    levels and risk of coronary heart disease. JAMA 2009;302:37-48.
19. Alfthan G, Pekkanen J, Jauhiainen M, et al. Relation of serum homocysteine and
    lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish
    population based study. Atherosclerosis. 1994;106:9-19.
20. Helfand M, Buckley DI, Freeman M, et al. Emerging risk factors for coronary heart
    disease: a summary of systematic reviews conducted for the U.D. Preventative Services
    Task Force. Annals of Internal Medicine 2009 Oct 6;151(7):496-507.
21. Pan], VanJT, Chan E, Kesala RL, Lin M, Charles MA. Extended-release niacin treatment
    of the atherogenic lipid profile and lipoprotein(a) in diabetes. Metabolism. 2002;51:1120-
    1127.
22. Rizzo M, Berneis K. Low-demity lipoprotein size and cardiovascular risk assessment
    [erratum in QJA12007;100:147]. QJAf. 2006;99:1-14.
23. Rizzo M, Berneis K. Who needs to care about small, dense low-density lipoproteins? Int
    J Clin Pract 2007:61;1949-1956.
24. Rajman I, Maxwell S, Cramb R, Kendall M. Particle size: The key to the atherogenic
    lipoprotein? QJAf 1994;87:709-720.
25. Backes JM, Gibson CA. Effect of lipid-lowering drug therapy on small-dense low-
    density lipoprotein. Arm Pharmacother. 2005;39:523-526.
26. Ridker PM, Danielson E, Fonseca FA, et al;JUPITER Srndy Group. Rosuvastatin to
    prevent vascular events in men and women with elevated C-reactive protein. N Engl ]
    Med. 2008;359:2195-2207.
27. Hoffmann TK, Tucker MA, Parker DL. Emerging risk factors and risk markers for
    cardiovascular disease: Looking beyond NCEP ATP III. Formulary 2009:44;237-247
28. Smieja M, Yusuf S, Lonn E, et al. Inflammatory markers and risk of subsequent
    cardiovascular events in the HOPE trial [abstract]. American Heart Association Scientific
    Sessions; November 11-14, 2001; Anaheim, Calif

								
To top