Running head: HYPERLIPIDEMIA
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Hyperlipidemia
Denise Richard & Melissa Wilson
State University of New York Institute of Technology
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Hyperlipidemia
Currently over 71 million adults in the United States over the age of 20 have
hyperlipidemia, yet only 34 million are currently being treated and only 23 million had their low
density lipoprotein (LDL) cholesterol under control ("Vital signs: Prevalence," 2011).
Hyperlipidemia is considered an insidious disease, which often goes unrecognized and untreated
due to the lack of obvious symptoms (Rosenson, 2013). Despite the absence of symptoms,
hyperlipidemia is a leading risk factor in the development of chronic illnesses such as
atherosclerosis and coronary heart disease (CHD) which can ultimately cause premature death.
(“Prevalence of Cholesterol,”2012; Rosenson, 2013). Fortunately, a person’s risk can be
significantly reduced with the implementation of dietary changes, weight loss, regular exercise,
and medication therapy (Rosenson, 2013). Given the potential severity of hyperlipidemia, the
focus of this literature review is to examine current treatment regimens and determine not only
the efficacy of these treatments but also identify the barriers that stand in the way of their
implementation.
Literature Review
An extensive review of the literature was performed to identify relevant research
regarding the treatment of hyperlipidemia. The literature review entailed retrieving pertinent
information utilizing CINAHL, Medline, Science Direct and PubMed databases through the
Cayan Library at the State University of New York Institute of Technology. The search was
confined to research literature published within the period of 2009-2014. Fourteen research
studies focusing on hyperlipidemia treatment were selected for inclusion. The key words utilized
to carry out the search included: “adult hyperlipidemia”, “pediatric hyperlipidemia”,
“hyperlipidemia treatment”, as well as “hypercholesterolemia treatment”.
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Current State
Research has long since established that hyperlipidemia is a leading risk factor in the
development of atherosclerosis and CHD, yet the prevalence of uncontrolled high LDL
cholesterol, although improving, remains a major health concern ("Vital signs: Prevalence,"
2011). Despite evidence that cardiovascular morbidity and mortality can be significantly reduced
by regular cholesterol screening and early intervention, this medical condition continues to go
undiagnosed and untreated in the United States (Vijan, 2013; “Vital signs: Prevalence”, 2011).
A review of data from the National Health and Nutrition Survey conducted by the Center
for Disease Control (CDC), examined prevalence, treatment, and control of high LDL-C among
adults over the age of 20 (“Vital signs: Prevalence”, 2011). Findings revealed that low income,
limited access to healthcare, lack of quality care, and nonadherence to medication regimens all
play a major role in the current issue of poor hyperlipidemia control (“Vital signs: Prevalence”,
2011).
Current Guidelines
While the United States, Europe, and Canada all offer varying guidelines in regards to
the management of hyperlipidemia, there is unanimous agreement that therapeutic lifestyle
changes are essential and that the LDL cholesterol should be the main target of therapy
(Alexander et al., 2009; Ewang-Emukowhate & Wierzbicki, 2013; Last, Ference, & Falleroni,
2011). Currently the most nationally recognized guidelines regarding hyperlipidemia treatment
are the Adult Treatment Panel (ATP) III guidelines (see Appendix A), which support a treat to
target approach and are considered more aggressive than other guidelines (Last, Ference &
Falleroni, 2011). The ATP III guidelines were implemented by the National Cholesterol
Education Program (NCEP) in collaboration with the National Heart, Lung, and Blood Institute,
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American College of Cardiology (ACC), and the American Heart Association (AHA) to provide
clinicians with standardized practice guidelines to utilize in the treatment of hyperlipidemia in
adults (AHA, 2013). The guidelines were not implemented to replace clinical decision making,
but rather to provide the health care provider with a standardized reference for treatment options
(Stone et al., 2013). Current ATP III guidelines focus not only on treatment of patients with
known CHD but also on primary prevention in persons with multiple risk factors (“ATP
Guidelines,” 2004).
pediatric guidelines. In 2006, the NHLBI spearheaded the development of an expert
panel to address research findings suggestive of a correlation between childhood obesity and the
development of CHD in adulthood (Allcock, Gardner & Sower, 2009). As a result,
comprehensive evidence based guidelines were developed to address the known risk factors in
the development of CHD in the pediatric population as a way to assist pediatric practitioners in
the promotion, identification and management of pediatric cardiovascular health (“ATP
Guidelines,” 2006).
Credible Authorities
There are a multitude of credible authorities that endorse the use of ATP III guidelines in
the management of screening, prevention, and hyperlipidemia treatment. These authorities
include but are not limited to the National Heart, Lung, and Blood Institute (NHLBI), American
College of Cardiology (ACC), the American Heart Association (AHA), the American Academy
of Pediatrics (AAP), as well as the American Academy of Family Physicians (AAFP).
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Risk Assessment
According to the ATP III guidelines, the initial step in management of hyperlipidemia is
to determine CHD risk (Bertoni, Ensley, & Goff, 2012). Risk is determined by lipoprotein levels,
the presence of atherosclerotic disease, as well as evidence of major risk factors (“ATP
Guidelines,” 2004). Analysis of a person’s fasting lipid panel is performed to determine whether
lipoprotein levels are within normal limits. Next, a review of the medical history is performed to
determine the presence of atherosclerotic disease, which equates high risk for CHD events, such
as clinical CHD, symptomatic coronary artery disease (CAD), peripheral artery disease,
abdominal aortic aneurysm, and diabetes (“ATP Guidelines,” 2004). Lastly, evidence of major
risk factors such as cigarette smoking, hypertension (BP > 140/90 mmHg or use of
antihypertensive medication), family history of premature CHD (male first degree relative < 55
years; female first degree relative < 65 years), and age (men > 45 years; women > 55 years) is
determined (“ATP Guidelines,” 2004). If two or more risk factors are present without CHD or
CHD risk equivalent, completion of the Framingham table (see Appendix B), a risk assessment
tool used to calculate the ten-year risk of coronary events is warranted (“ATP Guidelines,”
2004). The statistical results of the Framingham scoring system assist in the determination of the
most appropriate treatment regimen (“ATP Guidelines,” 2004).
Nonpharmacological Treatment
ATP III guidelines recommend that the initial treatment for hyperlipidemia be
nonpharmacological in nature and focused upon therapeutic lifestyle changes (Kelly, 2010).
According to ATP III guidelines, the establishment of LDL goal for therapy, the need for
therapeutic lifestyle changes, and drug consideration are all necessary to determine an
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individual’s risk category. Once risk category is determined, the clinician and patient can decide
whether lifestyle modification can be attempted by itself or in conjunction with pharmacological
treatment (2004). Research suggests that addressing modifiable risk factors such as diet, exercise
and smoking can have a positive effect on total cholesterol, LDL cholesterol, HDL cholesterol,
as well as triglycerides, which decreases the risk of CHD (Bright et al., 2012; Cochrane et al.,
2012; Fritsch, Montpellier & Kussman; Kelly, 2010).
There is a great deal of evidence that suggests that the use of formal programs to educate
and coach individuals with hyperlipidemia on lifestyle choices can be beneficial (Bright et al.,
2012; Fritsch et al., 2009; Tressler et al., 2013). Many employers offer programs in the
workplace to promote optimal health amongst their employees. Course curriculum varies from
program to program; however, all of them stress the importance of following a diet low in
saturated fats, smoking cessation, and participating in 30 minutes of aerobic exercise on a daily
basis (Bright et al., 2012; Fritsch et al., 2009; Gepner et al., 2011; Rosenson, 2013; Tressler et
al., 2013).
Pharmacological Treatment
In cases where individuals have an increased risk for CHD or have been unsuccessful at
therapeutic lifestyle changes, pharmacological treatment is often indicated. According to Reindl,
Wright & Wargo (2010) 3-Hydroxy-3-methylglutaryl-coenzymes A (HMG-CoA) reductase
inhibitors (statins) are the most effective agents at reducing LDL-C levels, which decreases the
occurrence of atherosclerotic events as well as cardiovascular morbidity and mortality (p. 1459).
For this reason statins are currently the most commonly used class of medication for the
treatment of hyperlipidemia (Zhang et al., 2013). Additional classes of medications used to treat
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hyperlipidemia include bile acid sequestrants, nicotinic acids and fibric acids (Zhang et al.,
2013).
Adherence
Despite the fact that research suggests statins are the most effective medication class for
the reduction of LDL-C levels, lack of adherence and underutilization are common problems
associated with their use (Gadkari & McHorney, 2012; Reindl, Wright & Wargo, 2010;
Wiegand, McCombs & Wang, 2012; Zhang et al., 2013). In a study conducted by Wiegand,
McCombs, & Wang, 65% of the study participants were noted to be noncompliant with the
prescribed treatment (2012). Predictors of nonadherence included individuals with the presence
of poly pharmacy, age 45-55 years, a previous diagnosis of Diabetes and male gender (Wiegand
et al., 2012).
side effects. Although highly effective, statins can cause unpleasant adverse effects such
as myalgia, hepatotoxicity, gastrointestinal disturbances, and headaches, which can ultimately
lead to lack of adherence (Reindl, Wright & Wargo, 2010). In a retrospective cohort study an indepth review of reasons for the discontinuation of statins were investigated (Zhang et al., 2013).
The results of the study suggested that adverse reactions to statins were the leading cause of
temporary discontinuation, yet most patients who were restarted on the same statin were still able
to tolerate it 12 months after the initial adverse event (Zhang et al., 2013). In addition to
restarting the same statin, research indicates that changing to another statin or alternate day
dosing are viable options to consider for patients who experience adverse effects (Reindl, Wright
& Wargo, 2010).
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Race
Current research suggests that lack of medical treatment adherence in minorities is
multifactorial in nature (Ratanawongsa, Zikmund-Fisher, Couper, Van Hoewyk & Powe, 2010).
African Americans and Hispanics have noticeably higher LDL and total cholesterol levels when
compared to Caucasians, which predisposes them to a higher risk of mortality and morbidity
(Willson, Neumiller, Sclar, Robison & Skaer, 2010). In spite of this increased risk, research
indicates that African Americans and Hispanics are less likely to be knowledgeable about having
high cholesterol, less likely to undergo regular cholesterol screening, as well as less likely to
adhere to a medication regimen to reduce their lipid levels (Ratanawongsa et al., 2010).
Literature has also identified that the Asian population has a significant predisposition to
heart disease ("South asians and," 2013). Asians tend to have elevated triglyceride levels, low
HDL and in many cases normal to very mildly elevated LDL levels ("South asians and," 2013).
Hyperlipidemia can be difficult to treat in Asians because they may not meet the target goal for
treatment of hyperlipidemia when in essence the medication prescribed may be too low (Chan et
al., 2012). The literature indicates that research is lacking among the Asian populations in
regards to the effectiveness of treatment (Chan et al., 2012).
Ethnicity
According to the Center for Disease Control and Prevention, heart disease is the leading
cause of death among ethnic minorities such as African Americans, Hispanics and Whites in the
United States today (2014). In addition, heart disease is currently the second leading cause of
death amongst Alaskan natives, Pacific Islanders, and American Indians (cdc.gov, 2014).
Research suggests that when compared to whites, ethnic minorities tend to be less informed
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about hyperlipidemia as well as less involved with the decision making process for treatment
(Ratanawongsa, 2010).
Socioeconomic Status
Research indicates that African Americans and Hispanics tend to have lower incomes as
well as an increased incidence of lack of health insurance (Zikmund-Fisher, et al., 2010). Thus,
this population is often less likely to be evaluated by a primary care physician on a regular basis,
putting them at a higher risk for the development of hyperlipidemia (Mosca, Bhuachalla &
Kenny, 2013; Zikmund-Fisher, et al., 2010). Individuals who have limited financial resources
tend to eat items higher in saturated fats because they are typically less expensive. Unfortunately,
this increases their risk for the development of high cholesterol levels and the development of
CHD (Leung et al., 2012).
Literature Similarities
There were several significant similarities noted in the literature review of
hyperlipidemia. One of the most significant is the widespread use of the ATP III guidelines to
treat hyperlipidemia (Cochrane et al., 2012; Eaton et al., 2011; Fritsch, Montpellier & Kussman,
2009; Tressler et al., 2013). Although the ATP III guidelines are from 2004, and are due to be
updated in the very near future, they are still considered a pertinent resource for clinicians.
Another similarity noted in the review of research was the overwhelming belief that therapeutic
lifestyle modification is the key to the treatment and prevention of hyperlipidemia (Cochrane et
al., 2012; Eaton., 2011; Fritsch, Montpellier & Kussman, 2009). Lastly, there is consensus that
low income, limited access to healthcare, lack of quality care, and nonadherence to medication
puts African American and Hispanic populations at greater risk for development of
hyperlipidemia (Ratanawongsa et al., 2010; Zikmund-Fisher, et al., 2010).
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Literature Differences
Although there were many similarities in the review of the literature there were also
many differences noted as well. A variety of different reasons regarding lack of adherence to
medication treatment was noted. These included adverse effects to statin therapy, medication
affordability, perceived need for medication, forgetfulness, as well as carelessness (Gadkari &
McHorney, 2012; Reindl et al., 2010; Roth et al., 2010; Zhang et al., 2013). There were also
differing views on how to treat hyperlipidemia in the Asian population (Chan et al., 2012; Palo
Alto Medical Foundation, 2014). Finally, there were differing views on whether black and
Hispanic populations preferred to have health care providers dictate their treatment regimen or
whether they were even likely to seek a health care provider for the detection of hyperlipidemia
(Zikmund-Fisher, et al., 2010).
Gaps in Literature
There are gaps in the literature regarding not only how to increase the number of people
being treated for hyperlipidemia but also how to increase the number of people who have their
LDL levels under control. Thus, additional studies must be performed to identify solutions to
these potentially life threatening issues. Furthermore, there are only limited studies regarding the
proper treatment of hyperlipidemia in the Asian population. In order to better care for this
population, additional studies must be performed. Lastly, further research regarding how to
increase medication adherence is warranted.
Final Thoughts
Despite efforts to provide early screening and treatment, hyperlipidemia remains a major
health issue that often goes unrecognized and untreated. Reasons for this include limited income,
lack of access to health care, denial, nonadherence to medication regimen, and lack of
HYPERLIDIPEMIA
knowledge regarding the disease process as well as the increased risk of developing CHD. The
evidence suggests that it is essential that patients receive regular screening, are provided with
education regarding the disease and how to reduce their risk factors, as well as proper medical
treatment if lifestyle modification fails to correct the issue.
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References
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cardiovascular risk. International Journal Of Endocrinology, 1-4.
Bertoni, A., Ensley, D., & Goff, D. (2012). 30,000 fewer heart attacks and strokes in North
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Bright, D. R., Kroustos, K. R., Thompson, R. E., Swanson, S. C., Terrell, S. L., & DiPietro, N.
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Chan, R. H., Chan, P. H., Chan, K. K., Lam, S. C., Hai , J. J., Wong, M. K., … Lee, S. W.
(2012). The CHEPUS Pan-Asian survey: high low-density lipoprotein cholesterol goal
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Ewang-Emukowhate, M., & Wierzbicki, A. (2013). Lipid-lowering agents. Journal Of
Cardiovascular Pharmacology And Therapeutics, 18(5), 401-411.
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Fritsch, M., Montpellier, J., & Kussman, C. (2009). Worksite wellness: A cholesterol awareness
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Gadkari, A., & McHorney, C. (2012). Unintentional non-adherence to chronic prescription
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Heart disease facts. (2013, August 8). Retrieved from www.cdc.gov
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Last, A., Ference, J., & Falleroni, J. (2011). Pharmacologic treatment of hyperlipidemia.
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Leung, C. W., Ding, E. L., Catalano, P. J., Villamor, E., Rimm, E. B., & Willet, W. C. (2012).
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Mosca, I., Bhuachalla, B., & Kenny, R. (2013). Explaining significant differences in subjective
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Reindl, E. K., Wright, B. M., & Wargo, K. A. (2010). Alternate-day statin therapy for the
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Rosenson, R. S. (2013). High cholesterol treatment options. Retrieved from www.uptodate.com
South asians and cholesterol. (2013). Retrieved from www.pamf.org
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in adults (adult treatment panel iii). (2004). Retrieved from www.nhlbi.nih.gov
Tressler, M. C., Greer, N., Rector, T. S., Ishani, A., & Ercan-Fang, N. (2013). Factors associated
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Wiegand, P., McCombs, J., & Wang, J. (2012). Factors of hyperlipidemia medication adherence
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Willson, M., Neumiller, J., Sclar, D., Robison, L., & Skaer, T. (2010). Ethnicity/race, use of
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Zhang, H., Plutzky, J., Skentzos, S., Morrison, F., Mar, P., Shubina, M., & Turchin, A. (2013).
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Zikmund-Fisher, B., Couper, M., Singer, E., Levin, C., Fowler, F., Ziniel, S., Ubel, P., &
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Appendix A
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Appendix B
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Appendix C
Summary of Findings from Literature Review
Studies
Bright et al.
(2012)
Focus
Evaluate the
effectiveness
of multidisciplinary
disease state
management
pilot program
Subjects
N=20
Population
Adult employees of
private self-insured
university
Chan et al.
(2012)
N=561
Adults currently being
treated for
hyperlipidemia
Assess the
Cochrane et al. value of
(2012)
tailored
lifestyle
support,
including
motivational
interview with
ongoing
support
N=601
Adults with estimated
CVD risk of > 20%
Age
18
years
of age
or
older
Method
Retrospective
review
Findings
Improved clinical outcomes after
three months.
18
years
of age
or
older
18
years
of age
or
older
Cross
sectional
observational
study
Participants were able to achieve high
attainment rate of LDL goal despite
major cardiovascular risk factors.
Retrospective
review of
randomized
trial
Average population CVD risk
decreased from 32.9% to 29.4% in
NHS Health Check only group.
Participants believed participation in
program was beneficial.
CVD risk decreased from 31.9% to
29.2% in the NHS Health Check plus
additional lifestyle support group.
Prevalence of HTN, high cholesterol
and smoking significantly reduced in
both groups (p<0.01).
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Eaton et al.
(2011)
Fritsch,
Montpellier, &
Kussman
(2009)
Determine
N=4,105
whether
intervention
based on
patient
activation and
physician
design support
tool more
effective than
usual care for
improving
adherence to
NCEP
guidelines
Adult patients from 30
primary care practices
in Southern New
England
Determine
impact of
education and
coaching on
lifestyle
choices and
lipid values
among
employees w/
Hyperlipidemia
Employees with
diagnosis of
hyperlipidemia
N=139
18
years
of age
or
older
Randomized
control trial
Both randomized practice groups
improved screening (89%) screened.
74% of patients in both groups were
at their LDL and non-HDL
cholesterol goals.
No statistically significant difference
between practice groups in screening
or percentage of patients who
achieved LDL and non-HDL goals.
18
years
of age
or
older
Retrospective
Review
Physicians who made high use of
decision support tools were more
likely to have patients at LDL
cholesterol goals than low use or no
use physicians.
Participants had an overall reduction
of 5.2% in total cholesterol.
No significant change in HDL levels.
Lipid based interventions at worksite
can elicit positive changes in lifestyle
and improved lipid levels.
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Gadharki &
McHorney
(2012)
Mosca,
Bhuachalla &
Kenny (2013)
N=24,017
Study
prevalence
and predictors
of
unintentional
medication
non-adherence
Determine the N=4,179
extent to
which
socioeconomic
health
gradient
differs in
subjective and
objective
reports of
hyperlipidemia
and/or
hypertension
Adults with asthma,
hypertension, diabetes,
hyperlipidemia or
osteoporosis on chronic
prescription meds
40
years
of age
or
older
Cross
sectional
survey
Unintentional non-adherence does not
appear to be random and is predicted
by beliefs, chronic disease, and
sociodemographics.
Adults residing in
Ireland with diagnosis
of hyperlipidemia
and/or hypertension
50
years
of age
or
older
Retrospective
data analysis
Higher education and greater wealth
were associated with higher levels of
HDL cholesterol.
Association between socioeconomic
status and objectively measured
hypercholesterolemia and LDL
cholesterol were not significant.
Clear discrepancies in prevalence
rates and gradients by socioeconomic
status were found between subjective
and objective reports of both
disorders.
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Ratanawongsa
et al. (2010)
Investigate
N=738
whether
patient
race/ethnicity
is associated
with
experiences
discussing
cardiovascular
risk reduction
therapy with
health care
providers
Reindl, Wright Evaluate the
N=694
& Wargo
safety, efficacy
(2010)
and cost of
alternate-day
statin therapy
in the
treatment of
hyperlipidemia
English speaking U.S.
adults
Age 40
years
of age
or
older
Retrospective
cross
sectional
survey
Minorities had lower knowledge
scores than whites for hyperlipidemia.
Minorities were more likely than
whites to report that the health care
provider made the final decision for
treatment.
Minorities considering
hyperlipidemia therapy may be less
informed about and less involved in
the final decision making process.
Adults currently taking Age 18
statins on an alternate years
of age
or
older
Data analysis
of 17 trials
involving
alternate-day
statin dosing
Alternate day statin therapy may
decrease cost and therapy limiting
adverse reactions while potentially
increasing regimen adherence and
positively affecting the lipid panel.
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Roth et al.
(2010)
Tressler et al.
(2013)
Willson et al.
(2010)
Evaluate
N= 474
efficacy and
safety of fixed
dose
combinations
of rosuvastatin
and fenofibric
acid compared
with
Simvastatin in
patients with
high levels of
LDL and
Triglycerides
Adults with LDL-C
levels > 160 mg/dL and
< 240 mg/dL and TG >
150 mg/dL and < 400
mg/dL
Identify
factors related
to achieving a
LDL<100
mg/dL
Examine the
extent of
racial/ethnic
disparities in
treatment of
hyperlipidemia
Veterans with known
DM and one additional
risk factor such as
HTN, elevated Hgb
A1C, or elevated LDL.
Patients who visited
office for
hyperlipidemia.
N= 556
N=
26,624,035
18
years
of age
or
older
Randomized
double blind
study
Patients with high LDL-C and TG
levels tolerated combination
treatment with rosuvastatin/fenofibric
acid well.
Each of the rosuvastatin/fenofibric
acid doses produced greater
reductions in LDL-C and
improvements in other parameters,
compared with Simvastatin 40 mg.
18
years
of age
or
older
20
years
of age
or
older
Data analysis
from
randomized
control trial
Patients who reached goal LDL had
higher rates of pre-existing CAD,
CVA< CHF, and Statin use.
Retrospective
data analysis
Use of pharmacotherapy for
hyperlipidemia varied by ethnicity
and race.
Disparity noted in cholesterol
screening, diet, nutrition, exercise
counseling by ethnicity and race.
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ZikmundFisher et al.
(2010)
Zhang et al.
(2013)
Identify
N= 3010
decision
prevalence
and decision
making
process re:
hyperlipidemia as
well as a
variety of
other medical
conditions.
Investigate the N=107,835
reasons for
statin
discontinuatio
n and the role
of statinrelated events
or symptoms
believe to have
been caused
by statins in
routine care
settings
U.S. adults in
households with
telephones
40
years
of age
and
older
Telephone
interview
survey
82.2% of participants reported
making at least one medical decision
in last 2 years.
Participants made more medical
decisions if they had a PCP or were in
poorer health.
Participants made less medical
decisions if they had lower education,
were male, or under the age of 50.
Adults who received a
statin prescription
18
years
of age
or
older
Retrospective
cohort study
Statin related events are commonly
reported and often lead to statin
discontinuation.
Most patients who are rechallenged
can tolerate satins long term.
Findings suggest that statins may
have other causes, are tolerable, or
may be specific to individual statins
rather than the entire drug class.