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Provident
News
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Kristen Taggart, Regulatory Specialist at the Addison
site, passed the certification exam for Registered Health Information
Administrator (RHIA) offered by the American Healthcare Information Management
Association. Congratulations Kristen!
Our Bloomington site has consolidated operations at the
1st Street location. All site
activity now happens all under one roof! Our former officemate Dr. Calli has moved
into neighboring office space.
Daniel Hedinger, RN, MSN, NP has recently left to pursue
new career opportunities in the corporate world. Daniel has been a sub-investigator for
several Provident trials. We wish Daniel well in his new endeavors!
Our Addison site is up and running! We have completed 2 trials and are on track
to complete the 3rd by the end of this year. We currently have 5 trials enrolling with 12 more to begin before the
end of the first quarter of 2009! Great
work Addison!
Dr. Maki has published Practical Lipid Management: Concepts and Controversies with Dr.
Peter Toth. This would make a great
stocking stuffer!
Recent and Upcoming Publications and
Presentations
Publications
Maki KC, Mustad V, Dicklin MR, Geohas J. Postprandial metabolism with
1,3-diglyceride oil vs. equivalent intakes of long-chain and medium-chain
triglyceride oils. Nutrition. 2008 (in press).
Maki KC, Reeves MS, Farmer M, Yasunaga K, Noburu M, Katsuragi Y, Komikado M,
Tokimitsu I, Wilder DM, Jones F, Blumberg JB, Cartwright Y. Green tea catechin consumption enhances
exercise-induced abdominal fat loss. J Nutr. 2008 (in press).
Maki KC, Kanter M, Rains TM, Hess SP, Geohas J. Acute effects of low insulinemic sweeteners on postprandial insulin and
glucose concentrations in obese men. Int J Food Sci Nutr. 2008 (in press).
Sanchez-Muniz FJ, Maki KC,
Schaefer EJ, Ordovas JM. Serum lipid and antioxidant
responses in hypercholesterolemic men and women receiving plant sterol esters
vary by apolipoprotein E genotype. J Nutr. 2009;139:1-7.
Maki KC, Carson ML, Miller MP, Kerr Anderson
WH, Turowski M, Reeves MS, Kaden V, Dicklin MR. Hydroxymethylcellulose lowers cholesterol in statin-treated men and
women with primary hypercholesterolemia. Eur
J Clin Nutr. 2008 (in press).
Toth PP, Maki
KC. A commentary on the implications of the ENHANCE (ezetimibe and
simvastatin in hypercholesterolemia enhances atherosclerosis regression) trial:
should ezetimibe move to the “back of the line” as a therapy for dyslipidemia? J Clin Lipidol. 2008;2:313-317.
Maki KC, Reeves MS,
Carson ML, Miller MP, Turowski M, Rains TM, Anderson K, Papanikolaou Y, Wilder
DM. Dose-response characteristics of
high-viscosity hydroxypropylmethylcellulose in subjects at risk for the
development of type 2 diabetes mellitus. Diabetes Technol
Ther. 2008 (in press).
Voss AC, Maki KC, Carvey TW, Hustead DS, Alish C, Fix B, Mustad VA. Effect of two
carbohydrate-modified tube-feeding formulas on metabolic responses in patients
with type 2 diabetes. Nutrition. 2008;24:990-997.
Maki KC, McKenney JM, Reeves MS, Lubin BC,
Dicklin MR. Effects of adding prescription omega-3 fatty acid ethyl esters to
simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women
with mixed dyslipidemia. American Journal of Cardiology. 2008;102:429-33. Erratum Am J Cardiol. (in press).
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Abstracts/Presentations
American Heart Association – 49th Cardiovascular Disease Epidemiology and Prevention Conference. Maki KC, Davidson MH, Doyle
RT, Ballantyne CM. Effect
of Prescription Omega-3 Fatty Acids on Non-HDL Cholesterol (Stratified by
Baseline LDL Cholesterol Level) in Statin-Treated Patients with
Hypertriglyceridemia. March 11-14, 2009, Poster.
American Heart Association – 49th Cardiovascular Disease Epidemiology and Prevention Conference. Davidson MH, Maki
KC, Feinstein S, Bell M. Triglyceride/High-density
Lipoprotein Cholesterol Ratio is the Strongest Predictor of Carotid
Intima-media Thickness Progression. March 12, 2009, Poster.
American Osteopathic Academy of Sports Medicine. Reeves MR. Judicious
Use of NSAIDs in Athletic Populations. October 29th, 2008. Oral presentation.
American Dietetic Association 2008. Maki KC, Carson, ML, Miller, MP, Anderson WHK, Turowski M, Reeves
MS, Dicklin MR. Hydroxypropylmethylcellulose lowers cholesterol in statin-treated men
and women with primary hypercholesterolemia. October 28, 2008. Oral presentation, Session 112.
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Books and Book Chapters
·
Toth
PP, Maki KC. Practical Lipid
Management: London: John Wiley & Sons. Practical Lipid Management: Concepts and Controversies, is a text on the clinical
management of dyslipidemias. As its title suggests, the book provides a
straightforward and practical approach to the identification and treatment of
abnormalities in lipid metabolism. The target audience consists of family
physicians, internists, nurse practitioners, physician assistants,
cardiologists, endocrinologists and allied health professionals involved in the
care of patients with lipid disorders. The book is available for purchase at
Amazon.com.
·
The
book Therapeutic Lipidology edited by Drs. Michael Davidson, Peter Toth and Kevin Maki is
available for purchase at Amazon.com.
·
Maki KC.
High-viscosity hydroxypropylmethylcellulose (HV-HPMC) a promising agent for metabolic
risk factor management. ACS Press, 2008
(in press).
 
·
Maki KC, Matsuo N, Dicklin MR. Clinical studies evaluating the benefits
of diacylglycerol for managing excess adiposity. In: Katsuragi Y, Yasukawa T, Matsuo N,
Flickinger BD, Tokimitusu I, and Matlock MG. (eds) Chapter 10. Diacylglycerol Oil, AOCS Press, 2nd ed. 2008.
·
Maki, KC and Dicklin M. How well do various lipids
and lipoprotein measures predict cardiovascular disease morbidity and mortality. In: Toth PP, Sica D. (eds). Clinical Challenges in Lipid Disorders.
Oxford: Clinical Publishing. June, 2008.
·
Huth
PJ, Rains TM, Yang Yifan, Philips
SM. Current and emerging role of whey protein on muscle accretion. In: Onwulata CI and Huth PJ. (eds) Chapter
13. Whey Processing, Functionality and
Health Benefits. Wiley-Blackwell. 2008.
Rosuvastatin
to Prevent Vascular Events in Men and Women with Elevated C-Reactive
Protein. Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Jr., Kastelein
JJP, et al for the Justification for the Use of Statins in Prevention: an
Intervention Trial Evaluating Rosuvastatin (JUPITER) Study Group
Background: Statins are recommended as first-line therapy for prevention of
cardiovascular events in high-risk patients, including those with
hyperlipidemia, diabetes, and cardiovascular disease. However, many cardiovascular events occur in
people for whom lipid drug therapy is not recommended under the current
guidelines. High-sensitivity C-reactive
protein (hs-CRP) is an inflammatory biomarker that is predictive of cardiovascular
events in normolipidemic and hyperlipidemic individuals. Studies have demonstrated that statin therapy
reduces hs-CRP levels. However, whether
or not lowering hs-CRP with statin therapy translates to reductions in
cardiovascular events is unknown. The
JUPITER trial was conducted to evaluate whether rosuvastatin (20 mg/d),
compared with placebo, would decrease the rate of occurrence of first major
cardiovascular events (nonfatal myocardial infarction, nonfatal stroke,
arterial revascularization, hospitalization for unstable angina, death due to
cardiovascular causes) in otherwise healthy individuals with elevated hs-CRP
and low-density lipoprotein cholesterol (LDL-C) levels below 130 mg/dL.
Methods: This was a randomized, double-blind, placebo-controlled trial conducted
at 1,315 sites in 26 countries. Men aged
50 years and older, and women aged 60 years and older, with no history of
cardiovascular disease, LDL-C <130 mg/dL, hs-CRP ≥2 mg/L, and
triglycerides <500 mg/dL were eligible for enrollment. Subjects were assigned randomly (1:1) to
receive rosuvastatin (20 mg/d) or matched placebo pills for up to 5 years. Follow-up visits were conducted at 13 weeks
and twice annually thereafter. Laboratory evaluations, pill counts, and assessments of cardiovascular
and other adverse events were performed during follow-up.
Results: A total of 17,802 subjects were randomly assigned to treatment, 8901 to
each group (rosuvastatin 20 mg/d or placebo). The majority of subjects were white (71.1%) and male (61.8%) with a
median age of 66 years (range 60 – 71 years). At baseline, median (interquartile range) LDL-C and hs-CRP levels were
108 mg/dL (94 – 119 mg/dL) and 4.3 mg/L (2.8 – 7.2 mg/L), respectively. At 12 months, rosuvastatin therapy reduced
LDL-C by 50% and hs-CRP by 37% compared with placebo. The study was terminated on a recommendation
from the data safety monitoring committee after a median follow-up of 1.9 years
because of benefits observed in the rosuvastatin group.
The rates of the primary endpoint,
first occurrence of a major cardiovascular event, were 0.77 and 1.36 per 100
person-years of follow-up in the rosuvastatin and placebo groups, respectively
(hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 -
0.69, p <0.00001). Corresponding
rates were 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI,
0.30 – 0.70, p = 0.0002); 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI,
0.34 – 0.79, p = 0.002); 0.41 and 0.77 for revascularization or unstable angina
(hazard ratio, 0.53; 95% CI, 0.40 – 0.70, p <0.00001); 0.45 and 0.85 for the
combined endpoint of myocardial infarction, stroke, or death from
cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 – 0.69, p <
0.00001); and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95%
CI, 0.67 – 0.97, p = 0.02).
Similar results were observed in
subgroup analyses in which the study sample was stratified by age,
race/ethnicity, risk factors (smoking status, body weight, metabolic syndrome,
family history of cardiovascular disease), and Framingham risk score. Compared with the rosuvastatin group, the
control group had a significantly higher incidence of death from cancer (58 vs.
35 events, p = 0.02). The incidence of
newly diagnosed diabetes (physician-reported) was significantly higher in the
rosuvastatin group (270 vs. 216 reports, p = 0.01).
Conclusion: These findings demonstrate that, compared with placebo, rosuvastatin (20
mg/d) significantly reduced the incidence of major cardiovascular events and
death from any cause in otherwise healthy subjects with elevated hs-CRP and
relatively normal levels of LDL-C.
Dr.
Maki’s Commentary. In 1998, the
publication of the Air Force/Texas Coronary Atherosclerosis Prevention Study
results showed that treatment with a statin (lovastatin) was effective for
primary prevention of cardiovascular events (relative risk 0.63, p < 0.001)
in subjects with low HDL-C, most of whom (83%) would not have qualified for
lipid drug therapy under the guidelines in force at the time (1). This confirmed that the overriding policy
question was not who could potentially have their cardiovascular event risk
lowered by statin therapy, but rather for whom is treatment
cost-effective. The results from JUPITER
underscore this point and add a new element to the debate, the question of
whether, and if so, when clinicians should test for elevated hs-CRP as part of
cardiovascular disease risk assessment.
Current recommendations from the
American Heart Association and Centers for Disease Control and Prevention
suggest screening for elevated hs-CRP only in those at moderately high (10-20%)
10-year CHD event risk based on Framingham risk scoring (2). Additional analyses from the JUPITER database
may help to determine whether hs-CRP screening might be helpful to identify
those who, on the basis of their Framingham risk score, would otherwise be
considered at low or moderate risk, but whose CHD event risk is actually higher
due to elevated hs-CRP. Use of hs-CRP
may also help to refine recommendations for who should receive very aggressive
therapy with LDL-C and non-HDL-C goals of <70 and <100 mg/dL,
respectively.
The JUPITER results provide clear
evidence that those with elevated hs-CRP are at increased CHD risk and that
rosuvastatin therapy lowers this risk. However, JUPITER did not answer the question of whether hs-CRP reduction per se should be a target of
therapy. An additional outstanding
question is the mechanisms that account for the increased risk associated with
elevated hs-CRP. Is hs-CRP elevation reflecting
vascular inflammation, dysregulation of adipose tissue resulting in the release
of pro-inflammatory cytokines, greater hepatic sensitivity to inflammatory
stimuli, or does hs-CRP itself promote some aspect of the atherothrombotic
process? Results from genetic studies indicate
that polymorphisms associated with elevated CRP are not themselves predictive
of cardiovascular disease risk, suggesting that CRP itself is not raising risk,
but instead that acquired hs-CRP elevation is a marker for some process that is
proatherogenic and/or prothrombotic (3, 4). One challenge associated with using hs-CRP clinically as a
cardiovascular risk marker is that it increases transiently for reasons that
may be unrelated to atherothrombotic risk, such as after a minor trauma or
during an infection such as the common cold. Lipoprotein associated phospholipase A2 is a marker that is believed to
be more specific for vascular inflammation and, like hs-CRP, is a strong
predictor of cardiovascular event risk (5). At present it is not clear whether these markers provide comparable information
regarding event risk and what the implications might be of elevations in one,
the other or both concurrently.
Many additional questions remain as
well, including the degree to which treatment with drugs other than
rosuvastatin, including other statins, might benefit those with elevated hs-CRP
levels and whether greater hs-CRP reduction will translate into greater risk
reduction. Thus, JUPITER is a major
milestone in our understanding of risk reduction with lipid-altering drug therapy, it is not clear at present how the results from
JUPITER will be incorporated into treatment guidelines.
References
1.
Downs
JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events
with lovastatin in men and women with average cholesterol levels: results of
AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615-22.
2.
Pearson
TA, Mensah, GA, Alexander RW, Anderson JL, Cannon III RO, Criqui M, et al. Markers of inflammation and cardiovascular
disease. Applications to clinical and public health practice. A statement for
healthcare professionals from the Center for Disease Control and Prevention and
the American Heart Association. Circulation. 2003;107:499-511.
3.
Schunkert
H, Samani N. Elevated c-reactive protein in atherosclerosis – chicken or egg. N Engl J Med. 2008;359:1953-1955.
4.
Zacho
J, Tybjaerg-Hansen A, Jensen JS, Grande P, Sillesen H, Nordestgaard BG. Genetically elevated c-reactive protein and ischemic vascular disease. N
Engl J Med. 2008;359:1897-1908.
5.
Davidson
MH, Corson MA, Alberts MJ, Anderson JL, Gorelick PB, Jones PH, et al. Consensus panel recommendation for
incorporating lipoprotein-associated phospholipase A2 testing into
cardiovascular disease risk assessment guidelines. Am J Cardiol. 2008;101:51F-57F.
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Provident has a team of research professionals
with extensive experience in the design and conduct of clinical trials to
evaluate pharmaceuticals, medical and functional foods, dietary supplements and
medical devices.
For
more information, visit our web site: http://www.providentcrc.com.
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