By Hilton Kolbe and
agencies
Dr. Elshazly is currently working in the Osler Internal
Medicine Residency program at Johns Hopkins Hospital in Baltimore, Maryland and
has also taken up Cardiology Fellowship at Cleveland Clinic, in Ohio. Dr. Al-Hijji, is currently doing his final
year of internal medicine residency at Johns Hopkins Hospital.
The title of the study is: Non-HDL Cholesterol, Guideline
Targets, and Population Percentiles for Secondary Prevention in a Clinical
Sample of 1.3 Million Adults The Very Large Database of Lipids (VLDL-2 Study).
The study presents a new analysis of 1.3 million individuals
that highlights the magnitude of patient-level discordance between LDL and
non-HDL percentiles.
According to the report, there is significant discordance
between LDL and non-HDL percentiles at lower LDL and higher triglyceride
levels.
In the study, Dr. Elshazly and colleagues wrote: “Current
non-HDL cutpoints for high-risk patients may need to be lowered to match
percentiles of LDL cutpoints. Relatively small absolute reductions in non-HDL
cutpoints result in substantial reclassification of patients to higher
treatment categories with potential implications for risk assessment and
treatment.”
The researchers investigated whether non-HDL goals should be
used at the same population percentiles as LDL goals, as suggested by previous
research. They examined lipid
profiles of 1,310,440 US adults (mean age, 59 years; 52% women) included
in the Very Large Database of Lipids. Participants had triglyceride
levels of less than 400 mg/dL and underwent lipid testing by vertical spin
density gradient ultracentrifugation (Atherotech) from 2009 to 2011.
“Low-density lipoprotein cholesterol (LDL-C) has always been
referred to as the “bad” cholesterol and high-density lipoprotein (HDL-C) as
the “good” cholesterol. However, as the prevalence of obesity, diabetes
mellitus and metabolic syndrome increased over the past few decades, we have
witnessed an increase in other types of “bad” cholesterol such as Very
Low-density lipoprotein, Intermediate density lipoprotein, cholesterol remnants
and Lipoprotein[a],” Dr. Elshazly said.
“All these atherogenic lipoproteins in addition to LDL-C are
included in non-HDL cholesterol, which is simply calculated by subtracting
HDL-C (good cholesterol) from total cholesterol and available in the standard
lipid profile at no additional cost or inconvenience. “
Dr. Elshazly said over the past two decades, numerous
studies have suggested that non-HDL-C is a better marker of cardiovascular
disease risk and a better target for lipid-lowering therapy than LDL-C but this
has not been reflected in the most recent cholesterol guidelines. The current
worldwide guidelines recommend using non-HDL-C only as a secondary treatment
target in patients with triglyceride levels of at least 200 mg/dl.
Therefore, we are potentially treating some patients only to their optimal LDL-C
goal while their non-HDL-C value remains above goal.
“Our research group at the Johns Hopkins Ciccarone Center
for prevention acquired a database of 1.3 million patients who underwent lipid
profiling by direct ultracentrifugation (Vertical Autoprofile test by
Atherotech, Birmingham, Alabama, USA) from 2009 to 2011. Their age, sex and
lipid parameter distributions closely matched those of the National Health and
Nutrition Examination survey, a nationally representative sample of the USA
population.,” he said.
“It is registered on clinicaltrials.gov
as the Very Large Database of Lipids (NCT01698489). We aimed to use this
gigantic database to highlight the amount of patient-level discordance between
non-HDL-C and LDL-C percentiles and the potential for inadequate treatment in
the structure of current guidelines.
“We found that a significant proportion of individuals are
reclassified to higher ATP III (Adult Treatment Panel III) treatment categories
when non-HDL-C is used to classify them rather than LDL-C. In addition, there
is significant discordance between population percentiles of LDL-C and
non-HDL-C particularly when accuracy is most crucial; at LDL-C in the treatment
range of high-risk patients and at high triglycerides.
“For example, in patients with LDL-C levels less than 70
mg/dl, 15% had a non-HDL-C value of at least 100 mg/dl, the cutpoint
recommended by guidelines, while 25% had a non-HDL-C level of at least 93
mg/dl, the cutpoint based on percentile equivalence. The percentages increased
to 22% and 50%, respectively, if triglycerides were 150 mg/dl to 199 mg/dl
concurrently.
“We concluded that lowering conventional non–HDL-C cutpoints
for high-risk patients to match percentiles of LDL-C cutpoints as well as wider
adoption of non–HDL-C in clinical practice might potentially improve secondary
prevention outcomes and residual risk assessment and treatment. Therefore,
clinicians should be more aggressive about treating their high-risk patients to
LDL-C as well as non-HDL-C goals. They should consider using lower non-HDL-C
goals for secondary prevention as highlighted in our study.”
Dr. Elshazly first got involve in the project in 2011 when
he I started working with the Ciccarone Center of Prevention of the Johns
Hopkins Department of Cardiology.
“We started working on this 1.3 million patients database
called the Very Large Database of Lipids and published our first paper in the
Journal of the American College of Cardiology (Martin SS. Blaha MJ, Elshazly
MB. Friedewald) of estimated versus directly measured low-density lipoprotein
cholesterol and treatment implications.
“We presented several abstracts from this database in the
American College of Cardiology meetings in 2012 and 2013, American Heart
Association meetings in 2012 and 2013 and Arteriosclerosis, Thrombosis and
Vascular Biology Scientific Sessions in 2013. And I also participated in an
interview on Yahoo Health with Dr. Blaha,” Dr. Elshazly said.
Later he moved on to work on his non-HDL-C study with his
mentors Dr. Steven Jones and Dr. Seth Martin at Johns Hopkins Hospital, who are
experts in the fields of lipids and atherosclerosis.
Dr. Elshazly was
lavish in praise of his medical and research training in Doha. “WCMC-Q had a
great impact on what I am doing today. There were tremendous opportunities to
do research in medical school such as summer research scholarships to WCMC-NY as
well as state supported funds to do research in Qatar such as UREP and QNRF and
I participated in both.
“In addition, WCMC-Q was my road to joining internal
medicine residency at Johns Hopkins followed by cardiology fellowship at the
Cleveland Clinic. Therefore, I will always be grateful to Qatar Foundation,
WCMC-Q and Qatar’s leadership for their investment in research and the human
potential and I hope I will be able to use my research expertise to help
advance medicine and cardiovascular research in the Middle East,” Dr. Elshazly
said.
The study population included 1,310,440 U.S. adults who had
triglyceride levels below 400 mg/dL. Their mean age was 59 years, and 52% were
women. The authors found that LDL-C cutpoints of 70 mg/dL, 100 mg/dL, 130
mg/dL, 160 mg/dL and 190 mg/dL corresponded to the same population percentiles
as non-HDL-C levels of 93 mg/dL, 125 mg/dL, 157 mg/dL, 190 mg/dL and 223 mg/dL,
respectively.
When patients were reclassified by non-HDL-C, a significant
proportion moved to a higher treatment category compared with LDL-C, especially
high-risk patients and patients with a triglyceride level of 150 mg/dL or
greater.
Fifteen percent of patients with an LDL-C level below 70
mg/dL had a non-HDL-C level of 100 mg/dL, the guideline-based cutpoint, while
25% had a non-HDL-C of 93 mg/dL or greater, the percentile-based cutpoint. When
triglyceride levels between 150 and 199 mg/dL were also considered, 22% of
patients with an LDL-C level below 70 mg/dL had a non-HDL-C level of 100 mg/dL
and 50% had a non-HDL-C of 93 mg/dL or greater.
The authors acknowledged that clinical and demographic data
were limited and that they could not determine the effect of reclassification
on clinical outcomes, among other limitations. However, they concluded that
patient-level discordance exists between non-HDL-C and LDL-C percentiles,
especially at lower LDL-C and higher triglyceride levels, when they said
accuracy is most critical.
"Lowering conventional non-HDL-C cutpoints for
high-risk patients to match percentiles of LDL-C cutpoints as well as wider
adoption of non-HDL-C in clinical practice may potentially improve secondary
prevention outcomes and residual risk assessment and treatment," the
authors wrote.
The study results
were first published online August 21, 2013 by the Journal of the American
College of Cardiology.
PANEL BOX plus
photos for illustration
Study: Non-HDL
Cholesterol, Guideline Targets, and Population Percentiles for Secondary
Prevention in a Clinical Sample of 1.3 Million Adults The Very Large Database
of Lipids (VLDL-2 Study).
Mohamed B. Elshazly, MD; Seth S. Martin, MD; Michael J.
Blaha, MD, MPH; Parag H. Joshi, MD; Peter P. Toth, MD, PhD, FACC; John W.
McEvoy, MB BCh; Mohammed A. Al-Hijji, MD; Krishnaji R. Kulkarni, PhD; Peter O.
Kwiterovich, MD; Roger S. Blumenthal, MD, FACC; Steven R. Jones, MD, FACC
J Am Coll Cardiol.
Abstract
Objectives
To examine patient-level discordance between population
percentiles of non-HDL cholesterol (non-HDL-C) and LDL cholesterol (LDL-C).
Background
Non-HDL-C is an alternative to LDL-C for risk stratification
and lipid-lowering therapy. The justification for the present guideline-based
non-HDL-C cutpoints of 30 mg/dL higher than LDL-C cutpoints remains largely
untested.
Methods
We assigned population percentiles to non-HDL-C and
Friedewald-estimated LDL-C values of 1,310,440 U.S. adults with triglycerides
< 400 mg/dL who underwent lipid testing by vertical spin density gradient
ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011.
Results
LDL-C cutpoints of 70, 100, 130, 160, and 190 mg/dL were in
the same population percentiles as non-HDL-C values of 93, 125, 157, 190, and
223 mg/dL, respectively. Non-HDL-C reclassified a significant proportion of
patients within a higher treatment category compared with Friedewald LDL-C,
especially at LDL-C levels in the treatment range of high-risk patients and at
triglyceride levels ≥ 150 mg/dL. Of patients with LDL-C < 70 mg/dL, 15% had
a non-HDL-C ≥ 100 mg/dL (guideline-based cutpoint) and 25% had a non-HDL-C ≥ 93
mg/dL (percentile-based cutpoint); 22% and 50% respectively if triglycerides
concurrently 150-199 mg/dL.
Conclusions
There is significant patient-level discordance between
non-HDL-C and LDL-C percentiles at lower LDL-C and higher triglycerides; a
finding with implications for treatment of high-risk patients. Current
non-HDL-C cutpoints for high-risk patients may need to be lowered to match percentiles
of LDL-C cutpoints. Relatively small absolute reductions in non-HDL-C cutpoints
result in substantial reclassification of patients to higher treatment
categories with potential implications for risk assessment and treatment.
Clinical trial info VLDL-2;
NCT01698489
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