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.
To examine patient-level discordance between population percentiles of non-HDL cholesterol (non-HDL-C) and LDL cholesterol (LDL-C).
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.
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.
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.
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