Risk of Major Cardiovascular Events by LDL-Cholesterol Level (mg/dL): Among those treated with high-dose statin therapy, more than 40% of patients failed to achieve an LDL-cholesterol target of less than 70 mg/dL.
Reporter: Aviva Lev-Ari, PhD, RN
Lower LDL Still Best: Very Low Levels of LDL Linked with Reduced CV Events
AMSTERDAM, THE NETHERLANDS — The question of how low LDL-cholesterol levels should be in the present statin era, recently addressed with the new US clinical guidelines, is once again questioned with the new publication of a patient-level meta-analysis of eight clinical trials investigating statin therapy[1].
The new meta-analysis, published July 28, 2014 in the Journal of the American College of Cardiology, suggests that lowering LDL-cholesterol levels to very low levels results in a significant reduction in cardiovascular events. Individuals with LDL-cholesterol levels <50 mg/dL had a significantly lower risk of major cardiovascular events compared with individuals who had higher LDL-cholesterol levels, including those with LDL levels 50 to <75 mg/dL and 75 to <100 mg/dL.
The Results From the Meta-analysis
The investigators, including first author Dr Matthijs Boekholdt (Academic Medical Center), analyzed eight trials and 38 153 patients treated with statin therapy. The studies included some of the landmark statin trials, including AFCAPS-TexCAPS , 4S , LIPID , SPARCL , TNT , IDEAL , and JUPITER .
The investigators observed a large degree of interindividual variability in the reductions of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B (apoB) levels with statin therapy. Among those treated with high-dose statin therapy, more than 40% of patients failed to achieve an LDL-cholesterol target of less than 70 mg/dL.
Compared with individuals with LDL-cholesterol levels >175 mg/dL, which served as the reference group, individuals who achieved lower levels of LDL cholesterol had a significantly lower risk of major cardiovascular events. For those with LDL-cholesterol levels <50 mg/dL, 50 to <75 mg/dL, and 75 to <100 mg/dL, the relative reduction in risk was 56%, 49%, and 44%, respectively. Regarding the end point of major coronary events and cerebrovascular events, a similar trend was observed with lower LDL cholesterol levels.
Risk of Major Cardiovascular Events by LDL-Cholesterol Level (mg/dL)
| Outcome | LDL <50 | 50 to <75 | 75 to <100 | 100 to <125 | 125 to <150 | 150 to <175 | > 175 |
| Major cardiovascular events | 0.44 (0.35–0.55) | 0.51 (0.42–0.62) | 0.56 (0.46–0.67) | 0.58 (0.48–0.69) | 0.64 (0.53–0.79) | 0.71 (0.56–0.89) | 1.00 (ref) |
References
- Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoprotein and the risk for cardiovascular events. J Am Coll Cardiol 2014; DOI:10.1016.j.jacc.2014.02.615. Available at:http://content.onlinejacc.org/journal.aspx
- Ben-Yehuda O, DeMaria AN. LDL-cholesterol after the ACC/AHA 2013 guidelines. J Am Coll Cardiol 2014; DOI:10.1016.j.jacc.2014.05.020. Available at: http://content.onlinejacc.org/journal.aspx
SOURCE
http://www.medscape.com/viewarticle/828967?nlid=62503_2562&src=wnl_edit_medp_card&uac=93761AJ&spon=2
Other related articles published in this Open Access Online Scientific Journal include the following:
- Endothelium, Angiogenesis, and Disordered Coagulation
What is the Role of Plasma Viscosity in Hemostasis and Vascular Disease Risk?
Larry H Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN
Special Considerations in Blood Lipoproteins, Viscosity, Assessment and Treatment
Larry H Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN
Larry H Bernstein, MD, FACP
Stephen J Williams, PhD
Nitric Oxide Function in Coagulation – Part II
Larry H Bernstein, MD, FACP
Nitric Oxide, Platelets, Endothelium and Hemostasis (Coagulation Part II)
Larry H Bernstein, MD, FACP
Aviva Lev-Ari, PhD, RN
- Hypertension BioMarkers
Hypertension – JNC 8 Guideline: Henry R. Black, MD, Michael A. Weber, MD and Raymond R. Townsend, MD
Aviva Lev-Ari, PhD, RN
Justin D. Pearlman, MD, PhD and Aviva Lev-Ari, PhD, RN
Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus
Justin D. Pearlman, MD, PhD and Aviva Lev-Ari, PhD, RN
Arterial Hypertension in Young Adults: An Ignored Chronic Problem
Manuela Stoicescu, MD, PhD
An Important Marker of Hypertension in Youth
Manuela Stoicescu, MD, PhD
IF Elevated Pediatric Blood Pressure THEN High Adult Arterial Stiffness
Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
- Inflammatory, Atherosclerotic and Heart Failure Markers
Cardiovascular Risk: C-Reactive Protein BioMarker and Plasma Fibrinogen
Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
The Cardiorenal Syndrome in Heart Failure: Cardiac? Renal? syndrome?
Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
Voice from the Cleveland Clinic: On the New Lipid Guidelines and On the ACC/AHA Risk Calculator
Aviva Lev-Ari, PhD, RN
Atherogenesis: Predictor of CVD the Smaller and Denser LDL Particles
Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
Recombinant Human Lecithin-Cholesterol Acyltransferase (rhLCAT): New Biomarker for Atherosclerosis
Aviva Lev-Ari, PhD, RN
Identification of Biomarkers that are Related to the Actin Cytoskeleton
Larry H Bernstein, MD, FCAP
Leptin Signaling in Mediating the Cardiac Hypertrophy associated with Obesity
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Publications on Heart Failure by Prof. William Gregory Stevenson, M.D.
Aviva Lev-Ari, PhD, RN
Aviva Lev-Ari, PhD, RN
2012pharmaceutical
Amandeep Kaur
Aashir Awan, Phd
Abhisar Anand
Adina Hazan
Alan F. Kaul, PharmD., MS, MBA, FCCP
alexcrystal6
anamikasarkar
apreconasia
aviralvatsa
David Orchard-Webb, PhD
danutdaagmailcom
Demet Sag, Ph.D., CRA, GCP
Dror Nir
dsmolyar
Ethan Coomber
evelinacohn
Gail S Thornton
Irina Robu
jayzmit48
jdpmd
jshertok
kellyperlman
Ed Kislauskis
larryhbern
Madison Davis
marzankhan
megbaker58
ofermar2020
Dr. Pati
pkandala
Rosalind Codrington, PhD
ritusaxena
Rick Mandahl
sjwilliamspa
Srinivas Sriram
stuartlpbi
Dr. Sudipta Saha
tildabarliya
vaishnavee24
zraviv06
zs22
This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.
This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.