Improving Statin Adherence Would Reduce Need For Expensive PCSK9 Inhibitors

MedicalResearch.com Interview with:
Julia M. Akeroyd, MPH

Center for Innovations in Quality, Effectiveness, and Safety (IQuESt)
Michael E. DeBakey Veteran Affairs Medical Center
Salim S Virani, MBBS, Ph.D.
Baylor College of Medicine

MedicalResearch.com: What is the background for this study?

Response: In the recently published Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial, treatment with evolocumab resulted in a 15% relative (1.5% absolute) risk reduction of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD) at a median follow-up of 2.2 years. Given the high cost of evolocumab, there is a need to identify what proportion of ASCVD patients would qualify for evolocumab based on FOURIER entry criteria and how eligibility would change if maximal doses of evidence-based lipid lowering therapies were required.

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Many Eligible Groups Not Receiving Recommended Statin Therapy

MedicalResearch.com Interview with:
Dr. Yashashwi Pokharel MD, MSCR
Department of Cardiovascular Research
Saint Luke’s Mid-America Heart Institute
Kansas City, Missouri and
Salim S. Virani, MD PhD, FACC, FAHA
Associate Professor, Section of Cardiovascular Research
Associate Director for Research, Cardiology Fellowship Training Program
Baylor College of Medicine
Investigator, Health Policy, Quality and Informatics Program
Michael E. DeBakey Veterans Affairs Medical Center HSR&D Center of Innovation
Staff Cardiologist, Michael E. DeBakey Veterans Affairs Medical Center
Houston, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Unlike the previous cholesterol management guideline that recommended use of either statin and non-statin therapy to achieve low density lipoprotein cholesterol (LDL-C) target, the 2013 American College of Cardiology/American Heart Association cholesterol management guideline made a major paradigm shift by recommending statin focused treatment in 4 specific patient groups and replaced LDL-C target with fixed statin intensity treatment (moderate to high intensity statin therapy).

With this change, it was speculated that a large number of patients would be eligible for statin treatment (in one study, up to 11.1% additional patients were expected to be eligible for statin therapy). Our study provided the real world trends in the use of statin and non-statin lipid lowering therapy (LLT) from a national sample of cardiology practices in 1.1 million patients 14 months before and 14 months after the release of the 2013 guideline.

We found a modest, but significant increasing trend in the use of statin therapy in only 1 of the 4 patient groups eligible for statin therapy (i.e., 4.3% increase in the use of moderate to high intensity statin therapy in patients with established atherosclerotic cardiovascular disease). We did not find any significant change in non-statin LLT use. Importantly, about a third to half of patients in statin eligible groups were not receiving moderate to high intensity statin therapy even after the publication of the 2013 guideline.

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PCSK9 Inhibition with Alirocumab Increases Removal of LDL Cholesterol

MedicalResearch.com Interview with:
Henry N. Ginsberg, MD

Irving Institute for Clinical and Translational Research
Columbia University
Columbia College of Physicians and Surgeons
New York, NY

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies in mice and cells have identified increased hepatic low density lipoprotein (LDL) receptors as the basis for LDL lowering by PCSK9 inhibitors, but there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism, particularly effects on very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) or LDL metabolism.

This study in 18 healthy subjects, found that alirocumab decreased the number of IDL and LDL particles in the circulation, and their associated cholesterol and apoB levels by increasing efficiency of the clearance of IDL and LDL. There were not effects on VLDL metabolism. The increased clearance of IDL meant that less LDL was produced from IDL, which is the precursor of LDL. Thus, the dramatic reductions in LDL cholesterol resulted from both less LDL being produced and more efficient clearance of LDL. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.

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Meta-analysis of Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk

MedicalResearch.com Interview with:
Dominik D Alexander, PhD, MSPH

Principal Epidemiologist
EpidStat Institute
Ann Arbor, MI Seattle, WA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years, the body of scientific literature on n-3 LCPUFA (EPA/DHA) intake and coronary heart disease (CHD) risk has exploded with mixed results. It was only logical to conduct a comprehensive meta-analysis of randomized controlled trials (RCTs) to estimate the effect of EPA+DHA on CHD, and to conduct a comprehensive meta-analysis of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk.

Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA
provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event.

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Some Type 2 Diabetics May Benefit From Adding Fenofibrate To Statins

MedicalResearch.com Interview with:

Marshall B. Elam PhD MD Professor Pharmacology and Medicine (Cardiovascular Diseases) University of Tennessee Health Sciences Center Memphis

Dr. Marshall B. Elam

Marshall B. Elam PhD MD
Professor Pharmacology and Medicine
(Cardiovascular Diseases)
University of Tennessee Health Sciences Center
Memphis

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This manuscript presents the findings of extended follow up of patients with Type 2 Diabetes who were treated with fenofibrate, a member of a group of triglyceride lowering medications known as fibrates or PPAR alpha agonists, as part of the Action to Control Cardiovascular Risk in T2DM (ACCORD) study.

ACCORD was designed to test the effect of intensive treatment of cardiovascular risk factors including blood glucose, blood pressure and lipids on risk of heart attack, stroke and cardiac death in patients with Type 2 Diabetes.

The lipid arm of ACCORD tested the hypothesis that adding fenofibrate to statin therapy would further reduce risk of these cardiovascular events.

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Familial Hypercholesterolemia Diagnosed Through EHR and Genetics Data

MedicalResearch.com Interview with:

Michael F. Murray MD Geisinger Health System Danville, PA 17822

Dr. Michael Murray

Michael F. Murray MD
Geisinger Health System
Danville, PA 17822

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The DiscovEHR cohort was formed as a result of a research collaboration between Geisinger Health System and Regeneron Pharmaceuticals. There are over 50,000 patient participants in the cohort who have volunteered to have their de-identified genomic sequence data linked to their de-identified EHR data for research purposes. We report in this paper findings around the identification of 229 individuals (1:256) with pathogenic or likely pathogenic variants in one of the three genes (LDLR, APOB, PCSK9) associated with Familial Hypercholesterolemia (FH). The study found that these individuals are unlikely to carry a diagnosis of FH and are at risk for early coronary artery disease.

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PCSK9 Inhibitor Praluent Substantially Reduced LDL-C Cholesterol

MedicalResearch.com Interview with:

Dr. Eli M. Roth MD, FACC President, Medical Director Sterling Research Group Cincinnati, OH

Dr. Eli Roth

Dr. Eli M. Roth MD, FACC
President, Medical Director
Sterling Research Group
Cincinnati, OH

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: At this year’s AHA 2016, we presented a pharmacodynamics analysis of ODYSSEY CHOICE I, which evaluated the effects of Praluent 300 mg administered every four weeks (Q4W) for 24 weeks in hypercholesterolemia patients at moderate to very high cardiovascular risk who were on maximally tolerated statin or no statin and/or other lipid-lowering therapies.

The pharmacodynamic analysis of CHOICE I in patients on statins supports the use of Praluent 300 mg Q4W as an alternative starting dose for patients who prefer a Q4W dosing regimen and demonstrates the value of LDL-C based dosing interval adjustment. The findings from this analysis were consistent with prior ODYSSEY Phase 3 studies, showing that Praluent substantially reduced circulating free PCSK9 concentration, resulting in significant LDL-C reductions. Additionally, Praluent was generally well tolerated.

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Byproduct of Sweet Potato Waste Offers Clue To Lipid Metabolism

MedicalResearch.com Interview with:
Dr. Koji Ishiguro

National Agriculture and Food Research Organization
Japan

MedicalResearch.com: What is the background for this study?

Response: -Sweet potato (Ipomoea batatas L.) roots are not only used for human consumption, they are used to make starch materials, processed foods, and distilled spirits in Japan. Starch use accounts for about 15% (131,500 tons) of total sweet potato production. Starch residues are discharged during starch production and are mainly used in animal feed and compost. Large amounts of the wastewater, which can cause serious environmental problems, are discarded after clarification. Investigation into the uses of the by-products of the sweet potato starch industry would benefit both the environment and industry.

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High Intensity Statins Increase For High Risk Atherosclerotic Patients, But Lagging in Women and Minorities

MedicalResearch.com Interview with:

Fatima Rodriguez, MD, MPH Division of Cardiovascular Medicine and Cardiovascular Institute Stanford University Stanford, CA

Dr. Fatima Rodriguez

Fatima Rodriguez, MD, MPH
Division of Cardiovascular Medicine and Cardiovascular Institute
Stanford University
Stanford, CA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The 2013 ACC/AHA cholesterol management guidelines emphasized that high-risk patients with atherosclerotic disease should be on high-intensity statins. We sought to determine how these guidelines are being adopted at the Veterans Affairs (VA) Health System and to identify treatment gaps.

Our main findings were that the use of high-intensity statins increased from 23 to 35% following the guideline release for these high-risk patients. However, high-intensity statin use was lowest in Hispanics and Native Americans. Women, older adults, and patients with peripheral arterial and cerebrovascular disease were also less likely to undergo statin intensification after the release of the guideline. We also noted geographic and institutional differences across VA hospitals in rates of high-intensity statin use for secondary prevention.

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Americans Continue To Have Better Lipid Profiles

MedicalResearch.com Interview with:
Asher Rosinger, PHD, MPH
Epidemic Intelligence Service Officer, Centers for Disease Control and Prevention
Division of Health and Examination Nutrition Examination Surveys, Analysis Branch
National Center for Health Statistic

MedicalResearch.com: What is the background for this study?

Response: Total cholesterol, triglycerides, and low-density lipoprotein (LDL) levels are linked to coronary heart disease and cardiovascular events. Between 1999 and 2010, total cholesterol, triglycerides, and LDL levels declined among U.S. adults. We used new data from the 2011-2014 nationally representative National Health and Nutrition Examination Survey (NHANES) to determine if earlier trends continued.

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Cardioprotective Effect of PCSK9 Inhibitors Should Outweigh Potential Harm of Diabetes Risk

MedicalResearch.com Interview with:
Brian A. Ference, M.D
Division of Cardiovascular Medicine
Wayne State University School of Medicine
Detroit, MI

MedicalResearch.com: What are the main findings?

Response: Lifelong exposure to modestly lower plasma LDL-C levels caused by rare loss-of-function mutations in the PCSK9 gene is associated with a substantially lower lifetime risk of developing cardiovascular disease. This discovery motivated the development of monoclonal antibodies directed against PCSK9 which have now been shown to reduce plasma LDL-C levels by 50-60%. The cardiovascular medicine community is early anticipating the results of two large cardiovascular outcome trials that will determine if lowering LDL-C levels by inhibiting PCSK9 will reduce the risk of cardiovascular events.

Because monoclonal antibodies and other therapies directed against PCSK9 are designed to recapitulate the phenotype of PCSK9 loss-of-function mutations, we reasoned that it may be possible to anticipate the efficacy and safety results of the ongoing cardiovascular outcome studies by more precisely characterizing the effect of genetic variants in the PCSK9 gene on the risk of both cardiovascular events and new onset diabetes.

To do this, we a constructed genetic score consisting of multiple independently inherited variants in the PCK9 gene to create an instrument that mimics the effect of PCSK9 inhibitors. We then compared the effect of genetic variants that mimic the effect of PCSK9 inhibitors with the effect of genetic variants in the HMGCR gene that mimic the effect of statins to make inferences about the likely effect of PCSK9 inhibitors on the risk of cardiovascular events and new onset diabetes as compared to treatment with a statin.

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Phase1 Trial Supports PCSK9-Inhibitor Inclisiran For Reducing LDL Cholesterol

MedicalResearch.com Interview with:

Kevin Fitzgerald, Ph.D. Alnylam Pharmaceuticals Cambridge, MA 02142

Dr. Kevin Fitzgerald

Kevin Fitzgerald, Ph.D.
Alnylam Pharmaceuticals
Cambridge, MA 02142

MedicalResearch.com: What is the background for this study?

Response: Inclisiran (ALN-PCSsc) is a subcutaneously administered RNAi therapeutic targeting PCSK9 in development for the treatment of hypercholesterolemia. The Phase 1 trial of inclisiran was conducted in the U.K. as a randomized, single-blind, placebo controlled, single ascending-and multi-dose, subcutaneous dose-escalation study in 69 volunteer subjects with elevated baseline LDL-C (≥ 100 mg/dL). The primary objective of the study was to evaluate the safety, side effect profile, and pharmacodynamics effects of inclisiran.

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Hypertriglyceridemia Markedly Increases Risk of Acute Pancreatitis

MedicalResearch.com Interview with:
Borge G. Nordestgaard, MD, DMSc

Professor, University of Copenhagen
Chief Physician, Dept. Clinical Biochemistry, Herlev and Gentofte Hospital
Copenhagen University Hospital
Herlev, Denmark

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Acute pancreatitis is an inflammatory disorder of the pancreas with gallstones and high-alcohol consumption as leading risk factors, while mild-to-moderately increased plasma triglycerides hitherto has been overlooked. We surprisingly found that the risk of developing acute pancreatitis was increased already from triglycerides of 175 mg/dL (2 mmol/L) and above. When triglycerides were above 443mg/dL (5mmol/L) the risk was increased a massive 9-fold. Interestingly, this risk was higher than the corresponding 3.4-fold higher risk for myocardial infarction.

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Systematic Review Finds PCSK9 Inhibitors Reduce LDL-C and Are Well Tolerated

MedicalResearch.com Interview with:

Prof. Dr. Ioana Gouni-Berthold MD

Dr. Gouni Gerthold

Prof. Dr. Ioana Gouni-Berthold MD
Center for Endocrinology, Diabetes and Preventive Medicine (ZEDP)
University of Cologne
Cologne, Germany

MedicalResearch.com: What is the background for this study?

Response: In Europe, up to half of the population aged between 35 and 64 has hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C]), putting them at risk of heart disease. Despite increased treatment rates in recent years, many patients still do not receive adequate therapy, and heart disease remains the biggest cause of death in the USA and most European countries.

Two drugs, alirocumab and evolocumab, have recently been approved for lowering LDL-C in patients with hypercholesterolaemia as an ‘add-on’ therapy to other lipid-lowering medication, or for use alone in patients unable to tolerate statins. These drugs have a unique mode of action– they inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that binds to LDL receptors and targets them for degradation. In the absence of PCSK9, the LDL receptor recycling is restored and the receptors are able to remove LDL from the blood.

Both alirocumab and evolocumab have been tested in numerous patient populations in phase 3 trials; albeit evolocumab has an additional indication of homozygous familial hypercholesterolemia. We therefore felt that there was a need to collate the available data to assess the efficacy and safety of each agent. We chose reduction in LDL-C as our outcome of interest, because this was the primary endpoint of the pivotal clinical trials.

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Linoleic Acid (Omega-6) in Fatty Tissue Linked To Lower Mortality

MedicalResearch.com Interview with:

David Iggman, MD, PhD Unit for Clinical Nutrition and Metabolism Department of Public Health and Caring Sciences Uppsala University, Uppsala Center for Clinical Research Dalarna Falun, Sweden

Dr. David Iggman

David Iggman, MD, PhD
Unit for Clinical Nutrition and Metabolism
Department of Public Health and Caring Sciences
Uppsala University, Uppsala
Center for Clinical Research Dalarna
Falun, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is some controversy regarding which dietary fats are preferable and in what amounts, not least regarding the polyunsaturated fats. It is also challenging to adequately assess peoples intakes of dietary fats.

The main findings of this study was that among fatty acids in the body (reflecting the intake during the last year or so), linoleic acid (omega-6) was associated with lower mortality in 71-year-old men with 15 years follow-up.

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Not Enough Evidence To Recommend For or Against Cholesterol Screening In Children and Teens

MedicalResearch.com Interview with:

Dr. David Grossman M.D., M.P.H. Vice chair of the U.S. Preventive Services Task Force and Professor at the University of Washington Schools of Public Health and Medicine

Dr. David Grossman

Dr. David Grossman M.D., M.P.H.
Vice chair of the U.S. Preventive Services Task Force and
Professor at the University of Washington Schools of Public Health and Medicine

MedicalResearch.com: What is the background for this recommendation?

Response: The Task Force recognizes the importance of cardiovascular health for young people. Children and adolescents with high cholesterol are more likely to become adults with high cholesterol, and high cholesterol in adulthood can lead to serious health outcomes such as heart attacks and strokes. However, when the Task Force reviewed evidence for cholesterol screening in children and adolescents without any signs or symptoms, we found that there is not enough evidence to recommend for or against screening. In the face of unclear evidence, the Task Force is calling on the research community to prioritize studies on screening and treatment of lipid disorders in children and teens to help us all learn more about the impact that screening at an early age may have on the cardiovascular health of adults.

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Too Much ‘Good Cholesterol’ HDL Can Also Be A Bad Thing

MedicalResearch.com Interview with:

Ziyad Al-Aly, MD, FASN Assistant Professor of Medicine Washington University School of Medicine Co-Director, Clinical Epidemiology Center Associate Chief of Staff for Research and Education Veterans Affairs Saint Louis Health Care System

Dr. Ziyad Al-Aly

Ziyad Al-Aly, MD, FASN
Assistant Professor of Medicine
Washington University School of Medicine
Co-Director, Clinical Epidemiology Center
Associate Chief of Staff for Research and Education
Veterans Affairs Saint Louis Health Care System

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: I think the most important, and novel finding is that elevated levels of HDL-cholesterol (which is thought of as the good cholesterol) are associated with increased risk of death. Previously it was thought that high HDL (increased good cholesterol) is a good thing.

We used Big Data approach (over 16 million person-years; 1.7 million people followed for over 9 years) to evaluate the relationship between HDL-Cholesterol (the good cholesterol) and risk of death. We found that low HDL is associated with increased risk of death (which is expected and consistent with prior knowledge). The novel and unexpected finding is the observation that high HDL-Cholesterol is also associated with increased risk of death. The relationship between HDL-Cholesterol levels and risk of death is a U-shaped curve where risk is increased at both ends of the HDL-C values spectrum (at both low and high end); Too low and too high is associated with higher risk of death. The findings may explain why clinical trials aimed at increasing HDL-Cholesterol levels failed to show improvement of clinical outcomes.

This finding was not expected, and has not been reported previously in large epidemiologic studies such as Framingham Heart Study and others. The Framingham Heart study and others significantly advanced our understanding of the relationship between cholesterol parameters (including HDL-Cholesterol) and clinical outcomes. However, these studies are limited in that the number of patients in these cohorts was several thousands which is relatively small compared to what a Big Data approach (millions of patients) enables us to see. Big Data approach allows a more nuanced (a more detailed) examination of the relationship between HDL and risk of death across the full spectrum of HDL levels.

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US Task Force Reviews Lipid Screening For Children and Adolscents

MedicalResearch.com Interview with:

Paula Lozano, MD MPH Associate Medical Director, Research and Translation Group Health Physicians SENIOR INVESTIGATOR Group Health Research Institute Metropolitan Park East Seattle, WA 98101

Dr. Paula Lozano

Paula Lozano, MD MPH
Associate Medical Director, Research and Translation
Group Health Physicians
Senior Investigator
Group Health Research Institute
Metropolitan Park East
Seattle, WA 98101

MedicalResearch.com: What is the background for this study?

Response: This wasn’t a study, but rather a study of studies, to support the US Preventive Services Task Force in updating its previous recommendation of

I: insufficient to assess the balance of benefits and harms. We conducted two systematic evidence reviews of screening children and adolescents:

1. for familial hypercholesterolemia (FH, a genetic disorder that interferes with the body’s ability to metabolize cholesterol and can result in early coronary heart disease); and

2. for multifactorial dyslipidemia—which we defined as elevated LDL cholesterol or total cholesterol, not caused by familial hypercholesterolemia. LDL and total cholesterol were of interest because they are considered atherogenic.

One of the challenges of lipid screening in youth is that blood levels of these atherogenic lipids are known to fluctuate during the course of childhood and adolescence. It’s sort of a W-shaped curve, with a peak at age 9-11 years. So for a given child, the definition of what’s an elevated LDL or total cholesterol level will change with age. Also, two-thirds of kids identified as having high cholesterol through universal screening would not go on to have high cholesterol as adults.

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Study Evaluates Effects of Polyunsaturated Fats on Development of Diabetes

MedicalResearch.com Interview with:

Dr. Fumiaki Imamura Ph.D. MRC Epidemiology Unit University of Cambridge

Dr. Fumiaki Imamura

Dr. Fumiaki Imamura Ph.D.
MRC Epidemiology Unit
University of Cambridge

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There was insufficient evidence for effects of polyunsaturated fatty acids (PUFA) intake or blood biomarkers on the development of type 2 diabetes. For instance, previous studies using PUFA biomarkers had a maximum of only 673 type 2 diabetes cases. In the EPIC-InterAct Study – a large European collaborative, prospective study where 12,132 diabetes cases were ascertained during its follow-up – we found diverse associations of blood levels of different types of PUFAs with incidence of type 2 diabetes.

Despite this diversity, clinically relevant results were observed for major polyunsaturated fatty acids. Higher blood levels of total omega-6 PUFAs and the major omega-6 PUFA (linolenic acid) were associated with a lower risk of developing type 2 diabetes. Likewise, levels of alpha linolenic acid, known as a plant-origin omega-3 PUFA, were associated with lower type 2 diabetes risk. Marine-origin omega-3 PUFAs, including docosahexaenoic acid (DHA), showed inconsistent associations with type 2 diabetes risk.

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Niacin-Laropiprant Reduced Quality of Life-Adjusted Survival and Increased Hospital Costs in HPS2-THRIVE

MedicalResearch.com Interview with:
Seamus Kent, MSc, Research Fellow and
Borislava Mihaylova, MSc DPhil, Associate Professor
Health Economics Research Centre,
Nuffield Department of Population Health
University of Oxford, UK

MedicalResearch.com: What is the background for this study?

Response: Niacin lowers the LDL cholesterol and increases the HDL cholesterol and it was hoped this would translate into reduced risks of vascular events. This hypothesis was assessed in the Heart Protection Study 2 – Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial in which over 25,000 adults aged 50 to 80 years with prior cardiovascular disease were randomised to either niacin-laropiprant or placebo, in addition to effective LDL-cholesterol lowering therapy, and followed for about 4 years. Previously published results from the study demonstrated that niacin-laropiprant did not significantly reduce the risk of major vascular events but did significantly increase the risk of various adverse events including infections, bleeding, gastrointestinal, musculoskeletal, skin, and diabetes-related events.

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Statins Reduces But Don’t Eliminate Risk of CAD In Familial Hypercholesterolemia

MedicalResearch.com Interview with:
Joost Besseling, PhD-student

Academic Medical Center
Dept. of Vascular Medicine
Amsterdam

MedicalResearch.com: What is the background for this study? 

Response: It was unkown to what extent statin therapy reduces the risk for coronary artery disease and mortality in patients with heterozygous familial hypercholesterolemia (FH). One previous study found that the relative risk reduction was 76%, but the study population in this study consisted of with a very severe FH phenotype. This result is therefore an overestimation of the risk reduction in the general heterozygous familial hypercholesterolemia population.

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Familial Hypercholesterolemia, Widely Under-Diagnosed, Raises Risk of Atherosclerotic Cardiovascular Disease

MedicalResearch.com Interview with:

Amanda M. Perak, MD Division of Cardiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, and Department of Preventive Medicine Northwestern University Feinberg School of Medicine

Dr. Perak

Amanda M. Perak, MD
Division of Cardiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, and
Department of Preventive Medicine
Northwestern University Feinberg School of Medicine

Donald M Lloyd-Jones, MD/ScM (senior author)
Senior Associate Dean for Clinical and Translational Research; Chair, Department of Preventive Medicine
Director, Northwestern University Clinical and Translational Sciences Institute (NUCATS) and Eileen M. Foell Professor
Professor in Preventive Medicine-Epidemiology and Medicine-Cardiology

MedicalResearch.com: What is the background for this study?

Response: Heterozygous familial hypercholesterolemia, or FH, affects up to 1 in 200 individuals in the United States. FH is a genetic disorder that should be suspected in individuals with very high levels of low-density lipoprotein cholesterol (LDL-C; at least 190 mg/dL) plus a first-degree relative with similar degree of high cholesterol or with premature coronary heart disease. Individuals with FH are exposed to high levels of “bad” cholesterol from birth, so if they are not treated with cholesterol-lowering therapy, they are at elevated risk for atherosclerotic cardiovascular disease (ASCVD; diseases related to hardening of the arteries, including heart attack and stroke). However, these risks previously had not been well quantified in untreated individuals with familial hypercholesterolemia in the general US population.

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Large Harvard Study Confirms Health Benefits of Unsaturated Fats

MedicalResearch.com Interview with:

Daniel (Dong) Wang, MD, ScD, Research Fellow Department of Nutrition | Harvard T.H. Chan School of Public Health Boston, MA 02115

Dr. Wang

Daniel (Dong) Wang, MD, ScD, Research Fellow
Department of Nutrition | Harvard T.H. Chan School of Public Health
Boston, MA 02115

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There has been widespread confusion in the biomedical community and the general public about the health effects of specific types of fat in the diet. In particular, the role of unsaturated fats vs. saturated fat in cardiovascular disease prevention remains controversial. Our study is by far the most detailed and powerful examination of this very important research topic, i.e., health effects of specific types of dietary fats, because of very large sample size (more than 120,000 men and women), repeated and validated measurements of diet and lifestyle over an extended follow-up (up to 32 years). In addition, our study is able to examine a much broader range of outcomes, including total mortality and mortality due to cardiovascular disease, cancer, neurodegenerative disease and respiratory disease.

We found that different types of dietary fat had different associations with mortality. Consuming higher amounts of unsaturated fats- mainly from plant-based foods like olive oil, canola oil, soybean oil and nuts – was associated with lower mortality, while higher consumption of saturated-found in red meat, butter, cheese, and ice cream- and trans fats- predominantly from hydrogenated oils- was linked with higher mortality compared with the same number of calories from carbohydrates. Most importantly, replacing saturated fats with unsaturated fats conferred substantial health benefits, including lowering risk of all-cause premature death and premature death due to cardiovascular disease, cancer, neurodegenerative disease and respiratory disease.

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HDL May Be Overrated as Independent Risk Factor for Heart Disease

MedicalResearch.com Interview with:

Michael Miller, MD, FACC, FAHA Professor of Cardiovascular Medicine, Epidemiology & Public Health University of Maryland School of Medicine Staff Physician, Baltimore VAMC Director, Center for Preventive Cardiology University of Maryland Medical Center Baltimore, Maryland

Dr. Michael Miller

Michael Miller, MD, FACC, FAHA
Professor of Cardiovascular Medicine, Epidemiology & Public Health
University of Maryland School of Medicine
Staff Physician, Baltimore VAMC
Director, Center for Preventive Cardiology
University of Maryland Medical Center
Baltimore, Maryland

MedicalResearch.com: What is the background for this study?
Dr. Miller: It has become an article of faith that HDL (the good cholesterol) is an independent risk factor for heart disease. However, previous studies did not examine the importance of HDL after accounting for both LDL (bad cholesterol) and triglycerides (blood fats).  This is important because HDL is associated with LDL and triglycerides. We hypothesized that if HDL is truly an independent risk factor, then low HDL levels in isolation would continue to be linked to an increased risk of heart disease while high HDL levels would continue to protect the heart even if LDL and triglycerides levels were elevated.

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Not All Patients Require High Intensity Statins To Achieve LDL Control

MedicalResearch.com Interview with:

Martha M. Rumore, PharmD, JD, MS, LLM, FAPhA Associate Professor, Social, Behavioral & Administrative Pharmacy Touro College of Pharmacy New York, NY 10027 & Of Counsel Sorell, Lenna, & Schmidt, LLP

Dr. Martha Rumore

Martha M. Rumore, PharmD, JD, MS, LLM, FAPhA
Associate Professor, Social, Behavioral & Administrative Pharmacy
Touro College of Pharmacy
New York, NY 10027
& Of Counsel Sorell, Lenna, & Schmidt, LLP

MedicalResearch.com: What is the background for this study?

Dr. Rumore: The management of lipid therapy is only one component that affects overall cardiovascular outcomes.This study is one of the first to look at the benefits of dose titration versus intensity-based statin therapy.  To evaluate whether patients titrated on statin therapy using ATPIII algorithm with an LDL goal of <100mg/dL also met the 2013 ACC/AHA Guideline for Management of Blood Cholesterol goal of ≥40% LDL reduction from baseline compared to inpatients initiated on high-moderate intensity statin (HIS).  Other objectives included comparison of algorithms to lower LDL ≥40%, final dose, adverse drug events (ADEs), clinic visits to goal, and cardiovascular event occurrence.

MedicalResearch.com: What are the main findings?

Dr. Rumore: 981 patients were included- 43% were titrated and 57% achieved LDL<100; 38% achieved both LDL <100mg/dL and LDL ≥40% reduction; 58% received HIS and 53% achieved LDL <100; 43% achieved both LDL <100mg/dL and LDL ≥40% reduction.

Initiating patients on  High Intensity statins was not more effective than dose titration in achieving <100mg/dL and ≥40% LDL reduction;X2=0.006,N=159,p=0.938. A 50% LDL reduction in patients that also achieved an LDL <100 was 54% and 48%, in titration and HIS groups, respectively; X2=0.611,N=159,p=0.434.  The titration group required an average of 4.3 clinic visits to achieve goal, compared to 3.1 visits for HIS; p=0.309; 95% CI(-1.36,1.06).

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