When It Comes to LDL-C, “You Really Can’t Be Too Low”

MedicalResearch.com Interview with:

Marc S. Sabatine, MD, MPH  Chairman | TIMI Study Group  Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine Brigham and Women's Hospital  Professor of Medicine | Harvard Medical School

Dr. Marc Sabatine

Marc S. Sabatine, MD, MPH
Chairman | TIMI Study Group
Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine
Brigham and Women’s Hospital
Professor of Medicine | Harvard Medical School

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

Response: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease.

The initial statin trials studied patients with high levels of LDL-C, and showed a benefit by lowering LDL-C.

We and others did studies in patients with so-called “average” levels of LDL-C (120-130 mg/dL), and also showed clinical benefit with lowering.

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Not All HDL Cholesterol is Good – Size Matters

MedicalResearch.com Interview with:

Samar R. El Khoudary, PhD, MPH, BPharm, FAHA Associate Professor, Epidemiology PITT Public Health Epidemiology Data Center University of Pittsburgh Pittsburgh, PA 15260 

Dr. El Khoudary

Samar R. El Khoudary, Ph.D., M.P.H. BPharm, FAHA
Associate Professor
Department of Epidemiology
University of Pittsburgh Graduate School of Public Health

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

Response: The background for this study is based on the current measurements used to determine cardiovascular disease risk in postmenopausal women. Higher levels of HDL “good cholesterol” as measured by the widely available clinical test, HDL-Cholesterol, may not always be indicative of a lower risk of cardiovascular disease in postmenopausal women.

HDL is a family of particles found in the blood that vary in sizes, cholesterol contents and function. HDL particles can become dysfunctional under certain conditions such as chronic inflammation. HDL has traditionally been measured as the total cholesterol carried by the HDL particles, known as HDL cholesterol. HDL cholesterol, however, does not necessarily reflect the overall concentration, the uneven distribution, or the content and function of HDL particles.

We looked at 1,138 women aged 45 through 84 enrolled across the U.S. in the Multi-Ethnic Study of Atherosclerosis (MESA), a medical research study sponsored by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH). MESA began in 1999 and is still following participants today. We assessed two specific measurements of HDL: the number and size of the HDL particles and total cholesterol carried by HDL particles. Our study also looked at how age when women transitioned into post menopause, and the amount of time since transitioning, may impact the expected cardio-protective associations of HDL measures.

Our study points out that the traditional measure of the good cholesterol, HDL cholesterol, fails to portray an accurate depiction of heart disease risk for postmenopausal women. We reported a harmful association between higher HDL cholesterol and atherosclerosis risk that was most evident in women with older age at menopause and who were greater than, or equal to, 10 years into post menopause. In contrast to HDL cholesterol, a higher concentration of total HDL particles was associated with lower risk of atherosclerosis. Additionally, having a high number of small HDL particles was found beneficial for postmenopausal women. These findings persist irrespective of age and how long it has been since women became postmenopausal.

On the other hand, large HDL particles are linked to an increased risk of cardiovascular disease close to menopause. Women are subject to a variety of physiological changes in their sex hormones, lipids, body fat deposition and vascular health as they transition through menopause. We are hypothesizing that the decrease of estrogen, a cardio-protective sex hormone, along with other metabolic changes, can trigger chronic inflammation over time, which may alter the quality of HDL particles. Future studies should test this hypothesis.

The study findings indicate that measuring size and number of HDL particles can better reflect the well-known cardio-protective features of the good cholesterol in postmenopausal women. Continue reading

Individuals With Very High Levels of Lipoprotein(a) May Benefit Most From LDL(a)-Lowering Drugs

MedicalResearch.com Interview with:

Dr. Stephen Burgess PhD Programme Leader at the Medical Research Council Biostatistics Unit University of Cambridge

Dr. Burgess

Dr. Stephen Burgess PhD
Programme Leader at the Medical Research Council Biostatistics Unit
University of Cambridge

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

Response: Lipoprotein(a) is a lipoprotein subclass, and an important biomarker for coronary heart disease. As a clinical biomarker, it has a similar story to LDL-cholesterol (“bad” cholesterol), in that it is thought to be a causal risk factor for coronary heart disease, and so is a potential target for drug development. However, while drugs that lower LDL-cholesterol, such as statins, have been successful in reducing coronary heart disease risk, drugs that lower lipoprotein(a) have not as yet been successful. New drugs are currently in development that specifically target lipoprotein(a) and can lower lipoprotein(a) concentrations by 80-90%. We performed this study to investigate whether these drugs are likely to be successful in reducing coronary heart disease risk.

We compared individuals with naturally-occurring genetic variants that predispose them to a higher or lower lifetime concentration of lipoprotein(a) as a way of mimicking a randomized controlled trial. This approach has previously been undertaken for other biomarkers, including LDL-cholesterol. We found that having 10mg/dL lower genetically-predicted concentration of lipoprotein(a) was associated with a 5.8% reduction in coronary heart disease risk.

However, associations between genetically-predicted LDL-cholesterol and coronary heart disease risk are quantitatively much stronger than the proportional effect of LDL-cholesterol lowering on coronary heart disease risk as estimated by statin trials. This is because differences in genetic variants reflect lifelong changes in LDL-cholesterol, whereas statin trials only lower LDL-cholesterol for a few years. Hence, using the ratio between the genetic and trial estimates for LDL-cholesterol, we estimate that lowering lipoprotein(a) by 10mg/dL in a short-term clinical trial would only reduce coronary heart disease risk by 2.7%. To obtain the same reduction in coronary heart disease risk of around 20% as observed in statin trials, lipoprotein(a) would have to be lowered by around 100mg/dL. This explains why previous trials of less specific and less potent lipoprotein(a)-lowering drugs have failed to demonstrate benefit.

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Statins Underused in Veterans with Severely Elevated Cholesterol

MedicalResearch.com Interview with:

Fatima Rodriguez, MD, MPH Division of Cardiovascular Medicine Stanford University Stanford, CA 94305-5406,

Dr. Rodriguez

Fatima Rodriguez, MD, MPH
Division of Cardiovascular Medicine
Stanford University
Stanford, CA 94305-5406,

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

Response: Individuals with LDL-cholesterol levels above 190mg/dL are often underdiagnosed and undertreated, yet remain at high-risk of cardiovascular disease. In a national sample of veterans, we identified over 60,000 patients who met criteria for uncontrolled, severe hypercholesterolemia based on an index LDL-C value ≥190mg/dL. We found that only half of these high-risk patients are being treated with statins, and less than 10% are on high-intensity statin therapy as recommended by the 2013 ACC/AHA guidelines. We also found that both older and younger patients were less likely to be treated with statins. Women were less likely to be treated with statins, whereas minority groups and those with a diagnosis of hypertension were more likely to be treated. Disparities in use of statins were also noted by geographic region and hospital teaching status. Continue reading

African Americans Less Likely To Be Treated With Statins

MedicalResearch.com Interview with:

Michael G. Nanna, MD Fellow, Division of Cardiology Duke University Medical Center Durham, NC

Dr. Nanna

Michael G. Nanna, MD
Fellow, Division of Cardiology
Duke University Medical Center
Durham, NC

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

Response: We know that African Americans are at higher risk for cardiovascular disease than white patients. We also know that African American individuals have been less likely to receive statin therapy compared to white individuals in the past. However, the reasons underlying these racial differences in statin treatment are poorly understood. We set out to determine if African American individuals in contemporary practice are treated less aggressively than whites and, if so, we wanted to investigate potential reasons why this might be the case.

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LPA Gene Variants Linked To Cardiac Events Despite Statins

MedicalResearch.com Interview with:

Wei-Qi Wei, MD, PhD Assistant Professor Department of Biomedical Informatics Vanderbilt University Nashville, TN 37203

Dr. Wei-Qi Wei

Wei-Qi Wei, MD, PhD
Assistant Professor
Department of Biomedical Informatics
Vanderbilt University
Nashville, TN 37203

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

Response: The study was motived by the clinical observation that some patients develop coronary heart disease events despite taking statins, one of our most effective drugs to reduce cardiovascular risk. We collected data within the eMERGE network of people taking statins and monitored them for development of coronary heart disease events over time.  We  conducted a genome-wide association study of those with events compared to those without events.

Our results showed that single nucleotide polymorphisms (SNPs) on the LPA gene were associated with a significantly increased risk of coronary heart disease events. Individuals with the variant were 50% more likely to have an event. More importantly, even among patients who achieved ideal on-treatment LDL cholesterol levels (<70 mg/dL), the association remained statistically significant.

We then did a phenome-wide association study to see if other diseases or conditions were associated with these LPAvariants. The major associated conditions were all cardiovascular. This sort of study can highlight potential other indications for a drug targeting this pathway and suggest potential adverse events that might be experienced from targeting this pathway. Clearly, more and larger studies will be needed to truly understand the potential risks and benefits of a future drug targeting this pathway.  Continue reading

Patients With Highest LDL Levels Benefit Most From Lipid-Lowering Drugs

MedicalResearch.com Interview with:

Dr. Jennifer Robinson, MD MPH professor of epidemiology, University of Iowa College of Public Health. CREDIT Tom Langdon

Dr. Robinson

Dr. Jennifer Robinson, MD MPH
Professor, Departments of Epidemiology & Medicine
Director, Prevention Intervention Center
Department of Epidemiology
University of Iowa

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

Response: Compared to previous placebo-controlled statin trials, the FOURIER trial where all patients were on high or moderate intensity statin, had no reduction in cardiovascular or total mortality and the reduction in cardiovascular events was less than expected.  However, other PCSK9 inhibitor trials performed in populations with higher baseline low density lipoprotein cholesterol (LDL-C) had cardiovascular risk reductions similar to that in the statin trails.

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Very High ‘Good Cholesterol’ HDL Linked To Increased Risk of Infections

MedicalResearch.com Interview with:

Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital, Denmark

Prof. Nordestgaard

Børge G. Nordestgaard, MD, DMSc
Professor, University of Copenhagen
Chief Physician, Dept. Clinical Biochemistry
Herlev and Gentofte Hospital
Copenhagen University Hospital, Denmark 

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

Response: For decades research into the role and function of high-density lipoprotein (HDL) has revolved around the believe that HDL protects against atherosclerotic cardiovascular disease. However, results from large genetic studies and from large randomized clinical trials with HDL cholesterol elevating drugs have all indicated that there is no causal association between HDL cholesterol and risk of atherosclerotic cardiovascular disease.

Given the hitherto strong focus on cardiovascular disease, little is known about the possible role of HDL in other aspects of human health and disease. Preclinical evidence has indicated that HDL might be of importance for normal function of the immune system and susceptibility to infectious disease, but it had never previously been investigated if levels of HDL cholesterol is associated with the risk of infectious disease in individuals from the general population. In the present study we tested this hypothesis in more than 100.000 Danes from the population at large.

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Statins: Large Disparity Between US/Canadian/UK and European Guidelines

MedicalResearch.com Interview with:

Borge G. Nordestgaard,

Borge G. Nordestgaard

Børge G. Nordestgaard, MD, DMSc
Department of Clinical Biochemistry
Herlev and Gentofte Hospital, Copenhagen University Hospital
Herlev, Denmark

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

Response: Five major organizations recently published guidelines for using statins to prevent atherosclerotic cardiovascular disease  — the American College of Cardiology/American Heart Association (ACC/AHA) in 2013, the United Kingdom’s National Institute for Health and Care Excellence (NICE) in 2014, and in 2016 the Canadian Cardiovascular Society (CCS), the US Preventive Services Task Force (USPSTF), and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS). We applied these five guidelines to a contemporary study cohort of 45,750 40-75 year olds from the Copenhagen General Population Study.

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Frequent Take-Out Food Linked To Increased Cholesterol and Obesity in Children

MedicalResearch.com Interview with:

Dr. Angela S Donin Population Health Research Institute, St George’s University of London, London, UK

Dr. Donin

Dr. Angela S Donin
Population Health Research InstituteSt George’s
University of London
London, UK 

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

Response: There are increasing numbers of takeaway outlets, particularly in deprived neighbourhoods. This is driving an increase in consumption of takeaway meals, which previous evidence has shown is linked to higher risks of heart disease, type 2 diabetes and obesity. Little is known about the dietary and health impact of high consumption of takeaway foods in children.

This research found children who regularly ate takeaway meals had higher body fat and cholesterol compared to children who rarely ate take away meals, they also had overall poorer diet quality.

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Praluent May Reduce Need For Apheresis In Some Patients With Familial Hypercholesterolemia

MedicalResearch.com Interview with:

Dr. Jay Edelberg VP Head of CV Development and Head Global CV Medical Affairs

Dr. Edelberg

Dr. Jay Edelberg MD, PhD
VP Head of CV Development and
Head Global CV Medical Affairs
Sanofi 

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

Response: Patients with heterozygous familial hypercholesterolemia (HeFH) are often not able to achieve their target low-density lipoprotein cholesterol (LDL-C) levels, and some may require lipoprotein apheresis (LA) to lower their “bad cholesterol.” Apheresis is a procedure similar to kidney dialysis, where bad cholesterol is mechanically removed from the blood. It is an invasive, expensive, and time-consuming treatment for patients, as well as physicians.

The Phase III ESCAPE clinical study looked at the potential effect of LA on total Praluent, free and total PCSK9 concentrations, as well as the combined pharmacodynamics effect of total Praluent on LDL-C-lowering.

Praluent levels remained unaffected by apheresis, and Praluent consistently suppressed free PCSK9 levels in patients with HeFH, regardless of LA treatment. This analysis further confirms clinical ESCAPE data that Praluent can be used in conjunction with LA and may reduce or potentially eliminate the need for LA in some patients.

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Lack of Response to LDL-Lowering Praluent Rare

MedicalResearch.com Interview with:

Dr. Jay Edelberg VP Head of CV Development and Head Global CV Medical Affairs

Dr. Edelberg

Dr. Jay Edelberg MD, PhD
VP Head of CV Development and
Head Global CV Medical Affairs
Sanofi

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

Response: Clinical trials of lipid-lowering therapies (LLTs), including statins, often report variations in treatment response regarding effects on low density-lipoprotein cholesterol (LDL-C) levels, although LDL-C reductions are fairly consistent between trials. Praluent is generally well tolerated, however hyporesponsiveness exists in few patients.

Potential causes for variation in patient responsiveness to Praluent include lack of receipt of active study drug, changes in concurrent LLTs, inaccurate or unrepresentative baseline lipid levels, concurrent acute-phase illness, and biological nonresponsiveness.

This analysis evaluated patients pooled from 10 ODYSSEY trials to assess characteristics of patients with hyporesponsiveness to Praluent, defined as <15% LDL-C reduction from baseline at all analyzed time points.

Overall, only 1% of patients (n=33) had <15% LDL-C reduction at all time points. Prolonged hyporesponsiveness to Praluent was rarely associated with Praluent antidrug antibodies. Of the 33 patients with <15% LDL-C reduction at all study timepoints, 27 had undetectable or missing alirocumab levels, absence of pharmacokinetics analyses, or early treatment discontinuation.

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Cellular Protein Nrf1 Protects Against Fatty Liver

MedicalResearch.com Interview with:

Gokhan S. Hotamisligil MD PhD

Dr. Hotamisligil

Gokhan S. Hotamisligil MD PhD
J.S. Simmons Professor of Genetics and Metabolism
Chair, Department of Genetics and Complex Diseases
Department of Genetics and Complex Diseases
Department of Nutrition
Harvard Stem Cell Institute

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

Response: Cholesterol is often considered a ‘bad’ nutrient, as it has been strongly linked to a cluster of metabolic diseases. In reality however, cholesterol is absolutely vital for the health of all animal cells, serves as an essential building block for all membranes and precursor for essential molecules.  It usually only becomes toxic when cells are exposed to high levels or free forms of cholesterol or when it is stored in excess.

The reasons why cholesterol over-accumulates or causes excessive damage in cells of some people is not entirely clear, as cells are normally should be able to remove such excesses, and there remains key mechanistic gaps in our understanding of how cells control the molecular process of sensing excess cholesterol, engage ways of removal and launch countermeasures to defend their integrity. Filling this gap may reveal a new path toward alleviating the burden of cholesterol-related diseases.

To this end, we identified a new signal pathway mediated by a protein called Nrf1, which enables cells to know when to remove cholesterol, thereby preventing excess cholesterol storage. We show that Nrf1 directly senses cholesterol in a strategic subcellular compartment called the endoplasmic reticulum and coordinates an adaptive and defensive responses that protects the cells and promotes the removal of cellular cholesterol. Continue reading

LPA Gene Variant May Help Identify Increased Risk of Aortic Stenosis 

MedicalResearch.com Interview with:

Aortic Stenosis Blaus Image Wikipedia

Aortic Stenosis Blaus Image Wikipedia

Hao Yu Chen, MSc
Department of Medicine
McGill University
Montreal, Quebec, Canada
Senior author: George Thanassoulis, MD, MSc

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

Response: Aortic stenosis, a narrowing of the main valve of the heart, is the most common type of valve disease in the US. Present in more than 2.5 million individuals in North America, aortic stenosis can lead to heart failure and death. However, there is little known about the causes of aortic stenosis and how it should be treated.

Previously, we have demonstrated that variants of the gene LPA are associated with the development of aortic stenosis. A better understanding of how this region contributes to aortic stenosis could identify higher-risk individuals and inform the development of new medical therapies for aortic stenosis.  Continue reading

Hormones Affect Carotid Plaque Stability and Stroke Vulnerability

MedicalResearch.com Interview with:

Marija Glisic Epidemiology, Erasmus MC

Marija Glisic

Marija Glisic
Epidemiology, Erasmus MC 

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

Response: Carotid atherosclerosis is one of most important risk factors for developing stroke. Carotid atherosclerotic plaques characterized by lipid core presence and intraplaque haemorrhage are considered to be unstable, and therefore more prone to rupture and lead to consequent stroke. Sex differences have been observed in carotid plaque composition as well as in stroke incidence. Sex hormones, particularly estrogen and testosterone actions are suggested to underlie the observed sex differences in atherosclerosis. Experimental evidence suggests a direct action of estradiol and testosterone on the vascular system, affecting various mechanisms that may impact plaque composition and subsequently stroke risk.

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Study Finds ACE Inhibitors and Statins Can Be Safe In Type I Diabetes

MedicalResearch.com Interview with:
M. Loredana Marcovecchio, M.D.
Clinical Scientist and
Professor David Dunger M.D.
Director of Research
Professor of Paediatrics
University of Cambridge

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

Response: The efficacy and safety of ACE Inhibitors and statins in adolescents have been shown in the context of hypertension and familial hypercholesterolemia, respectively. However, there is a lack of data on the long-term use of these drugs in those with type 1 diabetes and, in particular, there is no clear indication for their use in patients with increased albumin excretion.

The Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) was a multi-centre, international study, set up by investigators in the UK, Australia and Canada to explore if drugs already used to lower blood pressure (ACE inhibitors) and cholesterol levels (Statins) in adults with diabetes could reduce the risk of kidney, eye and cardiovascular disease in adolescents with Type 1 diabetes.

Neither ACE inhibitors nor statins significantly reduced the albumin-creatinine ratio during the 2-4 year trial period. However, some of the secondary outcomes suggest that the drugs may have important benefits.

Treatment with the ACE inhibitor resulted in a 43% reduction in the rates of progression to microalbuminuria, which was not statistically significant, but it could have important clinical implications. Preventing even intermittent cases of microalbuminuria is known to reduce the future risk of kidney and cardiovascular complications.

Statin therapy led to reduced levels of lipid levels, which could reduce long-term risk for cardiovascular complications.

These findings could translate into long-term benefits, but follow-up of this unique cohort will be essential. The essential biological samples and data provided by the participants will continue to inform our future understanding and our options for effective therapies for this vulnerable group of young people with type 1 diabetes.

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Praluent Plus Statins Reduce LDL In High Risk Cardiovascular Patients

MedicalResearch.com Interview with:

VP Head of Cardiovascular Development and Head Global Cardiovascular Medical Affairs Sanofi

Dr. Edelberg

Dr. Jay Edelberg MD, PhD
VP Head of Cardiovascular Development and
Head Global Cardiovascular Medical Affairs
Sanofi 

MedicalResearch.com: What should readers take away from the data that Sanofi and Regeneron is presenting at ESC Congress 2017?   

Response: This year at European Society of Cardiology (ESC,) we are pleased to present analyses that further demonstrate additional efficacy and tolerability of Praluent (alirocumab).

While statins remain the first-line treatment, Praluent has shown a consistent benefit as an additional therapy to high-intensity statins in patients with clinical atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH), allowing many patients to achieve low-density lipoprotein (LDL) cholesterol levels previously considered unattainable in this patient population.

Our data further emphasize the need for additional cholesterol-lowering options in these high cardiovascular (CV) risk patient populations, including individuals living with diabetes 

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Positive Emotions Predict Health Lipid Profiles In Western, But Not Eastern Cultures

MedicalResearch.com Interview with:

Jiah Yoo Ph.D. Student in Social Psychology University of Wisconsin-Madison Madison, WI 53706 

Jiah Yoo

Jiah Yoo
Ph.D. Student in Social Psychology
University of Wisconsin-Madison
Madison, WI 53706 

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

Response: A growing number of studies have shown that positive emotions predict better physical health. However, a caveat of these findings is that most studies have been conducted with Western samples. As cultural psychologists, we have learned that European American cultural contexts are particular in that positive emotions are highly valued and emphasized. For example, in East Asian cultures, it is a commonly shared view that positive emotions have some dark sides such as that they are fleeting, may attract unnecessary attention from others, and can be a distraction from focusing on important tasks. Given the cultural differences in emotions, we thought it would be important to test whether the established link between positive emotion and enhanced physical health are relevant to other cultural contexts, such as those in East Asia.

We focused on blood lipids profiles, one of the major risk factors for heart diseases, as objective measures of health. Because of the global prevalence of coronary artery diseases, blood lipids are considered important indices of biological health in many Western and East Asian countries. In addition, blood lipids are largely influenced by lifestyles and behavioral factors so we further tested the role of various health behaviors (i.e., dietary habits, body mass index, smoking, alcohol consumption) in the lipids-emotion link in different cultures.

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Hyperlipidemia Linked To Lower Breast Cancer Mortality, Perhaps Due To Statin Therapy

MedicalResearch.com Interview with:

Dr Rahul Potluri Senior author and founder of the ACALM Study Unit Aston Medical School Aston University Birmingham, UK

Dr. Potluri

Dr Rahul Potluri
Senior author and founder of the ACALM Study Unit
Aston Medical School
Aston University
Birmingham, UK

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

Response: The links between hyperlipidaemia and cancer has been exciting scientists in recent years.  We have previously shown an association with breast cancer and hyperlipidaemia using a cross-sectional dataset in 2014.

In 2016 we showed that in patients with the four main cancers in the UK (namely Breast, Lung, Colon and Prostate) that the presence of hyperlipidaemia improved the long term mortality and prognosis of these patients.  In this study utilising a big data, longitudinal study methodology, we looked at 16043 healthy women above the age of 40 with hyperlipidaemia and compared these to an age and gender matched control sample of 16043 healthy women without high cholesterol. We then followed up these patients and found that subsequent breast cancer rates in the women with hyperlipidaemia were 45% lower. Subsequent mortality in those patients who developed breast cancer was also 40% lower in the hyperlipidaemia group compared to the non-hyperlipidaemia controlled sample.

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PCSK 9 Inhibitors May Be Cost Effective For Subset of High Risk Patients, If Price is Right

MedicalResearch.com Interview with:

Gregg C. Fonarow, MD, FACC, FAHA Eliot Corday Professor of Cardiovascular Medicine and Science Director, Ahmanson-UCLA Cardiomyopathy Center Co-Chief of Clinical Cardiology, UCLA Division of Cardiology Co-Director, UCLA Preventative Cardiology Program David Geffen School of Medicine at UCLA Los Angeles, CA, 90095-1679

Dr. Gregg Fonarow

Gregg C. Fonarow, MD, FACC, FAHA
Eliot Corday Professor of Cardiovascular Medicine and Science
Director, Ahmanson-UCLA Cardiomyopathy Center
Co-Chief of Clinical Cardiology, UCLA Division of Cardiology
Co-Director, UCLA Preventative Cardiology Program
David Geffen School of Medicine at UCLA
Los Angeles, CA 

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

Response: The study identifies the clinical and economic consequences of treating a population of patients with established atherosclerotic cardiovascular disease (ASCVD ) at high-risk of cardiovascular (CV) events and defines the cost-effectiveness of the PCSK-9 inhibitor evolocumab under various clinical scenarios. The analysis is based on the clinical outcomes from the Repatha Outcomes Study (FOURIER) in patients with established atherosclerotic cardiovascular disease (ASCVD), such as those who have already had a heart attack or stroke who require additional therapy.

This is the first cost-effectiveness assessment of evolocumab using a model based on a high-quality outcomes trial, combined with U.S. clinical practice data. The analysis identifies the types of high-risk patients for whom this therapy is both clinically beneficial and cost-effective. This study utilized cost-effectiveness and value thresholds employed by the World Health Organization and the American College of Cardiology/American Heart Association.

Evolocumab was found to exceed generally accepted cost-effectiveness thresholds at current list price. However, this medication could be a cost-effective treatment for patients with established ASCVD in the U.S. when the net price is at or below $9,669 per year.

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Familial Hypercholesterolemia: “Junk” RNA May Facilitate Gene Therapy

MedicalResearch.com Interview with:

Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679 

Dr. Sallam

Tamer Sallam, MD PhD
Assistant Professor of Medicine
Co-Director UCLA Center for Lipid Management
Lauren B. Leichtman and Arthur E. Levine CDF Investigator
Assistant Director, STAR Program
Division of Cardiology, Department of Medicine
David Geffen School of Medicine at UCLA
Los Angeles, California 90095-1679

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

Response: This study is extension of our previous work published in Nature showing that a gene we named LeXis (Liver expressed LXR induced sequence) plays an important role in controlling cholesterol levels. What is unique about  LeXis is that it belongs to a group of newly recognized mediators known as long noncoding RNAs. These fascinating factors were largely thought to be unimportant and in fact referred to as “junk DNA” prior the human genome project but multiple lines of evidence suggest that they can be critical players in health and in disease.

In this study we tested whether we can use  LeXis “gene therapy”  to lower cholesterol and  heart disease risk. This type of approach is currently approved or in testing for about 80 human diseases.

Our finding was that a single injection of LeXis compared with control significantly  reduced heart disease burden in mouse subjects. Although the effect size was moderate we specifically used a model that mimics a very challenging to treat human condition known as familial hypercholesterolemia..Familial hypercholesterolemia is one of the most common genetic disorders affecting up to 2 million Americans and characterized by 20 fold  fold increase risk of early heart attacks and often suboptimal response to currently available treatments.

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Even After Rebates, Use of PCSK9 Inhibitor Would Still Cost Over $5 Million To Prevent One Stroke

MedicalResearch.com Interview with:

Inmaculada Hernandez, PharmD, PhD Assistant Professor of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy Pittsburgh, PA 1526

Dr. Hernandez

Inmaculada Hernandez, PharmD, PhD
Assistant Professor of Pharmacy and Therapeutics
University of Pittsburgh School of Pharmacy
Pittsburgh, PA 1526

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

Response: A few months ago, the results of the FOURIER trial were published. This trial was the first one to evaluate the efficacy of PCSK9 inhibitors in the prevention of cardiovascular events, since the approval of these agents was based on trials that evaluated their efficacy in reducing levels of LDL-C. The results of the FOURIER trial did not meet the expectations generated by prior studies that had simulated how much the risk of cardiovascular events should decrease based on the observed reduction in LDL-C levels. A few hours after the publication of the results of the FOURIER trial, Amgen (evolocumab´s manufacturer) announced that it would be willing to engage in contracts where the cost of evolocumab would be refunded for those patients who suffer a heart attack or a stroke while using the drug.

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PCSK9 Inhibitor Praluent Added to Statins Improved Lipid Profile in Diabetes

MedicalResearch.com Interview with:

Dr-Robert-R-Henry.jpg

Dr. Henry

Robert R. Henry, M.D.
Professor of Medicine
Member of the ODYSSEY DM Steering Committee and
Director of the Center for Metabolic Research
VA San Diego Healthcare System

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

Response: The ODYSSEY DM-DYSLIPIDEMIA trial was a randomized, open-label, parallel-group study designed to evaluate the superiority of Praluent versus usual care in 413 patients with type 2 diabetes with mixed dyslipidemia at high cardiovascular (CV) risk, not adequately controlled with maximally tolerated dose (MTD) statins. The primary endpoint was percent change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to week 24.

In ODYSSEY DM-DYSLIPIDEMIA, Praluent 75 mg was added to MTD statins, with dose adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose.

Results from the ODYSSEY DM-DYSLIPIDEMIA study found that Praluent added to MTD statins showed significant reduction in non-HDL-C and other lipid parameters compared to those on usual care.

Praluent was superior to usual care in lowering non-HDL-C (37.3 percent and 4.7 percent, for the usual care arm). The mean difference between the two treatment arms was -32.5 percent (p<0.0001).

Praluent in combination with MTD statins reduced LDL-C by 43 percent from baseline compared to a 0.3 percent increase for usual care (p<0.0001). Treatment with Praluent also improved the overall lipid profile.

There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Furthermore, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk.

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Adding Praluent (Alirocumab) To Statins Reduces LDL in High Cardiovascular Risk Diabetics

MedicalResearch.com Interview with:

Lawrence Leiter, M.D. MDCM, FRCPC, FACP, FACE, FAHA Chair of the ODYSSEY DM Steering Committee and Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute St. Michael’s Hospital University of Toronto, Canada

Dr. Lawrence Leiter

Lawrence Leiter, M.D. MDCM, FRCPC, FACP FACE, FAHA
Chair of the ODYSSEY DM Steering Committee and
Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute
St. Michael’s Hospital
University of Toronto, Canada

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

Response: The ODYSSEY DM-INSULIN trial was a randomized, double-blind, placebo-controlled, multicenter study that evaluated alirocumab (Praluent) in 517 patients with insulin treated type 1 and type 2 diabetes with high cardiovascular (CV) risk and hypercholesterolemia despite maximally tolerated dose (MTD) statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24.

Alirocumab 75 mg every two weeks was added to MTD statins, with the dose increased at week 12 to 150 mg every two weeks if the LDL-C at week 8 was greater than or equal to 70 mg/dL. In fact, only about 20% of the alirocumab treated participants required the higher dose.

Results of the type 2 diabetes study population (n=441) showed that the addition of alirocumab to MTD statin therapy, reduced LDL-C by 48.2 percent from baseline compared to a 0.8 percent increase for placebo. The mean difference between the two treatment arms was -49 percent (p<0.0001). Treatment with alirocumab also improved the overall lipid profile. Furthermore, no new safety issues were identified.

There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Additionally, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk.

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Cholesterol Uptake Capacity, a New Indicator of HDL Functionality, for Cardiovascular Risk Stratification in the Real World.

MedicalResearch.com Interview with:
Amane Harada, PhD
Senior Researcher
Central Research Laboratories, Sysmex Corporation
Kobe, Japan

Ryuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of MedicineRyuji Toh, MD, PhD
Associate Professor
Division of Evidence-based Laboratory Medicine
Kobe University Graduate School of Medicine
Kobe, Japan 


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

Response: High-density lipoprotein (HDL) exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative functions as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become “dysfunctional” HDL under pathological conditions.

Recent studies have demonstrated that cholesterol efflux capacity of HDL is a better predictor of CVD than HDL-C, suggesting that not only the quantity, but also the quality of HDL may significantly modulate and predict the progression of cardiovascular disease.

However, the conventional procedure for efflux capacity assay requires radiolabeling and cells, and the procedures are time consuming. Therefore, its clinical application is impractical.

To solve those problems, we have recently developed a new assay system to evaluate the capacity of HDL to accept cholesterol, named “uptake capacity”.

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