AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids / 15.01.2015

Jean-Claude Tardif MD Professor of Medicine Director of the Research Centre Montreal Heart Institute Montreal, Quebec CanadaMedicalResearch.com Interview with: Jean-Claude Tardif MD Professor of Medicine Director of the Research Centre Montreal Heart Institute Montreal, Quebec Canada MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Tardif: Epidemiological and mechanistic studies have suggested that high-density lipoproteins (HDL) could have beneficial cardiovascular properties. However, several medications targeting HDL have failed in recent clinical trials, including the CETP inhibitor dalcetrapib in the dal-Outcomes trial. We hypothesized that dalcetrapib would be beneficial in the subset of patients with the appropriate genetic profile. We conducted the pharmacogenomic analysis of approximately 6000 patients from the dal-Outcomes study which showed that patients with the AA genotype at a specific genetic location (rs1967309) of the adenylate cyclase (ADCY9) gene benefited from a 39% reduction in cardiovascular events including cardiovascular death, myocardial infarction, stroke, unstable angina and the need for coronary revascularization when treated with dalcetrapib compared to placebo. In contrast, patients with the GG genotype had a 27% increase in cardiovascular events. We then obtained confirmatory evidence from the dal-Plaque-2 imaging study which revealed that patients with the protective genotype (AA) had a reduction in their carotid artery wall thickness and that those with the genotype associated with clinical harm (GG) had an increase in their wall thickness. (more…)
Author Interviews, Heart Disease, Lipids, PLoS / 11.12.2014

MedicalResearch.com Interview with: Prof. Erik Ingelsson, MD, PhD, FAHA Professor of Molecular Epidemiology and Andrea Ganna PhD student Uppsala University Medical Research: What is the background for this study? What are the main findings? Response: Coronary heart disease (CHD) comprises a major cause of morbidity and mortality throughout the world. Measurement of metabolites, small molecules, in the blood could allow earlier diagnosis and inform about mechanisms leading to CHD. We examined the metabolic profiles (including thousands of metabolites) of blood samples from more than 3,600 individuals from Sweden that had been followed-up for up to 10 years, and found two lipid-related metabolites, lysophosphatidylcholine and sphingomyelin that reduced the risk of developing coronary heart disease and another lipid metabolite, monoglycerides, that was instead associated with increased risk. (more…)
Author Interviews, Kidney Disease, Lipids / 01.12.2014

Thomas Weichhart, PhD Associate Professor, Medical University of Vienna Institute of Medical Genetics Vienna AustriaMedicalResearch.com Interview with: Thomas Weichhart, PhD Associate Professor, Medical University of Vienna Institute of Medical Genetics Vienna Austria Medical Research: What is the background for this study? Dr.  Weichhart: Impairment of high-density lipoprotein (HDL) function has been associated with cardiovascular events in patients with kidney failure on hemodialysis. The protein composition of HDLs is altered in these patients presumably compromising the cardioprotective effects of HDLs. In an earlier study we found that two proteins in particular, namely Serum Amyloid A (SAA) and Surfactant Protein B (SP-B), are significantly raised in the HDL of dialysis patients, and these also contribute towards HDL losing its protective effect. In the current study we have now developed an novel test that can quickly and directly measure the SAA and SP-B bound to HDL. (more…)
Author Interviews, General Medicine, Heart Disease, Lipids / 21.11.2014

Thomas M. Maddox MD MSc Cardiology, VA Eastern Colorado Health Care System Associate Director, VA CART ProgramMedicalResearch.com Interview with: Thomas M. Maddox MD MSc Cardiology, VA Eastern Colorado Health Care System Associate Director, VA CART Program Associate Professor, Department of Medicine University of Colorado School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Maddox: With the release of the updated cholesterol guidelines last year and their significant changes in recommendations, we wanted to see what the potential impact would be on U.S. cardiovascular practices.  Specifically, we were interested in present cholesterol treatment and testing patterns, and how they would potentially need to change under the new guidelines. We used the PINNACLE registry to conduct our investigation.  Under the sponsorship of the American College of Cardiology, the registry collects EMR data from 111 cardiovascular practices around the U.S.  We analyzed cholesterol treatment and testing patterns in approximately 1.2 million patients.  We found that most patients qualified for cholesterol treatment with statins, but 32.4% weren't currently prescribed them.  We also found that 22.6% of patients were being treated with non-statin lipid-lowering therapies which, under the new guidelines, aren't currently recommended for cholesterol treatment.  Finally, we found that 20.8% of patients underwent repeated LDL-C testing, which may not be necessary under the new guidelines. (more…)
Aging, Lipids / 10.11.2014

Sofiya Milman, M.D. Assistant Professor of Medicine Divisions of Endocrinology and Geriatrics Albert Einstein College of MedicineMedicalResearch.com Interview with: Sofiya Milman, M.D. Assistant Professor of Medicine Divisions of Endocrinology and Geriatrics Albert Einstein College of Medicine   Medical Research: What is the background for this study? What are the main findings? Dr. Milman: Aging is a major risk factor for many diseases, including cardiovascular disease, dementia, and diabetes. Yet, individuals with exceptional longevity delay the onset of most diseases and often escape from age-related illnesses altogether. Exceptional longevity is an inherited trait. A unique cholesterol profile has been previously associated with longevity and specific genetic variations. This profile included elevated levels of high-density lipoprotein (HDL) cholesterol or “good” cholesterol and large HDL particles. The present study explored whether elevated HDL cholesterol levels and genes that control HDL cholesterol can predict survival in individuals age 95 years or older. The study found that higher levels of HDL cholesterol were related to longer survival in women, but not in men. Higher HDL cholesterol level was also seen in individuals without cognitive problems and diabetes. On the other hand, both men and women with larger HDL particle size and higher levels of APOA1, a protein component of HDL cholesterol, exhibited longer survival. Variants in two genes, the CETP and APOA1, were related to higher HDL cholesterol levels. (more…)
Author Interviews, Heart Disease, JACC, Lipids / 31.10.2014

Prof. Frank B Hu Department of Nutrition Department of Epidemiology Harvard School of Public HealthMedicalResearch.com Interview with Frank B. Hu, MD, PhD Professor of Nutrition and Epidemiology Harvard School of Public Health Professor of Medicine Harvard Medical School Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Hu: There has been much confusion and sensational headlines about the role of different types of fat in coronary heart disease.  A recent meta-analysis suggested that higher saturated fat intake was not associated with coronary heart disease (CHD), but people don't consume saturated fat in isolation from other components of diet. Typically people swap for one type of fat for another. Therefore it is important to look at replacement nutrient when we talk about health effects of saturated fat. Randomized clinical trials have shown that replacing saturated fat with polyunsaturated fat reduces total and LDL cholesterol. Thus it is important to examine whether such replacement confers long-term beneficial effects on heart disease prevention. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the link between dietary intake of linoleic acid (the predominant type of polyunsaturated fat) and heart disease risk in generally healthy people. We identified 13 published and unpublished cohort studies with a total of 310,602 individuals and 12,479 total  coronary heart disease events including 5,882 CHD deaths. We found that dietary linoleic acid intake is inversely associated with  coronary heart disease risk in a dose-response manner—meaning, higher intake of linoleic acid resulted in a lower risk of CHD. Comparing the highest to the lowest level of consumption, dietary linoleic acid was associated with a 15% lower risk of  coronary heart disease events and a 21% lower risk of CHD deaths. These results were independent of common coronary heart disease risk factors such as smoking and other dietary factors such as fiber consumption. (more…)
Author Interviews, Heart Disease, JAMA, Lipids / 29.10.2014

George Thanassoulis, MD MSc FRCP(C) Director, Preventive and Genomic Cardiology FRQ-S Clinician-Scientist/Chercheur-Boursier Clinicien Assistant Professor of Medicine, McGill University McGill University Health Center Montreal, QCMedicalResearch.com Interview with: George Thanassoulis, MD MSc FRCP(C) Director, Preventive and Genomic Cardiology FRQ-S Clinician-Scientist/Chercheur-Boursier Clinicien Assistant Professor of Medicine, McGill University McGill University Health Center Montreal, QC Medical Research: What is the background for this study? What are the main findings? Dr. Thanassoulis: Although LDL-C (i.e. bad cholesterol) has been linked with aortic valve disease in several prior reports, randomized trials to lower cholesterol in aortic valve disease were not effective suggesting that cholesterol may not be important in valve disease. To address this, we performed a Mendelian randomization study, that showed that a genetic predisposition to LDL-C, was associated with both calcium deposits on the aortic valve and aortic stenosis (I.e. Valve narrowing).  These results can be viewed as the effect of a life-long increase in LDL-C on the incidence of aortic valve disease and suggest that increases in LDL-C cause aortic stenosis.   (more…)
Author Interviews, JAMA, Lipids, UCSF / 15.10.2014

MedicalResearch.comInterview with: Mary Malloy, M.D. Co-director of the Adult Lipid Clinic and the director of the Pediatric Lipid Clinic UCSF Medical Center Medical Research: What are the main findings of the study? Dr. Malloy: We studied an individual whom we found to be homozygous for a rare loss of function mutation in apolipoprotein E. Because apolipoprotein E is necessary for clearance of lipoproteins from plasma, he has very high levels of cholesterol and triglycerides in blood, and unusual and very severe xanthomas. He had no evidence of neurocognitive or retinal defects. (more…)
Author Interviews, JCEM, Lipids, Prostate Cancer / 13.10.2014

Emma H. Allott PhD Division of Urology, Department of Surgery, Duke University School of Medicine Cancer Prevention, Detection, and Control Program, Duke Cancer Institute Division of Urology, Veterans Affairs Medical Center Durham Durham, North Carolina.MedicalResearch.com Interview with: Emma H. Allott PhD Division of Urology, Department of Surgery, Duke University School of Medicine Cancer Prevention, Detection, and Control Program, Duke Cancer Institute Division of Urology Veterans Affairs Medical Center Durham Durham, North Carolina. Medical Research: What are the main findings of the study? Dr. Allott: Relative to normal triglyceride levels, high triglycerides (≥150 mg/dl) were associated with 35% increased risk of prostate cancer recurrence. In addition, we found that each 10 mg/dl increase in total serum cholesterol above the abnormal cut-off value of 200 mg/dl was associated with a 9% increased risk of prostate cancer recurrence, while each 10 mg/dl increase in HDL (high density lipoprotein; “good” cholesterol) below the abnormal cut-off value of 40 mg/dl was associated with a 39% increased risk of prostate cancer recurrence. These findings suggest that normalization, or even partial normalization, of serum lipid levels among men with dyslipidemia may reduce the risk of prostate cancer recurrence. (more…)
Author Interviews, Lancet, Lipids / 02.10.2014

MedicalResearch.com Interview with: Dr. Raul Santos Unidade Clínica de Lipides InCor-HCFMUSP Sao Paulo, Brazil. Medical Research: What are the main findings of the study? Dr. Santos: Evolocumab 420 mg injected subcutaneously every 4 weeks reduced LDL-C by 31% on average, in relation to placebo, in Homozygous familial hypercholesterolemia patients that were using maximally tolerated lipid lowering therapy but not on lipid apheresis regimen. Patients were separated according to the type of LDL receptor mutation, those with at least one allele codifyng a defective mutation on the LDL receptor (residual receptor activity 2-25%) had on average a 41% reduction on LDL-cholesterol. The 2 patients  homozygotes with alleles that codify a null mutation )receptor activity < 2%), did not respond to treatment. This was expected since PCSK9 inhibitors need a functional LDL receptor do work. Basically they increase the expression of the receptor that facilitates the clearance from plasma of circulating LDL particles. In those patients with defective LDL receptor  mutations there was 24% reduction of lipoprotein(a) concentrations, an extra risk factor for cardiovascular disease in familial hypercholesterolemia patients. (more…)
Author Interviews, General Medicine, Lancet, Lipids / 02.10.2014

Professor F. J. Raal FRCP, FRCPC, FCP(SA), Cert Endo, MMED, PhD Director, Carbohydrate & Lipid Metabolism Research Unit Professor & Head, Division of Endocrinology & Metabolism Faculty of Health Sciences, University of the Witwatersrand Johannesburg Hospital Johannesburg South AfricaMedicalResearch.com Interview with: Professor F. J. Raal FRCP, FRCPC, FCP(SA), Cert Endo, MMED, PhD Director, Carbohydrate & Lipid Metabolism Research Unit Professor & Head, Division of Endocrinology & Metabolism Faculty of Health Sciences, University of the Witwatersrand Johannesburg Hospital Johannesburg South Africa Medical Research: What are the main findings of the study? Dr. Raal: Heterozygous familial hypercholesterolaemia (HeFH)  is one of the most common inherited disorder in man affects between 1:250 to 1:300 persons worldwide. Thus, there are likely more than 3 million patients with heterozygous familial hypercholesterolaemia in the United States and Europe alone. The RUTHERFORD-2 study was a large world-wide multinational study  of the use of the PCSK9-inhibitor, evolocumab, in over 300 patients with heterozygous familial hypercholesterolaemia (HeFH). Evolocumab administered either 140 mg biweekly or 420 mg monthly as a subcutaneous injection, much like an insulin injection, was well tolerated with minimal side effects,  and markedly reduced levels of LDL cholesterol or “bad cholesterol”  by over 60% compared to placebo. (more…)
Author Interviews, Diabetes, Lipids, Statins / 22.09.2014

Prof. Moses Elisaf Professor of Internal Medicine University of Ioannina, GreeceMedicalResearch.com Interview with: Prof. Moses Elisaf Professor of Internal Medicine University of Ioannina, Greece Medical Research: What are the main findings of the study? Dr. Elisaf: We evaluated the effects of rosuvastatin in two groups of hyperlipidemic patients: one group had impaired fasting glucose (IFG) while the second group had normal fasting glucose. After study end, both groups had similar changes in their lipidemic profile. However, patients with IFG had a significant greater decrease in the cholesterol concentration of the more atherogenic small dense low-density lipoprotein (sdLDL) particles (-65.7%) compared with controls (-38.5%). Moreover, a greater increase in the mean LDL particle size was observed in the impaired fasting glucose group (+1.5% vs +0.4%). In addition, redistribution from the more atherogenic sdLDL to large buoyant LDL (lbLDL) subfractions was observed in the IFG group. (more…)
Author Interviews, Diabetes, Diabetologia, Heart Disease, Lipids / 19.08.2014

MedicalResearch.com Interview with: Prof. Michael d’Emden Endocrine Research Unit Royal Brisbane Hospital, Brisbane, Australia Medical Research: What are the main findings of the study? Prof. d’Emden: Our study is the largest trial of women having type 2 diabetes assessing the role of a fibric acid derivative, in this case fenofibrate, ever conducted.  There were 3657 female subjects randomized to placebo or fenofibrate.  The study demonstrated greater reductions in women of total cholesterol, triglycerides and LDL-cholesterol and greater increases in HDL-cholesterol.  In women, fenofibrate decreased total cardiovascular end-points by 30% compared with only 13% in men, although there was no-treatment-by-sex interaction.  The majority of end points assessed revealed a consistent trend to increased benefit being seen in women. (more…)
Author Interviews, Heart Disease, Lipids, NEJM / 17.07.2014

Professor Jane Armitage Professor of Clinical Trials and Epidemiology Clinical Trial Service Unit, Oxford Cardiovascular Science Oxford, United KingdomMedicalResearch.com Interview with: Professor Jane Armitage Professor of Clinical Trials and Epidemiology Clinical Trial Service Unit, Oxford Cardiovascular Science Oxford, United Kingdom Medical Research: What are the main findings of the study? Prof. Armitage: The study showed that adding extended release niacin with laropiprant (to reduce the flushing) to standard treatment including statins in people with heart disease or strokes did not improve their outcome or reduce the risk of recurrent heart attacks or strokes. (more…)
AHA Journals, Author Interviews, Lipids / 14.07.2014

Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI Director of Research, Cardiac Catheterization Laboratory Director, Cardiovascular Outcomes Group Associate Professor of Medicine, New York University School of Medcine Principal Investigator ISCHEMIA-CKD trialMedicalResearch.com Interview with: Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI Director of Research, Cardiac Catheterization Laboratory Director, Cardiovascular Outcomes Group Associate Professor of Medicine, New York University School of Medcine Principal Investigator ISCHEMIA-CKD trial Medical Research: What are the main findings of the study? Dr. Bangalore: Our objective was to evaluate whether non-fasting LDL has similar prognostic significance as that of the conventionally measured fasting LDL values. We found that in an analysis of over 16,000 patients from the National Health and Nutrition Examination Survey that the non-fasting LDL values had similar prognostic significance as that of fasting LDL values for the prediction of long term (up to 14 years) death or cardiovascular death, thus questioning the traditional practice of insisting that patients fast prior to blood draw for a lipid panel. This was also true for other components of the lipid panel including the triglycerides and total cholesterol. (more…)
Breast Cancer, Lipids / 07.07.2014

Dr. Rahul Potluri Honorary Clinical Lecturer in Cardiology School of Medical Sciences, Aston University Birmingham UK;MedicalResearch.com Interview with: Dr. Rahul Potluri Honorary Clinical Lecturer in Cardiology School of Medical Sciences, Aston University Birmingham UK; Medical Research: What are the main findings of the study? Dr. Potluri: Study was conducted by a retrospective analysis of more than 1 million anonymous patient records across the UK between 2000 and 2013 using the Algorithm for Comorbidities, Associations, Length of stay and Mortality (ACALM) protocol. There were 664,159 women and of these, 22 938 had hyperlipidaemia and 9 312 had breast cancer. Some 530 women with hyperlipidaemia developed breast cancer. A statistical model to study the association between hyperlipidaemia and breast cancer. They found that having hyperlipidaemia increased the risk of breast cancer by 1.64 times (95% confidence interval 1.50-1.79). (more…)
Author Interviews, Lipids, NEJM, Statins / 31.03.2014

Evan A. Stein, M.D., Ph.D. FRCP(C), FCAP Metabolic and Atherosclerosis Research Center Cincinnati, OH 45225,MedicalResearch.com Interview with: Evan A. Stein, M.D., Ph.D. FRCP(C), FCAP Metabolic and Atherosclerosis Research Center Cincinnati, OH 45225,   MedicalResearch.com: What are the main findings of the study? Dr. Stein: The study which is the first 52 week randomized double blind trial of a PCSK9 to report results (all others have been 12 weeks) demonstrated that the excellent LDL-C reductions of 55-60% seen at 12 weeks are maintained through 52 weeks, with no fall off in patient compliance, tolerability of efficacy. It also demonstrated that with longer treatment no new or unexpected side effects. The study also had a unique design in that prior to randomization to the PCSK9 inhibitor (evolocumab) or placebo patients had a run in period during which time they were assigned, based on NCEP-ATP III criteria, to appropriated background therapy which ranged from diet only, to atorvastatin 10 mg a day, to atorvatatin 80 mg a day or atorvastatin 80 mg a day plus ezetimibe - reflecting how these patients are treated in practice. Only then if their LDL-C was still above 75 mg/dL were they randomized into the treatment part of the study with the new drug. The study showed that irrespective of background therapy the reduction with evolocumab was consistent. (more…)
Author Interviews, Duke, Lipids, NEJM, Statins / 28.03.2014

Michael J. Pencina, PhD Professor of Biostatistics and Bioinformatics Director of Biostatistics Duke Clinical Research Institute Durham, NC 27710 MedicalResearch.com Interview with: Michael J. Pencina, PhD Professor of Biostatistics and Bioinformatics Director of Biostatistics Duke Clinical Research Institute Durham, NC 27710 MedicalResearch.com: What motivated your research? Dr. Pencina: After the new guidelines were issued last November, we were intrigued by the change in treatment philosophy from that based on cholesterol levels (used by the “old guidelines” known as NCEP ATPIII) to one based on 10-year risk of cardiovascular disease (used by the new AHA-ACC guidelines).  We were curious what the practical consequences of this shift would be. Furthermore, the media quoted a lot of experts making educated guesses on the impact.  We realized that this question can be answered much more precisely based on the NHANES data. (more…)
Author Interviews, Genetic Research, Lipids, University of Michigan / 19.03.2014

dr_cristen_j_willerMedicalResearch.com Interview with: Cristen J. Willer, PhD Assistant Professor Division of Cardiovascular Medicine, Dept of Internal Medicine Dept of Human GeneticsDept of Computational Medicine and Bioinformatics University of Michigan Ann Arbor, MI 48109-5618 MedicalResearch.com: What are the main findings of the study? Dr. Willer: We wanted to find new genes related to heart disease, so we examined the DNA of approximately 10,000 Norwegian individuals and found 10 genes that are important regulators of blood cholesterol levels. Nine of these were well known to be related to lipids, but one gene was new.  It turned out to be in a region we'd previously noticed to be related to cholesterol, but it was a big region and we hadn't been able to pinpoint the gene yet.  Using this new approach, focusing on DNA differences that result in slightly different proteins in people, we zeroed in on the gene.  We then altered this gene in mice, and saw the predicted changes in cholesterol levels in mice. (more…)
Annals Internal Medicine, Author Interviews, Heart Disease, Lipids, Nutrition / 17.03.2014

Rajiv Chowdhury MD, PhD Cardiovascular Epidemiologist Department of Public Health and Primary Care University of CambridgeMedicalResearch.com Interview with: Rajiv Chowdhury MD, PhD Cardiovascular Epidemiologist Department of Public Health and Primary Care University of Cambridge MedicalResearch.com: What are the main findings of the study? Dr. Chowdhury: Total saturated fatty acid, whether measured as a dietary intake variable or in the bloodstream as a biomarker, was not associated with coronary disease risk in combining all available prospective observational studies. Similarly, there were non-significant overall associations in the prospective studies that involved assessments of total monounsaturated fatty acids, long-chain omega-3 and omega-6 polyunsaturated fatty acids. However, we found diversity in the observational associations between specific circulating long-chain omega-3 and omega-6 fatty acids with coronary risk, with some evidence that circulating levels of eicosapentaenoic and docosahexaenoic acids (ie, the two main types of long-chain omega-3 polyunsaturated fatty acids), and arachidonic acid are each associated with lower coronary risk. Similarly, within saturated fatty acids, there were positive, however, non-significant associations observed for circulating blood composition of palmitic and stearic acids (found largely in palm oil and animal fats, respectively), whereas circulating margaric acid (a milk fat) had a significant inverse association. Additionally, when we investigated the randomised controlled trials that reported on the effects of omega-3 and omega-6 fatty acids on reducing coronary outcomes, there was no significant overall association observed. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Lipids / 02.01.2014

MedicalResearch.com Interview with: Dr. Bruce Reed PhD Professor of Neurology, Associate Director UC Davis Alzheimer's Disease Center Davis, CA 95616 Dr. Bruce Reed PhD Professor of Neurology, Associate Director UC Davis Alzheimer's Disease Center Davis, CA 95616 MedicalResearch.com: What are the main findings of the study? Dr. Reed: We found that high LDL cholesterol and low HDL cholesterol in blood  were both associated with higher amyloid deposition in the brain.  This is potentially very important because the deposition of amyloid seems to be a critical step that kicks off a whole chain of events that eventually lead to Alzheimer's disease.  It is widely believed (although not proven) that if this deposition of amyloid could be blocked that we could greatly decrease the incidence of Alzheimer's.  The connection to cholesterol is exciting because we know a fair amount about how to change cholesterol levels.  A great deal more research needs to be done, but this does suggest a potential new path toward trying to prevent AD. (more…)
Author Interviews, JAMA, Lipids, Thyroid Disease / 18.11.2013

Angela M. Leung, MD, MSc Clinical Assistant Professor of Medicine Division of Endocrinology, Department of Medicine University of California Los AngelesMedicalResearch.com Interview with: Angela M. Leung, MD, MSc Clinical Assistant Professor of Medicine Division of Endocrinology, Department of Medicine University of California Los Angeles   MedicalResearch.com: What are the main findings of the study? Dr. Leung: Despite current guidelines to screen for thyroid dysfunction as a secondary cause of newly-diagnosed hyperlipidemia, this was performed only about 50% of the time by primary care providers in over 8,700 patients at a large, urban Boston academic medical center. Approximately 5% of patients who had thyroid function checked were found to have hypothyroidism. The majority of hypothyroid patients who received treatment with levothyroxine had successful correction of the initial hyperlipidemia within one year. (more…)