Author Interviews, Heart Disease, Lipids / 11.07.2016

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. (more…)
AHA Journals, Author Interviews, Heart Disease, Lipids / 07.07.2016

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 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. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Lipids, Nutrition, Omega-3 Fatty Acids / 06.07.2016

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 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. (more…)
Author Interviews, Breast Cancer, Lipids, MRI, NYU / 09.06.2016

MedicalResearch.com Interview with: Sungheon G. Kim, PhD Associate Professor Department of Radiology NYU Langone and Researcher at the Center for Advanced Imaging, Innovation, and Research MedicalResearch.com: What is the background for this study? Dr. Kim: The role of fat in breast cancer development and growth has been studied extensively using body mass index (BMI), a measure of whole body fatness, and dietary fat intake in a number of epidemiological studies. However, there is a paucity of studies to assess the role of breast fat itself in breast cancer due to lack of a non-invasive and fast measurement method. Since breast fibroglandular cells are surrounded by breast fat cells, the characteristics of breast fat may have a stronger relationship with breast cancer development and growth than BMI and/or dietary fat. However, it is not trivial to study the role of breast fat, mainly due to the lack of a non-invasive and fast measurement method sensitive enough to important features of breast fat, such as types of fat. (more…)
Author Interviews, Diabetes, Endocrinology, Environmental Risks, Lipids / 27.05.2016

MedicalResearch.com Interview with: Maayan Yitshak Sade MPH Chief Scientific Officer Clinical Research Center, Soroka University Medical Center, Israel and   Victor Novack, MD, PhD Soroka University Medical Center and Ben-Gurion University in Beer Sheva, Israel   MedicalResearch.com: What is the background for this study? Response: Numerous studies found association between exposure the air pollution and increased risk of cardiovascular and respiratory diseases. In recent years links were found between air pollution and diabetes as well. The scientific evidence supports a causal association between air pollution and oxidative stress, possibly involving impaired metabolism of glucose and lipids. In a recent study performed by our group, we observed a significantly increased risk for ischemic stroke among young adults, associated with air pollution exposure. Following these findings, and as a part of the possible theory linking the association air pollution exposure and cardiovascular diseases, we sought to investigate if this association might be mediated through the well-established cardiovascular risk factors such as abnormal lipid and glucose metabolism. (more…)
AHA Journals, Author Interviews, Heart Disease, Lipids / 13.05.2016

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 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. (more…)
Author Interviews, Lipids, Pharmacology / 06.05.2016

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 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). (more…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids / 18.03.2016

MedicalResearch.com Interview with: Dr. Sarah de Ferranti MD MPH Boston Children’s Hospital Director, Preventive Cardiology Program Assistant Professor of Pediatrics Harvard Medical School MedicalResearch.com:  What are the main findings? Dr. de Ferranti: Familial hypercholesterolemia, or FH, is a genetic condition that causes severely elevated cholesterol levels from birth and is a leading cause of early heart attack. It is generally slowly progressive without symptoms until there is serious heart disease in the 3rd and 4th decade of life, making it important to look for it at a young age. Prior to this analysis it was thought that FH affected about 1 in 500 adults. The current study used data from 36,949 adults who took part in the 1999-2012 National Health and Nutrition Examination Survey (NHANES) and extrapolated to the 210 million U.S. adults aged 20 years and older. We identified cases of probably or definite Familial hypercholesterolemia in our analysis by using a combination of high levels of low-density-lipoprotein cholesterol (considered “bad” because it contributes to plaque buildup in arteries) and early heart disease in a person or close relative. (more…)
Author Interviews, Heart Disease, Lipids, Pharmacology, University of Pennsylvania / 03.03.2016

MedicalResearch.com Interview with: Dr. Richard L. Dunbar MD MS Assistant Professor of Medicine, Attending Physician, Preventive Cardiovascular Medicine Clinic, Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of MedicineMember, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine and Dr. Harsh Goel WellSpan Academic Hospitalists Department of Medicine, York Hospital, PA  MedicalResearch.com: What is the background for this analysis? Response: Niacin is the first cholesterol lowering treatment to prevent heart attacks and lower long term mortality. It thus provided the first proof that lowering cholesterol reduces cardiovascular risk. However, it is generally poorly tolerated due to almost universal flushing, limiting use. The better-tolerated statin drugs overshadowed niacin, rightly dominating hyperlipidemia therapy. Despite their advantages, statins are far from perfect, leaving important gaps. Firstly, at least 10% of patients simply don’t tolerate statins. Secondly, about 40% of patients have insufficient cholesterol lowering, leaving them far from their target LDL-cholesterol levels. Finally, even though statins lower cardiovascular risk, they by no means eliminate it and significant residual risk remains even in patients who respond to them. The relatively poor tolerance of niacin motivated development of an extended-release alternative which was dosed very differently from the established cardioprotective regimen used in the Coronary Drug Project (CDP) and the Stockholm Ischemic Heart Disease Study (SIHDS), the two landmark trials that proved niacin's benefits. These trailblazing trials used 3 grams of niacin divided throughout the fed portion of the day as 1 gram thrice daily with meals. In sharp contrast, the alternative regimen was severely handicapped by a profoundly lower dose of only 2 grams per day. Perhaps worse, the alternative regimen dosed all of the niacin at one sitting, at bedtime before the overnight fast, rather than three times a day before meals. We believe these were critical departures from the established cardioprotective niacin regimen, insofar as they severely undermined the alternative regimen’s efficacy. Accordingly, when added to statins, the alternative regimen failed to recapitulate the benefits seen with the established cardioprotective regimen in two recent large clinical trials, the AIM-HIGH trial and the HPS2-THRIVE trial. Besides the inherent flaws of the alternative regimen, there were also major issues with the trial designs which likely contributed to null results. From a practice standpoint, this is worrisome, because clinicians may draw erroneous conclusions from the trials of the alternative regimen, and thereby deny a significant population of hyperlipidemic patients the benefits of a well-proven cardioprotective therapy, i.e. the population which does not tolerate or does not respond adequately to statins (almost 50% of at risk patients). Hence, we embarked on a critical analysis and review of the alternative regimen with a special focus on the AIM-HIGH and HPS2-THRIVE trials to bring to light the pitfalls of comparing radically different regimens of what is nominally the same drug. (more…)
Author Interviews, Biomarkers, Heart Disease, Lipids / 19.02.2016

MedicalResearch.com Interview with: Lorenz Räber, MD, PhD Director Division CAD and MI INSELSPITAL, Bern University Hospital Bern, Switzerland Medical Research: What is the background for this study? Response: Inflammation is a key player in the pathobiology of atheorsclerosis. Inflammatory markers and specifically C-reactive protein (CRP) associate with statin-mediated clinical event reduction and plaque burden reduction in patients with stable CAD. Whether CRP correlates with changes in plaque composition, ie. an important presumed substrate of plaque vulnerability, remains unknown. We thought to assess compositional atheroma changes by means of virtual histology IVUS in relation to levels of hs-CRP in STEMI patients. For this purpose, we performed intracoronary imaging using virtual histology IVUS in the proximal part of the two non-infarct related coronary arteries of STEMI patients at baseline and 13 months follow-up (IBIS-4 study). A total of 44 patients with 80 vessels had serial imaging and hsCRP measurements available. Medical Research: What are the main findings? Response: This is the first study to show that serial changes and on-treatment levels of hs-CRP correlate with virtual histology IVUS-defined necrotic core content in patients with STEMI receiving high-intensity statin therapy. Patients with a low inflammatory activity are more likely to achieve a reduction in necrotic core, which represents a presumed substrate of plaque vulnerability. These findings may provide the basis for assessing inflammation at follow-up to monitor disease activity in STEMI patients. (more…)
Author Interviews, Lipids, Nutrition, Omega-3 Fatty Acids, Red Meat / 18.02.2016

MedicalResearch.com Interview with: Professor Chris Seal and Professor Carlo Leifert Nafferton Ecological Farming Group (NEFG),School of Agriculture, Food and Rural Development, Newcastle University Nafferton Farm, Stocksfield, Northumberland UK Medical Research: What is the background for this study? Response: In 2009 an FSA-sponsored study by Dangour et al. was published and concluded that there are no composition differences between organic and conventional crops and animal (meat and dairy) products. This contradicted the results of literature reviews, field experiments and retail surveys that many of the scientists involved in the EU-FP7 project QualityLowInputFoods (www.qlif.org/) had carried out or were in the process of completing in 2009. We therefore decided to put together an international team of scientists and carry out a larger, updated systematic literature reviews and meta-analyses to determine whether or not the Dangour et al (2009) study was justified in drawing the conclusions they had.  This took 5 years to complete. We reported on crops in 2014 (http://research.ncl.ac.uk/nefg/QOF/crops/) and the studies published now report the results on meat (http://research.ncl.ac.uk/nefg/QOF/meat/) and milk/dairy products (http://research.ncl.ac.uk/nefg/QOF/dairy/). Medical Research: What are the main findings? Response: 
  • both organic milk and meat contain around 50% more beneficial omega-3 fatty acids than conventionally produced products
  • organic meat had slightly lower concentrations of two saturated fats (myristic and palmitic acid) that are linked to an increased risk of cardiovascular disease
  • organic milk contains 40% more conjugated linoleic acid (CLA)
  • organic milk contains slightly higher concentrations of iron, Vitamin E and some carotenoids
  • conventional milk contained around 70% more of the essential mineral iodine and slightly more selenium
We feel the most important results in terms of nutrition is that both organic milk and meat contain around 50% more beneficial omega-3 fatty acids than conventionally produced products. Omega-3s are linked to reductions in cardiovascular disease, improved neurological development and function, and better immune function. Organic milk had 57% higher concentrations of the nutritionally most desirable, very long chain (VLC) omega-3 fatty acids eicosapentaenic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). Fatty acid profiles in milk are known to change very little during processing in to high fat dairy products such as butter and cheese. Omega-3s are linked to reductions in cardiovascular disease, improved neurological development and better immune function. The European Food safety Authority (EFSA) estimates that average dietary intakes of VLC omega-3 fatty acids account for less than half of what we need for optium health. The finding of substantially higher concentrations of iodine in conventional milk is also important information, especially for UK consumers, where iodized table salt is not widely available and dairy products are an important source of this nutrient. However, it should be pointed out that the Organic Milk Marketing Co-operative (OmsCo) has recently increased iodine fortification of organic dairy feeds and reports that levels of iodine in organic milk are now similar to those found in conventional milk (www.omsco.co.uk/_clientfiles/pdfs/omsco-iodine-levels.pdf). (more…)
Author Interviews, Lipids, Nutrition / 18.02.2016

MedicalResearch.com Interview with: Sachin A. Shah, Pharm.D. Residency Director & Regional Coordinator - Travis AFB Associate Professor of Pharmacy Practice TJ Long School of Pharmacy and Health Sciences University of the Pacific Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The link between serum cholesterol and cardiovascular mortality has been well established. Dietary sources of cholesterol can play a major role toward a beneficiary or unfavorable lipid profile. Fatty acids in foods typically fall within one of the four categories: saturated fats (SFAs), common in animal sources, trans fats (TFAs), common in processed foods, polyunsaturated fats (PUFAs), and monounsaturated fats (MUFAs), both common in plant-derived sources. Although low-fat diets are generally recommended, studies have indicated that altering the types of fats you consume may further modify the risk of dyslipidemia. We performed a meta-analysis of existing studies to determine the impact of avocados on the lipid profile. Ten unique studies incorporating 229 subjects were included. Avocado consumption significantly reduced TC, LDL-C, and TG by 18.80 mg/dL, 16.50 mg/dL, 27.20 mg/dL respectively. HDL-C decreased non-significantly. (more…)
Author Interviews, Lipids, Neurological Disorders / 18.01.2016

More on Lipids on MedicalResearch.com MedicalResearch.com Interview with: Noriko Osumi, DDS, PhD Director, Center for Neuroscience Professor, Department of Developmental Neuroscience Tohoku University School of Medicine Seiryo-machi, Aoba-ku, Sendai Japan  Medical Research: What is the background for this study? What are the main findings? Dr. Osumi: Omega-6 and omega-3 fatty acids are known to be important for brain growth. This is mainly because many researchers have shown that imbalance between these fatty acids during pregnancy causes several defects in future brain functions both in humans and rodents. Therefore, we asked the underlying mechanism how maternal intake of the omega-6 excess/omega-3 deficient dietary impairs brain development in mice using genetical rescue and comprehensive lipidomics together with neural stem cell biology. We have shown how these fatty acids affect brain growth, and revealed its molecular and cellular mechanisms. In particular, the reduced thickness of the cortex is due to precocious gliogenesis following neurogenesis, which may include epoxide metabolites of omega-6 fatty acids. (more…)
Author Interviews, Heart Disease, Lipids / 20.11.2015

MedicalResearch.com Interview with: Dr. Héctor González-Pacheco MD Coronary Care Unit, National Institute of Cardiology Mexico City, Mexico Medical Research: What is the background for this study? Dr. González-Pacheco: Epidemiological studies have provided robust evidence for an inverse correlation between plasma levels of high-density lipoprotein cholesterol (HDL-C) and cardiovascular risk. At hospital admission, a high percentage of patients with an acute coronary syndrome (ACS) have low HDL-C levels. Currently, the association of very low levels of HDL-C with early mortality in patients with ACS is still a topic of considerable interest. However, the possible mechanisms are not clear. Since an acute coronary syndrome induces an inflammatory response, and several chronic systemic diseases and acute critical illnesses with clear pro-inflammatory components have been associated with significantly reduced HDL-C levels, and investigators have shown an inverse correlation between HDL-C levels and the levels of pro-inflammatory cytokines, we hypothesized that reduced HDL-C levels in acute coronary syndrome might be associated to inflammatory mediators. We therefore sought to evaluate the correlation between HDL-C levels and biomarkers of inflammation available in routine laboratory screenings (high-sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, and serum albumin) in a retrospective cross-sectional study of patients with ST-elevation myocardial infarction (STEMI) or non-ST-elevation ACS (NSTE-ACS). Medical Research: What are the main findings? Dr. González-Pacheco: We found that approximately one-fifth of patients had very low HDL-C levels (<30 mg/dL). Baseline levels of hs-CRP were significantly higher in these patients than in those with low (30–39.9 mg/dL) and normal (≥40 mg/dL) HDL-C levels. In contrast, serum albumin values were lower in patients with very low HDL-C levels. WBC count did not differ significantly. Accordingly, hs-CRP levels ≥ 10 mg/L and serum albumin levels ≤ 3.5 mg/dL, were two strong independent predictors of very low HDL-C levels. We observed that patients with STEMI had higher expression of biomarkers of inflammation and lower levels of HDL-C, compared with NSTE-ACS patients, as well as a lack of significant difference in the extent of coronary disease among the categories of HDL-C levels. These findings suggest that the fall in HDL-C levels is in accordance with the severity of the inflammatory response and the extent of the myocardial damage. Our findings are consistent with previous studies, in which patients with very low HDL levels had a higher rate of in-hospital mortality compared with those of other HDL-C levels. (more…)
Author Interviews, Heart Disease, Lipids, Stanford / 13.11.2015

MedicalResearch.com Interview with: Liana Del Gobbo PhD Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; and Life Sciences Research Organization, Bethesda, MD Medical Research: What is the background for this study? What are the main findings? Dr. Del Gobbo: Accumulating evidence suggests that nut intake lowers risk of cardiovascular disease. But the specific mechanisms by which nuts may exert beneficial effects (eg. through lowering blood cholesterol, blood pressure, inflammation, etc.) were not clear. Two prior reviews on this topic only evaluated one type of nuts, and only a few cardiovascular risk factors. To address these knowledge gaps, we performed a systematic review and meta-analysis of controlled trials to examine the effects of eating tree nuts (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, Brazil nuts) on major cardiovascular risk factors including blood lipids (total cholesterol, LDL, HDL, triglycerides [TG]), lipoproteins (ApoA1, ApoB, ApoB100), blood pressure (systolic, SBP; diastolic, DBP), and inflammation (C-reactive protein, CRP) in adults 18 years or older without cardiovascular disease. A daily serving of nuts (1oz serving, or 28g per day) significantly lowered total cholesterol, LDL, ApoB, and triglycerides, with no significant effects on other risk factors, such as HDL cholesterol, blood pressure or inflammation. To give you an idea of a 1oz serving size of nuts, it is about 23 almonds, 18 cashews, 21 hazelnuts, 6 Brazil nuts, 12 macadamia nuts, 14 walnut halves, 20 pecan halves, 49 pistachios. We did not see any differences in cholesterol-lowering effects by nut type. (more…)
Author Interviews, BMJ, Lipids / 16.10.2015

MedicalResearch.com Interview with: Jamie Gaida, PhD Assistant Professor Discipline of Physiotherapy University of Canberra Medical Research: What is the background for this study? What are the main findings? Dr. Gaida: Cholesterol is essential for life but having too much circulating in your blood increases cardiovascular disease risk. A growing collection of evidence indicates that metabolic health (i.e. cholesterol and diabetes) is linked to musculoskeletal injuries. Tendons connect muscle to bone, and tendinopathy is condition where a person feels pain when using their tendons. People with Achilles tendinopathy experience pain when walking or when running, which limits their ability to be physically active. Tendinopathy also affects other tendons throughout the body, such as the rotator cuff tendons of the shoulder. This research identified all published research on the link between cholesterol levels and tendinopathy. We used a statistical technique called meta-analysis to combine these studies, which showed that cholesterol levels are linked to tendinopathy. However, the most interesting finding was that the pattern of cholesterol changes seen with tendinopathy matched the pattern of cholesterol changes that increase cardiovascular disease risk. It seems that what is bad for you heart is bad for your tendons. (more…)
Author Interviews, Heart Disease, Lipids / 25.09.2015

MedicalResearch.com Interview with: Dr Marcus Kleber PhD Post-doctoral researcher at the Vth Department of Medicine of the Medical Faculty Mannheim Heidelberg University Medical Research: What is the background for this study? What are the main findings? Dr. Kleber: Most trans fatty acids in our diet are industrially produced.  High concentrations of trans fatty acids are hazardous to human health but whether low concentrations are also harmful has not been studied in detail. We measured trans fatty acids in the erythrocyte membranes of our study participants  and found relatively low levels that were not associated with increased mortality. To the contrary, we found an association with a reduced risk for sudden cardiac death for higher concentrations of the naturally occurring trans fatty acid trans-palmitoleic acid that is ingested with milk and milk products. (more…)
Author Interviews, Inflammation, Lipids, University of Pennsylvania / 04.08.2015

Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of PennsylvaniaMedicalResearch.com Interview with: Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Medical Research: What is the background for this study? What are the main findings? Dr. Skarke: A growing body of publications suggests anti-inflammatory actions of fish oils. These health benefits are proposed to emerge from lipids called specialized pro-resolving mediators, (SPMs), which can be formed from omega-3 polyunsaturated fatty acids found in fish. A limitation to date, though, in this field is that there is little evidence of their formation in humans. And the cases where presence of these lipids is reported in humans, less rigorous analytical approaches, such as enzyme immunoassay (EIA), radioimmunoassay (RIA) or mass spectrometry without internal authentic standards, have been used. Thus, the specific aim for our study was to use state-of-the-art mass spectrometry to identify and quantify these specialized pro-resolving mediators. Several aspects of our study design set us apart from what was done in previous studies.
  • First, we biased our ability to detect SPMs formed in healthy volunteers by giving fish oil in high doses which had been previously shown to influence blood pressure and platelet aggregation under placebo-controlled conditions.
  • Second, we also looked at lower doses of fish oil, those more commonly consumed by the general public, for the formation of SPMs during an acute inflammatory response and its resolution.
  • Third, we relied in our measurements of SPMs on authentic internal standards. These deuterated lipids, d4-resolvin E1 for example, facilitate distinct identification of the naturally formed lipid.
  • And fourth, we achieved very low limit of detection levels, below 10 pg/ml for resolvin E1, for example.
The surprising finding of our studies is that we failed to detect a consistent signal of SPM formation in urine or plasma of healthy volunteers who had taken fish oil. Even more surprising was that we found no alteration in the formation of SPMs during the resolution of inflammation. These results let us question the relevance of endogenous specialized pro-resolving mediators to the putative anti-inflammatory effects of fish oils in humans. (more…)
Author Interviews, Diabetes, Lipids / 22.07.2015

Petter Bjornstad, MDFellow in Pediatric Diabetes & Endocrinology Children's Hospital Colorado & Barbara Davis Center for Childhood Diabetes Aurora, CO 80045MedicalResearch.com Interview with: Petter Bjornstad, MD Fellow in Pediatric Diabetes & Endocrinology Children's Hospital Colorado & Barbara Davis Center for Childhood Diabetes Aurora, CO 80045 MedicalResearch: What is the background for this study? Dr. Bjornstad: Apolipoprotein B (apoB) and non-high density lipoprotein-cholesterol (nonHDL-C) have been proposed to be superior indicators of cardiovascular (CV) risk than total cholesterol and/or low density lipoprotein-cholesterol (LDL-C). Some authors argue that while nonHDL-C and apoB correlate, they are not necessarily interchangeable, and may in fact provide unique information about cardiovascular risk. However, there are insufficient data on the concordance between apoB and nonHDL-C in adults with type 1 diabetes mellitus (DM) across a wide range of risk factors for cardiovascular disease. MedicalResearch: What are the main findings? Dr. Bjornstad: Adults with type 1 diabetes and elevated apoB (≥90mg/dL) and nonHDL-C (≥130mg/dL) had greater odds of coronary artery calcification progression compared to adults with type 1 diabetes and normal apoB and nonHDL-C (OR: 1.90, 95% CI 1.15-3.15), and compared to adults with type 1 diabetes with elevated apoB alone (OR: 2.86, 95% CI 1.43-5.74) adjusting for age, sex, duration, HbA1c and statins. We also obtained similar results with elevated apoB and nonHDL-C defined as ≥ the cohort means. Accordingly, we concluded that elevated apoB and nonHDL-C carry a greater risk of atherosclerosis than elevated apoB in the absence of elevated nonHDL-C in adults with type 1 diabetes.  (more…)
Author Interviews, Diabetes, Lipids, Ophthalmology / 06.07.2015

Dr Ruth Hogg, Lecturer Centre for Experimental Medicine (formerly Centre for Vision and Vascular Science) Institute of Clinical Science Block Belfast Northern IrelandMedicalResearch.com Interview with: Dr Ruth Hogg, Lecturer Centre for Experimental Medicine (formerly Centre for Vision and Vascular Science) Institute of Clinical Science Block Belfast Northern Ireland Medical Research: What is the background for this study? What are the main findings? Dr. Hogg: The development of Diabetic macular edema (DME) in patients with diabetes can result in severe visual loss.  Understanding the factors driving the development of these conditions is important for developing effective treatments.  The role of lipids has been suggested by previous studies however as the evidence overall appeared to have significant uncertainty we decided to undertake a systematic review and where possible perform a meta-analysis or results. The study revealed that the evidence of a relationship between blood lipid levels and Diabetic macular edema from cohort and case control studies was strong but evidence from the randomised control trials (RCTs) was weak.  The RCTS evaluated however were often not designed to look at Diabetic macular edema as an primary outcome, and this was often part of a secondary analysis leaving uncertainty over the power to detect the association.  (more…)
AHA Journals, Author Interviews, Lipids, Race/Ethnic Diversity / 25.06.2015

Carlos J. Rodriguez, MD, MPH Division of Public Health Sciences Department of Medicine Wake Forest School of Medicine Winston‐Salem, NC 27152MedicalResearch.com Interview with: Carlos J. Rodriguez, MD, MPH Division of Public Health Sciences Department of Medicine Wake Forest School of Medicine Winston‐Salem, NC 27152 MedicalResearch: What prompted you to study cholesterol in the Latino population? Please explain in detail. Dr. Rodriguez: Early in my career I noted that there were race-ethnic differences in the cholesterol profile between hispanics, african americans and non-hispanic whites. Hispanics are the largest ethnic minority group in the us yet prior studies of cholesterol in hispanics were relatively small, lacked adequate representation of diverse hispanic background groups for comparisons, and were not necessarily representative of nor generalizable to the hispanic population. The hispanic/latino adults in the hispanic community health study / study of latinos helped filled this critical gap. MedicalResearch: What do you think are the most significant findings from your study? What could have the greatest clinical implications and applications? Dr. Rodriguez: Several findings are important: less than half of those with high cholesterol were aware of their condition; less than a third of those with high cholesterol were being treated; and  among those receiving treatment, only two-thirds had cholesterol concentrations that were adequately controlled. (more…)
Author Interviews, Diabetes, Genetic Research, Lipids, PLoS / 31.05.2015

Dr. Yann C Klimentidis, PhD Assistant professor of Epidemiology and Biostatistics Mel and Enid Zuckerman College of Public Health University of Arizona Medical CenterMedicalResearch.com Interview with: Yann Klimentidis Ph.D. Assistant Professor Mel and Enid Zuckerman College of Public Health University of Arizona Medical Research: What is the background for this study? What are the main findings? Dr. Klimentidis: Previous studies have hinted at the possibility that genes which are associated with higher triglyceride levels may also be associated with lower type-2 diabetes. We set out  to test this hypothesis in multiple prospective cohort studies, in European-Americans and in African-Americans. We found that on a collective basis, the alleles which are associated with higher triglycerides are also associated with reduced type-2 diabetes risk. We also identified some individual genetic variants which are driving this trend. (more…)
Author Interviews, BMJ, Geriatrics, Lipids, Statins, Stroke / 19.05.2015

Christophe Tzourio, MD, PhD Professor of Epidemiology University of BordeauxMedicalResearch.com Interview with: Christophe Tzourio, MD, PhD Professor of Epidemiology University of Bordeaux Medical Research: What is the background for this study? What are the main findings? Dr. Tzourio: The efficacy of lipid-lowering drugs (LLD) - which include statins and fibrates - to reduce the risk of coronary events and stroke has already been demonstrated in randomized trials. However, these trials were performed on highly selected patients, usually of middle-age (50-70 yrs) and with a history of cardiovascular disease or a high vascular profile. There is therefore currently no indication on the benefit of these drugs in elderly individuals of the general population without a past-history of cardiovascular disease and guidelines do not recommend the use of lipid-lowering drugs in elderly individuals without clinical atherosclerotic disease. As there are not randomized trials in non-selected individuals in this age category, observational population-based cohorts are therefore the only alternative to study the impact of lipid-lowering drugs on the risk of cardiovascular diseases in the elderly. We analyzed data from the Three-City study, a community-based cohort in 7484 elderly individuals (mean age 74 years), followed-up during 9 years, without known history of vascular disease at baseline. We observed a one third decrease in the risk of stroke in lipid lowering drug users (hazard ratio 0.66, 0.49 to 0.90) compared with non-users. Reduction in stroke risk was similar for the statin and fibrate groups. No protective effect was seen on the risk of coronary heart disease. (more…)
Author Interviews, Brigham & Women's - Harvard, Cannabis, JAMA, Lipids, Pediatrics / 06.04.2015

Holly Gooding, MD, MS Harvard T.H. Chan School of Public Health Instructor in Pediatrics at Harvard Medical School Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital Division of General Internal Medicine, Brigham and Women’s Hospital Boston, MAMedicalResearch.com Interview with: Holly Gooding, MD, MS Harvard T.H. Chan School of Public Health Instructor in Pediatrics at Harvard Medical School Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital Division of General Internal Medicine Brigham and Women’s Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Gooding: As an adolescent medicine physician, I primarily care for patients between the ages of 12 and 30, although I first trained in internal medicine.  One of the things I noticed when I started working with this age group is that pediatric and adult guidelines differ for many conditions.  Cholesterol treatment is one condition that comes up frequently, because the NHLBI and the AAP recommend screening youth ages 17 to 21 for cholesterol problems. The study team and I set out to discover the proportion of American youth ages 17 to 21 who would meet criteria for pharmacologic treatment of abnormal cholesterol levels if clinicians applied the pediatric versus the adult guidelines.  We found that 2.6% of young people ages 17 to 21 would qualify for pharmacologic treatment of abnormal LDL cholesterol levels under the pediatric guidelines, but less than 1% would qualify under the adult guidelines.  This translates to almost 500,000 youth qualifying for treatment under the pediatric guidelines, but only about 78,000 under the adult guidelines.  Those who met pediatric criteria had lower LDL levels but higher proportions of high blood pressure, smoking, and obesity. (more…)
Author Interviews, Diabetes, Heart Disease, JAMA, Lipids, Statins / 11.03.2015

Joost Besseling PhD-student Academic Medical Center Dept. of Vascular Medicine AmsterdamMedicalResearch.com Interview with: Joost Besseling PhD-student Academic Medical Center Dept. of Vascular Medicine Amsterdam Medical Research: What is the background for this study? What are the main findings? Response: Statins are associated with an increased risk for type 2 diabetes mellitus (DM). The exact mechanism for this adverse event is largely unknown, although the upregulation of the low-density lipoprotein receptor (LDLR) has been suggested to play a role. In familial hypercholesterolemia (FH) the uptake of LDL-cholesterol via the LDLR is decreased due to a genetic defect. We found that the prevalence of type 2 DM is 50% lower in relative terms in patients with familial hypercholesterolemia. Moreover, there was a dose-response relationship: the more severe the genetic defect that causes familial hypercholesterolemia, the lower the prevalence of type 2 DM. (more…)
AHA Journals, Author Interviews, Heart Disease, Lipids / 09.02.2015

Ann Marie Navar-Boggan, MD PhD Fellow, Cardiovascular Disease Duke University School of Medicine MedicalResearch.com Interview with: Ann Marie Navar-Boggan, MD PhD Fellow, Cardiovascular Disease Duke University School of Medicine Medical Research: What is the background for this study? What are the main findings? Response: In this study of adults from the Framingham Offspring Study, we evaluated the impact of prolonged exposure to elevated cholesterol in early adulthood and future risk of coronary heart disease. In adults aged 55, the duration of time a person has been exposed to a non-HDL of >=160 mg/dL was associated with increased risk of coronary heart disease, and that risk was above and beyond the risk conferred by lipid levels at age 55. Every 10 years spent with a non-HDL of 160 or above was associated with a 39% increased future risk of coronary heart disease. We also looked at the association between prior average blood cholesterol between the age of 35 and 55, and found that every 10 mg/dL increase in prior average cholesterol above 125 mg/dL was associated with a 33% increased risk of coronary heart disease. These findings were particularly notable because the vast majority of adults with prolonged exposure to hyperlipidemia would not have been identified by the guidelines for statin therapy.​ (more…)
Author Interviews, Heart Disease, JACC, Lipids / 28.01.2015

MedicalResearch.com Interview with: Dong Zhao MD.PhD Deputy Director & Professor andDong Zhao MD.PhD Deputy Director & Professor and Dr. Que Qi, MD.PhD Assistant Professor Beijing Institute of Heart,Lung & Blood Vessel Diseases Capital Medical University Beijing Anzhen HospitalDr. Que Qi, MD.PhD Assistant Professor Beijing Institute of Heart,Lung & Blood Vessel Diseases Capital Medical University Beijing Anzhen Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Dong Zhao: Lower serum HDL-C level used to be considered as a key risk factor of atherosclerotic cardiovascular diseases. This knowledge was based on very consistent findings from researcher of basic science and observational studies of epidemiology. HDL-C has been also introduced as "good cholesterol" to the public. However, this well accepted knowledge was challenged when two large RCTs demonstrated that increased serum HDL-C by CETP inhibitor (ILLUMINATE and dal-OUTCOMES) failed to show benefits on reducing the risk of atherosclerotic cardiovascular disease. Therefore, many researchers questioned whether serum HDL-C can fully represent the capacity of cholesterol reverse transport of HDL particle, an underpinning of the anti-atherogenic function of HDL. And HDL particle number was considered to be better than HDL-C as a proper parameter to assess the function of HDL. In fact, RCTs that increased serum HDL-C substantially by CETP inhibitor had little effect on HDL particle number, thus resulting in increased cholesterol-overloaded HDL particle. Previous experimental studies observed that cholesterol-overloaded HDL particle exerted a negative impact on cholesterol reverse transport. However, it remains unclear whether cholesterol-overloaded HDL is involved in the development of atherosclerosis in humans. In our study, we measured HDL particle number using nuclear magnetic resonance spectroscopy, and calculated the ratio of HDL-C to HDL particles number to estimate the cholesterol content per HDL particle (HDL-C/P ratio). We found that cholesterol-overloaded HDL particles, indicated by high HDL-C/P ratio, are independently associated with the progression of carotid atherosclerosis in asymptomatic individuals from a community-based cohort study of the Chinese Multi-provincial Cohort Study-Beijing Project. (more…)
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…)