Red Meat Allergy Caused by Lone Star Tick Linked to Coronary Artery Disease

MedicalResearch.com Interview with:
“Lone Star Tick” by Katja Schulz is licensed under CC BY 2.0Jeffrey Wilson, MD, PhD

Research Fellow, Allergy & Immunology
University of Virginia 

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

Response: Galactose-α-1,3-galactose (α-Gal) represents an oligosaccharide that is present in mammalian products and is the causal allergen in a syndrome of delayed red meat allergy (commonly called α-Gal syndrome). Sensitization to this allergen has been linked to tick bites, specifically the lone star tick in the United States.

Thus, sensitization to α-Gal (and the prevalence of subjects with symptomatic red meat allergy) is relatively common where the lone star tick is common, i.e- the southeast.

For a variety of reasons we hypothesized that specific immune sensitization (which relates to IgE antibody production) to α-Gal would be a risk factor for coronary artery disease. To address this possibility we measured IgE specific to α-Gal in 118 adults subjects from central Virginia who had undergone advanced cardiac imaging with a technique called intravascular ultrasound. Out of the cohort 26% of the subjects in the study had the sensitivity to α-Gal.

The main finding was that subjects with the IgE sensitization to α-Gal had greater amounts of atherosclerosis, as well as atherosclerotic plaques with more unstable characteristics. This association was significant when controlled for traditional cardiovascular risk factors such as hypertension, diabetes and lipids levels.

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PlaqueTec Liquid Biopsies Give Alternative Data To Systemic Biomarkers

MedicalResearch.com Interview with:
PlaqueTec liquid biopsiesDr. Nick West, MD
PlaqueTec Chief Medical Officer and Consultant Interventional Cardiologist
Royal Papworth Hospital NHS Foundation Trust  

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

Response: Recent data have identified residual inflammatory risk as a potential therapeutic target to modulate future risk of coronary and vascular events independent of cholesterol lowering1. This approach has now been validated by the CANTOS study, showing reduction of peripheral blood levels of high-sensitivity CRP (hsCRP) and consequent reduction of the occurrence of major cardiac events in patients who had sustained a myocardial infarction2,3. Although controversy continues to rage regarding the relevance of ‘vulnerable plaque’ versus ‘vulnerable patient’ in the causation of acute coronary events, evolving data suggest a complex interplay between a proinflammatory milieu and ‘vulnerable’ plaque phenotypes 4,5 .

We used a novel dedicated intracoronary sampling catheter, the PlaqueTec Liquid Biopsy SystemTM (LBS), and sought to correlate systemic inflammatory indices with degree of local coronary inflammatory activity. The LBS has previously been validated to safely delineate the presence of gradients of inflammatory biomolecules in human coronary artery disease6. We measured blood levels of a large panel of inflammatory biomolecules using multiplexed assays in peripheral blood and in coronary-derived blood samples after balloon dilatation of coronary stenoses during coronary angioplasty, and assessed systemic levels of hsCRP by ELISA.

MedicalResearch.com: What are the main findings? 

Response: Statistical analysis using K-means indicated our patient population (n=23), predominantly patients with stable angina, segregated into 2 discrete clusters of high and low overall coronary inflammatory states. However, when compared with peripheral (systemic) levels of the same inflammatory biomolecules in each cluster, there was no meaningful relationship. Additionally, there was no difference between median hsCRP measurements between the 2 clusters. Taken together, these data suggest that simply measuring peripheral markers of inflammation may not be able to determine local inflammatory activity within the coronary artery itself. 

MedicalResearch.com: What should readers take away from your report?
What recommendations do you have for future research as a result of this work?

Response: These data provide interesting and hypothesis-generating data that explore the mechanisms of benefit in vascular risk by reducing systemic inflammation; rather than hsCRP acting as a simple ‘barometer’ for likelihood of events, it appears that presence of coronary inflammation may be an independent entity. Further studies are needed to address the complex relationship between systemic and coronary inflammation, and their respective interaction with ‘vulnerable’ plaque phenotypes in modulating patient events.

Disclosures: Dr West acts as a consultant to, and holds equity in, PlaqueTec Ltd.

Citations:

  1. Ridker PM. Residual inflammatory risk: addressing the obverse side of the atherosclerosis prevention coin. Eur Heart J 2016; 37: 1720-22.
  2. Ridker PM, Everett BM, Thuren T et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; 377: 1119-31.
  3. Ridker PM, MacFadyen JG, Everett BM et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomissed controlled trial. Lancet 2018; 391: 319-28.
  4. Libby P, Pasterkamp G. Requiem for the vulnerable plaque. Eur Heart J 2015; 36: 2984-7.
  5. Hansson GK, Libby P, Tabas I. Inflammation and plaque vulnerability. J Intern Med 2015; 278: 483-93.
  6. West NEJ, Corrigan JP, Owen RHG et al. Percutaneous sampling of local biomolecule gradients across coronary artery atherosclerotic plaques. J Am Coll Cardiol Basic Trans Science 2017; 2: 646-54.

Citation:

PlaqueTec Data Presented at EAS Show Lack of Correlation 
between Localised Coronary Artery Inflammatory Biomarker Expression and Systemic Elevation of Biomarkers including hsCRP

 

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Epigenetic DNA Variants Predictive of Coronary Artery Disease

MedicalResearch.com Interview with:

Stella Aslibekyan, PhD Associate Professor PhD Program Director Department of Epidemiology University of Alabama at Birmingham

Dr. Aslibekyan

Stella Aslibekyan, PhD
Associate Professor
PhD Program Director
Department of Epidemiology
University of Alabama at Birmingham

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

Response: When the human genome was sequenced in 2003, there were somewhat unrestrained expectations of unraveling all etiologic mysteries and discovering breakthrough treatments. Needless to say, that did not happen, in part because individual genetic variants can only account for a small fraction of trait variability. Since then, epigenetics– the study of mitotically heritable changes in gene expression– has emerged as another promising avenue for understanding disease risk. The best studied epigenetic process in humans is DNA methylation, and earlier studies (including some from our group) have shown interesting associations between changes in methylation in specific genomic regions and cardiovascular disease traits, e.g. plasma cholesterol levels.

In this project, we have combined DNA methylation data on thousands of individuals from multiple international cohorts and interrogated epigenetic contributions to circulating tumor necrosis factor alpha (TNFa), a marker of systemic inflammation. We identified and replicated several epigenomic markers of TNFa, linked them to variation in gene expression, and showed that these methylation changes (which were located in interferon pathway genes) were predictive of coronary heart disease later in life. Interestingly, the variants we discovered were not sequence-dependent (in other words, they were not associated with any genetic mutations), highlighting the role of the environment.

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First Diagnostic Blood Test for Coronary Artery Plaque Detection

MedicalResearch.com Interview with:

Szilard Voros, MD, FACC, FSCCT, FAHA CEO of Global Genomics Group

Dr. Voros

Szilard Voros, MD, FACC, FSCCT, FAHA
CEO of Global Genomics Group 

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

Response: Atherosclerotic coronary artery disease (ASCAD) is the leading cause of death and morbidity in the United States and worldwide, despite relatively successful medical therapies such as statins, like Zocor or Lipitor. A significant majority of patients with ASCAD present with sudden cardiac arrest, and the clinical evaluation of those patients who present with chest pain to their physicians is very inefficient. Based on current clinical guidelines, patients who present to their physician with complaints of new onset chest pain or its equivalent, such as exertional dyspnea should be assessed for the probability of the presence of significant ASCAD based on simple clinical predictors. Approximately 60% of such patients have an intermediate probability, and they are typically referred for initial non-invasive evaluation, such as a stress test with cardiac imaging, or for some other type of non-invasive test. Strikingly, no more that 5% of such stress tests performed in the United States are actually positive, and even when patients with positive stress test are taken for invasive coronary angiography, no more than 40% have significant ASCAD.

A blood test that could serve as first step, as a “gatekeeper”, to non-invasive evaluation, would be highly desirable. Global Genomics Group, or G3, has performed one of the largest, unbiased, mass-spectrometry-based discovery studies in over 1,000 patients who underwent detailed cardiac CT to assess the presence or absence of ASCAD, by measuring over 1,000 metabolites from the blood. Using sophisticated bioinformatics tools, the researchers identified 8 important metabolites that were significantly abnormal in patients with ASCAD, and generated a biomarker signature for the detection of ASCAD based on those analytes, called “knowPLAQUETM”. The biomarker signature was generated in approximately 800 subjects, and was validated in an independent set of approximately 400 subjects, showing an area under the curve (“AUC”) of 0.82 for the diagnosis of Atherosclerotic coronary artery disease. This biomarker signature can be adapted relatively easily on commercial mass spectrometry platforms, and the researchers anticipate that this signature may be available for physicians to use by 2018. In addition to its diagnostic power, this biomarker signature also has uncovered important biological insights for the development of ASCAD, which can be leveraged for therapeutic purposes.

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Southern Diet May Raise Risk of Coronary Artery Disease

James M. Shikany, DrPH Professor of Medicine Division of Preventive Medicine University of Alabama at Birmingham Birmingham, AL

MedicalResearch.com Interview with:
James M. Shikany, DrPH
Professor of Medicine
Division of Preventive Medicine
University of Alabama at Birmingham
Birmingham, AL

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Shikany: There is a growing interest in the field of nutritional epidemiology in relating overall dietary practices to various disease endpoints. For example, the assessment of dietary patterns in a population may be more meaningful than concentrating on isolated nutrients or foods because they more closely reflect how people eat in the real world. Previously, we looked at how the degree to which one adhered to 5 dietary patterns identified in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study was associated with the risk of stroke. In the current study, we investigated how the degree to which one adhered to these dietary patterns was related to the risk of incident acute coronary heart disease.

The main finding was that a Southern dietary pattern (characterized by added fats, fried foods, eggs and egg dishes, organ meats, processed meats, and sugar-sweetened beverages) was associated with a significantly greater hazard of incident acute coronary heart disease in REGARDS participants. The association persisted following adjustment for sociodemographics, lifestyle factors, and energy intake. Specifically, following multivariable adjustment, participants in the highest quartile of consumption of the Southern pattern experienced a 56% greater hazard of incident coronary heart disease compared with those in the lowest quartile of consumption of this pattern. Another pattern we observed – the Plant-based pattern – characterized by vegetables, fruits, beans, yogurt, poultry, and fish was not associated with an increased risk of coronary heart disease.

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No Adverse Effects of Short-Term Daily Egg Ingestion in Coronary Artery Disease

David L. Katz, MD, MPH, FACPM, FACP Director, Yale University Prevention Research Center Griffin HospitalMedicalResearch.com Interview with:
David L. Katz, MD, MPH, FACPM, FACP
Director, Yale University Prevention Research Center
Griffin Hospital

 

Medical Research: What are the main findings of the study?

Dr. Katz: We did not see any adverse effects of short-term, daily egg ingestion in adults with established coronary artery disease.

Medical Research: What was most surprising about the results?

Dr. Katz: Eggs are routinely banned from ‘heart healthy diets.’  in particular eggs are always absent from cardiac care units, with egg beaters substituting.  However, these same units routinely serve products with refined starch and added sugar.  The scientific basis for excluding eggs from diets to improve cardiac health has long been suspect.  Here, we show that in the short term at least, there are no discernible harms of daily egg ingestion even in adults with heart disease.
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Using Coronary Fractional Flow Reserve To Predict Clinical Outcomes

Nils P. Johnson, M.D., M.S. Assistant Professor - Cardiovascular Medicine Department of Internal Medicine University of Texas Health Science Center Houston TexasMedicalResearch.com Interview with
Nils P. Johnson, M.D., M.S.
Assistant Professor – Cardiovascular Medicine
Department of Internal Medicine
University of Texas Health Science Center
Houston Texas

Medical Research: What are the main findings of the study?

Dr. Johnson: Our study had 3 main findings.

  • First, the numeric fractional flow reserve (FFR) value related continuously to risk, such that clinical events increased as FFR decreased and revascularization showed larger net benefit  for lower baseline FFR values.
  • Second, fractional flow reserve measured immediately after  stenting also showed an inverse relationship with prognosis, likely due to its relationship with diffuse disease.
  • Third, an fractional flow reserve-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.
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Coronary Artery Disease: Evaluation of Darapladib for Atherosclerotic Plaques

Professor Harvey White MB ChB DSc FRACP FACC FESC FAHA FHKCC (Hon) FCSANZ FRSNZ La'auli (matai); Prince Mahidol Laureate; John Neutze Scholar Director of Coronary Care & Green Lane Cardiovascular Research Unit, Green Lane Cardiovascular Service Auckland City Hospital Victoria St West Auckland 1142 NEW ZEALANDMedicalResearch.com Interview with:
Professor Harvey White
MB ChB DSc FRACP FACC FESC FAHA FHKCC (Hon) FCSANZ FRSNZ La’auli (matai); Prince Mahidol Laureate; John Neutze Scholar, Director of Coronary Care & Green Lane Cardiovascular Research Unit, Green Lane Cardiovascular Service
Auckland City Hospital NEW ZEALAND

MedicalResearch.com: What are the main findings of the study?

Prof. White:   During follow-up (median 3.7 years), the composite primary end point (cardiovascular death, myocardial infarction or stroke) occurred in 9.7% of the 7,924 patients randomly assigned to darapladib and 10.4% of the 7,904 patients in the placebo group (HR 0.94, 95% CI 0.85-1.03 p=0.199).

In the first prespecified secondary endpoint of major coronary events (CHD death, MI or urgent revascularization) compared with placebo, darapladib reduced the rate (9.3% vs. 10.3%; HR=0.9; 95% CI, 0.82-1 p=0.045). Total coronary events (14.6% vs. 16.1%; HR = 0.91; 95% CI, 0.84-0.98,p=0.019). (CHD death, MI, any coronary revascularization, hospitalization for unstable angina) were also reduced. No major safety concerns arose during the trial. Continue reading

Saturated Fatty Acid Not Associated with Coronary Artery Disease?

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.

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