Diabetic Atherosclerosis Management Can Be Personalized Using Coronary Artery Calcium Score

MedicalResearch.com Interview with:
Dr. MalikDr. Shaista Malik MD PhD MPH
Director of Samueli Center For Integrative Medicine
Assistant Professor, School of Medicine
University of California, Irvine

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

Response: Having diabetes has been considered to be a risk equivalent to already had a myocardial infarction for predicting future cardiovascular events.  We were interested in testing whether further risk stratification in those with diabetes and metabolic syndrome, using coronary artery calcium (CAC), would result in improved prediction of cardiovascular events.

We found that CAC score was associated with incident coronary heart disease and cardiovascular disease more than a decade after the scoring was performed.  We also found that even after we controlled for the duration of diabetes (of 10 years or more), insulin use, or hemoglobin A1c level, coronary artery calcium remained a predictor of cardiovascular events.

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Thyroid Function Associated With Atherosclerotic Cardiovascular Morbidity and Mortality

MedicalResearch.com Interview with:
Arjola Bano, MD, DSc

PhD candidate
Departments of Internal Medicine and Epidemiology
Erasmus Medical Center, Rotterdam, The Netherlands

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

Response: Atherosclerosis is a chronic condition, characterized by the accumulation of lipids and fibrous elements in the arterial walls. It can progress insidiously from an asymptomatic narrowing of the arterial lumen (subclinical phase) to the clinical onset of vascular events (as coronary heart disease or stroke) and death. Despite advances in prevention and treatment, atherosclerotic diseases remain a leading cause of mortality worldwide. Therefore, identifying additional modifiable risk factors for atherosclerosis is of major importance.

So far, the role of thyroid hormone on atherosclerosis remains unclear. Moreover, a comprehensive investigation exploring the link of thyroid function with the wide spectrum of atherosclerosis, including subclinical atherosclerosis, clinical atherosclerosis and atherosclerotic mortality, within the same population is lacking.

Therefore, in a prospective study of 9231 middle-aged and elderly people, we explored the association of thyroid function with subclinical atherosclerosis (coronary artery calcification), atherosclerotic events (fatal and nonfatal coronary heart disease or stroke) and atherosclerotic mortality (death from coronary heart disease, cerebrovascular or other atherosclerotic disease). Higher free thyroxine (FT4) levels were associated with higher risk of subclinical atherosclerosis, atherosclerotic events and atherosclerotic mortality, independently of cardiovascular risk factors.

The risk of atherosclerotic mortality increased with higher FT4 levels (HR; CI: 2.35; 1.61-3.41 per 1 ng/dl) and lower thyroid-stimulating hormone (TSH) levels (HR; CI: 0.92; 0.84-1.00 per 1 logTSH), with stronger estimates among participants with a history of atherosclerotic disease (HR; CI: 5.76; 2.79-11.89 for FT4 and 0.81; 0.69-0.95 for TSH).

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Stem Cells Drive Vascular Calcification in Arteriosclerosis

MedicalResearch.com Interview with:
Rafael Kramann, MD, FASN
RWTH Aachen University
Division of Nephrology and Clinical Immunology
Pauwelsstr 30
52074 Aachen, Germany

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

Response: Vascular calcification contributes centrally to the increased cardiovascular morbidity and mortality in patients with diabetes or chronic kidney disease.

Vascular calcification is of major clinical importance as it predicts cardiovascular events, affects plaque stability contributing to stroke and myocardial infarction and also contributes to chronic heart failure by stiffening of the arterial wall. However, the cellular origin of vascular calcification is incompletely understood. While it is known that resident vascular smooth muscle cells and circulating macrophages are involved the contribution of adventitial cells is controversial and partly unknown.

Our data indicates that adventitial progenitor cells marked by expression of Gli1 are key drivers of vascular calcification in athero- and arteriosclerosis. Genetic ablation of this cell population completely abolished vascular calcification in a mouse model of high lipid load and chronic kidney disease. Identification of this progenitor population might be the first step towards a cell-specific targeted therapy of vascular calcification.

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Protein Irisin Linked to Muscle Wasting and Atherosclerosis in Dialysis Patients

Tae-Hyun Yoo MD PhD Department of Internal Medicine, College of Medicine Severance Biomedical Science Institute, Brain Korea 21 PLUS Yonsei University, Seoul, KoreaMedicalResearch.com Interview with:
Tae-Hyun Yoo MD PhD
Department of Internal Medicine, College of Medicine
Severance Biomedical Science Institute, Brain Korea 21 PLUS
Yonsei University, Seoul, Korea

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

Dr. Tae-Hyun Yoo: Sarcopenia, reduction in muscle mass, is frequently observed in PEW and is prevalent in chronic kidney disease (CKD) patients. In ESRD patients, sarcopenia is significantly associated with greater mortality. Skeletal muscles produce and release myokines, which  suggested to mediate their protective effects. Irisin, a novel myokine, has been introduced to drive brown-fat-like conversion of white adipose tissue and has beneficial effects of skeletal muscle on energy homeostasis and glucose metabolisms. Therefore, we hypothesized that irisin had significant association with sarcopenia and cardiovascular disease in dialysis patients. In peritoneal dialysis patients, serum irisin was positively correlated with mid-arm muscle circumference and thigh circumference. In addition, serum irisin was a significant independent predictor for carotid atherosclerosis even after adjustment for high-sensitivity C-reactive protein in these patients. This study demonstrated that serum irisin was significantly associated with sarcopenia and carotid atherosclerosis in peritoneal dialysis patients.

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Elevation of Both apoB and nonHDL-C Imply Greater Atherosclerosis Risk in Type 1 Diabetes

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.  Continue reading

Key Study Shifts Focus To Smooth Muscle Cells In Atherosclerotic Heart Disease

Dr. Gary K OwensRobert M. Berne Cardiovascular Research Center University of Virginia, Charlottesville, VirginiaMedicalResearch.com Interview with:
Dr. Gary K Owens Ph.D
Robert M. Berne Cardiovascular Research Center
University of Virginia, Charlottesville, Virginia

Medical Research: What is the background for this study?

Dr. Owens: The leading cause of death in the USA and worldwide is cardiovascular disease with many of the clinical consequences including heart attacks (myocardial infarctions) and strokes being secondary consequences of atherosclerosis, commonly referred to as hardening of the arteries. Importantly, a heart attack is not caused by gradual narrowing of a large coronary artery by the atherosclerotic plaque, but rather is caused by acute rupture of a plaque that results in a catastrophic thrombotic event that can completely occlude a major coronary artery shutting off blood supply to a major heart region. Similarly, rupture of a plaque can result in formation of a thrombus that breaks off and circulates to a cerebral vessel where it can occlude blood flow to a brain region leading to a stroke. As such, it is critical to understand the mechanisms that regulate the stability of plaques, and the likelihood of plaque rupture.

The general dogma among clinicians and cardiovascular researchers has been that atherosclerotic plaques that have an abundance of macrophages and macrophage-derived foam cells relative to smooth muscle cells (SMC), the cells that normally line all of your blood vessels, are less stable and more prone to rupture with subsequent clinical consequences. However, the evidence for this is based on use of methods that are unreliable in identifying which cells within the plaque are truly derived from macrophages versus SMC, and even more importantly, what mechanisms regulate phenotypic transitions of these cells that are critical in the pathogenesis of this disease. Indeed, results of studies in cultured smooth muscle cells and macrophages have shown that each cell can express markers of the other cell type in response to stimuli likely to be present within advanced atherosclerotic lesions while down-regulating expression of their typical cell selective markers. As such, previous studies in the field have likely mis-identified which cell is which in many cases.

The goals of our studies were to clearly identify which cells within advanced atherosclerotic lesions are derived from SMC, to determine the various phenotypes exhibited by these cells and their functional role in lesion pathogenesis,  and to determine what regulates these phenotypic transitions.

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Carotid Artery Stenting: Comparison Of Embolic-Prevention Devices

Jay Giri, MD MPH Director, Peripheral Intervention Assistant Professor of Clinical Medicine University of PennsylvaniaMedicalResearch.com Interview with
Jay Giri, MD MPH
Director, Peripheral Intervention
Assistant Professor of Clinical Medicine
University of Pennsylvania

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

Dr. Giri: Carotid artery stents are placed by vascular surgeons or interventional cardiologists to decrease the risk of long-term stroke in patients with severe atherosclerotic disease of the carotid artery.  When these procedures are performed, there is a risk of releasing small amounts of debris into the brain’s circulation, causing a stroke around the time of the procedure (peri-procedural stroke).  In order to mitigate this issue, embolic protection devices (EPD) have been developed to decrease the chances of small debris reaching the brain.

Two types of EPD exist.  The first is a small filter meant to catch the debris released by placement of the carotid stent (distal filter EPD).

The second is a more complex device type that leads to transient halting of blood flow to the brain in the carotid artery being stented (proximal EPD). Debris-containing blood is removed from the body prior to allowing normal blood flow to proceed back to the brain after stent placement.

Our prior research has shown that nearly all (>95%) of domestic carotid stenting procedures are performed with utilization of one of these devices.  We sought to compare important clinical outcomes of stroke and death between these 2 device types within a large national sample of patients undergoing carotid stenting.

Some small prior studies have investigated whether the total amount of debris reaching the brain is less with proximal embolic protection devices.  These studies have shown mixed results.  However, no prior study has investigated important clinical outcomes of stroke and death in relation to these devices.

We found that overall uptake of proximal embolic protection devices utilization in America has not been robust.  Less than 7% of all domestic CAS procedures are performed with this technology.   Our analysis showed that in-hospital and 30-day stroke/death rates with proximal EPD and distal filter EPD were similar (1.6% vs. 2.0%, p = 0.56 and 2.7% vs. 4.0%, p = 0.22, respectively).

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Low Vitamin D in Childhood Linked To Early Atherosclerosis

MedicalResearch.com Interview with:
Markus Juonala, MD, PhD
University of Turku Finland

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

Response: Earlier studies suggest that low vitamin D levels may be associated with cardiovascular disease. We wanted to study whether low childhood vitamin levels predict carotid intima-media thickness, a marker of early atherosclerosis, in adulthood. We observed that those children with vitamin D in lowest quartile had increased risk for high carotid intima-media thickness.

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Carotid Atherosclerosis Predicted by Cholesterol-Overloaded HDL Particles

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.

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Nanoparticle Exposure May Increase Atherosclerosis and Heart Disease Risk

MedicalResearch.com Interview with:
Lauren Petrick Ph.D.
The Lipid Research Laboratory
Rappaport Faculty of Medicine and Research Institute
The Technion Center of Excellence in Exposure Science and Environmental Health (TCEEH), Technion, Haifa, Israel

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

Dr. Petrick: Nanoparticles are becoming ubiquitous in our environment, leading to higher chances of exposure. This exposure may be especially chronic for those employed in research laboratories and in high tech industry where workers handle, manufacture, use and dispose of nanoparticles. Furthermore, nanoparticle exposure to the general population occurs in the form of ultrafine particles (UFP) primarily from transportation exhaust. While nanoparticle toxicity has been investigated in general terms, its atherogenic effects and mechanisms of nanoparticle atherogenicity are not yet clear. Therefore, we decided to expose engineered silica nanoparticles to macrophages in order to investigate cell atherogenicity and cytotoxicity. What we found is that the nanoparticles were cytotoxic and increased oxidative stress and triglyceride (TG) accumulation in the cells.  Triglyceride accumulation in macrophages was not due to a decrease in triglyceride cell secretion or to an increased triglyceride biosynthesis rate, but was the result of attenuated triglyceride hydrolysis secondary to decreased lipase activity and both adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein expression. This supports a possible role for ultrafine particles in exacerbating atherosclerosis development, and shows increased cardiovascular risk associated with nanoparticle exposure. Continue reading