22ndAnnuAl updAte

2010 -2011

FACING OFF AGAINST HEART DISEASE

THE JOHNS HOpkINS

CICCARONE CENTER

FOR THE pREvENTION

OF HEART DISEASE

On the Cover

The staff members and fellows of the

Johns Hopkins Ciccarone Center for the

Prevention of Heart Disease include:

(Top row, left to right)

Catherine Campbell, MD;

Rhondalyn McLean, MD;

Chiadi Ndumele, MD;

Khurram Nasir, MD;

Roger S. Blumenthal, MD;

(Second row, left to right)

Sherita Golden, MD;

Gary Gerstenblith, MD;

Elizabeth Ratchford, MD;

Aaron Horne, MD;

(Third row, left to right)

Rani Hasan, MD;

Wendy Post, MD;

Michael J. Blaha, MD;

Ahmed Haitham, MD;

(Fourth row, left to right)

J. Bill McEvoy, MD;

Michael Minder, MD;

Erin Michos, MD;

(Fifth row, left to right)

Kerunne Ketlogetswe, MD;

Andrew P. DeFilippis, MD;

Michael G. Silverman, MD;

Rinky Bhatia, MD;

Dominique Ashen, PhD, CRNP; and

Steven Jones, MD.

Message from the Director

Wrapping Up Another Busy and productive Year

The Johns Hopkins Ciccarone Center for the prevention of Heart Disease recently completed its 21st year of service, and it was our most

productive to date. For the second straight year, members of the Ciccarone Center co-authored more than 100 scientific publications in many of the leading cardiology and internal medicine publications. One of the most important articles, led by dr. Michael Blaha, was published in the Lancet, the world’s second-most influential medical journal.

Dr. Blaha and colleagues looked at individuals in the Multi-Ethnic Study of Atherosclerosis who met entry criteria for the landmark JUpITER study (men at least 50 years of age, women at least 60 years of age, normal LDL-cholesterol < 130 mg/dL and an elevated measure of inflammation [high sensitivity C-reactive protein or hsCRp >2 mg/L]). Current national guidelines recommend the use of statin therapy in this group of individuals. However, we showed that these individuals experienced an extremely low cardiac event rate if they had no coronary calcification but a relatively high event rate if they had a coronary calcium score of at least 100, regardless of their hsCRp level.

previously it had been thought that those individuals with a normal hsCRp would have a low rate of future events, but we discovered that this was not the case if those individuals had a moderate amount of coronary calcification. We concluded that selective use of coronary artery calcium measurements could be used to target subgroups of patients who would be expected to derive the most and least absolute benefit from statin and aspirin therapy over the next six years. We believe that focusing drug therapy on the subset of individuals with normal lipids and at least moderate subclinical atherosclerosis should allow for more cost-effective use of prescription medications. The results, published in the Lancet, along with another study that Ciccarone staff members published in the Journal of the American College of Cardiology, call into question the usefulness of an hsCRp level of above 2 mg/L to effectively risk stratify persons with normal lipid values.

drs. Blaha, J. Bill Mcevoy, Steven Jones, Khurram nasir, and I also wrote an article, featured in the Journal of the American College of Cardiology, discussing the potential usefulness and limitations of repeating a coronary calcium scan a few years after an initial scan to assess coronary artery calcium progression. Members of our research group also will be presenting data on this controversial topic at the upcoming 2011 scientific sessions of the American Heart Association.

Another high-profile study that the Ciccarone Center staff published this year, in the Archives of Internal Medicine, was led by dr. Mcevoy. His group studied 1,000 asymptomatic middle-aged individuals who underwent coronary CT angiography for assessment of their coronary arteries and compared them to another

1,000 similar individuals who did not have CT angiography; we found that this test was associated with increased use of important preventive medications, but increased invasive testing with no evidence of reduced cardiovascular events at 18 months. They concluded that a screening coronary CT angiogram in asymptomatic adults should not be considered a justifiable test at this time because it is associated with extra radiation

exposure, it requires intravenous contrast, and there was no reduction in subsequent event rates after getting the test results. This article, featured in the “Less is More” section of the Archives of Internal Medicine, strongly indicates that physicians should not order this more expensive screening test in persons without cardiac symptoms. A senior physician from the National Heart Lung and Blood Institute, dr. Michael lauer wrote a very favorable editorial commentary about Dr. McEvoy’s article complementing the study design.

Our group has continued to be a research leader on atherosclerosis imaging and blood biomarkers to improve cardiovascular disease risk prediction. dr. Chiadi ndumele, who joined our Ciccarone Center faculty this year after serving as Chief Cardiology Fellow, was lead author of an article in the prestigious journal Arteriosclerosis, Thrombosis, and Vascular Biology. We found that fat deposition in the liver, obesity, and the prediabetic state were associated with increased systemic inflammation as measured by the biomarker hsCRp.

We at the Ciccarone Center are very proud of the publication in March 2011 of the comprehensive textbook Preventive Cardiology: A Companion to Braunwald’s Heart Disease, for which I served as co-editor-in-chief. We were pleased to dedicate the book to the memory of dr. Kenneth l. Baughman, who exemplified a tremendous commitment and personal passion for the principles and teachings of preventive cardiology. Dr. Baughman was a close friend and mentor to Drs. Jones, Wendy post, and to me, and was instrumental in the growth and development of the Ciccarone Center.

[ continued ]

Several Ciccarone staff members contributed chapters to this important book. drs. Blaha, ty Gluckman, and I co-wrote the lead chapter, “preventive Cardiology: past, present, and Future,” while dr. nasir and I co-wrote “Role of vascular Computed Tomography in Evaluation and prevention of Cardiovascular Disease.” dr. Gary Gerstenblith was the senior author of the chapter “Cardiovascular Aging: The Next Frontier in Cardiovascular prevention,” and dr. Jones was senior author of the chapter on “Endothelial Function and Dysfunction.” In addition, dr. elizabeth Ratchford co-authored the chapter on “Exercise for Restoring Health and preventing vascular Disease.”

In addition to Preventive Cardiology—A Companion to Braunwald’s Heart Disease, drs. Blaha, ndumele, Gluckman, Kerunne Ketlogetswe, and I were honored to write a state-of-the-art chapter on comprehensive primary and secondary prevention strategies for coronary heart in the equally noteworthy textbook Hurst’s The Heart, edited by dr. Valentin Fuster.

Genetic epidemiology has been a major emphasis of the research of drs. post and Catherine Campbell. In one of their most important projects, they performed a genome-wide association study to look for genetic variants associated with aortic valve and mitral annular calcium in about 7,000 individuals. One genetic variant in the lipoprotein(a) gene was strongly associated with aortic valve calcium. They replicated this result in other populations and found that this variant was also associated with aortic valve stenosis. They then performed other analyses that supported a causal role for lipoprotein(a) in the development of aortic valve calcification. Two genetic variants in another gene involved in inflammation were associated with mitral annular calcium. Dr. Campbell will be presenting this work at the prestigious Northwestern Cardiovascular Young Investigative Forum and at the upcoming American Heart Association meeting.

Staff at the Ciccarone Center do more than just “show” their knowledge in prestigious publications — they share it through teaching. This year we were proud to serve as mentors to members of the Hopkins Osler Internal Medicine residency in clinical research activities. As part of this collaboration, dr. Jonathan Rubin published an article in Atherosclerosis that found that an elevated resting heart rate was associated with an increased incidence and progression of coronary atherosclerosis. He also served as the lead author of a featured publication in Circulation:

Cardiovascular Imaging that revealed that elevated levels of hsCRp are associated with an increased prevalence of partially calcified coronary artery plaques, which are thought to be the sites of future unstable plaques.

Also, dr. Michael Silverman published a superb review on the effects of adding cholesterol-lowering agents other than statins to affect the progression of atherosclerosis. He is also in the process of submitting two other important papers for publication. dr. C. Michael Minder published in Archives of Internal Medicine an excellent defense of the rationale for the selective use of statin therapy in asymptomatic adults with at least one cardiovascular risk factor. dr. Haitham Ahmed published an excellent review in American Journal of Cardiology on the effects of physical activity on subclinical atherosclerosis, inflammation, and risk of developing blood clots.

Finally, in closing, it is with a heavy heart that I report the passing of Irvin Gomprecht on July 18, 2011. Irv was a friend and magnificent supporter of both Johns Hopkins and the Ciccarone Center, in particular. For the past eight years, he and his wife, Ginger Harteveldt Gomprecht, have been extremely generous in their sponsorship of our research efforts. In particular, they have helped sustain the work of dr. Khurram nasir, one of our amazing postdoctoral fellows who has been in

charge of creating and updating several large multi-site datasets that contained results of cardiac risk factors, measurements of subclinical atherosclerosis, blood biomarkers, and stress-testing results. Dr. Nasir also has been a superb mentor to many of our fellows over the years and he has been the driving force behind a great deal of our research productivity.

We cannot thank Irv and Ginger Gomprecht enough for all that they have done to support the mission of the Ciccarone Center. And, on a personal note,

I am indebted to Irv, who was a very close friend of mine and like an uncle to me. I will greatly miss our fun times together, whether on the golf course or at dinner with Ginger and Wendy, as well as his sage counsel and advice.

Sincerely,

Roger S. Blumenthal, MD, FACC, FAHAprofessor of Medicine/CardiologyDirector, Johns Hopkins Ciccarone Center for the prevention of Heart Disease

Mes

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Irv and Ginger Gomprecht

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this past year has been a momentous one for the Johns Hopkins Ciccarone Center for the prevention of Heart disease, in terms of accomplishing our goals and continuing our work in creating excellent clinical care, educating health care practitioners, and studying better ways to prevent heart disease. Following is a brief overview of some of what we achieved.

Stanley l. Blumenthal, Md, Research Awards Since 2004, the annual Stanley L. Blumenthal, MD, Preventive Cardiology Research Awards have been presented to the Hopkins postdoctoral fellows, graduate students, or residents submitting the best abstracts to the American Heart Association or American College of Cardiology Scientific Sessions.

This year we added several new categories, which allowed us to support more innovative projects and give out more awards. First place in the Oral COmpetitiOn went to michael J. Blaha, mD, who along with andrew DeFilippis, mD, Juan J. rivera, mD, roger S. Blumenthal, mD, Khurram nasir, mD, and others, presented “Association between hsCRP≥2, Coronary Artery Calcium, and Adverse Events — Implications for the JUPITER Population: Multi-Ethnic Study of Atherosclerosis (MESA).” amir pourmorteza, mD, won second place in the Oral Competition for “A New Method for Cardiac Computed Tomography Regional Function Assessment: Stretch Quantifier for Endocardial Engraved Zones (SQUEEZ).” His senior mentors were albert C. lardo, mD, and elliot r. mcVeigh, mD. We ended up with a tie for third place in the Oral COmpetitiOn between angel Chan, mD, who presented “Autologous Tissue Engineering Scaffolds for Cellular Cardiomyoplasty” (along with her mentors Brian O’rourke, mD, Jennifer elisseeff, mD, and m. roselle abraham, mD), and Dong i. lee, mD (along with manling Zhang, mD, and David a. Kass, mD) who presented “A Novel PDE1a Inhibitor, PF-2163, Suppresses Cardiac Hypertrophy through the regulation of TRPC6/Cn/NFAT signaling.”

There were also two first place award winners in the pOSter COmpetitiOn in BaSiC SCienCe: peter andersen, mD, for “Direct Cell Contact with Visceral Endoderm Mediates Induction of Mesoderm via a Fibronectin1/Beta-Integrin/Wnt Pathway,” and Jonathan Kirk, mD, with Weidong Gao, mD, and David Kass, mD, for “Cardiac Resynchronization Therapy Globally Restores the Myofilament’s Response to Calcium.”

The second place winner for the pOSter COmpetitiOn in BaSiC SCienCe was “Altered myocyte PDE5 targeting by pressure overload,” presented by manling Zhang, mD, and David Kass, mD.

Another tie occurred in the pOSter COmpetitiOn FOr CliniCal SCienCe. First place was awarded to Catherine Campbell, mD, who presented “A Genome Wide Association Study Identifies LPA as a Major Locus for Aortic Valve Calcification and IL1F9 as a Possible Locus for Mitral Valve Calcification,” along with Christopher J. O’Donnell, mD, and Wendy S. post, mD, for the CHARGE Extracoronary Calcium Working Group.

The other top presentation in the pOSter COmpetitiOn FOr CliniCal SCienCe was “Apolipoproteins Do Not Add Predictive Value Beyond Cholesterol Measures Among Individuals With Obesity and Insulin Resistance Syndromes: The ARIC Study” by Chiadi e. ndumele, mD, Brad astor, mD, Samia mora, mD, roger S. Blumenthal, mD, a. richey Sharrett, mD, Christie m. Ballantyne, mD, and Josef Coresh, mD. aditya Bhonsale, mD, Dmitri Gagarin, mD, Darshan Dalal, mD, ryan tedford, mD, Stuart D. russell, mD, theodore abraham, mD, Harikrishna tandri, mD, Daniel p. Judge, mD, and Hugh Calkins, mD, took home the second place award in the Poster Competition for Clinical Science for “Incidence and Predictors of ICD therapy in Patients with Arrhythmogenic Right Ventricular Dysplasia Undergoing ICD implantation for Primary Prevention.”

News & Highlights

Dr. Chiadi Ndumele

p.J. Schafer Cardiovascular Research GrantsThe P.J. Schafer Cardiovascular Research Grants fund the efforts of clinical investigators seeking a better

understanding of how to diagnose premature heart disease and prevent sudden cardiac death. Previous recipients of this prestigious award, which is given to a junior faculty member, include rhondalyn mclean, mD, erin

michos, mD, richard George, mD, and Saman nazarian, mD.

The 2011-2012 grant was awarded to Oscar Cingolani, mD, for his research on the characterization of “cardioprotective” proteins and molecular pathways that play a role in cardiac arrest and the transition to heart failure. Specifically, Dr. Cingolani, who is an assistant professor of medicine at The Johns Hopkins University School of Medicine, Division of Cardiology, attends at the Johns Hopkins Hospital Coronary Care Unit. He is studying changes in the amount of thrombospondin-4 in the heart and how this protein affects early mortality. Scientific data already suggest that thrombospondins play a key role in cardiac adaptation to stress situations, such as high blood pressure and myocardial infarction. Dr. Cingolani, who also teaches pathophysiology to medical students, aims to elucidate the mechanism(s) by which thrombospondins seem to act in these situations, as well as to explore whether patients with premature heart attacks might have a genetic defect that lead to an inadequate cardiac expression of these proteins.

Hopkins Cardiology is indebted to paul and Vivian Schafer of the P.J. Schafer Foundation for their hard work and generous contributions in support of cutting-edge research geared to the prevention of sudden cardiac death, which took the life of their son, p.J. Schafer.

To make donations or sign up for the P.J. Schafer golf tournament go to http://www.pjschafer.com/

100-plus publications! The Ciccarone Center continues to publish important original research articles, editorials, and review articles in many of the world’s top cardiology, internal medicine, epidemiology, endocrinology, and genetics journals.

From October 2010 to September 2011, the Center showed some amazing productivity, publishing more than 100 articles of significant basic and clinical research findings, commentaries, and review articles in leading medical journals, including:

• American Journal of Cardiology (10 publications)• American Journal of Epidemiology (3 publications)• Archives of Internal Medicine (3 publications)• Arteriosclerosis, Thrombosis & Vascular Biology

(4 publications) • Atherosclerosis (10 publications)• British Medical Journal (1 publication)• Circulation (3 publications)• Circulation: Cardiovascular Genetics (1 publication)• Circulation: Cardiovascular Imaging

(3 publications)• Circulation: Cardiovascular Quality & Outcomes

(1 publication)• Diabetes Care (2 publications)• Heart (1 publication)• International Journal of Cardiology (1 publication)• Journal of Clinical Endocrinology and Metabolism

(1 publication)• Journal of the American College of Cardiology

(10 publications)• Lancet (1 publication)• PLoS Genetics (1 publication)• PLoS One (2 publications)• Stroke (1 publication)

Dr. Oscar Cingoliani

thank You!The Ciccarone Center is indebted to the following supporters for their extraordinary assistance and backing of our clinical research activities over the past year: nicholas and Suellen paleologos; Ginger and Irv Gomprecht; Irene pollin; Richard and Katharine Amato; Charles and Sandy Zeiler; donald Shepard; thaddeus Shelly; Michael lenkin; John Heyman; dr. ty Gluckman; Mort libov and Ann neumann; paul and Vivian Schafer; and Gary Gill. Much of the Ciccarone Center’s remarkable success over the past year, including our publications track-record, development achievements, and innovations in patient care, could not happen without the very generous patronage of these individuals.

Dr. Rhondalyn McLean

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Since 1990, the mission of the Ciccarone Center for the prevention of Heart disease has been three-fold:• To create excellent clinical care for people at risk

of developing heart disease• To educate health care practitioners about how

to better identify and care for patients at risk of developing heart disease

• To establish rigorous research programs to study better prevention of heart disease

Relentless pursuit of these goals over the past 21 years has led to the creation of one of the fastest growing clinical and research programs at Johns Hopkins, which is highly regarded for its innovative and effective approaches to cardiovascular disease prevention and treatment.

Clinical CareThe trademark of the Ciccarone Center is its comprehensive approach, which involves both global assessment and aggressive management of multiple risk factors (not just single risk factors, such as high blood pressure or high cholesterol) contributing to the development and progression of atherosclerosis. Our clinical center is dedicated to:• The detection and management of individuals

at risk for accelerated atherosclerosis (primary prevention) to prevent or delay the onset of cardiovascular disease, and

• The management of patients with established vascular disease (secondary prevention) to reduce recurrent cardiovascular events and decrease mortality.

educationOur educational efforts are aimed at the medical community and the general public. The Ciccarone Center also serves as a model for teaching the art of prevention of cardiovascular disease to fellows, residents, and students at the Johns Hopkins School of Medicine and the Bloomberg School of Public Health.

Our physicians and nurse practitioner are also lecturers for medical and nursing students and physicians at Hopkins and at national meetings. Hopkins Medicine also organizes meetings to address educational issues for the public.

ResearchAs part of Johns Hopkins, the Ciccarone Center for the Prevention of Heart Disease is committed to conducting cutting-edge research on atherosclerosis and risk factors for heart disease. We conduct research on two levels:• Clinical research studies of cardiovascular

disease involving informed, consenting adults, and

• Basic research and experiments at the cellular and subcellular levels to decipher the molecular reactions leading to atherosclerosis.

A personalized, Comprehensive Approach The Ciccarone Center specializes in managing adults who are at high risk for future cardiovascular disease because of the presence of multiple cardiac risk factors (such as hypertension, dyslipidemia, diabetes, smoking, sedentary lifestyle, or overweight status) or a history of known cardiovascular or peripheral arterial disease.

The Ciccarone Center’s personalized, comprehensive approach to lifestyle and medical management can slow the progression of cardiovascular disease and decrease one’s future risk of a heart attack, stroke, bypass surgery, angioplasty, or stenting. We also sponsor research that includes both clinical trials and basic molecular studies.

Several groups of patients have been of particular interest to the Ciccarone Center:• Women and ethnic minorities• Patients with metabolic disorders, in particular

inherited dyslipidemias, the metabolic syndrome, and diabetes

• Patients with the accelerated atherosclerosis• Persons with a family history of coronary heart

disease or stroke• Persons with recurrent chest pain but no

established cardiovascular disease• Heart and renal transplant patients• Patients with peripheral arterial disease

State-of-the-Art testingWe are especially interested in individuals who develop cardiovascular disease before the age of 65. We have special expertise in the screening and management of asymptomatic family members of persons with premature atherosclerotic disease. Our team may selectively employ state-of-the-art testing

What Is the Ciccarone Center?

to help identify factors contributing to heart disease clustering in families.

For an individual patient, we may use the latest assessment techniques to measure lipoproteins (total cholesterol, high-density lipoprotein-cholesterol [HDL-C], LDL-C, and triglyceride levels) and apolipoproteins (Lp[a], apolipoproteins A-1 and B) as well as nontraditional risk factors, such as high-sensitivity C-reactive protein (hsCRP), and measurements of lipoprotein size and number. However, for many individuals these emerging risk factors are often not needed to optimize their management in a cost-effective manner.

Advanced diagnostic tools Among asymptomatic adults with no history of cardio-vascular disease, we may use a 64-slice or a 320-slice multidetector computed tomography (MDCT) scan of the chest to measure the amount of coronary artery calcification. The presence of elevated coronary artery calcification (e.g. > 75th percentile for one’s age and gender) or thickened carotid arteries is a sign of acceler-ated atherosclerosis for one’s age and may lead to more aggressive attempts at comprehensive risk factor changes through both medical management and lifestyle modi-fication. Occasionally, a cardiac CT angiogram may also be indicated in patients with atypical chest pain and in-conclusive stress test results. After an initial comprehen-sive evaluation, we can inform a patient whether his/her management might be changed by some of the more sophisticated laboratory and diagnostic testing that we can provide.

Improving lifestyle HabitsDominique ashen, phD, Crnp, a nurse practitioner who specializes in helping people improve their lifestyle habits, assists patients with behavior changes such as:• Following healthier diets• Maintaining a prudent body weight• Smoking cessation• Maintaining a regular aerobic program• Coping better with stress

We also refer patients to the Johns Hopkins Clinical exercise Center as well as to the state-of-the-art maryland athletic Club (maC) Healthy Start program to optimize their lifestyle habits. We encourage all individuals with known cardiovascular disease, peripheral arterial disease, diabetes, or congestive heart failure to participate in a supervised exercise program. 4

Wha

t is

the

Cic

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ente

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Our MissionWe have built the Johns Hopkins

Ciccarone Center for the prevention of

Heart disease with the following goals

in mind:

1. provide a center dedicated to

clinical patient care and the

global assessment of risk factors

for cardiovascular disease, which

enables patients to receive:

• the latest information on the

prevention of atherosclerotic

vascular disease,

• comprehensive management of

risk factors for cardiovascular

disease, and

• high-quality care that is

integrated into the other health

promotional resources of Johns

Hopkins.

2. Create a center at Johns Hopkins

for the education of health care

providers in the area of prevention

of cardiovascular disease. teaching

by our physicians and nurse

practitioner broadly targets

Hopkins nurses, medical students,

fellows, and physicians as well as

the community at large.

3. Foster cardiovascular research,

including both clinical trials and

basic molecular studies.

5

A listing of the publications by the staff of the Johns Hopkins Ciccarone Center for the prevention of Heart disease, from October 2010 through September 2011

1. Blaha mJ, Budoff MJ, DeFilippis ap, Blankstein R, rivera JJ, Agatston A, O’Leary DH, Lima J, Blumenthal rS, nasir K. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet. 2011 Aug 20;378(9792):684-92.

Summary: The landmark Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial showed that some patients with LDL-cholesterol (LDL-C) <130 mg/dL and high-sensitivity C-reactive protein (hsCRP) concentrations of >2 mg/L benefit from treatment with rosuvastatin, although the absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values. CAC further stratifies risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with normal LDL-C and at least moderate subclinical atherosclerosis should allow for more appropriate allocation of resources.

2. Malik S, Budoff MJ, Katz R, Blumenthal rS, Bertoni AG, nasir K, Szklo M, Barr RG, Wong ND. Impact of subclinical atherosclerosis on cardiovascular disease events in individuals with metabolic syndrome and diabetes: The multi-ethnic study of atherosclerosis. Diabetes Care. 2011 Aug 15. [Epub ahead of print]

Summary: While metabolic syndrome and diabetes generally confer a greater cardiovascular disease (CVD) risk, recent evidence suggests that these individuals have a wide range of risk. We evaluated whether screening for CAC and carotid intimal medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with metabolic syndrome and diabetes. We concluded that individuals with metabolic syndrome or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events are improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with metabolic syndrome and diabetes and support the latest recommendations regarding CAC screening in those with diabetes.

3. Jensky NE, Hyder JA, Allison MA, Wong N, Aboyans V, Blumenthal rS, Schreiner P, Carr JJ, Wassel CL, Ix JH,

Criqui MH. The association of bone density and calcified atherosclerosis is stronger in women without dyslipidemia: The multi-ethnic study of atherosclerosis. Journal of Bone & Mineral Research. 2011 Aug 10. [Epub ahead of print]

Summary: We tested whether the association between bone mineral density (BMD)

and CAC varies according to dyslipidemia in community-living individuals. The inverse association of BMD with CAC proved stronger in women without dyslipidemia. These data argue against the hypothesis that dyslipidemia is the key factor responsible for the inverse association of BMD with atherosclerosis.

4. tison GH, Blaha mJ, Budoff MJ, Katz R, rivera JJ, Bertoni AG, Wong ND, Blumenthal rS, Szklo M, Eng J, Tracy R, nasir K. The relationship of insulin resistance and extracoronary calcification in the multi-ethnic study of atherosclerosis. Atherosclerosis. 2011 Jul 6. [Epub ahead of print]

Summary: We hypothesized that insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA-IR), is independently associated with prevalent and incident extra-coronary calcification (ECC). We concluded that HOMA has a positive and graded association with ECC, but not independently of cardiovascular risk factors, particularly metabolic syndrome components.

5. rubin J, Blaha mJ, Budoff MJ, rivera JJ, Shaw LJ, Blankstein R, Mallah MA, Carr JJ, Jones DL, Blumenthal rS, nasir K. The relationship between resting heart rate and incidence and progression of coronary artery calcification: The multi-ethnic study of atherosclerosis (MESA). Atherosclerosis. 2011 Jun 25. [Epub ahead of print]

Summary: Elevated resting heart rate has been independently associated with cardiovascular and all-cause mortality. The pathophysiological mechanisms by which this increased risk occurs are unclear. We hypothesized that elevated resting heart rate would be associated with increased development of atherosclerosis, as assessed by the incidence and progression of CAC. We concluded that elevated resting heart rate, a well-described predictor of cardiovascular mortality with unclear mechanism, is associated with increased incidence and progression of coronary atherosclerosis among individuals free of CVD at baseline.

Original Research — publications

Dr. Michael

Blaha and others

researched the

relationship of

insulin resistance

and extracoronary

calcification in the

multi-ethnic study of

atherosclerosis.

6. Blankstein R, Budoff MJ, Shaw LJ, Goff DC Jr, Polak JF, Lima J, Blumenthal rS, nasir K. Predictors of coronary heart disease events among asymptomatic persons with low low-density lipoprotein cholesterol MESA (Multi-Ethnic Study of Atherosclerosis). Journal of the American College of Cardiology. 2011 Jul 19;58(4):364-74.

Summary: Our aim was to identify risk factors for CHD events among asymptomatic persons with low (≤130 mg/dl) LDL-C. Among persons with low LDL-C, older age, male sex, hypertension, diabetes, and low HDL-C are associated with adverse CHD events. Even after accounting for all such variables, the presence of CAC provided incremental prognostic value. These results may serve as a basis for deciding which patients with low LDL-C may be considered for more aggressive therapies. An elevated hsCRP was not predictive of events in this population of individuals with normal LDL-C.

7. mcevoy JW, nasir K, Blumenthal rS. Calcium score reclassification: how should baseline risk be measured? Journal of the American College of Cardiology. 2011; Jun 14;57(24):2456-7.

Summary: A coronary artery score measurement to reclassify persons to either a low or high risk category has implications for preventive therapy strategies for patients in the broad intermediate cardiac risk category that need to be tested in a prospective, randomized manner.

8. mcevoy JW, Blaha mJ, nasir K, Yoon YE, Choi EK, Cho IS, Chun EJ, Choi SI, rivera JJ, Blumenthal rS, Chang HJ. Impact of coronary computed tomographic angiography results on patient and physician behavior in a low-risk population. Archives of Internal Medicine. 2011 Jul 25;171(14):1260-8.

Summary: We studied asymptomatic patients from a large health-screening program. Our study population comprised 1,000 patients who

underwent coronary CT angiography (CCTA) as part of a prior study and a matched control group of 1,000 patients who did not. We assessed medication use, secondary test referrals, revascularizations, and cardiovascular events at 90 days and 18 months. An abnormal screening CCTA result was predictive of increased aspirin and

statin use at 90 days and 18 months, although medication use lessened over time. Screening CCTA was associated with increased invasive testing, without any difference in events at 18 months. Screening CCTA in asymptomatic adults should NOT be considered a justifiable test at this time.

9. ndumele Ce, nasir K, Conceiçao RD, Carvalho JA, Blumenthal rS, Santos RD. Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased systemic inflammation. Arteriosclerosis, Thrombosis and Vascular Biology. 2011 Aug;31(8):1927-32.

Summary: The goal of this study was to assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with elevated hsCRP levels. We evaluated 2,388 individuals without clinical cardiovascular disease between December 2004 and December 2006. Hepatic steatosis was diagnosed by ultrasound, and the metabolic syndrome was defined using National Heart, Lung, and Blood Institute criteria. We concluded that hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased odds of high hsCRP levels.

10. Blaha mJ, rivera JJ, Budoff MJ, Blankstein R, Agatston A, O’Leary DH, Cushman M, Lakoski S, Criqui MH, Szklo M, Blumenthal rS, nasir K. Association between obesity, high-sensitivity C-reactive protein ≥2 mg/L, and subclinical atherosclerosis: implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis. Arteriosclerosis, Thrombosis and Vascular Biology. 2011 Jun;31(6):1430-8.

Summary: Levels of hsCRP are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however, the association of hsCRP and atherosclerosis, independent of obesity, remains unknown. We concluded that high hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with carotid intima-media thickness (cIMT) in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independently of hsCRP status.

11. Blumenthal rS, Hasan rK. “Actually, it is more of a guideline than a rule.” Journal of the American College of Cardiology. 2011 Apr 12;57(15):1601-3.

Summary: This editorial discusses the challenges of designing a randomized controlled trial of coronary calcium scanning to improve risk prediction. It also emphasizes the theme of the iconic movie “Ghostbusters.”

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12. rubin J, Chang HJ, nasir K, Blumenthal rS, Blaha mJ, Choi EK, Chang SA, Yoon YE, Chun EJ, Choi SI, Agatston AS, rivera JJ. Association between high-sensitivity C-reactive protein and coronary plaque subtypes assessed by 64-slice coronary computed tomography angiography in an asymptomatic population. Circulation: Cardiovascular Imaging. 2011 May 1;4(3):201-9.

Summary: We evaluated 1,004 asymptomatic South Korean subjects (mean age, 49±9 years) who underwent coronary computed tomography angiography (CCTA) as part of a health screening evaluation. We examined the association between increasing CRP levels and plaque subtypes using multivariable linear and logistic regression analysis. We concluded that elevated levels of CRP are associated with an increased prevalence of mixed coronary atherosclerotic plaque (MCAP) as assessed by CCTA. Longitudinal studies will determine if the excess risk observed in persons with elevated CRP may be mediated, at least in part, by an increased burden of MCAP.

13. Blaha mJ, Blumenthal rS, Budoff MJ, nasir K. Understanding the utility of zero coronary calcium as a prognostic test: a Bayesian approach. Circulation: Cardiovascular Quality and Outcomes. 2011 Mar 1;4(2):253-6.

Summary: This article discusses the proper interpretation of a zero coronary calcium score, which depends on whether the patient is asymptomatic, has atypical chest discomfort, or clearly angina discomfort.

14. Okwuosa TM, Greenland P, Lakoski SG, Ning H, Kang J, Blumenthal rS, Szklo M, Crouse JR 3rd, Lima JA, Liu K, Lloyd-Jones DM. Factors associated with presence and extent of coronary calcium in those predicted to be at low

risk according to Framingham risk score (from the Multi-Ethnic Study of Atherosclerosis). American Journal of Cardiology. 2011 Mar 15;107(6):879-85.

Summary: Even among asymptomatic persons at low risk (<10% risk of

an MI over the next decade) according to the Framingham risk score, high CAC scores signify a greater predicted risk of CHD events. We determined the noninvasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3,046 individuals at a low 10-year predicted risk (Framingham risk score <10%) of CHD events. In low-risk persons, the traditional risk factors alone predicted advanced CAC with high discrimination and calibration. The

biomarker combinations with and without cIMT were also significantly associated with advanced CAC; however, the improvement in the prediction and estimation of the clinical risk were modest compared to the traditional risk factors alone.

15. Hamirani YS, nasir K, Blumenthal rS, Takasu J, Shavelle D, Kronmal R, Budoff M. Relation of mitral annular calcium and coronary calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]). American Journal of Cardiology. 2011 May 1;107(9):1291-4.

Summary: Atherosclerosis is a complex diffuse disorder. The close correlation between CAC score on computed tomography and extent and severity of coronary atherosclerosis is well established. It has been suggested that mitral annular calcification (MAC) may be a manifestation of generalized atherosclerosis. We observed a strong association between MAC and increasing burden of CAC. This association

weakened but persisted after adjustment for age, gender, and other traditional risk factors. These findings suggest that presence of MAC is an indicator of atherosclerotic burden rather than just a degenerative change of the mitral valve.

16. Deckers JW, Blumenthal rS. Statins for primary prevention of cardiovascular disease. British Medical Journal. 2011 Feb 16;342:d1048-9.

Summary: This insightful editorial discusses the rationale for selective use of statin therapy in asymptomatic adults with multiple risk factors who have never had a prior CVD event.

17. tota-maharaj r, Blaha mJ, rivera JJ, Henry TS, Choi EK, Chang SA, Yoon YE, Chun EJ, Choi SI, Blumenthal rS, Chang HJ, nasir K. Differences in coronary plaque composition with aging measured by coronary computed tomography angiography. International Journal of Cardiology. 2011 Feb 10. [Epub ahead of print]

Summary: Little is known about the independent impact of aging on coronary plaque morphology and composition in the era of CCTA. We studied 1,015 consecutive asymptomatic South Korean subjects (49±10years, 64% men) who underwent 64-slice CCTA during routine health evaluation. Coronary plaque characteristics were analyzed on

a per-segment basis according to the modified AHA classification. In conclusion, CCTA is an effective method for measuring age-related differences in the burden of individual coronary plaque subtypes. Future research is needed to determine

whether the increase in mixed and calcified plaques seen with aging produce an independent contribution to the age-related increase in cardiovascular risk.

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Dr. Rani Hasan

co-authored an

article discussing the

challenges of designing a

randomized controlled

trial of coronary calcium

scanning to improve risk

prediction.

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18. Blaha mJ, DeFilippis ap, rivera JJ, Budoff MJ, Blankstein R, Agatston A, Szklo M, Lakoski SG, Bertoni AG, Kronmal RA, Blumenthal rS, nasir K. The relationship between insulin resistance and incidence and progression of coronary artery calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care. 2011 Mar;34(3):749-51. Epub 2011 Feb 3.

Summary: We sought to determine whether insulin resistance predicts the incidence and progression of CAC. We studied 5,464 MESA participants not on hypoglycemic therapy. Each had baseline HOMA-IR and baseline and follow-up CAC scores. Incident CAC was defined as newly detectable CAC; progression was defined as advancing CAC volume score at follow-up. HOMA-IR predicts CAC incidence and progression, but not independently of metabolic syndrome.

19. muñoz D, Blumenthal rS. Statins for secondary prevention: might less in fact be more? Nature Reviews Endocrinology. 2011 Mar;7(3):131-2. Epub 2011 Feb 1.

Summary: This commentary discusses the dangers of drug interactions between high dose simvastatin and certain medications and suggests that the dose of simvastatin should be lowered to no more than 40 mg and in the presence of certain other medications, either 10 or 20 mg.

20. Ahmadi N, Hajsadeghi F, Blumenthal rS, Budoff MJ, Stone GW, Ebrahimi R. Mortality in individuals without known coronary artery disease but with discordance between the Framingham risk score and coronary artery calcium. American Journal of Cardiology. 2011 Mar 15;107(6):799-804.

Summary: A risk-management approach based on the Framingham risk score (FRS), although useful in preventing future CAD events, is unable to identify a considerable portion of patients with CAD who need aggressive medical

management. CAC, an anatomic marker of atherosclerosis, correlates well with presence and extent of CAD. This study investigated mortality risk associated with CAC score and FRS in subjects classified as “low risk” versus “high risk” based on FRS. In conclusion, the prognostic value of CAC to predict future mortality is far superior to the FRS. Addition of CAC score to FRS significantly improves the identification and prognostication of patients without known CAD.

21. Feuchtner GM, Cury RC, Jodocy D, Friedrich GJ, Blumenthal rS, Budoff MJ, nasir K. Differences in coronary plaque composition by noninvasive computed tomography angiography in individuals with and without obstructive coronary artery disease. Atherosclerosis. 2011 Mar;215(1):90-5.

Summary: CCTA has emerged as a promising non-invasive tool to detect CAD, which provides additional information about atherosclerotic

plaque composition. We assessed whether differences in plaque composition and plaque burden exist across patients with more advanced as well as <50% coronary stenosis. Plaque composition is different according to severity of CAD with a higher mixed plaque and lesser non-calcified plaque burden among those patients with ≥50% stenotic CAD. These findings should

stimulate further investigations to assess the prognostic value of coronary plaque subtypes according to their underlying composition.

22. Budoff MJ, nasir K, Katz R, Takasu J, Carr JJ, Wong ND, Allison M, Lima JA, Detrano R, Blumenthal rS, Kronmal R. Thoracic aortic calcification and coronary heart disease events: the multi-ethnic study of atherosclerosis (MESA). Atherosclerosis. 2011 Mar;215(1):196-202.

Summary: The presence and extent of CAC is an independent predictor of CHD morbidity and mortality. Few studies have evaluated interactions or independent incremental risk for

coronary and thoracic aortic calcification (TAC). The independent predictive value of TAC for CHD events is not well-established. This study used risk factor and computed tomography scan data from 6,807 participants in MESA. Using the same images for each participant, TAC and CAC were each computed using the Agatston method. Our study indicates that TAC is a significant predictor of future coronary events only in women, independent of CAC. On studies obtained for either cardiac or lung applications, determination of TAC may provide modest supplementary prognostic information in women with no extra cost or radiation.

23. Sanchez DR, Diez Roux AV, michos eD, Blumenthal rS, Schreiner PJ, Burke GL, Watson K. Comparison of the racial/ethnic prevalence of regular aspirin use for the primary prevention of coronary heart disease from the multi-ethnic study of atherosclerosis. American Journal of Cardiology. 2011 Jan;107(1):41-6.

Summary: The regular use of aspirin (≥3 days/week) was examined in a cohort of 6,452 White, Black, Hispanic, and Chinese patients without cardiovascular disease in 2000 to 2002 and 5,181 patients from the same cohort in 2005 to 2007. Framingham risk scores were stratified into low (<6% risk of MI over next decade), increased (6% to 9.9%), and high (≥10%) risk. In 2000 to 2002 prevalences of aspirin use were 18% and 27% for those at increased and high risk, respectively. In conclusion, regular aspirin use in adults at increased and high risk for CHD remains suboptimal. Important racial/ethnic disparities exist for unclear reasons.

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Dr. Erin Michos and

colleagues reviewed

the implications of a

JUPITER subanalysis

and the broader role

of statins among older

adults.

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24. Silverman mG, Blaha mJ, Blumenthal rS. Adjunctive lipid lowering therapy in the era of surrogate endpoints. Cardiology Review. 2011 Jan-Feb;19(1):17-22.

Summary: Statins have been shown to reduce cardiovascular events. However, despite widespread use of statin therapy, residual cardiovascular risk remains, and this has left clinicians searching for an effective adjunctive therapy to optimize lipid profiles and reduce risk further. Our article provides clinicians with a practical approach to making decisions regarding adjunctive therapy in the absence of clinical outcomes data. Three ongoing clinical outcomes trials evaluating niacin and ezetimibe in combination with a statin will provide more definitive evidence regarding the safety and efficacy of these agents as adjunctive therapy.

25. Aboyans V, McClelland RL, Allison MA, McDermott MM, Blumenthal rS, Macura K, Criqui MH. Lower extremity peripheral artery disease in the absence of traditional risk factors. The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2011 Jan;214(1):169-73.

Summary: Lower-extremity peripheral artery disease (LE-PAD) is strongly related to traditional risk factors (smoking, hypertension, dyslipidemia, diabetes). We hypothesized that the prevalence of LE-PAD in the absence of traditional CVD risk factors is not negligible, and that this condition would remain associated with subclinical atherosclerosis in other territories. In the absence of traditional CVD risk factors, LE-PAD is still fairly common and associated with coronary artery disease.

26. Long SB, Blaha mJ, Blumenthal rS, michos eD. Clinical utility of rosuvastatin and other statins for cardiovascular risk reduction among the elderly. Clinical Interventions in Aging. 2011;6:27-35.

Summary: Age is one of the strongest predictors of CVD risk. Treatment with statins can significantly reduce CVD events and mortality in both primary and secondary prevention. Yet despite the high CVD risk among the elderly, there is underutilization of statins in this population (ie, the treatment-risk paradox). Few studies have investigated the use of statins in the elderly, particularly for primary prevention and, as a result, guidelines for treating the elderly are limited. JUPITER is the largest primary prevention statin trial and enrolled a substantial number of elderly adults. Among the 5,695 JUPITER participants ≥ 70 years of age, the absolute CVD risk reduction associated with rosuvastatin was actually greater than for younger participants. The implications of this JUPITER subanalysis and the broader role of statins

among older adults is the subject of this review.

27. Yoon YE, Chang HJ, Cho I, Jeon KH, Chun EJ, Choi SI, Bae HJ, rivera JJ, nasir K, Blumenthal rS, Lim TH. Incidence of subclinical coronary atherosclerosis in patients with suspected embolic stroke using cardiac computed tomography. International Journal of Cardiovascular Imaging. 2010 Nov 10. [Epub ahead of print]

Summary: The purpose of this study was to

investigate the incidence of subclinical CAD in patients with suspected acute embolic stroke or transient ischemic attack (TIA) using 64-row multi-slice computed tomography (MSCT) and to examine its association with conventional risk stratification. In logistic regression analysis, only CACS independently predicted the presence ≥50% occult CAD evidenced by CCTA. Subclinical CAD, including ≥50% stenotic disease, is highly prevalent in patients who had

suffered a suspected embolic stroke. The current guideline for further cardiac testing may have limited value to identify patients with ≥50% CAD in this patient

population, which can be improved by adopting CACS.

28. Blaha mJ, Budoff MJ, rivera JJ, Khan AN, Santos RD, Shaw LJ, Raggi P, Berman D, Rumberger JA, Blumenthal rS, nasir K. Relation of aortic valve calcium detected by cardiac computed tomography to all-

cause mortality. American Journal of Cardiology. 2010 Dec 15;106(12):1787-91.

Summary: Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as CAC. Although CAC is an established predictor of cardiovascular events, limited evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 ± 10 years, 69% men), who were free of known coronary heart disease and were undergoing computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC.

29. mcevoy JW, Blaha mJ, Defilippis ap, Budoff MJ, nasir K, Blumenthal rS, Jones Sr. Coronary artery calcium progression: an important clinical measurement? A review of published reports. Journal of the American College of Cardiology. 2010 Nov 9;56(20):1613-22.

Summary: Baseline CAC accurately identifies coronary atherosclerosis and improves prediction of future cardiac events. However, whether knowledge of progression of CAC scores over time further improves risk prediction is unclear. We conducted a comprehensive review of published reports on CAC

Dr. J.W. McEvoy and others

discuss whether coronary

artery calcium progression

is an important clinical

measurement.

10

progression and found that CAC progression correlates with worsening atherosclerosis and may facilitate prediction of future cardiac events. These findings support the notion that slowing CAC progression with therapeutic interventions might provide prognostic benefit. However, despite promising early data, such interventions (most notably with statin therapy) have not been shown to slow the progression of CAC in any randomized controlled trial to date, outside of post hoc subgroup analyses. Thus, routine quantification of CAC progression cannot currently be recommended in clinical practice.

30. Wong ND, Lopez VA, Allison M, Detrano RC, Blumenthal rS, Folsom AR, Ouyang P, Criqui MH. Abdominal aortic calcium and multi-site atherosclerosis: the Multiethnic Study of Atherosclerosis. Atherosclerosis. 2011 Feb;214(2):436-41.

Summary: Abdominal aortic calcification (AAC) is a measure of subclinical CVD. Data are limited regarding its relation to other measures of atherosclerosis. Among 1,812 subjects within the population-based MESA, we examined the cross-sectional relation of AAC with CAC, ankle brachial index (ABI), and CIMT, as well as multiple measures of subclinical CVD. Our study found that AAC is associated with an increased likelihood of other vascular atherosclerosis and its additive prognostic value to these other measures is of further interest.

31. Harrington C, Horne a Jr, Hasan rK, Blumenthal rS. Statin therapy in primary prevention: new insights regarding women and the elderly. American Journal of Cardiology. 2010 Nov 1;106(9):1357-9.

Summary: This commentary examines recent clinical trials that had large numbers of women and elderly men and discusses the implications of these results for inclusion into the upcoming new National Cholesterol Education Program guidelines.

32. Criqui MH, McClelland RL, McDermott MM, Allison MA, Blumenthal rS, Aboyans V, Ix JH, Burke GL, Liu K, Shea S. The ankle-brachial index and incident cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis). Journal of the American College of Cardiology. 2010 Oct 26;56(18):1506-12.

Summary: Abnormal ABIs, both low and high, are associated with elevated CVD risk. However, it is unknown whether this association is consistent across different ethnic groups, and whether it is independent of both newer biomarkers and other measures of subclinical atherosclerotic CVD. In this study, both a low and a high ABI were associated with elevated CVD risk in persons free of known CVD, independent of standard and novel risk factors, and independent of other measures of subclinical CVD. Further research should address the cost-effectiveness of measuring the ABI

in targeted population groups. 33. Lakoski SG, Cushman M, Siscovick DS, Blumenthal rS, Palmas W, Burke G, Herrington DM. The relationship between inflammation, obesity and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA). Journal of Human Hypertension. 2011 Feb;25(2):73-9.

Summary: It has been suggested that inflammation is important in the etiology

of hypertension and that this may be most relevant among obese persons.

To study this, we examined the independent relationships between obesity, inflammation-related proteins (interleukin-6 (IL-6), CRP and fibrinogen) and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis. The relationship between inflammation-related proteins and hypertension risk was predominantly explained by other hypertension risk factors. Obesity, independent of inflammation, remained a potent risk factor for future hypertension.

34. Kanjanauthai S, nasir K, Katz R, rivera JJ, Takasu J, Blumenthal rS, Eng J, Budoff MJ. Relationships of mitral annular calcification to cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2010 Dec;213(2):558-62.

Summary: The relationship between MAC, a fibrous, degenerative calcification of the mitral valve, and CVD risk factors is not well defined. Thus, we performed a cross-sectional study to determine which CVD risk factors are independently associated with MAC. We concluded that age, female gender, diabetes, and increased BMI were significantly associated with MAC. Prevalence of MAC was strongly associated with female gender and increasing age in all ethnicities.

35. Giles JT, Allison M, Blumenthal rS, post W, Gelber AC, Petri M, Tracy R, Szklo M, Bathon JM. Abdominal obesity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics. Arthritis & Rheumatism. 2010 Nov;62(11):3173-82.

Summary: Abdominal adiposity, especially visceral adiposity, is emerging as a recognized cardiometabolic risk factor. This study was undertaken to investigate how abdominal fat is distributed in rheumatoid arthritis (RA), and its RA-related determinants. We compared men and women with RA with non-RA controls from MESA.

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Dr. Aaron Horne’s

commentary examines

recent clinical trials that

had large numbers of

women and elderly

men and discusses the

implications of these

results.

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The distribution of abdominal fat differs significantly by RA status. Higher VFA in men with RA, and the more potent association of VFA with cardiometabolic risk factors in men and women with RA, may contribute to cardiovascular risk in RA populations.

36. nasir K, rivera JJ, Yoon YE, Chang SA, Choi SI, Chun EJ, Budoff MJ, Blumenthal rS, Chang HJ. Variation in atherosclerotic plaque composition according to increasing coronary artery calcium scores on computed tomography angiography. International Journal of Cardiovascular Imaging. 2010 Dec;26(8):923-32.

Summary: This study examines the prognostic importance of noncalcified, partially calcified (mixed), and predominantly calcified plaques on CCTA and the effect of the absolute coronary calcium scores on the composition of the various plaques.

37. rubin J, nasir K, Agatston AS, Blumenthal rS, rivera JJ. Coronary arterial calcium and outcomes. Current Cardiovascular Imaging Reports. 2010;3:342-9.

Summary: This is an excellent review of the strengths and limitations of coronary artery calcium measurements to improve CVD risk prediction.

38. mcevoy JW, Blaha mJ, Blumenthal rS, Jones Sr, nasir K. Potential use of coronary artery calcium progression to guide therapy and management of patients at risk for coronary artery disease. Current Treatment Options in Cardiovascular Medicine. Forthcoming 2011.

Summary: This review examines the strengths and limitations of the existing data purporting to show an incremental prognostic benefit of looking at progression of CAC.

39. DeFilippis ap, Blaha mJ, ndumele C, Budoff MJ, Lloyd-Jones D, McClelland RL, Lakoski SG, Cushman M, Wong ND, Blumenthal rS, Lima J, nasir K. The association of the Framingham and Reynolds risk scores with incidence and progression of coronary artery calcium in MESA. Journal of the American College of Cardiology. Forthcoming 2011.

Summary: This innova-tive study found that the Reynolds Risk Score was modestly better than the traditional Framingham risk score in predicting the incidence of new coronary calcification and the progression of exist-ing calcification. This observation also applied to clinical events.

40. ahmed Hm, Blaha mJ, nasir K, rivera JJ, Blumenthal rS. Effects of physical activity on cardiovascular

disease. American Journal of Cardiology. Forthcoming 2011.

Summary: This paper provides a comprehensive look at the benefits of increased physical activity on lipid changes, thrombotic, inflammatory factors, and measures of subclinical atherosclerosis.

41. minder Cm, Blaha mJ, tam lm, munoz D, michos eD, Kaul S, Blumenthal rS. Making the case for selective use of statins in the primary prevention setting. Archives of Internal Medicine. Forthcoming 2011.

Summary: In this paper, we refute the incorrect

view expressed by several members of the Archives editorial board in their “Less is More” column that lipid lowering is rarely indicated in the primary prevention setting.

42. Blaha mJ, Gluckman tJ, Blumenthal rS. Preventive cardiology: past, present, and future. In: Blumenthal RS, Foody JM, Wong ND eds. Preventive Cardiology: A Companion to Braunwald’s Heart Disease. Philadelphia, PA: W.B. Saunders; 2011; Chapter 1:1-13.

Summary: The majority of improvement in rates of mortality from CVD since 1960 has

been the result of prevention strategies and not treatment of acute CVD. Prevention occurs at three levels: primordial, primary, and secondary. National guidelines direct population-based and individual-based preventive care. This chapter offers an easy to remember memory tool that facilitates comprehensive preventive care: The Ciccarone Center ABCDE approach.

43. Blaha mJ, Blumenthal rS. Contemporary interpretation of lipid guidelines in modern medicine. In: Januzzi JL Jr, ed. Cardiac Biomarkers in Clinical Practice. Sudbury, MA: Jones & Bartlett; 2011; Chapter 29: 679-716.

Summary: This chapter provides an in-depth look at the evidence base for our current national and international guidelines on cholesterol management through lifestyle and pharmacologic therapy.

44. Blaha mJ, Ketlogetswe KS, ndumele Ce, Gluckman tJ, Blumenthal rS. Prevention strategies for coronary heart disease. In: Fuster V, ed. Hurst’s The Heart. New York, NY: McGraw-Hill; 2010; Chapter 51:1183-1215.

Summary: This state-of-the-art examination of comprehensive primary and secondary prevention strategies is a superb discussion of the impact of clinical trials and epidemiologic studies on our current national guidelines.

Dr. Michael Minder disputes

the view that lipid lowering is

rarely indicated in the primary

prevention setting.

Dr. Haithan Ahmed’s

paper provides a

comprehensive look at

the benefits of increased

physical activity on lipid

changes, thrombotic,

inflammatory factors, and

measures of subclinical

atherosclerosis.

12

45. nasir K, Blumenthal rS, Wong ND, Budoff MJ. Role of vascular computed tomography in evaluation and prevention of cardiovascular disease. In: Blumenthal RS, Foody JM, Wong ND eds. Preventive Cardiology: A Companion to Braunwald’s Heart Disease. Philadelphia, PA: W.B. Saunders; 2011; Chapter 27:443-460.

Summary: Traditional global risk assessment approaches for CHD tend to underestimate long-term CVD risk in middle-aged men and in postmenopausal women with multiple risk factors. Non-contrast enhanced CT detection of CAC improves the ability to predict CVD risk. This chapter provides a superb review of the strengths and limitations of cardiac CT and CTA to measure coronary calcification and to provide information about the location, severity, and characteristics of atherosclerotic plaque.

46. Blaha mJ, Panjrath G, Chacko M, Schulman SP. Localized calcific constrictive pericarditis masquerading as a basal aneurysm. Journal of the American College of Cardiology. 2011 May 3;57(18):e65.

47. Lee YL, Blaha mJ, Jones Sr. Statin therapy in the prevention and treatment of atrial fibrillation. Journal of Clinical Lipidology. 2011 Jan-Feb;5(1):18-29.

Summary: Atrial fibrillation (AF) is the most common adult rhythm disorder, and it is associated with a substantial rate of morbidity and economic burden. There is an increasing body of literature in which the authors investigated the pleiotropic effects of statin therapy in relation to AF. Its utility in patients with paroxysmal AF may be limited to the prevention of incident AF, but it does not appear to inhibit the progression of paroxysmal AF to chronic AF. Further large scale, randomized, placebo-controlled studies are needed in perioperative use in noncardiac surgery and in patients undergoing ablation or cardioversion of AF.

48. tison GH, Blaha mJ, nasir K. Atherosclerosis imaging in multiple vascular beds—enough heterogeneity to improve risk prediction? Atherosclerosis. 2011 Feb;214(2):261-3.

Summary: This editorial review looks at the incremental predictive value of finding above average amounts of subclinical atherosclerosis in vascular territories other than the coronary circulation and its potential effect on cardiovascular risk prediction.

49. Chantler PD, Nussbacher A, Gerstenblith G, Schulman SP, Becker LC, Ferrucci L, Fleg JL, Lakatta EG, Najjar SS. Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside. American Journal of Physiology: Heart and Circulatory Physiology. 2011 May;300(5):H1914-22.

Summary: The coupling between arterial elastance (E(A); net afterload) and left ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by single-nucleotide polymorphisms (SNPs) infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.

50. tison GH, ndumele Ce, Gerstenblith G, Allison MA, Polak JF, Szklo M. Usefulness of baseline obesity to predict development of a high ankle brachial index (from the Multi-Ethnic Study of Atherosclerosis). American Journal of Cardiology. 2011 May 1;107(9):1386-91.

Summary: An abnormally high ABI is associated with increased all-cause and cardiovascular mortality. The relation of obesity to incident high ABI has not been characterized. The aim of this study was to investigate the hypothesis that increased obesity — quantified by body weight, body mass index, waist circumference, and waist-to-hip-ratio — is positively associated with a high ABI

(≥1.3) and with mean ABI increases over a 4-year follow-up. Independent, positive, and graded associations of increasing obesity with prevalent and incident high ABI and with mean increases in ABI values over time were found. Weight and body mass index seemed to be at least as strongly, if not more strongly, associated with a high ABI than were measures of abdominal obesity.

51. Hays AG, Hirsch GA, Kelle S, Gerstenblith

G, Weiss RG, Stuber M. Noninvasive visualization of coronary artery endothelial function in healthy subjects and in patients with coronary artery disease. Journal of the American College of Cardiology. 2010 Nov 9;56(20):1657-65.

Summary: The goal was to test 2 hypotheses: first, that coronary endothelial function can be measured non-invasively and abnormal function detected using clinical 3.0-T magnetic resonance imaging (MRI); and second, that the extent of local CAD, in a given patient, is related to the degree of local abnormal coronary endothelial function. We concluded that endothelial-dependent coronary artery dilation and increased blood flow in healthy subjects, and their absence in CAD patients, can now be directly visualized and quantified non-invasively. Local coronary endothelial function differs between severely and mildly diseased arteries in a given CAD patient. This novel, safe method may offer new insights regarding the importance of local coronary endothelial function and improved risk stratification in patients at risk for and with known CAD.

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Dr. Gary Gerstenblith

explored the connection

between exercise and

arterial-ventricular coupling

abnormalities in older healthy

persons.

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52. Kiani AN, post WS, Magder LS, Petri M. Predictors of progression in atherosclerosis over 2 years in systemic lupus erythematosus. Rheumatology (Oxford). 2011 Aug 28. [Epub ahead of print]

Summary: Cardiovascular disease remains the major cause of death in systemic lupus erythematosus (SLE). We assessed the degree to which cardiovascular risk factors and disease activity were associated with 2-year changes in measures of subclinical atherosclerosis. Our data did not provide evidence of an association between measures of SLE disease activity (SLEDAI, anti-dsDNA, anti-phospholipid and treatment) and progression of subclinical atherosclerosis. Age and hypertension were associated with the progression of carotid IMT and plaque. Age, smoking and cholesterol were associated with progression of CAC.

53. Shimbo D, Muntner P, Mann D, Barr RG, Tang W, post W, Lima J, Burke G, Bluemke D, Shea S. Association of left ventricular hypertrophy with incident hypertension: the multi-ethnic study of atherosclerosis. American Journal of Epidemiology. 2011 Apr 15;173(8):898-905.

Summary: Increased LV mass and changes in LV geometry may precede hypertension onset. The authors examined the associations of LV mass and geometry, assessed by cardiac magnetic resonance imaging, with hypertension incidence in 2,567 normotensive participants enrolled in 2000-2002 in MESA. Higher levels of LV concentric geometry, defined by higher LV mass to end-diastolic volume quartiles, were associated with higher risk of incident hypertension in a fully adjusted model. In a final model containing both quartiles of LV mass and LV mass/volume, along with all covariates including baseline blood pressure, higher

LV mass quartiles were associated with incident hypertension, whereas higher LV mass/volume quartiles were not.

In this multiethnic cohort, alterations in LV mass preceded hypertension onset among normotensive individuals.

54. Zhang Y, post WS, Dalal D, Bansal S, Blasco-Colmenares E, Jan De Beur S, Alonso A, Soliman EZ, Whitsel EA, Brugada R, Tomaselli GF, Guallar E.

Serum 25-hydroxyvitamin D, calcium, phosphorus, and electrocardiographic QT interval duration: findings from NHANES III and ARIC. Journal of Clinical Endocrinology and Metabolism. 2011 Jun;96(6):1873-82.

Summary: Disturbances in 25-hydroxyvitamin D, calcium, and phosphorus concentrations have been associated with increased risks of total and cardiovascular mortality. It is possible that changes in electrocardiographic QT interval duration may mediate these effects, but the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration has not been evaluated in general population samples. The objective of the study was to evaluate the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration in two large samples of the U.S. population. QT interval duration was inversely associated with the serum total and ionized calcium and

positively associated with serum phosphorus.

55. Huang CC, Liu K, Pope RM, Du P, Lin S, Rajamannan NM, Huang QQ, Jafari N, Burke GL, post W, Watson KE, Johnson C, Daviglus ML, Lloyd-Jones DM. Activated TLR signaling in atherosclerosis among women with lower Framingham

risk score: the multi-ethnic study of atherosclerosis. Public Library of Science One. 2011;6(6):e21067.

Summary: Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis, the leading cause of CVD. However, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis. Gene expression profiles of peripheral blood may be a useful tool to identify individuals with significant burden of atherosclerosis, even among those with low predicted risk by clinical factors. Furthermore, our data suggest an intimate connection between atherosclerosis and the innate immune system and inflammation via TLR signaling in lower risk individuals.

56. Arking DE, Junttila MJ, Goyette P, Huertas-Vazquez A, Eijgelsheim M, Blom MT, Newton-Cheh C, Reinier K, Teodorescu C, Uy-Evanado A, Carter-Monroe N, Kaikkonen KS, Kortelainen ML, Boucher G, Lagacé C, Moes A, Zhao X, Kolodgie F, Rivadeneira F, Hofman A, Witteman JC, Uitterlinden AG, Marsman RF, Pazoki R, Bardai A, Koster RW, Dehghan A, Hwang SJ, Bhatnagar P, post W, Hilton G, Prineas RJ, Li M, Köttgen A, Ehret G, Boerwinkle E, Coresh J, Kao WH, Psaty BM, Tomaselli GF, Sotoodehnia N, Siscovick DS, Burke GL, Marbán E, Spooner PM, Cupples LA, Jui J, Gunson K, Kesäniemi YA, Wilde AA, Tardif JC, O’Donnell CJ, Bezzina CR, Virmani R, Stricker BH, Tan HL, Albert CM, Chakravarti A, Rioux JD, Huikuri HV, Chugh SS. Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. Public Library of Science Genetics. 2011 Jun;7(6):e1002158.

Summary: Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping. Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD.

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57. Soliman EZ, Prineas RJ, Case LD, Russell G, Rosamond W, Rea T, Sotoodehnia N, post WS, Siscovick D, Psaty BM, Burke GL. Electrocardiographic and clinical predictors separating atherosclerotic sudden cardiac death from incident coronary heart disease. Heart. 2011 Jul 20. [Epub ahead of print]

Summary: To identify specific ECG and clinical predictors that separate atherosclerotic SCD from incident CHD (non-fatal events and non-sudden death) in the combined cohorts of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study. This analysis included 18,497 participants (58% females, 24% black individuals, mean age 58 years) who were initially free of clinical CHD. SCD and CHD have many risk factors in common. Hypertension, race/ethnicity, BMI, heart rate, QTc, abnormally inverted T wave in any ECG lead group and level of ST elevation in V2 have the potential to separate between the risks of SCD and CHD. These results need to be validated in another cohort.

58. Zhang Y, Ouyang P, post WS, Dalal D, Vaidya D, Blasco-Colmenares E, Soliman EZ, Tomaselli GF, Guallar E. Sex-steroid hormones and electrocardiographic QT-interval duration: Findings from the Third National Health and Nutrition Examination Survey and the Multi-Ethnic Study of Atherosclerosis. American Journal of Epidemiology. 2011 Aug 15;174(4):403-11.

Summary: The association between physiologic levels of sex hormones and QT-interval duration in humans was

evaluated using data from 727 men enrolled in the Third National Health and Nutrition Examination Survey and 2,942 men and 1,885 postmenopausal women enrolled in MESA. Testosterone, estradiol, and sex hormone-binding globulin levels were measured in serum and free testosterone was calculated from those values. The findings suggest that testosterone levels may explain differences in QT-interval duration between men and women and could be a contributor to population variability in QT-interval duration among men.

59. Yeboah J, Bertoni AG, Herrington DM, post WS, Burke GL. Impaired fasting glucose and the risk of incident diabetes mellitus and cardiovascular events in an adult population: MESA (Multi-Ethnic Study of Atherosclerosis). Journal of the American College of Cardiology. 2011 Jul 5;58(2):140-6.

Summary: The purpose of the study was to assess the cardiovascular risk of impaired fasting glucose (IFG). The associations between IFG, incident type 2 diabetes mellitus (T2DM), and CV events remains unclear. The MESA study included participants who were 45 to 84 years or age and free of clinical CV disease at baseline. Having IFG was not independently associated with an increased short-term risk for incident CV events. These data reiterate the importance of intervention for persons with IFG to reduce their incidence of T2DM.

60. Zhang Y, post WS, Blasco-Colmenares E, Dalal D, Tomaselli GF, Guallar E. Electrocardiographic QT interval and mortality: A meta-analysis. Epidemiology. 2011 Sep;22(5):660-70.

Summary: Extremely abnormal prolongation of the electrocardiographic QT interval is associated with malignant ventricular arrhythmias and sudden cardiac death. However, the implications of variations in QT-interval length within normal limits for mortality in the general population have been unclear. We found consistent associations between prolonged QT interval and increased risk of total, cardiovascular, coronary, and sudden cardiac death. QT-interval length is a determinant of mortality in the general population.

61. Kim C, Diez-Roux AV, Nettleton JA, Polak JF, post WS, Siscovick DS, Watson KE, Vahratian AM. Sex differences in subclinical atherosclerosis by race/ethnicity in the multi-ethnic study of atherosclerosis. American Journal of Epidemiology. 2011 Jul 15;174(2):165-72.

Summary: Sex differences in CVD mortality are more pronounced among non-Hispanic whites than other racial/ethnic groups, but it is unknown whether this variation is present in the earlier subclinical stages of disease. The authors examined racial/ethnic variation in sex differences in CAC and cIMT at baseline in 2000-2002 among participants (n = 6,726) in MESA using binomial and linear regression. Models adjusted for risk factors in several stages: age, traditional cardiovascular

disease risk factors, behavioral risk factors, psychosocial factors, and adult socioeconomic position. In conclusion, coronary artery calcification is differentially patterned by sex across racial/ethnic groups.

Dr. Wendy Post

collaborated on a study

whose purpose was to

assess impaired fasting

glucose and the risk of

incident diabetes mellitus

and cardiovascular events

in an adult population.

15

62. Kawut SM, Bagiella E, Lederer DJ, Shimbo D, Horn EM, Roberts KE, Hill NS, Barr RG, Rosenzweig EB, post W, Tracy RP, Palevsky HI, Hassoun PM, Girgis RE; ASA-STAT Study Group. Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA-STAT. Circulation. 2011 Jun 28;123(25):2985-93.

Summary: Pulmonary arterial hypertension (PAH) is a progressive disease that causes exercise limitation, heart failure, and death. We performed a randomized, double-blind, placebo-controlled 2×2 factorial clinical trial to determine the safety and efficacy of aspirin and simvastatin in patients with PAH. Neither aspirin nor simvastatin had a significant effect on the 6-minute walk distance, although patients randomized to simvastatin tended to have a lower 6-minute walk distance at 6 months. These results do not support the routine treatment of patients with PAH with these medications.

63. Zhang Y, post WS, Dalal D, Blasco-Colmenares E, Tomaselli GF, Guallar E. Coffee, alcohol, smoking, physical activity and QT interval duration: results from the Third National Health and Nutrition Examination Survey. Public Library of Science One. 2011 Feb 28;6(2):e17584.

Summary: Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration. We studied 7,795 men and women from NHANES III. Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors, including coffee and tea intake, smoking, and physical activity.

64. Lettre G, Palmer CD, Young T, Ejebe KG, Allayee H, Benjamin EJ, Bennett F, Bowden DW, Chakravarti A, Dreisbach A, Farlow DN, Folsom AR, Fornage M, Forrester T, Fox E, Haiman CA, Hartiala J, Harris TB,

Hazen SL, Heckbert SR, Henderson BE, Hirschhorn JN, Keating BJ, Kritchevsky SB, Larkin E, Li M, Rudock ME, McKenzie CA, Meigs JB, Meng YA, Mosley TH, Newman AB, Newton-Cheh CH, Paltoo DN, Papanicolaou GJ, Patterson N, post WS, Psaty BM,

Qasim AN, Qu L, Rader DJ, Redline S, Reilly MP, Reiner AP, Rich SS, Rotter JI, Liu Y, Shrader P, Siscovick DS, Tang WH, Taylor HA, Tracy RP, Vasan RS, Waters KM, Wilks R, Wilson JG, Fabsitz RR, Gabriel SB, Kathiresan S, Boerwinkle E. Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. Public Library of Science Genetics. 2011 Feb 10;7(2):e1001300.

Summary: CHD is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study in 8,090 African Americans from five population-based cohorts. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.

65. Petri MA, Kiani AN, post W, Christopher-Stine L, Magder LS. Lupus Atherosclerosis Prevention Study (LAPS). Annals of the Rheumatic Diseases. 2011 May;70(5):760-5.

Summary: CVD is one of the major causes of death in SLE. A study (200 patients with SLE without clinical CVD randomized to receive atorvastatin 40 mg daily or an identical placebo) was undertaken to investigate whether treatment with statins would reduce subclinical measures of atherosclerosis over a 2-year period. However, this study provided no evidence that atorvastatin reduces subclinical measures of atherosclerosis or disease activity over 2 years in patients with SLE. In fact, it does not reduce biochemical measures of inflammation. The anti-inflammatory effects of statins observed in the general population were not replicated in this SLE clinical trial.

66. Jain A, McClelland RL, Polak JF, Shea S, Burke GL, Bild DE, Watson KE, Budoff MJ, Liu K, post WS, Folsom AR, Lima JA, Bluemke DA. Cardiovascular imaging for assessing cardiovascular risk in asymptomatic men versus women: the multi-ethnic study of atherosclerosis (MESA). Circulation: Cardiovascular Imaging. 2011 Jan;4(1):8-15.

Summary: CAC, carotid IMT, and LV mass and geometry offer the potential to characterize incident CVD risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD. The study sample consisted of 4,965 MESA participants (48% men; mean age, 62±10 years). There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.

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67. Shen H, Damcott CM, Rampersaud E, Pollin TI, Horenstein RB, McArdle PF, Peyser PA, Bielak LF, post WS, Chang YP, Ryan KA, Miller M, Rumberger JA, Sheedy PF 2nd, Shelton J, O’Connell JR, Shuldiner AR, Mitchell BD. Familial defective apolipoprotein B-100 and increased low-density lipoprotein cholesterol and coronary artery calcification in the old order amish. Archives of Internal Medicine. 2010 Nov 8;170(20):1850-5.

Summary: Elevated LDL-C levels are a major CVD risk factor. Genetic factors are an important determinant of LDL-C levels. To identify single nucleotide polymorphisms associated with LDL-C and subclinical coronary atherosclerosis, we performed a genome-wide association study of LDL-C in 841 asymptomatic Amish individuals aged 20 to 80 years, with replication in a second sample of 663 Amish individuals. We also performed scanning for CAC in 1,018 of these individuals. We concluded that the presence of R3500Q, the mutation responsible for familial defective apolipoprotein B-100, is a major determinant of LDL-C levels and CAC in the Amish.

68. Wassel CL, Pankow JS, Rasmussen-Torvik LJ, Li N, Taylor KD, Guo X, Goodarzi MO, Palmas WR, post WS. Associations of SNPs in ADIPOQ and subclinical cardiovascular disease in the multi-ethnic study of atherosclerosis (MESA). Obesity (Silver Spring). 2011 Apr;19(4):840-7.

Summary: Circulating adiponectin is associated with both clinical and subclinical CVD. Variants of the adiponectin gene (ADIPOQ) are associated with clinical CVD, but little is known about associations with subclinical CVD. We studied the association of 11 ADIPOQ SNPs with common and internal cIMT, presence of CAC, and CAC scores (in those with CAC) in 2,847 participants in MESA. There appears to be an

association between ADIPOQ SNPs and subclinical CVD in African Americans and Hispanics. Replication as well as assessment of other ADIPOQ SNPs is warranted.

69. musunuru K, post WS, Herzog W, Shen H, O’Connell JR, McArdle PF, Ryan KA, Gibson Q, Cheng YC, Clearfield E, Johnson AD, Tofler G,

Yang Q, O’Donnell CJ, Becker DM, Yanek LR, Becker LC, Faraday N, Bielak LF, Peyser PA, Shuldiner AR, Mitchell BD. Association of single nucleotide polymorphisms on chromosome 9p21.3 with platelet reactivity: a potential mechanism for increased vascular disease. Circulation: Cardiovascular Genetics. 2010 Oct;3(5):445-53.

Summary: Genome-wide association studies have identified a locus on chromosome 9p21.3 to be strongly associated with myocardial infarction/coronary artery disease and ischemic stroke. To gain insights into the mechanisms underlying these associations, we hypothesized that SNPs in this region would be associated with platelet reactivity across multiple populations. Subjects in the initial population included 1,402 asymptomatic Amish adults in whom we measured platelet reactivity and CAC. Our results suggest that risk alleles at 9p21.3 locus may have pleiotropic effects on myocardial infarction/coronary artery disease and stroke risk, possibly through their influence on platelet reactivity.

70. Shen H, Bielak LF, Ferguson JF, Streeten EA, Yerges-Armstrong LM, Liu J, post W, O’Connell JR, Hixson JE, Kardia SL, Sun YV, Jhun MA, Wang X, Mehta NN, Li M, Koller DL, Hakonarson H, Keating BJ, Rader DJ, Shuldiner AR, Peyser PA, Reilly MP, Mitchell BD. Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification. Arteriosclerosis, Thrombosis and Vascular Biology. 2010 Dec;30(12):2648-54.

Summary: The vitamin D endocrine system is essential for calcium homeostasis, and low levels of vitamin D metabolites have been associated with CVD risk. We hypothesized that DNA sequence variation in genes regulating vitamin D metabolism and signaling pathways might influence variation in CAC. A common SNP in the CYP24A1 gene was associated with CAC quantity in 3 independent populations. This result suggests a role for vitamin D metabolism in the development of CAC quantity.

71. Criqui MH, Kamineni A, Allison MA, Ix JH, Carr JJ, Cushman M, Detrano R, post W, Wong ND. Risk factor differences for aortic versus coronary calcified atherosclerosis: the multi-ethnic study of atherosclerosis. Arteriosclerosis, Thrombosis and Vascular Biology. 2010 Nov;30(11):2289-96.

Summary: The goal of this study was to compare and contrast CAC with abdominal aortic calcium (AAC) in terms of their associations with traditional and novel CVD risk factors. AAC showed stronger correlations with most CVD risk factors than did CAC. The predictive value of AAC compared with CAC for incident CVD events remains to be evaluated.

72. Golden SH. Emerging therapeutic approaches for the management of diabetes mellitus and macrovascular complications. American Journal of Cardiology. 2011 Aug 2;108(3 Suppl):59B-67B.

Summary: Type 2 DM affects an estimated 26 million people in the U.S. and is the 7th leading cause of death. While effective therapy can prevent or delay the complications that are associated with diabetes, according to the Center for Disease Control, 35% of Americans with DM are undiagnosed, and another 79 million Americans have blood glucose levels that greatly increase their risk of developing DM in the next several years. This article reviews established and emerging therapeutic approaches for managing DM and prevention of macrovascular complications.

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73. Golden SH, Wand GS, Malhotra S, Kamel I, Horton K. Reliability of hypothalamic-pituitary-adrenal axis assessment methods for use in population-based studies. European Journal of Epidemiology. 2011 Jul;26(7):511-25.

Summary: Population-based studies have been hampered in exploring hypothalamic-pituitary-adrenal axis (HPA) activity as a potential explanatory link between stress-related and metabolic disorders due to their lack of incorporation of reliable measures of chronic cortisol exposure. The purpose of this review is to summarize current literature on the reliability of HPA axis measures and to discuss the feasibility of performing them in population-based studies.

74. Champaneri S, Wand GS, Malhotra SS, Casagrande SS, Golden SH. Biological basis of depression in adults with diabetes. Current Diabetes Reports. 2010 Dec;10(6):396-405.

Summary: Diabetes and depression are common comorbid conditions. Although certain health behaviors and risk factors partially explain the association of depression and diabetes, other potential mechanisms have yet to be elucidated. The objectives of this review were to summarize and review the recent evidence showing alterations of these three biological systems—HPA axis, SNS, and inflammatory cascade—in depression, diabetes, and diabetes-related risk factors.

75. Brewer LC, michos eD, Reis JP. Vitamin D in atherosclerosis, vascular disease, and endothelial function. Current Drug Targets. 2011 Jan;12(1):54-60.

Summary: Vitamin D deficiency has been linked to an increased risk of hypertension, diabetes, congestive heart failure, peripheral arterial disease, MI, CVA, and related mortality, even after adjustment for traditional cardiovascular risk factors. Accumulating evidence from experimental, clinical, and epidemiological studies suggests that vitamin D may also be associated with several indices of vascular function, including the development

and progression of atherosclerotic cardiovascular disease. These findings may provide at least a partial explanation for several recent epidemiologic studies implicating low vitamin D status in the pathogenesis of cardiovascular disease. However, large-scale, well-conducted, placebo controlled clinical trials testing the efficacy of vitamin D supplementation in delaying, slowing, or reversing the atherosclerotic disease process have not yet been conducted. Until the results of these studies are available, we believe it is premature to recommend vitamin D as a therapeutic option in atherosclerosis.

76. ratchford eV, Black JH 3rd. Approach to smoking cessation in the patient with vascular disease. Current Treatment Options in Cardiovascular Medicine. 2011 Apr;13(2):91-102.

Summary: In the patient with vascular disease, cigarette smoking is particularly perilous; the benefits of smoking cessation greatly exceed any risks associated with pharmacologic treatment. Multiple clinical trials have demonstrated the efficacy of pharmacologic therapy for smoking cessation. In parallel with aggressive counseling and pharmacotherapy for smoking cessation, cardiovascular risk reduction is critical.

77. Konerman M, Kulkarni K, Toth PP, Jones Sr. Evidence of dependence of lipoprotein(a) on triglyceride and HDL metabolism. Journal of Clinical Lipidology. Forthcoming 2011.

78. ratchford eV, Gutierrez J, Lorenzo D, McClendon MS, Della-Morte D, DeRosa JT, Elkind MSV, Sacco RL, Rundek T. Short-term effect of atorvastatin on carotid artery elasticity. Stroke. Forthcoming 2011.

79. Stewart KJ, ratchford eV, Williams MA. Exercise for restoring health and preventing vascular disease. In: Blumenthal RS, Foody JM, Wong ND eds. Preventive Cardiology: A Companion to Braunwald’s Heart Disease. Philadelphia, PA: W.B. Saunders; 2011; Chapter 33:541-550.

Summary: Individuals with heart disease can benefit greatly from exercise training and other aspects of cardiac rehabilitation and secondary prevention programs. Exercise training plays a critical role as a primary treatment of patients with peripheral arterial disease, with the goal of improving quality of life and functional capacity.

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Dr. Sherita Golden reviewed

evidence showing alterations

of three biological systems in

depression, diabetes, and

diabetes-related risk factors.

80. mclean rC, Hirsch GA, Becker LC, Kasch-Semenza L, Gerstenblith G, Schulman SP. Polymorphisms of the beta adrenergic receptor predict left ventricular remodeling following acute myocardial infarction. Cardiovascular Drugs and Therapy. 2011 Jun;25(3):251-8.

Summary: Prior studies demonstrate an association between specific beta-adrenergic receptor (β-AR) polymorphisms and clinical outcomes in patients with chronic heart failure and following acute coronary syndromes. The underlying mechanism may be due to differences in left ventricular remodeling. This study was undertaken to explore the relationship between LV remodeling after myocardial infarction and polymorphisms in the cardiac β1-AR and β2-AR genes. We found that polymorphisms of the β1-AR and β2-AR genes are associated with differential LV remodeling in patients treated with a β1 receptor antagonist following ST-segment elevation myocardial infarction.

81. Gluckman tJ, mclean rC, Schulman SP, Kickler TS, Shapiro EP, Conte JV, McNicholas KW, Segal JB, Rade JJ. Effects of aspirin responsiveness and platelet reactivity on early vein graft thrombosis after coronary artery bypass graft surgery. Journal of the American College of Cardiology. 2011 Mar 1;57(9):1069-77.

Summary: The purpose of this study was to determine if an incomplete response to or inadequate antiplatelet effect of aspirin, or both, contribute to saphenous vein graft (SVG) occlusion after coronary artery bypass graft (CABG) surgery. Aspirin-insensitive thromboxane generation measured by UTXB(2) and shear-dependent platelet hyper-reactivity measured by Platelet Function Analyzer-100 CADP CT are novel independent risk factors for early SVG thrombosis after CABG.

82. Najaar SS, Lakatta EG, Gerstenblith G. Cardiovascular aging: the next frontier in cardiovascular prevention. In:

Blumenthal RS, Foody JM, Wong ND eds. Preventive Cardiology: A Companion to Braunwald’s Heart Disease. Philadelphia, PA: W.B. Saunders; 2011; Chapter 25:415-432.

Summary: Age is the dominant risk for CVD, but it has traditionally been viewed as a nonmodifiable risk factor. This chapter examines physiologic aging and clinical interventions to slow this process. Future studies should examine

whether such interventions can slow the process of accelerated cardiovascular aging and attenuate the impact of age as the dominant risk factor for CVD.

83. Corretti MC, Panjrath GS, Jones Sr. Endothelial function and dysfunction. In: Blumenthal RS, Foody JM, Wong ND eds. Preventive Cardiology: A Companion to Braunwald’s Heart Disease. Philadelphia, PA: W.B. Saunders; 2011; Chapter 32:526-540.

Summary: Vascular endothelium is a vast dynamic paracrine system that regulates several key biologic and molecular functions serving to maintain vascular health and homeostasis. Ongoing research in the development and application of noninvasive imaging techniques to measure endothelial function and dysfunction continues to focus on therapeutic strategies and prognosis.

84. Michtalik HJ, Yeh HC, Campbell CY, Haq N, Park H, Clarke W, Brotman DJ. Acute changes in N-terminal pro-B-type natriuretic peptide during hospitalization and risk of readmission and mortality in patients with heart failure. American Journal of Cardiology. 2011 April 15;107(8):1191-5.

85. Ketlogetswe KS, Aoki J, Traill TA, Cingolani OH. Severe aortic regurgitation secondary to antisynthetase syndrome. Circulation. 2011 Jul 19; 124(3):e40-1.

86. Larocca CA, mcevoy JW, Ellis CL, Junkins-Hopkins J, Kolb T, Baer AN, Garibaldi BT. Schnitzler’s syndrome associated with pancreatitis: a disease of IL-1 dysregulation. Clinical Rheumatology. 2011 June 28. [Epub ahead of print]

87. mcevoy JW. Letter regarding “Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. Circulation. 2011 May 10;123(18):e585; author reply e586-7.

88. mcevoy JW, Blaha mJ, nasir K. Metabolically benign obesity: a wolf in sheep’s clothing. Atherosclerosis. 2011 July;217(1):74-6. Epub 2011 March 12.

89. Voros S, rivera JJ, Berman DS, Blankstein R, Budoff MJ, Desai MY, Hecht HS, nasir K, Santos RD, Taylor AJ, Weissman G. Society for Atherosclerosis Imaging and Prevention Tomographic Imaging and Prevention Councils. Guideline for minimizing radiation exposure during acquisition of coronary artery calcium scans with the use of multidetector computed tomography. Journal of Cardiovascular Computed Tomography. 2011 Mar-April;5(2):75-83.18

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Dr. Kerunne S. Ketlogetswe

co-authored an article

about severe aortic

regurgitation secondary to

antisynthetase syndrome.

Dr. Elizabeth Ratchford

investigated the efficacy

of pharmacologic therapy

for smoking cessation

in relation to CVD risk

reduction.

90. Khan A, nasir K, Khosa F, Saghir A. Sarwar S, Clouse ME. Prospective gating with 320-MDCT angiography: effect of volume scan length on radiation dose. American Journal of Roentgenology. 2011 Feb;196(2):407-11.

91. Murphy MK, Brady TJ, nasir K, Gazelle GS, Bamberg F, Truong QA, Mamuya WS, Abbara S, Lee TH, Blankstein R. Appropriateness and utilization of cardiac CT: implications for development of future criteria. Journal of Nuclear Cardiology. 2010 Oct;17(5):881-9.

92. Coylewright M, Rice K, Budoff MJ, Blumenthal rS, Greenland P, Kronmal R, Barr RG, Burke GL, Tracy R, post WS. Differentiation of severe coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. Forthcoming 2011.

Summary: Both high and very high levels of coronary artery calcium are associated with an elevated risk of CHD events in those without symptomatic CHD at baseline; however, very high CAC is associated with an increased risk of angina, but not CHD death or MI, as compared to high CAC.

93. Reed RM, Iacono A, DeFilippis ap, Jones Sr, Eberlein M, Lechtzin N, Girgis RE. Statin therapy is associated with decreased pulmonary vascular pressures in severe COPD. Journal of Chronic Obstructive Pulmonary Disease. 2011;8:96-102.

94. Reed RM, Iacono A, DeFilippis ap, Eberlein M, Girgis RE, Jones Sp. Advanced chronic obstructive pulmonary disease is associated with high levels of high-density lipoprotein cholesterol. Journal of Heart and Lung Transplantation. Forthcoming 2011.

95. DeFilippis ap, Blaha mJ, Jacobson T. Omega-3’s for cardiovascular disease prevention. Current Treatment Options

in Cardiovascular Medicine. 2010; 12:365:365-60.

96. Blaha mJ, nasir K. No justification for coronary CT angiography among low-intermediate risk individuals with CAC=0. Radiology. Forthcoming 2011.

97. nasir K, rubin J, Blaha mJ, Shaw LJ, Blankstein R, rivera JJ, Khan A, Berman D, Raggi P, Callister T, Rumberger J, Min J, Jones SR, Blumenthal rS,

Budoff MJ. Interplay of coronary artery calcification and traditional risk factors for the prediction of all-cause mortality in asymptomatic individuals. Circulation: Cardiovascular Imaging. Forthcoming 2011.

Summary: While both risk factors and CAC were associated with increasing CVD risk, CAC provides classification across a wider range of risk levels than traditional risk factors alone. Even among individuals with no risk factors, increased CAC is associated with a significantly higher CVD risk. While the absence of CAC is associated with very low intermediate term mortality, individuals with no risk factors but severe CAC have a high event rate.

98. ashen mD. Cost-effective prevention of coronary heart disease. The Journal for Nurse Practitioners. Nov/Dec 2010;6:754-764.

99. Amin NP, Blaha mJ, Chow GV, Blumenthal rS, ashen mD. Comprehensive lipid management in the coronary artery disease patient. Current Cardiovascular Risk Reports. Forthcoming 2011.

100. Reed R, Hashmi S, Eberlein M, Iacono A, Netzer G, DeFilippis a, Girgis R, Toth P, Scharf S, Jones S. Impact of lung transplantation on serum lipids in COPD. Respiratory Medicine. Forthcoming 2011. 101. Konerman M, Kulkarni K, Toth PP, Jones Sr. Lipoprotein(a) particle concentration and lipoprotein(a) cholesterol assays yield discordant classification of patients defining four physiologically discrete groups. Journal of Clinical Lipidology. Forthcoming 2011.

102. Bis JC, Kavousi M, Francheschini N, Isaacs A, Abecasis GR, Schminke U, post WS, Smith AV, et al. Meta-analysis of genome-wide association studies from CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque. Nature Genetics. 2011 Sept 11. [Epub ahead of print]

19

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Dr. Andrew DeFilippis

studied Omega-3’s for

cardiovascular disease

prevention.

Dr. Dominique

Ashen researched

cost-effective

prevention of heart

disease.

20

A listing of the late-breaking clinical research data presented at major cardiology meetings by the faculty and fellows of the Johns Hopkins Ciccarone Center for the prevention of Heart disease, during the course of 2011.

Presentations at the 2011 Scientific Sessions of the American Heart Association (AHA)

1. Budoff MJ, Wong ND, post WS, Blumenthal rS, Kronmal R, Guerci A, Lima J, Liu K, Shea S, Bertoni A, Szklo M, Detrano R. Progression of coronary calcium and incident coronary heart disease events: The multi-ethnic study of atherosclerosis. Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

2. Narla V, Blaha mJ, nasir K, Blumenthal rS, Jenny NS, michos eD. Resting heart rate is associated with c-reactive protein in the multi-ethnic study of atherosclerosis (MESA). Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

3. Yeboah J, Redline S, Johnson C, Tracy R, Ouyang P, Blumenthal rS, Burke GL, Herrington DM. Association between sleep apnea, snoring, incident cardiovascular events and all-cause mortality in an adult population. Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

4. tota-maharaj r, Blumenthal rS, Blaha mJ, nasir K, Budoff MJ, Shaw LJ, Blankstein R. Coronary artery calcium predicts coronary heart disease events even at the extremes of age. Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

5. rubin J, Matsushita K, Ballantyne CM, Nambi V, Hoogeven R, Sharrett AR, Blumenthal rS, Coresh J, Selvin E. Association of cardiovascular risk factors with minimally elevated cardiac troponin t detected by a novel highly sensitive assay. Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

6. Blaha mJ, DeFilippis ap, Blumenthal rS, Budoff MJ, nasir K. Comparing zero coronary artery calcium with other negative risk factors for coronary heart disease: MESA. Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

7. Silverman mG, Blaha mJ, Budoff MJ, Blankstein R, Sibley CT, Blumenthal rS, nasir K. Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: The Multi-Ethnic Study of Atherosclerosis (MESA). Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

8. Thanassoulis G, Campbell CY, Owens DS, Smith JG, Budoff MJ, Allison MA, Carr J, Criqui MH, Heckbert SR, Kathiresan S, Erbel R, Rotter JL, O’Donnell CJ, post WS. A

meta-analysis of genome wide association studies identifies novel loci for aortic valvular and mitral annular calcium and implicates LPA in the development of aortic stenosis. Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

9. mcevoy JW, Blaha mJ, Lima JAC, Bluemke DA, Hundley WG, Min JK, Shaw LJ, Lloyd-Jones DM, Barr RG, Budoff MJ, Blumenthal rS, Nasir K. Cigarette smoking: relationship with inflammation, arterial stiffness, and subclinical atherosclerosis.

The Multi-Ethnic Study of Atherosclerosis (MESA). Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

10. mcevoy JW, Blaha mJ, Lima JAC, Bluemke DA, Hundley WG, Min JK, Shaw LJ, Lloyd-Jones DM, Barr RG, Budoff MJ, Blumenthal rS, Nasir K. Cigarette smoking: interaction between inflammation, subclinical atherosclerosis and events. The Multi-Ethnic Study of Atherosclerosis (MESA). Paper presented at: 2011 AHA Scientific Sessions; November 12-16, 2011; Orlando, FL.

Original Research — presentations

Dr. Catherine Campbell

presented a paper at

the 2011 AHA Scientific

Sessions that analyzed

a number of studies to

identify new causes for

the development of aortic

stenosis.

Dr. Rajesh Tota-Maharaj’s

AHA presentation

examined how CAC

predicts coronary heart

disease events even at the

extremes of age.

Presentations at the 2011 Scientific Sessions of the American College of Cardiology (ACC)

1. Ketlogetswe K, Blaha mJ, Budoff MJ, Khan AN, rivera JJ, Shaw LJ, Berman DS, Raggi P, Min JK, Callister TQ, Rumberger JA, Blumenthal rS, nasir K. Increasing coronary artery calcium is associated with increased all-cause mortality among asymptomatic individuals with a family history of coronary heart disease. Journal of the American College of Cardiology. 2011;57:E640.

2. tota-maharaj r, Blaha mJ, Muse ED, Blumenthal rS, Budoff MJ, Shaw LLJ, Berman DS, Rana JS, nasir K. The utility of coronary artery calcium in predicting mortality at extremes of age: evaluation of an asymptomatic referred cohort. Journal of the American College of Cardiology. 2011; 57:E882.

3. rivera JJ, nasir K, Zhu X, Superko R, Blumenthal rS, Agatston AS. Association between LDL and HDL sub-fractions with subclinical atherosclerosis and inflammation. Journal of the American College of Cardiology. 2011; 57:1468.

4. rivera JJ, nasir K, Superko R, Zhu X, Blumenthal rS, Agatston AS. Carriers of the KIF6 719Arg allele have a higher Lp(a) concentration and predominantly small LDL particles despite similar traditional lipoprotein levels. Journal of the American College of Cardiology. 2011; 57:1300.

5. rivera JJ, nasir K, Zhu X, Superko R, Blumenthal rS, Agatston AS. ApoB/Apo A ratio is associated with progression of carotid artery intima-media thickness in clinically asymptomatic individuals free of known CHD. Journal of the American College of Cardiology. 2011; 57:1587.

Presentations at the Arteriosclerosis, Thrombosis & Vascular Biology Annual Conference 2011

1. Jones Sr, Kulkarni K. The ability of lipoprotein cholesterol and subfractions, Apo AI, and triglycerides to predict extent of HDL lipidation and HDL particle structure. Paper presented at: Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2011; April 28-30, 2011; Chicago, IL.

2. Jones Sr, Kulkarni K. Dense/buoyant LDL subfraction cholesterol ratio predicts LDL modal density phenotype. Paper presented at: Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2011; April 28-30, 2011; Chicago, IL.

3. Jones Sr, Kulkarni K. The relative ability of HDL-C and HDL subfractions, triglycerides, triglyceride/HDL-C ratio, apoB, hsCRP, Homocysteine and glycemic status to predict the presence of small dense LDL. Paper presented at: Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2011; April 28-30, 2011; Chicago, IL.

4. Reed R, Girgis R, Toth PP, Kulkarni K, Asztalos B, Jiang XC, Jones Sr. Characterization of lipids and abnormally high HDL-C in patients with severe chronic obstructive pulmonary disease evaluated for lung transplantation. Paper presented at: Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2011; April 28-30, 2011; Chicago, IL.

Dr. Steven Jones led four

important presentations at the

2011 Arteriosclerosis, Thrombosis,

and Vascular Biology Annual

Conference in Chicago.

Ori

gina

l Res

earc

h —

pre

sent

atio

ns

21

The Ciccarone Center – Uniting the proud Traditions of Hopkins

The Ciccarone Center for the Prevention of Heart Disease was founded in 1989 in memory of Henry A. “Chic” Ciccarone, a legendary athlete and lacrosse coach at Johns Hopkins who died at age 50 after his third heart attack.

But he was more than that. In the way he led his teams and his life, Chic embodied all that Johns Hopkins itself represents: dedication, excellence, leadership.

With intense, energetic competitiveness, pride, and engaging, infectious humor, Chic compiled an extraordinary record of achievements in athletics. As a three-time All-American midfielder and team captain, he won nearly every major Hopkins lacrosse award and was named to the All-Time Hopkins lacrosse team upon his graduation in 1962.

In 1989, the friends and former players of Coach Ciccarone began raising funds for the development of a comprehensive program geared toward the prevention of coronary heart disease events. The Ciccarone Center sought to unite the proud traditions of Hopkins lacrosse and Hopkins Medicine.

We all have a stake in winning the battle against heart disease. By joining the team at the Ciccarone Center, by sharing our enthusiasm and dedication to it, your support of coronary disease prevention will protect your life and the lives of those you love.

22

How to Contact the Center

We see patients Monday through Friday at the Johns Hopkins Ciccarone Center at Green Spring Station and on Mondays at the Johns Hopkins Outpatient Center. Drs. Michos and Bhatia also see patients at Odenton. At each location we can perform exercise stress tests, treadmill stress echo tests, echo Doppler tests, EKG’s, Holter monitors and refer patients for cardiac CT scans. Vascular ultrasound testing and consultations are available in White Marsh, Columbia, Odenton, and at Green Spring Station.

Appointments at the Johns Hopkins Ciccarone Center at Green Spring Station location can be scheduled at 410-583-2740. (Drs. Blumenthal, Post, Ashen, Ratchford)

Appointments at the Johns Hopkins Outpatient Center can be scheduled at 410-502-0550 or 410-955-7376. (Drs. Jones, Blumenthal, and Blaha)

Appointments at the Johns Hopkins Cardiology Center at Odenton can be scheduled at 410-874-1520. (Drs. Michos, Bhatia, and Ratchford)

Appointments for Vascular medicine consultations or vascular ultrasound testing can also be scheduled through Dr. Ratchford’s office at 410-616-7225.

Support the prevention of Heart Disease

Heart disease is America’s #1 killer — more than cancer and accidents combined. Our goal at the Ciccarone Center is to stop heart disease before it develops through an aggressive program of risk assessment and comprehensive lifestyle and medical management.

like all pioneering medical programs, however, we are in constant pursuit of funding to accelerate our progress. We depend on the support of generous donors to thrive.

When you give to the Ciccarone Center, you’re ensuring that, if you or a loved one is at risk for

heart disease or stroke, you’ll have a program to help prevent it. Or if you already have heart disease, you’ll maximize your opportunity for an active, enjoyable life.

Contribute to the future of heart disease research, education, and patient care. make a donation to the Ciccarone Center. today.

Gifts may be made in the form of cash, securities, real estate or personal property. For more information, please call 410-516-6607. Or go online: http://jhu.plannedgifts.org/ 23

The Johns Hopkins Ciccarone Centerfor the prevention of Heart Disease

www.hopkinsmedicine.org/heart410.583.2740