Historical Studies

Epidemiology of Diabetes Complications Phase II: Renewal (EDC)

Originating Department:University of Pittsburgh
Principal Investigator: Trevor Orchard MD, M Med Sci, FAHA, FACE
URL Co-Investigator: Emma Barinas-Mitchell, PhD

The main objectives of this study are to determine the distribution of PWV in the Type 1 diabetics patients, the association with clinical and subclinical (CAC) CVD, other diabetes complications and 30 year history of risk factors including glycemic control. The URL will be responsible for training and certification of staff on the SphygomoCor XCEL EM4C PWV machine.

Dementia. Vascular Moderators of Amyloid-Related Decline: From normal cognition to dementia (GEMS)

Originating Department: University of Pittsburgh
Principal Investigator: Oscar Lopez, MD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

This is a renewal of the PPG-Dementia study to examine the interaction between vascular factors and amyloid deposition in the transition from normal aging to cognitively-impaired aging. These participants will undergo PET/PiB scans, a battery of neuropsychological and physical functioning assessments, as well as carotid IMT and aortic PWV testing.

Subclinical vascular disease and AD pathology in the transition from midlife to old age (HEARTSCORE)

Originating Department: University of Pittsburgh
Principal Investigator: Oscar Lopez, MD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

This is an R01 to test the hypothesis that midlife systemic atherosclerosis and arteriosclerotic vascular disease, irrespective of subsequent treatment, is a major risk factor for the development of AD pathology, and its clinical expression.

Pediatric Depression and Subsiquent Cardiac Risk Factors: A Longitudinal Study (HuCardio)

Originating Department: Semmelweis University Budapest, Hungary
Principal Investigator: Maria Kovacs, PhD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

This study is a follow-up of an existing cohort of young adults, who have had juvenile-onset depression, with average age at first depression episode onset at 9 years (n=325); their never depressed siblings (n=325); and unrelated normal control peers (n=155). The hypotheses address the levels of CHD risk markers as function of subject group, the role of behavioral risk factors in adolescence in the link between depression and preclinical physiological outcomes, the impact of developmental trajectories of stress and rick variables on physiological outcomes among probands-sibs, and the most “cardiotoxic” clinical features of depression. The URL is the training and QC center for the arterial stiffness assessment utilizing the Complior machines.

Resistance and Cardiorespiratory Time-matched Exercise in Youth: A Randomized Clinical Trial (RCT:RCT)

Originating Department: Children’s Hospital of Pittsburgh
Principal Investigator: SoJung Lee, PhD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

This is an exercise intervention to examine the effect of aerobic exercise, resistance exercise and standard care control (no exercise) on traditional and non-traditional risk factors for CVD and subclinical vascular changes in overweight youth.

A Phase I/II Pilot Study of Dipyridamole as a Modulator of Immune Activation and Systemic Inflammation in HIV-1-Infected Subjects on Antiretroviral Therapy (DIPY)

Originating Department: University of Pittsburgh Medical Center (UPMC)
Principal Investigator: Sharon Riddler
URL Co-Investigator: Emma Barinas-Mitchell, PhD

This is a Phase I/II, randomized, double blind, two-arm, partial cross-over, single-site, pilot study evaluating the effect of oral dipyridamole (DP) on immune activation and inflammation in HIV-1-infected, ART-treated subjects with HIV-1 RNA less than 50 copies/mL and CD4+ cell counts less than or equal to 500/mm³.

Neurological Pathways Linking Stress to Atherosclerosis (PIP)

Originating Department: University of Pittsburgh
Principal Investigator: Peter Gianaros, PhD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

This study tests the central hypothesis that exaggerated blood pressure reactivity to psychological stress and greater preclinical carotid atherosclerosis are commonly associated with stress-induces hyperactivity in a network of brain systems that both process psychological stressors and regulate autonomic, neuroendocrine, and cardiovascular activity. This is the second visit of these participants.

Sleep, Circadian Rhythms & Cardiometabolic Risk in Retired Shift Workers (SIR)

Originating Department: University of Pittsburgh
Principal Investigator: Daniel Buysse, MD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

The SIR study is being conducted to see if a past history of shift work (working at night on a permanent or rotating basis) has any long-term effect on a person’s sleep patterns, and daily rhythms in physiology (circadian rhythms), as well as on their health and well-being Poor sleep health can increase the risk of health issues such as depression, cognitive impairment, cardiovascular disease and diabetes. The URL performs Carotid Intima-Media Thickness measures, as well as Brachial Artery flow mediated dilatation FMD to assess cardiovascular risk.

THS Ectopic Fat. T2DM, Coronary Artery Calcification and Ectopic Fat Depots in African Men

Originating Department: University of Pittsburgh
Principal Investigator: Iva Moljkovic, MD, PhD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

The THS Ectopic Fat study is an ancillary study of the Tobago Health Study (THS) to determine the association of ectopic fat (muscle, liver, abdominal and pericardial) with coronary artery calcification in African American men at high risk for type 2 diabetes in the Tobago Health Study. Carotid IMT and pulse wave velocity will also be assessed as additional measures of subclinical vascular disease. This work is partially funded by the URL including training for pulse wave velocity and IMT.

Femoral Atherosclerosis in Functional Status and CVD Events (FEMA)

Originating Department: University of Pittsburgh
Principal Investigator: Christina Wassel, PhD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

This studies an NHLBI funded study to examine the role of atherosclerosis in the femoral artery and inflammation as a predictor of functional status and CVD morbidity/mortality in the San Diego Population study. The URL has developed a protocol for reading the femoral ultrasound images and is the reading center.

Mechanisms Linking Hot Flashes to Cardiovascular Risk (MS Heart)

Originating Department: University of Pittsburgh
Principal Investigator: Rebecca C. Thurston, PhD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

Based on preliminary data collected in the URL, Dr. Thurston was funded in 2011 an R01 to assess mechanisms for the link between hot flashes, CVD risk factors and subclinical CVD changes in menopausal women. This grant was funded August 2011 and URL clinic visits, which include brachial artery reactivity testing, as a measure of endothelial function, and carotid IMT, began January 2012.

Long Term Consequences of Systemic Lupus Erythematosus: Vascular and Bone Complications (LUPUS Chicago/SOLVABLE)

Originating Department: Northwestern University
Principal Investigator: Rosalind Ramsey-Goldman, MD, Dr.PH
URL Co-Investigator: Emma Barinas-Mitchell, PhD

This is an NIH funded study of cardiovascular and bone health endpoints in women with lupus and controls out of Northwestern University. The URL is currently reading second and third follow-up scans and provides ongoing quality control feedback to the ultrasound lab at Northwestern.

Mobility and Independent Living in Elders (MILE)

Originating Department: University of Pittsburgh
Co- Investigator: Dr. PS Reddy
Local Consultants: Anne M. Newman, MD, MPH, Jane A. Cauley, DrPH, Joseph M. Zmuda, PhD, Clareann H. Bunker, PhD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

The MILE study is an observational study originally designed to enroll 500 men and women (250 each) age ?60 in selected geographic regions in the Andhra Pradesh Province of India to establish a longitudinal cohort study in India to define the prevalence, incidence and risk factors for disability and age-related disease in this population. It involves a collaborative effort between the University of Pittsburgh, Share India, the Reach project, and the Mediciti Institute of Medical Sciences (MIMS). The URL has provided carotid training for 3 sonographers. This work is partially funded by the URL.

Effect of Reducing Inflammation with Low Dose Methotrexate on Inflammatory Markers and Endothelial Function in Treated and Suppressed HIV Infection (A5314)

Originating Department: University of Pittsburgh Medical Center (UPMC)
Principal Investigator: Sharon Riddler
URL Co-Investigator: Emma Barinas-Mitchell, PhD

A5314 is a phase II, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of low dose methotrexate (LDMTX) for the treatment of HIV-associated inflammation.

Microvascular endothelial dysfunction and atherosclerosis following vascular-mediated preterm birth (WISH 2015)

Originating Department: University of Pittsburgh Medical Center (UPMC)
Principal Investigator: Janet Catov, PhD
URL Co-Investigator: Emma Barinas-Mitchell, PhD

The purpose of this research study is to enroll women who participated in the Women and Infant Study of Healthy Hearts (WISH) to review any changes in hardening of the arteries and/or plaque in the veins and arteries. The results of these tests will help researchers understand changes to blood vessels and their functions as well as the relationship between cardiovascular disease in women with and without pre-term birth, or women who have their babies early.

Maternal Vascular Adaption to Healthy Pregnancy (MVP2)

Originating Department: University of Pittsburgh
Principle Investigator: Mansi Patel
Co-Investigators: Emma Barinas-Mitchell, PhD; Mindy L. Columbus, MS, MPH

(Maternal Vascular Adaption to Healthy Pregnancy) The purpose of this study is to understand how measures taken in the common carotid arteries can be used to follow the vascular adaptation to pregnancy and to determine the degree to which arteries stiffen in response to this physiological challenge. This is a follow-up visit of participants in the MVP study.

Mechanisms linking hot flashes and cardiovascular disease (HTFLSH)

Originating Department: University of Pittsburgh
Principal Investigator: Rebecca C. Thurston, PhD
Co-Investigator: J. Richard Jennings, PhD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This research is designed to examine the relations ship between menopausal hot flashes and cardiovascular function in women. Hot flashes are experienced by most midlife women. Hot flashes are associated with reported sleep disruption, poorer memory performance, depressed mood and overall poorer quality of life. Most women with menopausal systems, principally hot flashes, seek treatment for them.

Study of Women’s Health Across the Nation (SWAN IV) Hormonal Predictors of Perimenopausal Morbidity

Originating Department: Psychology
Site Principal Investigator: Karen A. Matthews, PhD
Coordinating Center PI: Maria M. Brooks, PhD

SWAN is the parent study for the SWAN Heart ancillary study led by Kim Sutton-Tyrrell and for which various subclinical measures were carried out in the URL. SWAN is a multi-center, multi-ethnic longitudinal cohort study of the menopausal transition. The URL will be the training and reading site for carotid IMT for 6 sites. The SWAN IV resubmission was just funded to begin May 2009. The carotid training will be held in August 2009 and 12 year follow-up visits are slated to began in November 2009.

A Phase III Comparative study of 3 non-nucleoside reverse transcriptase inhibitor (NNRTI)-Sparing antiretroviral regimens for treatment-naive HIV1 infected volunteers. (A5260)

Originating Department: Medicine
Principle Investigator: Sharon Riddler, MD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This multi-centered clinical trial will evaluate the metabolic and subclinical CVD effects of a specific antiretroviral therapy. The URL will be one of the ultrasound labs performing carotid IMT and brachial artery reactivity tests. Two URL sonographers have undergone carotid IMT and BART protocol training at the University of Wisconsin Atherosclerosis Imaging Research Program.

Adult Health and Behavior Phase 2 (AHAB2)

Originating Department: University of Pittsburgh
Principal Investigator: Stephen Manuck, PhD
Co-Investigator: Kim Sutton-Tyrrell, Dr. PH

This program project (Biobehavioral Studies of CVD Program Project, PI: Steve Manuck, has three objectives: 1) Establish whether psychosocial and lifestyle-related risk factors for CVD are associated with the reactivity of key neural structures underlying emotional processing and appetitive motivation; 2) evaluate stress-related features of the social environment as they relate to subclinical CVD; and 3) evaluate omega-3 fatty acids as a mechanism of action of several behavioral and biological CVD risk factors. 530 middle-aged adults without clinically apparent atherosclerosis are being recruited to undergo neuroimaging, neuroendocrine assays, personality and behavior assessments, vascular imaging and genetic testing.

Insulin Secretion/Action and Cardiovascular Disease Risk Assessment in Youth with Type 2 Diabetes Mellitus. (DKS)

Originating Department: Children’s Hospital of Pittsburgh
Principal Investigator: Fida Bacha, MD
Co-Investigator: Silva Arslanian, MD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

Type 2 diabetes mellitus (T2DM), formerly known as non-insulin-dependent diabetes mellitus, has typically been considered a disease of adulthood. In the past 15 years or so, we started to see this disease in children in increasing numbers. Insulin is a hormone that regulates blood sugar levels and fat metabolism. In this particular type of diabetes, the insulin levels in the body are not deficient or absent as they are in the more common type of childhood diabetes, known as Type 1, or insulin-dependent diabetes mellitus. The main problem appears to be a resistance to the action of insulin in the body. In order for the body to make up for this decreased insulin action, it produces more insulin. Children who are overweight, who have a family history of T2DM, who are in the minority ethnic groups (such as African-, Mexican-, or native-Americans) and who have dark and velvety skin areas (such as the back of the neck, armpits, knuckles) are at increased risk of developing T2DM. Children who have T2DM are also at increased risk of heart and blood vessel complications and high blood pressure compared with their healthy peers. In order to understand this disease process better, we invite you to participate in our research study.

Obesity, insulin resistance, and bone metabolism in adolescents with PCOS: Effects of insulin sensitizers versus oral contraceptives. (KPCO)

Originating Department: Children’s Hospital of Pittsburgh
Principle Investigator: Silva Arslanian, MD
Co-Investigator: Fida Bacha, MD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This study aims to investigate effects of 2 different treatments on the well-described hormonal and metabolic disturbances in PCOS, targeting a population of overweight/obese girls with PCOS at high risk to develop impaired glucose tolerance14-16 and type 2 diabetes mellitus17. The two treatments, drospirenone-ethinylestradiol and rosiglitazone, will address the two different literature-proposed pathophysiological mechanisms responsible for PCOS. As the inflammatory, hormonal, metabolic, and body composition characteristics of PCOS also have an effect on bone mass and metabolism, we propose to examine the bone status at baseline as well as effects of treatment in this population. They will be compared longitudinally to a control group of untreated overweight/obese, otherwise healthy adolescent females because bone turnover markers and bone mineral density change during normal puberty.

Maternal Vascular Adaption to Healthy Pregnancy (MVP)

Originating Department: University of Pittsburgh
Principle Investigator: Candace K. McClure, PhD
Co-Investigator: Kim Sutton-Tyrrell, Dr.PH
EDC Project Coordinator: Janet Catov

Are Overweight Children with TIDM at increased risk of CVD (ODK)

Originating Department: Children’s Hospital of Pittsburgh
Principle Investigator: Ingrid Libman, MD
Co-Investigator: Silva Arslanian, MD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This is a K23 career award submitted to NIDDK for the assessment of CVD risk factors and carotid IMT and aPWV in overweight children with Type 1 diabetes. The PI will also receive training in the lab in carotid ultrasound scanning. This study was initiated during this progress period.

Study of Women’s Health Across the Nation (SWAN IV) Hormonal Predictors of Perimenopausal Morbidity

Originating Department: Psychology
Principal Investigator: Karen A. Matthews, PhD
Co-Investigator: Kim Sutton-Tyrrell, Dr.PH
EDC Project Coordinator: Joyce Bromberger, PhD

Epidemiology of cardiovascular risk factors in women (HWS)

Originating Department: Epidemiology
Principal Investigator: Lewis H. Kuller, MD, Dr.PH
Co-Investigator: Sheryl F. Kelsey, PhD
EDC Project Coordinator: Karen Matthews, PhD

This long-term study of the changes in CVD risk factors and subclinical CVD in women that have been followed since pre-menopause has recently been funded for its 12th postmenopausal visit. These women are now an average of 10 years post menopausal. For this visit, repeated measures of carotid IMT and plaque and aortic PWV will be performed in the URL.

Physical Activity in Youth (PAY) implications for reversing risk factors for cardiovascular disease and type 2 diabetes mellitus

Originating Department: Children’s Hospital
Principal Investigator: Sojung Lee, PhD
Co-Investigator: Silva Arslanian. MD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This is a pilot study led by Dr. SoJung Lee who is a pediatric endocrinologist affiliated with the Division of Weight Management and Wellness. This study will examine the effect of regular physical activity alone (i.e., without calorie restriction) on abdominal obesity, ectopic fat, inflammatory biomarkers, and traditional and non-traditional risk factors for CVD and subclinical vascular changes (aortic pulse wave velocity as a measure of arterial stiffness and carotid IMT) in overweight youth.

Pittsburgh Project on Brain Pathways to Heart Health (Pgh Pathways Project) (PIP)

Originating Department: University of Pittsburgh
Principal Investigator: Peter Gianaros PHD
Co-Investigator: Howard J. Aizenstein, MD, PhD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This study tests the central hypothesis that exaggerated blood pressure reactivity to psychological stress and greater preclinical carotid atherosclerosis are commonly associated with stress-induced hyperactivity in a network of brain systems that both process psychological stressors and regulate autonomic, neuroendocrine, and cardiovascular activity.

In Vivo PiB PET Amyloid Imaging: Normals, MCI & Dementia (Project 4: Modulators of Cognitive Transition in Normal Aging. (PPG)

Originating Department: University of Pittsburgh
Principal Investigator: Oscar Lopez MD
Co-Investigator: Julie C. Price, PhD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

These two projects, led by investigators from the Alzheimer’s Disease Research Center, Department of Neurology and Epidemiology, are part of a program project grant to follow some of the participants of the GEM (Ginkgo Evaluation of Memory) study. For this study, participants 85 years and older will undergo PET/PiB scans, a battery of neuropsychological and physical functioning assessments, as well as carotid IMT and aortic PWV testing.

Postprandial glycemia in the free living condition and cardiometabolic risk in obese youth (PPGK)

Originating Department: Children’s Hospital
Principal Investigator: Kara Hughan, MD, MHSc
Co-Investigator: Silva Arslanian, MD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This study is investigating the effects of postprandial hyperglycemia in free living conditions and the metabolic syndrome and cardiovascular disease risk in high risk overweight youth. The overall objective of this research study is to apply continuous glucose monitoring (CGM) in obese youths at high risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) to assess the relationship between glycemia by OGTT vs by CGM under free living conditions, and the association with early signs of subclinical atherosclerosis.

Pulse Wave Velocity for Revealing Effects of Disease Indices Correlating Arterial Stiffness in SLE (PREDICTS & PLAQ)

Originating Department: University of Pittsburgh
Principal Investigator: Susan Manzi, MD, MPH
Co-Investigator: Robyn Domsic, MD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This competing renewal was funded early of 2006 to continue collecting longitudinal data on women with lupus including coronary calcification, carotid ultrasound and plaque and vascular stiffness measures. There are two components to this grant. The first component (PLAQ) is to measure carotid IMT, adventitial diameter and plaque morphology in women with lupus (n=220) and controls (165) with previous URL visits. The second component (PREDICTS) is an observational longitudinal study evaluating the association between lupus disease activity and arterial stiffness in women with active Lupus. This study will evaluate progression of arterial stiffness measured by aortic pulse wave velocity (aPWV) over a three-year period in lupus women (n=125) between the ages of 18 and 45 compared to age- and race-matched controls (n=125). The Lupus patients will have two additional aPWV measures, one timed to a disease flare and one after treatment when flare is resolved. URL clinic visits for both components began in March of 2007. To date, the URL has seen 87 and 89 participants from the PLAQ and PREDICTS studies, respectively. Due to the older carotid ultrasound and PWV technology being used for the PLAQ study (to allow for comparison to previous scans), the URL is also collecting data using the newer carotid ultrasound machine (Antares) on a subsample of the participants (n=20).

Mechanisms linking hot flashes and cardiovascular disease (HTFLSH)

EBCT and Risk Assessment among Japanese and US Men in the Post World War II birth cohort (JUMP)

Originating Department: University of Pittsburgh, Department of Epidemiology
Principal Investigator: Akira Sekikawa, MD, PhD
Co-Investigator: Lewis H. Kuller, M.D., Dr.PH
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This is a population-based study of middle aged men (40-49) from the Post World War II birth cohort. 300 white men and 100 black men from Allegheny County, PA, 300 Japanese American men from the population-based sample recruited from the offspring of the members of the Honolulu Heart Program cohort, and 300 Japanese men, randomly selected from Kusatsu City, were recruited and underwent subclinical testing (carotid IMT and plaque, pulse wave velocity and coronary and aortic calcification). The URL serves as the carotid and PWV testing site for the Pittsburgh site and as the carotid IMT training and reading center for all sites. Baseline ultrasound visit for the Pittsburgh cohort was completed in 2006 and offsite reading was completed in 2007. NIH funding was obtained to collect longitudinal subclinical CVD data on this cohort beginning in July, 2008. To date, 153 participants have been seen in the URL. Follow-up clinic visits for the Japan site have started and clinic visits for the Hawaii site are set to begin early in 2010.

Risk Factors for Vascular Stiffness and Effect of Dietary Variables (SAVE)

Originating Department: Epidemiology
Principal Investigator: Kim Sutton Tyrrell, Dr.PH
Co-Investigator: Laura S. Kinzel, MS, RD, LDN
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This is a 4-year NIH funded study following 349 overweight and obese women and men 18-45 years of age with lifestyle intervention including one arm with sodium restriction. The URL was involved in coordinating the start up of the study including coordinating the pre-pilot and pilot study, development of new URL data collection forms and implementation of new heart rate variability technology in the lab for this study. Participants are currently undergoing 5 URL tests (carotid scan, Complior PWV, Colin PWV, EFS and ANSAR). The URL is also responsible for data entry of all URL data. Recently, SAVE recruitment ended with a total of 349 participants randomized.

The effects of Aromatase inhibitors on the gonadal hormone profile and cardiovascular risk factors in postmenopausal women with non-metastatic breast cancer. (SILHOUETTE)

Originating Department: Children’s Hospital of Pittsburgh
Principle Investigator: J van Londen, MD, MS
Co-Investigator: Susan L. Greenspan, MD
EDC Project Coordinator: Kim Sutton Tyrrell, Dr.PH

This study is designed to confirm and extend our preliminary research results in a prospective setting, increase our knowledge of the effect and time of onset of aromatase inhibitors on hormonal milieu and anthropometric/metabolic measures which has been under-explored thus far.

Epidemiology of Cardiovascular Disease in Women with Rheumatoid Arthritis

Originating Department: Rheumatology and Clinical Immunology
Principal Investigator: Mary Chester Wasko, MD, MSc
Research Coordinator: Amy Cunningham

Rheumatoid arthritis (RA) patients suffer significant reduction in life expectancy due in part to premature cardiovascular (CV) disease, especially myocardial infarction and congestive heart failure. Women ages 30-60 appear to be at highest risk. In this four year study, a total of 100 women between the ages of 30 – 60 will be studied. Carotid ultrasounds will be performed on all of the participants.

Effects of Weight Loss and Orlistat on Insulin Resistance, Tissue Lipid and Atherosclerosis in Type 2 Diabetes Mellitus

Originating Department: Epidemiology
Principal Investigator: David E. Kelley, MD
Research Coordinator: Cindy Kern, RN, CCRC

The goal of this study is to investigate the effects of weight loss in patients with Type 2 Diabetes Mellitus achieved by diet, exercise and administration of the recently approved weight loss medication orlistat, on tissue content of lipid in liver, skeletal muscle and as visceral fat.

The study will:

Examine the effect of changes in body composition on insulin resistance and metabolic control
Examine the effect of changes on progression of atherosclerosis in coronary arteries and aorta and
Examine whether changes in adiposity reduce levels of inflammatory markers (as risk factors linking obesity and atherosclerosis).
Risk Factors for Vascular Stiffness and Effects of Dietary Variables: (VAST)
Originating Department: Epidemiology
Principal Investigator: Kim Sutton-Tyrrell, Dr.PH
Research Coordinator: Trina Thompson, RN, MPH, RVT

Vascular stiffness can be viewed as a measure of the biologic aging of the arterial vessels. A total of 1250 participants are being studied ranging from 20-70 years of age. A variety of vascular stiffness methodologies will be used and carotid duplex scans will also be performed on most participants.

The study will:

Determine risk factors associated with vascular stiffness, by measuring vascular stiffness in three different ways in a variety of populations.
Determine the reliability of various measures of arterial stiffness. These comparisons will help researchers establish standards for measurement and reporting vascular stiffness.
Prevalence and Progression of Subclinical Atherosclerosis Through the Menopausal Transition (SWAN Heart)
Originating Department: Epidemiology
Principal Investigator: Kim Sutton-Tyrrell, Dr.PH
Research Coordinator: Alicia Colvin, BA

This is a coordinated project between the University of Pittsburgh and Rush-Presbyterian-St.Luke’s Medical Center in Chicago. Subclinical atherosclerosis will be evaluated in 728 African American and Caucasian women enrolled in the Study of Women Across the Nation (SWAN), a multicenter study characterizing the biological and psychological sequelae of menopause. Serial measures of coronary and aortic calcification (by EBCT), carotid atherosclerosis, endothelial function and aortic stiffening will be performed two years apart. The prevalence and progression of subclinical atherosclerosis will be evaluated in relation to serial measures of ovarian function, psychosocial and behavioral factors, markers of clotting and inflammation as well as traditional cardiovascular risk factors, all collected in SWAN.

The study will evaluate the extent to which diminishing ovarian function affects vascular function and accelerates the development of atherosclerosis in the coronary arteries, aorta, and carotid arteries.

Pittsburgh Healthy Heart Project (PHHP)

Originating Department: Department of Psychology
Principal Investigator: Thomas W. Kamarck, PhD

This project is designed to examine a variety of biobehavioral influences on the 3-year progression of subclinical cardiovascular disease (carotid atherosclerosis and left ventricular mass) in asymptomatic older adults. The lab performs carotid IMT measures, echocardiography and vascular stiffness measures (PWV).

We hypothesize:

That individuals who show exaggerated cardiovascular reactivity to psychological challenge may show an increased rate of disease progression, and
That exposure to frequent and intense psychological challenge during daily life, as measured by ambulatory monitoring methods, may exacerbate these effects.
That differences in the types and frequency of socially supportive transactions may be associated with altered rates of disease progression.
That differences in endothelial functioning and vascular stiffening may mediate some of these observed associations between behavioral factors, on the one hand, and subclinical disease, on the other.
Diabetes Prevention Program: (DPP)
Originating Department: Psychology
Principal Investigator: Rena R. Wing, PhD
EDC Research Coordinator: Gaye Koenning, MS, RD

The purpose of this study is to prevent or delay the development of noninsulin dependent diabetes mellitus (NIDDM) in individuals who are at high risk for its development by virtue of having impaired glucose tolerance. Lifestyle intervention and two pharmacologic treatments (metformin and troglitazone) will be studied. Secondary goals are to reduce macrovascular risk factors that accompany IGT and NIDDM. The lab performs carotid duplex scans for this study.

Risk of Coronary Heart Disease in Women with Polycystic Ovary Syndrome (CHARM/PCO)

Originating Department: Epidemiology
Principal Investigator: Evelyn O. Talbott, Dr.PH
EDC Project Leaders: Jeannie Zaboroski Dr.PH

PCOS is a reproductive endocrine disorder characterized by lack of ovulation and excess male hormones (androgens). It affects approximately 5% of all women and appears to be related to early heart disease in females. In Phase I of the study (1992-1994), PCOS cases were found to have an adverse lipid and metabolic profile that conferred increased cardiovascular risk. During Phase II (1997-99), intima-media thickness (IMT) and plaque formation in the carotid arteries were evaluated in PCOS cases and controls 30+ years of age and older by B-mode ultrasonography at the Ultrasound Research Laboratory. Mean intima-media wall thickness was greater for women with PCOS than controls, particularly among women aged 45 years and older, suggesting early vascular changes in these relatively young women. The URL is conducting these important follow-up studies.

The study will:

Identify the risk factors for premature atherosclerosis and heart disease among women with PCOS.
Evaluate progression of vascular disease in this high-risk PCOS population as measured by increased IMT and plaque development since baseline.
Carotid Atherosclerosis and its Relationship to Risk Factors Pre and Post-menopause (HWS & WHLP)
Originating Department: Epidemiology
Principal Investigator: Kim Sutton Tyrrell, Dr.PH

Analysis stage

The purpose of this study is to evaluate risk factors for early atherosclerosis in women and to compare the prevalence and extent of disease before and after menopause. The risk of atherosclerosis rises after women go through menopause. Changes in risk factors such as blood pressure, weight and lipid values which accompany menopause are likely to be part of the reason. The Women’s Healthy Lifestyle Project (WHLP) is a clinical trial testing the efficacy of dietary intervention in preventing an increase in LDL cholesterol at the time of menopause. We propose to obtain carotid ultrasound exams in 420 of these women. The prevalence and extent of carotid atherosclerosis in these premenopausal women will be compared to a cohort of women enrolled in the Healthy Women Study (HWS) who are 5 to 8 years postmenopausal and have been followed since premenopause. A comparison of carotid atherosclerosis between the HWS and WHLP cohorts will allow us to determine the extent to which this disease was present prior to menopause. This work will also allow us to establish a baseline measure of carotid atherosclerosis so that these women can be evaluated for future progression of atherosclerosis following menopause.

Epidemiology of Cardiovascular Disease in Lupus Women (LUPUS)

Originating Department: Rheumatology
Principal Investigator: Susan Manzi, MD, MPH
EDC Project Coordinator: Shirley Fitzgerald, MS

This study is designed to establish a large cohort (n=400) of women with lupus and to (1) estimate the prevalence of subclinical vascular disease measured by carotid duplex scanning and flow-mediated endothelial dilation and compare this to results in a comparison group of similar age and distribution, (2) to determine the risk factors associated with subclinical vascular disease and (3) to determine if the presence of subclinical vascular disease predicts clinical events (myocardial infarction, angina, stroke, and transient ischemic attack).

Carotid Disease and Reactivity in Postmenopausal Women

Originating Department: Psychology
Principal Investigator: Karen Matthews, PhD
Co-Investigator: Kim Sutton Tyrrell, Dr.PH

This project is one of four that comprise a Program Project grant. In this study, carotid atherosclerosis will be measured in the first 400 participants who are five years post menopausal in order to evaluate the reactivity hypothesis and to test if the relationship between stress-induced responses and atherosclerosis vary according to women’s exposure to post menopausal hormone replacement therapy and to other key biological risk factors, especially waist-hip ratio, resting blood pressure, and fasting insulin, and glucose levels. The extent that associations between psychosocial characteristics and atherosclerosis are mediated by cardiovascular responses to stress will be examined.

Antecedents of the Type A Behavior Pattern (Project Pressure)

Originating Department: Cardiovascular Behavioral Medicine
Principal Investigator: Karen A. Matthews, PhD
Research Coordinator: Diana Buck

Adolescence is an important period to study the development of cardiovascular disease (CVD) risk factors because CVD risk factors track in adolescents and predict clinical CVD later in life and because behavioral and biological risk factors tend to cluster together in adolescents. This study proposes to re-assess 165 black and white, male and female high school students enrolled in Project Pressure three years after their initial assessment to address key hypotheses regarding the early emergence of behavioral risk factors for CVD in adolescence and their antecedents and consequences.

The following hypotheses will be tested:

Adolescents who are from low SES families will report more stressful life circumstances, including unfair treatment and discrimination, will be more mistrustful of others, and more vigilant for possible threat, will exhibit greater vascular resistance responses to stressful tasks; and will have elevated scores for subclinical CV markers, compared to adolescents from higher SES families.
Adolescents who report more stressful life circumstances, unfair treatment, and discrimination and who are high in hostility, vigilance for threat, and CV responses to stress will have elevated scores for subclinical CV markers, i.e. IMT, vascular stiffness, and LVM.

A Program Project Grant entitled: Biobehavioral studies of cardiovascular disease. Project 2: Blood pressure, reactivity, metabolism and serotonin.

Originating Department: Department of Psychology and the Division of Clinical
Pharmacology, Department of Medicine
Principal Investigator: Matthew F. Muldoon, MD, MPH
Research Coordinator: Jennifer White

Many risk factors for heart disease — including high blood pressure, high cholesterol, high blood sugar or diabetes, obesity, and altered regulation of the heart and blood vessels by the nervous system — tend to cluster in the same individuals. The purpose of this study is to measure these risk factors and the degree of early atherosclerosis (hardening of the arteries, which causes heart attacks and strokes) in a group of 300 healthy adults between 35 and 55 years of age.

Specific Aims

Are biological, psychosocial, socio-environmental, and lifestyle-related risk factors for cardiovascular disease correlated with individual differences in brain serotonin (serotonergic responsivity)?
Are individual differences in brain serotonin the, or one of the, causes of clustering of risk factors within individuals?
Do differences in brain serotonin correlate with early vascular disease, measured as carotid artery thickness and endothelial function?

The Epidemiology of Diabetes Intervention and Complications (EDIC)

Originating Department: Dept. of Epidemiology
Principal Investigator: Trevor J. Orchard
Research Coordinator: Nancy Silvers

The EDIC study is primarily an epidemiologic investigation of the natural history of vascular disease in IDDM, which takes advantage of an intention-to-treat analysis based on previous involvement of the study population in the DCCT. In 2001 a genetic sub study was approved which added diabetic and non-diabetic parents/siblings to the study.

We will:

Study risk factors for the later complications of diabetes including advanced kidney disease (renal failure), macrovascular complications (including coronary heart disease) and lower extremity arterial disease – complications that could not be studied in the DCCT.
Study the natural history of macro and micro vascular disease in IDDM, which also takes advantage of an “intention-to-treat analysis” based on previous involvement of the study population in the DCCT.
Treatment influences on cognitive and cerebrovascular consequences of hypertension (PET)
Originating Department: Cardiovascular Psychophysiology
Principal Investigator: J. Richard Jennings, PhD
Research Coordinator: Mary Assenat

Hypertension contributes to significant cardiovascular morbidity and mortality in the U.S. and often goes undetected and untreated. This study looks at the cerebrovascular and cognitive performance effects of hypertension and hypertension treatment. PET scans, MRI scans, brachial artery ultrasound, and neuropsychological testing are used for evaluations. Participants are men and women between ages 35 and 65 years with untreated hypertension. We provide either a beta-blocker or an ACE inhibitor throughout the study to control hypertension.

Specific aims:

The ACE inhibitor, lisinopril, will be superior to the beta-blocker, atenolol, in normalizing regional cerebral blood flow.
The ACE inhibitor, lisinopril, will be superior to the beta blocker, atenolol, in enhancing working memory performance; and that this effect will be larger in those hypertensive patients that prior to treatment show relatively reduced cerebrovascular reserve and working memory capability.

Fetal Growth Restriction and Maternal Cardiovascular Risk (WISH)

Originating Department: Graduate School of Public Health
Principal Investigator: Roberta Ness
EDC Project Coordinator: Gail Harger

This is an NHLBI funded study comparing cardiovascular risk factors and subclinical atherosclerosis (carotid IMT, PWV and endothelial function testing) among women who delivered babies with intrauterine growth retardation (IUGR) and control women without IUGR babies. The last participant for WISH was seen in the URL in January 2009 for a total of 663 tested. Recruitment of 200 additional women was initiated last year as part of a URL research and development supported pilot study evaluating women with pre-term births.

Preventing Adverse Effects of Class II and Class III Obesity Re-Energize with Nutrition, Exercise and Weight loss (RENEW)

Originating Department: Division of Endocrinology & Metabolism
Principal Investigator: Bret Goodpaster
EDC Project Coordinator: Angela DiPasquale

This is a lifestyle intervention study funded by the PA Department of Health of 120 individuals with class II and III obesity collecting similar data to the SAVE study. The URL clinic visits take place at the ONRC clinic in Montefiore (UPMC). The URL has done extensive work in adapting the NIA PWV system and devising a protocol for both the carotid IMT and the PWV measures for obese participants and currently provides one tech, and the PWV system for RENEW. In order to compare the SAVE and RENEW cohorts, the URL also conducted a pilot study comparing the new Complior PWV system to the traditional NIA PWV system, as well as the two ultrasound scanners being used for measuring carotid IMT. To date and through this progress period, there have been 217 RENEW participant visits.

Ovarian Aging Study pilot study (OVA)

Originating Department: University of California, San Francisco
Principal Investigator: Maria E. Bleil, PhD
EDC Project Coordinator: Emma Barinas-Mitchell, PhD

This is a pilot study to examine the relation between reproductive aging and early markers of CVD risk among pre-menopausal women. The current study will include a representative subsample of participants (n=175) from an existing population-based, multi-ethnic cohort of 978 premenopausal women in the OVA Study who will return for a 3-year follow-up study visit. Antral follicle count (AFC), an index of total follicular reserve, and change in AFC over 3 years, an index of the rate of follicular loss, will be examined in relation to preclinical atherosclerotic disease indexed by carotid artery intima-medial thickness (CIMT). The URL has certified the CA site sonographer for collecting carotid scan images and reads the carotid scans.

Preterm Delivery and Maternal Cardiovascular Disease Risk (POUCH MOMS)

Originating Department: University of Pittsburgh
Co-Principal Investigator: Janet Catov, PhD
EDC Project Coordinator: Emma Barinas-Mitchell, PhD

This is a follow-up study of women enrolled in the Pregnancy Outcomes and Community Health (POUCH) Study, a prospective cohort enrolled from 1998-2004 designed to examine pathways to preterm delivery. The current project will evaluate CVD risk factors and carotid IMT and adventitial diameter a decade later in women with prior preterm births. The URL functions as the carotid training, QC, and reading center.

Ectopic Cardiovascular Fat and Subclinical Atherosclerosis (PVATPITT)

Originating Department: University of Pittsburgh
Principal Investigator: Samar El Khoudary, PhD
EDC Project Coordinator: Emma Barinas-Mitchell, PhD

This is a small pilot study to assess perivascular adipose tissue in a sample of 100 Pittsburgh participants from the Study of Women’s Health Across the Nation (SWAN).

Effect of Weight Loss on Atherogenic Risk in Distinct Obesity Phenotypes in Teens (New York) (OAB)

Originating Department: Albert Einstein College of Medicine
Principal Investigator: Unab Khan, MD, MS
URL Co-Investigator: Emma Barinas-Mitchell, PhD

This study was funded via a K-23 grant to evaluate 200 obese adolescents at baseline and 9 months following a clinic based weight management program. The URL provides the training and reading for carotid IMT measurements. This project is partially funded by the URL.