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Cardiovascular Disease Epidemiology Training Program

Atherosclerosis Risk in Communities (ARIC) 
An NHLBI sponsored, multi-centered, observational, prospective study of risk factors for atherosclerosis.  Included were 11,475 whites and 4,260 African-Americans aged 45-64 at baseline (1986-89), from four U.S. communities--Washington County, MD (Johns Hopkins); Forsyth County, NC (Bowman-Gray/University of North Carolina); Jackson, MI (University of Mississippi); and suburban Minneapolis, MN (University of Minnesota).  Data collected at baseline included demographic factors, traditional cardiovascular risk factors, anthropometry, ECG, pulmonary function, carotid arterial ultrasonography and extensive laboratory evaluations of lipoproteins and clotting factors.  Serum and leukocyte samples were taken and frozen for future studies.  The fourth clinic visit (9-year follow-up) was completed in 1998.   Surveillance for coronary artery disease events in these communities is ongoing.  A future visit of a selected subgroup of participants at each site is scheduled to begin in 2005.  This visit will include contrast-enhanced magnetic resonance imaging of the carotid arteries to identify areas of vulnerable plaques.  ARIC investigators at Johns Hopkins include Drs. Josef Coresh (Principal Investigator), Moyses Szklo, Frederick Brancati, Richey Sharrett and Brad Astor.  Data are available for analyses by trainees.  In addition, linking of this data to other data sets collected in Washington County (CLUE I, 1975 private census) offer excellent opportunities for long term longitudinal studies.

ARIC Ancillary Study of Susceptibility Genes for Diabetes, Obesity, and Hyperinsulinemia

ARIC Ancillary Study of Susceptibility Genes for Type 2 Diabetes - Funded by NIDDK, this project seeks to identify associations between functional variants (if known) or estimated haplotypes in candidate susceptibility genes and the risk of type 2 diabetes in a community-based sample of approximately 9000 middle-aged adults from the ARIC cohort.  The list of candidate genes to be evaluated include genes on chromosome 1 (fine mapping project for evidence linkage on chromosome 1), ENPP1, IRS2, and INPPL1, CEBPa, and SREBP1.  Genotyping for multiple SNPs in the aforementioned genes began in March of 2003 at the University of Maryland.  We expect the majority of the genotyping to be completed by summer 2004.  Strengths of this study include its large sample size, an extensive database of traits and behaviors related to diabetes and cardiovascular disease, and the opportunity to investigate gene-gene and gene-environment interactions.  Dr. Brancati is the PI of the project, and Dr. Coresh and Dr. Kao are two key co-Investigators.  This work dove?tails with 2 additional ancillary ARIC studies--one on susceptibility genes for cardiovascular disease headed by Dr. Eric Boerwinkle at the University of Texas, the other on inflammatory and other molecular mediators of diabetes and CVD risk headed by Dr. James Pankow at the University of North Carolina.  By sharing data between studies, Drs. Brancati, Boerwinkle, and Pankow aim to create a unified database for genetic-molecular studies in ARIC.  Two of our former doctoral students--Hsien-Hsien Lei and Linda W.H. Kao conducted their thesis research within the Susceptibility Genes project.  Both collected original genotype data at the bench, via a close collaboration with Dr. Alan Shuldiner, a molecular geneticist, formerly at Johns Hopkins, now Professor of Medicine and Director of the Divisionof Diabetes, Metabolism, and Nutrition at the University of Maryland.

African-American Study of Kidney Disease and Hypertension (AASK)

African-American Study of Kidney Disease and Hypertension (AASK; PI, L. Appel) was a NIDDK-sponsored, multi-center, randomized trial with a 2 x 3 factorial design that tested the effects of two levels of blood pressure control and three different anti-hypertensive regimens on the progression of renal insufficiency in 1,094 African-Americans (64 at Hopkins) with hypertension-related renal disease.  The study population consists of 1094 African-Americans (64 at Hopkins) with hypertension-related renal insufficiency (i.e. a glomerular filtration rate of 20-65 ml/min/1.73 m2).  The study found that angiotensin-converting enzyme (ACE) inhibitors, compared with calcium channel blockers, slowed kidney disease progression by 36%, and reduced the risk of kidney failure by 48% in patients with albuminuria (>1g/day).  The database from this trial provides excellent opportunities for secondary analyses by fellows at Hopkins. 

The Continuation of AASK Cohort Study
Following completion of the AASK trial, the NIDDK funded continued follow-up of AASK participants to investigate the environmental, socio-economic, genetic, physiologic, and other co-morbid factors that influence progression of kidney disease in this well-characterized cohort of African Americans with hypertensive kidney disease.

Cardiovascular Health Study (CHS)
An NHLBI sponsored multi-centered, observational, population based study of risk factors for cardiovascular disease and stroke among men and women 65 and older. The study enrolled 5,201 men and women in four U.S. communities (Forsyth Country, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania).  The data includes extensive interview and physical examination data that establish the presence of cardiovascular disease, disability, and risk factors for cardiovascular disease, as well as carotic ultrasound, echo-cardiographic , and brain MRI data.  These data can be used for student research projects.  Drs. Fried, Szklo, Comstock, and Powe are Hopkins investigators on this project.

Choices for Health Outcomes in Caring for ESRD (CHOICE) 

The CHOICE Study was initiated in October 1995 to examine the impact of dialysis modality, patient preferences and management choices on the outcomes and costs of care. The study was funded by the Agency for Health Care Policy Research (AHCPR) as a Patient Outcomes Research Team (PORT).   Dr. Neil Powe is the Principal Investigator of the PORT.  Drs. Klag, Coresh, and Astor and Ms. Fink are co-investigators. The CHOICE Cohort Study is one of the projects within CHOICE and is based on a collaborative relationship between the Johns Hopkins University and Dialysis Clinic Inc. (DCI), a non-profit chain of dialysis clinics headquartered in Nashville, TN. DCI administers 143 dialysis clinics, 80 of which participate in CHOICE. The dialysis centers in CHOICE are located in 17 states across the country.  The study design is a concurrent prospective study of incident cases of ESRD.  Between 10/95 and 6/98, CHOICE recruited from these clinics 923 participants (80% on hemodialysis, 20% on peritoneal dialysis), 895 of whom have participated in the specimen bank. Another 118 CHOICE participants recruited from two non-DCI clinics were not included in the CHOICE specimen bank. As of 11/03, the mean follow-up per DCI participant was 2.6 years. A total of 108 patients are still enrolled and actively being followed.  This cohort represents the largest cohort of incident dialysis patients ever actively followed.  These impressive recruitment results are even more remarkable considering the intensive data burden for patients who enroll in CHOICE.  This study has provided the setting for several recent doctoral dissertations (Drs. Longenecker, Astor, and Liu).

CHOICE Cohort Specimen Bank 
In 10/95, a specimen bank was established at the DCI central laboratory under the direction of Dr. Coresh. This laboratory annually processes over 3 million routine laboratory tests for patient care. Results are transmitted electronically to the DCI central Medical Information System (MIS), facilitating the collection of laboratory data for the CHOICE study. Nesting this study within a large and efficient laboratory ensures the ability to retain staff, maintain equipment, and ensure quality supervision.  A manual of operations for the CHOICE specimen bank was produced after several collaborative meetings between the investigators at Johns Hopkins, the staff at the DCI laboratory, and the DCI Information Management System Division.  This manual defines the procedures for specimen collection, identification, transport and storage. A customized computer program (Freezer Works, Seattle, Washington) is used to manage the serum bank and to provide printed labels and tracking numbers for specimens. Quality control procedures are implemented on a continuous basis.  An average of 1500 vials are stored each month at -80° Celsius. Half of the vials from each visit are periodically shipped to a similar freezer at Johns Hopkins for redundancy. The collection, identification, transport and storage of specimens is ongoing and efficient. Over 98% of specimens are stored within 48 hours of phlebotomy, and 91% within 24 hours.  As of 3/30/04 the specimen bank contained 88,146 vials from 13,035 visits by 895 patients.  We have thus far collected 11,683 buffy coat specimens from 834 participants.  A total of 38,586 serum vials have also been stored on 880 CHOICE participants.  Of 818 participants, 247 (30.2%) are African American, 528 (64.5%) are White, and 43 (5.3%) are from other races.  As part of a collaboration with Drs.  Zager and Shah at the University of New Mexico to study the role of the aldolase reductase gene in diabetic ESRD, DNA on 801 CHOICE Study participants has already been extracted.  The median DNA yield using half the buffy coat from one visit was 30 Fg, with a range of 13 to 169 mcg.  This amount provides more than ample DNA for determination of a large number of genetic markers.  We have banked buffy coat from a median of 7 visits and therefore should have an average of 240 Fg of DNA per participant.

From the last week in August through November 1974, a total of 25,620 serum specimens were collected in Washington County, MD for a research serum bank.  An additional 182 specimens were obtained in the summer of 1975, making a total of 25,802.  Linkage of the records from this program to those of a private census in the summer of 1975 indicated that almost a third of the adult population of the county had participated.  Participation was best in the age group 35 to 65 years, and was slightly better among females, the better-educated, and nonsmokers.   The stored serum has been used for numerous nested case-control studies.  Dr. Comstock is the founder of this serum data bank and actively encourages students and faculty to take advantage of this valuable resource.

Starting at the end of May 1989, and ending in November 1989, a total of 32,320 blood specimens were collected in Washington County, MD for a second research serum bank.  Preliminary information indicates that about one-third of the population participated, with somewhat greater participation this time among older persons. In addition to storing two 5 ml aliquots of plasma, another small aliquot was preserved with metaphosphoric acid to allow subsequent ascorbic acid assays.  The buffy coat has also been stored at ?70o C.  A brief medical history, a food frequency questionnaire and toenail clippings are available.  These data can be used by future trainees.  Dr. Comstock is the founder of this serum data bank and actively encourages students and faculty to take advantage of this valuable resource.

Chronic Renal Insufficient Cohort (CRIC) 
This NIDDK multicenter cohort study is a longitudinal cohort study of 3,000 persons, ages 21 to 74, with mild to moderate chronic renal insufficiency.  The hypotheses are that a set of nontraditional risk factors is associated with a) progression of chronic renal insufficienty and b) cardiovascular disease and meseaurs of cardiovascular disease progression.  The cohort will be racially and ethnically diverse (40% white/Caucasian, 40% African American, and 20% other), and approximately half will have a diagnosis of diabetes mellitus. Participants in this seven-year prospective study reflect the racial, ethnic, and gender composition of the U. S. ESRD patient population.  Data and specimens obtained in this study will serve as a national resource for investigating chronic renal disease and cardiovascular disease. Establishing this cohort of patients and following them prospectively will also provide an opportunity to examine genetic, environmental, behavioral, and nutritional factors in this population. The study will also assess health care issues and quality of life outcomes.  Baseline data are currently being collected.

Diabetes Prevention Program (DPP) 
This NIDDK-sponsored multi-center (n=25) trial aims to test behavioral and pharmacologic interventions to prevent diabetes and diabetes-related vascular disease in 3,600 adults with impaired glucose tolerance.  The Hopkins research team is headed by Dr. Christopher Saudek, with Dr. Brancati as co-Principal Investigator, and Dr. Kerry Stewart as Co-Investigator.  This team plays a leading role nationally, chairing 3 key committees: a) Screening & Eligibility, b) Outcomes, c) Recruitment Coordination.  The extensive DPP database includes: a) traditional CVD risk factors, b) carotid ultrasonography, c) abdominal fat CT scans, d) extensive dietary, behavioral, and psychological data, and e) oral glucose tolerance tests.  In addtion, DPP maintains a serum and DNA bank.  Since DPP will be in the field through 2003, it will also serve as a venue for ancillary studies.  Drs. Saudek and Brancati are pleased to make this data source available to trainees.

Dietary Approaches to Stop Hypertension (DASH)
(DASH1; PI, L.Appel) was an  NHLBI-sponsored, multi-center, randomized feeding study that tested the effects on blood pressure of whole dietary patterns in 459 persons (124 at Hopkins) with high normal or Stage 1 hypertension.   In DASH1, a post-doctoral fellow (E.Miller) completed and published a major ancillary study at the Hopkins clinical center. As in other trials, the Hopkins clinical center stored specimens of blood and urine at baseline and follow-up. Also, Dr. Appel has a copy of the trial-wide database, available for secondary analyses.

Dietary Approaches to Stop Hypertension 2 (DASH2)

PI, L.Appel) is a NHLBI-sponsored randomized feeding study that will test the impact on blood pressure of three levels of salt intake in two dietary patterns.  The three levels of salt intake (per 2100 kcal) are 150 mmol/d (roughly corresponding to average American intake), 100 mmol/d (corresponding to current national recommendations) and 50 mmol/d (corresponding perhaps to an ideal level of intake).  One of the two dietary patterns corresponds to a typical American diet; the other corresponds to the DASH combination dietary pattern.  Participants receive all of their food for 14 weeks.  The study population will include 400 persons (100 at Hopkins) with above optimal blood pressure and Stage 1 hypertension (systolic BP: 120-159 and diastolic BP of 80-95).  Fellows at Hopkins may apply to conduct secondary analyses from this impressive database.

Egyptian National Hypertension Project 
This large study has carefully collected data on a national probability sample of approximately 5,000 Egyptians.  The data was collected as part of a collaborative effort involving NHLBI, Johns Hopkins, Cairo University and the Egyptian Ministry of Health.  The study includes socio-demographic and health characteristics on all participants.  In addition, detailed data including echo?cardiography, ECG's, and serum and urine laboratory measurements are available on all hypertensives and a random sample of the non-hypertensives.  In selected subgroups, carotid ultrasound measurements, ambulatory blood pressure measurements, and skin color reflectometry have been obtained.  This unique data set is extremely valuable in providing high quality data on a probability sample of an entire economically developing country.  The Principal Investigator, Dr. Appel, welcomes trainee participation in pursuing research questions in this unique dataset.

Incident End-Stage Renal Disease and CVD in a National Cohort 
With support from the Health Care Financing Administration, Drs. Brancati and Powe, in collaboration with officials at HCFA and NCHS, have conducted a non-concurrent prospective cohort study of incident ESRD in a cohort 9,000 adults aged 30-74 who were surveyed in 1976-80 in the course of the Second Health and Nutrition Examination Survey (NHANESII).  Baseline data on exposures derives from the NHANESII database, including data on tradtional CVD risk factors, oral glucose tolerance testing, and extensive health questionnaires.  Data on outcomes derives from 3 independent sources which were linked to NHANESII by name, date of birth, and other personal identifiers: a) National Death Index, b) Social Security Death Index, and c) HCFA National ESRD Registry.  (Linked data on death is now available on-line for public use; ESRD data remains available only at Hopkins).  Studies currently underway by trainees include: Risk of CVD Death in Subclinical States of Glucose Intolerance; Burden of CVD Death Related to Type 2 Diabetes; Comparison of Risk Factors for CVD vs ESRD.

Johns Hopkins Coronary Artery Disease Study 
This study enrolled 99 men aged 50 or less and 103 women aged 60 or less who underwent coronary arteriography at Johns Hopkins Hospital.  Each subject underwent an interviewer administered questionnaire of risk factors for coronary artery disease and a brief physical examination.  In addition, blood was collected and analyzed for lipid, lipoprotein, and apolipoprotein levels.  Serum and DNA were frozen and are available for future studies.

Johns Hopkins Coronary Artery Disease Family Study 
This study enrolled the first degree family members of probands who participated in the Johns Hopkins Coronary Artery Disease Study.  Over 1000 subjects in 120 families have been enrolled.  Each subjects underwent an interviewer administered questionnaire of risk factors for coronary artery disease and a brief physical examination.  In addition, blood was collected and analyzed for lipid, lipoprotein, and apolipoprotein levels.  Serum and DNA were frozen and are available for future studies.

Incident CVD in a National Cohort of Diabetic Elders 
Directed by Dr. Frederick Brancati in collaboration with Dr. Gerry Anderson of the Department of Health Policy and Management, this project aims to identify socio-demographic and clinical care factors which predict incident CVD, CVD-related health care utilization, and CVD death in a nationally representative cohort of diabetic 188,000 adults aged 65 and older.  This cohort is drawn from a 5% probability sample of all US Medicare beneficiaries in 1994.  Two years of follow-up are currently available; 3 additional years of follow-up will become available by 2001.  All data are derived from Medicare claims, including information on age, sex, race, and county of residence, as well as medical conditions, outpatient visits, hospitalization, diagnostic and therapeutic procedures, and death.  The large sample size provides the opportuntiy to investigate less common cardiovascular events such as lower extremity amputation related to peripheral vascular disease, aneurysmal diseases, and complications of medical procedures.  The dataset also provides data on cost and utilization of direct relevance to policy making.

Multi-Ethnic Study of Atherosclerosis (MESA)
The major goals of this project are to determine characteristics related to the progression of subclinical to clinical cardiovascular disease, identify factors related to the newer measures of subclinical disease and examine these relationships to existing measures, and to develop population based methods suitable for application in future screening of persons at high risk.  A diverse and representative sample of approximately 7,000 men and women aged 45 to 84 without clinical history or symptoms of coronary artery disease were recruited from six field centers. The Baltimore field center recruited nearly 1,100 ethnically and socio-economically diverse women and men from along the Baltimore Metro line, which has as its final stop Johns Hopkins Hospital. The wide range of socio-economic among various ethnicities to be sampled in Baltimore provides an excellent opportunity to investigate the relationships of ethnicity to subclinical and clinical cardiovascular disease, controlling for socioeconomic status.  Field center examinations consisted of anthropometry, ankle and arm blood pressure, phlebotomy, electrocardiography, carotid ultrasound for intima-medial thickness, brachial ultrasound for vascular reactivity, magnetic resonance imaging of the heart, and electron beam computerized tomography (EBCT) for coronary calcium, as well as collection of information on demographic characteristics, socioeconomic status, smoking history, physical activity, diet, and medical history.  Traditional and novel serum measurements will include lipoprotein analysis, measures of hemostasis, infection, and inflammation, and genetic testing. Two of four planned visits have been completed.  Follow-up for morbidity, medical care, and mortality will be obtained by annual telephone contact, medical record review, and death certificate surveillance. For out-of-hospital deaths, investigation will include physician and proxy interviews.  Morbidity events will include angina, myocardial infarction, transient ischemic attacks, stroke, and congestive heart failure. Medical care variables will include hospitalizations, interventions, and medications.  The investigators leading this project, Drs. Szklo (PI) and Lima (Co-PI), gladly invite trainees to plan ancillary studies and conduct analyses of existing data using this novel database.

(PI: L. Appel) is a NHLBI-sponsored randomized trial that will test the impact on blood pressure of 2 comprehensive lifestyle intervention programs in comparison to a traditional, information-oriented advice program.  One of the lifestyle intervention programs will promote weight loss, exercise, sodium reduction and moderation of alcohol intake.  The other program will promote a desirable dietary pattern in addition to weight loss, exercise, sodium reduction and moderation of alcohol intake.  The desirable dietary pattern is based upon results of the DASH clinical trial which demonstrated that a diet rich in fruits, vegetables and low-fat dairy products and reduced in saturated fat, total fat and cholesterol can lower blood pressure substantially.  The duration of the intervention period is 18 months.  The study population will include 800 persons (200 at Hopkins) with above optimal blood pressure or Stage 1 hypertension (systolic BP: 120-159 and diastolic BP of 80-95).  As in prior trials conducted by Dr. Appel, this trial provides an impressive infrastructure for ancillary studies that could be conducted by fellows at Hopkins.

Population Based Case-Control Study of End-Stage Renal Disease 
For his doctoral dissertation Dr. Perneger (1993a) conducted a population-based case-control study of ESRD in collaboration with Drs. Whelton and Klag.  The study population consisted of community-dwelling residents of Maryland, Virginia, West Virginia and Washington D.C., 20-64 years old, who possessed a telephone.  Cases were new patients who started ESRD therapy between 1/1/91 and 7/31/91.  Of the 752 eligible patients, 716 (95%) were interviewed and age matched population controls were selected by random digit dialing. Questionnaire data was collected on a  wide range of exposures and it is planned to collect DNA samples on all participants.

Project Sugar  
This NIH-sponsored randomized, controlled trial with 4 parallel arms sought to determine the benefits of behavioral interventions on control of CVD risk factors in 186 urban African Americans with type 2 diabetes.  The 3 intervention arms are: a) Nurse-Case Manager intervention, b) Community Health Worker intervention, c) Combined NCM-CHW intervention, which were compared to usual care alone.  The extensive database includes detailed information on attitudes, social support, health behaviors, mental health, glycemic control, and microalbuminuria, as well as information on traditional CVD risk factors.  Participants were followed for up to three years.  This project provided the setting for a former doctoral trainee, Tiffany Gary, to conduct her masters and thesis research.  The baseline and follow-up data from this study are available to trainees.

Project Sugar II 
This randomized controlled trial was designed to test the hypothesis that a primary-care-based NCM plus CHW team approach is an effective, practical, and economically feasible strategy for translating current knowledge about type 2 diabetes into high-quality health care for urban African-Americans.  Participants were randomized t a) usual medical care plus minimal telephone intervention implemented by a trained lay health educator (control group) or b) usual medical care plus intensive intervention implemented by a nurse case manager (NCM)/community health worker (CHW) team.  A total of 542 urban African-Americans with type 2 diabetes were enrolled and followed for 2 years.  Follow-up was completed recently, and both baseline and follow-up data are available to trainees.

Risk Factors for End-Stage Renal Disease in MRFIT Screenees 
Over 350,000 men were screened in 1973-1975 for entry into the MRFIT clinical trial and approximately 160,000 men and women were screened for possible inclusion in HDFP. Drs. Klag and Brancati have collaborated with the MRFIT and HDFP investigators in studying risk factors for vascular disease in the kidney.  

The Johns Hopkins Precursors Study
This is a prospective longitudinal study of 1,337 medical students in the classes of 1948-64.  The study was initiated in 1947 and has conducted annual follow-up ever since.  As such, it is one of the longest continuously functioning studies of its kind.  It has contributed over 120 peer-reviewed manuscripts to the scientific literature.  The Precursors Study is funded by three NIH RO-1 awards and is a major scientific resource available to students. In addition to information on over 6,000 variables at baseline, a multitude of data are available over follow-up, including morbidity and mortality. A number of pre- and post-doctoral trainees have taken advantage of this resource to answer important scientific questions and to publish first author manuscripts and many more research questions can be addressed by future trainees.

The Sleep Heart Health Study (SHHS)  
SHHS was established in 1994 as a multicenter cohort study of the cardiovascular consequences of sleep-disordered breathing (SDB).  The study's principal aims are to assess SDB as a risk factor for adverse cardiovascular outcomes, including incident CHD events, stroke, and hypertension, and accelerated increase in blood pressure with age.  The SHHS protocol added an assessment of SDB to ongoing cohort studies of cardiovascular and other diseases, including the Framingham Offspring and Omni cohorts, the Hagerstown and Minneapolis/St. Paul sites of the Atherosclerosis Risk in Communities (ARIC) Study, the Hagerstown, Sacramento, and Pittsburgh sites of the Cardiovascular Health Study (CHS), the Strong Heart Study sites in South Dakota, Oklahoma, and Arizona, and cohort studies of respiratory disease in Tucson and of hypertension in New York.  The SHHS has collected high quality polysomnography (PSG) data obtained in the home from 6,440 participants and these data have been scored at the Central Reading Center.  The SHHS cohort includes 3,039 men and 3,401 women 40 years of age or more, of whom 8.2% are African American, 9.6% are American Indian, 1.3% are Asian, and 4.2% are Hispanic.  In addition to PSG, data collection covered snoring and sleepiness and quality of life (QOL).  Outcome assessment protocols are in place for all cohorts and the second SHHS exam is now in progress.  Initial cross-sectional findings show that SDB is common and associated with hypertension and self-reported cardiovascular disease (CVD).  Drs. Jon Samet and Naresh Punjabi direct the Johns Hopkins SHHS center, and would be delighted to have additional trainees work with this dataset.

National Mortality, Morbidity, and Air Pollution Study (NMMAPS) 
Time-series studies have shown associations between air pollution concentrations and CVD morbidity and mortality.  These studies have largely been conducted within single cities with varying methods. Key questions remain unaddressed concerning the findings, including 1) the extent of the heterogeneity of air pollution effects across locations and its sources; 2) the effect of measurement error on the estimated effect of air pollution; and 3) the public health significance of the short-term associations.  NMMAPS comprises the development of methods to address these questions and their application to national data sets on mortality and hospitalization among persons 65 years of age and older, as an index of morbidity.  For analyzing mortality data from multiple locations and summarizing the findings, a Bayesian hierarchical regression method has been developed and applied to data from 20 cities.  Time-series analyses of Medicare data from multiple locations are in progress.  Frequency domain regression methods have been used to assess mortality displacement, with the initial finding that air pollution effects can be assessed in time-response bands that are relatively resistant to short-term mortality displacement.  The conceptual basis of measurement error in time-series studies has been developed and the consequences of measurement error are being comprehensively explored using available data sets.  In the next phase of NMMAPS, the morbidity and mortality analyses will be completed and the combined analyses of CVD morbidity and mortality will be undertaken.  The methods of NMMAPS should prove useful for future surveillance for the cardiopulmonary effects of air pollution.  The study’s PI, Dr. Jon Samet, believes that this dataset would be an excellent research setting for trainees interested in the possible environmental basis of CVD.

Trials of Hypertension Prevention-Phase 1 
(TOHP1, Co-PI: L.Appel) was an NHLBI-sponsored, multi-center clinical trial that evaluated the short-term effects of 3 single component lifestyle interventions (weight loss, reduced sodium intake and stress management) and 4 nutrient supplements (magnesium, calcium, potassium and fish oil) on blood pressure in 2,182 persons (289 at Hopkins) with a diastolic blood pressure of 80-89 mmHg.  In addition to the trialwide database, the Hopkins clinical center stored specimens of blood and urine at baseline and follow-up, and conducted an ancillary study on cardiovascular reactivity.  In a follow-up study, a graduate student (J.He) completed his dissertation and subsequently published several articles.  New fellows have the opportunity for additional ancillary investigations and secondary analyses.

Trials of Hypertension Prevention-Phase 2 
(TOHP2, Co-PI: L.Appel) was an NHLBI-sponsored  2x2 factorial trial that tested the long-term effects on blood pressure and incident hypertension of a reduced sodium intake and/or weight loss in 2,382 overweight individuals (262 at Hopkins) with a diastolic blood pressure of 83-89 mmHg.  As in TOHP1, the Hopkins clinical center stored specimens of blood and urine at baseline and follow-up; opportunities for ancillary investigations and for secondary analyses are available.

Trial of Non-Pharmacologic Interventions in the Elderly 
(TONE, Co-PI: L.Appel) was an NIA/NHLBI sponsored clinical trial that tested the efficacy of sodium reduction and/or weight loss in maintaining satisfactory BP control in 975 elderly persons (301 at Hopkins) after withdrawal of anti-hypertensive medications.  As in TOHP1 and 2, the Hopkins clinical center stored specimens of blood and urine at baseline and follow-up.  Also, Dr. Appel has a copy of the trialwide database, from which a fellow could perform secondary analyses.

Womens Health & Aging Study (WHAS I and WHAS II)
Participants in this NIA-sponsored observational study are selected at random from among women aged 65 and over living in community residences in 12 zip codes areas of Baltimore City and County. The initial sample includes 5, 500 women, stratified by age so as to ensure sufficient numbers in the oldest age groups. A brief screening interview is identifying approximately 1,700 women who are moderately to severely disabled. Of these, 1,000 agreed to participate in WHAS I--a study aimed at identifying predictors of functional decline in moderately disabled women.  These women completed a baseline interview and an examination conducted in their homes by a nurse practitioner that includes performance-base measures of disability. Follow-up interviews are conducted with participants every six months.  An important component of the investigation is the determination of the causes of the disability experienced by these women. The study is primarily investigating the role of major chronic diseases in causing disability, including coronary heart disease, congestive heart failure, stroke, intermittent claudication, diabetes.  Data from the interviews are supplemented by information abstracted from medical records at hospitals and physicians offices to verify the presence and severity of specific diseases and conditions. A team of clinicians reviews each case and decides what conditions cause the limitations of functioning. The three-year follow-up information will be used to assess the long term changes in disability and factors that influence the direction and rate of change. In addition, the study will assess the role of cognition and a range of other psychosocial factors in modifying the ways in which diseases cause disability.  Similar procedures have been followed in a cohort of 600 non-disabled women (selected from the original sampling frame) with the goal of identifying predictors of early (as opposed to late) functional decline (WHAS II).  The investigation represents a next step in the progression of epidemiologic research on older populations. It addresses a need for more detailed, more biomedically oriented research to be done on a smaller, more intensively studied yet representative sample of older women. The results of this study are expected to break new ground by identifying the opportunities for prevention of disability progression in older adults.  Both studies are led by Dr. Linda Fried, in collaboration with Dr. Jack Guralnick at NIA, who has already mentored several post-doctoral fellows with this dataset.  Dr. Fried invites further participation by students in the training program.

Project WIN
(PI: L.Appel) is a single center, randomized trial, sponsored by the Bristol-Meyers Squibb Foundation, that will determine the effectiveness of a comprehensive lifestyle intervention program on blood pressure in 60 African-American women.  The lifestyle intervention will be a culturally appropriate program, adapted from successful interventions that accomplished lifestyle changes in predominantly non-African-American populations.  The intervention will promote  weight loss, exercise, sodium reduction, moderation of alcohol intake, and a desirable dietary pattern.  A unique aspect of this program will be delivery of the intervention by trained community workers.  Recruitment will be complete in October 1999; data collection will be complete one year later.   Results of this trial should provide evidence on the effectiveness of culturally appropriate, lifestyle intervention programs that could be implemented in the general community.

Public-Use Datasets
Several unique public-use datasets have been the subject of extensive investigation by members of the Hopkins team.  The familiarity produced by this prior work will facilitate subsequent investigations by trainees.  These datasets include: - Medicare ESRD Registry, used by Drs Klag, Brancati, and Powe to investigate incident ESRD trends- NHANESII Mortality Follow-up Study, used by Dr. Brancati to investigate CVD death- NHANESIII, used by Drs. Coresh and Astor to investigate renal insufficiency and by Dr. Brancati to investigate the possible role of hepatitis and liver disease as risk factors for the occurrence of diabetes.