Utrecht Cardiovascular Cohort - The Second Manifestations of ARTerial disease Study

The prognosis of patients with vascular disease or vascular risk factors is
largely determined by the progression of atherosclerosis. Therefore patients
with symptomatic vascular disease are treated for multiple purposes: to improve
vascularization to the specific organs and to improve the traditional risk
factors, reducing morbidity and mortality caused by cardiovascular disease. The
traditional risk factors (smoking, cholesterol, hypertension) can only
partially predict the prognosis of the individual patient. Other factors which
may contribute to the progression of atherosclerosis in patients with
clinically manifest vascular disease are hardly known.

In 1996 the Second Manifestations of ARTerial disease (SMART) study was started
at the University Medical Centre Utrecht (UMCU). This study started solely as a
research study and was independent of patient care. Later, in 2002, SMART was
fully integrated into patient care and since that time it consists of two
parts: 1) a patient care component and 2) a scientific component. These two
components are not always strictly seperated. For example, sometimes for the
scientific research data is used from patient care. But when a tumor of the
kidney is found by an abdominal ultrasound, the treating physician and the
patients will be informed immediately.

Patients visiting the UMCU for the first time with a TIA (transient ischemic
attack), stroke, carotid stenosis, peripheral vascular disease, aneurysm
abdominal aorta, angina pectoris, myocardial infarction, renal insufficiency,
diabetes mellitus, hyperlipidemia, hypertension, HIV, preeclampsia and
intrauterine growth retardation in the past, will be asked to participate in
the UCC-SMART Study and are offered the patient care part and the scientific
part.

The purpose of UCC-SMART is to create multidisciplinary care of patients with
cardiovascular disease and to create at the same time, by building a vascular
cohort, a scientific infrastructure.

The main questions of UCC-SMART are:
* What is the risk profile of patients at high cardiovascular risk and what is
the interdependence of these risk factors?
* What factors predict morbidity, mortality and diabetes in a high-risk
population and what are the differences between different vascular beds and
risk factors?
* What is the additional prognostic value of new cardiovascular risk factors
(genes, exosomes, adipokines, coronary calcium and other imaging parameters)
for new vascular events and mortality?
* Does the use of the UCC-SMART risk score (risk mapping, multidisciplinary
therapy advice) improve patient care?

To answer many scientific questions results of new tests that have not been
entered are neccessary as well as data from patient care
Other scientific questions are elaborated in various substudies.

UCC-SMART is an ongoing prospective cohort study. All included patients are
asked to complete a questionnaire annually. The treating physician carries out
the examinations he or she considers to be neccessary for the primary visit.
Subsequently the research nurse or doctor's assistent approaches, orally or in
writing, the patient to participate in UCC-SMART. After approval an appointment
will be made to perform the remaining tests.
The studies take a total of 3 hours and are all performed at the same morning.
First, fasting blood samples and a urine portion of the patient will be
obtained. After this, in the radiology department, multiple tests will be
performed. Next an ECG will be made, after this a CT scan.


The inclusion of patients is largely delegated to the cooperating divisions
(vascular center, vascular medicine, infectious diseases, neurology,
obstetrics, cardiology and cardiac surgery) each following their own
procedures. To detect patients with clinically manifest disease, EZIS is used.
These patients receive, after an appropiate waiting time, the information
leaflet of SMART. If the patient is interested, he or she will send the signed
informed consent back to the SMART office. A nurse of the SMART office will
contact the patient by telephone and checks whether all information is clear.
The patients are given the opportunity to ask questions and after this an
appointment for the screening will be made.

Nature of investigations
The following studies are carried out in the framework of UCC-SMART :
* A questionnaire on heart disease in which the following types of questions
are discussed. The questions are as follows: 1. General | 2. Familiy history of
cardiovascular disease | 3. Heart | 4 Brains | 5. Legs | 6. Blood pressure,
diabetes , cholesterol | 7. use of oral contraceptives, menstruation, pregnancy
| 8. Smoking, alcohol, nutrition | 9. Physical exercise | 10. Quality of life .

Several risk factors are determined:
• blood pressure
• height, weight , waist and hip
• Hb , Ht
• total cholesterol , triglycerides, HDL-C, LDL-C, (fasting ) glucose and HbA1c
• TSH and Insulin
• HsCRP
• Apo B
• serum creatinin, microalbuminuria and creatinin
•Troponin
•NT-pro-BNP
•Plateletfunction
•Insulin
•GWAS
* The screening conducted studies / measurements :
• Ultrasound of the abdomen, with the questions: abdominal aortic aneurysm
(max. AP diameter juxta -renal and infra -renal aortic ) and kidney atrophy (
kidney length and volume ) bilaterally
• duplex examination of the carotid arteries on both sides, to show a carotid
stenosis
• the ankle - brachial index at rest for diagnosis of peripheral artery disease
• intra-abdominal fat with ultrasound
• a 12-lead electrocardiogram
• CT scan of heart and neck vessels

* Of all patients in the UCC-SMART cohort the biological material is stored .
Blood is stored in -80 ° C freezers, in the form of serum, citrated plasma,
EDTA - plasma and packed red cells. Urine is stored in normal form and in
acidified ( pH = 2-3 ) frozen form and stored at -20 º C. DNA is isolated and
stored .

If the ultrasound examinations, ECG or the EAI are performed less than a half
year ago or a CT scan of the heart and neck vessels was made less than a year
ago in the UMCU, those results will be acquired. If the treating physician
requests tests which are included in the SMART screening these results will be
used. Sometimes a is patient included in the UCC-SMART study after the second
visit to the treating physician. Results of the laboratory tests closest to the
first clinic visit will be collected to avoid influence of already established
therapy.

Therapy advice
The screening results will be collected the same day and prepared for the
therapeutic advice. In a multidisciplinary advisory committee, under the
responsibility of a vascular internist, a definitive treatment advice is
formulated. This committee meets once a week.
To formulate the therapeutic advice the multidisciplinary guideline
Cardiovascular riskmanagement is used. For blood pressure, this means that a
maximum value of 140/90 mmHg is accepted.
The cholesterol policy depends on the absolute 10-year risk of the patient. If
LDL > 2.5 mmol / l with a low absolute 10-year risk of 10 %, LDL reduction is
not recommended. With a high absolute risk (> 20 %), it is recommended to lower
LDL. With an absolute 10-year risk between 10-20 % the cholesterol policy
depends on other risk factors as recommended in the guidelines. In diabetic
patients and glucose abnormalities the ADA guidelines are consulted.
In case of an abnormal ankle-brachial index, the guidelines peripheral vascular
disease will be used. For smoking and obesity, lifestyle advices will be given.
If a carotid stenosis >70% is determined by duplex the patient will be, in
consultation with the treating physician, referred to a neurologist.
The therapy advice will be send to the referring specialist or the GP. The
patient receives a summary of the results of the screening, also stating which
attention and / or treatment is needed: the so-called personal screening
profile. Results falling in the normale range and not judged by the vascular
team as abnormal, will not be listed in the screening profile. The time period
between screening and completion of the screening profile is 1.5 - 2 weeks.

Follow-up
All patient in the cohort will be followed. This means that of all patients in
the UCC-SMART cohort the occurence of new vascular events is accurately
recorded. The patient is approached once a year with a short questionnaire
whether he / she has been hospitalized and whether in the past year diabetes
mellitus or dementia has been diagnosed. If a vascular complication has
occured, this will be further investigated. At the beginning of the study the
patients are asked to inform the SMART office in case of rehousing. If patients
find the follow-up to burdersome, possible endpoints will be collected via the
GP.

The burden of patients for participating in the study is the time needed for
all examinations. In contrast, the patients receive a structured therapeutic
advice

Adverse events
Complications caused by an examination of the UCC-SMART study is reported
according to the appropriate channels (MIP). Endpoints are not considered
adverse events because in UCC-SMART no experimental interventions take place.

Incidental and secondary findings
Incidental findings are often detected by the staff of the radiology
department. If an incidental finding is found, the UCC-SMART doctor is
informed. Findings found with an ultrasound are discussied with the
radiologist. The radiologist determines further management (supplementary
investigations or other follow-up). Every incidental finding will be recorded
in the file of the patients. Uncomplicated cysts and known abnormalities do not
require consultation.

If abnormalities are found, such as aneurysm of the abdominal aorta >3.5cm,
abnormal blood tests or ECG abnormalities with clinical consequences, the SMART
doctor is always informed and the SMART doctor presents the found abnormalities
to the appropiate specialist from the UCC-SMART study and the treating
physician to determine further management. The SMART doctor does not discuss
findings directly with the patient. A short report of the findings and
consequences will be made by the SMART doctor and will be send to the treating
physician and the GP.

The following guidelines concerning incidental findings are followed:
- only inform the patient about incidental findings if therapeutic consequences
are neccessary
- advice on the incidental finding and possible therapeutic consequences will
be sought by relevant experts
- Incidental findings are well communicated to the specialist or GP
- All findings and actions are documented in the status of the patient