Clinical trial NCT03178448: PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events
Official title: PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Healthy Subjects
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2017-06-07
Enrollment: 3067
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The target population of the study consists of community population aged 50-75 years in Lishui city in southeast of China.

Brief summary: The objective of this study is to characterize the prevalence of clinical or subclinical polyvascular lesions and 4-year progression rate of plaque in intracranial and carotidal arteries in a Chinese community population using vascular imaging techniques; to investigate the both traditional and emerging genetic, metabolomic, and environmental risk factors of presence and progression of intracranial and carotidal plaque; and to investigate the association between polyvascular lesions and future risk of cognitive impairment, cardio-/cerebrovascular events and death.

Detailed description: Atherosclerosis is the most common cardiovascular disease and accounts for the greatest number of cardiovascular and cerebrovascular events and death. Polyvascular lesions with coexistent lesions (especially atherosclerosis) in multiple arterial territories (at least 2 of coronary, cerebral, lower extremity arteries), could be associated with higher risk of future cardio-/cerebrovascular diseases. However, previous studies either roughly defined polyvascular diseases according to established clinically recognized arterial diseases in multiple arterial territories, or tested multiterritorial subclinical atherosclerosis without tests of intracranial and peripheral arteries. Furthermore, recent research also showed that cardiometabolic diseases and cardiovascular risk factors are associated with worse cognitive abilities. A thorough evaluation of multiterritorial lesions in whole body used advanced vascular imaging techniques is required to precisely assess the association of polyvascular lesions with future cardio-/cerebrovascular events and cognitive impairment.

Additionally, Asian population might have higher prevalence of intracranial atherosclerosis than the Caucasian, and intracranial atherosclerosis is the most common cause of ischemic stroke in Asia population. However, there are limited data about the prevalence and progression of intracranial atherosclerosis in Chinese population. More and more studies have shown that presence and progression of atherosclerotic plaque is not only related to the degree of stenosis, but also with plaque characteristics such as rich lipid core, plaque hemorrhage and inflammatory cell infiltration. High-resolution magnetic resonance (HR-MRI) can not only show the degree of arterial stenosis, the size of atherosclerotic plaque, but also can analyze the composition of the plaque to assess the stability of the plaque. HR-MRI techniques enable early detection of atherosclerosis, characterization of the atherosclerotic composition and burden. It is important to estimate the prevalence and progression rate of intracranial atherosclerotic plaque based on HR-MRI and to estimate its traditional and emerging determinants in Chinese population.

In this study, a total of 3000 subjects aged 50 to 75 years from 6 villages and 4 communities in Lishui city, Zhejiang province, China, will be enrolled. All the eligible subjects in the selected villages/community will be enrolled based on cluster sampling.

All the participants will be interviewed at baseline and followed up for 4 years. Data collection at baseline will be performed through face-to-face interviews by trained interviewers (neurologists from participating hospitals) with a standardized protocol. Baseline data include demographics, medical history, cardiovascular risk factors, dietary habits, physical activity, lifestyle, medication use, electrocardiogram, vascular imaging tests and Montreal Cognitive Assessment (MoCA). Blood and urine samples will also be collected at baseline to test genetic and metabolomic markers.

The sequences of brain MRI included T1,T2, FLAIR, DWI,ADC,MRA,SWI,T2\*,T1-VISTA, SNAP,3D-T1,resting-state fMRI and DTI. Baseline vascular imaging tests include HR-MRI sequences in intracranial and carotidal arteries, computed tomographic angiography (CTA) in coronary, aorta, renal, hepatic, pancreatic and iliofemoral arteries, and fundus fluorescein photography (retinal photography) in retinal vessel. All MRI scans were performed on 3.0 T Philips scanners. CTA scans were performed on third-generation dual-source Siemens system (SOMATOM Force). HR-MRI sequences were performed both at baseline and after 4 years to identify intracranial and carotidal atherosclerotic stenosis and plaque and measure the intracranial and carotidal vessel wall, lumen area, and plaque when present. Additionally, heart function will be tested using color Doppler echocardiography, and ankle-brachial index will be tested using Doppler ultrasound. All the imaging techniques will be conducted in a fixed machine by fixed trained investigators based on a standardized protocol. These imaging techniques enable early detection of intracranial and extracranial vascular lesions, characterization of the atherosclerotic composition and burden, and monitoring of plaque progression in intracranial and carotidal arteries.

Routine follow-up will be performed each year to collect cardio-/cerebrovascular events and death after enrollment. A further face-to-face interview will be performed at 2 years and 4 years to collect brain MRI scanning and cognitive impairment. At 2-year and 4-year follow-up visits, standard clinical and neuropsychologic assessments will be performed, including MoCA, Mini-Mental State Exam scores, Geriatric Depression Scale, Digit Span, Rey Auditory Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Trail Making A and B, Stroop Task, Verbal Fluency Test, Boston Naming Test, Clock Drawing Test, Symbol Digit Modalities Test, Neuropsychiatric Inventory and Clinical Dementia Rating. Fasting blood and morning urine samples will be collected at each follow-up visit following same protocol as that at baseline.

The protocol of this study was approved by the ethics committee of Beijing Tiantan Hospital and Lishui Hospital of Zhejiang University. All participants provided written informed consents before entering the study.

Eligibility criteria: Inclusion Criteria:

* Community population in Lishui city;
* Age between 50 and 75 years.

Exclusion Criteria:

* Mental illness;
* Advanced cancers or any disease that decreases life expectation to ≤4 years;
* Allergy to iodine contrast, renal failure with creatinine clearance \<60 mL/min, or blood urea nitrogen (BUN) or creatinine (CR) more than upper limit of the normal range that contraindicates CTA;
* Pacemaker, implantable automatic defibrillator, or any implanted device that contraindicates MRI.

Primary outcomes:
measure: New composite vascular event 1
timeFrame: 4 years
measure: New composite vascular event 2
timeFrame: 4 years
Secondary outcomes:
measure: Prevalence of polyvascular lesions, including atherosclerotic stenosis and plaque;
timeFrame: at baseline
measure: 4-year progression rate of atherosclerotic plaque in intracranial and carotidal arteries.
timeFrame: 4 years
measure: Fatal or nonfatal MI;
timeFrame: 4 years
measure: Fatal or nonfatal stroke;
timeFrame: 4 years
measure: Transient ischemic attack (TIA)
timeFrame: 4 years
measure: All causes of death (cardiovascular or noncardiovascular death);
timeFrame: 4 years
measure: Hospitalizations for vascular events;
timeFrame: 4 years
measure: Vascular interventions;
timeFrame: 4 years
measure: Other vascular events (PAD, subclavian steal syndrome and systemic thromboembolic events);
timeFrame: 4 years
measure: New diagnosed diabetes mellitus;
timeFrame: 4 years
measure: New diagnosed chronic kidney disease;
timeFrame: 4 years
measure: Cognitive impairment measured by the Montreal Cognitive Assessment (MoCA).
timeFrame: 4 years
Other outcomes:
Locations:
city: Lishui
country: China
facility: Lishui Hospital of Zhejiang University (the Central Hospital of Lishui)
state: Zhejiang
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
Study officials:
References:
citation: Pan Y, Cai X, Jing J, Wang S, Meng X, Mei L, Yang Y, Jin A, DongXiao Y, Li S, Li H, Wei T, Wang Y, Wang Y. Differential associations of lipoprotein(a) level with cerebral large artery and small vessel diseases. Stroke Vasc Neurol. 2022 Jul 18;7(6):534-40. doi: 10.1136/svn-2022-001625. Online ahead of print.
citation: Pan Y, Jing J, Cai X, Wang Y, Wang S, Meng X, Zeng C, Shi J, Ji J, Lin J, Lyu L, Zhang Z, Mei L, Li S, Li S, Zhu W, Li H, Wei T, Wang Y. PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE)-a population-based prospective cohort study: rationale, design and baseline participant characteristics. Stroke Vasc Neurol. 2021 Mar;6(1):145-151. doi: 10.1136/svn-2020-000411. Epub 2020 Aug 30.