Lifestyle, Biomarkers and Atherosclerosis the LBA study

Transcription

1 Lifestyle, Biomarkers and Atherosclerosis the LBA study Ulrika Fernberg

2 Aim of the LBA study The aim of the project is to assess vessel wall structure and function in a large cohort of young individuals and to compare the subgroups with the lowest and highest intima-media thickness. This approach will help to identify biomarkers and lifestyle factors involved in the preclinical process of vessel wall remodeling preceding atherosclerosis

3 Study population Recruitment of 1000 subjects aged 18.0 to 25.9 years (50% females), non-smokers without known disease - self-reported healthy Recruitment by advertising and social media Two visits, about 1 hour each, no premium paid (breakfast offered and some results)

4 Baseline measurements (all subjects) First visit Questionnaires for assessment of demographic data and family background variables and heredity for cardiovascular disease + RAND-36; questionnaire on health & quality of life Dietary habits will be evaluated using Livsmedelsverkets questionnaire Matvanekollen ( and devide the participats into three groups based on fruit&vegetable consumption, fat consumption etc

5 Baseline measurements (all subjects) First visit Blood pressure Flow mediated dilatation (FMD); high resolution ultrasound (GE Vivid E9, UK) Blood sampling Height, weight and waist circumference and body fat percentage (Tanita impedance scale ) Breakfast + Handing out accelerometer (Actigraph ) for physical activity registration (1 week)

6 Baseline measurements (all subjects) Second visit Feedback on blood analyses Hand grip Intima-media thickness in a. carotis communis; high resolution ultrasound (GE Vivid E9, UK) Blood pressure (second check) Aortic pulse wave velocity as an index of aortic stiffness and pulse wave analysis to determine central blood pressure (SphygmoCor ) Submaximal ergometer bike test (modified Åstrand, heart rate steady state for calculation of max VO 2 )

7 Blood analyses (all subjects) Venous blood sample (100 ml in total) Preparation and freezing procedures (plasma, serum, cells, PBMC) Detection of total cholesterol, HDL and LDL cholesterol, triglycerides, ApoB/ApoA, high sensitivity CRP, insulin, glucose, orosomukoid Extraction of DNA for later genetic analyses Extended analyses in subgroups, for example genotypes

8 Subgroup analyze of peripheral blood flow Laser Doppler flowmetry (PeriFlux system 5000, Perimed AB), a measure of peripheral circulation will be estimated and compared with measures of ultrasound vessel results and pulse wave velocity in a subsample of 100 randomly selected subjects

9 Flow mediated dilatation, a. brachialis Foto: Anita Hurtig-Wennlöf

10 Flow mediated dilatation, a. brachialis Ghiadoni, L, et al. Evaluation of endothelial function by flow mediated dilation: methodological issues and clinical importance. High Blood Press Cardiovasc Prev. 2015;22(1):

11 Flow mediated dilatation, a. brachialis Preocclusion Flow Vessel diameter Occlusion 5 minutes Postocclusion Flow Vessel diameter 30s Vessel diameter 45s Vessel diameter 60s Vessel diameter 90s

12 Flow mediated dilatation, a. brachialis Nichols, WW, O Rourke MF, Vlachopoulos C. McDonald s Blood Flow in Arteries, Theoretical, Experimental and Clinical Principles. 6th edition. CRC Press, London,

13 Flow mediated dilatation, a. brachialis Nichols, WW, O Rourke MF, Vlachopoulos C. McDonald s Blood Flow in Arteries, Theoretical, Experimental and Clinical Principles. 6th edition. CRC Press, London,

14 Intima media thickness, a carotis communis Martini. Fundamentals of Anatomy and Physiology. Ninth edition. Pearson, San Fransisco,

15 Intima media thickness, a carotis communis Foto: Ulrika Fernberg

16 Pulse wave analysis, a. radialis Foto: Ulrika Fernberg

17 Pulse wave analysis, a. radialis Nichols, WW, O Rourke MF, Vlachopoulos C. McDonald s Blood Flow in Arteries, Theoretical, Experimental and Clinical Principles. 6th edition. CRC Press, London,

18 Pulse wave analysis, a. radialis Nichols, WW, O Rourke MF, Vlachopoulos C. McDonald s Blood Flow in Arteries, Theoretical, Experimental and Clinical Principles. 6th edition. CRC Press, London, 2011 Adji, A, et al. Arterial stiffness, its assessment, prognostic value, and implications for treatment. Am J Hypertens. 2011;24(1):

19 Pulse wave velocity, a. carotis & a. femoralis

20 Peripheral blood flow, laser doppler (Perimed) Foto: Eva Oskarsson

21 Laser doppler technique

22 Provocation with heat or occlusion Minson, C. T. Thermal provocation to evaluate microvascular reactivity in human skin. 2010;109(4):

23 Study status report Data collection closed in June subjects included (1/3 males) Holiday Cleaning data procedure Affected accelerometry files (firmware issue) Compiling a database Working with first manuscript

24 Preliminary results Carotid intima media thickness 0,50±0,06 mm VO 2 ml/kg/min woman 37,8±8,5, men 42,9±9,8 Carotid intima media thickness was correlated to systolic blood pressure, waist circumference and VO 2, P<0,

25 Preliminary results Using a risk score (Wildman), 12.1% of the participants were classified as being at risk for CVD. Food habits did not differ between those at risk and the rest. Aerobic fitness measured as VO 2 ml/kg/min however differed, 46.5% of persons at risk had low aerobic fitness compared to 23.4% of the non-risk participants, P<

26 Wildman s risk score Wildman, R. P et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES ). Arch Intern Med. 2008;168(15):

27 Preliminary results In the studied population 15.3% was insulin resistant (HOMA-IR) before the age of 26 years. 35.1% of the females and 24.5% of the males had low HDL-C according to Wildman s cutoff. Higher VO 2 was significantly associated with beneficial levels of HOMA-IR, HDL-C, body fat, indicating that higher aerobic fitness is protective in this age group

28 Questions?

29 Thank you for listening!