Lifestyle, Biomarkers and Atherosclerosis –the LBA study

Ulrika Fernberg

2016-10-11 1

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.

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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)

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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” (www.slv.se/MatvanekollenProjekt) and devide the participats into three groups based on fruit&vegetableconsumption, fat consumption etc

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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)

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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 VO2)

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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

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Subgroup analyze of peripheral blood flow

Laser Doppler flowmetry (PeriFlux system 5000,Perimed AB) , a measure of peripheral circulation will beestimated and compared with measures of ultrasoundvessel results and pulse wave velocity in a subsample of100 randomly selected subjects

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Flow mediated dilatation, a. brachialis

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Foto: Anita Hurtig-Wennlöf

Flow mediated dilatation, a. brachialis

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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):17-22

PreocclusionFlowVessel diameter

Flow mediated dilatation, a. brachialis

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Occlusion 5 minutes

PostocclusionFlowVessel diameter 30sVessel diameter 45sVessel diameter 60sVessel diameter 90s

Flow mediated dilatation, a. brachialis

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Nichols, WW, O’Rourke MF, Vlachopoulos C. McDonald’s Blood Flow in Arteries, Theoretical, Experimental and Clinical Principles. 6th edition. CRC Press, London, 2011

Flow mediated dilatation, a. brachialis

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Nichols, WW, O’Rourke MF, Vlachopoulos C. McDonald’s Blood Flow in Arteries, Theoretical, Experimental and Clinical Principles. 6th edition. CRC Press, London, 2011

Intima media thickness, a carotiscommunis

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Martini. Fundamentals of Anatomy and Physiology. Ninth edition. Pearson, San Fransisco, 2011www.skane.se

Intima media thickness, a carotiscommunis

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Foto: Ulrika Fernberg

Pulse wave analysis, a. radialis

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Foto: Ulrika Fernberg

Pulse wave analysis, a. radialis

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Nichols, WW, O’Rourke MF, Vlachopoulos C. McDonald’s Blood Flow in Arteries, Theoretical, Experimental and Clinical Principles. 6th edition. CRC Press, London, 2011

Pulse wave analysis, a. radialis

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Nichols, WW, O’Rourke MF, Vlachopoulos C. McDonald’s Blood Flow in Arteries, Theoretical, Experimental and Clinical Principles. 6th edition. CRC Press, London, 2011Adji, A, et al. Arterial stiffness, its assessment, prognostic value, and implications for treatment. Am J Hypertens. 2011;24(1):5-17

Pulse wave velocity, a. carotis & a. femoralis

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www.complior.com

Peripheral blood flow, laser doppler (Perimed)

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Foto: Eva Oskarsson

Laser doppler technique

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www.perimed-instruments.com

Provocation with heat or occlusion

2016-10-11 22www.perimed-instruments.com

Minson, C. T. Thermal provocation to evaluate microvascular reactivity in human skin. 2010;109(4):1239-46

Study status report

• Data collection closed in June 2016• 834 subjects included (1/3 males)

• Holiday

• Cleaning data procedure• ”Affected accelerometry files” (firmware issue)• Compiling a database• Working with first manuscript

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Preliminary results

• Carotid intima media thickness 0,50±0,06 mm

• VO2 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 VO2, P<0,05

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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 VO2 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<0.01.

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Wildman’s risk score

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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 1999-2004). Arch Intern Med. 2008;168(15):1617-24

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 VO2 was significantly associated with beneficial levels of HOMA-IR, HDL-C, body fat, indicating that higher aerobic fitness is protective in this age group.

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Questions?

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Thank you for listening!

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