Approved research

The pathogenesis, predictive value and clinical utility of arterial stiffness.

Lay summary

We will: 1. Identify genes and risk factors related to arterial stiffness (AS) assessed using a) the PulseTrace device (PTD) and b) magnetic resonance imaging (MRI); 2. Identify genes and risk factors predicting worsening PTD-AS and identify if PTD-AS predicts worsening blood pressure; 3. Use genetic information to explore the direction of causal relationships linking arterial stiffness, hypertension and cardiovascular events. 4. Examine whether AS assessed by PTD or MRI predicts cardiovascular events beyond that achieved using traditional risk factors. 5. Assess whether particular antihypertensive drug classes are associated with preferential clinical benefits in relation to arterial stiffness. Arterial stiffness is an independent predictor of cardiovascular events that can be measured noninvasively using the PulseTrace device (PTD) and by assessing aortic distensibility and pulse wave velocity using magnetic resonance imaging (MRI). The main aim of this research is to better understand the molecular mechanisms leading to arterial stiffness. By understanding these mechanisms, appropriate treatments can be developed that could reduce the risk of heart attacks and strokes especially in patients predisposed to arterial stiffness such as those with diabetes. Cardiovascular disease has major health, economic and societal impacts so there could be widespread benefits from this research. Routinely collected UK Biobank data from baseline, follow-up and imaging examinations and conventional statistical methods including genome-wide association studies will be used to: a) Identify genes and traditional cardiovascular risk factors related to arterial stiffness (AS) and worsening of AS; b) Assess whether AS has a causal role in cardiovascular events (Mendelian randomisation studies) and incident hypertension (traditional epidemiology); c). Assess whether AS assessed by PTD and MRI predict cardiovascular events beyond that achieved using traditional risk factors;[1,2] d) Relate antihypertensive drug class used by participants to arterial stiffness, blood pressure levels and CVD events. We will study the subsets - people with: a) PulseTrace device (PTD)-measured arterial stiffness (AS) data (n~200K) b) Magnetic Resonance Imaging (MRI) derived data on aortic distensibility/pulse wave velocity (n~100K) c) Manchester-based participants with baseline and 4-year follow-up data who had AS assessed by PTD or MRI at any time (~10K). These participants will be involved in cross-sectional, prospective, genome-wide association and Mendelian randomisation studies.