The epidemiology of hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations

Donaldson, James W. (2016) The epidemiology of hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations. PhD thesis, University of Nottingham.

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Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited genetic disorder of blood vessel development characterised by mucocutaneous telangiectasia and arteriovenous malformations (AVMs). There are no recent epidemiological studies of the prevalence of HHT in the UK, and no population-based studies investigating the burden of disease complications and mortality in this country.

Some of the most devastating complications of HHT such as stroke and cerebral abscess arise as a result of AVMs developing in the pulmonary circulation. Current evidence for the management of pulmonary AVMs using percutaneous embolisation derives from relatively small cohorts published by specialist centres worldwide. No studies have attempted to pool this published literature to summarise the complication rates and efficacy of embolisation. Additionally, there is uncertainty as to whether the apparent low mortality associated with treatment of PAVMs (published in the worldwide literature) is also replicated in the experiences of UK centres currently undertaking the procedure.


This research project used large-scale, representative primary care (The Health Improvement Network - THIN) and secondary care (Health Episode Statistics - HES) databases to investigate the prevalence, comorbidities and mortality related to HHT, and the mortality related to treatment for pulmonary AVMs. We further used epidemiological methods to summarise the worldwide published literature regarding the safety and efficacy of percutaneous embolisation as a treatment for pulmonary AVMs.

The specific questions addressed in the studies were;

1. What is the current UK prevalence of HHT and how does this vary with respect to sociodemographic factors?

Using a primary care database (THIN), prevalence rates and adjusted prevalence rate ratios were calculated for HHT and pulmonary AVMs stratified for age group, sex, calendar year, socioeconomic status and geographical location.

2. What are the significant complications and comorbidities associated with HHT?

A case-control study using THIN examined the common complications associated with a diagnosis of HHT and looked at commoner cardiovascular and malignant comorbidities that may be associated with a diagnosis of HHT.

3. What is the mortality related to HHT in the UK?

A case-control study in THIN compared mortality between over 600 cases of HHT with age, sex and primary care practice matched controls, analysing mortality trends by age, sex and socioeconomic status.

4. What is the safety and effectiveness of percutaneous embolisation as a treatment for pulmonary arteriovenous malformations?

A systematic review and meta-analysis of published studies worldwide looking at safety and effectiveness of embolisation was undertaken.

5. What are the current mortality trends in England for patients undergoing percutaneous embolisation for treatment of pulmonary arteriovenous malformations?

Using an extract from the HES database linked to Office for National Statistics death data we investigated mortality associated with embolisation for arteriovenous malformation in England over a 15 year period.


1. The minimum prevalence of diagnosed HHT in the UK was calculated to be 1 in 9,400, with the disease more commonly diagnosed in the female sex, those from older age groups, those from higher socioeconomic groups and patients from certain geographical areas of the UK.

2. A variety of haemorrhagic and neurological complications were commoner in HHT than matched controls including stroke (odds ratio (OR) 1.81) , cerebral abscess (OR 30), epistaxis (OR 11.6) and gastrointestinal haemorrhage (OR 6.08). The odds of cardiac failure (OR 2.36) and colon cancer (OR 2.76) were significantly higher in those with HHT when compared to controls.

3. The hazard ratio for death in HHT cases was twice as high as their matched controls. The median age at death in HHT cases was three years younger than their matched controls.

4. Percutaneous embolisation appears to be a safe procedure for embolisation of pulmonary arteriovenous malformations with a major complication in less than 1% of procedures undertaken. It is effective in 84% of patients who undergo embolisation, or in 90% of lesions treated.

5. The mortality associated with percutaneous embolisation between 1997 and 2011 in England is very low and may be zero.


HHT has a UK prevalence in line with that described in studies from other countries worldwide, though as this prevalence is only in those with diagnosed disease, the true prevalence is likely to be significantly higher. HHT is associated with significant haemorrhagic and neurological complications and HHT cases have a higher mortality than their matched controls. Percutaneous embolization appears to be a safe and effective treatment for pulmonary AVMs worldwide and is associated with a very low mortality in England.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Fogarty, A.
McKeever, T.
Keywords: Hereditary haemorrhagic telangiectasia, Pulmonary arteriovenous malformations
Subjects: W Medicine and related subjects (NLM Classification) > WG Cardiocascular system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 38737
Depositing User: Donaldson, James
Date Deposited: 16 Dec 2016 06:40
Last Modified: 12 Oct 2017 21:49

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