White matter damage is associated with poor outcome in vascular surgery claudicant patients


The results of the BAROSLEEP study, published in the December issue of the European Journal of Vascular and Endovascular Surgery, show that microstructural white matter damage is associated with poor outcome in peripheral arterial disease patients with claudication requiring surgical revascularisation. Timo Laitio, Division of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland, the study lead investigator, spoke to Vascular News about the study and its clinical implications.

What was the objective of the BAROSLEEP study?


We started this investigator-initiated prospective trial in 2006 and patient recruitment ended in 2010. The primary objective of this study was to identify the group of the patients with peripheral arterial disease at the highest risk for major adverse cardiovascular and cerebral events after vascular operations and also develop new tools to identify these patients. It is common knowledge that vascular surgery patients are at exceedingly high risk of postoperative mortality or poor long-term prognosis in general. In the BAROSLEEP trial, we have investigated the following: 1) Preoperative alterations in autonomic nervous system (ie. heart rate variability and baroreflex sensitivity) during various sleep stages in patients with peripheral arterial disease with and without obstructive sleep apnoea scheduled for vascular surgery, and the association and predictive value of those alterations  with postoperative adverse events; 2) The predictive value of preoperative ischaemic white matter injuries for outcome; 3) and the relation between white matter injury and the severity of obstructive sleep apnoea in patients with peripheral arterial disease.

How was the study performed?


During the recruitment period (2006–2010), 142 eligible patients were screened, 82 were enrolled, and a written consent was obtained from each of them. Also, 20 healthy age-matched control patients were enrolled. Patients aged 40 years and over with peripheral arterial disease referred to Turku University Hospital (Turku, Finland) for elective subinguinal revascularisation were eligible for this prospective cross-sectional study. All patients and control subjects went through a preoperative polysomnography, physical examination and echocardiography. In 2008, we amended the MRI studies after we realised the potential of new imaging techniques as predictive tools in these patients. There had been MRI studies showing that patients with obstructive sleep apnoea have white matter injuries; however, patients with both peripheral arterial disease and obstructive sleep apnoea had not been studied in this respect. In BAROSLEEP, a follow-up of up to seven years was carried out.

What are the results and how do you interpret them?


Patients with obstructive sleep apnoea and peripheral arterial disease have significant, diffuse and widespread white matter injuries, and their severity is associated with long-term prognosis. Our findings demonstrate that diffusion tensor imaging of magnetic resonance may also have prognostic value not only in patients with acute neurological syndromes but also in a population with chronic, systemic disease. The spatial distribution of microstructural white matter alterations in current patients was very widespread with no clear predisposition to specific parts of the brain. We consider this to reflect the diffuse nature of small vessel disease of the brain in our patient group. Numerous studies have shown that the loss of white matter microintegrity demonstrated with diffusion tensor imaging is associated with arterial hypertension, elevated pulse pressure, diabetes, metabolic syndrome and peripheral arterial disease itself. Therefore, lower white matter fractional anisotropy values may reflect worse overall cardiorespiratory and metabolic status of patients. This could explain current results where peripheral arterial disease patients with lower white matter fractional anisotropy values had poorer long-term outcome with higher incidence of major adverse cardiac events.

What has the study concluded?


Results of the BAROSLEEP trial have led us to the following conclusions:

  • Obstructive sleep apnoea is common in peripheral arterial disease with an incidence of 85 % and it is mainly undiagnosed (Eur Respir J 2013 Mar, 41:616-20)
  • Obstructive sleep apnoea is associated with major cardiac events and is associated with poor long-term outcome in patients with peripheral arterial disease. Obstructive sleep apnoea might have an important role in the pathogenesis of cardiovascular morbidity and mortality in these patients (Eur Respir J 2014; 43: 1652-60)
  • Microstructural white matter damage was associated with poor outcome in peripheral arterial disease patients with claudication requiring surgical revascularisation, and its extent may have clinical value in risk stratification.(Eur J Vasc Endovasc Surg 2014; 48:687-93).


How can the results of the study impact clinical practice?


We should keep in mind that a major part of these patients have obstructive sleep apnoea and the patients with Apnea-Hypopnea Index (AHI) higher than 20 have higher risk than the others for major postoperative cardiac events. AHI correlates very highly to oxygen desaturation index (ODI). So, monitoring ODI before surgery may enable us to identify a patient with relatively higher risk. We need further understanding of whether any intervention is able to improve the prognosis of those patients with AHI over 20. In addition, a patient with obstructive sleep apnoea and peripheral arterial disease cannot be recognised by classical signs of obstructive sleep apnoea eg. obesity or daytime sleepiness. These patients do not have such signs or symptoms. Moreover, more severe preoperative white matter injury in patients who will have major adverse cardiac events during long-term follow-up was shown in a group of patients, not individually.

What are the next steps in this investigation?


We will need further understanding of the clinical impact of white matter injuries in these patients, its progress during time and relation with the progress of the peripheral arterial disease itself and also how all this is related to eg. neurocognitive impairment or whether treatment changes the progress of white matter injury. The significance of white matter injury should be studied at an individual level. That will need further knowledge of the normal values in different age groups and also in different parts of the brain. We included patients with very strict inclusion criteria and therefore further studies are warranted with more severe peripheral arterial disease.