Purpose:

Cardiac allograft vasculopathy (CAV) remains one of the primary causes of death in long-term follow-up after heart transplantation (HTx) and is the most limiting factor leading to reduced graft function. The prevalence of CAV has not significantly been reduced despite the development of novel immunosuppressive medications.

In addition to immunological pathogenesis, several non-immunological factors are well known risk factors for native coronary artery disease as well as CAV eg. smoking, diabetes, and hypercholesterolemia. Furthermore, increasing data suggests induction of atherosclerosis and cardiovascular disease are associated with air pollution. Therefore, we hypothesized that air pollution could also play a role in the development of CAV.

Methods:

In order to assess the potential impact of air pollution on CAV, we selected 50 consecutive patients with angiographic-confirmed moderate or severe CAV (ISHLT 2 or 3) that visited our out-patient clinic and 52 consecutive patients without CAV (ISHLT 0). All patients were at least 5 years post-HTx. Based on air pollution data published by the German Environment Office, we estimated the exposure of all patients to particulate matter (PM) of different sizes (eg. PM2.5 and PM10) By stepwise forward and backward Cox regression, we analyzed PM2.5 and PM10 load, body mass index, CMV-infection, postoperative need for dialysis, diabetes, and hypertension, as potential risk factors.

Results:

There were no statistically significant differences between patients with or without CAV concerning body mass index, donor and recipients' CMV-antigen status, previous CMV-infection, number of previous organ rejections, diabetes, or hypertension. However, both regression types found dialysis (p<0.0010, HR=9.0) and PM10 (p=0.016, HR=1.15) to be independent significant risk factors for advanced CAV. A significantly higher number of patients with progressed CAV were exposed to higher air pollution than patients without CAV. The rate of CAV in patients exposed to <15 [micro]g/m³ PM10 was 25%; 15-20[micro]g/m³ – 46%; 20-25[micro]g/m³ – 55%; and >25[micro]g/m³ – 69%. Interestingly, PM2.5 load was not an independent risk factor in our population.

Conclusion:

Air pollution should be considered as an additional risk factor in the development of CAV after HTx. Further investigations are necessary to confirm these observations in a larger study population and to identify the underlying pathological mechanisms.

CITATION INFORMATION: Bara C, Böthig D, Scheibner Y, Bobylev D, Przybylek B, Haverich A. Air Pollution – An Additional Risk Factor for Developing Cardiac Allograft Vasculopathy. Am J Transplant. 2016;16 (suppl 3).

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