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Association of mild hyperhomocysteinemia with cardiac graft vascular disease
Insights
Mild hyperhomocysteinemia is common in heart transplant recipients and significantly more frequent in those with graft vasculopathy. Elevated homocysteine may play a role in the development of this vascular complication.
Area of Science:
- Cardiology
- Transplantation Immunology
- Vascular Biology
Background:
- Mild hyperhomocysteinemia is an established risk factor for vascular disease in non-transplant patients.
- Graft vasculopathy is a major cause of late graft loss after heart transplantation.
- The association between hyperhomocysteinemia and graft vasculopathy remains unclear.
Purpose of the Study:
- To investigate the association between hyperhomocysteinemia and graft vascular disease in heart transplant recipients.
- To compare plasma homocysteine levels in patients with and without graft vasculopathy.
Main Methods:
- Fasting total plasma homocysteine levels were measured in 18 heart transplant recipients with graft vasculopathy and 18 matched recipients without graft vasculopathy.
- Graft vasculopathy was diagnosed by coronary angiography, defined as stenoses >= 25% or aneurysms.
- All patients were receiving cyclosporine immunosuppression.
Main Results:
- Hyperhomocysteinemia (>= 15 micromol/l) was prevalent in heart transplant recipients.
- Hyperhomocysteinemia was significantly more frequent in patients with graft vasculopathy (17/18) compared to those without (11/18).
- Mean plasma homocysteine levels were significantly higher in the graft vasculopathy group (23.6+/-7.8 micromol/l) versus the control group (16.9+/-7.1 micromol/l, P=0.01).
Conclusions:
- Hyperhomocysteinemia is common in heart transplant recipients and strongly associated with graft vasculopathy.
- Elevated homocysteine levels in these patients may be multifactorial, potentially linked to renal failure, azathioprine treatment, or genetic factors.
- Homocysteine may contribute to the pathogenesis of graft vascular disease, independent of immunological factors.
Abstract:
In non-transplant patients mild hyperhomocysteinemia is an independent risk factor for vascular disease. The aim of this study was to determine whether hyperhomocysteinemia is associated with graft vascular disease. Fasting total plasma homocysteine was assessed in 18 patients with graft vasculopathy and 18 transplanted patients without graft vasculopathy matched for age, sex and the time since transplant. All were on cyclosporin. Graft vasculopathy was defined at coronary angiography as stenoses > or = 25%, or aneurysms. We found that hyperhomocysteinemia ( > or = 15 micromol/l) is common among transplanted heart recipients and significantly more frequent in the patients with graft vasculopathy (17/18 versus 11/18). Accordingly, the mean homocysteinemia was significantly higher in the group with graft vasculopathy (23.6+/-7.8 versus 16.9+/-7.1 micromol/l, P=0.01). The elevation of homocysteine plasma levels in the heart transplant recipients has probably multiple causes. The main cause seems to be renal failure. Additional causes could be azathioprine treatment or genetic polymorphisms. These results suggest that besides the immunological factors, homocysteine can play an additional role in the pathogenesis of graft vascular disease.