Specialist registrar in renal medicine at Ninewells Hospital, Dundee, Dr Graham Stewart told delegates: "The effect of this on subsequent end-stage renal failure cardiovascular mortality isn't yet known, but is an exciting potential therapeutic option."

He explained that LVH was common in patients approaching end-stage renal failure (ESRF) but was also seen early in the progression of the disease.

This caused particular problems because the hypertrophied myocardium in uraemic patients was less compliant, less-well oxygenated, and more at risk of ischaemia and arrhythmias. It was, therefore, along with ischaemic heart disease, a major risk factor for death in renal patients.

Anaemia, he continued, played an important role on the development of LVH in uraemic patients. In observational studies both anaemia and hypertension are associated with the presence of LVH. Moreover, a reduction in haemoglobin levels has been shown to be closely correlated with growth of the left ventricle in patients with declining renal function.

"The hypertrophied hearts of uraemic patients have a reduced capillary density and a resultant reduction in blood supply," Graham Stewart told delegates.

"Those blood vessels also have impaired function. They don't vasodilate the way they should do. In addition, factors such as fibrosis of heart muscle around the vessels interferes with dilatation. So, the muscle becomes ischaemic. The clinical results of this in dialysis patients are silent myocardial ischaemia evident with elevated troponin -T levels and arrythmias leading to sudden death."

"We know that having left ventricular hypertrophy on dialysis is associated with at least a threefold increase in mortality. And a study from Glasgow in the late 1990s has shown that even in patients who have had successful transplantation, those with left ventricular hypertrophy or dilatation when they came in for transplant, were more likely to subsequently die."

"The natural history of LVH in progressive renal disease has been made clearer by a Canadian observational study which looked at the impact of reduced haemoglobin on left ventricular mass in a group of almost 450 patients with varying degrees of chronic renal failure. It followed them up for a year doing cardiac examinations at the start and the end of the period. It found that overall 34% had left ventricular hypertrophy and the predisposing factors for that were reduced haemoglobin, increased systolic blood pressure and reduced creatinine clearance."

"More importantly 28% of those with mild disease had left ventricular hypertrophy, and over the year 25% of the total group significantly increased their left ventricular mass," he said. "The factors associated with left ventricular growth were an increase in systolic blood pressure and reduction in haemoglobin."

"The influence of anaemia and hypertension on LV mass was also demonstrated in similar research carried out in Glasgow. Although the LVM of patients with primary renal disease was significantly greater than matched controls, even when excretory function was near normal. An increase in LV mass was only seen when creatinine clearance fell below 60ml/min, a level of function recognised to be associated with the development of renal anaemia."

"The relationship between anaemia and LVH was explored further using cardiac MRI to measure and calculate cardiac output and vascular resistance in a sub group of these patients. Comparing normals, CRF patients (Creat. ~200µmol), and haemodialysis patients we found significantly greater LV mass between all three groups with worsening renal function. While the greater LV mass in CRF patients was due to an increased vascular resistance, in the haemodialysis patients it was the result of increased cardiac output with associated vasodilatation. These are physiological changes that occur in the context of anaemia, and indeed our haemodialysis patients had a significantly lower haemoglobin level than the other groups."
"It appears therefore that patients with renal disease have increased LV mass at an early stage, largely due to vascular stiffness and elevated blood pressure. When anaemia develops there is accelerated LV growth with the result we are familiar with of more than 70% of patients reaching ESRF with LVH."

"What remains to be proven is whether the treatment of anaemia can alter the excessive cardiovascular death rate seen in ESRF. While we know from several small studies that that it is possible to regress LVH in advanced CRF and ESRF, we also know from the Normalisation of Haematocrit Trial that partial correction of anaemia in patients with ESRF and clinically evident cardiovascular disease does not improve survival. This may be because these patients have cardiac disease that is already too advanced."

"The intriguing question, which will hopefully be answered by trials such as CREATE, is whether the prevention of anaemia with early EPO therapy in CRF can prevent the detrimental effect on the heart and reduce subsequent cardiovascular mortality."

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