VALIDD: Lowering Blood Pressure Improves Diastolic Dysfunction

March 26, 2007

March 26, 2007 (New Orleans, LA) - Lowering blood pressure can improve diastolic dysfunction even in patients with mild hypertension, a new study has shown.

The Valsartan in Diastolic Dysfunction (VALIDD) trial, presented today at the American College of Cardiology 2007 Scientific Sessions, is the first large-scale randomized trial to assess a therapeutic intervention for improvement of diastolic function using new noninvasive Doppler technology. The study's primary objective was to compare the effect on diastolic dysfunction of two antihypertensive regimens--one based on an inhibitor of the renin angiotensin system (RAS) and one based on other medications--in patients with mild hypertension. While there was no difference between these two groups, both groups showed a substantial reduction in blood pressure that was itself associated with a significant improvement in diastolic dysfunction.

Lead investigator Dr Scott Solomon (Brigham and Women's Hospital, Boston, MA) said: "Our study has shown an important result. Diastolic dysfunction is an important pathophysiology between hypertension and heart failure, affecting around half of hypertension patients. Patients with diastolic dysfunction have an increased risk of developing heart failure, but there is no targeted therapy for this condition. This study suggests that lowering blood pressure is the most important thing we can do for patients with hypertension and diastolic dysfunction and shows that we need to be more aggressive in this regard even in patients with only mildly elevated blood pressure."

Dr Randall C Starling (Cleveland Clinic, OH), cochair of the late-breaking clinical-trial session at which these results were presented, agreed. "Although this trial did not show a difference between the two regimens studied, there is still a very important public-health message here," he commented.

Introducing the trial, Solomon noted that although many studies have shown that treating hypertension can regress left ventricular hypertrophy (LVH), the effect on diastolic dysfunction is not known. "There is a tremendous amount of research focusing on systolic function, but there is very little information on diastolic function, which is also an important cause of heart failure," he said. The recent availability of Doppler tissue-imaging technology now allows diastolic dysfunction to be measured easily in a noninvasive way and so should lead to more studies in this field. As inhibition of the renin angiotensin system brings about other benefits than just lowering blood pressure, such as better regression of LVH and reduction of myocardial fibrosis, Solomon and his colleagues tested the hypothesis that lowering blood pressure with a RAS inhibitor would improve diastolic function to a greater extent than blood-pressure lowering without inhibiting the RAS.

In the study, 482 patients older than age 45 with a history of or untreated hypertension and without heart failure underwent screening for diastolic dysfunction using tissue Doppler assessment of myocardial relaxation velocities. The 384 patients with evidence of diastolic dysfunction based on low lateral annular relaxation velocities (<10 cm/s if age 45-55; <9 cm/s if age 55-65; <8 cm/s if age > 65) were randomized to blood-pressure lowering with the angiotensin receptor blocker valsartan 320 mg daily vs blood-pressure lowering without RAS inhibitors for 38 weeks. In addition to study medication, patients were given standard blood-pressure-lowering drugs, such as diuretics, beta blockers, or calcium-channel blockers if needed, with the aim of achieving a target blood-pressure rate of 135/80 mm Hg in both treatment groups. Change in diastolic dysfunction (as measured by diastolic relaxation velocities) between baseline and 38 weeks was compared.

Results showed that at baseline patients had only mildly elevated blood pressure (an average of 144/86 mm Hg) and that after treatment there was a greater than 10-mm-Hg reduction in blood pressure in both treatment groups. Diastolic function was also improved significantly in both groups, although the improvement observed in the valsartan group was similar to that in the other antihypertensive group.

Diastolic function as assessed by diastolic relaxation velocities

Time and difference Diastolic relaxation velocity (cm/s), valsartan group Diastolic relaxation velocity (cm/s), non-RAS-inhibitor group
At baseline 7.5 7.5
After 38 weeks of treatment 8.1 8.0
Change 0.6 0.44

Solomon pointed out that despite the fact all patients included in this study had hypertension, there was a very low incidence of LVH (less than 4%) or myocardial structural changes. "We thought we would have seen a higher prevalence of LVH and myocardial fibrosis and, if we had, we may have shown a more pronounced effect in the valsartan group.

"We are seeing the effect of a hemodynamic benefit in this study, but we may have seen a difference between the two groups if the condition of the population had not been so benign," he speculated. "We have shown that reducing blood pressure has a beneficial effect on diastolic function, but the question of whether there is an incremental effect of RAS inhibition will have to wait for further studies," he added.

Solomon and his colleagues are now planning another study in patients with more severe hypertension. This new study, known as EXCEED, will test a slightly different concept--whether more aggressive blood-pressure lowering improves diastolic dysfunction more than less aggressive blood-pressure lowering. Both groups will be treated with a combination of valsartan and amlodipine but at different doses to correlate with aggressive or less aggressive therapy.

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