Intensive Vasodilator Therapy in Patients With Essential Hypertension

Morphological changes are observed in the microvasculature of patients with essential hypertension. The lumen diameter is reduced in resistance arteries, but with no change in vessel cross-sectional area or wall mass. These structural changes are termed inward eutrophic remodelling and results in an increased wall:lumen ratio, caused by rearrangement of cell matrix and not by hypertrophy of smooth muscle cells in the vascular wall as observed in secondary forms of hypertension. The morphological changes also occur in the coronary arteries and cause a reduction in the ability to increase coronary perfusion as response to increased cardiac work. This is observed as a reduced coronary flow reserve in patients with sustained hypertension.

Two recently published clinical studies associates an increase in media:lumen ratio with an increased risk of cardiovascular events, and it therefore seems beneficial to normalize the vascular structure in patients with essential hypertension. It has previously been demonstrated that reversion of vascular remodelling and thereby normalization of the vascular structure, requires vasodilatation and not just blood pressure reduction, suggesting that patients with essential hypertension can benefit from antihypertensive treatment aimed to induce vasodilatation.

The purpose of this study is to determine whether add-on of intensive vasodilator therapy can improve the coronary perfusion (coronary flow reserve) and reduce the total peripheral resistance in patients with ongoing treatment for essential hypertension. We also aim to investigate whether changes in coronary flow reserve correlates better to changes in total peripheral resistance than changes in blood pressure. Particularly we aim to study if patients with high total peripheral resistance, despite blood pressure control, can benefit from intensive vasodilating therapy.

Inclusion criteria

• Ongoing antihypertensive treatment for >3 months
• Blood pressure >120/75 during antihypertensive treatment
• Ejection fraction > 45%

Exclusion criteria

• Blood pressure >160/100
• Pregnancy
• fertile women not using safe contraceptives
• known secondary hypertension
• valvular disease of haemodynamic significance
• known endocrine disease, nephropathy or hepatic disease
• present malignant disease
• known psychiatric disease
• abnormal lab tests of clinical significance
• known allergy to any study medication
• body mass index > 35
• Ongoing antihypertensive treatment with a combination of ACE-inhibitor and Calcium antagonist.