Adding thiazide to a renin-angiotensin blocker improves left ventricular relaxation and improves heart failure in patients with hypertension

Abstract

Hypertension is associated with an increased risk of diastolic dysfunction. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have failed to show improvement in clinical outcomes for patients with diastolic dysfunction. In this study, we investigated the effect of changing an ACEi or ARB to a combination of losartan and hydrochlorothiazide (HCTZ) on left ventricular (LV) preload and relaxation in patients with hypertension and diastolic dysfunction. We enrolled 371 hypertensive patients with diastolic dysfunction who had not achieved their treatment goals with an ACEi or ARB. We switched the ACEi or ARB to losartan/HCTZ and followed the patients for 24 weeks. The primary end points were changes in septal mitral annular velocity during diastole (e') and in the ratio of mitral inflow velocity to e' velocity (E/e' ratio) from baseline to the end of follow-up. Mean systolic and diastolic blood pressures (BP) decreased by 22 and 11 mm Hg, respectively, after changing from an ACEi or ARB to losartan/HCTZ. The e' velocity increased, and the E/e' ratio and brain natriuretic peptide level decreased significantly. High-sensitivity C-reactive protein also decreased significantly (0.50 vs. 0.29 mg dl(-1), P<0.0001). There were only slight or no changes in glucose levels, homeostasis model assessment insulin resistance (HOMA-R), uric acid and electrolytes after the drug change. Changing from an ACEi or ARB to losartan/HCTZ is associated with a reduction in BP, improvement in LV relaxation, improvement in heart failure state and attenuation of systemic inflammation with few adverse effects in patients with hypertension and diastolic dysfunction.

Figure 1

Changes in e′ velocity and E/e′ ratio for each quartile of systolic BP decrease after change to losartan/HCTZ. A greater reduction in systolic BP was associated with a greater increase in e′ velocity and a greater reduction in E/e′. The range of decrease in systolic BP was 72–35 mm Hg in Q1, 34–22 mm Hg in Q2, 21–13 mm Hg in Q3 and 12−27 mm Hg in Q4. Data are expressed as mean±s.d.

Figure 2

Relationship between changes in e′ velocity and changes in s′ velocity. There was a close relationship between changes in s′ velocity and changes in e′ velocity.

Figure 3

Comparisons of temporal changes in e′ velocity and E/e′ ratio between NYHA class, high and low hsCRP, and high and low HOMA-R. The magnitude of changes in e′ velocity and the E/e′ ratio was higher in patients with NYHA-2 or 3 than those with NYHA-1. The magnitude of changes in e′ velocity and the E/e′ ratio was greater in high hsCRP patients than in low hsCRP patients. The magnitude of changes in e′ velocity was greater in patients with high HOMA-R than in those with low HOMA-R. However, there was no difference in the E/e′ ratio between the two groups. A full color version of this figure is available at the Hypertension Research journal online.