Effect of Intensive Versus Standard Blood Pressure Lowering on Diastolic Function in Patients With Uncontrolled Hypertension and Diastolic Dysfunction

Abstract

Abstract-Diastolic dysfunction may precede development of heart failure in hypertensive patients. We randomized 228 patients with uncontrolled hypertension, preserved ejection fraction, and diastolic dysfunction to 2 targeted treatment strategies: intensive, with a systolic blood pressure target of Ͻ130 mm Hg, or standard, with a systolic blood pressure target of Ͻ140 mm Hg, using a combination of valsartan, either 160 or 320 mg, plus amlodipine, either 5 or 10 mg, with other antihypertensive medications as needed. any of the adverse sequelae of hypertension are the direct result of target-organ damage to the vasculature, the kidneys, and the heart. In the heart, long-standing hypertension serves as a stimulus for progressive fibrosis, ventricular hypertrophy, 1-3 and diastolic dysfunction, which may be one of the earliest manifestations of cardiac target-organ damage. 4 These changes may be accelerated by age and hypertension-related changes in central aortic stiffness, which may contribute to abnormal pulse wave reflection and enhanced pulsatile arterial load. Present in Յ50% of hypertensive patients, diastolic dysfunction likely represents an important intermediate in the development of heart failure, particularly in patients with preserved systolic function. 5,6 We have demonstrated previously that blood pressure lowering in patients with stage 1 hypertension is associated with improvement in diastolic function, whether a renin-angiotensin-aldosterone system inhibitor or non-renin-angiotensin-aldosterone system blood pressure lowering was used. 7 Because the degree of improvement in diastolic function appears to be closely tied to the degree of blood pressure lowering, we hypothesized that a strategy of aggressive blood pressure control (beyond the established Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure targets 8 ) would be more effective than a less intensive strategy in attenuating cardiac dysfunction. More aggressive targets have already been recommended in certain subgroups of patients, including those with diabetes mellitus, chronic kidney disease, and coronary artery disease. 9 The Exforge Intensive Control of Hypertension to Evaluate Efficacy in Diastolic Dysfunction (EXCEED) Trial was designed to prospectively test the hypothesis that, among patients with uncontrolledContinuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. The principal investigator and steering committee wrote the article, made the decision to submit for publication, and take responsibility for its contents. This trial has been registered at www.clinicaltrials.gov (identifier NCT00523549).

Treatment of Isolated Left Ventricular Diastolic Dysfunction in Hypertension

“…As may be seen in Table 4 and Figure 4 of the study, 10 BP reduction by either treatment regimen was associated with improvement in the Doppler parameter of LV diastolic function. Given the SDs seen in Table 3, withingroup variability of end-study systolic BP prevailed on between-group differences, generating a significant overlap in final BP levels in the 2 groups.…”

“…On a separate issue, the study by Solomon et al 10 showed that final brachial and central systolic BPs were slightly lower in patients in the intensive treatment arm compared with those in the standard treatment arm; in contrast, LV mass and left atrial volume index regressions, augmentation index reduction, and LV ejection fraction increase were similar in the 2 treatment regimens. A seducing hypothesis is that LV mass regression and arterial stiffness reduction in hypertension may be more relevant (or more reliable) than BP lowering as predictors of LV diastolic function improvement during treatment in arterial hypertension.…”

“…In contrast, tissue Doppler imaging and color M-mode-derived parameters of LV diastolic function, such as EЈ and E-wave propagation rate, are significantly less preload dependent, 12 and their combination with traditional Doppler parameters allow for better representation of LV relaxation and LV chamber compliance. 12 Solomon et al 10 found that EЈ increased and E/EЈ decreased with BP lowering, suggestive of improved LV relaxation and increase in LV compliance. Therefore, increase in E and in E/A and shorter isovolumic relaxation time and E deceleration time reported at followup 10 could be put in the right context of true improvement in LV diastolic relaxation (and LV suction capability) with BP lowering.…”

“…12 Solomon et al 10 found that EЈ increased and E/EЈ decreased with BP lowering, suggestive of improved LV relaxation and increase in LV compliance. Therefore, increase in E and in E/A and shorter isovolumic relaxation time and E deceleration time reported at followup 10 could be put in the right context of true improvement in LV diastolic relaxation (and LV suction capability) with BP lowering.…”

Sex-specific differences in cardiac maladaptation to hypertension and arterial stiffening

“…Overall, the risk of new-onset HF significantly decreased by 24% per 5-mmHg reduction in www.kardiologiapolska.pl Sex-specific differences in cardiac maladaptation to hypertension and arterial stiffening systolic BP. Moreover, BP-lowering drugs were shown to reduce LV mass [71] and improve LV diastolic function [72] thus reversing two major cardiac consequences of hypertension. Studies investigating sex-specific effects of anti-hypertensive treatment on LVH came to discrepant and inconclusive findings so far [73][74][75][76].…”