Successful treatment of hypertension accounts for improvements in markers of diastolic function − a pilot study comparing hydrochlorothiazide-based and amlodipine-based treatment strategies

Abstract

C urrent hypertension treatment trials attribute relative differences in benefits associated with various treatment regimens to unique pharmacological benefits. These studies typically aim for a treatment systolic blood pressure (BP) goal of lower than 140 mmHg, rather than a deliberate aim to normalize BP (1-3). At study completion, up to 25% of treated subjects in these clinical trials ultimately have BP levels above the treatment goal, and a more substantial proportion of patients have a BP above the 'optimal' BP of lower than 120/80 mmHg. Epidemiological studies showed that, compared with optimal BP, 'high-normal' BP (130/85 mmHg to 139/89 mmHg) is associated with a higher risk-adjusted hazard ratio for cardiovascular disease (4), and that those with 'high-normal' BP have a RR of 2.3 for the development of cardiovascular disease in 10 years compared with those with 'optimal' BP (5). Hence, to unequivocally address the contributions of BACKGROUND: There is controversy regarding whether blood pressure (BP) medications have relevant therapeutic benefits beyond those due to lowering of BP. OBJECTIVE: To show that rapid successful treatment of hypertension leads to improvement in cardiac morphology and function regardless of the pharmacological agents used. METHODS: Hypertension was defined as an average 24 h ambulatory BP of higher than 135/85 mmHg in 38 subjects with a mean (± SD) age of 54±7 years. Patients were randomly assigned to treatment with a diureticbased (n=20) or a calcium channel blocker (CCB)-based (n=18) medication. All subjects were followed every two weeks, and similar additional medications were added until the BP was lower than 125/80 mmHg, then followed monthly for a total of six months. Echocardiography with tissue Doppler imaging was performed, and was repeated after six months of aggressive pharmacotherapy and lifestyle management. RESULTS: Baseline ambulatory BP monitoring and echocardiographic measures of diastolic function were similar between both treatment groups. Subjects received 3.5±1 pills and 11±2 follow-up visits. The average 24 h BP was reduced from 145/91 mmHg to 124/75 mmHg (P<0.001) in the CCB group. A greater lowering from 143/91 mmHg to 117/72 mmHg occurred in the diuretic group (P=0.02 for the difference between groups) at six months. There was significant improvement in tissue Doppler imaging diastolic function parameters in both groups, with a trend toward greater improvement in the diuretic group. The left ventricular mass/ height 2.7 index decreased from 40 g/m 2.7 to 37 g/m 2.7 in the diuretic group (P=0.02), whereas a nonsignificant change (41 g/m 2.7 to 42 g/m 2.7 ) occurred in the CCB group. CONCLUSIONS: Aggressive BP lowering is associated with improved left ventricular diastolic function and mass proportional to the extent of BP normalization.

Mathematical modeling of antihypertensive therapy

“…The model predicts a decrease in the active peak filling rate for all drugs, whereas the early peak filling rate remains almost the same for all drugs, with the exception of bisoprolol, which increases this rate. This behaviour is consistent with the dynamics found for peak filling velocities in a number of experimental studies for amlodipine ( Ogunyankin and Day, 2009 ), bisoprolol ( de Teresa et al, 1994 ), HCTZ ( Ogunyankin and Day, 2009 ; Little et al, 2006 ), and losartan ( Little et al, 2006 ). However, it should be noted that other dynamics may be observed in patients with comorbidities.…”

Comparative efficacy of different types of antihypertensive drugs in reversing left ventricular hypertrophy as determined with echocardiography in hypertensive patients: A network meta‐analysis of randomized controlled trials

“…Overall, the systematic review and network meta‐analysis included 46 clinical studies involving 5074 hypertensive patients 13‐58 . The follow‐up time ranged from 3 months to 24 months with a mean of 7 months.…”