Abstract-Antihypertensive treatment can improve tissue Doppler indices of left ventricular diastolic function in the shortterm, but little is known about the longer-term effect of different antihypertensive treatments on progression of left ventricular diastolic function and left ventricular hypertrophy. We hypothesized that long-term treatment of hypertension will lead to improvements in left ventricular hypertrophy and diastolic function. We collected detailed cardiovascular phenotypic data on 1006 participants from a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial. Patients randomized to either an amlodipine±perindopril-based or an atenolol±bendroflumethiazide-based regimen underwent conventional and tissue Doppler echocardiography at time of control of blood pressure after randomization (≈1.5 years; phase 1) and after a further 2 years of antihypertensive treatment (phase 2). There were no prerandomization data. Five hundred thirty-six patients had complete data collection at both phases. Left ventricular mass index regressed from phase 1 to 2 with no significant difference between treatment groups (amlodipine: 119.5-116.8; atenolol: 122.9-117.5; P<0.001 for both). Conversely, tissue Doppler diastolic indices did not change in the amlodipine±perindopril-based regimen (E/e′, 7.5-7.6 cm/s; P=not significant), but deteriorated in the atenolol±bendroflumethiazide-based regimen (E/e′, 8.0-8.5 cm/s; P<0.01). Despite regression of left ventricular hypertrophy, there was no associated improvement in diastolic function. In fact, long-term treatment with atenolol±bendroflumethiazide resulted in a progressive deterioration in E/e′. This may be a factor contributing to the previously described worse clinical outcome in patients treated with atenolol±
Methods
PatientsThe population, methods, and response rate for the ASCOT study are described in detail elsewhere. 17 In brief, ASCOT was a randomized clinical trial of BP-lowering therapy in 19 257 men and women aged 40 to 79 years with hypertension. Hypertension was defined as either untreated (systolic BP ≥160 mm Hg and diastolic BP ≥100 mm Hg at screening and randomization) or inadequately treated hypertension (systolic BP ≥140 mm Hg and diastolic BP ≥90 mm Hg at randomization). As well as hypertension the patients required ≥3 prespecified cardiovascular risk factors from previously identified LVH on echocardiography or electrocardiography, other specified electrocardiography abnormalities, type 2 diabetes mellitus, peripheral vascular disease, previous transient ischemic attacks or stroke, male sex, age ≥55 years, microalbuminuria/proteinuria, smoking, plasma total cholesterol/high-density lipoprotein ratio ≥6, and family history of ischemic heart disease in a first-degree relative (males aged <55 years, females aged <60 years). Patients with known ischemic heart disease or heart failure were excluded. The patients were then randomized to either atenolol±bendroflumethiazide-K (atenolol±bendroflumethiazide-based regimen) or amlodipine±perindopril (amlodipine±p...