Effect of Antihypertensives on Diastolic Function
Abstract & Commentary
By Michael H. Crawford, MD
Source: Tapp RJ, et al. Differential effects of antihypertensive treatment on left ventricular diastolic function. J Am Coll Cardiol. 2010;55:1875-1881.
Heart failure due to diastolic dysfunction is common in hypertensive patients, yet little is known about the effect of antihypertensive agents on diastolic dysfunction. A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) evaluated diastolic function by echo-Doppler techniques and addressed the effect of beta blocker plus diuretic vs. a calcium blocker plus an ACE inhibitor. In the main trial, death or myocardial infarction was less on amlodipine plus perindopril as compared to atenolol plus thiazide diuretic. Enrolled patients had hypertension and at least three other cardiovascular disease risk factors. A subgroup of 1,006 patients from two centers in the British Isles underwent more detailed evaluation, including echo-Doppler studies and BNP at one year after randomization. Baseline characteristics in the two treatment groups in this substudy population were similar. Systolic blood pressure was reduced equally in the two groups, but heart rate was lower on the beta blocker-based therapy. Early diastolic mitral annular tissue Doppler velocity (E') was lower on the atenolol regimen (7.9 vs. 8.8 cm/s; p < 0.001). Mitral valve velocity (E) over E' and BNP were higher on the atenolol regimen (8.1 vs. 7.8; p = 0.013) and (37 vs. 19 pg/mL; p < 0.001). These differences remained significant after adjusting for age and sex. Adjustment for systolic blood pressure, left ventricular mass, and heart rate attenuated the difference in E/E', but not E', on BNP. The authors concluded that in an ASCOT study subgroup, echo-Doppler diastolic function was better on the amlodipine-based treatment vs. the atenolol-based treatment, and these differences were independent of blood pressure lowering and other loading factors known to affect diastolic function measures.
This is an interesting substudy of ASCOT that used sophisticated echo-Doppler measures to assess diastolic function in a largely male, elderly, European population with risk factors for coronary disease in addition to their hypertension. The treatment regimens were referred to as amlodipine based or atenolol based because only 40% of the patients required the second study drug to achieve blood pressure targets (perindopril and a thiazide, respectively). Although systolic blood pressures were not different at the end of one year, there was a small but statistically significant difference in diastolic blood pressure in favor of amlodipine-based therapy (80 vs. 82 mmHg; p = 0.012). They found that tissue Doppler-based measures of diastolic function (E', E/E') were better at one year on amlodipine-based therapy. E/E' could be explained by the lower heart rate on atenolol, but there were other measures that supported a true improvement in diastolic function on the amlodipine-based therapy. BNP was lower, left ventricular end-diastolic dimension was lower (4.84 vs. 4.92 cm, p = 0.046), and left atrial dimension was lower (4.14 vs. 4.25 cm, p = 0.022) on the amlodipine-based therapy. Also, there was a trend toward lower left ventricular mass on amlodipine (118 vs. 122 g/m2, p = 0.089). The aggregate of these data suggest a real difference in diastolic function. However, the differences in echo-Doppler parameters could be explained by the combined effect of heart rate differences, diastolic blood pressure differences, and the mechanism of action of the drugs. All the drugs except atenolol lower peripheral resistance. Atenolol reduces heart rate and myocardial contractility. Ejection fraction was identical in the two groups (69%), but it is an insensitive measure of left ventricular contractility.
The major strengths of this study are the relatively large study population for a study of this type and the use of sophisticated echo-Doppler techniques for measuring diastolic function. The major weaknesses are that there were no baseline measures of diastolic function and not each patient in a group was on the same drugs. Thus, any differences cannot be attributed to any particular drug or combination. However, if these differences are accurate reflections of diastolic function, then there is a potential to reduce or delay the onset of heart failure in patients with hypertension by selecting antihypertensive drug strategies shown to improve diastolic function.