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Effects of calcium channel antagonists on left ventricular hypertrophy and diastolic function in patients with
Takeshi Takami1, Minori Shigematsu
1Clinic Jingumae, Kashihara, Nara, Japan. takami66@maple.ocn.ne.jp
Insights
Amlodipine and cilnidipine improved left ventricular hypertrophy and diastolic function in hypertensive patients, unlike nifedipine CR. N-type calcium channel blockade contributes to these beneficial effects.
Area of Science:
- Cardiology
- Pharmacology
- Hypertension Research
Background:
- Hypertension commonly causes left ventricular (LV) hypertrophy and diastolic dysfunction.
- Antihypertensive effects on LV structure/function may depend on mechanisms beyond blood pressure reduction, such as sympathetic nervous system and renin-angiotensin system modulation.
Purpose of the Study:
- To investigate the effects of amlodipine and cilnidipine, calcium channel antagonists with differing N-type channel blockade, on LV hypertrophy and diastolic function in patients with essential hypertension.
- To compare these effects with nifedipine CR, which lacks N-type channel blockade.
Main Methods:
- Randomized controlled trial involving patients with essential hypertension assigned to amlodipine, cilnidipine, or nifedipine CR for 6 months.
- Left ventricular mass index assessed by M-mode echocardiography.
- Diastolic function evaluated using E/A ratio and E wave deceleration time via pulse Doppler echocardiography.
Main Results:
- All three drugs significantly reduced blood pressure without intergroup differences.
- Significant reductions in LV mass index were observed by 3 months with cilnidipine and 6 months with amlodipine, but not nifedipine CR.
- Cilnidipine and amlodipine significantly improved diastolic function (decreased deceleration time, increased E/A ratio) after 3 months, while nifedipine CR did not.
Conclusions:
- Long-acting calcium channel antagonists exhibit varied effects on hypertensive left ventricular hypertrophy and diastolic function.
- Amlodipine and cilnidipine improved LV structure and function, whereas nifedipine CR did not.
- Suppression of sympathetic nerve activity via N-type calcium channel blockade appears crucial for improving LV hypertrophy and diastolic function in hypertension.
Abstract:
Hypertensive patients characteristically exhibit left ventricular (LV) hypertrophy and diastolic dysfunction. The effects of antihypertensive agents on LV hypertrophy and diastolic dysfunction do not always correlate with the degree of blood pressure reduction, but their effects on the sympathetic nervous system and renin-angiotensin system (RA system) are thought to be important. We investigated the effects of amlodipine and cilnidipine, N- and L-type calcium channel antagonists that suppress both blood pressure elevation and sympathetic activities, on LV hypertrophy and diastolic function. Patients with essential hypertension were randomly assigned to receive either amlodipine, cilnidipine or nifedipine CR (which does not block N-type calcium channels) for 6 months. The LV mass index was determined using M-mode echocardiography. The E/A ratio, i.e., the ratio of maximum amplitude between the early diastolic wave (E wave) and the atrial systolic wave (A wave) in the LV inflow pattern, and the deceleration time for the E wave were determined using pulse Doppler echocardiography. Systolic and diastolic blood pressures significantly decreased from the baseline values in all three groups, with no significant differences among the groups. The LV mass index had significantly decreased when it was evaluated 3 months after the initiation of treatment in the cilnidipine group and when it was evaluated 6 months after the initiation of treatment in the amlodipine group; only a slight decrease was observed in the nifedipine CR group. A significant decrease in the deceleration time and a significant increase in the E/A ratio were observed after 3 months of treatment in the cilnidipine and amlodipine groups but not in the nifedipine CR group. Thus, the effects of long-acting calcium channel antagonists on hypertensive LV hypertrophy and LV diastolic function varied from one antagonist to the other. Left ventricular hypertrophy and diastolic function improved in the cilnidipine and amlodipine groups, but not in the nifedipine CR group. These results indicate that the suppression of sympathetic nerve activity by the blockade of N-type calcium channels contributes to the improvement of LV hypertrophy and diastolic function.
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