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(Hypertension. 2007;50:e72.)
© 2007 American Heart Association, Inc.

Letters to the Editor

Response to Amlodipine and Stroke Prevention

Ji-Guang Wang; Yan Li

Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

We very much appreciate the comments and hypotheses of Balligand and Godfraind.¹ Our quantitative overview on amlodipine and angiotensin receptor blockers demonstrated that calcium channel blockade by the use of amlodipine substantially reduced the risk of stroke and myocardial infarction.² Blood pressure gradients between randomized groups of trials largely account for the benefit of amlodipine versus other antihypertensive agents. However, amlodipine indeed produced benefits beyond brachial blood pressure measured in the clinic, particularly against stroke. We believe that the benefit of amlodipine beyond brachial blood pressure to a large extent could be attributable to the better blood pressure control in the whole circulatory system and over 24 hours, although other mechanisms, such as the prevention of intima-media thickening by calcium channel blockade,³ may also play a role. In the Conduit Artery Function Evaluation substudy of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm, amlodipine reduced central systolic blood pressure more than alenolol, despite similar reductions in the brachial systolic blood pressure.⁴ In the ambulatory blood pressure monitoring substudy of the Valsartan Antihypertensive Long-Term Use Evaluation Trial, amlodipine reduced ambulatory systolic blood pressure beyond 20 hours after drug intake more than valsartan and really provided 24-hour blood pressure control.⁵

The underlying mechanisms for the advantages of amlodipine in blood pressure control and in the prevention of stroke and myocardial infarction definitely warrant further investigation. The hypotheses of Balligand and Godfraind¹ are intriguing. Both tissue selectivity and blood pressure variability may contribute to the interpretation of the benefit of amlodipine versus other antihypertensive drugs. Tissue selectivity might be relevant for various dihydropyridine calcium channel blockers, which provided similar protection against stroke but different protection against myocardial infarction. Compared with placebo, only amlodipine, but not nifedipine gastro-intestinal therapeutic system or nisoldipine, prevented myocardial infarction. Blood pressure variability is a complicated issue. It may indicate beat-to-beat (short time) or 24-hour blood pressure (circadian) variability or the 2 in combination. What Balligand and Godfraind¹ discussed was actually the beat-to-beat blood pressure variability, which has quite different clinical implications from that of 24-hour blood pressure variability. Experimental studies in rodents suggested that higher beat-to-beat blood pressure variability might confer cardiovascular risk. Twenty-four–hour blood pressure variability mainly reflects the circadian variation in relation to physical activity. The nighttime hypertension or nondipping status, which, in fact, means smaller variability, is associated with a higher cardiovascular risk in various populations. Nonetheless, the clinical relevance of the endothelial NO synthase activation in the determination of blood pressure variability (short-time beat-to-beat) and in the prevention of stroke and other cardiovascular diseases by antihypertensive treatment should be elucidated, although the results of a recent study in humans did not support the notion that dynamic oscillations of blood pressure depend critically on NO activity.⁶

	Acknowledgments

 
Disclosures

None.

	References

Top References

 

1. Balligand J-L, Godfraind T. Amlodipine and stroke prevention. Hypertension. 2007; 50: e71.[Free Full Text]
2. Wang JG, Li Y, Franklin SS, Safar M. Prevention of stroke and myocardial infarction by amlodipine and angiotensin receptor blockers: a quantitative overview. Hypertension. 2007; 50: 181–188.[Abstract/Free Full Text]
3. Wang JG, Staessen JA, Li Y, Van Bortel LM, Nawrot T, Messerli FH, Safar M. Carotid intima-media thickness and antihypertensive treatment: a meta-analysis of randomized trial. Stroke. 2006; 37: 1933–1940.[Abstract/Free Full Text]
4. The CAFE Investigators. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006; 113: 1213–1225.[Abstract/Free Full Text]
5. Pedersen OL, Mancia G, Pickering T, Hoegholm A, Julius S, Kjeldsen SE, Nielsen ES, Refsgaard J, Weber M; VALUE trial group. Ambulatory blood pressure monitoring after 1 year on valsartan or amlodipine-based treatment: a VALUE substudy. J Hypertens. 2007; 25: 707–712.[Medline] [Order article via Infotrieve]
6. Cooke WH, Zhang R, Zuckerman JH, Cui J, Wilson TE, Crandall CG, Levine BD. Does nitric oxide buffer arterial blood pressure variability in humans? J Appl Physiol. 2002; 93: 1466–1470.[Abstract/Free Full Text]

This Article Extract Full Text (PDF) All Versions of this Article: 50/4/e72    most recent HYPERTENSIONAHA.107.096842v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, J.-G. Articles by Li, Y. Search for Related Content PubMed Articles by Wang, J.-G. Articles by Li, Y.