0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous?

Franz H. Messerli, MD; Giuseppe Mancia, MD; C. Richard Conti, MD; Ann C. Hewkin, MSc; Stuart Kupfer, MD; Annette Champion, MBA; Rainer Kolloch, MD; Athanase Benetos, MD; and Carl J. Pepine, MD
[+] Article and Author Information

From St. Luke's-Roosevelt Hospital, New York, New York; University of Milan, Milan, Italy; University of Florida, Gainesville, Florida; Abbott, Abbott Park, Illinois; Medizinische Klinik, Bielefeld, Germany; and Hôpital Brabois, University of Nancy, Nancy, France.


ClinicalTrial.gov identifier: NCT00133692.

Note: The first author, Dr. Messerli, has had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Grant Support: By research grants from Abbott.

Potential Financial Conflicts of Interest: Employment: F.H. Messerli (Abbott, Novartis, Pfizer Inc., Sankyo), A.C. Hewkin (Abbott), S. Kupfer (Abbott), A. Champion (Abbott); Consultancies: F.H. Messerli (Abbott, Norvartis, Pfizer Inc., Merck & Co. Inc.), C.J. Pepine (Abbott Laboratories, CV Therapeutics); Honoraria: G. Mancia (Pfizer Inc., Novartis Pharma, Sanofi-Synthelabo, Servier, Abbott, Merck Sharp & Dohme, Bayer, Boehringer Ingelheim), A. Benetos (Abbott, Servier, Bayer); Stock ownership or options (other than mutual funds): A.C. Hewkin (Abbott), S. Kupfer (Abbott), A. Champion (Abbott); Expert testimony: F.H. Messerli (Novartis); Grants received: F.H. Messerli (Novartis), C.J. Pepine (Abbott Laboratories, AstraZeneca, Berlex Laboratories Inc., CV Therapeutics, GlaxoSmithKline, King Pharmaceuticals Inc., Millennium Pharmaceuticals, Inc., Monarch Pharmaceuticals, Pfizer Inc., Sanofi-Aventis, Schering-Plough, Wyeth-Ayerst Laboratories); Grants pending: F.H. Messerli (GlaxoSmithKline); Patents received: C.J. Pepine (University of Florida). Abbott markets 2 of the study drugs (verapamil and trandolapril) and their fixed-dose combination.

Requests for Single Reprints: Franz H. Messerli, MD, Division of Cardiology, St. Luke's-Roosevelt Hospital, 1000 Tenth Avenue, New York, NY 10019; e-mail, Fmesserli@aol.com.

Current Author Addresses: Dr. Messerli: Division of Cardiology, St. Luke's-Roosevelt Hospital, 1000 Tenth Avenue, New York, NY 10019.

Dr. Mancia: Dipartimento di Medicina Clinica, Università degli Studi di Milano–Bicocca, Ospedale San Gerardo di Monza, Via Donizetti 106, 20052 Monza, Milan, Italy.

Drs. Conti and Pepine: Division of Cardiovascular Medicine, 1600 SW Archer Road, Box 100277, Gainesville, FL 32610-0277.

Ms. Hewkin: DR435, AP9A, Abbott, 200 Abbott Park Road, Abbott Park, IL 60045.

Dr. Kupfer: 640 Colwyn Terrace, Deerfield, IL 60015.

Ms. Champion: DR439, AP30-3, Abbott, 200 Abbott Park Road, Abbott Park, IL 60045-6145.

Dr. Kolloch: Gilead Medical Center, University of Munster, Munster, Germany.

Dr. Benetos: Centre de Geriatrie, Hôpital Brabois, University of Nancy, 54511 Nancy-les-Vandoeuvre, France.

Author Contributions: Conception and design: F.H. Messerli, G. Mancia, S. Kupfer, R. Kolloch, C.J. Pepine.

Analysis and interpretation of the data: F.H. Messerli, G. Mancia, C.R. Conti, A.C. Hewkin, S. Kupfer, A. Champion, R. Kolloch, A. Benetos, C.J. Pepine.

Drafting of the article: F.H. Messerli, G. Mancia, A.C. Hewkin, S. Kupfer, R. Kolloch, A. Benetos, C.J. Pepine.

Critical revision of the article for important intellectual content: F.H. Messerli, G. Mancia, C.R. Conti, S. Kupfer, A. Champion, R. Kolloch, A. Benetos, C.J. Pepine.

Final approval of the article: F.H. Messerli, G. Mancia, C.R. Conti, R. Kolloch, A. Benetos, C.J. Pepine.

Provision of study materials or patients: F.H. Messerli, C.R. Conti, C.J. Pepine.

Statistical expertise: F.H. Messerli, A.C. Hewkin.

Obtaining of funding: C.J. Pepine.

Administrative, technical, or logistic support: C.J. Pepine.

Collection and assembly of data: F.H. Messerli, C.J. Pepine.


Ann Intern Med. 2006;144(12):884-893. doi:10.7326/0003-4819-144-12-200606200-00005
Text Size: A A A

The Table shows demographic data and baseline characteristics of patients by systolic pressure and diastolic pressure categories. Patients with low systolic pressure tended to be leaner and male and had a higher incidence of MI, cancer, and heart failure than did those with high systolic pressure. Patients with low diastolic pressure tended to be older, leaner, female, and white and had a higher incidence of MI, cancer, heart failure, and diabetes compared with those with high diastolic pressure.

First Page Preview

View Large
First page PDF preview

Figures

Grahic Jump Location
Figure 1.
Incidence of the primary outcome (first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke) by systolic blood pressure and diastolic blood pressure strata.

Error bars represent 95% CIs.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Unadjusted and adjusted hazard ratios for the primary outcome by systolic blood pressure and diastolic blood pressure strata.

The CIs are plotted as dotted lines. See text for further details.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Incidence of total myocardial infarction (MI) and total stroke by diastolic blood pressure strata.
Grahic Jump Location
Grahic Jump Location
Figure 4.
Analysis of clinically significant interactions of baseline covariates and diastolic blood pressure for the primary outcome.

*Coronary artery bypass graft or percutaneous coronary intervention.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Diastolic blood pressure in coronary artery disease
Posted on June 27, 2006
Thomas Weber
Cardiology Dept, Klinikum Wels, Austria, St Vincent´s Clinic, Sydney, Australia
Conflict of Interest: None Declared

In a recent issue of the Annals, Messerli et al provide new insights into the J-curve discussion in patients with hypertension and coronary artery disease (CAD) [1]. Briefly, they observed an increase in all-cause mortality and myocardial infarctions with lower diastolic blood pressure in the INVEST population, hypertensive patients with CAD, treated with a verapamil sustained release or atenolol-based strategy [2]. In the discussion, the authors mention impaired coronary perfusion, increased pulse pressure and arterial stiffness, and underlying chronic illness as possible pathophysiologic mechanisms.

Clearly, we cannot speculate on the latter, but would like to support the two other explanations due to the following reasons: First, mean patient age in INVEST was 66 years. Generally, in this age group, isolated systolic hypertension (ISH) is by far the most common phenotype of hypertension [3], a condition characterized by widened pulse pressure, increased arterial stiffness, increased/premature arterial wave reflections, therefore decreased diastolic blood pressure and impaired coronary perfusion [4,5]. In the original publication, more than 50% of patients had "controlled" diastolic blood pressure at baseline, raising the possibility of ISH in many of them. It would be very interesting to perform complementary analysis in ISH patients, if they had been identified at baseline. Second, Chirinos et al [6] as well as our group [7] recently observed that increased arterial wave reflections, one of the main pathophysiologic principles contributing to an increased pulse pressure in these patients, are accompanied by an increase in major adverse cardiovascular events including myocardial infarction and death in CAD patients. In the Chirinos paper [6] as well as in a prior study showing a relationship between increased arterial wave reflections and the presence and extent of CAD [8], a lower diastolic blood pressure was a predictor of the unfavourable endpoint. Moreover, in the latter study, systolic blood pressure was identical in CAD and non-CAD patients, and the significant difference in pulse pressure was mediated mainly by a lower diastolic blood pressure in the CAD group. In other words, the only clue to the altered arterial characteristics in CAD patients was a lower diastolic pressure. Of note, most of the CAD patients in that study were treated hypertensives with a mean age of 63.8 years and, therefore, quite comparable to the INVEST population.

In conclusion, although arterial properties were not reported in the INVEST study [1,2], the increased risk accompanying a lower diastolic blood pressure in treated hypertensive patients with CAD might be explained by increased arterial wave reflections and arterial stiffness.

Thomas Weber

Johann Auer

Michael F. O`Rourke

Bernd Eber

1 ... Messerli FH, Mancia G, Conti R, et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006; 144:884-93

2 ... Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. J Am Med Ass 2003; 290:2805-16

3 ... Franklin SS, Jacobs MJ, Wong ND, et al. Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives - analysis based on NHANES III. Hypertension 2001; 37:869-74

4 ... Nichols WW, O´Rourke MF. McDonald´s Blood Flow in Arteries. 5th ed. London, England:Hodder-Arnold, 2005

5 ... Franklin SS. Hypertension in older people: Part 1. J Clin Hypertens 2006; 8:444-9

6 ... Chirinos JA, Zambrano JP, Chakko S, et al. Aortic pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease. Hypertension 2005;45:980"“985

7 ... Weber T, Auer J, O´Rourke MF, et a. Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions. Eur Heart J 2005; 26:2657-63

8 ... Weber T, Auer J, O´Rourke MF, et al. Arterial stiffness, wave reflections and the risk of coronary artery disease. Circulation 2004; 109:184-198

Conflict of Interest:

None declared

How to reduce systolic blood pressure without lowering the diastolic ?
Posted on July 1, 2006
Hean T Ong
HT Ong Heart Clinic, Penang, MALAYSIA
Conflict of Interest: None Declared

Messerli and colleagues suggest that there is a nadir for diastolic blood pressure below which coronary perfusion is impaired and cardiovascular events increased (1). Yet, numerous trials including VALUE and ASCOT clearly show that the arm treated to the lower blood pressure produce less cardiovascular events (2,3). How can we seek to "lower blood pressure" and yet try to "not lower diastolic blood pressure excessively" since all present anti-hypertensive agents lower both diastolic and systolic pressures??

References: 1. Messerli FH, Mancia G, Conti R, et al. Dogma disputed: Can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006; 144:884-893.

2.Julius S,Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial.Lancet 2004; 363: 2022 -31.

3. Dahlof B,Sever PS,Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005; 366:895-906.

Conflict of Interest:

None declared

Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)