Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Published Ahead of Print
    • Archive
    • Supplemental Issues
    • Collections - French
    • Collections - English
  • Info for
    • Authors & Reviewers
    • Submit a Manuscript
    • Advertisers
    • Careers & Locums
    • Subscribers
    • Permissions
  • About CFP
    • About CFP
    • About the CFPC
    • Editorial Advisory Board
    • Terms of Use
    • Contact Us
  • Feedback
    • Feedback
    • Rapid Responses
    • Most Read
    • Most Cited
    • Email Alerts
  • Blogs
    • Latest Blogs
    • Blog Guidelines
    • Directives pour les blogues
  • Mainpro+ Credits
    • About Mainpro+
    • Member Login
    • Instructions
  • Other Publications
    • http://www.cfpc.ca/Canadianfamilyphysician/
    • https://www.cfpc.ca/Login/
    • Careers and Locums

User menu

  • My alerts

Search

  • Advanced search
The College of Family Physicians of Canada
  • Other Publications
    • http://www.cfpc.ca/Canadianfamilyphysician/
    • https://www.cfpc.ca/Login/
    • Careers and Locums
  • My alerts
The College of Family Physicians of Canada

Advanced Search

  • Home
  • Articles
    • Current
    • Published Ahead of Print
    • Archive
    • Supplemental Issues
    • Collections - French
    • Collections - English
  • Info for
    • Authors & Reviewers
    • Submit a Manuscript
    • Advertisers
    • Careers & Locums
    • Subscribers
    • Permissions
  • About CFP
    • About CFP
    • About the CFPC
    • Editorial Advisory Board
    • Terms of Use
    • Contact Us
  • Feedback
    • Feedback
    • Rapid Responses
    • Most Read
    • Most Cited
    • Email Alerts
  • Blogs
    • Latest Blogs
    • Blog Guidelines
    • Directives pour les blogues
  • Mainpro+ Credits
    • About Mainpro+
    • Member Login
    • Instructions
  • RSS feeds
  • Follow cfp Template on Twitter
Article CommentaryCommentary

Uncertainty about the systolic blood pressure target in people with diabetes

Michael Allen, Kim Kelly and Kim Fleming
Canadian Family Physician February 2013, 59 (2) 128-131;
Michael Allen
Director of Evidence-based Programs in Continuing Medical Education at Dalhousie University in Halifax, NS
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: michael.allen@dal.ca
Kim Kelly
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kim Fleming
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • eLetters
  • Info & Metrics
  • PDF
Loading

The article by Campbell et al1 on hypertension in people with type 2 diabetes, which appeared in the September 2011 issue of Canadian Family Physician, provides a succinct overview of the topic and important information for family physicians. Our aim is to complement the article by expanding on some management areas where there is uncertainty, specifically the definition of hypertension and the current recommended target blood pressure (BP) of less than 130/80 mm Hg. While the article by Campbell et al refers to both systolic BP (SBP) and diastolic BP (DBP), most of our comments will address the former, as SBP is considered more important for determining the risk of cardiovascular events.2,3

Hypertension in people with diabetes is defined as the presence of SBP greater than 130 mm Hg or DBP greater than 80 mm Hg,1 the implication being that people with diabetes who have BPs greater than these values should receive treatment. Indeed, the current Canadian hypertension guideline recommends that treatment be initiated at a BP of 130/80 mm Hg or greater.4 However, family physicians might not know that in the most recent Canadian Diabetes Association (CDA) guideline this is a grade D, or consensus, recommendation.5 Indeed, no study has compared the effects of starting therapy in patients with diabetes with SBPs of 130 to 139 mm Hg compared with patients with SBPs of 140 mm Hg or greater, the recommended level for starting therapy in people without diabetes.6 Thus, as indicated by the grade D rating of the CDA recommendation, there is considerable uncertainty about the SBP at which to initiate treatment.

This uncertainty extends to the SBP treatment target of less than 130 mm Hg. While there is no doubt that lowering SBP lowers cardiovascular risk in people with diabetes, the level to which it should be lowered is uncertain. Campbell et al correctly point out several studies that have shown benefit with antihypertensive therapy in decreasing microvascular and macrovascular outcomes.7-13 However, mean SBP in the active therapy group was lowered to less than 130 mm Hg in only one study: the ABCD NT (Appropriate Blood Pressure Control in Diabetes—Normotensive) trial.11 In 4 studies,7,8,12,13 subjects were not randomized to different BP targets but to different drug regimens versus placebo, and it is not possible to definitively determine if the observed benefit was derived from reaching specific SBP targets or from the drugs. In 2 studies,7,8 benefits in renal outcomes were independent of mean BPs.

Results of ABCD NT

The ABCD NT trial is the only randomized controlled trial (RCT) cited by the CDA guideline to support a target SBP of less than 130 mm Hg.5 This small study randomized 480 patients with type 2 diabetes to different DBP targets. The intensive therapy group received nisoldipine or enalapril to achieve a DBP reduction of 10 mm Hg from the baseline measurement. The moderate therapy group received placebo and aimed for a DBP of 80 to 89 mm Hg. After a mean of 5.3 years, the achieved BPs were 128/75 mm Hg and 137/81 mm Hg in the intensive and moderate therapy groups, respectively. There was no statistically significant difference in the primary outcome of change in creatinine clearance. However, there was benefit in some secondary outcomes including stroke, proteinuria, and retinopathy.

The CDA acknowledges the limitations of ABCD NT and gives the recommendation to achieve an SBP of less than 130 mm Hg a grade C evidence level, indicating it is based on a non-randomized clinical trial or cohort study. The CDA also cites 2 cohort studies supporting an SBP target of less than 130 mm Hg.14,15 However, while these 2 observational studies indicate fewer microvascular and macrovascular outcomes with lower SBP, they do not prove that lowering SBP with antihypertensive medication will lead to fewer such outcomes and do not provide definitive evidence for a specific treatment target. Again, family physicians might not be aware of the low quality of evidence supporting the recommended SBP target of less than 130 mm Hg.

Results of ACCORD BP

The publicly funded ACCORD BP (Action to Control Cardiovascular Risk in Diabetes—Blood Pressure) trial was designed to address this lack of RCT evidence16 and, according to the CDA guidelines, would provide stronger evidence for an optimal SBP treatment target.5 The ACCORD BP trial was a large study (N = 4733) that randomized patients with type 2 diabetes to a target SBP of less than 120 mm Hg or less than 140 mm Hg.16 Mean baseline BP was 139/76 mm Hg. Both groups were allowed to take the same medications. After a mean of 4.7 years, mean BPs were 119/64 mm Hg and 134/71 mm Hg in the intensive and moderate treatment groups, respectively. There was no significant difference between the 2 groups in the primary composite outcome of myocardial infarction (MI), stroke, and death. There was a statistically significant reduction in the risk of stroke (2.6% vs 1.5%, absolute risk reduction 1.1%, number needed to treat 92 [95% CI 53 to 356]). However, there was also an increase in serious adverse events with a number needed to harm of 50 (95% CI 35 to 87) (Table 1).16,17 While ACCORD BP did not test an SBP target of less than 140 mm Hg against a target of less than 130 mm Hg, it is unlikely that a target of 130 mm Hg would be preferable, as even a target of 120 mm Hg did not provide beneft.16 An SBP target of less than 120 mm Hg might lead to a small reduction in stroke, and some patients might wish to incur the extra costs and possible adverse effects of intensive BP lowering if they place a high value on stroke prevention.18

View this table:
  • View inline
  • View popup
Table 1

Results of the ACCORD BP trial16: A) Efficacy outcomes and B) adverse events.

Evidence for identifying an SBP target

The RCT evidence for and against an SBP target of less than 130 mm Hg revolves around 2 studies, ABCD NT11 and ACCORD BP.16 The CDA and the Canadian Hypertension Education Program have not changed their recommendations since ACCORD BP was published and presumably are basing their recommendations on ABCD NT. Table 24,5,11,16 summarizes the key features of the 2 RCTs.

Uncertainty about efficacy is not the only factor to consider when identifying an appropriate SBP target. It is also important to consider the safety and practicality of reaching the target. Osher et al aimed to reduce BP in 257 patients with type 2 diabetes to less than 130/85 mm Hg, as was recommended when the study was conducted.19 Initial mean BP was 159/86 mm Hg, reflecting that most patients were already taking antihypertensive medications. An SBP of 130 mm Hg was reached by only 33% of patients, and DBP was lowered to 70 mm Hg or lower in 57% of patients. Lower DBPs were associated with advancing age, higher initial SBPs, and pre-existing coronary artery disease. The decline in DBP was not associated with any drug class or combination of drugs. The authors concluded that attempted lowering of SBP to less than 130 mm Hg is associated with inordinate lowering of DBP in a substantial number of patients. They also questioned if the benefits of tight SBP control to less than 130 mm Hg outweighed the risks of excessive diastolic reduction, especially in older patients with diabetes or those with coronary artery disease and diabetes.

The question of harm from excessive lowering of DBP remains unanswered. A recent meta-analysis of 31 BP-lowering trials in 73 913 persons with diabetes found no evidence of increased risk of MI from excessive lowering of DBP.20 However, this finding was not based on individual patient data but on meta-regression, which is like an epidemiologic study of the included RCTs. Therefore, results might have been affected by unknown confounding variables.18,21

A secondary analysis of INVEST (International Verapamil-Trandolapril Study) did find evidence of harm. The original INVEST trial randomized 22 576 patients with hypertension and coronary artery disease to antihypertensive therapy based on either a calcium channel blocker or a β-blocker.22 After a mean of 2.7 years, there was no significant difference in the primary composite outcome of all-cause death, nonfatal MI, and nonfatal stroke between the 2 treatment groups. The secondary analysis explored the relationship between achieved SBP and DBP and the primary outcome and its individual components.23 The primary outcome, total MI, and total stroke occurred more frequently with a DBP lower than 70 mm Hg than with a DBP of 70 to 90 mm Hg (Table 3).17,23 Although the analysis was based on patient-level data, it has limitations, as it was a post hoc observational study of an RCT and included only 6400 patients with diabetes. Nevertheless, physicians should be aware of the possibility of harm from excessive lowering of DBP when trying to achieve a target SBP of 130 mm Hg or less.

View this table:
  • View inline
  • View popup
Table 2 Summary of the ACCORD BP16 and ABCD NT11 trials
View this table:
  • View inline
  • View popup
Table 3

Association between achieved DBP and outcomes in INVEST reanalysis

Summary

Patients with diabetes benefit from antihypertensive treatment. The uncertainty is in the recommended target of 130 mm Hg or lower. Achieving such a target can be difficult and there is the possibility of harm. The 2013 American Diabetes Association has updated its target SBP position statement. It states there is level B evidence from well-conducted cohort studies that “People with diabetes and hypertension should be treated to a systolic blood pressure goal of < 140 mm Hg.”24 It also states there is level C evidence from poorly controlled or uncontrolled studies that “Lower systolic targets, such as < 130 mm Hg, may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden.”24

Acknowledgment

The Dalhousie Academic Detailing Service is funded by the Nova Scotia Department of Health and Wellness through the Drug Evaluation Alliance of Nova Scotia (DEANS). Dr Allen is Director of the Dalhousie Academic Detailing Service and has received funds for research and program development from DEANS. Ms Kelly is employed by the Capital Health Drug Evaluation Unit which receives funding from DEANS. Ms Fleming is employed by the Dalhousie Academic Detailing Service. None of the authors receive any form of funding from industry.

Footnotes

  • Competing interests: None declared

  • The opinions expressed in commentaries are those of the authors. Publication does not imply endorsement by the College of Family Physicians of Canada.

  • La traduction en français de cet article se trouve à www.cfp.ca dans la table des matières du numéro de février 2013 à la page e66.

  • This article has been peer reviewed. Can Fam Physician 2013;59:128-30

  • Copyright© the College of Family Physicians of Canada

References

  1. ↵
    1. Campbell NR,
    2. Gilbert RE,
    3. Leiter LA,
    4. Larochelle P,
    5. Tobe S,
    6. Chockalingam A,
    7. et al
    . Hypertension in people with type 2 diabetes. Update on pharmacologic management. Can Fam Physician 2011;57:997-1002 (Eng), e347-53 (Fr).
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Franklin SS
    . Systolic blood pressure: it's time to take control. Am J Hypertens 2004;17(12 Pt 2):49S-54S.
    OpenUrl
  3. ↵
    1. Stamler J,
    2. Stamler R,
    3. Neaton JD
    . Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med 1993;153(5):598-615.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Hypertension Canada [website]
    2012 CHEP recommendations for management of hypertension. Markham, ON: Canadian Hypertension Education Program; 2012. Available from: http://hypertension.ca/images/stories/dls/2012gl/2012CompleteCHEPRecommendationsEN.pdf Accessed 2013 Jan 14.
  5. ↵
    1. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee
    Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2008;32(Suppl 1):S1-201.
    OpenUrl
  6. ↵
    1. Mancia G,
    2. Laurent S,
    3. Agabiti-Rosei E,
    4. Ambrosioni E,
    5. Burnier M,
    6. Caulfeld MJ,
    7. et al
    . Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009;27(11):2121-58.
    OpenUrlCrossRefPubMed
  7. ↵
    1. Brenner BM,
    2. Cooper ME,
    3. de Zeeuw D,
    4. Keane WF,
    5. Mitch WE,
    6. Parving HH,
    7. et al
    . Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345(12):861-9.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Lewis EJ,
    2. Hunsicker LG,
    3. Clarke WR,
    4. Berl T,
    5. Pohl MA,
    6. Lewis JB,
    7. et al
    . Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345(12):851-60.
    OpenUrlCrossRefPubMed
    1. UK Prospective Diabetes Study Group
    Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317(7160):703-13. Erratum in: BMJ 1999;318(7175):29.
    OpenUrlAbstract/FREE Full Text
    1. Estacio RO,
    2. Jeffers BW,
    3. Gifford N,
    4. Schrier RW
    . Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care 2000;23(Suppl 2):B54-64.
    OpenUrlPubMed
  9. ↵
    1. Schrier RW,
    2. Estacio RO,
    3. Esler A,
    4. Mehler P
    . Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int 2002;61(3):1086-97.
    OpenUrlCrossRefPubMed
  10. ↵
    1. Patel A,
    2. MacMahon S,
    3. Chalmers J,
    4. Neal B,
    5. Woodward M,
    6. Billot L,
    7. et al
    . Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007;370(9590):829-40.
    OpenUrlCrossRefPubMed
  11. ↵
    1. Heart Outcomes Prevention Evaluation Study Investigators
    . Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000;355(9200):253-9. Erratum in: Lancet 2000;356(9232):860.
    OpenUrlCrossRefPubMed
  12. ↵
    1. Adler AI,
    2. Stratton IM,
    3. Neil HA,
    4. Yudkin JS,
    5. Matthews DR,
    6. Cull CA,
    7. et al
    . Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000;321(7258):412-9.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Orchard TJ,
    2. Forrest KY,
    3. Kuller LH,
    4. Becker DJ
    Pittsburgh Epidemiology of Diabetes Complications Study. Lipid and blood pressure treatment goals for type 1 diabetes: 10-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications Study Diabetes Care 2001;24(6):1053-9.
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. Cushman WC,
    2. Evans GW,
    3. Byington RP,
    4. Goff DC Jr.,
    5. Grimm RH Jr.,
    6. Cutler JA,
    7. et al
    . Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362(17):1575-85. Epub 2010 Mar 14.
    OpenUrlCrossRefPubMed
  15. ↵
    1. Dalhousie University
    . Katie Clinical Significance Calculator. Halifax, NS: Dalhousie University; 2011. Available from: http://katie.dal.ca/tools.htm. Accessed 2013 Jan 11.
  16. ↵
    1. Allen MJ,
    2. Kelly KD,
    3. Fleming I
    . Meta-analysis supports ACCORD blood pressure but effect of excessive DBP lowering uncertain. J Hypertens 2012;30(2):436-8.
    OpenUrlPubMed
  17. ↵
    1. Osher E,
    2. Greenman Y,
    3. Tordjman K,
    4. Kisch E,
    5. Shenkerman G,
    6. Koffer M,
    7. et al
    . Attempted forced titration of blood pressure to <130/85 mm Hg in type 2 diabetic hypertensive patients in clinical practice: the diastolic cost. J Clin Hypertens (Greenwich) 2006;8(1):29-34.
    OpenUrl
  18. ↵
    1. Reboldi G,
    2. Gentile G,
    3. Angeli F,
    4. Ambrosio G,
    5. Mancia G,
    6. Verdecchia P
    . Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients. J Hypertens 2011;29(7):1253-69.
    OpenUrlCrossRefPubMed
  19. ↵
    1. Thompson SG,
    2. Higgins JP
    . How should meta-regression analyses be undertaken and interpreted? Stat Med 2002;21(11):1559-73.
    OpenUrlCrossRefPubMed
  20. ↵
    1. Pepine CJ,
    2. Handberg EM,
    3. Cooper-DeHoff RM,
    4. Marks RG,
    5. Kowey P,
    6. Messerli FH,
    7. et al
    . A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 2003;290(21):2805-16.
    OpenUrlCrossRefPubMed
  21. ↵
    1. Messerli FH,
    2. Mancia G,
    3. Conti CR,
    4. Hewkin AC,
    5. Kupfer S,
    6. Champion A,
    7. et al
    . Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006;144(12):884-93.
    OpenUrlCrossRefPubMed
  22. ↵
    1. American Diabetes Association
    . Standards of medical care in diabetes—2013. Diabetes Care 2013;36(Suppl 1):S11-66. Available from: http://care.diabetesjournals.org/content/36/Supplement_1/S11.full. Accessed 2013 Jan 14.
    OpenUrlFREE Full Text
PreviousNext
Back to top

In this issue

Canadian Family Physician: 59 (2)
Canadian Family Physician
Vol. 59, Issue 2
1 Feb 2013
  • Table of Contents
  • About the Cover
  • Index by author
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on The College of Family Physicians of Canada.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Uncertainty about the systolic blood pressure target in people with diabetes
(Your Name) has sent you a message from The College of Family Physicians of Canada
(Your Name) thought you would like to see the The College of Family Physicians of Canada web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Uncertainty about the systolic blood pressure target in people with diabetes
Michael Allen, Kim Kelly, Kim Fleming
Canadian Family Physician Feb 2013, 59 (2) 128-131;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Share
Uncertainty about the systolic blood pressure target in people with diabetes
Michael Allen, Kim Kelly, Kim Fleming
Canadian Family Physician Feb 2013, 59 (2) 128-131;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Results of ABCD NT
    • Results of ACCORD BP
    • Evidence for identifying an SBP target
    • Summary
    • Acknowledgment
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

  • Incertitude entourant les seuils de pression artérielle systolique chez les personnes diabétiques
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Evaluating routine pediatric growth measurement as a screening tool for overweight and obese status
  • Widespread misconceptions about pregnancy for women living with obesity
  • Social prescribing
Show more Commentary

Similar Articles

Navigate

  • Home
  • Current Issue
  • Archive
  • Collections - English
  • Collections - Française

For Authors

  • Authors and Reviewers
  • Submit a Manuscript
  • Permissions
  • Terms of Use

General Information

  • About CFP
  • About the CFPC
  • Advertisers
  • Careers & Locums
  • Editorial Advisory Board
  • Subscribers

Journal Services

  • Email Alerts
  • Twitter
  • RSS Feeds

Copyright © 2021 by The College of Family Physicians of Canada

Powered by HighWire