Hypertension in diabetes mellitus
The best ways to treat
by Sajjad Tavassoly and Ally PH Prebtani, MD
Vol.20, No.05, August 2012

Diabetes mellitus (DM) and hypertension (HTN) are two of Canada’s most common and worrisome diseases. It’s estimated that 2 million Canadians are living with type 2 DM and another 6 million have been diagnosed with HTN.1,2 The mortality and morbidity rates are higher when patients have a combination of both DM and HTN. This combination is by no means a rare one, with over 1 million Canadians having been diagnosed with both diseases.1 Mortality rates for patients diagnosed with both these conditions are 2 times greater than those diagnosed with HTN only.1 It’s critical to correctly diagnose patients with HTN based on standards to prevent further complications.

The Canadian Diabetes Association (CDA) guidelines on the diagnosis of HTN3 are as follows.

Hypertension in patients with diabetes:

  • systolic BP of>130 mm Hg, or
  • diastolic BP of> 80 mm Hg

Approach:

  • set target BP at 130/80 mm Hg
  • treat with antihypertensive medication
  • advise on lifestyle interventions

The high morbidity of having both DM and HTN arises from its association with serious cardiovascular diseases (CVDs) including stroke, coronary artery disease, heart failure, and kidney disease.4,5 Research suggests that up to 75% of CVD in patients with type 2 DM and HTN may be contributed significantly to HTN alone.6 HTN negatively affects vital organs such as the kidneys (proteinuria, chronic renal failure and end-stage renal disease), the heart (left-ventricular hypertrophy, atrial fibrillation, angina, myocardial infarction and congestive heart failure) and brain (stroke, dementia and retinopathy). Complications associated with HTN are worsened in the presence of diabetes and are the main causes of death in people diagnosed with DM and HTN.7 Furthermore, the UK Prospective Diabetes Study Group (UKPDS) has shown that treating patients for HTN significantly lowers cardiovascular complications.8 Such findings have led to the well-established and most cost-effective practice of treating HTN in diabetics to reach a target BP of130/80 mm Hg.3

Achieving the target

Target BP for patients diagnosed with DM and HTN is mainly achieved through pharmacological agents; however, the adaptation and maintenance of a healthy lifestyle is crucial. It’s critical for patients to attain global vascular health through smoking cessation, lipid control, weight control and physical activity. Table1 contains further recommendations on lifestyle interventions for treating HTN. On a pharmacological approach, CDA recommends angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) as first-line treatment.3 These recommendations are supported by several randomized controlled studies9-11 and are currently being applied in clinical settings. ACEIs and ARBs also have additional renal benefits, which make them desirable for HTN in diabetics.3 An alternative first-line treatment recommended by the Canadian Hypertension Education Program (CHEP) is long-acting dihydropyridine calcium channel blockers (CCBs) and low-dose thiazide or thiazide-like diuretics.12 Even though these first-line treatments have been effective in lowering BP, achieving the target BP in diabetics with HTN remains a challenge.13 A review of 24 observational studies indicates that only12% of diabetics were able to reach a BP of130/85 mm Hg.14 As a result, it may be necessary to increase drug dosage accordingly or rely on combination therapy to achieve target BP. Table 2 contains treatment recommendations for HTN in association with DM.

Drug combination

First-line treatment combinations may be used to achieve target BP. However, a combination of an ACEI and an ARB has shown to have undesirable effects with no additional advantage in achieving target BP,15,16 and so should be avoided. It’s important to note that 3-4 medications may be required to obtain target BP in diabetics.17 Other add-on drugs may be spironolactone or beta-blockers.18,19 Keep in mind that nonsteroidal anti-inflammatory drugs (NSAIDs) can block the effects of some antihypertensive medications.20 Information on several therapeutic drugs is presented in Table 3.

Resistance

In many cases, patients with higher doses or multiple classes of hypertensive medication will still remain HTN resistant. It’s essential to investigate the obstacles associated with HTN resistance. Pay particular attention to secondary HTN. Even though up to 95% of HTN cases are thought to result from essential HTN, it’s crucial to consider and test patients for secondary HTN. Information on the consideration and testing for secondary HTN is presented in Table 4. Medication adherence is another factor associated with HTN resistance. Research has shown that patients taking 4 daily doses of medication have an adherence percentage of only 51% compared to 79% for those with only1 dose of daily meds.21 These findings suggest a better adherence with single pill combination therapy. Single pill combination therapy may also be more cost effective. Table 5 contains information on medication costs. Also, the common co-existence of sleep apnea and HTN should be investigated since the treatment of obstructive sleep apnea has shown to improve essential HTN.22 In cases of HTN resistance, other factors such as extracellular volume expansion, white coat HTN and pseudo-HTN should be considered.

Home BP measurement

Encourage patients to regularly conduct home blood pressure measurements, which have high reliability and afford several advantages. Those with white coat HTN will be able to obtain more reliable readings in their own homes. Home BP measurements may confirm the diagnosis of hypertension, improve BP control and encourage medication adherence.23 Practitioners may provide patients with resources on how to carry out home BP measurements. A video on how to conduct this measurement is available at http://targethypertension.ca/resources/Video.

The bottom line

Coexistence of DM and HTN is associated with high mortality and morbidity due to serious CVD, especially stroke. Treating HTN in people with diabetes is achieved through the use of antihypertensive medications. Lifestyle interventions including the maintenance of healthy body weight and the reduction of alcohol and sodium uptake are also essential in achieving and maintaining target BP. Therapies that down-regulate the stimulation of renin-angiotensin system (RAS) have promising effects, but it may be necessary to include add-on drugs for optimal results. Cases of high BP resistance require attention and should be investigated for associated secondary causes.

 

Reference

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  2. Supina AL, et al. Clin Ther 2004;26(4):598-606.
  3. 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. Available from: www.diabetes.ca/files/cpg2008/cpg-2008.pdf Accessed April 2, 2012.
  4. American Diabetes Association. Diabetes Care 2002;25(1):199-201.
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  9. Lewis EJ, et al; Collaborative Study Group. Renopro­tective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. NEJM 2001;345:851-60.
  10. Brenner BM, et al; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. NEJM 2001;345:861-9.
  11. The ACE Inhibitors in Diabetic Nephropathy Trialist Group. Ann Intern Med 2001;134:370-9.
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  13. Putnam W, et al. Can Fam Physician 2009;55(July):728-34.
  14. McLean DL, et al. Can J Cardiol 2006;22(10):855-60.
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  16. Yusuf S, et al. NEJM 2008;358(15):1547-59.
  17. Pool JL. Am J Hypertens 2003;16(11 Pt 2):36S-40S.
  18. UK Prospective Diabetes Study Group. (UKPDS 39). BMJ 1998;317:713-20.
  19. Schjoedt KJ, et al. Kidney Int 2005;68:2829-36.
  20. Schwartz G. Health Care Guideline: Hypertension Diagnosis and Treatment. Thirteenth Edition. En ICSI. Institute for Clinical Systems Improvement. 2010. Available from: www.icsi.org/hypertension_4/hypertension_diagnosis_and_treatment_4.html. Accessed April 3, 2012.
  21. Claxton AJ, et al. Clin Ther 2001;23(8):1296-310.
  22. Silverberg D, et al. Am Fam Physician 2002;65:229-36.
  23. Rabi DM, et al. The 2011 Canadian hypertension education program recommendations for the management of hypertension: blood pressure measurement, diagnosis, assessment of risk, and therapy. Can J Cardiol 2011;27:415-33.
  24. Padwal R, et al. Applying the 2005 Canadian Hyperten­sion Education Program recommendations: 3. Lifestyle modifications to prevent and treat hypertension. CMAJ 2005;173(7):749-51.
  25. Canadian Hypertension Education Program Recommen­dations. “Part 2: Recommendations for Hypertension Treatment.” 2012.
  26. C. Health. Aldactone (spironolactone). MediResource Inc. 2011 Available from: http://chealth.canoe.ca/condition_info_details.asp?disease_id=194 Accessed April 1, 2012.
  27. Onusko E. Am Fam Physician 2003;67:67-74.

Sajjad Tavassoly is completing his Bachelor of Health Sciences (Honours), Class of 2014, McMaster University.

Ally PH Prebtani, MD, FRCPC, is Associate Professor of Medicine and Program Director of the Endocrinology & Metabolism Residency Training Program at McMaster University in Hamilton, ON. He is also Director of the Internal Medicine International Health Program at McMaster University.

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