James R. Sowers MD, and James Reed, MD
For the National Heart Lung Blood Institute, NIH
National High Blood Pressure Education Program (NHBPEP)
James R. Sowers, MD
Professor of Medicine and Cell Biology
Chief, Endocrinology, Diabetes And Hypertension
SUNY Health Science Center at Brooklyn
Representative from the American Diabetes Association
to the NHBPEP Coordinating Committee
James Reed, MD
Professor of Medicine
Director, Clinical Research Center
Morehouse School of Medicine
Representative from the International Society of Hypertension
in Blacks & the NHBPEP Coordinating Committee
The purpose of this clinical advisory update is to alert clinicians about new information to be used in their clinical practice. Therapy in patients with hypertension and diabetes begins with weight reduction, increased physical activity and moderation of salt and alcohol intake.1,2 The goal blood pressure is 130/85 mm Hg. If it is not reached, then pharmacological intervention is indicated.1,2 Based on clinical trial results,4 classes of drugs are effective first-line therapy in these patients (Fig 1). Most hypertensive diabetic patients will require the use of more than one agent to achieve a therapeutic goal of 130/85.2
Because proteinuria is a harbinger for CVD and renal disease,3 ACE inhibitors may afford unique benefits in preventing CVD as well as diabetic nephropathy.1,2 The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial4 showed cardioprotective effect of ACE inhibitors. Recently, the UK Prospective Diabetes Study Group reported5,6 blood pressure lowering with an atenolol based program was just as effective as a captopril based regimen in reducing the incidence of diabetic complications (both microvascular and macrovascular). Many required these drugs plus a diuretic to achieve "tight control of 144/82 mm Hg". In patients assigned to less tight control (154/87 mm Hg), there was less use of multiple antihypertensive agents. Risk reductions in the group assigned to tight blood pressure control were 24% in diabetes-related end points, 32% in deaths related to diabetes, 44% in strokes, and 37% in microvascular end points, predominantly diabetic retinopathy. These results suggest that combination therapy with either an ACE inhibitor or a beta blocker are very effective in reducing macrovascular and microvascular events providing blood pressure is adequately lowered.
Low dose thiazide diuretics (i.e., 25 mg or less of hydrochlorothizide or chlorthialidone daily), are effective and safe antihypertensive agents in type II diabetic patients.1,2 In the Systolic Hypertension in the Elderly (SHEP) study, elderly type II diabetic men had reductions in stroke and coronary heart disease similar to those without diabetes.7 Low dose diuretics are not associated with significant metabolic abnormalities.1,2 Lower dose diuretics in conjunction with ACE inhibitors usually produces substantial synergism in reducing blood pressure, and use of these agents together, further minimizes potential metabolic problems. Diuretics are important because of the salt sensitivity and expanded plasma volume that is often present in diabetic patients8 particularly in those requiring several drugs to control blood pressure levels of <130/85.
Results from the subset analysis of type II diabetics in the Hypertension Optimal Treatment (HOT) trial9 and a recent sub-analysis of this cohort in the Sys-Eur Trial10 suggest that further reduction in diastolic blood pressure below 85 mm Hg is beneficial. HOT also confirmed that multiple drug regimes are required to reach goal for most hypertensive diabetics. In the Sys-Eur trial, while systolic blood pressure was reduced by a comparable amount in each group (-22±16 mm Hg, nondiabetic vs. -22.1±14 mm Hg, diabetic group), the risk reduction in mortality from CVD was 13% for the nondiabetics and 76% for the diabetic patients.10 Thus, the benefit conferred per mm Hg blood pressure reduction appears to be greater in persons with type II diabetes than in those with hypertension but no coexistent diabetes mellitus. Data from a large trial that was recently reported also supported this notion.11
- National High Blood Pressure Education Program Working Group report on hypertension in diabetes.Hypertension 1994;23:145-158.
- Sixth Report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI). Arch Int Med 1997;157:2413-2446.
- Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Int Med 1997;157:1413-1418.
- Estacio RO, Schrier RW Antihypertensive therapy in type 2 diabetes: implications of the appropriate blood pressure control in diabetes (ABCD) trial. Am J Cardiol 1998; 12(9B):9R-14R.
- UKPDS Group. UK Prospective Diabetes Study 38: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. BMJ 1998;317:703-713.
- UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-853.
- Curb JD, Pressel MS, Cutler JA, Applegate WB, et al. Effect of a diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated hypertension. JAMA 1996;276:1886-1892.
- Sowers JR. Hypertension in type II diabetes: update on therapy. J Clin Hypertens 1999;1:41-47.
- Hansson L, Zanchetti A,Carruthers SB, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood pressure-lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. HOT Study Group. Lancet 1998;351:1755-1762.
- Staussen JA, Fagard R, Thys L, et al., for the Systolic Hypertension-Europe (Syst-Eur) trial investigators. Morbidity and mortality in the placebo-controlled European trial on isolated systolic hypertension in the elderly. Lancet 1997;350:757-764.
- Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342(3):145-153.
Acknowledgements: The authors with to thank Ed Roccella, Marvin Moser, Joe Izzo and Sheldon Sheps for their thoughtful input. We also wish to thank Paddy McGowan for her help in preparing this update.
TREATMENT GOAL < 130/85 MM HG
|Initiate Pharmacologic Selection (in alphabetical order) plus Lifestyle Modifications
ACE inhibitors, beta blockers, calcium antagonists, and diuretics in low dose are preferred because of clinical trial data/
(ACE inhibitors are drugs of choice in patients with albuminuria/ proteinuria.)
|Add a second or third agent, one of which should be a diuretic, if not already prescribed|
Algorithm for antihypertensive therapy in the diabetic person.
*An adequate response means goal blood pressure achieved or considerable progress made.