1999 Clinical Advisory: Treatment Of Hypertension and Diabetes
James R. Sowers MD, and James Reed, MD
For the National Heart Lung Blood Institute, NIH
National High Blood Pressure Education Program (NHBPEP)
Correspondence to:
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
References
- 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.) |
Inadequate Response* |
Inadequate Response* |
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.
|