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. |