In type 2 diabetes, hypertension is often present as part of treatment of hypertension in adult patients with diabetes (Technical Review) …
POSITION
STATEMENT
Hypertension Management in Adults With Diabetes
AMERICAN DIABETES ASSOCIATION
H
ypertension defined as a blood pressure 140/90 mmHg is an extremely common comorbid condition in diabetes, affecting 20 60 of patients with diabetes, depending on obesity, ethnicity, and age In type 2 diabetes, hypertension is often present as part of the metabolic syndrome of insulin resistance also including central obesity and dyslipidemia In type 1 diabetes, hypertension may reflect the onset of diabetic nephropathy Hypertension substantially increases the risk of both macrovascular and microvascular complications, including stroke, coronary artery disease, and peripheral vascular disease, retinopathy, nephropathy, and possibly neuropathy In recent years, adequate data from welldesigned randomized clinical trials have demonstrated the effectiveness of aggressive treatment of hypertension in reducing both types of diabetes complications Scope These recommendations are intended to apply to nonpregnant adults with type 1 or type 2 diabetes Target audience These recommendations are intended for the use of health care professionals who care for patients with diabetes and
hypertension, including specialist and primary care physicians, nurses and nurse practitioners, physicians assistants, educators, dietitians, and others
Method These recommendations are based on the American Diabetes Association Technical Review Treatment of Diabetes in Adult Patients with Hypertension A technical review is a systematic review of the medical literature that has been peer-reviewed by the American Diabetes Associations Professional Practice Committee Evidence review: hypertension as a risk factor for complications of diabetes Diabetes increases the risk of coronary events twofold in men and fourfold in women Part of this increase is due to the frequency of associated cardiovascular risk factors such as hypertension, dyslipidemia, and clotting abnormalities In observational studies, people with both diabetes and hypertension have approximately twice the risk of cardiovascular disease as nondiabetic people with hypertension Hypertensive diabetic patients are also at increased risk for diabetesspecific complications including retinopathy and nephropathy In the UK Prospective Diabetes Study UKPDS epidemiological study, each 10-mmHg decrease in mean systolic blood
pressure was associated with reductions in risk of 12 for any complication related to diabetes, 15 for deaths related to diabetes, 11 for myocardial infarction, and 13 for microvascular complications No threshold of risk was observed for any end point
Evidence for target levels of blood pressure in patients with diabetes The UKPDS and the Hypertension Optimal Treatment HOT trial both demonstrated improved outcomes, especially in preventing stroke, in patients assigned to lower blood pressure targets Optimal outcomes in the HOT study were achieved in the group with a target diastolic blood pressure of 80 mmHg achieved 826 mmHg Randomized clinical trials demonstrate the benefit of targeting a diastolic blood pressure of 80 mmHg Epidemiological analyses show that blood pressures 120/70 mmHg are associated with increased cardiovascular event rates and mortality in persons with diabetes Therefore, a target blood pressure goal of 130/80 mmHg is reasonable if it can be safely achieved There is no threshold value for blood pressure, and risk continues to decrease well into the normal range Achieving lower levels, however, would increase the cost of care as well as drug side effects and is
often difficult in practice Whether even more aggressive treatment would further reduce the risk is an unanswered question, but may be answered by clinical trials now in progress Evidence for non-drug management of hypertension Dietary management with moderate sodium restriction has been effective in reducing blood pressure in individuals with essential hypertension Several controlled studies have looked at the relationship between weight loss and blood pressure reduction Weight reduction can reduce blood pressure independent of sodium intake and also can improve blood glucose and lipid levels The loss of one kilogram in body weight has resulted in decreases in mean arterial blood pressure of 1 mmHg The role of very low calorie diets and pharmacologic agents that induce weight loss in the management of hypertension in diabetic patients has not
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The recommendations in this paper are based on the evidence reviewed in the following publication: The treatment of hypertension in adult patients with diabetes Technical Review Diabetes Care 25:134 147, 2002 The initial draft of this position statement was prepared by Carlos Arauz-Pacheco, MD, Marian A Parrott, MD, MPH, and Phillip
Raskin, MD The paper was peer-reviewed, modified, and approved by the Professional Practice Committee and the Executive Committee, October 2001 Abbreviations: ACE, angiotensin-converting enzyme; ALLHAT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; ARB, angiotensin receptor blocker; DCCB, dihydropyridine calcium channel blocker; HOT, Hypertension Optimal Treatment; JNC VI, Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; UKPDS, UK Prospective Diabetes Study 2004 by the American Diabetes Association
DIABETES CARE, VOLUME 27, SUPPLEMENT 1, JANUARY 2004
Position Statement
been adequately studied Some appetite suppressants may induce increases in blood pressure levels, so these must be used with care Given the present evidence, weight reduction should be considered an effective measure in the initial management of mild-to-moderate hypertension, and these results could probably be extrapolated to the diabetic hypertensive population Sodium restriction has not been tested in the diabetic population in controlled clinical trials However, results from controlled trials in essential
hypertension have shown a reduction in systolic blood pressure of 5 mmHg and diastolic blood pressure of 23 mmHg with moderate sodium restriction from a daily intake of 200 mmol [4,600 mg] to 100 mmol [2,300 mg] of sodium per day A dose response effect has been observed with sodium restriction Even when pharmacologic agents are used, there is often a better response when there is concomitant salt restriction due to the aforementioned volume component of the hypertension that is almost always present The efficacy of these measures in diabetic individuals is not known Moderately intense physical activity, such as 30 45 min of brisk walking most days of the week, has been shown to lower blood pressure and is recommended in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure JNC VI The American Diabetes Association Consensus Development Conference on the Diagnosis of Coronary Heart Disease in People with Diabetes has recommended that diabetic patients who are 35 years of age or older and are planning to begin a vigorous exercise program should have exercise stress testing or other appropriate noninvasive testing
Stress testing is not generally necessary for asymptomatic patients beginning moderate exercise such as walking Smoking cessation and moderation of alcohol intake are also recommended by JNC VI and are clearly appropriate for all patients with diabetes Evidence for drug therapy of hypertension There are a number of trials demonstrating the superiority of drug therapy versus placebo in reducing outcomes including cardiovascular events and microvascular complications of retinopathy and proS66
gression of nephropathy These studies used different drug classes, including angiotensin-converting enzyme ACE inhibitors, angiotensin receptor blockers ARBs, diuretics, and -blockers, as the initial step in therapy All of these agents were superior to placebo; however, it must be noted that many patients required three or more drugs to achieve the specified target levels of blood pressure control Overall there is strong evidence that pharmacologic therapy of hypertension in patients with diabetes is effective in producing substantial decreases in cardiovascular and microvascular diseases There are limited data from trials comparing different classes of drugs in patients with diabetes and
hypertension The UKPDS-Hypertension in Diabetes Study showed no significant difference in outcomes for treatment based on an ACE inhibitor compared with a -blocker There were slightly more withdrawals due to side effects and there was more weight gain in the -blocker group In postmyocardial infarction patients, -blockers have been shown to reduce mortality There are numerous studies documenting the effectiveness of ACE inhibitors and ARBs in retarding the development and progression of diabetic nephropathy ACE inhibitors have a favorable effect on cardiovascular outcomes, as demonstrated in the MICROHOPE study This cardiovascular effect may be mediated by mechanisms other than blood pressure reduction It is possible that other drug classes may behave similarly Some studies have shown an excess of selected cardiac events in patients treated with dihydropyridine calcium channel blockers DCCBs compared with ACE inhibitors Ongoing trials including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT study should help to resolve this issue DCCBs in combination with ACE inhibitors, -blockers, and diuretics, as in the HOT study and the Systolic
Hypertension in Europe Syst-Eur Trial, did not appear to be associated with increased cardiovascular morbidity However, ACE inhibitors and -blockers appear to be superior to DCCBs in reducing myocardial infarction and heart failure Therefore, DCCBs appear to be appropriate agents in addition to, but not instead of, ACE inhibitors and -blockers Non-DCCBs ie, verapamil and dil-
tiazem may reduce coronary events In short-term studies, non-DCCBs have reduced albumin excretion There are no long-term studies of the effect of -blockers, loop diuretics, or centrally acting adrenergic blockers on long-term complications of diabetes The -blocker arm of the ALLHAT study was stopped by the data and safety monitoring committee because of an increase in cases of new-onset heart failure in patients assigned to the -blocker While this could merely represent unmasking of heart failure in patients previously treated with an ACE inhibitor or a diuretic, it seems reasonable to use these as second-line agents when preferred classes have been ineffective or when other specific indications, such as benign prostatic hypertrophy BPH, are present Summary There is a strong epidemiological connection between
hypertension in diabetes and adverse outcomes of diabetes Clinical trials demonstrate the efficacy of drug therapy versus placebo in reducing these outcomes and in setting an aggressive blood pressurelowering target of 130/80 mmHg It is very clear that many people will require three or more drugs to achieve the recommended target Achievement of the target blood pressure goal with a regimen that does not produce burdensome side effects and is at reasonable cost to the patient is probably more important than the specific drug strategy Because many studies demonstrate the benefits of ACE inhibitors on multiple adverse outcomes in patients with diabetes, including both macrovascular and microvascular complications, in patients with either mild or more severe hypertension and in both type 1 and type 2 diabetes, the established practice of choosing an ACE inhibitor as the first-line agent in most patients with diabetes is reasonable In patients with microalbuminemia or clinical nephropathy, both ACE inhibitors type 1 and type 2 patients and ARBs type 2 patients are considered first-line therapy for the prevention of and progression of nephropathy However, other strategies including
diuretic and -blocker based therapy are also supported by evidence Because of lingering concerns about the lower effectiveness of DCCBs compared with ACE inhibitors, ARBs, -blockers, or diuretics in decreasing coronary events and heart failure and in
DIABETES CARE, VOLUME 27, SUPPLEMENT 1, JANUARY 2004
Treatment of Hypertension
Table 1–Indications for initial treatment and goals for adult hypertensive diabetic patients
Systolic Diastolic Goal mmHg 130 80 Behavioral therapy alone 130139 8089 maximum 3 months then add pharmacologic treatment Behavioral therapy phar140 90 macologic treatment
pressure confirmed on a separate day C Orthostatic measurement of blood pressure should be performed when clinically indicated to assess for the presence of autonomic neuropathy E
Goals
Patients with diabetes should be treated to a systolic blood pressure 130 mmHg B Patients with diabetes should be treated to a diastolic blood pressure 80 mmHg B
reducing progression of renal disease in diabetes, these agents should be used as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure Other
classes, including -blockers, may be used under specific indications such as symptoms of BPH for -blockers or other agents have failed to control the blood pressure or have unacceptable side effects Blood pressure, orthostatic changes, renal function, and serum potassium should be monitored at appropriate intervals Treatment decisions should be individualized based on the clinical characteristics of the patient, including comorbidities as well as tolerability, personal preferences, and cost Recommendations Refer to Table 1 for recommendations on initial treatment and goals for adult hypertensive diabetic patients Screening and diagnosis
Treatment
Blood pressure should be measured at every routine diabetes visit Patients found to have systolic blood pressure 130 mmHg or diastolic blood pressure 80 mmHg should have blood
Patients with a systolic blood pressure of 130 139 mmHg or a diastolic blood pressure of 80 89 mmHg should be given lifestyle/behavioral therapy alone for a maximum of 3 months and then, if targets are not achieved, should also be treated pharmacologically with agents that block the renin-anglotensin system E Patients with hypertension systolic blood
pressure 140 mmHg or diastolic blood pressure 90 mmHg should receive drug therapy in addition to lifestyle/behavioral therapy A Multiple drug therapy two or more agents at proper doses is generally required to achieve blood pressure targets B Initial drug therapy for those with a blood pressure 140/90 should be with a drug class demonstrated to reduce CVD events in patients with diabetes ACE inhibitors, ARBs, -blockers, diuretics, calcium channel blockers A All patients with diabetes and hypertension should be treated with a regimen that includes either an ACE inhibitor or ARB If one class is not tol-
erated, the other should be substituted If needed to achieve blood pressure targets, a thiazide diuretic should be added E If ACE inhibitors or ARBs are used, monitor renal function and serum potassium levels E While there are no adequate head-tohead comparisons of ACE inhibitors and ARBs, there is clinical trial support for each of the following statements: In patients with type 1 diabetes with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy A In patients with type 2 diabetes, hypertension, and
microalbuminuria, ACE inhibitors and ARBs have been shown to delay the progression to macroalbuminuria A In those with type 2 diabetes, hypertension, macroalbuminuria 300 mg/day, and renal insufficiency, an ARB should be strongly considered A In elderly hypertensive patients, blood pressure should be lowered gradually to avoid complications E Patients not achieving target blood pressure on three drugs, including a diuretic, and patients with a significant renal disease should be referred to a physician experienced in the care of patients with hypertension E
Bibliography Arauz-Pacheco C, Parrott MA, Raskin P: The treatment of hypertension in adult patients with diabetes Technical Review Diabetes Care 25:134 147, 2002 Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, Tuttle K, Douglas J, Hsueh W, Sowers J: Preserving renal function in adults with hypertension and diabetes: a consensus approach Am J Kid Dis 36: 646 661, 2000
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Source:mrrc.isr.umich.edu
