L.N. is a 49-year-old white woman with a history of type 2 diabetes,obesity, hypertension, and migraine headaches. The patient was diagnosed with type 2 diabetes 9 years ago when she presented with mild polyuria and polydipsia. L.N. is 5′4″ and has always been on the large side,with her weight fluctuating between 165 and 185 lb.

Initial treatment for her diabetes consisted of an oral sulfonylurea with the rapid addition of metformin. Her diabetes has been under fair control with a most recent hemoglobin A1c of 7.4%.

Hypertension was diagnosed 5 years ago when blood pressure (BP) measured in the office was noted to be consistently elevated in the range of 160/90 mmHg on three occasions. L.N. was initially treated with lisinopril, starting at 10 mg daily and increasing to 20 mg daily, yet her BP control has fluctuated.

One year ago, microalbuminuria was detected on an annual urine screen, with 1,943 mg/dl of microalbumin identified on a spot urine sample. L.N. comes into the office today for her usual follow-up visit for diabetes. Physical examination reveals an obese woman with a BP of 154/86 mmHg and a pulse of 78 bpm.

  1. What are the effects of controlling BP in people with diabetes?

  2. What is the target BP for patients with diabetes and hypertension?

  3. Which antihypertensive agents are recommended for patients with diabetes?

Diabetes mellitus is a major risk factor for cardiovascular disease (CVD). Approximately two-thirds of people with diabetes die from complications of CVD. Nearly half of middle-aged people with diabetes have evidence of coronary artery disease (CAD), compared with only one-fourth of people without diabetes in similar populations.

Patients with diabetes are prone to a number of cardiovascular risk factors beyond hyperglycemia. These risk factors, including hypertension,dyslipidemia, and a sedentary lifestyle, are particularly prevalent among patients with diabetes. To reduce the mortality and morbidity from CVD among patients with diabetes, aggressive treatment of glycemic control as well as other cardiovascular risk factors must be initiated.

Studies that have compared antihypertensive treatment in patients with diabetes versus placebo have shown reduced cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS), which followed patients with diabetes for an average of 8.5 years, found that patients with tight BP control (< 150/< 85 mmHg) versus less tight control (< 180/< 105 mmHg) had lower rates of myocardial infarction (MI), stroke, and peripheral vascular events. In the UKPDS, each 10-mmHg decrease in mean systolic BP was associated with a 12% reduction in risk for any complication related to diabetes, a 15% reduction for death related to diabetes, and an 11% reduction for MI. Another trial followed patients for 2 years and compared calcium-channel blockers and angiotensin-converting enzyme (ACE) inhibitors,with or without hydrochlorothiazide against placebo and found a significant reduction in acute MI, congestive heart failure, and sudden cardiac death in the intervention group compared to placebo.

The Hypertension Optimal Treatment (HOT) trial has shown that patients assigned to lower BP targets have improved outcomes. In the HOT trial,patients who achieved a diastolic BP of < 80 mmHg benefited the most in terms of reduction of cardiovascular events. Other epidemiological studies have shown that BPs > 120/70 mmHg are associated with increased cardiovascular morbidity and mortality in people with diabetes. The American Diabetes Association has recommended a target BP goal of < 130/80 mmHg. Studies have shown that there is no lower threshold value for BP and that the risk of morbidity and mortality will continue to decrease well into the normal range.

Many classes of drugs have been used in numerous trials to treat patients with hypertension. All classes of drugs have been shown to be superior to placebo in terms of reducing morbidity and mortality. Often, numerous agents(three or more) are needed to achieve specific target levels of BP. Use of almost any drug therapy to reduce hypertension in patients with diabetes has been shown to be effective in decreasing cardiovascular risk. Keeping in mind that numerous agents are often required to achieve the target level of BP control, recommending specific agents becomes a not-so-simple task. The literature continues to evolve, and individual patient conditions and preferences also must come into play.

While lowering BP by any means will help to reduce cardiovascular morbidity, there is evidence that may help guide the selection of an antihypertensive regimen. The UKPDS showed no significant differences in outcomes for treatment for hypertension using an ACE inhibitor or aβ-blocker. In addition, both ACE inhibitors and angiotensin II receptor blockers (ARBs) have been shown to slow the development and progression of diabetic nephropathy. In the Heart Outcomes Prevention Evaluation (HOPE)trial, ACE inhibitors were found to have a favorable effect in reducing cardiovascular morbidity and mortality, whereas recent trials have shown a renal protective benefit from both ACE inhibitors and ARBs. ACE inhibitors andβ-blockers seem to be better than dihydropyridine calcium-channel blockers to reduce MI and heart failure. However, trials using dihydropyridine calcium-channel blockers in combination with ACE inhibitors andβ-blockers do not appear to show any increased morbidity or mortality in CVD, as has been implicated in the past for dihydropyridine calcium-channel blockers alone. Recently, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in high-risk hypertensive patients,including those with diabetes, demonstrated that chlorthalidone, a thiazide-type diuretic, was superior to an ACE inhibitor, lisinopril, in preventing one or more forms of CVD.

L.N. is a typical patient with obesity, diabetes, and hypertension. Her BP control can be improved. To achieve the target BP goal of < 130/80 mmHg, it may be necessary to maximize the dose of the ACE inhibitor and to add a second and perhaps even a third agent.

Diuretics have been shown to have synergistic effects with ACE inhibitors,and one could be added. Because L.N. has migraine headaches as well as diabetic nephropathy, it may be necessary to individualize her treatment. Adding a β-blocker to the ACE inhibitor will certainly help lower her BP and is associated with good evidence to reduce cardiovascular morbidity. Theβ-blocker may also help to reduce the burden caused by her migraine headaches. Because of the presence of microalbuminuria, the combination of ARBs and ACE inhibitors could also be considered to help reduce BP as well as retard the progression of diabetic nephropathy. Overall, more aggressive treatment to control L.N.'s hypertension will be necessary. Information obtained from recent trials and emerging new pharmacological agents now make it easier to achieve BP control targets.

  • Hypertension is a risk factor for cardiovascular complications of diabetes.

  • Clinical trials demonstrate that drug therapy versus placebo will reduce cardiovascular events when treating patients with hypertension and diabetes.

  • A target BP goal of < 130/80 mmHg is recommended.

  • Pharmacological therapy needs to be individualized to fit patients'needs.

  • ACE inhibitors, ARBs, diuretics, and β-blockers have all been documented to be effective pharmacological treatment.

  • Combinations of drugs are often necessary to achieve target levels of BP control.

  • ACE inhibitors and ARBs are agents best suited to retard progression of nephropathy.

Evan M. Benjamin, MD, FACP, is an assistant professor of medicine and Vice President of Healthcare Quality at Baystate Medical Center in Springfield, Mass.

ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel-blocker vs. diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
American Diabetes Association:Hypertension management in adults with diabetes (Position Statement).
Diabetes Care
(Suppl. 1):
Geiss LS:Mortality in NIDDM. In
Diabetes in America.
2nd ed. Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennett PH, Eds. Washington, D.C., U.S. Department of Health and Human Services, National Institutes of Health,
(NIH publ. no. 95-1468), p.
Hansson L,Zanchetti A, Carruthers SG, 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.
Huang ES, Meigs JB, Singer DE: The effect of interventions to prevent CV disease in patients with type 2 diabetes mellitus.
Am J Med
Tuomelehto J,Rastenyte D, Birkenhager WH, Thijs L, Antikainen R, Bulpitt CJ, Fletcher AE,Forette F, Goldhaber A, Palatini P, Sarti C, Fagard R: Effects of calcium blockade in older patients with diabetes and systolic hypertension.
N Engl J Med
U.K. Prospective Diabetes Study Group:Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS 39).
Wingard DL: Heart disease and diabetes. In
Diabetes in America.
2nd ed. Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennett PH, Eds. Washington, D.C., U.S. Department of Health and Human Services, National Institutes of Health,
(NIH publ. no. 95-1468), p.