Pharmaceutical Treatment of Hypertension and Dyslipidemia in People With Diabetes: An Educator’s Perspective: Part I: Hypertension

M.J. is a 50-year-old white man who has had type 1 diabetes since age 20. He also has known retinopathy that has required laser treatment. He has no microalbuminuria. Treatment for depression was initiated more than 1 year ago. He has erectile dysfunction.

M.J. presents for his routine quarterly follow-up appointment with a blood pressure of 142/92 mmHg. He is on a four-shot insulin regimen using glargine and aspart. On physical exam, he has noted peripheral neuropathy. His family history includes hypothyroidism in his mother and hypertension in his father.

Physical examination and laboratory assays yield the following data:

• Height: 72 inches

• Weight: 171 lb

• BMI: 23 kg/m²

• Random capillary blood glucose: 126 mg/dl

• Triglycerides: 105 mg/dl

• Total cholesterol: 170 mg/dl

• HDL cholesterol: 69 mg/dl

• LDL cholesterol: 95 mg/dl

• Creatinine: 1.2 mg/dl

• Hemoglobin A₁c: 7.5%

• Electrocardiogram: normal

• Stress thalium: normal

The patient’s current medications and supplements include:

• ramipril, 5 mg daily initially (renal protection)

• insulin: glargine, 16 units a.m. and 20 units p.m.; aspart, 2 units/15 g carbohydrate for breakfast and 1 unit/15 g carbohydrate for lunch, dinner, and snacks

• simvastatin, 40 mg daily

• aspirin, 325 mg daily

• sertraline hydrochloride, 100 mg daily

• alpha lipoic acid, 300 mg three times a day

M.J. does not have a regular physical activity program and eats most of his lunches in restaurants. He consumes one to four alcoholic beverages in the evening and does not smoke. Diet history reveals that the carbohydrate content of his lunches and dinners varies greatly from meal to meal. Snacks are usually from the vending machine at work. His diet is estimated to include a daily average of 2,400 calories made up of 35% total fat, 12% saturated fat, 13% protein, and 52% carbohydrate

He bases his insulin doses on a sliding scale and not by anticipating his carbohydrate intake using a carbohydrate-to-insulin ratio.

Hypertension, a common comorbid condition in diabetes, is defined as a blood pressure ≥ 140/90 mmHg and increases the risk of both macrovascular and microvascular complications. M.J. has microvascular disease as evidenced by retinopathy and erectile dysfunction, presumably secondary to diabetic neuropathy. For people with diabetes, it is recommended that the target for blood pressure–lowering should be < 130/80 mmHg.1 

The U.K. Prospective Diabetes Study2 and the Hypertension Optimal Treatment (HOT) study3 both demonstrated improved outcomes, especially in preventing stroke, in patients assigned to lower blood pressure targets. In the HOT study, the epidemiological analysis showed that blood pressures ≥ 120/70 mmHg are associated with increased cardiovascular event rates and mortality in people with diabetes. There is no threshold value for blood pressure, and risk continues to decrease well into the normal range.

For treatment of high blood pressure, the American Diabetes Association recommends therapeutic lifestyle change (TLC) for a maximum of 3 months if blood pressure is 130–139 mmHg systolic or 80–89 mmHg diastolic. Medication should be initiated after 3 months if TLC does not decrease the blood pressure. However, in instances in which the systolic is ≥ 140 mmHg or the diastolic is ≥ 90 mmHg (as in the case above), medication should be started immediately in conjunction with TLC.1 

Lifestyle modifications to manage hypertension recommended in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) include weight reduction in individuals who are overweight or obese, dietary sodium reduction, physical activity, and moderate alcohol consumption.4 Table 1 lists lifestyle modifications to manage hypertension. Note the column that quantifies the benefit on systolic blood pressure of each lifestyle modification.4 

In the case above, M.J. needs to modify his cardiovascular risk factors. His diet is high in fat and sodium as noted by his eating restaurant lunches and vending machine snacks. Strategies to improve the quality of his food intake should include reduction in fats and sodium and an increase in the number of fruits and vegetables eaten daily. Referral to a dietitian for medical nutrition therapy would be appropriate. Instruction on the Dietary Approaches to Stop Hypertension (DASH) meal plan would be beneficial.4 Information on the DASH meal plan is available at the referenced Web site.

M.J’s alcohol intake is of concern because of his neuropathy, as well as the effect of alcohol on his triglycerides and hypertension. His provider would also need to quantify how much alcohol he is taking in. According to JNC 7, moderate consumption of alcohol means no more than two drinks (24 oz. of beer, 10 oz. of wine, or 3 oz. of 80-proof whiskey) per day in most men and no more than one drink per day in women and lighter individuals.

Encouraging physical activity (at least 30 minutes per day, most days of the week) would be ideal for this patient. However, his provider would need to further investigate whether his peripheral neuropathy is the reason behind his lack of physical activity.

Because M.J.’s blood pressure is > 140/90 mmHg, medication to treat his hypertension should be started immediately. For pharmacological management of hypertension in individuals with diabetes, most patients will require more than one medication to achieve adequate hypertension control. First-line therapy will likely be an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blockers (ARBs). M.J. has already been started on an ACE inhibitor because studies have shown that, in people with type 1 diabetes, ACE inhibition will delay the progression of nephropathy with or without hypertension.5 In addition, patients who are 55 years of age or older and have an additional cardiovascular risk factor should be started on an ACE inhibitor regardless of their blood pressure, because this has been shown to reduce cardiovascular mortality.4 However, his current reno-protective dose will need to be increased to a therapeutic dose for lowering his blood pressure.

By blocking ACE, ACE inhibitors prevent the formation of angiotensin II. This action results in arteriolar and venous dilation, reducing total peripheral resistance and arterial blood pressure. ACE inhibitors also suppress aldosterone secretion, increase renal blood flow, and increase circulating levels of vasodilating cytokine, bradykinin.

The ARBs act by blocking the effect of angiotensin II on specific tissue recptors. Unlike ACE inhibitors, these drugs do not inhibit the enzyme that catalyzes the conversion of angiotensin I to angiotensin II, nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. If ACE inhibitors or ARBs are used, monitor renal function and serum potassium levels.

Other strategies include the use of diuretics or b-blockers. Both have been repeatedly shown to be beneficial in reducing cardiovascular disease events during the treatment of uncomplicated hypertension and are therefore preferred agents for initial therapy. The ALLHAT study6 concluded that thiazide-type diuretics are comparable in most instances to ACE inhibitors or calcium channel–blockers in preventing one or more major forms of cardiovascular disease.

The hypotensive effect of this drug class is mediated by decreased plasma volume and arteriolar vasodilation. Thiazides had been avoided in the past in people with diabetes, but hyperglycemia is not a significant issue at lower doses (< 25 mg daily).

b-blockers decrease heart rate, force of heart contractions, cardiac output, and rennin excretion. They also have the potential to mask symptoms of hypoglycemia (at higher doses) and some may worsen lipid panels (although carvedelol has favorable effects on HDL cholesterol and trigylcerides). Table 2 provides a complete listing of antihypertensives with dosing recommendations, possible side effects, and other useful information.

Finally, because M.J. may need multiple drugs from different classes to control his hypertension, there are combination medications that usually contain a diuretic along with an ACE inhibitor, ARB, or b-blocker. These are also listed in Table 2.

Regular blood pressure monitoring should occur to verify that the goals for therapy are being achieved. Home monitoring devices may be prescribed, but clinicians should verify that patients are using the correct size of cuff and are using the equipment correctly. Lying and standing blood pressures should be monitored in the medical office to verify that patients are not experiencing orthostatic hypotension. Titration should be done carefully, especially in the elderly, to prevent hypotension and potential falls.

Hypertension substantially increases the risk of both macrovascular and microvascular complications including stroke, coronary artery disease, peripheral vascular disease, retinopathy, nephropathy, and possibly neuropathy. For M.J., it is imperative that adequate blood pressure control be achieved through medication and therapeutic lifestyle change. He already has retinopathy and neuropathy. It is crucial that he achieve acceptable blood pressure control to prevent further damage.

This article was adapted from a teleconference of the same title that was presented in spring 2003. The teleconference was developed by the American Diabetes Association Education Council, chaired by Paula Yutzey, RN, CDE. Committee members included Belinda P. Childs, ARNP, MN, BC-ADM, CDE; Marjorie Cypress, MS, C-ANP, CDE; Deborah Hinnen, ARNP, BC-ADM, CDE, FAAN; Davida F. Kruger, MSN, APRN-BC, BC-ADM; and Melinda Maryniuk, MEd, RD, CDE.

Special thanks to Stephanie Dunbar who coordinated this project and to Julie Miller, PharmD, for her work on Table 2.