Hypertension in Diabetes Patients
Hypertension should be treated aggressively in diabetic patients, especially if there is evidence of renal disease. Hypertension is a “silent” disease with no obvious symptoms; as a result, most patients do not seek medical attention. It is twice as common in people with diabetes, and, in most patients, multiple checks may be required to confirm a diagnosis. Hypertension contributes to the development and progression of the chronic complications of diabetes, such as retinopathy, nephropathy, and various forms of cardiovascular disease. By achieving and maintaining blood pressure within the normal ranges, the risk of other complications can be minimized. In other words, tight blood pressure control is associated with fewer diabetes-related deaths. Approximately 65% of people with diabetes die from heart disease and stroke.
Lifestyle changes in people with diabetes are the first step towards the treatment of hypertension. Making nutritional changes, losing weight, increasing physical activity, and limiting alcohol intake are some steps that should be taken. The second step is pharmacotherapy, especially in patients with blood pressure of 140/90 mmHg or higher. Diabetic patients need ongoing support from their families and caregivers to make and maintain these changes. In fact, caregivers have a tremendous role in the health and well-being of the person with diabetes and hypertension.
Because some antihypertensive medications may worsen diabetes control and have unpleasant side effects, they are not taken as prescribed. The question is which antihypertensive drug has the best possible outcome and least undesirable effects in patients with diabetes and hypertension. In any event, patients with diabetes require ongoing monitoring and support to get the maximum benefit from changes in their lifestyle and from their antihypertensive medication. According to the American Diabetes Association, 71% of people with diabetes have hypertension and only 12% have well-controlled blood pressure.
Overall, the Joint National Committee recommends three blood pressure goals: < 140/90 mmHg for uncomplicated hypertension; < 130/80 mmHg for hypertensive patients with diabetes; and < 125/75 mmHg for patients with renal insufficiency and proteinuria less than 1 g/24 h.
Classification of hypertension
There are three categories of hypertension in patients with diabetes:
- Primary, or essential, hypertension is the most common type of hypertension in persons with diabetes. Its cause is unknown.
- Secondary hypertension, which includes hypertension associated with diabetic renal disease as well as hypertension from other diseases, contributes to 5% to 10% of the cases.
- Other problematic manifestations of blood pressure control may be associated with both primary and secondary hypertension. Examples are isolated systolic hypertension and orthostatic hypotension, which will be briefly discussed in the following section.
Etiology
It must be emphasized that hypertension, regardless of its cause, is one of the primary risk factors for cardiovascular disease, stroke, renal disease, and diabetes. Hypertension accelerates the progression of macrovascular and microvascular disease in diabetes and is often associated with early mortality. Its effects on vascular complications must be considered a major risk factor in diabetes.
Diagnosis of hypertension
Multiple measurements over one to several weeks are required to confirm hypertension. Average levels of diastolic blood pressure of greater than or equal to 90 mmHg and/or systolic blood pressure of greater than or equal to 140 mmHg are required for diagnosis. After the diagnosis is made, controlling hypertension requires proper treatment and ongoing monitoring. For the person with diabetes, the goal of therapy is to decrease blood pressure to < 130/80 mmHg. This more aggressive goal for persons with diabetes has been established because control of hypertension in persons with diabetes has been demonstrated to reduce the rate of progression of diabetic nephropathy and reduce the complications of hypertensive nephropathy, cerebrovascular disease, and cardiovascular disease. All patients with diabetic hypertension should be monitored for microalbuminuria, which is a cardiovascular risk factor. In the Hypertension Optimal Therapy (HOT) study, people with diabetes who kept their diastolic blood pressure at 80 (vs 90 mmHg) had a 51% lower risk of experiencing a cardiovascular event.
The United Kingdom Prospective Diabetes Study (UKPDS), a 10-year study of more than 1,000 people who had type 2 diabetes and hypertension, clearly demonstrated that blood pressure control is important. Aggressive treatment of even mildly elevated blood pressure was shown to be beneficial. The UKPDS showed that lowering blood pressure to a mean level of 144/82 mmHg significantly reduced vision loss, diabetes-related deaths, strokes, heart failure, and various microvascular complications; the control group, which had more health-related problems, maintained an average blood pressure of 154/87 mmHg.
Isolated systolic hypertension is a systolic blood pressure > 140 mmHg with a diastolic reading of < 90 mmHg, according to the International Society of Hypertension. Isolated systolic hypertension is most common in the elderly, and elevations above 140 mmHg increase the risk for a cardiovascular event. A systolic blood pressure of 150 mmHg places a person at a two times higher risk of having a stroke or heart attack. Lifestyle changes, especially following a healthy diet and decreased intake of sodium, have been helpful for some. However, multiple medications, including a diuretic, are needed for treatment.
Orthostatic hypotension is a significant drop in blood pressure upon standing (a greater than 30 mmHg drop in systolic or a 10 mmHg drop in diastolic pressure within two minutes of going from supine to standing). It often happens in persons who have had diabetes for a long time and is related to autonomic neuropathy. The use of some medications (such as methyldopa) or dehydration is also a contributor to orthostatic hypotension. Nerves that normally help the blood flow toward the heart are not working properly. Dizziness, lightheadedness, visual changes, falls, and injury can also occur.
Treatment by Lifestyle Changes
Lifestyle modifications have been proven to help with blood pressure control. In people with stage 1 hypertension (140/90 mmHg), with no other risk factors and no target organ damage, lifestyle changes alone may control blood pressure; others need to couple lifestyle modifications with drug therapy. People with diabetes need medication in addition to lifestyle treatment if blood pressure is stage 1 or higher. The following are some American Diabetes Association recommendations:
Weight loss of even 10 to 20 lb can help control elevated blood pressure in people who are overweight. Weight loss can be achieved if an individualized program of mild caloric restriction (250 to 500 fewer calories per day) and increased caloric expenditure (physical activity) is followed. An additional benefit of weight loss involves improved blood glucose control. People with diabetes who have high-normal blood pressure (between 130/80 and 140/90 mmHg) can try lifestyle modifications for three to six months prior to treatment with medications.
Excess alcohol intake can cause elevated blood pressure and stroke. Alcohol should be limited to no more than two drinks per day for men and no more than one drink per day for women. One serving is equal to 1 oz of liquor, 5 oz of wine, or 12 oz of beer.
Many people with hypertension are sensitive to sodium and will benefit from limiting the amount of salt in their diets. Most sodium (salt) that we eat comes from processed (packaged) foods, which should be eliminated from the diet. For people with diabetes and high blood pressure, it is recommended that sodium intake be less than 2,400 mg per day. One teaspoon of table salt supplies 2,300 mg of sodium. To help limit sodium in the diet, choose single serving items with less than 400 mg of sodium per serving. For entrees (such as frozen dinners), select ones with less than 800 mg of sodium.
It is reported that low dietary intake of potassium has also been linked to high blood pressure. Getting adequate potassium from fruits and vegetables may be helpful. Use caution administering a high potassium diet if the person has renal disease or is using an ACE inhibitor or a potassium-sparing diuretic, as they may need less potassium. Since abnormal blood potassium levels can be life-threatening, monitoring levels is important for persons taking certain medications and for those with renal disease. Low magnesium levels have been documented in persons with types 1 and 2 diabetes mellitus and are most likely due to increased urinary losses, as can occur with high blood glucose levels or diuretic use. Dietary sources of magnesium include whole grains, green leafy vegetables, legumes, nuts, and fish. Those with renal disease need to use caution with magnesium supplementation.
Cigarette smoking contributes to cardiovascular diseases. As a result, smoking cessation is highly recommended as an adjunct to hypertension management. Smoking status should be regularly assessed and help should be offered to those who use tobacco products. If a person wants to make a quit attempt, nicotine replacement (patches, gum, spray, inhaler) may be helpful aids as well as the medication bupropion (Zyban). Several quit attempts may be necessary before a person is successful. Among individuals who smoke, an estimated 85% have tried to quit or would like to quit. Over 75% of people who make a quit attempt are unsuccessful the first time, but motivated smokers will likely be able to quit.
Physical Activity: Regular physical activity plays a role in preventing cardiovascular disease, and it can improve blood glucose and blood pressure control. It is important to check with the physician before recommending an activity program to the person with diabetes. A preactivity examination is also recommended to look for previously undiagnosed neuropathy, retinopathy, nephropathy, and, particularly, ischemic heart disease—all of which could be aggravated by some forms of activity. If there are no contraindications, 30 minutes of moderate-intensity physical activity, such as walking or riding a stationary bicycle, on most days is recommended. Activity can be split into several 5- to 10-minute segments throughout the day.
For persons with diabetes who use insulin or blood glucoselowering medications, education on hypoglycemic prevention and treatment is needed. Modification in the activity plan may be required if the person has complications associated with diabetes. People who have decreased sensation in their feet should pursue low or nonweight-bearing activities and avoid weightlifting if retinopathy is present.
Finally, stress management training may help the person handle stressful life situations and stick to lifestyle modifications. Many people smoke, eat, or drink in response to stress, so encouraging them to find other methods to deal with stress can be helpful.
Diagnostic Tests
In patients with diabetes, suspect all long-term complications with hypertension and perform the following tests:
Nephropathy: Creatinine clearance and urinary protein excretion, including screening for microalbuminuria.
Cardiovascular disease: Fasting lipid profile (total cholesterol, HDL [high-density lipoprotein] cholesterol and triglycerides).
Pharmacotherapy
Diabetes mellitus increases the risk of cardiovascular disease two to four times, which in turn predisposes patients to renal injury. Therefore, tight control of hypertension is necessary to prevent microalbuminuria that proceeds to proteinurea and in turn to end-stage renal disease.
In general, diabetic patients with hypertension need more than one type of medication. The choice of antihypertensive drug should be determined by the drug’s capacity to (1) lower blood pressure, (2) protect the diabetic patient’s kidneys from ongoing injury, and (3) avoid side effects. Antihypertensive agents that reduce proteinuria in diabetic patients with hypertension include ACE inhibitors, angiotensin II receptor blocker (ARBs), and nondihydropyridine calcium channel blockers (CCBs) such as ver-apamil, but not short-acting dihydropyridine CCBs, which worsen proteinuria and accelerate renal injury. It is important for practicing clinicians to understand that even selecting the right drugs is not enough, as dietary sodium offsets the antihypertensive effects of ACE inhibitors, nondihydro-pyridine CCBs, and ARBs. Several studies have shown that sodium reduction is an effective way for older persons with hypertension to lower their blood pressure. That is why a multidisciplinary strategy that includes antihypertensive therapy, lifestyle changes, and dietary modification is necessary. The following are some of the considerations from the ALLHAT study (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack). The ALLHAT trial lasted 4.9 years and included more than 33,300 people (36% had diabetes).
Diuretics
Thiazide diuretics (such as hydrochlorothiazide or chlorthalidone) are recommended as the first-line treatment for hypertension based on the ALLHAT trial. Diuretics are one of the least expensive medications. They are particularly effective in treating hypertension associated with edema, nephrotic syndrome, and volume-dependent hypertension without edema, such as that seen in African-Americans and possibly those with type 2 diabetes. Persons with diabetes who are taking diuretics should use the lowest effective dose and frequently monitor potassium and blood glucose levels. If not used as first-line therapy. a low dose is often added as a second-line treatment in uncontrolled hypertension. It has been shown that the unfavorable effects of thiazide diuretics on lipid and glucose metabolism are dose related and do not generally occur if low doses are used.
Beta-Blockers
Beta-blockers (such as propranolol, atenolol, and metoprolol) have also been used as first-line treatment for hypertension in the general population. There are some concerns with using these drugs in people with diabetes. These drugs can mask symptoms of hypoglycemia, including tremor, rapid heart rate and palpitations; they can also decrease insulin secretion (and thus raise blood glucose) and slow recovery from hypoglycemia. Beta-blockers may also raise triglyceride levels, lower HDL cholesterol, and contribute to erectile dysfunction as well as exacerbate symptoms of peripheral vascular disease, a condition that is more common in diabetic patients. In general, if metabolic control of diabetes is problematic, carvedilol, a beta1-selective blocker, produces less aggravation of hyperglycemia and hyperlipidemia. Recommendations for persons with diabetes who are taking beta-blockers include testing blood glucose often and treating hypoglycemia when blood glucose is 70 mg/dL or lower, regardless of symptoms or lack of symptoms. Monitoring serum potassium level, lipid profile, and hemoglobin A1c are also recommended. Generic beta-blockers and diuretics are generally the least costly pharmacologic therapies. Newer classes of these drugs are up to 30 times more expensive.
ACE Inhibitors
ACE inhibitors (such as enalapril, captopril, and lisinopril) have received a great deal of attention because of their beneficial effects in people with diabetes. Not only do they lower blood pressure but they have also been demonstrated to reduce microalbuminuria and proteinuria and delay diabetic nephropathy in both normotensive and hypertensive patients with diabetes. They are still considered as first-line treatment in patients who have diabetic nephropathy, unless there are contraindications or side effects, such as cough, that the patient cannot tolerate. In those cases, an ARB can be considered as an alternative therapy. Recommendations for people with diabetes who are taking ACE inhibitors include monitoring serum potassium levels and kidney function. ACE inhibitors are contraindicated in pregnancy and should be used with caution in women of childbearing age. ACE inhibitors, like alpha-blockers and CCBs, do not adversely affect lipid or glucose metabolism. ACE inhibitors are commonly used in diabetic patients with nephropathy.
ARBs
ARBs (such as irbesartan, losartan, and candesartan) are similar in action to ACE inhibitors but work with a different mechanism; they may be used in place of ACE inhibitors if ACE inhibitors are not well tolerated. ARBs should be strongly considered for use in those with type 2 diabetes who also have hypertension, macroalbuminuria, nephropathy, or renal insufficiency. Like ACE inhibitors, ARBs have been shown to delay the progression of nephropathy in people with diabetes. Serum potassium and kidney function should also be monitored in those using ARBs.
CCBs
The safety of CCBs has been questioned over the years; however, the ALLHAT trial found them to be quite safe. A dihydropyridine CCB (amlodipine) was used in the ALLHAT trial. Nondihydropyridine CCBs (such as verapamil and diltiazem) may help to reduce albumin excretion and coronary events. There are differences between these two groups of calcium channel blockers. The nondihydropyridine group, which also lowers heart rate, has been shown to give additional protection to the kidneys, when combined with ACE inhibitors. Some people experience more edema with CCBs, and the agents may be less appropriate for the elderly. Amlodipine and felodipine may assist with the control of isolated systolic hypertension. Like ACE inhibitors, CCBs do not have adverse effects on glucose or lipid levels. Their role as renoprotective agents in diabetes has not been demonstrated.
Adrenergic (Alpha-1) Blockers
The use of adrenergic (alpha-1) blockers (such as prazosin, terazosin, and doxazosin) in diabetic patients with hypertension has been controversial. The adrenergic (alpha-1) portion of the ALLHAT study was discontinued because of a high rate of complications. These drugs are still considered appropriate to use as an adjunct to therapy in difficult-to-control cases. The alpha-blockers, such as prazosin, do not have adverse effects on glucose or lipid levels.
Educating the Patient
The pharmacist can offer recommendations to the patient and the provider regarding appropriate changes in drug regimens and diet. Discuss with the patient the side effects of each medication used in the control of diabetes and hypertension. Pharmacists play an important role by teaching patients how to measure blood pressure, use a blood glucose meter, and analyze blood glucose values. By educating the patient to have good control of preprandial and postprandial glucose levels and good control of their blood pressure, the pharmacist can help to reduce the morbidity and mortality of diabetes-related complications, thus lowering the costs of care associated with these diseases and maintaining quality of life.
Conclusion
Patients with both hypertension and diabetes are at high risk for both vascular and renal disease. They should therefore be treated with the appropriate antihypertensive drugs and be carefully monitored to ensure satisfactory blood pressure attainment and prevent end-organ complications. Hypertension treatment, especially in diabetic patients, involves considerable knowledge of the recommended lifestyle and diet changes and medications. Behavior and lifestyle changes are hard to make and even harder to sustain for most people. The key points are to treat hypertension aggressively and to keep blood glucose under control to minimize exacerbating complications. Many of the side effects of antihypertensive drugs do not help people “feel” better and, over time, people tend to decrease their adherence to therapies. Regular, long-term follow-up and monitoring, even by phone, can increase the number of people who follow prescribed treatments.
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