|
|
AN APPROACH TO THE MANAGEMENT OF THE HYPERTENSIVE PATIENT IN AN OUTPATIENT CLINIC
Preview Hypertension is defined as BP of greater than 140/90 mmHg. According to reports, there is an estimated 50 million adults in the U. S. with hypertension. Only 27 percent of the hypertensives are controlled satisfactorily2. A recently published report of JNC-VI provides guidelines for physicians to overcome the problem of controlling the BP of the hypertensive patients. There are several classes of anti-hypertensives available with different modes of action. Available also, are combination agents. It is up to the primary care physician to use the guidelines according to the clinical indications, so that the hypertensive patient is satisfactorily managed, thus preventing future complications of coronary artery disease, stroke, heart and renal failure. One of the most common reasons for office visits to physicians in the United States (U. S.) is for the treatment of hypertension, and for use of prescription drugs for such treatment.1 Primary care physicians are often the first to encounter the hypertensive patients. They are therefore responsible for a major part in how the disease progresses. An estimated 50 million adults in the U. S. have arterial hypertension.2 Arterial hypertension is diagnosed by a persistently elevated blood pressure (BP) of above 140/90 mmHg. It has been shown by studies conducted by the National Health and Nutritional Examination Survey (NHANES) report2, that only 27 percent of patients diagnosed and treated for hypertension had their BP at a level below 140/90 mmHg. Hypertension is known to be a major risk factor for the development of coronary artery disease, heart failure, renal failure, and stroke. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (JNC-VI) has provided new guidelines to help practitioners to improve the standard of care on hypertensive patients.3 Hypertension as classified by JNC-VI3 is divided in to three stages depending on the level of BP: In Isolated Systolic Hypertension (ISH): Follow up recommendations for hypertension Stage 1 To be confirmed within two months. Diagnostic Evaluation It is important to document an adequate history, physical examination, and baseline laboratory studies in patients with a BP of > 140/90 mmHg. Special consideration should be given to conditions influencing the development of hypertension such as concomitant disease processes producing secondary hypertension. These are: (a) Endocrine Disorders - namely Cushings Syndrome, Primary Aldosteronism, Pheochromocytoma, Thyroid disease, and Hyperparathyroidism; (b) Renal Disease - renal parenchymal disease, Diabetic nephropathy, Renovascular disease, and Vascular conditions (such as Coarctation of the aorta). White coat hypertension6, as well as isolated systolic hypertension as seen in the elderly, are other causes of increased BP. Attention to special ethnic populations such as the adult African American population in the U. S. with prevalence of 32.4 percent compared to 23.3 percent in the Caucasian population5 is important. Initial laboratory data should include a urinalysis, complete blood count, serum electrolytes, creatinine, fasting blood glucose levels, lipid profile with total and high density lipo-protein cholesterol, as well as an electro-cardiogram. Further studies will depend on any abnormalities as found in the screening tests. The physician should also assess the overall cardiovascular risk in the hypertensive patient. Pathophysiology Blood pressure is the product of cardiac output (CO) and the peripheral resistance (PR) of the arterioles. Cardiac output in turn depends on the stroke volume and the heart rate. Any condition that affects these parameters would cause a change in the level of BP. In special ethnic groups such as the African American adults, the pathphysiology of hypertension is different from the adult Caucasian population. In the former group, hypertension is the low-renin type, there is an expanded blood volume, with increased sensitivity of the blood pressure, to salt intake. They have an impaired ability to excrete ingested salt of up to 60 to 70 percent7, leading to an expansion of the intravascular volume. The most common type of hypertension in the elderly population is isolated systolic hypertension (ISH). As vascular rigidity increases beyond age 55, the stiffened blood vessels cause an increase in the total PR, thereby reducing the ability of the blood vessels to absorb the pressure created by the cardiac output. This in turn produces ISH, as well as combined systolic and diastolic hypertension. A group of patients, who show an increase in the BP at the doctor's office of values > 140/90 mmHg, while their out of office BP readings are below 130/85 mmHg4, are grouped as those with "White coat hypertension." Further follow up of these cases may be warranted. Managment of Hypertension Lifestyle modifications are important before pharmacological intervention is recommended by JNC- VI3. These are: (1) Weight Reduction - It has been documented that in the African American hypertensives, a reduction in body weight of as little as seven pounds, significantly reduced the BP8. Studies have also shown the efficacy of weight loss in improving hypertension in the elderly8. (2) Sodium Restriction - Restriction of sodium of up to 2,400 mgm/day has been recommended. (3) Limit Daily Alcohol Intake - For men, up to no more than one ounce of ethanol which includes 24 ounces of beer or two ounces of 100 proof whiskey, or 10 ounces of wine. In case of women, or lighter men, up to one half ounce of ethanol/day. (4) Aerobic Activity - Aerobic activity of 30-45 minutes per day for most of the days of the week. (5) Potassium Intake - Adequate dietary intake of 90 mmol/day. (6) Adequatte Calcium and Magnesium Intake. (7) Reduced Dietary Fat Intake - Intake of cholesterol and saturated fat should be reduced. (8) Stop Smoking. Pharmacological Interventions If lifestyle modifications do not achieve the goal of BP <140/90 mmHg, JNC-VI3 has recommended the initial choice of a diuretic or a beta blocker unless there is a contra-indication for such medications which warrant the use of a different initial agent, as shown below. The following special conditions would benefit by use of one of the agents in the cooresponding group of anti-hypertensives. This should determine which initial agent is used if one of the following conditions is present. Use of long acting antihypertensives are recommended due to improved compliance, and reduced cost of therapy. Studies show that only about 50 percent of patients with hypertension respond satisfactorily to monotherapy, and that treatment with two or more agents from different pharmacological classes is often necessary10. Major classes of antihypertensive agents available for outpatients These include (1) Diuretics, (2) Beta blockers, (3) ACE inhibitors, (4) Angiotensin II receptor antagonists, (5) Calcium channel blockers, (6) Alpha one blockers, and (7) Alpha one, beta blockers. It is recommended by JNC-V13 that the initial treatment of uncomplicated hypertension should be with diuretics or beta blockers, starting with a minimum dose and gradually increasing the dosage according to the response, unless there is a contra-indication to their use. Diuretics: Agents included in this group are Thiazides and potassium sparing diuretics. The principal mechanism of action is by inhibiting sodium and water reabsorption from the proximal part of the renal tubules. They are considered as the first line of therapy for those with uncomplicated hypertension, and a serum creatinine level below 1.5 mgm/dl, or for patients with concomitant systolic heart failure. Diuretics are effective agents for the treatment of hypertension in African-Americans. They are the drug of choice in the elderly with ISH20. It is mediated through volume changes11. Hydrochlorothiazide (HCTZ): This agent, which acts at the distal renal tubules, is inexpensive, and lowers the BP at doses between 12.5-25 mgm per day. In cases with a creatinine level of 2 mgm/dl or more, a loop diuretic such as Furosemide should be substituted12. Furosemide acts at the proximal and distal renal tubules and the loop of Henley. Combination type drugs containing as little as 6.25-12.5 mgm of HCTZ, with ACE inhibitors or beta blockers has been found to produce equivalent lowering of the BP in Caucasian as well as African American patients. Both loop and Thiazide diuretics may cause metabolic abnormalities. Potassium Sparing Diuretics: Examples are Amiloride, which acts at the distal convoluted tubules and collecting ducts, and Spirinolactone, which acts at the distal convoluted tubules. They are weaker anti- hypertensives as monotherapy, but are effective when used in combination with a Thiazide or loop diuretic by their synergistic actions. Beta Adrenergic Blockers They are indicated as first line agents for the treatment of uncomplicated hypertension, or hypertensive patients with cardiac arrythmias, hypertension with angina pectoris, or with a history of myocardial infarction, diastolic dysfunction, mitral valve prolapse, excessive sympathetic tone, hyperthyroidism with symptoms of thyroid storm, and for those with migraine headaches. Beta blockers are preferred for the treatment of hypertension in young Caucasians below 40-50 years of age. African Americans, however, respond less well to beta blockers14. Beta blockers produce negative inotropic (force of contractions) and chronotropic (rate of contractions) actions on the heart. The rate of contractions of the heart is decreased by slowing of the conduction through the sino atrial (SA) and Atrioventricular (AV) nodes. As the sympathetic tone is blocked, this can interfere with the symptoms of hypoglycemia in diabetic patients. Common adverse effects are depression, decreased exercise tolerance, sleep disturbances, and impotence. Beta selective blockers such as Atenolol, Metaprolol, and Bisoprolol produce less side effects. All beta blockers, including the cardio-selective agents, can exacerbate bronchial asthma. They may cause peripheral vascular disease, and diabetes mellitus at high doses15. They should not be used in the elderly hypertensive patient (>65 years) as initial therapy due to their effect of lowering the CO and increasing the systemic vascular resistance16. ACE Inhibitors ACE inhibitors act on the Renin-Angiotensin aldosterone (RAA) system. Renin is released from the kidneys in response to decrease in renal perfusion and decreased plasma volume. Renin converts angiotensinogen to Angiotensin I, which is in turn converted to Aniotension II by Angiotensin Converting Enzyme (ACE). Angiotensin II is a potent peripheral vasoconstrictor which also is a stimulator of Aldosterone from the adrenal cortex. Aldosterone causes sodium and water retention by the kidney. ACE inhibitors produce a decrease in Angiotensin II, thereby decreasing sodium and water retention, decreasing potassium excretion, and increasing arterial vasodilation. There is no decrease in the CO or heart rate (HR). CO is seen to improve with ACE inhibitors as seen in patients with systolic dysfunction17. Several ACE inhibitors are available. Some examples are Captopril (Capoten), Enalapril (Vasotec), Benazepril HCL (Lotensin), Lisinopril (Primivil), and Ramipril (Altace). Patients with sodium and water depletion, or those with a high baseline of circulating renin, respond better to ACE inhibitors. They are recommended for hypertensive patients with co-morbidities of left ventricular dysfunction, diabetes mellitus, and a previous history of a myocardial infarction (MI). Some of the adverse effects to be noted are hypotension, electrolyte dysfunction, angioedema, and a cough which could be distressing. They are used with caution in patients with a high serum creatinine level. Low doses are recommended initially, especially in the elderly to avoid hypotension and electrolyte disturbances of hyperkalemia. Angiotensin II Receptor Blockers (ARBs) They decrease the BP by inhibiting the coupling of the angiotensin II to angiotensin receptor subtype I. ARBs have not been recommended by JNC-VI for initial therapy of hypertension. They may be used as alternatives for patients suitable for the use of ACE inhibitors, but are unable to tolerate these agents. Some examples of ARBs are Losartan Potassium (Cozaar), Candesartan (Atacand), and Valsartan (Diovan). Calcium Channel Blockers (CCBs) CCBs reduce myocardial contractility, produce vasodilation and decrease systemic vascular resistance by inhibiting the reflux of calcium across cell membranes. Calcium is required inside the cell, for contraction of the cardiac and vascular smooth muscles. CCBs show distinctive actions in their subclasses, e.g. Verapamil and Diltiazem have shown a dose dependent negative inotropic effect on the myocardium. They slow atrioventricular conduction, and dilate peripheral arterioles, thereby decreasing the BP. Agents of the dihydropyridine class, which includes Nifedipine and Amlodipine, are potent peripheral vasodilators, and are more effective anti-hypertensives. CCBs are the choice for patients who are unable to use Beta blockers, but are hypertensive with angina, since CCBs dilate the coronary vasculature. Due to the risk of cardiovascular events, short acting CCBs should not be used in the treatment of hypertension18. Alpha I Blockers Lowering of BP by alpha I blockers occur by inhibition of post synaptic alpha I receptors on smooth muscles of veins and arteries. The mechanism of action is by vasodilation. Alpha I Blockers show a characteristic "first dose effect" - which is orthostatic hypotension with the first few doses of the drug, and may be minimized by slow titration of the dosage, and prescribing the initial doses at night. These agents have been recognized as suitable for initial therapy for hypertensive patients with combined conditions such as dyslipidemia, and benign prostatic hypertrophy3. They continue to be under-utilized. They have no effect on the lipid, glucose or electrolyte levels, and could be prescribed to those with bronchospasm and peripheral vascular disease. Once a day dose Alpha One Blockers are Doxazosin (Cardura), and Terazosin (Hytrin). However, Prazosin (Minipress) needs multiple dosing per day. Alpha I Beta Blockers Labetalol (Normodyne, Trandate) is an alpha I beta blocker. They are the least used in the treatment of hypertension. Combination Anti-hypertensive Agents Anti-hypertensives from two different classes have been combined in smaller dosages to provide an additive effect in lowering the BP, as well as producing lesser adverse effects. Mono therapy achieves the target BP level of 140/90 mmHg only in 50 percent of patients. Combination anti-hypertensive therapy is an option that is convenient due to single dose regimen, and low side effects22. Several combination agents are available that include the following22 from different groups of anti-hypertensives. Diuretic Combinations Beta Blockers and Diuretics ACE inhibitors and diuretics Calcium Channel Blockers and ACE Inhibitors Angiotensin II Receptor Antagonists and Diuretics Resistant Hypertension19 If the BP remains elevated, despite the use of multiple anti-hypertensives, the patient is considered to have resistant hypertension. Some of the factors which need to be evaluated in such cases are, the adequacy of the regimen, drug interactions, office or white coat hypertension, or noncompliance with therapy19. Such cases with poor response need to be referred to a hypertension specialist. * * * * About the Author This article represents the opinion of the author and does not reflect the official policy of the American Academy of General Physicians nor the institutions with which the author is affiliated. References (1) Woodwell DA. National ambulatory medical care survey: 1995 summary. Adv data 1997; 295:1-25 |
|