Hypertension or High Blood Pressure

            Hypertension is a "Silent Killer."  This is not a misnomer and it is not surprising that this disease is called as such.  It is a medical condition known to mankind for ages, and it has been studied extensively by epidemiologists and clinicians in recent years.  It can kill if not treated.

            The recommended care of  patients with Hypertension is based upon the findings from these studies.  Management of Hypertension requires skills from the health practitioner in enlisting the patient's cooperation and in selecting and monitoring and adjusting treatment.

The arterial blood pressure is regulated by a variety of inter-dependent mechanisms.  Inadequately compensated alterations in any of these mechanisms can lead to abnormal elevation of blood pressure.  An elevated arterial blood pressure is one of the most important public health problems in developed countries.  It is common, a symptomatic and that is the reason why it kills.  Although it is readily detectable, easily treatable, it often leads to lethal complications if left untreated.

The prevalence of Hypertension depends on both racial composition of the population and the criteria used to define the condition.  Hypertension occurs in more than 60 million Americans.  The prevalence in Caucasians is approximately 15 percent, but it is over 25 percent in the black population.  This marked racial difference in the rates of Hypertension remains somewhat unexplained.  The prevalence of Hypertension also increases with advancing age.  Hypertension is more common in men than in women up to approximately age 50.  the rate thereafter is higher in women.

 Genetic factors have long been assumed to be important in the genesis of Hypertension.  Most studies done so far support the concept that inheritance is multifactorial in that a number of different genetic defects each have an elevated blood pressure as one of their phenotypic expressions.  Both monogenic defects and susceptibility genes have now been reported which have as one of their consequences an increased arterial pressure.

 Environmental factors have also been implicated in the development of Hypertension, including salt intake, obesity,  occupation,  level of alcohol intake, family size and crowding.

 The measurable blood pressure of the general population demonstrates extreme variance.  There is a correlation  of mortality and morbidity with the level of systolic and diastolic blood pressure.  The correlation provides the basis for the arbitrary definition of abnormal blood pressure.  A diagnosis of Hypertension is made in an adult over 28 years of age if the average of two or more blood pressure measurements on at least two subsequent visits is 90 mm hg or higher diastolic or 140 mm hg systolic.  The blood pressure in healthy children and pregnant women is typically lower, so that readings in excess of 120/80 may be considered abnormal.  There is a condition called isolated systolic hypertension, which is defined as a systolic blood pressure greater than 160 mm hg in association with a diastolic blood pressure less than 85 mm hg.  It occurs more frequently in the elderly, beginning after the 5th decade and increasing with age.  It is important to recognize that isolated systolic hypertension is associated with increased incidence of cardiovascular and cerebrovascular complications and it must be treated.

 Classification of Blood Pressure for Adults Aged 18 Years And Older

 Category       Systolic Pressure (mm Hg)    Diastolic Pressure (mm Hg)

Normal                 Less than 130                                 less than 85

High Normal         130-139                                          85-89

Hypertension

Mild                     140-159                                          90-99

Moderate             160-179                                          100-109

Severe                  180-209                                          110-119

Very Severe         Equal or greater than 210           Equal or greater than 120

 Physiologic principles indicate that pressure is a direct function of flow and resistance.  The blood pressure is related to the cardiac output and the peripheral vascular resistance.  The cardiac output depends upon the contractibility of the myocardium, the heart rate and the intravascular blood volume.  The regulation of normal blood pressure depends upon several interrelated factors that modulate the output and resistance.  The autonomic nervous system is responsible for the regulation of abrupt hemodynamic alterations.   Other humoral factors regulate the blood pressure and the most important being the renin-antiotensin-aldosterone system.

  Despite the understanding of the mechanism regulating ambulatory blood pressure, monitoring can be of value in the following circumstances:

  Suspected  "white coat" Hypertension in which the increased blood pressure is associated with the stress of physician office visits;

 -            high normal blood pressure 130-139 mm Hg systolic, 85-89 mm Hg diastolic, with target organ damage;

 -                     Evaluation of possible drug resistance during the course of treating;

             -                     Episodic Hypertension;

             -                     Hypotensive symptoms associated with medication or autonomic dysfunction.

 What is target organ damage?

             Patients with untreated or uncontrolled Hypertention develop target organ damage due to longstanding effects of the increased blood pressure in the different organ of the body, the cardiovascular system, with the heart as the main target, the neurological system and the kidneys.   The most common cause of death is heart disease, stroke and renal failure.   Eye damage with retinopathy is very common.

How to Take Blood Pressure Measurements.

             Elevated blood pressure is usually discovered in asymptomatic individuals during screening - optimal detection and evaluation of hypertension requires accurate non invasive blood pressure measurements which should be obtained in a seated patient having the arm level with the heart.  A calibrated, appropriately fitting blood pressure cuff should be used because falsely high reading can be obtained if the cuff is too small.  Two readings should be obtained separated by two minutes.  Systolic blood pressure should be noted with the appearance of korotkoff sounds (phase I) and diastolic BP with the disappearance of sounds (phase V).  In certain patients, the korotkoff sounds do not disappear but will be pressing to 0 mm Hg.  In this case, the initial muffling of korotkoff sounds (Phase IV), should be taken as the diastolic blood pressure.  Hypertension should be confirmed in both arms and the higher reading should be used.

             We should also take into account the secondary causes of Hypertension, mostly the presence of medication that may affect blood pressure:  decongestants, nonsteroidal anti-inflammatory agents, exogenous thyroid hormones and recent high alcohol consumption.  The new electronically measured blood pressure monitoring are very helpful and can be used by anyone.

 Considerations for Therapy

             Before considering therapy, your health care practitioner will order laboratory assessments, which will help him or her to identify possible target organ damage and provide a baseline for assessing adverse effects of therapy.   Hyperlipidemia evaluation, evidence of diabetes, and assessment of cardiac function are very important.

             The goal of treatment for Hypertension is to prevent long-term sequelae or target organ damage.  Virtually every patient with a diastolic arterial pressure that persistently exceeds 90 mm Hg, or a patient over 65 years of age with a systolic arterial pressure over 160 mm hg is a candidate for diagnostic studies and for subsequent treatments.  The primary goal is to reduce blood pressure to less than 140/90 mm hg, which concurrently controlling other modifiable cardiovascular risk factors.  Isolated systolic Hypertension is associated with increased cerebrovascular and cardiac event.  Therefore, the therapeutic goal in this subset of patients should be to lower blood pressure to less than 140 mm Hg systolic.

 General Measures

            We must depart from the principle that no hypertensive patients should be left untreated except through his or her own volition.

             Most patients with Hypertension should be given the opportunity to achieve a reduction in blood pressure over an interval of three to six months by applying non-pharmacological modifications.  The general measures employed include:

      1.                  relief from stress;

2.                  dietary management;

3.                  regular aerobic exercises;

4.                  weight reduction (if needed).

 -            Relief from emotional and environmental stress is one of the reasons for the improvement of Hypertension that occurs when a patient is hospitalized.  It is impossible to extricate the hypertensive patient from all internal and external stress.  He or she should be advised to avoid unnecessary tensions.  In rare instances, it may be appropriate to recommend a change of job or of lifestyle.  It has been suggested that relaxation techniques also may lower arterial pressure.

 -            For dietary modifications, sodium restriction is an effective and safe means of lowering blood pressure modestly in hypertensive patients.  Sodium restrictions also may decrease drug resistance and enhance efficacy.  Total sodium chloride intake should be limited to 6 g. per day.  The use of potassium as a therapeutic agent is controversial, but may be of some benefit.  Normal serum potassium levels should be maintained in patients with spontaneous or drug induced hypokalemia.  Dietary intake of cholesterol and saturated fat should be reduced to lessen hyperlipidemia and to facilitate weight loss.

 -            Regular dynamic exercise is advised if the clinical status of the patient permits.  Repeated periods of exercise result in a significant reduction of blood pressure independent of weight loss or altered sodium excretion, decreasing all-cause risk and cardiovascular morbidity and mortality.  Exercise should be performed at least 3 times per week for at least 30 minutes, achieving 65 to 70% of a patient's predicted maximum heart rate.  Patients with known or suspected coronary artery disease and those older than 40 with multiple coronary risk factors should undergo exercise stress testing before beginning an exercise program.

 -            Weight reduction should be strongly encouraged in patients whose weight exceeds 10% of their ideal body weight.  Reduction of body weight, especially male-pattern obesity involving the trunk and upper body may obviate the need for drug therapy or decrease the amount of medication required to control Hypertension.  Weight loss is no recommended for pregnant patients with Hypertension.

             In summary, lifestyle modifications should be encouraged in all hypertensive patients, regardless of whether they require medication.  These changes may have beneficial effects on other cardio-vascular risk factors.  Patients who smoke should be advised to stop smoking because cessation of smoking is an effective means of reducing cardio-vascular risk and target organ damage.  Alcohol consumption should be decreased to 1 oz or less per day because, in large amounts, ethanol has a direct vasopressor effect and can exacerbate Hypertension.

 Anti-Hypertensive Drugs

            I must point out that an individualized approach to therapy is more favorable than the traditional stepped-care therapy.  A patient may have associated or inter-current conditions that must be taken into account.  To make rational use of anti-hypertensive drugs, the sites and mechanism of their actions, as well as their side effects must be understood.

 

            There are six classes of drugs and note that the most commonly prescribed of these drugs will be enumerated in this short piece:

 

-                     diuretics;

-                     antiadrenergic agents;

-                     vasodilators;

-                     calcium entry blockers;

-                     angiotension - converting enzyme (ACE) inhibitors; and

-                     angiotensive receptor antagonists.

 

Diuretics

 

            The most commonly used diuretics are the thiazides prototypes.  They have formed the cornerstone of most therapeutic programs designed to lower arterial pressure and they are usually effective within three to four days.  They have been shown to reduce morbidity and mortality in long-term trials.  Their early effect in the reduction of blood pressure is related to sodium diuresis and volume depletion by inhibition of tubular NACL absorption.  Reduction in peripheral vascular resistance has also been reported.  Despite their usefulness in the management of Hypertension, there has been increasing resistance in recent years to their continued use, primarily because of their adverse metabolic effects, which include: hypokalemia due to renal potassium loss, hyperucemia due to uric acid retention, carbohydrate intolerance given hyperglycemia and hyperlipidemia.  In lower doses, these side effects are very much less common.

 

            Furosemide, Bumetamide produce also sodium diuresis and volume depletion, but are not used extensively for Hypertension because of their short duration of action.  Furosemide is more useful in chronic renal failure.

 

            Spironolactone, triamterene and amiloride are potassium sparing diuretics that can be given along with thiazide diuretics to minimize renal potassium loss.  Most common side effects of these potassium sparing diuretics are hyperkalemia.  Patients with renal insufficiency or renal failure should not take these medicines.

 

The Anti-Adrenergic Agents or Adrenergic Antagonists

 

            This group of agents comprises:

 

-                     the alpha-adrenergic antagonists;

-                     the Beta-adrenergic antagonists;

-                     the agents with mixed properties both alpha and Beta; and

-                     the centrally acting adrenergic agents.

 A.            The Alpha-Adrenergic Antagonists

 The most commonly used agents of this group are:  Doxazosin, Prazosin, Terazosin.  They are called selective alpha adrenergic antagonists.  Their mechanism of action is to block the postsynaptic alpha-receptors producing arteriolar and venous vasodilation.  Side effects include syncope, orthostatic hypotension, dizziness, headache and drowsiness.  In most cases, side effects are self-limited and do not occur with continued therapy.

B.            The Beta-Adrenergic Antagonists

 The most commonly used agents of the group are:  Atenolol, Betaxolol, Bisoprolol, Metoprolol, Nadolol, Propanolol, Timodol, Acebutolol. 

             The mechanism of action of beta-adrenergic antagonists is competitive inhibition of the effects of catecholamines at beta-adrenergic receptors which decrease heart rate and myocardial contractility and cardiac output.   They are part of medical regimens proved to decrease the incidence of stroke and myocardial infarction.  They cause release of vasodilating prostaglandin decrease plasma volume and also may have a CNS-mediated antihypertenseive effect. 

             Although beta blockers are tolerated by the majority of patients as first-line treatment for uncomplicated hypertension, higher doses of beta blockers are associated with fatigue, nightmares, depression, reduced exercise tolerance, erectile dysfunction and sexual impotance , atrioventicular block and in some patients, bronchospasm. They may adversely affect lipid profiles and increase insulin resistance.  They are recommended as first-line therapy following myocardial infarction because these drugs consistently have been shown to improve survival rates in patients after acute myocardial infarction.  They are of particular advantage in patients with angina pectoris and either atrial fibrillation or tachydcardia.  They are not recommended for patients with brochospatic disease.

 The agents with mixed properties, such as Labetolol and Carvedilol, have both alpha and beta-adrenergic antagonist actions.  Side effects of Labetolol include hepato-cellular damage, postural hypotention, tremors, hypotension, reflex tachycardia.  Carvedilol appears to have a similar side effect profile to other beta-adrenergic antagonists.

 The centrally acting adrenergic agents, such as Clonidine, Methyldopa, Guanabenz, Guanfacine, are potent antihypertensive agents.  Their mechanism of action is to stimulate the presynaptic alpha 2 adrenergic receptors in the CNS.  This stimulation leads to a decrease in peripheral sympathetic tone, which reduces systemic vascular resistance.  Also, it causes a modest decrease in cardiac output and heart rate.  Renal blood flow is not compromised by centrally acting adrenergic agents.  

             Side effects of these centrally acting adrenergic agents include:  bradycardia, drowsiness, dry mouth, orthostatic hypotension, galatorrhea and sexual dysfunction.  It is not recommended to stop these medicines abruptly because abrupt cessation may precipitate an acute withdrawal syndrome of elevated blood pressure, tachycardia and diaphoresis.

 A.                 The Calcium Entry Blockers

     The calcium entry blockers are also called calcium channel antagonists.  They are effective agents in the treatment of Hypertension.  Calcium entry blockers lower blood pressure by reducing peripheral vascular resistance.  This is accomplished by blocking the influx of calcium through voltage-sensitive calcium channels located in smooth-mucle cell membranes.   Classes of calcium channel antagonists include:

         a)      The diphenylalkylamines such as Verapramil and Benzothiazepines such as Diltiazem, also called non dihydropyridines.  They have been shown to lower heart rate and decrease myocardial contractibility and atrioventicular conduction.  These drugs have added benefits in patients with proteinuria due to diabetic nephropathy and also can be used as an alternative for patients who are unable to tolerate beta blockers after myocardial infarction.  The nondihydropiridines are associated with constipation and changes in the cardiac conduction system or AV block in susceptible patients.

         b)      The dihydropyridines such as Nifediprine, Amlodipine, Felodipine, Nisoldipine, Isradipine, Nicardipine.  These drugs function primarily as pure peripheral vasodilators.  The side effects associated with the dihydropyridines include:  flushing, headache, dizziness, peripheral edema, which is not due to sodium retention, but to unopposed arteriolar dilatation.

        All calcium channel antagonists are metabolized in the liver.  Thus, in                     patients  with cirrhosis, the dosing interval should be adjusted accordingly

 B.  The Angiotension - Converting Enzyme (ACE) Inhibitors

                   The ACE inhibitors include:  Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Quinapril, Ramipril, Tandolapril.  They are effective antiphypertensive agents in a broad array of patients.  Their mechanism of action is to block the production of angiotension II, a vasoconstrictor, by inhibiting ACE competitively, thereby leading to arterial and venous vasodilatation and to natriuresis.  Ace inhibitors also increase level of vasodilatory bradykinins.

                  Some of these agents directly stimulate reduction of renal and endothelial vasodilatory prostaglandins.  Several clinical trials demonstrate compelling evidence for the use of ACE inhibitors in patients with heart failure, left ventricular dysfunction and diabetic renal disease.  Most studies suggest, however, that ACE inhibitors may be less effective than calcium channel blockers in terms of blood pressure reduction per se.

                Compared to other antihypertensive drugs, ace inhibitors have an excellent side effect profile.  They may cause, however, a chronic, non-productive cough, angioedema and hyperkalemia.  Overall, these drugs have demonstrated benefits among patients with hypertension who have had a myocardial infarction, who have known cardiovascular disease or who have diabetes.  They are contraindicated in patients with significant bilateral renal artery stenosis.

 Angiotensine - Receptor Blockers (ARB)

                They are fairly new antihyprtensive drugs that are affective in diverse patient populations.  The five agents on the market in the United States are Losartan, valsartan, Irbesartan, Candesartan and Eprosartan.  The main mechanism of action of these drugs is to antagonize the vasoconstrictive effects of angiotensin II at the AT1 receptor.  This action results in decreased peripheral vascular resistance.  In terms of their performance in lowering blood pressure, ARB's are similar to ACE inhibitors and other classes of antihypertesnive drugs.

             Some side effects of these drugs occur rarely, but include angioedema, allergic reaction, and rash.  The cough seen with ACE inhibitors occurs much less frequently with angiotensine - receptor blockers.  Renal hemodynamic alterations and hyperkalemia appear to be less than that seen with ACE inhibitors.

 Conclusion

   Hypertension is a chronic disease that must be treated.  I urge anyone suffering from this condition not to be discouraged in following their diet, performing regular exercises and taking medication under their health care provider's guidance.

                                                                         Joseph J. Nicolas, M.D.

104-105 Springfield Blvd.

Queens Village, NY  11429

Tel.  (718) 776-6050

Fax  (718) 776-6051

 

Sources:  Harrison Principles of Internal Medicine; The Washington Manual of Medical Therapeutics; Journal of Clinical Hypertension; Archive of Internal Medicine.        

(The above is provided solely for  informational purposes.  It is in no way to be construed as a substitute for professional medical care.)