Overview of the Medical Management of High Blood

Pressure in Adults

Luis Daniel Lugo, MDMedical Resident

Roger Williams Medical CenterBoston University School of Medicine

Providence, Rhode Island

Hypertension

• Hypertension affects approximately 75 million adults in the United States and is a major risk factor for stroke, myocardial infarction, vascular disease, and chronic kidney disease.

Introduction to HTN

• Hypertension (HTN)• Stage 1• 140 – 159 systolic• 90 – 99 diastolic

• Stage 2• Greater or equal to 160 systolic• Greater or equal to 100 diastolic

• Can be seen as isolated systolic or isolated diastolic

Introduction

• Malignant Hypertension• It refers to evident hypertension with retinal

hemorrhage, exudates or papilledema.

• Hypertensive Urgency• It refers to severe hypertension (diastolic >

120) in asymptomatic patients. • There is no proven benefit in the rapid

reduction of blood pressure in asymptomatic patients.

Primary Hypertension

• Essential Hypertension• Idiopathic • Increased sympathetic neural activity• Multiple risk factors: ethnicity, hereditary,

lifestyle… • Vitamin D deficiency is associated with

increased risk

Secondary Hypertension

• Secondary (Identifiable) Hypertension• It is associated with an identifiable process. • Renal disease• Drug related• Obstructive Sleep Apnea• Endocrine disorders• Mineralocorticoid imbalance (aldosteronism, Cushing’s)

• Thyroid disease

• Primary or essential hypertension accounts for 90-95% of adult cases, and secondary hypertension accounts for 2-10% of cases.

Complications related to HTN

• Premature cardiovascular disease

• Intracerebral hemorrhage

• Organ disease (particularly renal)

• Clinical trials have demonstrated the following benefits with antihypertensive therapy:• Average 35-40% reduction in stroke incidence• Average 20-25% reduction in myocardial infarction• Average >50% reduction in heart failure

Diagnosis

• Annual screening – recommended

• In the absence of end-organ damage, diagnosis of hypertension should not be made until the blood pressure has been measured on at least three to six visits spaced over a period of weeks to months.

• Postural hypotension• It is a 20 mmHg fall or greater fall in systolic

pressure upon rising from supine to an upright position.

White Coat Hypertension

• It is more common in the elderly. One way to minimize the white coat effect is to have the blood pressure measured while seated after five minutes in a quiet, unobserved setting by an automated device.

• Ambulatory blood pressure monitoring (ABPM): • Suspected episodic hypertension (pheochromocytoma)• HTN resistant to medication• Hypotensive symptoms while taking anti-HTN meds• Autonomic dysfunction

Evaluation

• History – assessment of precipitating factors, extend of organ damage, presence of risk factors

• PE – assessment of organ damage

• Laboratory:• Renal function tests, UA, electrolytes • Lipid profile • EKG • Microalbumin, ECHO, abdominal CT

Hypertensive Emergencies

• The most common clinical presentations of hypertensive emergencies are cerebral infarction (24.5%), pulmonary edema (22.5%), hypertensive encephalopathy (16.3%), and congestive heart failure (12%).

• Other clinical presentations associated with hypertensive emergencies include intracranial hemorrhage, aortic dissection, and eclampsia, as well as acute myocardial infarction.

Treatment

• Lifestyle modification• Dietary salt restriction • Weight loss• DASH diet • Exercise • Limited alcohol intake

Medical Therapy

• Main drugs:• Thiazide diuretics• Long-acting calcium channel blockers • ACE inhibitors / ARBs

• Single therapy may not adequately control the blood pressure, particularly in those whose blood pressure is 20/10 mmHg above goal. When more than one agent is needed, it is recommended to use an ACE inhibitor or ARB with a long-acting CCB.

Efficacy of Medical Therapy

• Each of the anti-hypertensive agents is roughly equally effective in lowering the blood pressure. There is, however, wide inter-patient variability as many patients will respond to one drug but not to another.

• Thiazide Diuretics• Chlorthalidone is superior than

hydrochlorothiazide• Both require K monitoring

Indications for Specific Drugs

• Young patients• Respond better to ACE inhibitors and ARBs

• Elderly patients and Black patients • Respond best to thiazide diuretics and long-

acting calcium blockers

• Consider sequential monotherapy (try drug 2 or drug 3 alone) when first choice therapy fails instead of trying combined therapy

Indications for Specific Drugs

• ACE inhibitors and ARBs • First line in all patients with HF or LV dysfunction, systolic

dysfunction, ST or non ST-segment elevation MI, diabetes and in patients with proteinuric chronic kidney disease.

• Both have cardioprotective effects

• Calcium Channel Blockers • Used in rate control for AF and for the control of angina.

• Beta Blockers • Not routine for HTN but are used in stable HF and post-

MI.

Sequential Monotherapy

• This regimen may minimize the side effects, maximize patient compliance and is as effective as some forms of combination therapy. However, over time, more than one drug will be needed.

Drug Dosing

• Good responders generally respond to lower doses with few side effects, while higher doses produce more side effects often with little further reduction in blood pressure.

Resistant Hypertension

• Resistant hypertension is commonly defined as a blood pressure (BP) level higher than 140/90 mm Hg despite treatment with antihypertensive agents of 3 or more different classes, of which 1 is a thiazide diuretic.

• A study demonstrated that the addition of low-dose spironolactone provides significant additive BP reduction in both black patients and white patients who have resistant hypertension, with or without primary hyperaldosteronism.

Dual therapy

• Starting with two drugs should be considered in patients with a baseline blood pressure above 160/100 mmHg. This increases the likelihood that the blood pressure will reach target at a reasonable time period.

The Goal

• The goal blood pressure is to reach below 140/90 mmHg or below 150/90 in patients 60 years or older.

• Clinical trials have shown benefit from lower blood pressures in patients with atherosclerotic disease and chronic kidney disease.

• It is recommended that, at least, one medication is given at bedtime, rather than taking all medications in the morning.

Medications

Diuretics

• Thiazide diuretics inhibit reabsorption of sodium and chloride mostly in the distal tubules –thereby increasing urine output. Long-term use of these drugs may result in hyponatremia.

• Chlorthalidone is indicated for the management of hypertension either alone or in combination with other antihypertensives.

• The initial dosage is 25 mg as a single daily dose. Dosage can be titrated to 50 mg if the clinical response is not adequate. If additional control is required, increase the dosage to 100 mg once daily, or a second antihypertensive drug may be added.

ACE inhibitors

• Angiotensin converting enzyme (ACE) inhibitors are the treatment of choice in patients with hypertension, chronic kidney disease, and proteinuria. ACE inhibitors reduce morbidity and mortality rates in patients with heart failure, patients with recent myocardial infarctions, and patients with proteinuric renal disease. ACE inhibitors appear to act primarily through suppression of the renin-angiotensin-aldosterone system.

• Lisinopril may be used as monotherapy or concomitantly with other classes of antihypertensive agents.

• The initial dose of lisinopril is 10 mg daily. The dosage can range from 20-40 mg/day as a single daily dose. Doses up to 80 mg/day have been used; however, they do not show a greater effect.

ARBs

• Generally, ACE inhibitors should remain the initial treatment of choice for hypertension. Angiotensin II receptor antagonists or angiotensin receptor blockers (ARBs) are used for patients who are unable to tolerate ACE inhibitors. ARBs competitively block binding of angiotensin-II to angiotensin type I (AT1) receptors, thereby reducing effects of angiotensin II–induced vasoconstriction.

• Losartan may be used alone or in combination with other antihypertensive agents, including diuretics.

• The initial dose is 50 mg daily; however, in patients on diuretic therapy, the initial dose is 25 mg daily. A low-dose diuretic (eg, hydrochlorothiazide) may be added if blood pressure is not controlled. Losartan can be titrated up to 100 mg daily.

Calcium Channel Blockers

• Calcium channel blockers (CCBs) can be divided into dihydropyridines and nondihydropyridines. Dihydropyridines bind to L-type calcium channels in the vascular smooth muscle, which results in vasodilatation and a decrease in blood pressure. They are effective as monotherapy in black patients and elderly patients.

• Amlodipine is a dihydropyridine CCB that has antianginal and antihypertensive effects. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

• 5 mg/day PO initially; may be increased by 2.5 mg/day every 7-14 days; not to exceed 10 mg/day PO; maintenance: 5-10 mg/day PO.

Central-acting (alpha2 agonist)

• Centrally acting alpha2-agonists stimulate presynaptic alpha2-adrenergic receptors in the brain stem, which reduces sympathetic nervous activity. These effects result in a decrease in peripheral resistance, renal vascular resistance, blood pressure, and heart rate.

• Clonidine can be used alone or in combination with other antihypertensives. Clonidine is associated with a rebound effect, especially at higher doses or with more severe hypertension.

• Immediate-release tablets: 0.1 mg PO q12hr. Range: 0.1-0.8 mg/day divided q12hr; not to exceed 2.4 mg/day.

Vasodilators

• Vasodilators relax blood vessels to improve blood flow, thus decreasing blood pressure. Hydralazine may lower blood pressure by exerting a peripheral, vasodilating effect through a direct relaxation of vascular smooth muscle.

• Hydralazine is indicated for essential hypertension, alone or as an adjunct.

• Initial dose is 10 mg given 4 times daily for the first 2 to 4 days, then 25 mg 4 times a day for 1 week. Hydralazine IV or IM is indicated for severe essential hypertension when the drug cannot be given orally or when there is an urgent need to lower BP.

Prognosis

• Most individuals diagnosed with hypertension will have increasing blood pressure (BP) as they age. Untreated hypertension is notorious for increasing the risk of mortality and is often described as a silent killer. Mild to moderate hypertension, if left untreated, may be associated with a risk of atherosclerotic disease in 30% of people and organ damage in 50% of people within 8-10 years after onset.

Death Prevention

• It is estimated that 1 death is prevented per 11 patients treated for stage 1 hypertension and other cardiovascular risk factors when a sustained reduction of 12 mm Hg in systolic BP over 10 years is achieved. However, for the same reduction is systolic BP reduction, it is estimated that 1 death is prevented per 9 patients treated when cardiovascular disease or end-organ damage is present.

References

• UpToDate. (2014). Overview of hypertension in adults. Retrieved from http://www.uptodate.com/contents/overview-of-hypertension-in-adults/.

• UpToDate. (2014). Choice of therapy in primary (essential) hypertension: Recommendations. Retrieved from http://www.uptodate.com/contents/choice-of-therapy-in-primary-essential-hypertension-recommendations/.

• Medscape. (2014). Hypertension. Retrieved from http://emedicine.medscape.com/article/241381-overview/.