Hypertension

Hypertension is a multisystem disease whose hallmark is the elevation of blood pressure. Primary hypertension has no apparent cause, constitutes the majority of cases, and is treated with measures to reduce blood pressure. Secondary hypertension does have an abnormality that is causing the elevation in blood pressure, such as a tumor that secretes hormones that raise blood pressure; removing the cause may be curative. Primary hypertension is generally not curable and needs to be managed as a chronic disease.

White coat hypertension
White coat hypertension may lead to sustained hypertension.

Diagnosis
A systematic review by the Rational Clinical Examination has reviewed the research on measuring the blood pressure.

If the diastolic pressure is below 110 mm Hg, it should be confirmed on two addition visits as some patients will have a lower blood pressure on repeat measurements. A larger cuff should be used for obese patients.

21% of patients with untreated borderline hypertension (diastolic pressure between 90 and 104 mm Hg) may have normal blood pressures outside of the doctor's office.

Some patients may have their blood pressure rise by as much as 25 mm Hg due to an alarm reaction upon seeing a doctor.

Elderly patients may have pseudohypertension due to inability of the blood pressure cuff to compress stiff arteries. Pseudohypertension may be detected by Osler's maneuver.

Excluding secondary hypertension
Listening for an abdominal bruit, especially if it is both systolic and diastolic, may help detect underlying renal artery stenosis.

Among patients with resistant hypertension (blood pressure >140/90 mm Hg despite a three drug regimen, 20% of patients had serum aldosterone and plasma renin activity ratio of more than 65:16 with a aldosterone concentration above 416 pmol/L. However, only 10% of all patients had primary aldosteronism. Half of these patients have a normal serum potassium.

Treatment
Current clinical practice guidelines are: In addition, drugs for hypertension (antihypertensives) have been reviewed by the Medical Letter.
 * The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)
 * 2007 guidelines by the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Several randomized controlled trials have shown that treating hypertension can reduce morbidity or mortality. These trials include:
 * MRC trial
 * Hypertension Detection and Follow-up Program
 * Treatment of Mild Hypertension Study (TOMHS)
 * Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
 * Veterans Affairs Cooperative trial
 * Losartan Intervention For Endpoint reduction in hypertension study (LIFE)

Treatment goals
Per the JNC7 Guidelines:
 * "Treating "most patients" SBP and DBP to targets that are <140/90 mmHg is associated with a decrease in cardiovascular complications. A more recent industry-sponsored, randomized controlled trial suggests benefit from treating any patient with a cardiac risk to a goal systolic pressure of 130 mm Hg. This is consistent with the HOPE trial. Although 39% of HOPE patients had diabetes, the benefit occurred in patients with and without diabetes.
 * In patients with hypertension and diabetes or chronic kidney disease, the BP goal is <130/80 mmHg.

The European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) 2007 guidelines add to diabetes and chronic kidney disease that tight control (<130/80 mmHg) is needed for patients with:
 * stroke
 * myocardial infarction
 * proteinuria

Non-drug treatment

 * See also salt and health
 * Exercise
 * Lifestyle modification

Initial medication
Clinical practice guidelines have tried to make blanket recommendations for all patients:
 * "Thiazide-type diuretics for most" patients are recommended by the JNC7 clinical practice guidelines. Chlorthalidone may be the best choice.
 * ß-blockers
 * ß-blockers are the preferred initial medication for patients with coronary heart disease according to a systematic review.
 * "ß-blockers, especially in combination with a thiazide diuretic, should not be used in patients with the metabolic syndrome or at high risk of incident diabetes" is noted by the European ESH/ESC clinical practice guidelines. The ESH/ESC guidelines cite the LIFE and ASCOT trials. Unlike the ALLHAT study, both of these trials were in largely anglo populations, supported by industry, and at the same institution. All patients in the LIFE trial had left ventricular hypertension (LVH). Based on these two trials, a meta-analysis has concluded that beta blockers should not be the first choice treatment.
 * For Stage 2 Hypertension' (SBP ≥ 160 or'' DBP≥100) consider starting two medications for more effect.



Refinements in selection
However, the Veterans Affairs Cooperative trial suggests the initial drug may be better selected based on the patient's age, race, and gender. The patient's demographic roughly corresponds with their renin profile, but is more predictive than the renin profile. The molecular basis is being determined.

In the Veterans Affairs Cooperative, among the the high renin demographic (young whites), diuretics had similar efficacy to placebo; whereas in the low renin demographic (older blacks), the ace-inhibitors had similar efficacy to placebo in the Veterans Affairs Cooperative Study Group on Antihypertensive Agents (see figure). Similarly, a meta-analysis has concluded that beta-blockers are a good first choice for younger patients, but not for older patients.

Several randomized controlled trials have compared initial medications for hypertension. As summarized in the table, the disparate results may be due to racial and gender differences in responses to medications. Race, gender, and age demographic may partly predict frequency of drug toxicity to different anti-hypertensive medications.

For patients with Stage 2 Hypertension (SBP > 160 or DBP > 100 mmHg), start with two drugs.

Contraindications
There are contraindications to each of the four major classes, even when other indicators suggest a particular class might be best for the hypertensive patients:
 * Beta-blockers: asthma, bradycardia and heart block
 * Diuretics: metabolic syndrome, hypokalemia
 * ACE inhibitors: pregnancy
 * Calcium channel blockers: constipation, irritable bowel syndrome

Comorbidities
Given that the antihypertensive is likely to be a lifelong treatment, selection also may be guided by other chronic diseases of the patient.
 * Beta-blockers: reduce benign essential tremor; may prevent migraine
 * Diuretics: heart failure
 * ACE inhibitors: protective of the kidneys, as in diabetes
 * Calcium channel blockers: also may prevent migraine; may relieve neuropathic pain

Resistant hypertension
Blood pressure may be difficult to treat, especially in older patients. Clinical practice guidelines from the American Heart Association (AHA) address the management of resistant hypertension.

Resistant hypertension is characterized by volume expansion and abnormalities of the renin-angiotensin system with high aldosterone and cortisol with low renin levels in the plasma in spite of many patients taking thiazide diuretics. { This suggests that high corticotropin may contribute, in some cases due to an abnormal cytochrome P-450 3A5 allele that may reduce metabolism of cortisol and corticosterone (a precursor of aldosterone). Resistent hypertension is also associated with insulin resistance.
 * Physiology

The AHA defines resistant hypertension as "blood pressure that remains above goal in spite of the concurrent use of 3 antihypertensive agents of different classes."
 * Evaluation

First, 'pseudoresistance' should be considered:
 * Medication noncompliance
 * Inadequate prescribing by the health care provider may be the most common cause of persistent hypertension.
 * White coat hypertension, pseudohypertension and other problems of measurement.

Next, secondary hypertension should be considered:
 * Renal artery stenosis may be the cause of as much as 30% of cases of truly resistant hypertension.
 * Primary aldosteronism underlies about 10% of cases of resistant hypertension.
 * Obstructive sleep apnea

The AHA recommends that one of the three medicines use for hypertension should be a diuretic.
 * Treatment

"Three drugs at half standard dose in combination" may be better than one drug at standard dose according to a systematic review.

In an unblinded, uncontrolled extension of the ASCOT randomized controlled trial, spironolactone 25-50 mg per day as a fourth medication reduced the blood pressure by 21.9/9.5. This result was not affected by whether one of the first three medications included a diuretic. A second study study, also uncontrolled, corroborated the role of spironolactone. In this study, 54% of patients were African-American, 45% had primary hyperaldosteronism.

Catheter-based renal sympathetic denervation has been studied for resistant hypertension.

Elderly patients
Treating patients aged 80 years or older for two years who have a systolic pressure over 160 mm hg (the average entry pressure was 173/91 mm Hg) and treating to 150/80 mm Hg may reduce morbidity. In this trial, the average seated blood pressure at the end of the study in the treatment group was 143/78.