Hypertension

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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.

Classification

Classification of blood pressure for adults[1]
Blood pressure classification Initial blood pressure mm Hg Followup recommended
SBP DBP
Normal <120 and <80 Recheck in 2 years
Prehypertension 120-139 or 80-99 Recheck in 1 year
Stage 1 Hypertension 140-159 or 90-99 Confirm within 2 months
Stage 2 Hypertension ≥ 160 or ≥100 "Evaluate or refer to source of care within 1 month. For those with higher pressures (e.g., >180/110 mmHg), evaluate and treat immediately or within 1 week depending on clinical situation and complications... 2 drug combination for most."

Diagnosis

A systematic review by the Rational Clinical Examination has reviewed the research on measuring the blood pressure.[2]

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.[3] A larger cuff should be used for obese patients.[4]

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.[5]

Some patients may have their blood pressure rise by as much as 25 mm Hg due to an alarm reaction upon seeing a doctor.[6]

Elderly patients may have pseudohypertension due to inability of the blood pressure cuff to compress stiff arteries.[7] Pseudohypertension may be detected by Osler's maneuver.[7]

Excluding secondary hypertension

Listening for an abdominal bruit, especially if it is both systolic and diastolic, may help detect underlying renal artery stenosis.[8]

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.[9]

Treatment

Current clinical practice guidelines are based on The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)[1] and the 2007 guidelines by the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).[10] Drugs for hypertension, called antihypertensives as a group, have been reviewed by the Medical Letter.[11]

Several randomized controlled trials have shown that treating hypertension can reduce morbidity or mortality. These trials include:

  • MRC trial[12]
  • Hypertension Detection and Follow-up Program[13]
  • Treatment of Mild Hypertension Study (TOMHS) [14]
  • Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).[15]
  • Veterans Affairs Cooperative trial[16][17]
  • Losartan Intervention For Endpoint reduction in hypertension study (LIFE)[18]

Treatment goals

Per the JNC7 Guidelines:[1]

  • "Treating "most patients" SBP and DBP to targets that are <140/90 mmHg is associated with a decrease in cardiovascular complications.
  • In patients with hypertension and diabetes or renal disease, the BP goal is <130/80 mmHg.

Non-drug treatment

Initial medication

Clinical practice guidelines have tried to make blanket recommendations for all patients:

Efficacy of different drugs. From Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.[16]

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.[16][17] The patient's demographic roughly corresponds with their renin profile, but is more predictive than the renin profile.[17] The molecular basis is being determined.[28]

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).[16] Similarly, a meta-analysis has concluded that beta-blockers are a good first choice for younger patients, but not for older patients.[29]

Predicting response to anti-hypertensives based on demographics
Category name demographics Comments Best anti-hypertensive categories
High renin demographic less than 50 years old, anglo salt-sensitive; diuretic responsive diuretics, calcium channel blockers
Low renin demographic more than 50 years old, non-anglo* ace-inhibitors, ß-blockers
* Obesity and female[30] are also associated with low renin.

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.[15][31][32][16][33] Race, gender, and age demographic may partly predict frequency of drug toxicity to different anti-hypertensive medications.[34]


Selected trials comparing initial medications
Trial Patients Intervention Result
Race BMI Age
(mean)
ALLHAT[15]
2002
47% anglo 30 70 Chlorthalidone Diuretics (chlorthalidone) better than calcium channel blockers and angiotensin-converting enzyme inhibitors
ANBP2[31]
2003
95% anglo 27 72 Hydrochlorothiazide Diuretics (hydrochlorothiazide) not as good angiotensin-converting enzyme inhibitors
ACCOMPLISH[33]
2008
84% anglo 31 68 Hydrochlorothiazide Diuretics (hydrochlorothiazide) not as good as calcium channel blockers

For patients with Stage 2 Hypertension (SBP >160 or DBP>100 mmHg), start with two drugs.[1]

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:

Comorbidities

Given that the antihypertensive is likely to be a lifelong treatment, selection also may be guided by other chronic diseases of the patient.

Resistant hypertension

Blood pressure may be difficult to treat, especially in older patients.[35][36] Clinical practice guidelines from the American Heart Association (AHA) address the management of resistant hypertension.[37]

Physiology

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[38][39] in spite of many patients taking thiazide diuretics.[39]{ This suggests that high corticotropin may contribute[39], in some cases due to an abnormal cytochrome P-450 3A5 allele that may reduce metabolism of cortisol and corticosterone (a precursor of aldosterone).[40] Resistent hypertension is also associated with insulin resistance.[41]

Evaluation

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."

First, 'pseudoresistance' should be considered:[37]

  • Medication noncompliance
  • Inadequate prescribing by the health care provider[42] may be the most common cause of persistent hypertension.[43][44]
  • White coat hypertension, pseudohypertension and other problems of measurement.[45]

Next, secondary hypertension should be considered:[37]

Treatment

The AHA recommends that one of the three medicines use for hypertension should be a diuretic.[37]

"Three drugs at half standard dose in combination" may be better than one drug at standard dose according to a systematic review.[23]

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.[47] A second study study, also uncontrolled, corroborated the role of spironolactone.[48] In this study, 54% of patients were African-American, 45% had primary hyperaldosteronism.

Catheter-based renal sympathetic denervation has been studied for resistant hypertension.[49]

Systolic hypertension

For more information, see: Systolic 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.[50] In this trial, the average seated blood pressure at the end of the study in the treatment group was 143/78.

Prognosis

References

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See also