Diagnosis and Management of Resistant Hypertension: A Review

Importance: Hypertension, defined as office systolic blood pressure (SBP) 130 mm Hg or greater and/or diastolic blood pressure 80 mm Hg or greater, affects 43.9% of women and 49.5% of men in the US. Approximately 19.7% of patients treated for hypertension have apparent resistant hypertension (blood pressure ≥130/80 mm Hg) despite using 3 or more antihypertensive medications, preferably a renin-angiotensin system blocker, a calcium channel blocker, and a thiazide-type diuretic, at maximally tolerated doses.

Observations: Approximately 10% of patients treated for hypertension have true resistant hypertension confirmed with home or 24-hour ambulatory blood pressure monitoring to exclude white-coat hypertension (approximately 37.5% of apparent resistant hypertension) and after excluding medication nonadherence (approximately 50%) and secondary hypertension such as primary aldosteronism (approximately 5%-25%). Conditions associated with resistant hypertension include obesity, diabetes, chronic kidney disease, and sleep apnea. Resistant hypertension is associated with increased risk of cardiovascular death vs controlled blood pressure at 5 years to 10 years (absolute risk increase, 10.3% [95% CI, 8.7%-12.1%]). Lifestyle modifications for resistant hypertension include a low-sodium diet (<1500 mg/d), reducing or avoiding alcohol, 150 min/wk or more of aerobic exercise, and weight loss. Illicit drugs (eg, cocaine) and medications that increase blood pressure (eg, nonsteroid anti-inflammatory drugs, serotonin-norepinephrine reuptake inhibitors) should be avoided. Sleep apnea should be treated when diagnosis is confirmed. Pharmacologic optimization includes use of combination tablets of antihypertensives; intensifying diuretic therapy by using chlorthalidone; and sequential addition of antihypertensive medications using evidence-based algorithms. In a meta-analysis of 20 studies (9 randomized clinical trials [RCTs] and 11 observational studies [331 participants]), use of antihypertensive therapies that combine 2 to 3 medications into a single formulation reduced SBP by -3.99 mm Hg (95% CI, -7.92 to -0.07) vs equivalent doses given separately. For patients with apparent or true resistant hypertension who have an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater and a serum potassium level of 4.5 mmol/L or less, adding spironolactone (25-50 mg/d) compared with placebo lowers office SBP by -13.3 mm Hg (95% CI, -17.89 to -8.72 [4 RCTs]) and 24-hour ambulatory SBP by -8.46 mm Hg (95% CI, -12.54 to -4.38 [2 RCTs]) in a network meta-analysis of 24 RCTs (3485 patients with resistant hypertension). A meta-analysis of 10 RCTs (2478 participants) reported that compared with a sham procedure, catheter-based renal denervation, which disrupts the sympathetic nerves in the renal artery walls, decreased 24-hour ambulatory SBP by -4.4 mm Hg (95% CI, -6.1 to -2.7) and office SBP by -6.6 mm Hg (95% CI, -9.7 to -3.6).

Conclusions and relevance: True resistant hypertension affects 10% of patients treated for hypertension and is diagnosed after excluding white-coat hypertension, medication nonadherence, and secondary hypertension such as primary aldosteronism. First-line treatment includes lifestyle modifications, diuretic therapy with chlorthalidone, and combination tablets of antihypertensives. Spironolactone and renal denervation decrease blood pressure in patients with true resistant hypertension.

Author/s:

Michel Azizi, Wanpen Vongpatanasin, Naomi D L Fisher, Felix Mahfoud, Laurence Amar, Ajay J Kirtane

Cardiovascular Events and Mortality in White Coat Hypertension: A Systematic Review and Meta-analysis

Brian Desmarais — Wed, 12 Jun 2019 01:48:41 +0000

Date Added:

June 11, 2019

Journal/Publication:

Annals of Internal Medicine

Publication Date:

June 11, 2019

URL:

Cardiovascular Events and Mortality in White Coat Hypertension: A Systematic Review and Meta-analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.7326/M19-0223

Keywords

blood pressure

stroke

cardiovascular

MeSH

White Coat Hypertension

blood pressure

cardiovascular diseases

Research Personnel

Blood Pressure Determination

hypertension

National Institutes of Health (U.S.)

stroke

Untreated white coat hypertension appears to increase the risk of adverse cardiovascular events and death by around 35%. James W. Mold, MD, MPH

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BACKGROUND:

The long-term cardiovascular risk of isolated elevated office blood pressure (BP) is unclear.

PURPOSE:

To summarize the risk for cardiovascular events and all-cause mortality associated with untreated white coat hypertension (WCH) and treated white coat effect (WCE).

DATA SOURCES:

PubMed and EMBASE, without language restriction, from inception to December 2018.

STUDY SELECTION:

Observational studies with at least 3 years of follow-up evaluating the cardiovascular risk of WCH or WCE compared with normotension.

DATA EXTRACTION:

2 investigators independently extracted study data and assessed study quality.

DATA SYNTHESIS:

27 studies were included, comprising 25 786 participants with untreated WCH or treated WCE and 38 487 with normal BP followed for a mean of 3 to 19 years. Compared with normotension, untreated WCH was associated with an increased risk for cardiovascular events (hazard ratio [HR], 1.36 [95% CI, 1.03 to 2.00]), all-cause mortality (HR, 1.33 [CI, 1.07 to 1.67]), and cardiovascularmortality (HR, 2.09 [CI, 1.23 to 4.48]); the risk of WCH was attenuated in studies that included stroke in the definition of cardiovascular events(HR, 1.26 [CI, 1.00 to 1.54]). No significant association was found between treated WCE and cardiovascular events (HR, 1.12 [CI, 0.91 to 1.39]), all-cause mortality (HR, 1.11 [CI, 0.89 to 1.46]), or cardiovascular mortality (HR, 1.04 [CI, 0.65 to 1.66]). The findings persisted across several sensitivity analyses.

LIMITATION:

Paucity of studies evaluating isolated cardiac outcomes or reporting participant race/ethnicity.

CONCLUSION:

Untreated WCH, but not treated WCE, is associated with an increased risk for cardiovascular events and all-cause mortality. Out-of-office BP monitoring is critical in the diagnosis and management of hypertension.

PRIMARY FUNDING SOURCE:

National Institutes of Health.

Author/s:

M.G., Cohen, J.B., Lotito, M.J., Denker, M.G., Cohen, D.L., Townsend, R.R.