Diagnosis and treatment of resistant hypertension

Figures & data

Table I. Main factors or causes of treatment-resistance pseudo-resistance in treated hypertensive patients (modified from ref. (15)).

Factors related to physician

• Improper blood pressure measurement

• Use of inappropriate antihypertensive medication

– Inadequate dosages

– Inappropriate combinations

• Physician inertia (failure to change or increase dose regimens, when not at goal)

• Poor communication between doctor and patient

• Complicated therapeutic plan (especially in the presence of multiple concomitant medications) or complicated dosing schedules of antihypertensive drugs.

Factors related to patient

• White-coat effect

• Drug-related side effects

• Non-adherence

• Inadequate patient education

• Concomitant use of oral contraceptives

• Concomitant use of anti-inflammatory or sympathomimetic agents

• Memory or psychiatric problems and cognitive disorders (elderly subjects)

• Costs of medication (in some healthcare systems)

Other causes

• Obstructive sleep apnoea syndrome

• Chronic kidney disease

• Primary or secondary hyperaldosteronism

• Severe atherosclerotic disease (calcification) of the arterial wall (elderly subjects)

• Aortic valve sclerosis with haemodynamically significant insufficiency

Figure 1. Proposed definition and treatment of true treatment-resistant hypertension. Both office and “out of office” blood pressure (obtained either by 24-h ambulatory monitoring and/or self measurement at home) have to be abnormally high in spite of a treatment consisting preferably of a thiazide or thiazide-like diuretic, a blocker of the renin–angiotensin system and a calcium antagonist. If needed, a beta-blocker, an anti-aldosterone or a loop diuretic, an α-blocker or a centrally acting sympatholytic drug might be added to the three-drug regimen, or replace one of the three first-choice options, if not tolerated.

Table II. Clinical variables showing differences between resistant hypertensive patients and hypertensive patients with blood pressure controlled with three or fewer antihypertensive drugs (from ref. (36)).

Parameters	OR	95% CI	p
Duration of hypertension	1.07	1.06–1.08	< 0.001
BMI ≥ 30 kg/m^2	1.62	1.32–1.99	< 0.001
Abdominal obesity (yes vs no)	1.43	1.16–1.76	0.001
LVH on ECG (yes vs no)	2.32	1.76–3.06	< 0.001
UAE > 30 mg/g	2.19	1.74–2.76	< 0.001
eGFR < 60 ml/min per 1.73 m^2	1.40	1.11–1.71	< 0.003

OR, multivariate odds ratio; BMI, body mass index; CI, confidence interval; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; UAE, urinary albumin excretion.

Table III. Clinical features in patients with true and white-coat resistant hypertension (RH) (from ref. (32)).

Parameters	True RH (n = 5182)	White-coat RH (n = 3113)	p
Age, years	64.0 ± 11.7^a	65.0 ± 10.9	< 0.001
Sex, % men	54.6	46.0	< 0.001
Duration of hypertension, years	11.4 ± 8.7	10.5 ± 8.2	< 0.001
Smokers, %	14.8	10.3	< 0.001
Diabetes, %	35.1	27.8	< 0.001
Creatinine, μmol/l	75 (62–89)^b	72 (61–84)	0.006
UAE, mg/g	11.0 (3.4–44.5)	7.0 (2.7–20.0)	< 0.001
LVH by ECG, %	18.5	14.4	< 0.001
Previous cardiovascular disease, %	19.1	16.2	0.001

^aMeans± SD, ^bmedian (interquantile range); UAE, urinary albumin excretion; LVH, left ventricular hypertrophy; ECG, electrocardiogram.

Table IV. Clinical conditions in which ACE inhibitors (ACE-Is), angiotensin receptor blockers (ARBs) and/or calcium antagonists (CAs) should be preferred (from ref. (2)).

	ACE-Is	ARBs	CAs
Asymptomatic organ damage
• Left ventricular hypertrophy	+	+
• Asymptomatic atherosclerosis	+		+
• Microalbuminuria	+	+
• Renal dysfunction	+	+
Clinical cardiovascular event
• Previous stroke	+ ^a	+ ^a	+ ^a
• Angina pectoris			+
• Previous myocardial infarction	+	+
• Heart failure	+	+
• Atrial fibrillation, prevention	+	+
• Atrial fibrillation, ventricular rate control	+	+	+ ^b
• Endstage renal disease	+	+
• Proteiunuria	+	+
• Peripheral arteriopathy	+		+
Other
• Isolated systolic hypertension (elderly)			+
• Metabolic syndrome	+	+
• Diabetes mellitus	+	+
• Pregnancy			+
• Blocks			+

^aAny agent effectively lowering blood pressure could be used in this condition. ^bNon-dihydropyridine calcium antagonist.

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