If a hypertensive patient’s blood pressure remains above target after receiving three antihypertensive medications, the condition is called intractable hypertension. The condition of controlled elevated blood pressure that requires at least 4 medications to lower it is also classified as intractable hypertension.
Intractable hypertension is a common clinical problem faced by both primary care physicians and specialists. While the exact epidemiology of intractable hypertension is unknown, clinical trials suggest that it is not uncommon, involving perhaps 20% to 30% of the study population. Advanced age and obesity are two strong risk factors for recalcitrant hypertension, and this becomes more common as patients increase in age and weight.
The prognosis of recalcitrant hypertension is unclear, but there is a high cardiovascular risk in patients with severe long-term complications, multiple other cardiovascular risk factors for obesity, sleep apnea syndrome, diabetes mellitus, and chronic kidney disease. The diagnosis of intractable hypertension requires proper blood pressure measurement techniques to confirm the diagnosis of persistently elevated blood pressure levels. Pseudo-resistance to medications due to poor patient compliance or white coat hypertension is ruled out. Intractable hypertension almost always has multiple etiologies.
Successful treatment of recalcitrant hypertension requires consideration of the adverse lifestyle factors that influence it, diagnosis and treatment of secondary causes of elevated blood pressure, and effective drug combination therapy.
”Patients should be aware of the importance of blood pressure control, and most need a combination of both lifestyle improvement and effective drug therapy,” according to David A. Calhoun, chair of the guideline writing committee.
”Physicians must recognize that special attention should be given to the screening and treatment of intractable hypertension.” Often diuretics are not used adequately in patients with intractable hypertension, and some patients may benefit from the addition of salt corticosteroid (specifically, aldosterone) receptor antagonists (MRAs) to their treatment regimen, according to the guidelines. MRAs can treat primary aldosteronism (proaldosterone), which was found to be present in 20% of patients with intractable hypertension in combination. the benefits of MRAs for intractable hypertension were not recognized until recently, but blood potassium levels should be measured at the time of use”.
Basic features of intractable hypertension
Systolic blood pressure is more difficult to control than diastolic blood pressure in patients with intractable hypertension. Advanced age, high baseline blood pressure levels, obesity, high salt diet, chronic kidney disease, diabetes mellitus, and left ventricular hypertrophy increase the risk of recalcitrant hypertension. Blacks and women are also risk factors for recalcitrant hypertension. Also, specific places of residence such as in the southeastern United States.
Lifestyle factors
Weight: Obesity is associated with severely elevated blood pressure and the need for a combination of multiple medications to control blood pressure. Thus, obesity is a common feature of recalcitrant hypertension. Reducing body weight, although not specifically assessed in patients with intractable hypertension, undoubtedly has benefits in terms of lowering blood pressure and reducing the variety of antihypertensive medications used.
Sodium: Patients with intractable hypertension often have a high salt diet and tend to be typically salt-sensitive patients, including those of advanced age, African Americans, and those with chronic kidney disease. In patients with generally elevated blood pressure, reducing dietary salt intake can lower systolic blood pressure by 5-10 mm Hg and diastolic blood pressure by 2-6 mm Hg, and the benefit is more pronounced in African-Americans and patients of advanced age.
Alcohol: High alcohol intake is associated with higher and less controllable blood pressure. In one study, a small sample of abstinent alcoholics had a 7.2 mm Hg reduction in 24-hour ambulatory systolic blood pressure and a 6.6 mm Hg reduction in diastolic blood pressure, and the prevalence of hypertension decreased from 42% to 12%.
Secondary causes of hypertension
Patients with intractable hypertension usually have an underlying irreversible cause of hypertension leading to resistance to treatment. Obstructive sleep apnea, organic renal disease, prodromal, and renal artery stenosis are all common in patients with intractable hypertension. Less common are pheochromocytoma, Cushing’s disease, hyperparathyroidism, aortic constriction, and intracranial tumors, and these abnormalities may require access to a specialist in order to facilitate enhanced blood pressure control.
Sleep apnea syndrome is present in 83% of patients with intractable hypertension. The effect of sleep apnea syndrome on blood pressure was more pronounced in men compared to women. Twenty percent of patients with intractable hypertension have combined aldosteronism, and serum potassium concentrations in these patients are mostly at normal levels. Cushing’s disease has target organ damage effects independent of elevated blood pressure, and aldosterone receptor antagonists are the most effective agents for its treatment. Several studies have shown that renal artery stenosis is the most common cause of secondary hypertension in the elderly, 90% of which is caused by atherosclerosis.
Adverse drug interactions: Some drugs that elevate blood pressure such as non-steroidal anti-inflammatory drugs (NSAIDs) include aspirin, selective COX-2 inhibitors, sympathomimetic drugs, central stimulants, oral contraceptives, erythropoietin, cyclocilin A, natural licorice and botanicals such as ephedrine. Acetaminophen has a mildly hypertensive effect, with NSAIDs having the most pronounced effect, and should therefore be preferred in the treatment of pain in hypertensive patients. It should be discontinued if possible. It is important to apply an effective multi-drug combination regimen to lower blood pressure.
Diuretics: Specialty reports of hypertension suggest that treatment failure is usually related in part to the lack or inadequate use of diuretics.
Salt corticosteroid receptor antagonists: When combined with existing multi-drug regimens, an MRA can provide significant antihypertensive benefit. A study of a small sample ingesting an average of four antihypertensive drugs found that the combination of an MRA reduced systolic blood pressure by an average of 25 mm Hg and diastolic blood pressure by 12 mm Hg.
Multiple drug combinations: The guideline development group wrote: “Continued combination of drugs with different mechanisms of action does not seem appropriate; therefore, triple therapy including ACEI/ARB, calcium antagonists, and thiazide diuretics is usually more effective and well tolerated. Ultimately, however, the choice of three or more medications should be individualized, taking into account the patient’s prior beneficiary medications, history of adverse events, other medical conditions such as chronic kidney disease, diabetes mellitus, and the patient’s financial limitations.
Dosage Usage: Studies have shown that patients who ingest at least 1 antihypertensive medication at bedtime have better control of blood pressure, particularly by lowering nocturnal blood pressure.
Measures to help patients take their medications should be taken in an orderly and moderate manner. Try to simplify prescriptions by applying long-acting combination medications and once-daily use. Frequent follow-up visits and home blood pressure monitoring help patients adhere to their daily regimen.
Recommendations for diagnosis and treatment of intractable hypertension.
1. Diagnosis: Patients who have received three appropriate doses of antihypertensive medications including reasonable use of diuretics and whose office blood pressure is greater than 140/90 or with diabetes mellitus, chronic kidney disease blood pressure greater than 130/80 mmHg or patients receiving four or more antihypertensive medications in order to achieve the office blood pressure standard.
2. To exclude pseudoresistance: How is the patient’s compliance with medical advice? To rule out the white coat phenomenon, obtain the patient’s blood pressure at home, at work or ambulatory
3.Identify reversible lifestyle: obesity, lack of physical activity, excessive alcohol intake high salt, low fiber diet.
4, Discontinue or reduce drugs that affect blood pressure: NSAIDs, sympathomimetic drugs, central stimulants, oral contraceptives, licorice infusion, ephedrine.
5.Screening for secondary factors of hypertension: obstructive sleep apnea (snoring, confirmed apnea, excessive daytime sleepiness), proaldosterone (elevated aldosterone-to-renin ratio), renal organic disease (creatinine clearance small 30 ml/min), renal artery stenosis (young women, known atherosclerosis, deteriorating renal function), pheochromocytoma (intermittent high blood pressure, palpitations, sweating, headache), Cushing’s syndrome (full-moon face, centripetal obesity, abdominal fat lines, interscapular fat deposits), aortic constriction (different pulsations in the brachial or femoral arteries, systolic murmur), and
6. Pharmacologic treatment: maximized diuretic therapy, including reasonable addition of salt corticosteroid receptor antagonists, combination of antihypertensive agents with different mechanisms of action, use of loop diuretics in chronic kidney disease and/or patient receiving strong dilation agents (e.g., long-pressin)
7. Referral to a specialist: referral to an appropriate specialist for known or suspected secondary hypertension, and referral to a hypertension specialist if the patient’s blood pressure remains uncontrolled after 6 months of treatment.