Hypertension

Primary hypertension

Hemodynamics and physiologic components (eg, plasma volume, activity of the renin-angiotensin system) vary, indicating that primary hypertension is unlikely to have a single cause. Even if one factor is recognized, multiple factors are probably involved in sustaining elevated blood pressure (the mosaic theory). Heredity is a predisposing factor, but the exact mechanism by which genetics plays a role is unclear. At younger ages, environmental factors (eg, dietary sodium, stress) seem to affect only people who are genetically susceptible; however, in patients > 65 years, high sodium intake becomes more likely to precipitate hypertension.

Secondary hypertension

Common causes include (1):

• Obstructive sleep apnea

• Renal parenchymal disease: Chronic glomerulonephritis or pyelonephritis, polycystic renal disease, lupus nephritis, obstructive uropathy

• Renovascular disease

• Primary aldosteronism (2)

• Other endocrine disorders (less common): Pheochromocytoma, Cushing syndrome, congenital adrenal hyperplasia, hyperthyroidism, hypothyroidism (myxedema), primary hyperparathyroidism, acromegaly, and mineralocorticoid excess syndromes other than primary aldosteronism

• Prescription or over-the-counter medications: Sympathomimetics (decongestants), nonsteroidal anti-inflammatory drugs (NSAIDs), antipsychotics, tyrosine kinase inhibitors, angiogenesis inhibitors, stimulants, corticosteroids, cocaine

• Vascular anomalies: Coarctation of the aorta

Licorice may contribute to worsening of blood pressure control. Diabetes is not considered a cause of secondary hypertension, although patients with diabetes commonly also are hypertensive.

Etiology references

1. 1. Rimoldi SF, Scherrer U, Messerli FH. Secondary arterial hypertension: when, who, and how to screen? Eur Heart J. 2014;35(19):1245–1254. doi:10.1093/eurheartj/eht534

2. 2. Brown JM, Siddiqui M, Calhoun DA, et al. The unrecognized prevalence of primary aldosteronism: A cross-sectional study. Ann Intern Med. 2020;173(1):10–20. doi:10.7326/M20-0065

Abnormal sodium transport

In many cases of hypertension, sodium transport across the vascular cell membrane is abnormal, because the sodium-potassium pump (Na+, K+-ATPase) is defective or inhibited, or because permeability to sodium ions is increased. The result is increased intracellular sodium and calcium, which makes the cell more sensitive to sympathetic stimulation. Because Na+, K+-ATPase may pump norepinephrine back into sympathetic neurons (thus inactivating this neurotransmitter), inhibition of this mechanism could also enhance the effect of norepinephrine, increasing BP. Defects in sodium transport may occur in children who are normotensive but have a parent with hypertension.

Sympathetic nervous system

Sympathetic stimulation increases blood pressure, usually more in patients with hypertension than in patients who are normotensive. Whether this hyperresponsiveness resides in the sympathetic nervous system or in the myocardium and vascular smooth muscle is unknown.

A high resting pulse rate, which may result from increased sympathetic nervous activity, is a well-known predictor of hypertension.

In some patients with hypertension, circulating plasma catecholamine levels during rest are higher than normal.

Renin-angiotensin-aldosterone system

The renin-angiotensin-aldosterone system helps regulate blood volume and therefore blood pressure. Renin, an enzyme formed in the juxtaglomerular apparatus, catalyzes conversion of angiotensinogen to angiotensin I. This inactive product is cleaved by angiotensin-converting enzyme (ACE), mainly in the lungs but also in the kidneys and brain, to angiotensin II, a potent vasoconstrictor that also stimulates autonomic centers in the brain to increase sympathetic discharge and stimulates release of aldosterone and vasopressin. Aldosterone causes sodium retention and vasopressin causes water retention, elevating BP. Aldosterone also enhances potassium excretion; low plasma potassium (< 3.5 mEq/L [< 3.5 mmol/L]) increases vasoconstriction through closure of potassium channels.

Renin secretion is controlled by at least 4 mechanisms, which are not mutually exclusive:

• A renal vascular receptor responds to changes in tension in the afferent arteriolar wall

• A macula densa receptor detects changes in the delivery rate or concentration of sodium chloride in the distal tubule

• Circulating angiotensin II has a negative feedback effect on renin secretion

• Sympathetic nervous system stimulates renin secretion mediated by beta-receptors (via the renal nerve)

Elevated angiotensin II levels are generally acknowledged to be responsible for renovascular hypertension, at least in the early phase, but the role of the renin-angiotensin-aldosterone system in primary hypertension is not established. However, in patients with African ancestry and older patients with hypertension, renin levels tend to be low (1). Older patients also tend to have low angiotensin II levels, which may be related to a more volume-dependent salt-sensitive form of hypertension.

Hypertension due to chronic renal parenchymal disease (renoprival hypertension) results from the combination of a renin-dependent mechanism and a volume-dependent mechanism. In most cases, increased plasma renin activity is not evident. Hypertension is typically moderate and sensitive to sodium and water balance.

Vasodilator deficiency

Deficiency of a vasodilator (eg, bradykinin, nitric oxide), rather than excess of a vasoconstrictor (eg, angiotensin, norepinephrine), may cause hypertension. Reduction in nitric oxide, due to stiff arteries, occurs with aging, and this reduction contributes to salt sensitivity (ie, lesser amounts of salt ingestion will raise BP) (2). With reduced nitric oxide, a large sodium load (eg, a salty meal) may increase systolic BP by > 10 to 20 mm Hg.

If the kidneys do not produce adequate amounts of vasodilators (because of renal parenchymal disease), blood pressure can increase.

Vasodilators and vasoconstrictors (mainly endothelin) are also produced in endothelial cells. Therefore, endothelial dysfunction greatly affects blood pressure.

Pathology and complications

No pathologic changes occur early in hypertension. Severe or prolonged hypertension damages target organs (primarily the cardiovascular system, brain, and kidneys), increasing risk of:

• Coronary artery disease (CAD) and myocardial infarction (MI)

• Heart failure

• Stroke (particularly hemorrhagic)

• Renal failure

• Death

Elevated BP levels lead to the development of generalized arteriolosclerosis and acceleration of atherogenesis. Arteriolosclerosis is characterized by medial hypertrophy, hyperplasia, and hyalinization of small arteries (arterioles), notably in the eyes and the kidneys. In the kidneys, the changes narrow the arteriolar lumen, increasing TPR; thus, hypertension leads to more hypertension. Furthermore, once arteries are narrowed, any slight additional shortening of already hypertrophied smooth muscle reduces the lumen to a greater extent than in normal-diameter arteries. These effects may explain why the longer hypertension has existed, the less likely specific treatment (eg, renovascular surgery) for secondary causes is to restore blood pressure to normal. Thus, earlier diagnosis and treatment of even modestly elevated BP (ie, systolic BP of 120 to 129 mm Hg, even if the diastolic BP is in normal range) may provide benefit, especially in younger patients with a family history of hypertension.

Because afterload is increased in patients with elevated BP, the left ventricle gradually hypertrophies, causing diastolic dysfunction. The ventricle eventually dilates, causing dilated cardiomyopathy and heart failure, often worsened by arteriosclerotic coronary artery disease. Thoracic aortic dissection is typically a consequence of hypertension; almost all patients with abdominal aortic aneurysms have hypertension.

Pathophysiology references

1. 1. Williams SF, Nicholas SB, Vaziri ND, Norris KC. African Americans, hypertension and the renin angiotensin system. World J Cardiol. 2014;6(9):878-889. doi:10.4330/wjc.v6.i9.878

2. 2. Fujiwara N, Osanai T, Kamada T, et al. Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension: modulation of nitric oxide synthesis by salt intake. Circulation. 2000;101:856–861. doi:10.1161/01.cir.101.8.856

Symptoms and signs reference

1. 1. Matsuoka S, Kaneko H, Okada A, et al. Association of retinal atherosclerosis assessed using Keith-Wagener-Barker system with incident heart failure and other atherosclerotic cardiovascular disease: Analysis of 319,501 individuals from the general population. Atherosclerosis. 2022;348:68-74. doi:10.1016/j.atherosclerosis.2022.02.024

Blood pressure measurement

The blood pressure used for formal diagnosis should be an average of 2 or 3 measurements taken in the office at different times under these conditions:

• Patient seated in a chair (not examination table) for > 5 minutes, feet on floor, back supported

• Upper limb supported at heart level with no clothing covering the area of cuff placement

• No exercise, caffeine, or tobacco use for at least 30 minutes

At the first visit, measure BP in both arms; subsequent measurements should use the arm that gave the higher reading.

A properly sized BP cuff is applied to the upper arm. An appropriately sized cuff covers two-thirds of the biceps; the bladder is long enough to encircle > 80% of the arm, and bladder width equals at least 40% of the arm’s circumference. Thus, patients with obesity usually require large cuffs.

Blood pressure may be measured by either auscultatory or oscillometric devices. Fully automated validated oscillometric devices may be preferred over the auscultatory method as they provide accurate BP measurements and reduce human error (1, 2). For the auscultatory measurement, the clinician inflates the cuff above the expected systolic pressure and gradually releases the air while listening with a stethoscope placed over the brachial artery. As the pressure falls, the pressure at which the first heartbeat is heard is systolic BP. Total disappearance of the sound marks diastolic BP. The same principles are followed to measure BP in a forearm (radial artery) and thigh (popliteal artery). Mechanical devices should be calibrated periodically.

Home blood pressure monitoring, combined with periodic clinician in-office measurements, can improve blood pressure control. However, cuffless home devices (such as smart watches) are not adequately precise, and should not be relied upon (1).

BP is measured in both arms because BP that is > 15 mm Hg higher in one arm than the other requires evaluation of the upper vasculature.

BP is measured in a thigh (with a much larger cuff) to exclude coarctation of the aorta, particularly in patients with diminished or delayed femoral pulses; with coarctation, BP is significantly lower in the legs than in the arms.

Variable measurements and hypertension

White coat hypertension is defined as BP that is elevated in the office but does not meet the criteria for hypertension based on out-of-office readings in untreated patients. The prevalence is approximately 10 to 20% of the population and is more common in children, older adults, and women, as well as those with office-based BP close to the diagnostic threshold.

White coat effect refers to BP that is elevated in the office but is normal during out-of-office readings, among patients who are on treatment for hypertension.

The data about treatment outcomes of patients with white coat hypertension are conflicting. Untreated white coat hypertension seems to be associated with more adverse cardiovascular outcomes compared to normotension. Patients with white coat hypertension have a 3- to 4-fold increased risk of developing sustained hypertension after 7 to 10 years compared to normotensive people (3). White coat effect does not appear to be associated with adverse cardiovascular outcomes.

Masked hypertension is defined as blood pressure that is consistently elevated outside the office, but in which office readings do not meet the criteria for hypertension in untreated people. This group of patients may represent 10 to 30% of the adult population and is more common in men, non-Hispanic Black people, and people with diabetes (4).

Masked hypertension and masked uncontrolled hypertension (in those being treated) are associated with increased cardiovascular risk, with mortality similar to the risk in patients with sustained hypertension (5).

Home or ambulatory BP monitoring is indicated when white coat hypertension or masked hypertension is suspected.

History

The history includes the:

• Duration of hypertension and previously recorded BP levels

• History or symptoms of coronary artery disease, heart failure, or obstructive sleep apnea

• Symptoms of, or personal or family history of, other relevant coexisting disorders (eg, stroke, renal dysfunction, peripheral arterial disease, dyslipidemia, diabetes, gout)

• Use of medications that predispose to hypertension (eg, NSAIDs, estrogen-containing oral contraceptives)

• Sleep duration

Social history includes exercise levels and use of tobacco, alcohol, and stimulants (including medications and illicit drugs).

A dietary history focuses on intake of salt and stimulants (eg, tea, coffee, caffeine-containing sodas, energy drinks).

Physical examination

The physical examination includes measurement of height, weight, and waist circumference; fundoscopic examination for retinopathy; auscultation for bruits in the neck and abdomen; and a full cardiac, respiratory, and neurologic examination. The abdomen is palpated for kidney enlargement and abdominal masses. Peripheral arterial pulses are evaluated; diminished or delayed femoral pulses suggest aortic coarctation, particularly in patients < 30 years. A unilateral renal artery bruit may be heard in thin patients with renovascular hypertension.

Testing

After hypertension is diagnosed based on blood pressure measurements, testing is needed to:

• Detect target-organ damage

• Identify cardiovascular risk factors

The more severe the hypertension and the younger the patient, the more extensive is the evaluation. For adults newly diagnosed with hypertension, tests should include (1):

• Urinalysis and urinary albumin:creatinine ratio; if abnormal, consider renal ultrasound

• Lipid panel, complete metabolic panel (including creatinine or cystatin C, potassium, and calcium), fasting plasma glucose or hemoglobin A1c, thyroid-stimulating hormone

• ECG

• Sometimes measurement of plasma free metanephrines (to detect pheochromocytoma)

• Sometimes a sleep study

Depending on results of the examination and initial tests, other tests may be needed. Basic laboratory testing should be repeated at least annually.

Renal ultrasound to evaluate kidney size may provide useful information if urinalysis detects albuminuria (proteinuria), casts, or microhematuria, or if serum creatinine or cystatin C is elevated.

Patients with hypokalemia unrelated to diuretic use are evaluated for high salt intake and for primary aldosteronism by measuring plasma aldosterone levels and plasma renin activity. Screening for primary aldosteronism is also recommended for patients with resistant hypertension, obstructive sleep apnea, or early stroke (< 40 years) (1).The prevalence of primary aldosteronism is higher than previously recognized, occurring in approximately 10 to 20% of patients with resistant hypertension (6, 7).

On ECG, a broad, notched P-wave indicates atrial hypertrophy and, although nonspecific, may be one of the earliest signs of hypertensive heart disease. Elevated QRS voltage, with or without evidence of ischemia, may occur later and indicates left ventricular hypertrophy (LVH). When LVH is seen on ECG, echocardiography is often done.

If coarctation of the aorta is suspected, echocardiography, chest CT, or MRI can confirm the diagnosis.

Patients with labile, significantly elevated BP and symptoms such as headache, palpitations, tachycardia, excessive perspiration, tremor, and pallor are screened for pheochromocytoma by measuring plasma free metanephrines and for hyperthyroidism, first by measuring thyroid-stimulating hormone (TSH).

A sleep study should be strongly considered in patients whose history suggests sleep apnea.

Left Ventricular Hypertrophy on ECG

Image

© Springer Science+Business Media

Patients with symptoms suggesting Cushing syndrome, systemic rheumatic diseases, eclampsia, acute porphyria, hyperthyroidism, myxedema, acromegaly, or central nervous system (CNS) disorders also require further evaluation.

Diagnosis references

1. 1. Writing Committee Members*, Jones DW, Ferdinand KC, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Hypertension. 2025;82(10):e212-e316. doi:10.1161/HYP.0000000000000249

2. 2. Muntner P, Shimbo D, Carey RM, et al. Measurement of blood pressure in humans: A scientific statement from the American Heart Association. Hypertension. 2019;73:e35–e66. doi:10.1161/HYP.0000000000000087

3. 3. Cohen JB, Lotito MJ, Trivedi UK, Denker MG, Cohen DL, Townsend RR. Cardiovascular events and mortality in white coat hypertension: A systematic review and meta-analysis. Ann Intern Med. 2019;170(12):853–862. doi:10.7326/M19-0223

4. 4. Wang YC, Shimbo D, Muntner P, Moran AE, Krakoff LR, Schwartz JE. Prevalence of masked hypertension among US adults with nonelevated clinic blood pressure. Am J Epidemiol. 2017;185(3):194–202. doi:10.1093/aje/kww237

5. 5. Pierdomenico SD, Pierdomenico AM, Coccina F, et al. Prognostic value of masked uncontrolled hypertension. Hypertension. 2018;72(4):862–869. doi:10.1161/HYPERTENSIONAHA.118.11499

6. 6. Burrello J, Monticone S, Losano I, et al. Prevalence of Hypokalemia and Primary Aldosteronism in 5100 Patients Referred to a Tertiary Hypertension Unit. Hypertension. 2020;75(4):1025-1033. doi:10.1161/HYPERTENSIONAHA.119.14063

7. 7. Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004;89(3):1045-1050. doi:10.1210/jc.2003-031337

Lifestyle modifications

Lifestyle modifications are recommended for all patients with elevated BP or any stage hypertension (2). The best proven nonpharmacologic interventions for prevention and treatment of hypertension include the following:

• Increased physical activity, ideally with a structured exercise program

• Weight loss, if appropriate

• Healthy diet rich in fruits, vegetables, whole grains, and low-fat dairy products, with reduced saturated and total fat content

• Reduced dietary sodium, optimally to < 1500 mg/day (approximately 3.75 g salt) , but at least a 1000 mg/day reduction

• Enhanced dietary potassium intake, unless contraindicated due to chronic kidney disease or use of medications that reduce potassium excretion

• Moderation in alcohol intake in those who drink alcohol to ≤ 2 drinks daily for men and ≤ 1 drink daily for women (one drink is about 12 oz of beer, 5 oz of wine, or 1.5 oz distilled spirits)

• Smoking cessation

Adequate sleep duration ( a minimum of 6 hours/night) is also recommended. Short sleep duration (typically defined as < 5 or 6 hours per night in adults, has been associated with hypertension (5). For example, studies suggest that optimizing sleep quality and duration (> 6 hours/night) improves blood pressure control in patients with chronic kidney disease (6).

Dietary modifications can also help control diabetes, obesity, and dyslipidemia. Patients with uncomplicated hypertension do not need to restrict their activities as long as blood pressure is controlled.

Medications

(See also Medications for Hypertension.)

The decision to treat with medication is based on the BP level and the presence of atherosclerotic cardiovascular disease (ASCVD) or its risk factors as determined by the PREVENT calculator (1). Patients with a 10-year predicted risk for CVD events ≥ 7.5% using PREVENT are considered to be at increased risk. 

Antihypertensive medication should be initiated for patients with hypertension who meet any of the following criteria (2):

• Average BP ≥ 140/90 mm Hg

• Existing cardiovascular disease (coronary heart disease, stroke, or heart failure) and average BP ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic

• Diabetes, chronic kidney disease or 10-year PREVENT cardiovascular risk ≥ 7.5% and average BP ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic

• Persistent average BP ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic after 3 to 6 months of lifestyle intervention

An important part of management is continued reassessment. If patients are not at goal BP, clinicians should strive to optimize adherence to the current regimen before switching or adding medications.

Treatment of  hypertension during pregnancy requires careful medication selection because some antihypertensive medications can harm the fetus.

Medication selection is based on several factors, including comorbidities, contraindications, and tolerability. For most patients, when selecting an agent for monotherapy, initial treatment may be with any of the following medication classes:

• Angiotensin-converting enzyme (ACE) inhibitor

• Angiotensin II receptor blocker (ARB)

• Dihydropyridine calcium channel blocker

• Thiazide diuretic (preferably a thiazide-like diuretic such as chlorthalidone or indapamide)Thiazide diuretic (preferably a thiazide-like diuretic such as chlorthalidone or indapamide)

Adults with stage 1 hypertension (systolic BP 130 to 139/diastolic BP 80 to 89 mm Hg) may be treated initially with a single first-line medication, with dose titration and sequential addition of other medications as needed to achieve blood pressure control (2). Adults with stage 2 hypertension (systolic BP  ≥ 140/diastolic BP  ≥ 90 mm Hg) should be treated initially with 2 first line medications: an ACE inhibitor or ARB combined with either a diuretic or a calcium channel blocker. When combination therapy is indicated, starting treatment with single pill combinations improves adherence (7, 8).

Signs of hypertensive emergencies require immediate blood pressure reduction with parenteral antihypertensives. Such signs may include seizures or focal neurologic symptoms, retinal hemorrhage, chest pain, dyspnea,or nausea and vomiting.

Some antihypertensives are avoided in certain disorders (eg, ACE inhibitors in severe aortic stenosis) whereas others are preferred for certain disorders (eg, calcium channel blockers for patients with angina pectoris, ACE inhibitors or ARBs for patients with diabetes and proteinuria—see tables Initial Choice of Antihypertensive Medication Class and Antihypertensives for Patients With Comorbidities).

If the goal BP is not achieved within 1 month, assess adherence and tolerability and reinforce the importance of following treatment. If patients are adherent with the regimen, the dose of the initial medication can be increased or a second medication added (selected from among medications recommended for initial treatment). Note that an ACE inhibitor and an ARB should not be used together. Therapy is titrated frequently.

If target BP cannot be achieved with 2 medications, a third medication from choices of initial medications is added. If such a third medication is not tolerated or is contraindicated, a medication from another class (eg, aldosterone antagonist) can be used. Patients with such difficult to control BP may benefit from consultation with a hypertension specialist. For resistant hypertension (BP remains above goal despite use of 3 different antihypertensive medications), 4 or more medications are commonly needed.

Achieving adequate blood pressure control often requires several evaluations and changes in pharmacotherapy. Reluctance to titrate or add medications to control BP must be overcome. Nonadherence to therapy, particularly because lifelong treatment is required, can interfere with adequate BP control. Education, with empathy and support, is essential for success.

Devices and physical interventions

Renal artery sympathetic nerve ablation is a potential option for uncontrolled hypertension, using percutaneous catheter-based radiofrequency devices, ultrasound, or the injection of neurolytic agents into tissues surrounding the renal vasculature (9). Several industry-funded sham-controlled studies with different patient populations (eg, untreated hypertension [10], treated hypertension [11], or resistant hypertension [12]) have demonstrated statistically and/or clinically significant reductions in systolic blood pressure. However, whether these devices reduce major cardiovascular events remains uncertain, with studies ongoing related to efficacy, patient selection, safety, and long-term impact on quality of life (13).

Baroreflex activation therapy has been proposed for management of resistant hypertension, but studies have not provided sufficient evidence to recommend the use of these devices (2). The therapy employs a battery-powered device surgically implanted around the carotid body to stimulate the baroreceptor and, in a dose-dependent manner, lower blood pressure. In one long-term follow-up study of patients with resistant hypertension who were included in earlier pivotal trials, baroreflex activation therapy maintained its efficacy for persistent reduction of office BP without major safety issues (14).

Resistant hypertension

Resistant hypertension is defined as blood pressure that is not controlled to goal despite adherence to 3 suitably dosed antihypertensive medications of different classes (including a diuretic) and after white coat effect is excluded. Blood pressure that requires 4 drugs to achieve control is also considered controlled resistant hypertension. Use of a mineralocorticoid receptor antagonist can be beneficial in attaining goal blood pressure (15).

Secondary causes of hypertension must be excluded as part of the evaluation for resistant hypertension. Hyperaldosteronism or subclinical hypercortisolism has been identified in 15 to 20% of cases of resistant hypertension.

Treatment references

1. 1. Khan SS, Coresh J, Pencina MJ, et al. Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement From the American Heart Association. Circulation. 2023;148(24):1982-2004. doi:10.1161/CIR.0000000000001191

2. 2. Writing Committee Members*, Jones DW, Ferdinand KC, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Hypertension. 2025;82(10):e212-e316. doi:10.1161/HYP.0000000000000249

3. 3. Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial. JAMA. 2016;315(24):2673-2682. doi:10.1001/jama.2016.7050

4. 4. White WB, Wakefield DB, Moscufo N, et al. Effects of Intensive Versus Standard Ambulatory Blood Pressure Control on Cerebrovascular Outcomes in Older People (INFINITY). Circulation. 2019;140(20):1626-1635. doi:10.1161/CIRCULATIONAHA.119.041603

5. Ta

6. 5. Thomas SJ, Calhoun D. Sleep, insomnia, and hypertension: current findings and future directions. J Am Soc Hypertens. 2017;11(2):122-129. doi:10.1016/j.jash.2016.11.008

7. 6. Ali W, Gao G, Bakris GL. Improved Sleep Quality Improves Blood Pressure Control among Patients with Chronic Kidney Disease: A Pilot Study. Am J Nephrol. 2020;51(3):249-254. doi:10.1159/000505895

8. 7. Parati G, Kjeldsen S, Coca A, Cushman WC, Wang J. Adherence to Single-Pill Versus Free-Equivalent Combination Therapy in Hypertension: A Systematic Review and Meta-Analysis. Hypertension. 2012;77(2):692-705. doi:10.1161/HYPERTENSIONAHA.120.15781

9. 8. WilliaMcEvoy JW, McCarthy CP, Bruno RM, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45(38):3912-4018. doi:10.1093/eurheartj/ehae178

10. 9. Rey-García J, Townsend RR. Renal Denervation: A Review. Am J Kidney Dis. 2022;80(4):527-535. doi:10.1053/j.ajkd.2022.03.015

11. 10. Böhm M, Kario K, Kandzari DE, et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020;395(10234):1444-1451. doi:10.1016/S0140-6736(20)30554-7

12. 11. Mahfoud F, Kandzari DE, Kario K, et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet. 2022;399(10333):1401-1410. doi:10.1016/S0140-6736(22)00455-X

13. 12. Bhatt DL, Vaduganathan M, Kandzari DE, et al. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial. Lancet. 2022;400(10361):1405-1416. doi:10.1016/S0140-6736(22)01787-1

14. 13. Rao A, Krishnan N. Update on Renal Sympathetic Denervation for the Treatment of Hypertension. Curr Cardiol Rep. 2022;24(10):1261-1271. doi:10.1007/s11886-022-01753-x

15. 14. de Leeuw PW, Bisognano JD, Bakris GL, Nadim MK, Haller H, Kroon AA, DEBuT-T and Rheos Trial Investigators. Sustained reduction of blood pressure with baroreceptor activation therapy: Results of the 6-year open follow-up. Hypertension. 2017;69:836–843. doi:10.1161/HYPERTENSIONAHA.117.09086

16. 15. Carey RM, Calhoun DA, Bakris GL, et al. Resistant hypertension: Detection, evaluation, and management: A Scientific Statement From the American Heart Association. Hypertension. 2018;72:e53–e90. doi: 10.1161/HYP.0000000000000084

Prognosis references

1. 1. Bourdillon MT, Song RJ, Musa Yola I, Xanthakis V, Vasan RS. Prevalence, Predictors, Progression, and Prognosis of Hypertension Subtypes in the Framingham Heart Study. J Am Heart Assoc. 2022;11(6):e024202. doi:10.1161/JAHA.121.024202

2. 2. Kannel WB, Gordon T, Schwartz MJ. Systolic versus diastolic blood pressure and risk of coronary heart disease. The Framingham study. Am J Cardiol. 1971;27(4):335-346. doi:10.1016/0002-9149(71)90428-0

3. 3. Dziedziak J, Zaleska-Żmijewska A, Szaflik JP, Cudnoch-Jędrzejewska A. Impact of Arterial Hypertension on the Eye: A Review of the Pathogenesis, Diagnostic Methods, and Treatment of Hypertensive Retinopathy. Med Sci Monit. 2022;28:e935135. doi:10.12659/MSM.935135