Essential hypertension
Essential hypertension, also known as primary or idiopathic hypertension, is defined as persistently elevated arterial blood pressure—typically systolic ≥130 mmHg or diastolic ≥80 mmHg—without an identifiable secondary cause such as renal or endocrine disorders.[1][2] This condition accounts for 90-95% of all hypertension cases among adults, making it the predominant form of high blood pressure worldwide.[3] Its etiology remains multifactorial and incompletely understood, involving genetic susceptibility interacting with environmental influences like excessive sodium intake, obesity, physical inactivity, and aging, which contribute to mechanisms such as increased peripheral vascular resistance, renal sodium retention, impaired pressure natriuresis, and heightened sympathetic nervous system activity.[4][1][5] If unmanaged, essential hypertension substantially elevates the risk of target organ damage, including left ventricular hypertrophy, atherosclerosis, stroke, heart failure, and chronic kidney disease, underscoring its role as a leading modifiable contributor to cardiovascular morbidity and mortality.[6][3] Diagnosis relies on repeated office or ambulatory blood pressure measurements after excluding secondary causes, while treatment emphasizes lifestyle interventions—such as dietary sodium reduction, weight loss, and aerobic exercise—often combined with antihypertensive medications like ACE inhibitors, diuretics, or calcium channel blockers to achieve blood pressure control and mitigate long-term complications.[1][2]Definition and Classification
Diagnostic Criteria and Staging
Diagnosis of essential hypertension begins with confirming sustained elevation of blood pressure (BP) through standardized office measurements, typically requiring an average of at least two readings on at least two separate occasions using a validated device and proper technique, such as the patient seated quietly for 5 minutes with arm supported at heart level.[7] Out-of-office monitoring, including ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM), is recommended to validate office readings and exclude white-coat or masked hypertension; for ABPM, daytime averages ≥130/80 mmHg or 24-hour averages ≥125/75 mmHg support diagnosis, while HBPM thresholds are ≥130/80 mmHg.[7] Essential hypertension is distinguished from secondary forms only after initial evaluation rules out identifiable causes, involving medical history, physical examination (e.g., assessing for bruits, organomegaly), and basic laboratory tests such as serum electrolytes, creatinine, urinalysis, and fasting glucose; advanced screening for secondary hypertension (e.g., aldosterone-renin ratio for primary aldosteronism) is pursued if features like onset before age 30, resistant BP, or hypokalemia are present, affecting approximately 5-10% of cases.[7] [8] Major guidelines differ in diagnostic thresholds: the 2025 AHA/ACC guideline defines hypertension at office systolic BP (SBP) ≥130 mmHg or diastolic BP (DBP) ≥80 mmHg, emphasizing earlier intervention in high-risk individuals (e.g., those with cardiovascular disease, diabetes, or chronic kidney disease), whereas the 2024 ESC guideline uses ≥140/90 mmHg for confirmed office BP, prioritizing out-of-office confirmation to reduce overdiagnosis.[7] [8] These discrepancies stem from varying interpretations of trial data on cardiovascular risk thresholds, with the lower AHA/ACC cutoff linked to reclassification of millions as hypertensive but supported by longitudinal studies showing risk escalation at 130/80 mmHg.[7] Staging classifies severity to guide management intensity, based on office BP levels:| Category | AHA/ACC 2025 (mmHg) | ESC 2024 (mmHg) |
|---|---|---|
| Normal/Optimal | <120 systolic and <80 diastolic | <120 systolic and <80 diastolic |
| Elevated/High-Normal | 120-129 systolic and <80 diastolic | 120-139 systolic or 70-89 diastolic |
| Stage 1/Grade 1 | 130-139 systolic or 80-89 diastolic | 140-159 systolic or 90-99 diastolic |
| Stage 2/Grade 2 | ≥140 systolic or ≥90 diastolic | 160-179 systolic or 100-109 diastolic |
| Stage 3/Grade 3 | N/A (included in Stage 2) | ≥180 systolic or ≥110 diastolic |
Distinction from Secondary Hypertension
Essential hypertension, also termed primary hypertension, is defined as persistently elevated blood pressure without an identifiable underlying etiology, representing 90-95% of adult cases.[3] Secondary hypertension, by contrast, arises from a detectable cause such as renal disease, endocrine disorders, or vascular abnormalities, accounting for 5-10% of hypertension in adults but a higher proportion (up to 30%) in younger patients under 30 years or those with resistant disease.[9][3] Clinical differentiation relies on historical, demographic, and phenotypic clues. Essential hypertension typically develops insidiously over years, often in middle-aged or older adults, with moderate severity responsive to standard pharmacotherapy.[9] Secondary forms more commonly manifest abruptly, with marked elevation (e.g., >180/110 mm Hg), poor control on three or more agents at optimal doses, or onset extremes—before age 30 or after 55 in previously normotensive individuals.[9] Suggestive features include disproportionate target organ damage, family history inconsistencies, or syndrome-specific signs like hypokalemia (aldosteronism), flank masses (polycystic kidney disease), or bruits (renal artery stenosis).[9][10] Diagnostic confirmation of essential hypertension requires exclusion of secondary causes via targeted evaluation. American Academy of Family Physicians guidelines advocate initial screening with electrocardiography, urinalysis, fasting glucose, complete blood count, lipid profile, serum creatinine, electrolytes, and thyroid-stimulating hormone for all new diagnoses, escalating to imaging or specialized tests (e.g., aldosterone-renin ratio, renal ultrasound) based on suspicion.[9] European Society of Cardiology protocols similarly emphasize screening in high-risk profiles, such as resistant hypertension or sudden exacerbations, to identify treatable etiologies before labeling as essential.[11] Failure to screen adequately risks missing reversible contributors, though over-investigation in low-risk essential cases yields low yield.[9]Epidemiology
Global Prevalence and Trends
Approximately 1.4 billion adults aged 30-79 years worldwide were estimated to have hypertension in 2024, representing about 33% of that age group.[6] This figure encompasses primarily essential hypertension, which accounts for 90-95% of cases globally, as secondary forms linked to identifiable causes like renal disease remain rare.[12] Absolute numbers have risen steadily due to population growth, aging demographics, and urbanization, from roughly 650 million in 1990 to 1.28 billion in 2019 among adults aged 30-79.[13] Age-standardized prevalence rates have shown relative stability or modest declines in recent decades. Between 2000 and 2010, global age-standardized hypertension prevalence increased by about 3.5% in men and 3.3% in women, but from 2010 to 2020, it decreased by 1.2% in men and 1.0% in women, reflecting partial successes in awareness and treatment in some regions.[14] However, two-thirds of affected individuals reside in low- and middle-income countries, where control rates often fall below 20%, limiting broader reductions.[15] Projections suggest that without accelerated interventions, the global burden could reach 1.56 billion cases by 2025, driven by persistent risk factors like obesity and salt intake.[13] Despite these trends, hypertension awareness, treatment, and control remain suboptimal worldwide, with only about one-third of cases effectively managed as of 2019 data.[16] Improvements in high-income settings contrast with stagnation in developing regions, underscoring disparities in healthcare access and lifestyle modifications.[12]Demographic Disparities
The prevalence of hypertension, predominantly essential in nature, exhibits significant variations across demographic groups, influenced by genetic, environmental, and socioeconomic factors. In the United States, age is a primary driver, with prevalence rising sharply from approximately 21.3% among adults aged 18-39 years to over 60% in those aged 60 and older, based on data from 2021-2023 national surveys.[17][18] This age-related increase reflects cumulative vascular stiffening and endothelial changes, though younger onset is observed in high-risk populations. Globally, similar patterns hold, with hypertension affecting fewer than 10% of individuals under 30 years but exceeding 50% in those over 70, per 2020 estimates from the World Health Organization and affiliated studies.[14] Sex differences show higher overall prevalence in men compared to women in the US, at 50.8% versus 44.6% among adults aged 18 and older during 2017-March 2020, though this gap narrows post-menopause due to estrogen loss accelerating vascular aging in women.[19] Incidence rates may vary inversely in certain cohorts, with some longitudinal studies reporting higher annual onset in older women (27.37 per 1,000 person-years) than men (16.06 per 1,000), potentially linked to longer life expectancy and hormonal shifts.[20] Internationally, male predominance persists in working-age groups across low- and middle-income countries, where prevalence reaches 30.6% overall but skews higher among men due to occupational and behavioral exposures.[14] Racial and ethnic disparities are pronounced, particularly in the US, where non-Hispanic Black adults face the highest prevalence at 58.0% (age-adjusted) from 2021-2023 data, compared to 44.5% overall and lower rates among non-Hispanic Whites (around 40-45%) and Hispanics.[21][22] Non-Hispanic Black individuals also experience earlier onset, with average diagnosis ages 5-10 years younger than Whites, contributing to greater cumulative vascular damage.[23] Asian Americans generally exhibit lower prevalence than Whites, while Hispanics show intermediate rates, patterns attributed partly to genetic polymorphisms in sodium handling and renin-angiotensin systems, alongside differential adiposity and diet.[24] These disparities persist even after adjusting for socioeconomic status, underscoring non-modifiable biological contributors alongside access barriers. Globally, analogous gradients appear in admixed populations, with higher burdens in African-descent groups in the Caribbean and sub-Saharan Africa.[25]| Demographic Group (US Adults ≥18, Age-Adjusted Prevalence, 2021-2023) | Percentage with Hypertension |
|---|---|
| Overall | 44.5% |
| Non-Hispanic Black | 58.0% |
| Men | 50.8% |
| Women | 44.6% |
Etiology and Risk Factors
Genetic and Inherited Factors
Essential hypertension exhibits significant heritability, with family and twin studies estimating that 30 to 50 percent of blood pressure variation is attributable to genetic factors.[29][30] This heritability arises from the aggregation of hypertension within families, where first-degree relatives of affected individuals face a twofold to fourfold increased risk compared to the general population, independent of shared environmental influences.[29] Twin studies, including those comparing monozygotic and dizygotic pairs, consistently demonstrate higher concordance rates for blood pressure traits in monozygotic twins, supporting additive genetic effects over environmental sharing alone.[31][32] The genetic architecture of essential hypertension is polygenic, involving numerous common variants with small individual effects rather than rare high-penetrance mutations typical of monogenic forms.[33] Genome-wide association studies (GWAS) have identified over 1,000 genetic loci associated with blood pressure traits, collectively explaining more than 60 percent of SNP-based heritability in large European-ancestry cohorts exceeding 1 million individuals.[34] These loci implicate pathways such as renal sodium handling, vascular smooth muscle contraction, and endothelial function, with no single gene accounting for a dominant proportion of risk.[35] In diverse populations, including those of African and Qatari ancestry, GWAS reveal both shared and population-specific variants, highlighting the role of evolutionary adaptations in blood pressure regulation.[36] Polygenic risk scores (PRS), which aggregate effects from hundreds of GWAS-identified variants, prospectively predict hypertension onset and cardiovascular events, with a one-standard-deviation increase in PRS linked to 40 to 50 percent higher odds of incident hypertension over 4 to 6 years.[37][38] Multi-ethnic PRS models enhance predictive accuracy across ancestries, improving upon clinical risk scores by 10 to 14 percent for hypertension incidence, though their utility diminishes in older adults due to gene-environment interactions.[39][40] While PRS stratify genetic susceptibility, they underscore that inherited factors interact with modifiable elements like diet and obesity, explaining only a portion of population-level variance.[41] Ongoing research integrates PRS with epigenetic markers to refine risk assessment, but clinical implementation remains limited by ancestry-specific performance and ethical considerations in screening.[42]Non-Genetic Non-Modifiable Factors
Age is a primary non-genetic non-modifiable risk factor for essential hypertension, with prevalence rising progressively after age 50 due to age-related arterial stiffening and reduced vascular compliance.[43] In the United States, hypertension affects approximately 60% of adults over 65, compared to less than 10% under 30, reflecting cumulative hemodynamic and structural changes independent of modifiable behaviors.[44] Sex influences hypertension risk, with men exhibiting higher incidence and earlier onset before age 50, while women experience a surge post-menopause due to estrogen decline, equalizing or exceeding male rates thereafter.[24] This pattern holds across cohorts, as evidenced by data showing men under 45 having twofold higher prevalence than women, reversing after 65.[45] Racial and ethnic disparities persist, with non-Hispanic Black adults facing the highest prevalence—about 55% in adults over 18—and earlier onset, often by age 30 in one-quarter of cases, compared to Whites at 45% overall and later diagnosis.[44] [24] Hispanic and Black populations show elevated lifetime risk, attributed partly to non-genetic factors like socioeconomic exposures, though genetic admixture complicates isolation.[46] Low birth weight, defined as under 2.5 kg, correlates with increased hypertension risk in adulthood via fetal programming mechanisms, including impaired nephrogenesis and heightened sympathetic activity.[47] Meta-analyses confirm an inverse linear association, with each 1 kg decrease in birth weight raising systolic blood pressure by 2-4 mmHg and hypertension odds by 20-50%, effects persisting after adjusting for adult factors.[48] [49] This link, observed in cohorts followed for decades, underscores early-life insults as non-modifiable contributors.[50]Modifiable Lifestyle Factors
Obesity represents a major modifiable risk factor for essential hypertension, with excess adiposity promoting insulin resistance, sympathetic nervous system activation, and renal sodium retention, thereby elevating blood pressure. Meta-analyses indicate that individuals with obesity face a 3.5-fold increased likelihood of developing hypertension compared to those with normal weight, and approximately 60% of hypertension cases may be attributable to elevated body mass index (BMI).[51] Sustained weight loss of 5-10 kg in overweight or obese adults can reduce systolic blood pressure by 5-20 mm Hg, underscoring the causal link between adiposity reduction and hemodynamic improvement.[52] Excessive dietary sodium intake causally contributes to hypertension by expanding plasma volume and impairing endothelial function, with population-level evidence showing a dose-dependent relationship. Reducing sodium intake from high levels (>150 mmol/day) to low levels (<50 mmol/day) lowers systolic blood pressure by an average of 6.7 mm Hg across diverse cohorts, while a more modest reduction of 4.4 g/day yields a significant population-wide drop in both systolic and diastolic pressures.[53][54] Adopting heart-healthy patterns like the Dietary Approaches to Stop Hypertension (DASH) diet, which emphasizes fruits, vegetables, and low-fat dairy while limiting sodium to <2,300 mg/day, further amplifies these benefits, reducing hypertension incidence by up to 35% in normotensive individuals.[7] Physical inactivity exacerbates hypertension risk through diminished vascular compliance and elevated sympathetic tone, whereas regular aerobic exercise induces vasodilation and reduces resting blood pressure. Systematic reviews of randomized trials demonstrate that structured physical activity interventions lower 24-hour ambulatory systolic blood pressure by 5.4 mm Hg in hypertensive patients, with isometric exercises showing the greatest efficacy (up to 8-10 mm Hg reductions).[55][56] Guidelines recommend at least 150 minutes of moderate-intensity aerobic activity weekly for primordial prevention, as adherence correlates with a 20-30% lower incidence of hypertension in longitudinal cohorts.[7] Excessive alcohol consumption exhibits a linear dose-response association with hypertension, independent of other factors, by disrupting baroreflex sensitivity and promoting sodium retention. Each 10 g/day increment in alcohol intake raises the relative risk of hypertension by approximately 6%, with no threshold below which risk plateaus; intakes exceeding 30 g/day (about two standard drinks) show particularly steep increases in systolic blood pressure.[57] Reducing consumption to <14 g/day in men and <7 g/day in women can lower systolic pressure by 3-4 mm Hg, with greater benefits in heavy drinkers.[58] Tobacco smoking serves as an independent risk factor for incident hypertension, primarily through endothelial damage and oxidative stress, despite its acute pressor effects often normalizing at rest in chronic users. Prospective cohort studies report that current smokers have a 1.5- to 2-fold higher risk of developing hypertension compared to never-smokers, with cessation attenuating this risk over time, particularly if avoiding substantial post-quit weight gain.[59][60] Smoking synergistically amplifies cardiovascular complications in hypertensive individuals, justifying its classification as a modifiable contributor despite nuanced effects on baseline blood pressure.[61]Associated Comorbidities
Essential hypertension frequently coexists with other chronic conditions, amplifying overall cardiovascular risk through shared pathophysiological mechanisms such as endothelial dysfunction, inflammation, and insulin resistance.[62] Common comorbidities include cardiovascular diseases (e.g., coronary artery disease, stroke, and heart failure), chronic kidney disease, type 2 diabetes mellitus, obesity, and dyslipidemia, which collectively contribute to higher morbidity and mortality rates.[63] These associations are bidirectional, with hypertension exacerbating target organ damage while comorbidities like obesity and diabetes promote vascular stiffness and sodium retention, perpetuating elevated blood pressure.[64] Cardiovascular diseases represent the primary complications of essential hypertension, with uncontrolled blood pressure serving as the leading modifiable risk factor for premature coronary events, stroke, and heart failure.[65] For instance, hypertension doubles the risk of coronary heart disease and increases stroke risk by 4-6 fold compared to normotensive individuals, driven by accelerated atherosclerosis and left ventricular hypertrophy.[66] In patients with hypertension, the prevalence of comorbid heart failure is elevated, particularly in those with concurrent diabetes or obesity, where systolic and diastolic dysfunctions are compounded by neurohormonal activation.[66] Chronic kidney disease (CKD) develops in approximately 20-30% of individuals with longstanding essential hypertension due to glomerular hypertension and microvascular injury, progressing to end-stage renal disease if untreated.[67] Hypertension accounts for nearly 30% of CKD cases globally, with albuminuria serving as an early marker of renal involvement that correlates with cardiovascular outcomes.[67] Type 2 diabetes mellitus co-occurs in up to 40-50% of hypertensive patients, forming part of the cardiometabolic cluster that heightens macrovascular complications; the presence of both conditions multiplies the risk of myocardial infarction and stroke beyond additive effects.[68] Similarly, obesity affects over 60% of those with hypertension, promoting sympathetic overactivity and leptin-mediated pressure elevation, while dyslipidemia (prevalent in ~58%) fosters plaque formation through oxidized LDL accumulation in arterial walls.[68] These metabolic comorbidities underscore the need for integrated management to mitigate synergistic risks.[69]Pathophysiology
Core Hemodynamic Alterations
Essential hypertension is characterized by sustained elevation in mean arterial pressure (MAP) primarily due to increased systemic vascular resistance (SVR), with cardiac output (CO) remaining normal or only modestly elevated in most established cases.[70] MAP is determined by the product of CO and SVR, where the former reflects stroke volume and heart rate, and the latter arises from arteriolar vasoconstriction and structural remodeling of resistance vessels.[71] In adults with primary hypertension, SVR is almost uniformly enhanced, reflecting a key hemodynamic anomaly driven by altered autoregulation and endothelial function in small arteries.[72] [70] In younger patients or early-stage hypertension, a hyperkinetic hemodynamic profile may predominate, featuring elevated CO from increased heart rate and stroke volume, alongside rising SVR that eventually stabilizes the pressure elevation as resistance dominates chronically.[73] A meta-analysis of hemodynamic studies confirmed that while SVR is consistently higher across primary hypertension cohorts, CO contributions are more variable, with significant elevations (e.g., 10-20% above normotensive levels) in subsets under 40 years old, transitioning to SVR-driven patterns with age and disease progression.[74] This age-dependent shift underscores how initial sympathetic overactivity boosts cardiac output, but long-term adaptations favor peripheral resistance as the core sustaining mechanism.[75] Additional alterations include reduced vascular compliance and augmented wave reflections, which amplify systolic pressure without proportionally increasing CO, further entrenching the hemodynamic burden on the left ventricle.[76] Impedance cardiography studies reveal that in mild essential hypertension, total peripheral resistance rises uniformly (often by 30-50% over normotensive baselines), while run-off indices and flow cessation pressures indicate impaired diastolic runoff, contributing to diastolic hypertension.[77] These patterns persist independently of severity in fixed hypertension, distinguishing essential from secondary forms where CO abnormalities (e.g., hypervolemia-driven) are more prominent.[76] Overall, SVR elevation represents the hallmark, with therapeutic targeting of resistance (e.g., via vasodilators) directly addressing this core pathophysiology.[78]Vascular and Endothelial Dysfunction
Endothelial dysfunction represents a core pathophysiological feature in essential hypertension, characterized by impaired endothelium-dependent vasodilation and a shift toward vasoconstrictive, pro-inflammatory, and prothrombotic states. The vascular endothelium regulates tone through release of nitric oxide (NO), prostacyclin, and endothelin, but in hypertension, NO bioavailability diminishes due to reduced endothelial nitric oxide synthase (eNOS) activity and increased degradation by reactive oxygen species (ROS). This dysfunction precedes overt hypertension and contributes causally to elevated peripheral resistance by promoting vasoconstriction and vascular remodeling.[79][80][81] A primary mechanism involves oxidative stress, where superoxide anions generated by sources such as NADPH oxidase react with NO to form peroxynitrite, uncoupling eNOS and perpetuating a vicious cycle of ROS production and endothelial injury. Studies in human essential hypertension models demonstrate that this oxidative imbalance correlates with reduced flow-mediated dilation, a marker of endothelial function, independent of vascular structural hypertrophy. Additionally, chronic hypertension fosters endothelial expression of adhesion molecules (e.g., VCAM-1, ICAM-1) and cytokines, amplifying low-grade inflammation that stiffens arteries and impairs baroreflex sensitivity.[82][83][84] Evidence from longitudinal cohorts indicates that endothelial dysfunction is detectable in pre-hypertensive states and predicts progression to sustained hypertension, with interventions like antioxidants or eNOS enhancers showing potential to restore function in early stages. In established essential hypertension, this dysfunction extends to microvascular beds, contributing to rarefaction and ischemia, while macrovascular effects include accelerated atherosclerosis via impaired anti-thrombotic properties. Notably, NO deficiency is posited as a primary driver, with genetic polymorphisms in eNOS linked to hypertension susceptibility in population studies.[85][86][87]Neurohormonal and Renal Mechanisms
Increased sympathetic nervous system activity contributes to essential hypertension by elevating norepinephrine levels, which promote vasoconstriction, increase cardiac output, and enhance renal sodium reabsorption. This overactivity is particularly evident in younger patients with essential hypertension, where sympathetic outflow can be 2-3 times higher than normal, and in normotensive offspring of hypertensive parents under stress conditions.[88] Sympathetic activation also stimulates renin release from juxtaglomerular cells via beta-1 adrenergic receptors, amplifying downstream effects on vascular tone.[70] The renin-angiotensin-aldosterone system (RAAS) plays a central role through angiotensin II-mediated vasoconstriction and aldosterone-induced sodium retention in the distal tubules, leading to volume expansion. High salt intake (9-12 g/day) can activate RAAS by elevating plasma and cerebrospinal fluid sodium, which stimulates angiotensin II production and, in turn, chronic sympathoexcitation via brain osmoreceptors.[88] Interactions between sympathetic overdrive and RAAS exacerbate hypertension, as angiotensin II infusion raises blood pressure by approximately 30 mm Hg within 24 hours, partly through central nervous system mechanisms that are blocked by sympathetic inhibitors like guanethidine.[70] Approximately 50-60% of essential hypertension cases exhibit salt sensitivity, linking RAAS dysregulation to impaired volume regulation.[1] Renal mechanisms in essential hypertension involve a blunted pressure-natriuresis response, where higher arterial pressure is required to achieve sodium balance compared to normotensives, effectively resetting the pressure-natriuresis curve rightward. This impairment arises from multiple renal defects, including enhanced sodium reabsorption via transporters like NHE3 and SGLT2, which shift to apical microvilli under chronic pressure elevation, sustaining hypertension through volume retention.[89] [70] Experimental evidence supports a causal role, as kidney transplantation from hypertensive donors induces hypertension in normotensive recipients, and renal sympathetic denervation attenuates salt-dependent hypertension in models like 5/6 nephrectomy. While some resetting may occur secondarily to prolonged hypertension, primary defects precede blood pressure elevation in genetic and infusion models.[89] [70]Diagnosis
Accurate Blood Pressure Assessment
Accurate blood pressure (BP) assessment is fundamental to diagnosing essential hypertension, as mismeasurements can lead to overdiagnosis from white coat hypertension—elevated office readings with normal out-of-office values—or underdiagnosis from masked hypertension, where office readings are normal but out-of-office values are elevated.[90][91] These discrepancies affect up to 15-30% of patients depending on population, underscoring the need for standardized protocols to minimize errors from factors like cuff size, patient positioning, or device validation.[92] The 2025 ACC/AHA guideline emphasizes out-of-office monitoring to confirm office readings, particularly for stage 1 hypertension (130-139/80-89 mm Hg), to align diagnosis with true ambulatory levels and reduce cardiovascular risk misestimation.[93][90] Standard office BP measurement requires a validated oscillometric or auscultatory device, appropriate cuff size (bladder encircling 80% of arm circumference), and patient preparation including avoidance of caffeine, exercise, or smoking for 30 minutes prior, with a 5-minute seated rest.[94][95] The patient must sit upright with back supported, feet flat and uncrossed, arm bare and supported at heart level (mid-sternum), without talking or leg crossing during readings.[96][97] At least two readings, taken 1-2 minutes apart, should be averaged after discarding the first if inconsistent; thresholds for hypertension remain ≥140/90 mm Hg in office settings per ESC/ESH 2023 guidelines, though ACC/AHA uses ≥130/80 mm Hg for higher-risk patients.[95][98] Automated office BP (AOBP) protocols, using unattended multiple readings, reduce observer bias and better approximate ambulatory values compared to manual methods.[99] Out-of-office methods enhance accuracy by capturing real-world variability. Ambulatory BP monitoring (ABPM), worn for 24 hours with readings every 15-30 minutes daytime and 30-60 minutes nighttime, diagnoses white coat hypertension if office BP ≥140/90 mm Hg but daytime ABPM <135/85 mm Hg, and masked hypertension if reversed; it predicts cardiovascular outcomes more reliably than office BP alone, with nocturnal dipping patterns indicating prognosis.[91][100] Home BP monitoring (HBPM), using validated devices with duplicate morning and evening readings over 7 days (discarding day 1), provides averages equivalent to daytime ABPM ≥135/85 mm Hg for hypertension confirmation, recommended by both ACC/AHA and ESC for borderline cases or treatment monitoring.[101][100] ABPM is particularly valuable for excluding secondary causes in essential hypertension suspects, as sustained elevations across awake, asleep, and 24-hour periods (e.g., >130/80 mm Hg 24-hour average) correlate with target organ damage independently of office values.[91][92]Clinical Evaluation and Exclusion of Secondary Causes
Clinical evaluation of patients with hypertension begins with a comprehensive medical history and physical examination to assess for features suggestive of secondary causes, which account for approximately 5% to 10% of cases overall but up to 20% to 30% in resistant hypertension.[7] Key historical elements include the age at onset (early-onset before age 30 years or late-onset after 55 years raises suspicion), pattern of blood pressure elevation (sudden acceleration or paroxysmal surges), family history of hypertension or endocrine disorders, symptoms such as headaches, palpitations, excessive sweating, snoring, or muscle weakness, and review of current medications (e.g., nonsteroidal anti-inflammatory drugs, corticosteroids, or oral contraceptives that may exacerbate blood pressure).[7][102] Lifestyle factors like excessive alcohol intake, high salt consumption, or obesity should also be documented, as they can mimic or contribute to secondary forms. Physical examination focuses on confirming hypertension through standardized office measurements in both arms (with inter-arm differences >10 mm Hg prompting further vascular evaluation) and identifying clinical clues such as abdominal or renal bruits (suggesting renovascular disease), radio-femoral delay or diminished femoral pulses (indicating coarctation of the aorta), cushingoid features, or signs of thyroid dysfunction.[7] Fundoscopic examination for retinopathy and assessment for orthostatic hypotension (a drop of ≥20 mm Hg systolic or ≥10 mm Hg diastolic) are essential to evaluate target organ damage and autonomic involvement. An electrocardiogram is routinely recommended to detect left ventricular hypertrophy or arrhythmias.[7] Laboratory investigations form the cornerstone of excluding secondary causes, starting with basic tests in all newly diagnosed patients: fasting glucose or HbA1c, lipid profile, serum electrolytes (particularly potassium for hypokalemia suggestive of primary aldosteronism), creatinine with estimated glomerular filtration rate, urinalysis for proteinuria or hematuria indicating renal parenchymal disease, urine albumin-to-creatinine ratio, and thyroid-stimulating hormone.[7] These identify common secondary etiologies like chronic kidney disease (prevalence ~14% in hypertensives) or hyperthyroidism.[7] In cases of suspicion—such as resistant hypertension (uncontrolled on ≥3 medications including a diuretic), severe elevation (>180/110 mm Hg), or specific biochemical abnormalities—targeted screening is indicated.[7]- Primary aldosteronism (prevalence 5%-25% in hypertensives, higher in resistant cases): Screen with plasma aldosterone-to-renin ratio (ARR; cutoff ~30 with aldosterone ≥10 ng/dL and suppressed renin); confirmatory tests include saline suppression if positive; recommended in resistant hypertension per AHA/ACC (Class 1, Level B-NR) and considered for all confirmed cases per ESC (Class IIa, Level B).[7]
- Pheochromocytoma/paraganglioma (rare, <1%): Plasma free metanephrines or 24-hour urinary metanephrines in patients with paroxysmal symptoms or sudden onset.[7]
- Renovascular hypertension: Renal artery Doppler ultrasound or CT/MRI angiography if asymmetric kidney size, bruits, or flash pulmonary edema; more common in fibromuscular dysplasia (young females) or atherosclerotic disease (older males with vascular risk).[7]
- Obstructive sleep apnea (prevalence 25%-50% in resistant hypertension): Questionnaires like STOP-BANG followed by polysomnography, especially in obese patients with snoring.[7]
- Other rare causes (e.g., Cushing's syndrome, coarctation): Low-dose dexamethasone suppression test or echocardiography as clinically indicated.