Hypertensive Heart Disease

Etiology

The vast majority (90% to 95%) of individuals with hypertension fall under the classification of primary or essential hypertension. The underlying etiology remains poorly understood but likely reflects a complex interplay between genetic and environmental factors. Several risk factors, including increasing age, family history, obesity, high sodium intake (greater than 3 g/day), physical inactivity, and excessive alcohol consumption, show strong and independent correlations with the development of hypertension. Hypertension often precedes the onset of heart failure by an average of 14.1 years.[4] Thus, the most significant HHD risk factors include genetic predisposition, overweight and obesity, environmental risk factors (diet, physical inactivity, alcohol consumption, gut microbiota), sodium intake, potassium levels, and physical fitness.

Unlike primary hypertension, secondary hypertension stems from a definable condition or agent and often requires tailored intervention. Renal parenchymal disease, renovascular disease, primary aldosteronism, obstructive sleep apnea (OSA), drug- or alcohol-induced hypertension, pheochromocytoma, paraganglioma, Cushing syndrome, hyperthyroidism, hypothyroidism, aortic coarctation, primary hyperparathyroidism, congenital adrenal hyperplasia, acromegaly, and medications (eg, amphetamines, nonsteroidal anti-inflammatory drugs, caffeine, antidepressants, antipsychotics, oral contraceptives) all represent established secondary causes of elevated blood pressure. These conditions warrant investigation, especially in patients with resistant or early-onset disease, as many are reversible with appropriate management.[5]

Epidemiology

Based on Global Burden of Disease data, HHD's prevalence from 1990 to 2019 increased from 146 to 240 years lived with disability per 100,000 individuals. The death rate due to HHD also rose in both men, from 10.3 to 12.8 per 100,000, and women, from 14.2 to 17.1 per 100,000. In 2019, HHD was responsible for 1.16 million deaths and 21.5 million disability-adjusted life years, with an overall global prevalence of 18.6 million cases. Africa has the highest age-standardized disability-adjusted life years due to HHD.[6] (Source: Khalid et al, 2024)

Hypertension is one of the most prevalent conditions in the U.S., affecting approximately 75 million adults, or 1 in 3 adults in the country. However, despite the high prevalence, only 54% of patients diagnosed with hypertension have adequate blood pressure control.[7] On a global scale, the prevalence of hypertension stands at 26.4%, impacting 1.1 billion people, yet only 1 in 5 individuals have their blood pressure effectively managed. Prolonged hypertension is a known risk factor for the development of heart failure, with one study finding a median time of 14.1 years between the onset of hypertension and the eventual progression to heart failure. Meta-analyses have consistently demonstrated a log-linear relationship between elevated blood pressure and an increased risk of cardiovascular disease, with the risk escalating significantly with age.

The prevalence of hypertension increases with age. Among patients aged 45 to 54 years, 36.1% of men and 33.2% of women are affected. In adults aged 55 to 64, 57.6% of men and 55.5% of women have hypertension. In adults aged 65 to 74, the prevalence rises to 63.6% in men and 65.8% in women. Among individuals aged 75 or older, the rates increase to 73.4% for men and 81.2% for women. Hypertension is more common in women and carries a greater risk of heart failure for women than men. The risk for women is 3 times higher, while for men, it is 2 times higher. Additionally, women are more likely to experience uncontrolled blood pressure, and recent studies have suggested that some antihypertensive medications may be less effective in women.

Certain ethnic groups exhibit a higher predisposition to hypertension. The prevalence of hypertension among the African American population is among the highest in the world, with 45.0% of men and 46.3% of women affected. By comparison, 34.5% of Caucasian men and 32.3% of Caucasian women are hypertensive, while 28.9% of Hispanic men and 30.7% of Hispanic women have the condition.[8] In addition to having the highest rate of hypertension, African Americans are at an increased risk of developing heart failure. This cohort also experiences higher average blood pressure, which develops at an earlier age and is less amenable to treatment. These factors contribute to increased mortality rates and a higher overall burden of disease in this population.

Pathophysiology

The heart adapts to chronically elevated afterload. According to the Law of Laplace, wall tension is equal to the product of transmural pressure and chamber radius, divided by twice the wall thickness, represented by the following equation:

Wall tension (T) = [Transmural pressure (P) × Radius (R)] / (2 × wall thickness)

In hypertension, elevated systemic vascular resistance increases wall stress. The heart compensates for this elevated wall tension by either increasing wall thickness, reducing the radius of the ventricular cavity, or both. The left ventricle responds by thickening its wall (LVH), thereby reducing wall tension.[9]

Structural Changes and Myocardial Ischemia

Hypertensive changes manifest as either hypertrophy (increased left ventricular mass) or remodeling (normal mass but increased relative wall thickness). LVH involves both myocyte enlargement and interstitial fibrosis. These structural changes result in a mismatch between myocardial oxygen demand and supply, often leading to myocardial ischemia. This condition typically arises from coronary microvascular dysfunction, where ischemia occurs despite normal epicardial coronary arteries. Subendocardial ischemia may present as ST-T changes on the electrocardiogram (ECG) and may cause hypertensive angina or silent ischemia.

Diastolic Dysfunction

LVH reduces ventricular compliance and impairs diastolic filling, leading to elevated left ventricular end-diastolic pressure (LVEDP), elevated left atrial pressure, and, if left untreated, pulmonary hypertension. Chronic diastolic dysfunction promotes left atrial dilation, fibrosis, and remodeling, increasing the risk of atrial fibrillation, which further compromises cardiac output and elevates stroke risk. Coronary reserve diminishes due to hypertrophy and remodeling. Potential mechanisms include perivascular fibrosis, small artery narrowing, arterial wall stiffening, endothelial dysfunction, and microvascular rarefaction.

Abnormal intracellular calcium handling further impairs relaxation. This delayed relaxation prolongs isovolumetric relaxation time, which produces characteristic findings on Doppler echocardiography, such as increased atrial contraction force and evidence of progressive diastolic dysfunction.

Left Ventricle Systolic Dysfunction

Persistent hypertension leads to myocyte apoptosis and interstitial fibrosis, resulting in dilation of the left ventricle and a progressive decline in contractility. When left untreated, the ejection fraction gradually decreases, representing the end stage of HHD. Cardiac fibrosis plays a central role in the loss of contractile function. Additional contributing mechanisms include neurohormonal imbalance, altered immune responses, gut microbiota, and metabolic dysfunction.

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the development of HHD. In the early phase, angiotensin II supports cardiac function by compensating for the elevated afterload. However, chronic stimulation leads to pathological myocardial hypertrophy via sustained activation of the Gαq signaling pathway. This same pathway also promotes apoptosis. Angiotensin II further exacerbates myocardial injury by generating reactive oxygen species, amplifying oxidative stress within the heart.

Chronic hypertension also induces excessive catecholamine release. Overstimulation of β1-adrenergic receptors promotes apoptosis of myocardial cells. Eventually, desensitization of these receptors occurs, impairing intracellular signaling and diminishing cardiac performance.

Natriuretic peptides, specifically atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), exert antifibrotic and antihypertrophic effects under normal conditions. However, prolonged elevation due to sustained hypertension leads to desensitization of natriuretic peptide receptors, attenuating these cardioprotective effects and contributing to HHD progression.

The heart primarily relies on fatty acids (60% to 90%) for the production of adenosine triphosphate (ATP), the molecule responsible for cellular energy. Glucose contributes a smaller share, ranging from 10% to 40%. In the early stages of HHD, fatty acid oxidation declines due to mitochondrial dysfunction. As HHD progresses, glucose oxidation also becomes impaired. The resulting shift toward increased glycolysis, uncoupled from oxidative phosphorylation—a Warburg-like effect—leads to lactic acid accumulation, intracellular acidosis, and reduced contractile function.

Additional metabolic disturbances include persistent mitochondrial dysfunction, which limits ATP availability and increases reactive oxygen species. Furthermore, dysregulated glucose metabolism leads to the accumulation of advanced glycation end products, which promote pro-inflammatory and profibrotic pathways. The net effect is diminished metabolic efficiency and worsening myocardial performance.

Gut microbiota modulate blood pressure regulation and may mitigate HHD, with dietary factors influencing their composition. Altered immune responses and chronic inflammation further enhance myocardial fibrosis and disease progression.

History and Physical

The history and physical examination are essential in evaluating patients for HHD, as most individuals with hypertension remain asymptomatic until complications emerge. Depending on disease progression, patients may present with asymptomatic LVH, myocardial ischemia, or signs and symptoms of heart failure.

History

Early-stage HHD is often silent and discovered incidentally on ECG or echocardiogram. Some individuals may report mild dyspnea, palpitations, or angina-like symptoms. As HHD advances, patients may exhibit signs of heart failure, including exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, pulmonary congestion (eg, cough, wheezing), and systemic congestion (eg, lower extremity edema, abdominal distension, or weight gain). Arrhythmia-related symptoms, such as palpitations, presyncope, syncope, or even SCD, may also occur. Exertional chest pain may reflect angina or underlying CAD. A history of poorly controlled hypertension is frequently present. Clinicians should assess the severity and duration of hypertension, current medications, and adherence to therapy.

Patients should undergo assessment for the presence of other major modifiable cardiovascular risk factors, such as hyperlipidemia, diabetes, alcohol use, salt intake, smoking, drug usage, and comorbid conditions, such as chronic kidney disease (CKD) or pulmonary disease. Diabetes mellitus is highly prevalent in this population and is considered a cardiovascular risk equivalent. Hypertension contributes significantly to the development of CAD, heart failure, atrial fibrillation, cerebrovascular disease (CVD), PAD, aortic aneurysms, and CKD. A comprehensive history is essential to assess for these conditions.

Family history should be reviewed for premature cardiovascular death, SCD, metabolic disorders, valvular abnormalities, stroke, or heart failure. OSA, a condition marked by repeated episodes of upper airway obstruction during sleep, is associated with refractory hypertension and LVH. Symptoms of OSA, such as loud snoring, witnessed apneas, excessive daytime sleepiness, or morning headaches, should be actively investigated.

Physical Examination

Blood pressure should be measured at every clinical visit. Out-of-office monitoring, using either home blood pressure monitoring or 24-hour ambulatory blood pressure monitoring, is recommended both for diagnosis and for guiding treatment. Ambulatory blood pressure monitoring is particularly valuable when a discrepancy is observed between in-office and home readings, as it offers a more accurate representation of a patient’s true blood pressure burden.[10]

A visible apical impulse may suggest LVH. A sustained, heaving impulse typically reflects concentric hypertrophy, while a laterally displaced impulse may indicate left ventricular dilation in advanced HHD. Suprasternal pulsations may suggest aortic dilatation. Aortic stenosis or sclerosis may also be evident.

On auscultation, an S4 heart sound is a key early finding in HHD, signifying a stiff, hypertrophied ventricle and underlying diastolic dysfunction. This finding is highly specific to hypertensive changes. An S3 sound, in contrast, indicates eccentric hypertrophy and is associated with systolic heart failure. Soft systolic murmurs may be heard, particularly in the setting of mitral regurgitation due to annular dilation or increased flow. Pulmonary rales may be present in patients with heart failure.

Patients at risk for atherosclerotic cardiovascular disease should be examined for carotid bruits and diminished peripheral pulses. Blood pressure should be measured in both arms, especially in patients presenting with acute symptoms, to assess for aortic dissection.

The funduscopic exam is an underutilized but informative tool for assessing the severity and chronicity of hypertension. This evaluation can reveal signs of hypertensive retinopathy, including arteriovenous nicking, cotton wool spots, retinal hemorrhages, exudates, and papilledema. Hypertensive retinopathy is graded using the Keith-Wagener-Barker classification as follows:

• Grade 1: Mild narrowing or tortuosity of retinal arterioles, reflecting early or asymptomatic hypertension.
• Grade 2: Definite arteriovenous nicking or arteriolar sclerosis, suggestive of more sustained or elevated blood pressure, often still asymptomatic.
• Grade 3: Retinal hemorrhages, exudates, and cotton wool spots. Blood pressure is typically significantly elevated and symptomatic, though end-organ damage may still be reversible.
• Grade 4: All findings of Grade 3 with the addition of papilledema and retinal edema. These patients often present with headaches, visual changes, dyspnea, or malaise and are at high risk for cardiovascular events. Urgent evaluation and close monitoring are warranted.

Patients with Grade 3 or 4 retinopathy should be referred immediately to ophthalmology for further evaluation and management of retinal involvement.

Evaluation

The workup for HHD should focus on identifying end-organ damage, assessing additional cardiovascular risk factors, and evaluating for secondary causes of hypertension when suggested by clinical features or physical examination. All patients should undergo both laboratory testing and cardiovascular imaging to assess the extent of target organ involvement.

Men with obesity are at elevated risk for OSA and should be screened using the STOP-BANG (snoring, tiredness, observed apnea during sleep, high blood pressure, body mass index > 35 kg/m², age > 50 years, neck circumference > 40 cm, male gender) questionnaire. If indicated, these men should be referred for formal sleep apnea evaluation. In addition, all patients should have their 10-year cardiovascular risk estimated using an established risk calculator to guide the intensity of therapeutic interventions.

Assessment of cardiovascular target organ damage includes a surface ECG, transthoracic echocardiography, carotid intima-media thickness measurement, pulse-wave velocity testing, and coronary artery calcium scoring. These tests help detect early structural or vascular changes that may guide treatment intensity and risk stratification.

Laboratory testing is recommended for all patients with HHD to assess underlying causes and associated cardiovascular risk factors. Recommended studies include fasting blood glucose, complete blood count, lipid profile, serum creatinine with estimated glomerular filtration rate, serum sodium, potassium, calcium, blood urea nitrogen, and thyroid-stimulating hormone, particularly in the context of atrial fibrillation. A urine analysis, including urine albumin-to-creatinine ratio, should be considered for assessing renal involvement. Additional laboratory studies may be required to evaluate for secondary causes of hypertension if clinically suspected.

Although ECG features of LVH correlate only weakly with echocardiographic or magnetic resonance imaging findings, several studies have linked these changes to adverse cardiovascular outcomes. In the context of HHD, characteristic ECG findings include LVH, left atrial enlargement (LAE), conduction abnormalities, ischemic changes, and arrhythmias.

LVH may be identified using several criteria. The Sokolow-Lyon criteria include an S wave in V1 plus an R wave in V5 or V6 measuring at least 35 mm or an R wave in aVL measuring at least 11 mm. The Cornell voltage criteria define LVH as an R wave in aVL plus an S wave in V3 greater than 28 mm in men or 20 mm in women. Other voltage criteria include an R wave in lead I greater than 14 mm, in aVL greater than 11 mm, or in V5 or V6 greater than 26 mm.

The Romhilt-Estes point score system offers a structured approach, where a score of 5 or more indicates LVH, and 4 points suggests LVH is possible.[11] The scoring includes the following:

• 3 points: S wave in V1 + R wave in V5 or V6 at least 35 mm, ST-T changes in leads with LVH, or LAE
• 2 points: Left axis deviation (LAD)
• 1 point: QRS duration over 90 msec or delayed intrinsicoid deflection in V5 or V6

Additional features of HHD on ECG include LAE, seen as a broad, notched P wave at least 120 msec in lead II (P-mitrale) or a biphasic P wave in V1 with a deep negative terminal portion. Conduction abnormalities may include LAD, left bundle branch block, or 1st-degree atrioventricular block. Evidence of myocardial ischemia or strain may manifest as ST depression and T wave inversion in lateral leads (I, aVL, V5-V6) or flattened or biphasic T waves. Arrhythmias such as premature ventricular contractions and atrial fibrillation may also be observed.

An echocardiogram is not recommended for the routine evaluation of all patients with hypertension. However, this modality should be considered in patients who either exhibit symptoms of heart failure, are younger than 18, or have chronic, uncontrolled hypertension.[12]

An echocardiogram is used to document the presence and degree of LVH. A left ventricular mass index over 115 g/m² in men) or 95 g/m² in women and a relative wall thickness exceeding 0.42 suggests concentric LVH.

The echocardiogram also documents the presence and stage of diastolic dysfunction. Earlier in the disease, impaired relaxation is indicated by a ratio of early diastolic filling velocity to atrial filling velocity (E/A ratio) of 0.8, signifying grade I diastolic dysfunction. As the disease progresses, this ratio increases to greater than 2, which suggests more severe diastolic dysfunction or grade III impairment. The ratio of early diastolic filling velocity to tissue Doppler early diastolic velocity (E/e' ratio) may also be elevated to greater than 1, indicating increased filling pressures in the heart. Additionally, a deceleration time exceeding 200 milliseconds may be observed in the early stages of diastolic dysfunction.

An echocardiogram may show a left atrial volume index exceeding 34 mL/m², suggesting atrial remodeling due to chronic pressure overload and diastolic dysfunction in HHD. Hypertension can cause aortic root enlargement, predisposing to aortic regurgitation. Late-stage HHD shows left ventricular systolic dysfunction. Global longitudinal strain is impaired in HHD before the decline in the ejection fraction. Other findings in HHD include mitral annular calcification or aortic sclerosis due to chronic pressure overload.

Treatment / Management

The American College of Cardiology and the American Heart Association updated the previous guidelines set by the 8th Joint National Committee (JNC8) in 2017, introducing a revised classification system for blood pressure. The updated guidelines categorize blood pressure into 4 distinct ranges: normal, elevated, stage 1 hypertension, and stage 2 hypertension.

Normal blood pressure is defined as an SBP below 120 mm Hg and a DBP under 80 mm Hg. Elevated blood pressure is identified when the SBP ranges from 120 to 129 mm Hg while the DBP remains below 80 mm Hg. Stage 1 hypertension is characterized by an SBP between 130 and 139 mm Hg or a DBP between 80 and 89 mm Hg. Stage 2 hypertension is diagnosed when the SBP exceeds 140 mm Hg or the DBP is 90 mm Hg or higher.

The treatment of hypertension involves the use of several classes of antihypertensive medications, often in combination, to achieve optimal control. Thiazide diuretics, particularly chlorthalidone, are considered first-line therapy for hypertension. These diuretics are especially important for patients with resistant hypertensive disease, as they help manage fluid retention and reduce blood pressure effectively.

Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are also first-line treatments for hypertension, particularly in patients with comorbid conditions, such as diabetes mellitus or CKD. These medications help relax blood vessels and reduce the workload on the heart. Calcium channel blockers are another first-line treatment option for hypertension. These agents work by relaxing and widening blood vessels, reducing systemic vascular resistance and cardiac afterload.

β-blockers are no longer recommended as first-line treatment for isolated hypertension. However, these drugs remain first-line therapy for conditions such as heart failure, ischemic heart disease, and atrial fibrillation. Vasodilators like hydralazine are not considered first-line therapy for hypertension. These agents should only be added when a 3rd or 4th medication is necessary to manage difficult-to-control hypertension or when contraindications exist for the standard first-line medications.

In many cases, adequate control of blood pressure requires the use of 2 or more antihypertensives, especially in patients with stage 2 hypertension. For these patients, treatment should begin with 2 antihypertensive medications, followed by reassessment within 30 days to evaluate the response to therapy. Combining 2 medications from similar classes, such as the combination of an ACEi and an ARB, should be avoided, as recommended by the JNC8 guidelines.

Management of heart failure should follow goal-directed medical therapy tailored to the individual patient's needs and condition. Recommendations from current guidelines provide several key considerations for managing patients with HHD. Blood pressure–lowering medications are advised for secondary prevention of cardiovascular disease in patients with an average SBP of 130 mm Hg or higher and a DBP of 80 mm Hg or higher.

Adults at risk for heart failure should aim for a blood pressure target of less than 130/80 mm Hg. For patients with hypertension and heart failure with reduced ejection fraction (HFrEF), guideline-directed medical therapy is recommended, with a target blood pressure of less than 130/80 mm Hg. Nondihydropyridine calcium channel blockers should be avoided in this population due to their negative inotropic effects.

In patients with heart failure with preserved ejection fraction (HFpEF), the presence of hypertension and volume overload warrants the use of diuretics for blood pressure control. For those who remain hypertensive after achieving euvolemia, ACEis or ARBs, along with β-blockers, should be initiated to achieve a target SBP of less than 130 mm Hg.

Differential Diagnosis

Several conditions can mimic the clinical, ECG, or echocardiographic features of HHD, making accurate diagnosis essential. Differentiating these entities, which include the conditions below, is critical to avoid misclassification and ensure appropriate management.

• Severe aortic stenosis
• Hypertrophic cardiomyopathy
• Infiltrative cardiomyopathies (eg, amyloidosis, sarcoidosis)
• Ischemic heart disease, including HFpEF or systolic dysfunction
• Athlete’s heart
• Sleep apnea
• Restrictive cardiomyopathies characterized by LAE and diastolic dysfunction

Recognizing these mimickers requires careful integration of clinical context, imaging findings, and, when necessary, advanced diagnostic testing. Early identification of alternative diagnoses can significantly influence prognosis and treatment strategy.

Prognosis

HHD is a chronic, progressive condition associated with a significantly increased risk of cardiovascular mortality. Hypertension remains one of the predominant risk factors for the development of multiple cardiovascular disorders, including CAD, CHF, atrial fibrillation, CVD, PAD, aortic aneurysm, and CKD. The overall prognosis of HHD depends on several factors, including the specific cardiac manifestations, the presence of concomitant cardiovascular disease or risk factors, and comorbid conditions. Cardiovascular risk calculators are available to aid in risk stratification, and patients should be categorized as high or low risk for cardiovascular events accordingly.

Specific manifestations of HHD, such as heart failure or atrial fibrillation, are associated with a markedly increased risk of cardiovascular mortality. Notably, patients with HFpEF exhibit a risk profile and morbidity burden comparable to those with HFrEF, with 6-month mortality rates reported to be as high as 16%.[13]

HHD accounts for approximately 1/4 of all cases of heart failure. Data from the Framingham Heart Study indicate that hypertension doubles the risk of developing heart failure in men and triples it in women after adjusting for age and other risk factors. The 2015 Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive blood pressure control, targeting an SBP of 120 mm Hg, was associated with a lower incidence of heart failure (1.3%) compared to a target of 140 mm Hg (2.1%). Effective management of hypertension has been linked to a 64% reduction in the incidence of heart failure.[14]

Key prognostic determinants in HHD include the degree of blood pressure control, presence and type of heart failure, ejection fraction, extent of LVH, presence of arrhythmias, and coexisting CAD or coronary artery ischemia, hypertensive nephropathy, or CVD. Compared to normotensive individuals, patients with HHD face a 2- to 4-fold increase in mortality. Among individuals who develop heart failure secondary to HHD, survival rates range from approximately 35% to 50%. Between 1990 and 2019, HHD accounted for 1,115,199 reported deaths in the U.S., with age-specific analyses revealing higher mortality in men and younger adult populations.[15] (Source: Abughazaleh et al., 2024)

Complications

HHD contributes to a wide spectrum of cardiovascular and systemic complications due to sustained pressure overload and vascular damage. These complications can be life-threatening and often coexist, compounding morbidity and increasing the risk of adverse outcomes. The most important of these conditions are listed below: 

• HFpEF
• HFrEF
• Atrial fibrillation with increased stroke risk
• Ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation/sudden cardiac arrest, particularly in advanced HHD [16]
• Bradyarrhythmias and conduction abnormalities, including atrioventricular blocks and left bundle branch blocks, which are due to myocardial fibrosis and electrical remodeling
• Myocardial infarction, which is a risk, even in nonatherosclerotic patients, due to coronary microvascular dysfunction
• Cerebrovascular complications, including hypertensive encephalopathy, intracerebral hemorrhage, and accelerated stroke (embolic or thrombotic)
• Concurrent complications of hypertension, such as retinopathy, hypertensive nephropathy, PAD, and aortic dissection or aneurysm [17]

Early recognition and management of these complications are essential to reduce morbidity and mortality in patients with HHD. A comprehensive, interprofessional approach is critical for optimizing outcomes in this high-risk population.