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HYPERTENSIVE HEART DISEASE: RISK FACTORS, COMPLICATIONS, AND
UNDERLYING MECHANISMS
Norboyeva Sevara Darvishaliyevna
Doctor at the Jizzakh branch of the Republican Specialized Scientific and Practical
Medical Center of Cardiology
Email: sevara104094@gmail.com
https://doi.org/10.5281/zenodo.13923635
Abstract
Hypertensive heart disease encompasses both functional and structural dysfunctions in
the left ventricle, left atrium, and coronary arteries, resulting from chronic uncontrolled
hypertension. Despite its prevalence, hypertensive heart disease is often underreported, and
the mechanisms contributing to its development and associated complications remain
inadequately defined. In this review, we provide a comprehensive overview of the current
understanding of hypertensive heart disease, focusing on the mechanisms involved in its
progression and complications, particularly left ventricular hypertrophy, atrial fibrillation,
heart failure, and coronary artery disease. Additionally, we highlight the roles of dietary salt,
immune responses, and genetic predisposition in the pathogenesis of hypertensive heart
disease.
Keywords
: hypertensive heart disease, heart failure, hypertension, coronary artery
disease, atrial fibrillation, immunity, salt
Introduction
Hypertensive heart disease refers to abnormalities in the heart's structure and function,
particularly affecting the left ventricle, left atrium, and intramural coronary arteries, as a result
of sustained elevated blood pressure. While the diagnostic criteria for hypertension differ
between the American and European guidelines, most recommendations align, and the
complications of chronic hypertension remain consistent. The criteria for defining hypertensive
heart disease are not universally standardized. However, the European classification proposed
by Gonzalez-Maqueda et al. from the Spanish Society of Cardiology uses the acronym "VIA" to
describe the alterations: changes in the left ventricle (V), myocardial ischemia (I), and atrial
fibrillation (A). Both European and American hypertension guidelines, as well as other
international societies, agree that hypertensive heart disease encompasses left ventricular
hypertrophy (LVH), left atrial dilation, systolic and diastolic dysfunction, along with clinical
symptoms such as arrhythmias, myocardial ischemia, and heart failure.
LVH is often one of the earliest indicators of hypertensive heart disease, initially acting as
a compensatory mechanism to reduce ventricular wall stress. However, LVH can progress to
more severe complications, including heart failure, arrhythmias, sudden cardiac arrest,
ischemic stroke, end-stage renal disease (ESRD), and death.
Globally, the age-standardized prevalence of hypertension is approximately 32% in
women and 34% in men. The prevalence of hypertension has been steadily rising, increasing
by more than 138% between 1990 and 2019, now affecting 20 million individuals. Among
people with hypertension, the prevalence of LVH is about 40%, with Black individuals tending
to have higher left ventricular mass and more severe diastolic dysfunction compared to their
White counterparts.
Risk Factors of Hypertensive Heart Disease
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Hypertension is the primary risk factor for the development of hypertensive heart
disease. Other contributing factors include older age, ethnicity, being overweight or obese,
physical inactivity, excessive dietary salt intake, smoking, alcohol consumption, and comorbid
conditions such as diabetes mellitus. These factors increase hemodynamic stress on the heart,
and over time, the left ventricle undergoes hypertrophy to manage the increased workload.
However, this compensatory hypertrophy eventually leads to heart failure.
Obesity is a particularly significant risk factor for hypertensive heart disease due to its
role in increasing renin secretion, mediated by leptin production from adipose tissue, which
elevates blood pressure and worsens existing hypertension. Additionally, obesity-induced
increases in sympathetic nervous system activity disrupt the div’s compensatory
mechanisms, such as the renin-angiotensin-aldosterone system (RAAS), further promoting
cardiac fibrosis and endothelial dysfunction. This combination of factors accelerates the
development and complications of hypertensive heart disease.
Beyond altering hemodynamics, obesity also contributes to hypertensive heart disease by
triggering inflammation, lipid accumulation in tissues, and dysregulation of several
intracellular signaling pathways. Obesity and hypertension often act synergistically through
overlapping neurohormonal pathways, further exacerbating hypertensive heart disease and its
associated complications, such as left ventricular hypertrophy (LVH) and heart failure. Despite
advancements in understanding these mechanisms, their complexity continues to challenge
researchers.
Mechanisms of Hypertensive Heart Disease and Its Complications
Hypertensive heart disease often leads to a range of complications, including diastolic
heart failure, systolic heart failure, or a combination of both. Individuals with hypertensive
heart disease are at an increased risk for atrial fibrillation (AFib), perioperative ischemia,
coronary artery disease, rehospitalization, kidney disease, heart valve diseases, aortic
dissection, intramural hematoma, and aortic ulcer.
Left Ventricular Hypertrophy (LVH) Mechanisms in Hypertensive Heart Disease
LVH is an early compensatory response to the hemodynamic overload caused by chronic
hypertension. It can predispose individuals with hypertension to cardiovascular events, even
in asymptomatic cases with coronary artery calcifications, or in individuals with hypertension
independent of treatment and other cardiovascular risk factors. Malignant LVH, characterized
by elevated biomarkers of cardiac injury (e.g., NT-proBNP, high-sensitivity cardiac troponin T),
is associated with severe outcomes such as heart failure with reduced ejection fraction, left
ventricular dysfunction, and cardiovascular death. Biomarker levels can help identify patients
at greater risk of adverse outcomes. It has also been observed that malignant LVH and related
complications are more pronounced in Black individuals compared to White individuals.
However, aggressive blood pressure control can prevent malignant LVH and reduce the risk of
adverse events.
The pathogenesis of LVH differs by sex, with factors such as aortic impedance, systemic
vascular resistance, and arterial compliance independently associated with wall thickness in
women, making LVH more common and pronounced in women. LVH can manifest in two
patterns: pathological or physiological. Pathological LVH involves increased extracellular
connective tissue without proportional capillary growth, leading to myocardial fibrosis and
diastolic dysfunction. In contrast, physiological LVH, such as that seen in response to physical
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exercise, involves balanced myocyte hypertrophy and microvessel expansion without negative
effects on left ventricular function.
Chronic hypertension leads to LVH through mechanisms such as gap junction
lateralization, increased oxidative stress, abnormal calcium homeostasis, and overexpression
of proteins like CD36 and matrix metalloproteinase-2 (MMP-2). These compensatory
mechanisms help manage increased cardiac stress but can progress to decompensated heart
failure if hypertension persists. LVH begins with myocyte hypertrophy, but prolonged elevated
blood pressure can lead to cardiomyocyte death and dilated cardiomyopathy, marking the
transition from compensated to decompensated heart failure. Structural changes in LVH may
present as concentric or eccentric hypertrophy, depending on factors such as pressure load
severity, genetic predisposition, and comorbidities.
The end result of LVH, if chronic hemodynamic stress continues, is progression to heart
failure, either with preserved or reduced left ventricular ejection fraction. Evidence supports
that LVH can regress with antihypertensive treatment, although variability in individual
responses, including sex differences, has been reported. In some cases, LVH persists despite
effective blood pressure control, reflecting the complexity of the condition.
Numerous proteins and mediators have been implicated in LVH development, including
angiotensin II, endothelin-1, norepinephrine, and several kinases. Angiotensin II, the primary
effector molecule of the renin-angiotensin-aldosterone system (RAAS), plays a critical role by
inducing vasoconstriction, promoting sodium and water retention, and exerting pro-
inflammatory and pro-fibrotic effects. These actions contribute to increased blood pressure and
the structural remodeling seen in hypertensive heart disease.
Therapies for Left Ventricular Hypertrophy
Patients with left ventricular hypertrophy (LVH) significantly benefit from intensive
blood pressure lowering (to less than 120 mmHg) to prevent complications. Several therapies
have demonstrated efficacy in reducing LVH and its associated risks in clinical trials. For
instance, the neprilysin inhibitor sacubitril, in combination with the angiotensin receptor
blocker (ARB) valsartan, has been shown to reduce left ventricular mass index more effectively
than the ARB olmesartan in patients with hypertension. Another trial reported that the
combination of the ARB telmisartan and simvastatin not only significantly lowered blood
pressure but also reversed LVH and improved left ventricular systolic function. Similarly, a
fixed-dose combination of perindopril, indapamide, and amlodipine (an ACE inhibitor, diuretic,
and calcium channel blocker, respectively) demonstrated the ability to reverse LVH and
improve outcomes in patients with essential hypertension over a 14-month period.
Additionally, a study by Lal et al. explored the use of allopurinol, a xanthine oxidase
inhibitor typically used to lower plasma uric acid in gout patients, and found that high doses of
allopurinol were more effective than febuxostat in reducing left ventricular mass and LVH.
However, caution is necessary when using allopurinol in normouricemic individuals with
controlled blood pressure, as it may increase oxidative stress.
Overall, the reversal of LVH appears to be more significant when both renin-angiotensin-
aldosterone system (RAAS) inhibitors and sympathetic nervous system (SNS) inhibitors are
used, rather than therapies that solely focus on blood pressure reduction. Other drugs and
natural compounds have also been reported in clinical trials to mitigate the progression of LVH,
including a nutraceutical combination of berberine, red yeast rice extract, and policosanol;
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azelnidipine; losartan; low-dose eplerenone; metformin in patients with coronary artery
disease without diabetes; and dietary interventions, such as low-fat and low-carbohydrate diets
and regular consumption of green tea.
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