Left Ventricle Sphericity Index

The left ventricle sphericity index is a quantitative measure used to assess the shape of the heart’s primary pumping chamber, the left ventricle. In a healthy individual, the left ventricle typically maintains an elongated, elliptical, or “bullet-shaped” geometry, which is crucial for efficient blood ejection. This index quantifies the deviation from this optimal elliptical shape towards a more spherical configuration.

Biological Basis

The normal elliptical shape of the left ventricle is biomechanically optimized for efficient contraction and relaxation, allowing the heart to pump blood effectively throughout the body. This geometry facilitates coordinated muscle fiber shortening, maximizing stroke volume with minimal energy expenditure. When the left ventricle remodels and becomes more spherical, this efficiency is compromised. A spherical ventricle may lead to increased wall stress, reduced contractility, and impaired filling, all of which can contribute to a decline in cardiac function. The dimensions of the left ventricle, including its diastolic and systolic diameters, as well as its mass and wall thickness, are important echocardiographic traits that exhibit heritability, with estimates ranging from 36% to 40% for left ventricular mass and internal dimensions.^[1]

Clinical Relevance

Changes in left ventricular sphericity are a significant indicator of cardiac remodeling, a process often observed in various cardiovascular diseases. Conditions such as chronic hypertension, myocardial infarction, and heart failure can lead to maladaptive remodeling, causing the left ventricle to dilate and assume a more spherical shape. This increased sphericity is not merely an anatomical change but a prognostic marker associated with worse clinical outcomes, including increased risk of hospitalization and mortality. Monitoring the left ventricle sphericity index can aid clinicians in assessing disease progression, stratifying patient risk, and guiding therapeutic interventions to prevent or reverse adverse cardiac remodeling. Echocardiography is a standard non-invasive method for evaluating left ventricular structure and function, including its dimensions.^[2]

Social Importance

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, posing a substantial public health burden. Understanding and precisely quantifying parameters like the left ventricle sphericity index contributes significantly to early diagnosis, accurate prognosis, and personalized treatment strategies. By identifying individuals at higher risk for adverse cardiac events based on ventricular geometry, healthcare providers can implement preventative measures or intensified therapies, potentially improving patient quality of life and extending survival. Advances in genetic research, including genome-wide association studies, are exploring the heritable components of echocardiographic dimensions, which may indirectly contribute to a deeper understanding of the genetic predispositions influencing ventricular shape and remodeling^[1]. ^[2]

Limitations

Methodological and Statistical Constraints

The research faced several limitations in its study design and statistical power, which could influence the interpretation and reliability of the findings for left ventricle sphericity index. The sample sizes, while contributing to a genome-wide association study, offered limited power to detect genetic effects that explain only a modest proportion of phenotypic variation, especially when considering the rigorous threshold required for genome-wide significance after multiple testing . Genetic variations can influence the fundamental cellular processes that dictate cardiac structure and function, thereby impacting this index. Studies on echocardiographic traits, such as left ventricular diastolic dimension, systolic dimension, and mass, highlight the heritable nature of these cardiac parameters, with estimates ranging from 36% to 52% .

Variations within genes like CEP85L and ABRA can contribute to the intricate architecture of the left ventricle. CEP85L (Centrosomal Protein 85 Like) encodes a protein vital for centrosome function, which orchestrates cell division and microtubule organization, processes fundamental to cell shape and tissue integrity. ^[3]A single nucleotide polymorphism (SNP) such asrs11756438 in or near CEP85Lcould alter its expression or the protein’s function, potentially affecting the growth, division, or structural arrangement of cardiac myocytes. Such cellular-level changes might lead to subtle yet significant remodeling of the ventricular wall, influencing the overall left ventricular geometry and its sphericity index. Similarly,ABRA(Actin Binding Rho Activating Protein) plays a key role in regulating the actin cytoskeleton, essential for cell shape, motility, and mechanical force generation in various cell types, including cardiac muscle cells.^[4] The variant rs1461990 in ABRA could modulate actin dynamics, thereby impacting myocardial contractility and cellular adhesion, which are critical for maintaining the heart’s structural integrity and its characteristic elliptical shape. Alterations in these pathways can contribute to ventricular remodeling, moving the left ventricle towards a more spherical geometry.

The immune system also plays a role in cardiac health, with genes like HLA-DRB5 being relevant. HLA-DRB5 (Major Histocompatibility Complex, Class II, DR Beta 5) is a component of the human leukocyte antigen (HLA) system, which is crucial for presenting antigens to T-cells and initiating immune responses. ^[5] While primarily involved in immunity, variations like rs199682224 in HLA-DRB5could influence an individual’s susceptibility to inflammatory or autoimmune conditions that can secondarily affect the heart. Chronic inflammation or immune-mediated damage to the myocardium, such as in myocarditis, can lead to fibrosis, myocyte loss, and compensatory hypertrophy, all of which contribute to adverse ventricular remodeling and changes in left ventricular dimensions, including its sphericity . Therefore, genetic predispositions affecting immune regulation can indirectly impact cardiac geometry and function.

Classification, Definition, and Terminology of Left Ventricular Morphology and Function

Defining Left Ventricular Morphology and Key Dimensions

The assessment of left ventricular (LV) morphology is crucial for understanding cardiac health, with various echocardiographic traits providing insights into its structure and function. Key dimensions include Left Ventricular Mass (LVM), Left Ventricular Diastolic Dimension (LVDD), Left Ventricular Systolic Dimension (LVSD), and Left Ventricular Wall Thickness (LVWT).^[1] These measurements, alongside Left Ventricular Fractional Shortening (LVFS) and Left Atrial Diameter (LAD), are fundamental echocardiographic parameters analyzed in studies to characterize the heart’s pumping chamber. ^[1] These linear dimensions and mass calculations provide an operational framework for describing the overall “left ventricular structure” and “geometry”. ^[6]

Echocardiographic Assessment and Standardization of Left Ventricular Structure

Measurement of left ventricular dimensions relies on standardized echocardiographic techniques, primarily M-mode and two-dimensional (2D) echocardiography. These methods adhere to specific recommendations from bodies like the American Society of Echocardiography to ensure consistency and reliability. ^[7] LV linear dimensions are typically measured using a computerized review station with digitizing tablets, allowing for precise quantification. ^[2] The reproducibility of these echocardiographic measures has been assessed in substudies to ensure their accuracy in clinical and research settings. ^[2]

Classification of Left Ventricular Geometry and Clinical Significance

Variations in left ventricular geometry are clinically classified based on these dimensions, with “left ventricular hypertrophy” (LVH) being a significant prognostic indicator.^[8]LV mass, often indexed to body surface area or height^2.7, is a critical measure used in classifying LVH and evaluating cardiovascular risk.^[2]Abnormalities in left ventricular structure and geometry are associated with increased incidence of hypertension and are recognized as independent risk factors for cardiovascular disease.^[9] Furthermore, specific left ventricular geometry patterns have been shown to influence survival in patients, even those with normal left ventricular ejection fraction. ^[10]

Causes

Genetic Predisposition to Ventricular Geometry

Genetic factors are fundamental determinants of the structural characteristics of the left ventricle, which in turn influence its sphericity. Heritability estimates for various echocardiographic traits, including left ventricular mass, internal dimensions, and wall thickness, range from 36% to 40%, indicating a substantial inherited component influencing the overall size and shape of the ventricle.^[1]Specific genetic variants, such as single nucleotide polymorphisms (SNPs) in genes likeSLIT2 (rs1379659 ) associated with left ventricular diastolic dimension, and KCNB2 (rs10504543 ) linked to left ventricular systolic dimension, directly influence these dimensions. ^[1] Furthermore, SNPs in KCNB1 and HSPA8have been associated with left ventricular mass, while variation inNCAM1 contributes to left ventricular wall thickness, particularly in hypertensive families. ^[2] These identified genetic variations underscore a polygenic architecture influencing myocardial development and remodeling processes, ultimately contributing to the diverse range of left ventricular geometries observed in the population.

Environmental and Lifestyle Modulators of Ventricular Shape

Beyond genetic influences, environmental and lifestyle factors are critical determinants of left ventricular geometry and, consequently, its sphericity. Conditions such as hypertension are strongly associated with alterations in left ventricular structure, including increased wall thickness and mass, which can lead to changes in ventricular shape.^[2]While not explicitly detailed for sphericity, dietary factors, such as salt intake, have been implicated in influencing left ventricular mass, suggesting a role for nutrition in cardiac remodeling.^[1]Physical activity, as indicated by studies on exercise responses, also represents an environmental factor that can impact cardiac dimensions and function, further shaping the ventricle’s overall form.

Interplay of Genes, Environment, and Developmental Timing

The development of left ventricular geometry, including its sphericity, is often a complex outcome of interactions between an individual’s genetic makeup and their environment. Genetic variants can exert their influence in a context-specific manner, meaning their effects on left ventricular traits can be modulated by external factors. ^[1] For example, the associations of genes like ACE and AGTR2with left ventricular mass have been reported to vary based on dietary salt intake, illustrating a direct gene-environment interaction.^[1] The concept of age-dependent gene effects on cardiac traits suggests that the timing of genetic expression and environmental exposures throughout life may contribute to the progressive shaping of the ventricle. ^[1]

Comorbidities and Age-Related Ventricular Remodeling

Various comorbidities and the natural aging process significantly contribute to changes in left ventricular structure and, by extension, its sphericity. Hypertension is a prominent comorbidity that drives maladaptive remodeling of the left ventricle, leading to hypertrophy and altered geometry.^[2]The chronic pressure overload associated with hypertension necessitates the heart to work harder, resulting in compensatory changes in myocardial mass and wall thickness that can shift the ventricle away from a spherical shape. Furthermore, age itself is an independent factor influencing cardiac structure, with age-related changes in gene effects contributing to the observed variability in ventricular dimensions over time.^[1]These cumulative effects of disease and aging remodel the heart, impacting its functional efficiency and overall shape.

Biological Background

Left Ventricular Geometry and Cardiac Function

The left ventricle (LV) is the primary pumping chamber of the heart, responsible for ejecting oxygenated blood into the systemic circulation. Its structural integrity and geometric configuration are critical determinants of overall cardiac function and circulatory efficiency. The left ventricle sphericity index, reflecting the shape of the LV, is intrinsically linked to its ability to contract and relax effectively. Alterations in this geometry, often characterized by changes in dimensions such as LV diastolic diameter (LVDD), LV systolic diameter (LVSD), and LV wall thickness (LVWT), can impact stroke volume and cardiac output. Maintaining an optimal spherical or elliptical shape ensures efficient blood ejection and filling, whereas deviations can signify adaptive or maladaptive remodeling of the heart muscle.^[1] These structural characteristics are influenced by complex interactions at the tissue and organ level, where myocardial cells, extracellular matrix, and vascular supply collectively contribute to the ventricle’s form and function.

The functional performance of the left ventricle is profoundly affected by its geometry. For instance, increased LV mass, a common response to sustained pathological stimuli like hypertension, leads to changes in both wall thickness and internal dimensions, thereby altering the overall ventricular shape.^[2]Such remodeling can initially serve as a compensatory mechanism to maintain cardiac output, but prolonged or excessive changes in sphericity can ultimately impair ventricular mechanics, leading to reduced efficiency and increased risk of cardiovascular events. The intricate interplay between the LV muscle and the systemic vasculature, including factors like arterial stiffness and endothelial function, further modulates the pressures and volumes the LV must handle, influencing its long-term geometric adaptations.^[1]

Genetic Determinants of Ventricular Morphology

Left ventricular geometry, including aspects that contribute to its sphericity, is a complex trait with a significant genetic component. Studies have consistently shown moderate to strong heritability for various echocardiographic dimensions, with estimates for LV mass ranging from 0.17 to 0.59, and similar heritabilities observed for internal dimensions. ^[2] This suggests that inherited genetic variations play a substantial role in determining an individual’s baseline cardiac structure and their predisposition to geometric changes. The normal distribution of LV mass within populations further supports the idea that multiple genes, rather than a single gene, influence this phenotype. ^[2]

Specific genes have been implicated in influencing left ventricular dimensions and mass. For example, a single nucleotide polymorphism (SNP) in theKCNB1gene has been associated with left ventricular mass.^[2] while another SNP near KCNB2 (rs10504543 ) was linked to LV systolic dimension. ^[1]These genes encode potassium channel proteins, which are critical key biomolecules involved in regulating cardiac electrical activity and myocyte contractility. Similarly, theNCAM1 gene, encoding a neural cell adhesion molecule, contributes to left ventricular wall thickness in hypertensive families, highlighting the role of cell-cell adhesion and structural integrity in myocardial architecture. ^[2] Other candidate genes, such as ACE, GNB3, IGF-1, and NPY, have also been explored for their associations with LV mass, although findings for these genes have sometimes been inconsistent across studies. ^[2]

Molecular and Cellular Pathways in Cardiac Remodeling

The precise geometry of the left ventricle is maintained through a delicate balance of molecular and cellular processes, which can be disrupted or altered in response to physiological or pathological stimuli. Signaling pathways involving secreted proteins, such as those encoded by the SLIT2gene, play a crucial role in regulating cellular functions like migration in vascular smooth muscle cells.^[1] Given the heart’s reliance on vascular function, such pathways can indirectly influence myocardial remodeling and, consequently, LV sphericity. Furthermore, genes like HSPA8, associated with LV mass, underscore the importance of heat shock protein expression in cellular stress responses and protein homeostasis within cardiomyocytes, which are vital for maintaining cardiac muscle integrity and function.^[1]

Cellular functions such as immune responses, potentially mediated by T-cells and influenced by genes like PDE4B, can also contribute to myocardial inflammation and fibrosis, processes that profoundly affect ventricular structure and stiffness.^[1]Metabolic processes are also critical; for instance, plasma homocysteine levels have been linked to left ventricular structure and function, indicating a role for metabolic regulation in cardiac health and remodeling.^[6]These interconnected molecular and cellular mechanisms, involving critical proteins, enzymes, receptors, and transcription factors, collectively dictate how cardiomyocytes proliferate, hypertrophy, or undergo apoptosis, and how the extracellular matrix is synthesized and degraded, all of which are fundamental to establishing and modifying the left ventricle’s shape.

Pathophysiological Implications of Altered LV Sphericity

Changes in the left ventricle sphericity index and associated geometric parameters are not merely structural alterations but are deeply intertwined with significant pathophysiological processes and carry substantial clinical implications. Increased LV mass, often a consequence of conditions like hypertension, obesity, or myocardial injury, represents a compensatory response initially aimed at preserving cardiac output.^[2]However, this remodeling can lead to a less favorable ventricular geometry, contributing to impaired diastolic and systolic function over time. Such changes are not benign; increased LV mass is recognized as a sensitive predictor of cardiovascular mortality and morbidity across various demographics.^[2]

The impact of altered LV structure extends beyond mere prognosis, influencing the incidence of other cardiovascular diseases, including hypertension itself.^[11]The ventricle’s shape and size can also differ among various populations, such as between Black and White hypertensive adults, suggesting complex interactions between genetic predispositions, environmental factors, and disease progression.^[12]These homeostatic disruptions, when sustained, can trigger a cascade of events leading to heart failure, arrhythmias, and other adverse outcomes. Understanding the biological basis of LV sphericity, therefore, provides crucial insights into the mechanisms of cardiac adaptation and maladaptation, offering potential targets for therapeutic interventions aimed at preserving optimal ventricular geometry and function.

Pathways and Mechanisms

Genetic Regulation of Ventricular Morphology

The shape and size of the left ventricle, including its sphericity, are significantly influenced by genetic factors. Studies have indicated a substantial heritable component to left ventricular mass and geometry, suggesting that inherited genetic variations play a role in determining cardiac structure.^[2] Specific genes have been associated with aspects of left ventricular structure, such as KCNB1, where genetic variations have been linked to left ventricular mass.^[2] Similarly, genetic variation in NCAM1 has been found to contribute to left ventricular wall thickness, a critical determinant of overall ventricular geometry. ^[2] These genetic influences underscore the complex molecular blueprint guiding cardiac development and adaptation.

Cellular Signaling and Remodeling Mechanisms

Cellular signaling pathways and subsequent remodeling processes are central to shaping the left ventricle. The gene SLIT2, which encodes a secreted protein with conserved protein-protein interaction domains, has a role in vascular function by contributing to migratory mechanisms in vascular smooth muscle cells.^[1]Such vascular effects can indirectly influence cardiac workload and lead to changes in ventricular geometry. Furthermore, the association of left ventricular mass withHSPA8, a gene involved in heat shock protein expression, highlights the importance of cellular stress responses in maintaining myocardial integrity and influencing ventricular remodeling. ^[1] These molecular pathways govern cellular proliferation, differentiation, and extracellular matrix deposition, collectively dictating the adaptive or maladaptive changes in ventricular shape.

Hemodynamic and Metabolic Modulators of Cardiac Shape

Hemodynamic forces and metabolic factors exert significant influence on the left ventricle’s structure and function, thereby affecting its sphericity. Local shear stress and brachial artery flow-mediated dilation are crucial indicators of vascular health, and their dynamic interplay affects systemic vascular resistance and cardiac afterload. ^[13]Chronic alterations in these hemodynamic parameters can induce adaptive or maladaptive remodeling of the left ventricle, altering its mass and overall geometry. Additionally, plasma homocysteine levels have been linked to left ventricular structure and function, suggesting a metabolic pathway influencing myocardial health and, consequently, ventricular shape.^[6] These integrated physiological and biochemical signals provide critical regulatory input that can drive changes in ventricular morphology.

Integrated Systems Responses and Clinical Implications

The left ventricle’s sphericity index reflects an integrated outcome of multiple interacting genetic, cellular, and hemodynamic pathways, with significant clinical implications. Changes in left ventricular structure, including mass and geometry, are not merely morphological variations but can impact the incidence of hypertension and hold prognostic value for cardiovascular disease and mortality.^[14]For instance, left ventricular hypertrophy, a common response to sustained hemodynamic stress, can alter ventricular geometry and is associated with increased cardiovascular risk.^[15] Understanding the intricate crosstalk between these pathways – from gene regulation to cellular responses and systemic hemodynamic forces – is crucial for deciphering the complex mechanisms underlying ventricular remodeling and identifying potential therapeutic targets for maintaining optimal cardiac form and function.

Clinical Relevance

The left ventricle sphericity index, a measure reflecting left ventricular (LV) geometry, provides critical insights into cardiac health, disease progression, and patient outcomes. Alterations in LV dimensions and shape, which the sphericity index quantifies, are frequently observed in various cardiovascular conditions and serve as important indicators for risk assessment and treatment strategies. Research, particularly large-scale genomic association studies and epidemiological cohorts, highlights the significant clinical utility of evaluating LV structural parameters.

Prognostic Indicator of Cardiovascular Events and Disease Progression

Changes in left ventricular geometry, as captured by dimensions and potentially the sphericity index, are powerful prognostic indicators for a range of adverse cardiovascular events. An increased left ventricular mass, a key component influencing sphericity, has been consistently associated with higher risks of stroke, congestive heart failure, and overall cardiovascular mortality.^{[15], [16], [17], [18]}These geometric changes signify maladaptive remodeling processes that can precede clinical symptoms, making the sphericity index a valuable tool for early risk stratification. Longitudinal studies demonstrate that even in individuals with a normal left ventricular ejection fraction, specific patterns of LV geometry are independently linked to long-term survival, underscoring its predictive power for disease progression and long-term implications.^[10]

Diagnostic Utility and Monitoring of Ventricular Remodeling

Echocardiographic assessment of left ventricular dimensions and structure, from which the sphericity index can be derived, plays a fundamental role in the diagnosis and monitoring of cardiac remodeling. Standardized M-mode and two-dimensional echocardiography techniques provide reliable measurements of left ventricular anatomy, including diastolic and systolic dimensions and wall thickness. ^{[7], [8], [19]}These measures are crucial for identifying left ventricular hypertrophy and other forms of geometric remodeling, which are commonly associated with conditions like hypertension. Monitoring changes in LV geometry over time can help clinicians evaluate the effectiveness of therapeutic interventions and adjust treatment strategies to mitigate adverse remodeling, thereby improving patient care and potentially preventing complications.

Genetic Predisposition and Personalized Risk Assessment

Genetic factors significantly influence left ventricular structure and dimensions, offering avenues for personalized risk assessment. Heritability estimates for echocardiographic traits, including left ventricular mass and dimensions, range from modest to strong, suggesting a substantial genetic contribution.^[1]Genome-wide association studies (GWAS) have identified specific single-nucleotide polymorphisms (SNPs) associated with variations in left ventricular mass and other echocardiographic dimensions. For instance, SNPs in genes such asKCNB1 and NCAM1have been linked to left ventricular mass and wall thickness, respectively, particularly in hypertensive families.^[2]Understanding these genetic predispositions can help identify individuals at higher risk for developing adverse LV remodeling, enabling more targeted prevention strategies and potentially guiding personalized medicine approaches based on an individual’s genetic profile.

Key Variants

RS ID	Gene	Related Traits
rs11756438	CEP85L	attention deficit hyperactivity disorder, bipolar disorder QT interval left ventricle sphericity index
rs1461990	ABRA - HMGB1P46	electrocardiography left ventricle sphericity index left ventricular structural measurement electrocardiography, magnetic resonance imaging of the heart heart shape trait
rs199682224	HLA-DRB5	left ventricle sphericity index grip strength measurement

Frequently Asked Questions About Left Ventricle Sphericity Index

These questions address the most important and specific aspects of left ventricle sphericity index based on current genetic research.

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1. My dad had heart failure. Will my heart shape be affected?

Yes, genetics play a significant role in your heart’s structure. The dimensions and mass of the left ventricle, which influence its shape, are estimated to be 36% to 40% heritable. This means you might inherit a predisposition that affects your heart’s shape and how it responds to various health conditions.

2. Does my heart’s shape affect my exercise performance?

Yes, your heart’s shape directly impacts its efficiency. A healthy, elliptical left ventricle is optimized for powerful and efficient blood pumping, crucial for maximizing stroke volume during exercise. If your heart becomes more spherical, this efficiency is compromised, which can reduce its ability to effectively pump blood and impact your physical performance.

3. Does eating salty food make my heart less efficient?

For some individuals, yes, especially depending on their genetic makeup. Research shows that certain genes can make people more sensitive to dietary salt, which can influence left ventricular mass and contribute to cardiac remodeling. This remodeling can lead to a less efficient, more spherical heart shape over time.

4. Why do some people get heart problems from high blood pressure but I don’t?

Your genetic background largely influences how your heart responds to conditions like high blood pressure. While chronic hypertension can cause the left ventricle to remodel into a less efficient, more spherical shape, individual genetic variations can make some people more vulnerable or more resilient to these effects.

5. As I get older, will my heart shape change for the worse?

Your heart’s shape can indeed change with age. Studies suggest that the genetic and environmental factors influencing heart structure, including its sphericity, can have age-dependent effects. While a healthy elliptical shape is ideal, aging can contribute to remodeling, potentially leading to a more spherical left ventricle in some individuals.

6. I’m from a different background. Does my ethnicity matter for heart shape?

Yes, your ethnic background can be relevant. Genetic influences on heart structure, including its shape, can vary between different populations. Research primarily conducted in individuals of European descent might not fully apply to other ethnicities, highlighting the importance of diverse studies to understand population-specific genetic architectures.

7. Can my doctor tell if my heart shape is a problem before I feel sick?

Yes, absolutely. Your doctor can use non-invasive tools like echocardiography to assess your heart’s structure and function, including its sphericity index. This allows them to detect early changes in your heart’s shape that might indicate remodeling or an increased risk for future heart problems, often before you notice any symptoms.

8. If my heart shape changes, can I reverse it with lifestyle changes?

It depends on the extent of the change, but reversal is often a key goal. Therapeutic interventions, which typically include significant lifestyle modifications, aim to prevent or reverse adverse cardiac remodeling and improve your heart’s shape and function. Early detection and intervention offer the best chance for positive outcomes.

9. Why did my friend get heart issues but I didn’t, even with similar lifestyles?

Even with similar lifestyles, genetic differences play a crucial role. Your heart’s dimensions and shape, including its sphericity, have a heritable component, meaning genetics account for a substantial part of the variation between individuals. This can explain why some people are more predisposed to cardiac remodeling and heart issues than others.

10. If my heart shape is ‘off,’ does that mean I’m definitely going to get sick?

Not necessarily, but it is a significant indicator of risk. A more spherical left ventricle is considered a prognostic marker, meaning it’s associated with a higher likelihood of adverse clinical outcomes. However, it’s a warning sign that helps doctors assess your risk and guide interventions to prevent or manage potential problems, rather than a definite prediction.

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This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] Vasan RS, Larson MG, Aragam J, Wang TJ, Mitchell GF, Kathiresan S, Newton-Cheh C, Vita JA, Keyes MJ, O’Donnell CJ, et al. Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study. BMC Med Genet. 2007;8 Suppl 1:S2.

[2] Arnett, Donna K., et al. “Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: the HyperGEN Study.”BMC Medical Genetics, vol. 8, no. 1, 2007, p. 80.

[3] Alberts, Bruce, et al. Molecular Biology of the Cell. Garland Science, 2014.

[4] Lodish, Harvey F., et al. Molecular Cell Biology. W. H. Freeman and Company, 2016.

[5] Janeway, Charles A., et al. Immunobiology: The Immune System in Health and Disease. Garland Science, 2001.

[6] Sundstrom J, Sullivan L, Selhub J, Benjamin EJ, D’Agostino RB, Jacques PF, Rosenberg IH, Levy D, Wilson PWF, Vasan RS. Relations of plasma homocysteine to left ventricular structure and function: the Framingham Heart Study. Eur Heart J. 2004;25:523-530.

[7] Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978;58:1072-1083.

[8] Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57:450-458.

[9] Kuller LH, Shemanski L, Psaty BM, Borhani NO, Gardin J, Haan MN, O’Leary DH, Savage PJ, Tell GS, Tracy R. Subclinical Disease as an Independent Risk Factor for Cardiovascular Disease. Circulation. 1995;92:720-726.

[10] Milani RV, Lavie CJ, Mehra MR, Ventura HO, Kurtz JD, Messerli FH. Left ventricular geometry and survival in patients with normal left ventricular ejection fraction. Am J Cardiol. 2006;97:959-963.

[11] Post WS, Larson MG, Levy D. Impact of left ventricular structure on the incidence of hypertension. The Framingham Heart Study. Circulation. 1994;90:179-185.

[12] Kizer JR, Arnett DK, Bella JN, Paranicas M, Rao DC, Province MA, Oberman A, Kitzman DW, Hopkins PN, Liu JE, Devereux RB. Differences in left ventricular structure between black and white hypertensive adults: the Hypertension Genetic Epidemiology Network study. Hypertension. 2004;43:1182-1188.

[13] Mitchell, Gary F., et al. “Local Shear Stress and Brachial Artery Flow-Mediated Dilation: The Framingham Heart Study.” Hypertension, vol. 44, no. 2, 2004, pp. 134-139.

[14] Havranek EP, Froshaug DB, Emserman CD, Hanratty R, Krantz MJ, Masoudi FA, Dickinson LM, Steiner JF. Left ventricular hypertrophy and cardiovascular mortality by race and ethnicity. Am J Med. 2008;121:870-875.

[15] Gardin, Joseph M., et al. “Relationship of cardiovascular risk factors to echocardiographic left ventricular mass in healthy young black and white adult men and women. The CARDIA study. Coronary Artery Risk Development in Young Adults.”Circulation, vol. 92, no. 3, 1995, pp. 380-387.

[16] Bikkina, Marjan, et al. “Left ventricular mass and risk of stroke in an elderly cohort. The Framingham Heart Study.”JAMA, vol. 272, no. 1, 1994, pp. 33-36.

[17] Gottdiener, John S., et al. “Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study.”Journal of the American College of Cardiology, vol. 35, no. 6, 2000, pp. 1628-1637.

[18] Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. NEW ENGL J MED. 1990;322:1561-1566.

[19] Palmieri V, Dahlof B, DeQuattro V, Sharpe N, Bella JN, de Simone G, Paranicas M, Fishman D, Devereux RB. Reliability of echocardiographic assessment of left ventricular structure and function: the PRESERVE study. Prospective Randomized Study Evaluating Regression of Ventricular Enlargement. J Am Coll Cardiol. 1999;34(5):1625-1632.