Aortic Disease
Aortic disease encompasses a spectrum of conditions affecting the aorta, the largest artery in the human body, which originates from the left ventricle of the heart and distributes oxygenated blood to the circulatory system. These diseases can compromise the aorta’s structural integrity or its ability to function effectively, leading to potentially severe health complications. Conditions include aortic aneurysms (abnormal bulges or dilations in the aortic wall), aortic dissections (tears in the inner layer of the aorta, allowing blood to flow between the layers), and aortic stenosis (narrowing of the aorta).
The biological basis of aortic disease is multifaceted, involving a complex interplay of genetic predispositions and environmental factors. Research, particularly through genome-wide association studies (GWAS), has been instrumental in identifying genetic variants associated with various cardiovascular conditions, some of which may contribute to aortic pathologies. For example, studies have investigated genetic variants linked to cardiac structure and function, providing insights into the broader mechanisms affecting the cardiovascular system, including the aorta . For instance, initial GWAS phases may have limited genomic coverage and power, with some studies calculating only approximately 50% power to detect certain effect sizes, reflecting the difficulties in recruiting large sample sizes for conditions that may be relatively rare or difficult to phenotype precisely[1]. This limitation means that genuine associations of moderate effect size might be masked, or studies may lack the power to identify associations with rare or poorly imputed genetic variants[2].
Furthermore, measurement errors in phenotypic assessment can bias estimates towards the null hypothesis, potentially obscuring true genetic associations. For example, M-mode echocardiography of the aortic root, while a common method, may be less accurate and could lead to an underestimation of aortic diameter compared to 2-dimensional imaging [2]. In addition, the comprehensiveness of genome-wide coverage can be incomplete, with genotyping arrays not always covering all common variations and often poorly covering rare variants or structural variants, thereby reducing the power to detect their potential impact on disease[3]. The necessity for replication studies is critical to confirm initial associations and mitigate spurious findings that can arise from genotyping errors or small systematic differences within large datasets [3].
Generalizability and Unaccounted Influences
Section titled “Generalizability and Unaccounted Influences”The generalizability of findings in aortic disease research can be constrained by the characteristics of the study populations and the challenges in accounting for complex biological and environmental interactions. Cohort bias can arise, as seen in studies where case subjects with a strong family history of premature disease are selected, which, while enhancing statistical power, might inflate estimated population attributable risks beyond those of sporadic cases[4]. This highlights the need for further analysis in a wider range of subjects to ensure findings are applicable across diverse populations. The potential for population structure to confound inferences in case-control association studies also warrants careful consideration, as systematic differences between ancestral groups can lead to spurious associations if not adequately addressed [3].
Moreover, complex diseases like aortic disease are influenced by a myriad of factors beyond genetics, including environmental exposures and gene-environment interactions, which are often not fully captured or accounted for in genetic studies[5]. While genetic studies provide valuable insights, a significant portion of disease heritability may remain unexplained due to these unmeasured or unknown environmental confounders, the aggregated effect of many common variants with very small individual effects, or the impact of rare variants not well-covered by current technologies[4]. Consequently, thorough investigation of candidate genes and fine mapping of associated regions are ongoing efforts to bridge these remaining knowledge gaps and provide a more complete understanding of aortic disease etiology[4].
Variants
Section titled “Variants”Genetic variations play a crucial role in an individual’s predisposition to various health conditions, including aortic disease, by influencing gene function and cellular pathways. The following variants are associated with genes involved in fundamental cellular processes, such as cell adhesion, signaling, metabolism, and quality control, all of which are critical for maintaining the structural integrity and healthy function of the aorta.
Genes influencing cellular structure, signaling, and adhesion are vital for the integrity and dynamic remodeling of the arterial wall. For example, rs574493019 is located in ARHGAP24(Rho GTPase Activating Protein 24), a gene that inactivates Rho GTPases, key regulators of the actin cytoskeleton, cell migration, and cell adhesion. Variations in ARHGAP24 could alter these fundamental cellular processes, potentially leading to dysregulated vascular remodeling and affecting endothelial integrity, which are central to the development of subclinical atherosclerosis[6]. YIPF7 (YIP1 family member 7), associated with rs534538229 , is involved in vesicle trafficking and Golgi apparatus function, essential for protein secretion and membrane organization. Proper cellular trafficking is crucial for the synthesis and maintenance of the extracellular matrix in blood vessels, and its disruption could contribute to structural weaknesses in the aorta. Similarly, rs574027 in NTM (Neurotrimin), a cell adhesion molecule, might affect cell-cell interactions and communication within the arterial wall, influencing processes like vascular remodeling and the overall health of the aorta [3].
Retinoid signaling and cellular metabolism also contribute significantly to vascular development and health. The variant rs564301985 is found in CRABP2(Cellular Retinoic Acid Binding Protein 2), which binds retinoic acid, a powerful signaling molecule derived from Vitamin A that regulates cell growth, differentiation, and tissue development. Retinoic acid signaling is critical for the proper formation and maintenance of vascular structures, and variations in CRABP2 could impact retinoid availability or signaling, potentially affecting the integrity of the aortic wall. Likewise,RDH13 (Retinol Dehydrogenase 13), associated with rs78152556 , is an enzyme involved in retinol metabolism, converting retinol to retinal. Genetic changes in RDH13 could lead to imbalances in retinoid levels, potentially contributing to abnormal vascular development or an increased risk for conditions affecting aortic root size and cardiac function[2]. Furthermore, rs564301985 is also associated with NES(Nestin), an intermediate filament protein expressed in progenitor cells and some vascular cells, particularly during vascular repair or disease states. Nestin’s role in cell plasticity and migration suggests that variants affecting its function could influence the regenerative capacity or pathological remodeling of the aorta, processes that are central to outcomes like major cardiovascular disease and heart failure[7].
Broader cellular processes, including gene expression regulation, mitochondrial function, and lipid metabolism, also impact aortic health. The variant rs184806872 in CTIF(CBP80/20-dependent translation initiation factor) is involved in mRNA translation and the nonsense-mediated mRNA decay (NMD) pathway, a critical cellular quality control mechanism. Dysregulation of NMD could lead to altered protein expression, impacting cellular homeostasis and contributing to cardiovascular pathologies.KCTD8(Potassium Channel Tetramerization Domain Containing 8), associated withrs534538229 , belongs to a family of proteins that often modulate ion channels or participate in ubiquitin ligase complexes, pathways crucial for cellular signaling in cardiac and vascular tissues. Furthermore, MAIP1 (Mitochondrial Associated Inner Membrane Protein 1), with variant rs59580441 , plays a role in mitochondrial function and lipid droplet formation. Mitochondrial dysfunction is increasingly implicated in cardiovascular diseases like atherosclerosis and vascular aging. Lastly, whileCRAT37 (rs192499149 ) is not a standard gene symbol, genes like CRAT (Carnitine O-palmitoyltransferase) are central to lipid metabolism, facilitating fatty acid transport for energy production. Dysregulation of lipid metabolism is a major contributor to atherosclerosis and other vascular diseases, affecting plaque accumulation and inflammation in arterial walls, including the aorta[6]. Thus, a variant in such a locus could potentially impact lipid homeostasis and contribute to the development of subclinical atherosclerosis and aortic calcification[6].
Key Variants
Section titled “Key Variants”Defining Aortic Disease and its Key Manifestations
Section titled “Defining Aortic Disease and its Key Manifestations”Aortic disease encompasses a spectrum of conditions affecting the aorta, the body’s largest artery, ranging from structural abnormalities to degenerative processes. While a comprehensive conceptual framework for all aortic diseases is broad, specific manifestations are precisely defined and clinically significant for diagnostic and prognostic purposes. Two such critical manifestations discussed in research include abdominal aortic calcification (AAC) and aortic root dimension. Abdominal aortic calcification specifically refers to the presence of calcium deposits within the walls of the abdominal aorta, serving as an indicator of arterial stiffening and the broader process of atherosclerosis[6]. Aortic root dimension, conversely, quantifies the diameter of the aortic root, which is the initial segment of the aorta as it emerges from the heart, and is a key measurable trait reflecting cardiac structure and function [8]. Understanding the precise definitions and measurement of these manifestations is fundamental for accurate diagnosis, risk stratification, and patient management.
Measurement Approaches and Diagnostic Criteria
Section titled “Measurement Approaches and Diagnostic Criteria”The accurate diagnosis and assessment of aortic disease manifestations rely on standardized measurement approaches and specific diagnostic criteria. Abdominal aortic calcification (AAC) is operationally defined and objectively measured using multidetector computed tomography (MDCT). Within this framework, a calcified lesion in the aorta is precisely identified as an area comprising at least three connected pixels exhibiting a CT attenuation value greater than 130 Hounsfield Units, based on 3D connectivity criteria[6]. A quantitative score for AAC is subsequently calculated by multiplying the area of such a calcified lesion by a weighted CT attenuation score, which is dependent on the maximal CT attenuation (Hounsfield Units) observed within that lesion. This scoring methodology is an adaptation of the original Agatston Score, modified for application with MDCT scan protocols [6]. For aortic root dimension, measurements are typically obtained through echocardiography, with categorization often established in relation to height- and sex-specific reference limits to ensure a standardized classification [2]. These quantitative phenotypes may also be adjusted for various covariates, including systolic blood pressure and the use of anti-hypertensive treatment, during genetic analyses to refine associations[6].
Classification and Clinical Significance
Section titled “Classification and Clinical Significance”Manifestations of aortic disease are classified based on their presence, severity, and overall impact on cardiovascular health, providing critical insights into an individual’s risk profile. Abdominal aortic calcification (AAC) is recognized as a significant measure of subclinical atherosclerosis across major arterial territories[6]. The quantitative scoring system for AAC provides a clear severity gradation, where higher scores indicate more extensive and advanced calcification within the abdominal aorta. This calcification is not merely an anatomical finding but serves as an important predictor of vascular morbidity and mortality, underscoring its profound prognostic significance[9]. Similarly, the classification of aortic root dimension, often categorized using height- and sex-specific reference limits, is crucial for identifying individuals at an elevated risk of adverse outcomes. An enlarged aortic root dimension is a useful predictor for serious cardiovascular events, including heart failure, stroke, cardiovascular mortality, all-cause mortality, and acute myocardial infarction, particularly in individuals aged 65 years or older[8]. These established classifications and diagnostic criteria are invaluable tools for risk assessment and for guiding appropriate clinical management strategies.
Diagnostic Assessment of Aortic Dimensions
Section titled “Diagnostic Assessment of Aortic Dimensions”The accurate and objective assessment of aortic dimensions constitutes a critical aspect in the evaluation of aortic disease. M-mode echocardiography is a method utilized for measuring the aortic root diameter, an objective indicator of aortic morphology. However, research indicates that M-mode measurements may be less accurate when compared to 2-dimensional imaging, potentially leading to an underestimation of the true aortic diameter[2]. This inherent variability in measurement precision between different diagnostic tools is of significant diagnostic value, as it highlights the importance of selecting robust assessment techniques for reliable characterization of aortic pathology and understanding potential phenotypic diversity.
Causes of Aortic Disease
Section titled “Causes of Aortic Disease”Aortic disease arises from a complex interplay of genetic predispositions, various health conditions, and the natural process of aging. Understanding these contributing factors is essential for comprehending the mechanisms underlying its development.
Genetic Predisposition and Inheritance
Section titled “Genetic Predisposition and Inheritance”Aortic disease has a significant genetic component, with various inherited variants contributing to an individual’s susceptibility. Genome-Wide Association Studies (GWAS) have been instrumental in identifying numerous genetic loci associated with cardiovascular traits, including those influencing cardiac structure and function.[10] These studies often employ additive-allele models of inheritance and family-based association testing to pinpoint these genetic influences. [7] Such genetic predispositions can manifest as Mendelian forms in some cases or, more commonly, as a polygenic risk resulting from the cumulative effect of multiple genetic variants.
Research indicates that specific genetic variants can impact the dimensions of the aortic root, a critical measure in aortic disease, although M-mode echocardiography measurements may sometimes underestimate aortic diameter.[10]Furthermore, a strong family history of premature cardiovascular conditions, such as coronary artery disease, highlights the inherited nature of these susceptibilities.[4]While specific loci for coronary artery disease have been identified, such as on chromosome 3q22.3,[11]the broader genetic landscape contributing to aortic disease likely involves a complex interplay of many variants, each exerting a modest effect.[10]
Comorbidities and Age-Related Influences
Section titled “Comorbidities and Age-Related Influences”Beyond direct genetic factors, the development and progression of aortic disease are significantly influenced by various comorbidities. Conditions such as diabetes, elevated systolic blood pressure, and pre-existing valve disease are recognized as important contributing factors to cardiovascular outcomes.[7]These health issues can exert chronic stress on the cardiovascular system, potentially altering the structural integrity and function of the aorta over time. For instance, hypertension can lead to increased shear stress on the aortic wall, while diabetes can contribute to systemic vascular damage, both indirectly impacting aortic health.
Age is another critical, non-modifiable factor that plays a substantial role in the risk of aortic disease. As individuals age, the aorta naturally undergoes degenerative changes, including stiffening and dilation, which increase susceptibility to various pathologies. Studies investigating genetic correlates often account for age-related phenotypes, underscoring its pervasive influence on cardiovascular health.[12]The cumulative effects of biological aging, combined with the presence of comorbidities, create a complex risk profile that significantly predisposes individuals to aortic diseases.
Biological Background
Section titled “Biological Background”The aorta, as the body’s largest artery, plays a pivotal role in the circulatory system, delivering oxygenated blood from the heart to the rest of the body. Aortic disease encompasses a range of conditions, including atherosclerosis, aneurysms, and dissections, all of which compromise the structural integrity and functional capacity of this vital vessel. Understanding the complex biological processes that maintain aortic health and the mechanisms that lead to its dysfunction is crucial for comprehending these pathologies.
Vascular Architecture and Homeostasis
Section titled “Vascular Architecture and Homeostasis”The aorta’s remarkable strength and elasticity are attributed to its unique multi-layered architecture, comprising the intima, media, and adventitia. The innermost intima is lined by endothelial cells, which form a crucial barrier regulating vascular tone, permeability, and inflammatory responses, thus maintaining a homeostatic environment within the vessel. The medial layer, primarily composed of vascular smooth muscle cells (VSMCs) embedded within an extracellular matrix rich in elastin and collagen, provides the mechanical resilience necessary to withstand pulsatile blood flow and regulate blood pressure. The intricate balance of cell-matrix interactions and cellular functions within these layers is continuously maintained through sophisticated regulatory networks.
Molecular and Cellular Mechanisms of Aortic Dysfunction
Section titled “Molecular and Cellular Mechanisms of Aortic Dysfunction”Aortic disease often begins with endothelial dysfunction, a state where the protective functions of endothelial cells are compromised, leading to increased permeability, inflammation, and oxidative stress. This dysfunction facilitates the infiltration of low-density lipoproteins and immune cells into the arterial wall, triggering a chronic inflammatory response. Monocytes recruited to the site differentiate into macrophages, which engulf oxidized lipids to become foam cells, a characteristic feature of early atherosclerotic lesions[13]. Concurrently, VSMCs in the medial layer can undergo phenotypic switching, migrating into the intima and contributing to plaque formation, further disrupting the structural integrity of the aorta. Processes like leukocyte recruitment are critical in the progression of atherosclerosis, highlighting the dynamic cellular interactions involved in disease development[14].
Genetic Influences on Aortic Health
Section titled “Genetic Influences on Aortic Health”Genetic predisposition significantly contributes to an individual’s susceptibility to aortic diseases, with numerous genetic mechanisms influencing vascular integrity and function. Genome-wide association studies (GWAS) have identified specific genetic variants associated with cardiovascular disease outcomes and subclinical atherosclerosis in major arterial territories[4]. These genetic loci often involve genes crucial for lipid metabolism, inflammatory pathways, extracellular matrix remodeling, and vascular smooth muscle cell function. Variations within these regulatory elements can alter gene expression patterns or protein activity, thereby influencing the aorta’s ability to maintain homeostasis, repair damage, or respond to pathological stimuli, ultimately increasing disease risk.
Systemic Interplay and Organ-Level Consequences
Section titled “Systemic Interplay and Organ-Level Consequences”Aortic disease is not an isolated pathology but is intricately connected to systemic physiological processes and has widespread consequences throughout the cardiovascular system. Systemic risk factors such as hypertension, dyslipidemia, and chronic inflammation exert continuous stress on the arterial tree, including the aorta, accelerating the progression of pathophysiological changes[13]. The stiffening or dilation of the aorta, common manifestations of aortic disease, significantly impacts cardiac function by increasing the workload on the heart (afterload), which can lead to left ventricular hypertrophy and eventually heart failure[10]. This highlights the complex interplay between the aorta and other organs, where systemic conditions drive local aortic pathology, which in turn exacerbates systemic cardiovascular dysfunction.
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Genetic Contribution to Arterial Vulnerability
Section titled “Genetic Contribution to Arterial Vulnerability”Genetic association studies have unveiled numerous loci associated with an increased susceptibility to various cardiovascular conditions, including subclinical atherosclerosis in major arterial territories and coronary artery disease[6]
Regulatory Influences on Cardiovascular Risk
Section titled “Regulatory Influences on Cardiovascular Risk”The identified genetic susceptibility loci suggest that regulatory mechanisms play a significant role in determining an individual’s risk for arterial diseases. These genetic associations imply perturbations in gene regulation or protein modification that can alter cellular functions critical for vascular integrity. Such regulatory dysfunctions, stemming from genetic predispositions, are thought to contribute to the pathogenic landscape of conditions affecting cardiac structure and function [2]
Systems-Level Interactions in Arterial Disease Susceptibility
Section titled “Systems-Level Interactions in Arterial Disease Susceptibility”The complex interplay of multiple genetic factors highlights the systems-level integration involved in arterial disease susceptibility. Rather than single gene effects, the cumulative impact of various genetic variants likely contributes to network interactions and hierarchical regulation within the cardiovascular system. This broader genetic architecture suggests an emergent property of disease risk, where multiple subtle genetic influences converge to affect overall arterial health, as seen in genome-wide associations for cardiovascular disease outcomes[7]
Clinical Relevance
Section titled “Clinical Relevance”Aortic disease encompasses a range of conditions affecting the body’s largest artery, with significant implications for patient morbidity and mortality. Understanding its clinical relevance involves considering diagnostic approaches, prognostic indicators, and its complex relationship with broader cardiovascular health. Genetic insights are increasingly contributing to a more nuanced understanding of individual risk and potential for personalized management strategies.
Diagnosis and Risk Assessment
Section titled “Diagnosis and Risk Assessment”The initial diagnosis and ongoing assessment of aortic disease frequently rely on structural evaluation, such as measuring aortic root dimension. While M-mode echocardiography is a common method, studies suggest that its measurements of aortic diameter may be less accurate and can underestimate the true dimension when compared to two-dimensional imaging[10]. Precise measurement is critical for establishing a baseline for disease progression and informing monitoring strategies. Beyond direct structural assessment, risk stratification for aortic disease can be enhanced by evaluating subclinical atherosclerosis across various arterial territories. Genome-wide association studies have identified specific genetic loci associated with measures like abdominal aortic calcification, which serves as a marker of widespread arterial disease[6]. Such genetic insights, integrated with traditional clinical risk factors, hold promise for identifying high-risk individuals and developing personalized prevention strategies.
Prognostic Value and Long-Term Implications
Section titled “Prognostic Value and Long-Term Implications”The structural characteristics of the aorta, particularly aortic root dimension and the presence of calcification, offer substantial prognostic value regarding future cardiovascular events. In individuals aged 65 years and older, the dimension of the aortic root has been demonstrated to predict the incidence of heart failure, stroke, cardiovascular mortality, all-cause mortality, and acute myocardial infarction[8]. This highlights its utility as a robust indicator of long-term cardiovascular health. Similarly, the presence of abdominal aortic calcific deposits is recognized as an important predictor of vascular morbidity and mortality, underscoring the systemic impact of arterial disease[9]. The identification of genetic findings, either individually or in combination, can also contribute to a clinically useful prediction of disease progression and overall outcomes[3], aiding in patient management and risk mitigation.
Comorbidities and Systemic Cardiovascular Impact
Section titled “Comorbidities and Systemic Cardiovascular Impact”Aortic disease is often closely linked with, and contributes to, a broad spectrum of cardiovascular comorbidities, reflecting its systemic nature throughout the body. Conditions such as heart failure, stroke, and myocardial infarction are directly associated with aortic pathology, as evidenced by the strong prognostic correlations with aortic root dimension[8]. These overlapping phenotypes necessitate a comprehensive assessment of overall cardiovascular health in patients presenting with aortic disease. The development and progression of aortic disease are frequently intertwined with broader subclinical atherosclerosis affecting other major arterial territories, including coronary artery calcification and carotid artery intima-media thickness[6]. Furthermore, established cardiovascular risk factors such as diabetes, hypertension, and hyperlipidemia play a significant role in the pathogenesis of both aortic disease and its associated conditions[4], emphasizing the need for holistic management strategies that address the entire burden of cardiovascular risk.
Frequently Asked Questions About Aortic Disease
Section titled “Frequently Asked Questions About Aortic Disease”These questions address the most important and specific aspects of aortic disease based on current genetic research.
1. My dad had an aortic aneurysm; will I get one too?
Section titled “1. My dad had an aortic aneurysm; will I get one too?”While having a close relative with an aortic aneurysm means you might have a higher genetic predisposition, it doesn’t guarantee you’ll develop one. Aortic disease involves a complex interplay of genetic factors and environmental influences. Understanding this family history can help you and your doctor consider personalized screening protocols.
2. Is a genetic test useful to know my aortic risk?
Section titled “2. Is a genetic test useful to know my aortic risk?”Yes, understanding your genetic predispositions can be very useful for risk stratification. While specific genetic loci for aortic diseases are still an active area of research, identifying genetic variants associated with cardiovascular health can help inform personalized screening and preventative strategies for individuals with higher susceptibility.
3. Why did my healthy friend get aortic disease, but I’m fine?
Section titled “3. Why did my healthy friend get aortic disease, but I’m fine?”Aortic disease has a multifaceted biological basis, meaning it’s not just about lifestyle. Some individuals may have genetic predispositions that increase their risk even if they maintain generally healthy habits, while others might be more resilient due to their genetic makeup. Environmental factors also play a significant role.
4. Can my healthy habits really overcome my family’s aortic history?
Section titled “4. Can my healthy habits really overcome my family’s aortic history?”While you can’t change your genetic predispositions, healthy habits are very important. Aortic disease is influenced by both genetics and environmental factors. Adopting preventative strategies and managing environmental risks can significantly impact your overall cardiovascular health, even with a family history.
5. Does my ethnic background affect my aortic disease risk?
Section titled “5. Does my ethnic background affect my aortic disease risk?”Yes, it can. Genetic studies need to consider population structure, as systematic differences between ancestral groups can influence risk estimations. This means that genetic risk factors and their prevalence might vary across different ethnic backgrounds, highlighting the importance of diverse research.
6. Could I have an aortic problem without knowing it?
Section titled “6. Could I have an aortic problem without knowing it?”Yes, it’s possible. Aortic diseases can sometimes progress without noticeable symptoms until they become severe. That’s why early and accurate diagnosis is crucial. Genetic insights can help identify individuals with a higher susceptibility, potentially enabling earlier, personalized screening.
7. Why do some people never get aortic issues, no matter what?
Section titled “7. Why do some people never get aortic issues, no matter what?”This often comes down to a combination of favorable genetic predispositions and beneficial environmental factors. Some individuals may have protective genetic variants or simply encounter fewer environmental triggers that contribute to aortic disease, leading to a lower overall risk.
8. Are heart problems and aortic problems linked genetically?
Section titled “8. Are heart problems and aortic problems linked genetically?”Yes, there’s evidence suggesting potential shared genetic pathways. Research has identified genetic variants linked to general cardiac structure and function, which can provide insights into the broader mechanisms affecting the cardiovascular system, including the aorta itself.
9. If I’m diagnosed, will my kids definitely inherit this risk?
Section titled “9. If I’m diagnosed, will my kids definitely inherit this risk?”Not “definitely,” but there’s a possibility of increased susceptibility. Aortic disease involves a complex interplay of multiple genetic factors, not usually a single gene, so your children would inherit a predisposition rather than a guaranteed condition. Their own environmental factors will also play a role.
10. Do my diet or exercise habits influence my aortic health?
Section titled “10. Do my diet or exercise habits influence my aortic health?”Absolutely. While genetics play a significant role, complex diseases like aortic disease are also heavily influenced by environmental exposures and gene-environment interactions. Maintaining a healthy diet and regular exercise are crucial components of managing overall cardiovascular health and can impact your aortic health.
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
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[3] Wellcome Trust Case Control Consortium. “Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.” Nature, vol. 447, no. 7145, 2007, pp. 661-678.
[4] Samani, N. J. “Genomewide association analysis of coronary artery disease.”N Engl J Med, vol. 357, no. 5, 2 Aug. 2007, pp. 443-453.
[5] Lopez, A. D. et al. “Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data.”Lancet, vol. 367, no. 9524, 2006, pp. 1747-57.
[6] O’Donnell, C. J. et al. “Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI’s Framingham Heart Study.”BMC Med Genet, 2007.
[7] Larson, M. G. et al. “Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes.”BMC Med Genet, 2007.
[8] Gardin, Judith M., et al. “Usefulness of Aortic Root Dimension in Persons > or = 65 Years of Age in Predicting Heart Failure, Stroke, Cardiovascular Mortality, All-Cause Mortality and Acute Myocardial Infarction (from the Cardiovascular Health Study).”The American Journal of Cardiology, vol. 97, no. 2, 2006, pp. 270–275.
[9] Wilson, Peter W. F., et al. “Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality.”Circulation, vol. 103, no. 11, 2001, pp. 1529-1534.
[10] Vasan, R. S. et al. “Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.” JAMA, 2009.
[11] Erdmann, J. et al. “New susceptibility locus for coronary artery disease on chromosome 3q22.3.”Nat Genet, 2009.
[12] Lunetta, Kathryn L., et al. “Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study.” BMC Medical Genetics, 2007. (PMID: 17903295).
[13] Libby, Peter. “Pathophysiology of coronary artery disease.”Circulation, vol. 111, no. 25, 28 June 2005, pp. 3481-3488.
[14] Galkina, Elena, and Klaus Ley. “Leukocyte recruitment in atherosclerosis.”Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 11, Nov. 2007, pp. 2292-2301.