Aortic Atherosclerosis
Aortic atherosclerosis is a chronic inflammatory disease characterized by the buildup of plaques within the aorta, the largest artery in the human body[1]. These plaques, composed of fats, cholesterol, calcium, and other substances, lead to the hardening and narrowing of the arterial walls, a process known as arteriosclerosis. This condition is a progressive disorder that can begin early in life and advance over decades.
The biological basis of aortic atherosclerosis involves a complex interplay of genetic predispositions and environmental factors. It is recognized as an inflammatory process[1], where damage to the arterial lining triggers an immune response and the accumulation of lipids. Over time, this leads to the formation of atherosclerotic plaques, which can calcify [2] and cause the aorta to stiffen [3]. Genetic factors are known to contribute significantly to the risk of developing atherosclerosis, including susceptibility to abdominal aortic aneurysms (AAA)[4]and variations associated with arterial stiffness[3]. Research also indicates that genetic variants can interact with environmental exposures, such as residential traffic pollution, to influence disease progression[5].
Clinically, aortic atherosclerosis is a major contributor to cardiovascular disease and its associated complications. It is a primary risk factor for conditions like abdominal aortic aneurysms, which are prevalent in older men and carry a high mortality risk if ruptured[4]. The presence of atherosclerosis in the aorta can also manifest as subclinical atherosclerosis, indicated by measures such as carotid intima-media thickness (CIMT) and plaque formation[6]. Furthermore, aortic calcification and valvular calcification are associated with aortic stenosis [2]and are independent predictors of cardiovascular events[7]. Advanced aortic atherosclerosis can lead to carotid artery stenosis, increasing the risk of stroke and other cardiovascular outcomes[8].
The social importance of aortic atherosclerosis stems from its significant impact on public health worldwide. As a leading cause of morbidity and mortality, it accounts for a substantial burden on healthcare systems, including numerous hospital admissions, surgical interventions, and deaths annually[4]. Understanding the genetic and environmental factors influencing aortic atherosclerosis is crucial for developing improved screening, prevention, and treatment strategies. Genomic research, including genome-wide association studies, aims to identify specific genetic variants that can predict disease risk and progression, offering potential targets for therapeutic interventions to reverse or attenuate arterial damage and prevent associated health complications[4].
Limitations
Section titled “Limitations”Genetic studies of aortic atherosclerosis, while advancing our understanding, are subject to several limitations that impact the interpretation and generalizability of their findings. These challenges stem from methodological constraints, the complexity of disease phenotypes, and the multifaceted etiology of atherosclerosis.
Methodological and Replication Challenges
Section titled “Methodological and Replication Challenges”Many genetic studies for aortic atherosclerosis encounter limitations related to their study design and statistical power. Phenotypic and study design heterogeneity can reduce the statistical power needed to detect modest genetic effects, especially for rare or poorly imputed single nucleotide polymorphisms (SNPs)[9]. Furthermore, measurement errors in phenotypic assessments, such as M-mode echocardiography for aortic root diameter, may introduce bias and potentially underestimate associations, skewing results towards the null hypothesis [9]. The reliance on common variant hypotheses in traditional genome-wide association studies (GWAS) might also limit the capture of the full genetic architecture of complex diseases [10].
A significant limitation across genetic research is the frequent lack of independent replication cohorts, which is crucial for confirming initial findings and strengthening confidence in identified associations [5]. While some studies achieve suggestive significance, broader replication in diverse populations is often needed to validate these associations fully [5]. The failure of even large-scale GWAS to consistently replicate positive associations for highly heritable cardiovascular diseases underscores this challenge[10]. Additionally, concerns about genomic inflation factors under polygenic inheritance models suggest that some reported effect sizes might be inflated, necessitating careful interpretation of findings [7].
Phenotypic Definition and Generalizability
Section titled “Phenotypic Definition and Generalizability”The precise definition and measurement of aortic atherosclerosis phenotypes present considerable challenges. For instance, using the number of diseased coronary vessels assesses clinically significant atherosclerosis but may overlook subclinical forms of the disease that could still be influenced by genetic factors[5]. Similarly, certain imaging techniques, like M-mode measurements of the aortic root, might be less accurate compared to 2-dimensional images, potentially leading to an underestimation of aortic diameter [9]. This variability and potential inaccuracy in phenotypic assessment can introduce noise and affect the ability to detect true genetic associations.
Another critical limitation concerns the generalizability of findings, particularly regarding ancestral diversity. Many studies have historically focused predominantly on individuals of European ancestry, which limits the applicability of their findings to other populations and may miss important population-specific genetic variants [10]. While some research attempts trans-ethnic interaction studies, comprehensive replication across distinct ethnic groups remains essential to ensure findings are universally relevant and not biased by specific population structures [5]. This lack of diverse representation can hinder the development of broadly effective diagnostic and therapeutic strategies.
Complex Etiology and Unexplained Variation
Section titled “Complex Etiology and Unexplained Variation”Aortic atherosclerosis is a complex disease influenced by a myriad of factors, and current research still faces challenges in fully elucidating its etiology. While genetic variants are increasingly identified, the interplay between genes and environmental exposures, such as residential traffic pollution, is known to significantly impact disease risk[5]. Studies that do not adequately account for these gene-environment interactions or other major cardiovascular risk factors might present an incomplete picture of the disease’s genetic architecture[11]. Understanding these intricate interactions is crucial, as they can confound genetic associations and contribute to the overall disease burden.
Despite significant advances in genetic research, a substantial proportion of the heritability for complex diseases like aortic atherosclerosis remains unexplained, a phenomenon often referred to as “missing heritability”[10]. This gap suggests that traditional GWAS based solely on common SNPs may not capture the full spectrum of genetic variation, including rare variants or structural variations, contributing to the disease[10]. Consequently, there remain considerable knowledge gaps regarding the precise role of many genetic variants in the inter-individual variability of quantitative measures of atherosclerosis, and the inconsistent findings from various candidate gene studies further highlight this ongoing challenge[11].
The NYAP2 (Neuronal Tyrosine-phosphorylated Adaptor Protein 2) gene encodes a protein involved in various cellular processes, including neuronal development and cytoskeletal regulation, which are fundamental for cell migration and adhesion. The variant rs529084429 , located near MIR5702, may influence the expression or function of NYAP2 or the microRNA MIR5702, potentially impacting pathways critical for vascular health. MicroRNAs like MIR5702are small RNA molecules that regulate gene expression by binding to messenger RNA, thereby affecting protein production. Dysregulation of such regulatory mechanisms can contribute to the complex pathology of aortic atherosclerosis, a condition characterized by plaque buildup and hardening of the arteries, as indicated by studies on related vascular issues like carotid intima-media thickness and plaque formation othelial cells, both of which play key roles in the development of atherosclerosis. This condition is characterized by the accumulation of plaque within the arterial walls, which can lead to hardening and narrowing of the vessel. While atherosclerosis can affect various arteries, its presence in the aorta is particularly significant due to the aorta’s critical role in systemic blood circulation. The term “subclinical atherosclerosis” is often used to describe the disease in its early stages, before the manifestation of overt symptoms[11].
A key manifestation and measurable aspect of aortic atherosclerosis is “aortic calcification,” particularly “abdominal aortic calcification (AAC)”[11]. These calcific deposits are not merely incidental findings; they serve as important predictors of future vascular morbidity and mortality[12]. A severe outcome of advanced aortic atherosclerosis can be an Abdominal Aortic Aneurysm (AAA), defined as an increase in the aortic diameter of 50% or more, or an increase in the infrarenal diameter of at least 30 mm, for which atherosclerosis is a primary risk factor[4].
Measurement Approaches and Diagnostic Criteria for Aortic Calcification
The diagnosis and assessment of aortic atherosclerosis, specifically its calcific burden, rely on precise operational definitions and measurement approaches. A calcified lesion within the aorta is identified as an area consisting of at least three connected pixels with a CT attenuation value exceeding 130 Hounsfield Units, determined using 3D connectivity criteria[11]. These calcium measurements are typically performed by trained technicians using specialized offline workstations to ensure accuracy and consistency [11].
The severity of abdominal aortic calcification (AAC) is quantified through a specific scoring algorithm. This involves multiplying the area of a calcified lesion by a weighted CT attenuation score, which is dependent on the maximal Hounsfield Units within that lesion[11]. This method is a modification of the widely recognized Agatston Score, adapted for use with Multidetector Computed Tomography (MDCT) scan protocols [11]. Such quantitative measures of AAC are crucial for assessing subclinical atherosclerosis across various arterial territories, alongside other indicators like coronary artery calcification (CAC) and carotid intima-media thickness (IMT)[11].
Terminology and Classification of Aortic Atherosclerosis
The nomenclature surrounding aortic atherosclerosis encompasses several key terms that describe its pathological features and clinical significance. “Aortic atherosclerosis” is the overarching term for the disease process in the aorta, while “abdominal aortic calcification (AAC)” specifically refers to the measurable calcium deposits that serve as a robust indicator of the disease’s presence and extent[11]. The term “calcified lesion” is used to describe the specific anatomical findings identified through imaging [11].
Aortic atherosclerosis is categorized under the broader classification of “subclinical atherosclerosis,” meaning the disease is present but has not yet caused symptoms[11]. While there isn’t a universally standardized staging system for aortic atherosclerosis described in the provided context, the quantitative scoring of AAC using the modified Agatston Score algorithm provides a dimensional approach to grading its severity[11]. It is important to differentiate aortic atherosclerosis from related but distinct conditions like Abdominal Aortic Aneurysm (AAA), which is a pathological dilatation of the aorta for which atherosclerosis is a major predisposing factor[4].
Causes
Section titled “Causes”Aortic atherosclerosis, a chronic inflammatory disease affecting the aorta, arises from a complex interplay of genetic predispositions, environmental exposures, and physiological changes over time. The condition involves the hardening and narrowing of the aorta due to plaque buildup, significantly contributing to cardiovascular morbidity.
Genetic Predisposition and Heritability
Section titled “Genetic Predisposition and Heritability”Genetic factors play a substantial role in an individual’s susceptibility to aortic atherosclerosis and related vascular conditions. For instance, the heritability of abdominal aortic aneurysms (AAA), a severe manifestation of aortic disease, is estimated to be as high as 70%, with a notable increase in incidence among first-degree relatives of affected individuals[4]. Genome-wide association studies (GWAS) have identified numerous common genetic variants linked to subclinical atherosclerosis, including those affecting carotid intima-media thickness (CIMT) and plaque formation[6].
Specific gene loci have been implicated in various aspects of aortic atherosclerosis. Variants within the DAB2IP gene, for example, confer susceptibility to abdominal aortic aneurysm[4], while common genetic variations in the 3’-BCL11B gene desert are associated with increased arterial stiffness, a key indicator of aortic health[3]. Further research has uncovered additional disease-specific risk loci for AAA[13] and highlighted the role of polygenic risk models, demonstrating that the cumulative effect of multiple genetic variants contributes to an individual’s overall risk profile [14].
Environmental Factors and Gene-Environment Interactions
Section titled “Environmental Factors and Gene-Environment Interactions”Environmental and lifestyle factors are critical drivers in the development and progression of aortic atherosclerosis. Smoking is a well-established and significant risk factor, strongly associated with the development of abdominal aortic aneurysms[4]. Beyond direct lifestyle choices, exposure to environmental pollutants also plays a role. Residential exposure to traffic, for instance, has been identified as an environmental factor influencing the progression of atherosclerosis[5].
Crucially, the interaction between an individual’s genetic makeup and environmental triggers can profoundly influence disease risk. Genetic variants, such as those found at the PIGR-FCAMR locus, have been shown to interact with environmental exposures, including residential traffic, to modulate the risk of coronary atherosclerosis[5]. This highlights how genetic predispositions can increase an individual’s vulnerability to the atherogenic effects of specific environmental factors, leading to varying disease outcomes depending on both inherited and external influences.
Age and Pathological Mechanisms
Section titled “Age and Pathological Mechanisms”Advanced age is a predominant non-modifiable risk factor for aortic atherosclerosis and related conditions. The prevalence of abdominal aortic aneurysms, for example, significantly increases with age, particularly in men over 65 years[4]. The underlying pathological process of atherosclerosis itself is widely recognized as an inflammatory disease, characterized by chronic inflammation within the arterial walls[1].
While specific comorbidities and medication effects are not extensively detailed, the presence of other vascular calcification, such as aortic-valve calcification, can be associated with the broader spectrum of aortic vascular disease[2]. The combination of an aging vasculature and persistent inflammatory processes contributes to the structural changes and plaque accumulation characteristic of aortic atherosclerosis.
Biological Background
Section titled “Biological Background”Aortic atherosclerosis is a complex vascular condition characterized by the buildup of plaques within the wall of the aorta, the largest artery in the body. This progressive disease involves intricate interactions between genetic predispositions, environmental factors, and a cascade of molecular and cellular events that disrupt normal arterial function. Understanding these biological underpinnings is crucial for comprehending the development and progression of this significant cardiovascular concern.
Pathophysiology: Inflammation and Cellular Dynamics in Arterial Walls
Section titled “Pathophysiology: Inflammation and Cellular Dynamics in Arterial Walls”Atherosclerosis is fundamentally an inflammatory disease, beginning with damage to the endothelial lining of the arterial wall[1]. This initial insult can trigger the recruitment of immune cells, such as monocytes, which differentiate into macrophages within the vessel wall. These macrophages engulf oxidized lipids, transforming into foam cells, a hallmark of early atherosclerotic lesions. Concurrently, vascular smooth muscle cells (VSMCs) undergo phenotypic changes, migrating from the medial layer to the intima, proliferating, and contributing to the extracellular matrix of the developing plaque[15]. These cellular activities, coupled with ongoing inflammation, contribute to the growth and instability of the atherosclerotic plaque.
The progression of atherosclerosis involves a delicate balance of molecular signaling pathways and metabolic processes. Dysregulation in lipid metabolism, oxidative stress, and inflammatory cytokine signaling perpetuates the disease. The accumulation of cholesterol and other lipids within the arterial wall is a central feature, further exacerbating the inflammatory response and encouraging plaque growth. These disruptions in homeostatic mechanisms lead to a chronic inflammatory state that remodels the arterial tissue, ultimately impairing its structural integrity and function.
Genetic Predisposition and Regulatory Mechanisms
Section titled “Genetic Predisposition and Regulatory Mechanisms”Genetic factors play a significant role in an individual’s susceptibility to atherosclerosis, influencing various aspects of its development, from lipid metabolism to vascular inflammation. Genome-wide association studies (GWAS) have identified numerous genetic variants associated with subclinical measures of atherosclerosis, such as carotid intima media thickness (cIMT) and plaque presence, across different arterial territories[16]. For instance, specific loci like PIGR-FCAMR have been linked to coronary atherosclerosis, with their effects sometimes modulated by interactions with environmental factors like residential traffic exposure[5]. These genetic associations highlight the importance of specific gene functions and regulatory networks in disease pathogenesis.
Beyond common variants, studies have also implicated genes like DAB2IP in susceptibility to abdominal aortic aneurysm, a condition often co-occurring with or influenced by atherosclerosis[4]. The genetic regulation of atherosclerosis-relevant phenotypes in human vascular smooth muscle cells further underscores the direct impact of genetic mechanisms on cellular functions critical to the disease[15]. Moreover, variations in gene desert regions, such as the 3’-BCL11B gene desert, have been associated with arterial stiffness, demonstrating how regulatory elements distant from protein-coding genes can influence vascular health[17]. These genetic insights provide targets for understanding the molecular pathways that drive atherosclerotic development.
Tissue-Level Changes: Arterial Stiffening and Calcification
Section titled “Tissue-Level Changes: Arterial Stiffening and Calcification”A hallmark of advanced atherosclerosis in the aorta and other large arteries is the progressive stiffening of the vessel wall. This loss of elasticity, measurable as carotid-femoral pulse wave velocity, is a significant indicator of cardiovascular risk[17]. Arterial stiffening is a consequence of chronic inflammation, degradation of elastic fibers, and increased collagen deposition within the arterial wall, processes intricately linked to the activity of VSMCs and the extracellular matrix. The stiffening affects the aorta’s ability to dampen pulsatile flow, increasing pressure on distal vessels and the heart.
Another critical pathophysiological process is arterial and valvular calcification, particularly noted in aortic-valve calcification and the development of aortic stenosis[2]. This involves the deposition of calcium phosphate crystals within the arterial wall or heart valves, a process that shares similarities with bone formation and is influenced by specific genetic variants, such as thers10455872 SNP [2]. These changes contribute to the overall structural degradation of the aorta, impairing its function and increasing the risk of adverse cardiovascular events.
Systemic Impact and Interconnected Vascular Conditions
Section titled “Systemic Impact and Interconnected Vascular Conditions”Aortic atherosclerosis is not an isolated condition; its effects extend systemically, impacting various arterial territories and contributing to a spectrum of cardiovascular diseases. While the aorta is a primary site, atherosclerosis can manifest in coronary arteries (leading to coronary atherosclerosis), carotid arteries (contributing to carotid intima media thickness and plaque), and arteries supplying the brain[5]. The presence of subclinical atherosclerosis in one major arterial territory often indicates systemic disease, with broad implications for overall cardiovascular health.
The chronic inflammatory and degenerative processes characteristic of atherosclerosis can also predispose individuals to other severe vascular conditions. For example, atherosclerosis contributes to the weakening of arterial walls, increasing the risk for aneurysms in the abdominal, thoracic, and intracranial arteries[14]. Furthermore, plaque rupture in the aorta or other major arteries can lead to thrombotic events, which are a major cause of stroke[18]. Therefore, aortic atherosclerosis is a central component of a broader landscape of vascular diseases, with shared genetic risk factors and interconnected pathophysiological mechanisms driving systemic consequences.
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Inflammatory Signaling and Cellular Responses
Section titled “Inflammatory Signaling and Cellular Responses”Aortic atherosclerosis is fundamentally an inflammatory disease, characterized by complex signaling pathways that drive its initiation and progression[1]. The activation of specific receptors on endothelial cells, smooth muscle cells, and immune cells triggers intricate intracellular signaling cascades, leading to the recruitment and activation of inflammatory cells like monocytes and T-lymphocytes. These cascades often culminate in the regulation of transcription factors, which in turn control the expression of genes involved in inflammation, cell adhesion, and extracellular matrix remodeling. Furthermore, feedback loops within these signaling networks can perpetuate the inflammatory state, contributing to chronic vascular damage and the sustained development of atherosclerotic plaques.
Genetic Regulation and Vascular Cell Phenotypes
Section titled “Genetic Regulation and Vascular Cell Phenotypes”Genetic variations play a significant role in modulating the susceptibility and progression of aortic atherosclerosis, profoundly influencing key regulatory mechanisms within vascular cells[15]. These genetic influences manifest through altered gene regulation, protein modification, and post-translational control, which collectively impact the function and phenotype of vascular smooth muscle cells (VSMCs) and other arterial wall components. Similarly, the detection of abdominal aortic calcification and coronary artery calcification provides valuable insights into the systemic atherosclerotic burden[11]. The ankle-brachial index (ABI) is another important diagnostic tool, reflecting peripheral artery disease, which often coexists with and signals broader aortic involvement[11]. These markers collectively contribute to a comprehensive risk assessment, guiding clinical decisions for preventive interventions.
Beyond diagnosis, these subclinical markers carry substantial prognostic value. Carotid atherosclerosis, encompassing CIMT and plaque, is a robust predictor of subsequent cardiovascular events, including myocardial infarction and stroke, with some studies suggesting a stronger predictive association in women compared to men[6]. Abdominal aortic calcific deposits have been specifically identified as significant predictors of vascular morbidity and mortality[11]. Furthermore, genetic variants linked to carotid-femoral pulse wave velocity indicate an increased risk for cardiovascular disease, highlighting aortic stiffening as a prognostic marker[3]. The presence of aortic-valve calcification also predicts incident aortic stenosis, underscoring its prognostic importance for valvular heart disease progression[2].
Associated Conditions and Complications
Section titled “Associated Conditions and Complications”Aortic atherosclerosis is rarely an isolated condition; its systemic nature means it frequently coexists with and contributes to a spectrum of other cardiovascular diseases and complications. Genetic studies have identified shared risk factors for subclinical atherosclerosis across various arterial territories, including coronary, carotid, and abdominal arteries, underscoring a generalized predisposition[11]. Consequently, findings in one vascular bed, such as carotid artery stenosis, often reflect a broader atherosclerotic burden throughout the arterial system [8].
The disease is a primary driver of major cardiovascular events, with ischemic stroke being a direct and severe complication, for which specific genetic loci have been associated with its subtypes[19]. Aneurysms, particularly abdominal aortic aneurysms (AAA), are also strongly linked to atherosclerosis, with distinct genetic risk loci identified for AAA[13]. Research indicates shared genetic risk factors across intracranial, abdominal, and thoracic aneurysms, suggesting common underlying pathways that are exacerbated by the atherosclerotic process [14]. Moreover, valvular calcification and aortic stenosis represent significant complications frequently observed in conjunction with aortic atherosclerosis[2].
Personalized Prevention and Treatment Strategies
Section titled “Personalized Prevention and Treatment Strategies”Identifying individuals at high risk for aortic atherosclerosis and its associated complications is paramount for developing personalized prevention and treatment strategies. Insights from genome-wide association studies offer opportunities for enhanced risk stratification, paving the way for more individualized preventive approaches[11]. For instance, genetic variants influencing carotid atherosclerosis or aortic stiffening can pinpoint individuals who may benefit from earlier or more intensive preventive measures[3]. Clinical trials, such as the JUPITER trial, have demonstrated the effectiveness of statins in preventing cardiovascular events, particularly in individuals with elevated risk markers, informing treatment selection[8].
Effective monitoring strategies for aortic atherosclerosis involve tracking both subclinical markers and genetic predispositions. For conditions like abdominal aortic aneurysms, population-based screening studies have shown a significant impact on mortality through early detection, supporting the implementation of targeted screening programs[20]. Furthermore, a deeper understanding of the genetic regulation of atherosclerosis-relevant phenotypes in human vascular smooth muscle cells, alongside gene-environment interactions, such as those involving genetic variants and residential exposure to traffic, offers critical insights into disease mechanisms[5]. These insights are vital for developing novel interventions aimed at attenuating or reversing arterial stiffening and preventing the associated morbidity and mortality[3].
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs529084429 | NYAP2 - MIR5702 | aortic atherosclerosis |
| rs564451966 | DAAM2 | aortic atherosclerosis |
Frequently Asked Questions About Aortic Atherosclerosis
Section titled “Frequently Asked Questions About Aortic Atherosclerosis”These questions address the most important and specific aspects of aortic atherosclerosis based on current genetic research.
1. My dad had this; will I definitely get it too?
Section titled “1. My dad had this; will I definitely get it too?”Not necessarily, but your risk is higher. Genetic factors significantly contribute to the risk of developing aortic atherosclerosis, so a strong family history means you may have inherited some predispositions. However, it’s not a certainty because environmental factors and lifestyle choices also play a crucial role.
2. Can I prevent this even if it runs in my family?
Section titled “2. Can I prevent this even if it runs in my family?”Absolutely. While your genes can increase your susceptibility, aortic atherosclerosis is a complex interplay of genetics and environment. Healthy lifestyle choices, such as diet, exercise, and avoiding certain environmental exposures, can significantly influence whether the disease develops or progresses, even with a genetic predisposition.
3. Does living near busy roads affect my risk?
Section titled “3. Does living near busy roads affect my risk?”Yes, it can. Research indicates that specific genetic variations can interact with environmental exposures like residential traffic pollution. This interaction can influence the progression of aortic atherosclerosis, suggesting that your environment can impact your genetic susceptibility.
4. Why do some healthy people still get hardened arteries?
Section titled “4. Why do some healthy people still get hardened arteries?”Even individuals with healthy lifestyles can develop hardened arteries due to strong genetic predispositions. Your genes can make you more susceptible to the underlying inflammatory processes and plaque buildup within the aorta, even in the absence of obvious lifestyle risk factors.
5. Can this problem start when I’m still young?
Section titled “5. Can this problem start when I’m still young?”Yes, it can. Aortic atherosclerosis is a progressive disorder that can actually begin early in life, advancing over decades. While symptoms often appear later, the initial stages of plaque formation and arterial wall changes can start much earlier than many people realize.
6. Is a genetic test useful to know my risk?
Section titled “6. Is a genetic test useful to know my risk?”Genetic tests are becoming increasingly useful for understanding individual risk. Genomic research aims to identify specific genetic variants that can predict your risk of developing aortic atherosclerosis and how it might progress. This information could eventually help tailor personalized prevention strategies.
7. Why are older men more likely to get this?
Section titled “7. Why are older men more likely to get this?”Abdominal aortic aneurysms, a serious complication of aortic atherosclerosis, are indeed more prevalent in older men. While the exact genetic mechanisms for this gender and age disparity are still being explored, it’s likely due to a combination of genetic factors, hormonal influences, and cumulative lifestyle exposures over time.
8. Can my genes make my arteries stiffen faster?
Section titled “8. Can my genes make my arteries stiffen faster?”Yes, they can. Research has identified specific genetic variations that are associated with arterial stiffness. These genetic factors can influence the rate at which your aorta and other arteries lose their elasticity and become stiffened, contributing to the progression of atherosclerosis.
9. Does having high cholesterol make my genes worse?
Section titled “9. Does having high cholesterol make my genes worse?”High cholesterol doesn’t “make your genes worse,” but it’s a critical environmental factor that interacts with your genetic predispositions. If you have genes that make you susceptible to plaque buildup, high cholesterol can significantly accelerate the formation of these plaques, worsening the disease process.
10. If my family has it, will my kids get it too?
Section titled “10. If my family has it, will my kids get it too?”Your children may inherit some of the genetic predispositions that run in your family. Genetic factors are known to contribute significantly to the risk of developing atherosclerosis. Therefore, if it’s prevalent in your family, early awareness and promoting healthy lifestyle choices are particularly important for your children.
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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[5] Ward-Caviness CK, et al. “A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic.”PLoS One, vol. 12, no. 3, 2017, p. e0173880.
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[9] Vasan, R. S., et al. “Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.” JAMA, vol. 302, no. 2, 2009, pp. 168–178.
[10] Wineinger, N. E., et al. “Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study.” BMC Med Genomics, vol. 4, 2011, p. 1.
[11] O’Donnell CJ, et al. “Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI’s Framingham Heart Study.”BMC Med Genet, vol. 8, Suppl 1, 2007, p. S4.
[12] Wilson, Peter W. F., et al. “Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality.”Circulation, vol. 103, no. 12, 2001, pp. 1529-1534.
[13] Jones, G. T., et al. “Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.”Circ Res, 2016.
[14] van ‘t Hof, F. N., et al. “Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.” J Am Heart Assoc, 2016.
[15] Aherrahrou, Reda, et al. “Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells.”Circulation Research, vol. 127, no. 12, 2020, pp. 1547-1563.
[16] Bis JC, et al. “Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque.” Nat Genet, vol. 43, no. 10, 2011, pp. 940-7.
[17] Mitchell GF, et al. “Common genetic variation in the 3’-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium.”Circ Cardiovasc Genet, vol. 4, no. 6, 2011, pp. 663-71.
[18] Malik R, et al. “Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.”Nat Genet, vol. 50, no. 4, 2018, pp. 524-537.
[19] Pulit, Sara L., et al. “Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.”The Lancet Neurology, vol. 16, no. 2, 2017, pp. 177-189.
[20] Klarin, Derek, et al. “Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program.”Circulation, vol. 142, no. 20, 2020, pp. 1930-1942.