Mean Arterial Pressure

Introduction

Background

Mean Arterial Pressure (MAP) is a critical physiological measurement that represents the average arterial pressure during a single cardiac cycle.^[1]It provides a comprehensive view of the pressure driving blood flow through the organs and tissues, making it a key indicator of tissue perfusion. MAP is commonly calculated using the formula: MAP = (Systolic Blood Pressure (SBP) / 3) + (2 × Diastolic Blood Pressure (DBP) / 3).^[2] Other equivalent formulations, such as MAP = (2 DBP + SBP)/3.^[3]or MAP = DBP + 1/3 Pulse Pressure (PP).^[4] are also used in research. For studies involving individuals on antihypertensive medication, blood pressure values are often adjusted, typically by adding 10 mmHg to SBP and 5 mmHg to DBP, to account for treatment effects.^[2] although some studies may apply different adjustments.^[3]

Biological Basis

Blood pressure, including MAP, is a complex trait influenced by a dynamic interplay of genetic predispositions, environmental factors, and their interactions.^[1] Research has consistently demonstrated that MAP exhibits established heritability, indicating a significant genetic component to its variability within populations.^[1]This heritability suggests that specific genetic variants contribute to an individual’s average arterial pressure. Genome-Wide Association Studies (GWAS) are powerful tools used to identify these genetic loci by analyzing millions of single nucleotide polymorphisms (SNPs) across the human genome.^[1] Identifying these genetic factors helps to uncover the underlying biological mechanisms that regulate blood pressure and arterial function.

Clinical Relevance

Mean Arterial Pressure is a highly relevant clinical parameter, serving as a robust predictor of cardiovascular disease risk and mortality.^[5]Alongside pulse pressure, MAP provides crucial insights into the health and stiffness of the large arteries. Deviations from a healthy MAP range can indicate various cardiovascular issues. Specifically, elevated MAP is a characteristic feature of hypertension, a condition recognized as a major risk factor for coronary heart disease and stroke.^[6]Even minor increases in blood pressure levels, including MAP, can lead to substantial effects on cardiovascular morbidity and mortality at the population level.^[6]Therefore, monitoring and managing MAP are essential components of cardiovascular health assessment and disease prevention.

Social Importance

Hypertension, characterized by persistently high blood pressure, poses a substantial global health challenge, affecting nearly 30% of the world’s adult population.^[1]It stands as the leading risk factor for mortality worldwide.^[1]Given MAP’s role as a key component and predictor of hypertension and cardiovascular disease, understanding its genetic and environmental determinants is of profound public health relevance.^[1]Research into MAP, particularly through large-scale genetic studies, contributes to a deeper understanding of blood pressure regulation. This knowledge is crucial for developing more effective strategies for the prevention, early detection, and treatment of cardiovascular diseases, ultimately aiming to reduce the global burden of these pervasive conditions.

Methodological and Statistical Considerations

The definition and measurement of mean arterial pressure (MAP) in genetic studies present several methodological challenges. MAP is often calculated indirectly from systolic and diastolic blood pressure (SBP and DBP) using a formula (e.g., MAP = SBP/3 + 2DBP/3), which inherently introduces assumptions and may not always reflect direct physiological measurements with complete accuracy.^{[2], [4], [7]} Furthermore, for participants taking anti-hypertensive medications, blood pressure values are commonly adjusted by adding fixed increments (e.g., 10 mmHg to SBP and 5 mmHg to DBP).^{[1], [2], [4]} While this imputation aims to increase statistical power, it represents an estimate rather than a true untreated value, potentially affecting the precision of genetic association analyses. Additionally, practices such as Winsorizing blood pressure values at four standard deviations or excluding extreme outliers can modify the observed phenotypic distribution, possibly reducing the ability to detect genetic effects relevant to individuals at the extremes of the blood pressure range.^{[2], [7]}Meta-analyses, while powerful for increasing sample size, can be affected by inconsistencies in underlying study methodologies. Variations in genotyping platforms, SNP quality control filters, imputation software, and reference human genomes across different contributing studies can introduce heterogeneity that, despite efforts to control it statistically (e.g., via Cochrane’s Q-test), may not be entirely resolved.^{[1], [2], [7]}Such residual heterogeneity can influence the reliability of pooled effect size estimates. Moreover, advanced statistical methods like multivariate Mendelian randomization (MVMR) can be limited by substantial collinearity between genetic instruments, potentially leading to unreliable estimates, especially when instruments are weak.^[8]

Generalizability and Ancestral Heterogeneity

A significant limitation of current research on mean arterial pressure genetics is the variable generalizability of findings across diverse ancestral populations. Many large-scale genome-wide association studies (GWAS) meta-analyses have primarily focused on specific ethnic groups, such as East Asian, European, Sub-Saharan African, or Hispanic/Latino cohorts.^{[1], [2], [3], [4], [9]} While efforts are made for trans-ethnic replication, these often reveal that allele-substitution effect sizes can differ significantly between distinct ethnic groups, even for blood pressure traits that show substantial genetic overlap.^[3] For example, specific variants such as rs17249754 and rs2681492 at _ATP2B1_, rs11191593 at _NT5C2_, and rs3824755 at _CYP17A1_ have shown evidence of trans-ethnic replication, but with varying effect sizes across ancestries.^[1]This suggests that genetic architectures influencing mean arterial pressure may not be identical across populations, limiting the direct applicability of findings from one ancestry to another. Furthermore, the absence of well-powered summary statistics from certain ancestral groups can impede the ability to replicate findings or conduct comprehensive trans-ethnic comparisons, leaving knowledge gaps regarding genetic influences in underrepresented populations.^[8]

Unaccounted Genetic and Environmental Influences

Despite the identification of numerous genetic loci associated with blood pressure regulation, these variants collectively explain only a modest proportion of the heritability of this complex trait.^[2]This phenomenon, often referred to as “missing heritability,” indicates that a substantial part of the genetic variation influencing mean arterial pressure remains undiscovered. This could be attributed to several factors, including the involvement of rare genetic variants, structural variations, or complex epistatic interactions that are not effectively captured by current GWAS methodologies focusing on common single nucleotide polymorphisms. Moreover, mean arterial pressure is a highly polygenic trait influenced by intricate gene-environment interactions. While research has begun to explore specific interactions, such as gene-age or gene-alcohol effects, the vast array of environmental confounders (e.g., external temperature) and their complex interplay with genetic factors is not yet fully characterized.^{[7], [8]}A comprehensive understanding of these multifaceted genetic and environmental contributions is essential for elucidating the complete etiology and regulatory mechanisms of mean arterial pressure.

Variants

Genetic variations play a significant role in influencing an individual’s mean arterial pressure (MAP) by affecting various biological pathways, from vascular tone regulation to cellular metabolism and immune responses. These variants can alter gene activity, protein function, or signaling pathways, ultimately contributing to differences in blood pressure regulation. Understanding these genetic influences provides insight into the complex mechanisms underlying cardiovascular health.

The potassium channelKCNK3 is crucial for regulating vascular tone, the degree of constriction in blood vessels, which directly impacts blood pressure. Variants such as rs1275984 and rs1275988 in this gene can influence how vascular smooth muscle cells contract or relax, thereby affecting MAP.^[10] Mutations in KCNK3have also been linked to pulmonary hypertension, highlighting its essential role in vascular function. Similarly, theNPR3gene encodes the natriuretic peptide receptor 3, which is responsible for clearing natriuretic peptides, hormones that help lower blood pressure by promoting vasodilation and salt excretion.^[11] Genetic variations like rs1177764 , rs9292468 , and rs10059884 may alter this clearance mechanism, affecting the body’s ability to manage blood pressure. The CLCN6gene, encoding a chloride channel, helps maintain cell volume and electrical activity, processes fundamental to the proper functioning of vascular smooth muscle. Variants such asrs149764880 , rs17037452 , and rs56153133 may modify ion transport across cell membranes, influencing vascular tone and subsequently MAP.^[6] The ALDH2 gene is critical for alcohol metabolism, specifically in breaking down acetaldehyde, a toxic compound produced during alcohol consumption. Variants like rs671 and rs2238151 can reduce the activity of the ALDH2 enzyme, leading to acetaldehyde accumulation, which has been associated with increased blood pressure, particularly in individuals who consume alcohol.^[7]This gene-alcohol interaction demonstrates a direct mechanism through which genetic factors can modulate mean arterial pressure. Another key gene involved in vascular function isARHGAP42, which acts as a Rho GTPase activating protein. This protein is important for controlling the actin cytoskeleton within cells, a process vital for the contraction and relaxation of vascular smooth muscle cells.^[10] Genetic variations such as rs633185 , rs7928576 , and rs1502284 in ARHGAP42 could modulate this pathway, affecting vascular tone and contributing to individual differences in MAP.

Genes with broader roles in cellular regulation and signaling also influence mean arterial pressure.PRDM8 is involved in chromatin modification and gene regulation, fundamental processes for cell development and differentiation, including those of vascular cells. The FGF5 gene encodes a fibroblast growth factor, a signaling protein important for cell growth, tissue repair, and vascular development. Variants associated with the PRDM8-FGF5 genomic region, including rs16998073 , rs10857147 , and rs13125101 , may influence these developmental pathways, indirectly affecting vascular structure and function.^[12] Similarly, NAA25is part of a complex that modifies proteins, a widespread process that impacts protein stability and function across various cell types, including those relevant to the cardiovascular system. Alterations caused by variants likers116873087 and rs17696736 could subtly affect protein activity pertinent to blood pressure regulation.^[2] The RGL3gene functions as a guanine nucleotide exchange factor for Ral GTPases, which are involved in diverse cellular activities such as vesicle trafficking and cell adhesion, processes that can indirectly affect vascular cell behavior and overall MAP.^[3] Variants rs167479 and rs3745688 may modulate these intricate cellular signaling networks.

The BLK gene, which encodes a B-lymphoid tyrosine kinase, is primarily known for its role in immune cell signaling. However, immune responses and inflammation are increasingly recognized for their significant impact on vascular health and blood pressure regulation. Variants like rs899366 , located in the region of BLK and LINC00208, may thus influence mean arterial pressure through interactions between the immune system and the vasculature.^[13] LINC00208 and LINC02227are long intergenic non-coding RNAs (lncRNAs), which are crucial regulators of gene expression. These lncRNAs can influence various biological pathways by modulating the activity of nearby or distant genes, including those involved in cardiovascular function or metabolic processes.^[14] The specific variant rs4371736 in LINC02227could alter the expression or function of genes critical for maintaining blood pressure homeostasis, contributing to individual differences in mean arterial pressure.

Key Variants

RS ID	Gene	Related Traits
rs1275984 rs1275988	RPL37P11 - KCNK3	diastolic blood pressure pulse pressure measurement mean arterial pressure systolic blood pressure total cholesterol measurement
rs16998073 rs10857147 rs13125101	PRDM8 - FGF5	diastolic blood pressure pulse pressure measurement glomerular filtration rate diastolic blood pressure, alcohol consumption quality systolic blood pressure, alcohol consumption quality
rs899366	BLK - LINC00208	mean arterial pressure
rs671 rs2238151	ALDH2	body mass index erythrocyte volume mean corpuscular hemoglobin concentration mean corpuscular hemoglobin coronary artery disease
rs116873087 rs17696736	NAA25	body weight tea consumption measurement alcohol consumption quality body height serum alanine aminotransferase amount
rs4371736	LINC02227	mean arterial pressure
rs149764880 rs17037452 rs56153133	CLCN6	diastolic blood pressure, alcohol drinking mean arterial pressure systolic blood pressure hypertension diastolic blood pressure
rs633185 rs7928576 rs1502284	ARHGAP42	diastolic blood pressure systolic blood pressure pulse pressure measurement mean arterial pressure hypertension
rs1177764 rs9292468 rs10059884	NPR3 - LINC02120	heel bone mineral density BMI-adjusted waist circumference systolic blood pressure mean arterial pressure pulse pressure measurement
rs167479 rs3745688	RGL3	diastolic blood pressure pulse pressure measurement mean arterial pressure systolic blood pressure hypertension

Defining Mean Arterial Pressure

Mean arterial pressure (MAP) is a crucial physiological parameter representing the average blood pressure in an individual’s arteries during one complete cardiac cycle. It is a composite measure that reflects the average perfusion pressure of organs, providing a more comprehensive insight into cardiovascular health than systolic blood pressure (SBP) or diastolic blood pressure (DBP) alone.^[8]Unlike pulse pressure (PP), which indicates vascular stiffness, MAP specifically reflects the average pressure levels throughout the cardiac cycle, offering additional perspectives on the determinants and consequences of blood pressure.^[14]

Operational Measurement and Calculation

The operational definition of mean arterial pressure involves its calculation from measured systolic and diastolic blood pressure values. Several formulas are employed across studies, commonly including MAP = SBP/3 + 2DBP/3.^[15] or the equivalent MAP = DBP + (SBP – DBP)/3.^[1] Another variant cited is MAP = ([2 × DBP] + SBP)/3.^[15] A critical aspect of measurement criteria involves adjustments for individuals taking anti-hypertensive medication (AHM), which can lower observed blood pressure levels. To account for this, some studies adjust recorded SBP and DBP by adding constant values; common adjustments include adding 10 mmHg to SBP and 5 mmHg to DBP.^[15] or, in other instances, adding 15 mmHg to SBP and 10 mmHg to DBP.^[9] These adjustments aim to estimate the unmedicated blood pressure levels for research and analytical purposes.

Classification and Research Context

Within classification systems, mean arterial pressure is primarily treated as a continuous trait, reflecting its nature as a gradient rather than a categorical state.^[9]This continuous characteristic allows for a dimensional approach to assessing cardiovascular risk and for detailed analysis in genetic studies, where small variations can be significant. While MAP itself is not typically categorized into distinct stages like hypertension, it is an integral component in the broader assessment of blood pressure status. Hypertension, for example, is defined by specific thresholds for SBP (≥140 mmHg) and/or DBP (≥90 mmHg), or by the use of anti-hypertensive medication, representing a categorical classification.^[1] The study of MAP, along with other blood pressure traits, is crucial in fields like genome-wide association studies (GWAS) to identify genetic variants influencing blood pressure regulation.^[8] Its high heritability, similar to other blood pressure traits, underscores the importance of genetic factors in its determination.^[14]Understanding MAP’s continuous nature and its relationship to established disease classifications contributes to a more nuanced understanding of cardiovascular health and disease risk.

Causes of Mean Arterial Pressure

Mean arterial pressure (MAP) is a critical physiological indicator, and its regulation is influenced by a complex interplay of genetic, environmental, and developmental factors. Understanding these diverse causes is essential for comprehending blood pressure homeostasis and the etiology of hypertension.

Genetic Predisposition

Mean arterial pressure is a highly heritable trait, with studies estimating its heritability to range from 30% to as high as 70% in twin populations . It is derived from systolic (SBP) and diastolic blood pressure (DBP) measurements, typically calculated as MAP = SBP/3 + 2*DBP/3.^{[1], [2]}As a fundamental physiological index, MAP is an independent and significant determinant of cardiovascular disease (CVD) risk and mortality worldwide.^{[1], [14]}The regulation of MAP is a complex interplay of genetic, environmental, and lifestyle factors, reflecting intricate biological mechanisms at molecular, cellular, tissue, and organ levels.^{[8], [14]}

Physiological Regulation and Organ-Level Interactions

The maintenance of MAP is a tightly regulated homeostatic process involving the coordinated function of several organ systems, primarily the heart, blood vessels, and kidneys. Blood pressure, including MAP, is fundamentally determined by cardiac output (the volume of blood pumped by the heart per minute) and systemic vascular resistance (the resistance to blood flow offered by all systemic vasculature).^[10] Vascular tone, which is the degree of constriction of blood vessels, is a critical component of systemic vascular resistance and is influenced by various local and systemic signals.^[10] The kidneys play a pivotal role in long-term blood pressure regulation by controlling fluid balance and electrolyte homeostasis, thereby affecting blood volume and cardiac output.^[10]

Molecular and Cellular Mechanisms

At the molecular and cellular level, MAP regulation involves complex signaling pathways, critical proteins, enzymes, receptors, and hormones that dictate cellular functions within the cardiovascular and renal systems. For instance, the enzyme phosphodiesterase 3A (PDE3A) is a key player in vascular smooth muscle cell function, and pharmacological inhibitors ofPDE3A have been shown to lower blood pressure.^[10]The potassium channelKCNK3is crucial for regulating vascular tone by controlling membrane potential in vascular smooth muscle cells.^[10] Furthermore, IGFBP3(insulin-like growth factor binding protein 3) modulates the actions of insulin-like growth factors, which are circulating hormones that influence vascular smooth muscle cell function.^[10] Another important protein, phosphoinositide 3-kinase gamma (PIK3CG), is implicated in cardiac function and heart failure, highlighting its role in the heart’s contribution to blood pressure regulation.^{[6], [16], [17]}

Genetic and Epigenetic Influences

MAP is recognized as a highly heritable trait, with genetic factors accounting for approximately 25% to 70% of its variance across different populations.^{[2], [14]} Genome-wide association studies (GWAS) have identified numerous genetic variants associated with blood pressure traits, including MAP, with over 2,000 such variants reported.^[8] Specific genetic loci, such as those near FIGN (rs13002573 ), CHIC2 (rs871606 ), PIK3CG (rs17477177 ), NOV (rs2071518 ), and ADAMTS-8 (rs11222084 ), have been significantly associated with MAP.^[6] Beyond direct genetic variants, epigenetic mechanisms also contribute to MAP regulation; for example, PRDM6acts as an epigenetic regulator influencing the phenotypic plasticity of vascular smooth muscle cells by suppressing differentiation and maintaining their proliferative potential.^[10]Additionally, interactions between genes and environmental factors, such as gene-sodium.^[15] and gene-alcohol interactions (e.g., near SLC16A9).^[7] further underscore the complex genetic architecture of MAP.

Pathophysiological Processes and Disease Mechanisms

Elevated MAP is a critical predictor for a range of adverse cardiovascular outcomes, including stroke and coronary heart disease, and is considered the leading risk factor for global mortality.^{[1], [18]}Disruptions in the intricate homeostatic mechanisms governing MAP can lead to hypertension, a condition where sustained high blood pressure increases the risk of organ damage and cardiovascular events.^[7] For example, MAP provides independent prognostic information in patients with left ventricular dysfunction.^[19]The genetic and molecular pathways involved in MAP regulation are also implicated in specific disease mechanisms, such as mutations inKCNK3which are associated with pulmonary hypertension, and genetic variants nearPRDM6that are linked to intracranial aneurysm.^[10]Furthermore, large artery stiffness, which is closely related to blood pressure dynamics, is a known contributor to hypertension and increased cardiovascular risk.^[20]

Neurohumoral and Receptor-Mediated Regulation

Mean arterial pressure (MAP) is intricately controlled by neurohumoral pathways that govern vascular tone and cardiac output. The Renin-Angiotensin System (RAS) is a critical regulator, where genes likeAGT (angiotensinogen) and ACE(angiotensin-converting enzyme) play central roles in its cascade, affecting blood pressure homeostasis and fluid-electrolyte balance.^[13] Similarly, adrenergic signaling, mediated by receptors such as ADRB1(beta-1 adrenergic receptor), influences cardiovascular function and contributes to pressure regulation.^[13]Beyond these well-known systems, various G-protein coupled receptors (GPCRs) mediate the release of hormones like follicle-stimulating hormone, luteinizing hormone, and thyroid hormone, which significantly impact myocardial activity and blood pressure.^[14]The Gonadotropin-Releasing Hormone (GNRH) signaling pathway, involving GNRH receptors coupled with G-proteins, is implicated in cardiovascular processes.^[14]Furthermore, the Epidermal Growth Factor Receptor (EGFR) signaling network, including the “EGFR smrte pathway,” “GAB1 signalosome,” and “SHC1 events in EGFR signaling,” is crucial, asGAB1 is recruited to activated EGFR through GRB2, thereby affecting downstream signals that modulate MAP.^[14]

Metabolic and Endothelial Modulators

Metabolic pathways significantly contribute to mean arterial pressure regulation, particularly through the biosynthesis of vasoactive substances. Tyrosine metabolism, for instance, is a direct precursor for catecholamine biosynthesis, leading to the production of dopamine, noradrenaline, and adrenaline, all of which are well-known regulators of blood pressure.^[14] Endothelial function is also paramount, with nitric oxide synthase (NOS3 or eNOS) playing a key role in producing nitric oxide, a potent vasodilator that influences vascular tone and blood pressure.^[13] The integration of various metabolic factors extends to pathways involving folate metabolism, such as those influenced by MTHFR(methylenetetrahydrofolate reductase), which is associated with cardiovascular disease risk and blood pressure regulation.^[13]Platelet function also impacts hemodynamics; pathways like “platelet aggregation plug formation” and “integrin alphaiib beta3 signaling” are crucial for normal hemostasis, but pathological activation can affect intravascular hemodynamics and contribute to blood pressure changes and cardiovascular diseases like stroke and atherosclerosis.^[14]

Genetic and Epigenetic Control of Vascular Homeostasis

Genetic and epigenetic mechanisms provide a foundational layer of mean arterial pressure control, influencing gene expression and protein function. Transcription factors likeOSR1 (odd-skipped related 1) are critical in influencing renal mass and function, while GATA4is enriched in cardiovascular disease-related biological functions, highlighting their roles in organ development and regulation relevant to blood pressure.^[10]Epigenetic modifications, such as DNA methylation, are increasingly recognized for their role in blood pressure regulation, with variants nearPRDM6(PR/SET domain containing 6) acting as epigenetic regulators of vascular smooth muscle cell phenotypic plasticity.^[10] Beyond transcriptional control, post-translational modifications and allosteric regulation of proteins are vital. Pharmacological inhibitors of PDE3A(phosphodiesterase 3A) are known to lower blood pressure, indicating its role in vascular smooth muscle relaxation.^[10]Potassium channels likeKCNK3(potassium two pore domain channel subfamily K member 3) are essential for regulating vascular tone, whileIGFBP3(insulin-like growth factor binding protein 3) modulates the actions of insulin-like growth factors, which influence vascular smooth muscle cell function.^[10] Other relevant proteins include ATP2B1 (ATPase plasma membrane Ca2+ transporting 1), CSK (c-src tyrosine kinase), ARSG (arylsulfatase G), CSMD1 (CUB and Sushi multiple domains 1), and serum/glucocorticoid regulated kinase (SGK) genes, all implicated in blood pressure regulation through diverse cellular processes.^[10]

Systems Integration and Organ-Specific Contributions

Mean arterial pressure regulation involves complex systems-level integration, where various pathways crosstalk and contribute through distinct organ systems. TheEGFR signaling pathway, for instance, demonstrates intricate interactions where GAB1, SHC1 events, and EGFR downregulation can directly or indirectly affect downstream signals, illustrating pathway crosstalk in blood pressure control.^[14] Similarly, L1 signal transduction can interact with FGF receptor(fibroblast growth factor receptor) to activate DAG (diacylglycerol), leading to arachidonic acid production, which is important in regulating hemodynamics.^[14] Renal function is a primary determinant of blood pressure, with genes like ARHGAP24 (Rho GTPase activating protein 24) influencing podocyte formation, OSR1 affecting renal mass, SLC22A7 (solute carrier family 22 member 7) encoding a key renal solute transporter, and TBX2(T-box transcription factor 2) being determinants of renal function and chronic kidney disease.^[10]The cardiovascular system as a whole is critically involved, with gene enrichment in categories such as “Cardiovascular Diseases,” “Heart Failure,” “Cardiomegaly,” “Hypertrophy,” “Heart,” “Aorta,” “Myocardium,” and “Cardiac Arrhythmias,” indicating a broad network of interacting genes likeAGT, NPPA, ACE, NOS3, ADRB1, MTHFR, FBN1, GATA4, and KCNJ11 that collectively influence MAP.^[13]

Disease-Relevant Mechanisms and Therapeutic Insights

Dysregulation within these complex pathways often underlies conditions like hypertension and other cardiovascular diseases. Essential hypertension and pulmonary hypertension are examples where specific pathways, such as the Renin-Angiotensin System or those involving vascular tone regulators likeKCNK3, are compromised.^[13]Pathological thrombus formation, mediated by processes like “platelet aggregation plug formation” and “integrin alphaiib beta3 signaling,” can lead to serious cardiovascular events such as stroke and atherosclerosis, directly impacting mean arterial pressure and overall cardiovascular health.^[14] Understanding these mechanisms also reveals potential therapeutic targets. For instance, pharmacological inhibitors of PDE3A have demonstrated efficacy in lowering blood pressure, suggesting PDE3A as a viable target for antihypertensive therapies.^[10]Furthermore, epigenetic modifications, such as the attenuation of mitochondrial superoxide dismutase 2, are being explored as new therapeutic targets for conditions like pulmonary arterial hypertension, highlighting the growing importance of epigenetic regulation in disease management.^[10]

Clinical Relevance

Mean arterial pressure (MAP), defined as the average pressure in the arteries, is a crucial physiological parameter with significant clinical relevance.^[1]It is typically calculated from systolic (SBP) and diastolic blood pressure (DBP) measurements, often as DBP + (SBP–DBP)/3 or SBP/3 + 2DBP/3.^[1]Hypertension, characterized by elevated blood pressure, affects a substantial portion of the adult population globally and is a primary risk factor for mortality.^[1] MAP is a complex trait influenced by both genomic and environmental factors, with studies indicating its established heritability, ranging from approximately 42.7% to 54.7%.^[1] Genome-wide association studies (GWAS) have identified specific genetic loci, such as rs17477177 near PIK3CG and those associated with long-term average MAP like rs11191580 , rs12579302 , and rs11105364 , that influence MAP levels.^[6]

Prognostic Value and Risk Stratification

MAP serves as an independent predictor of cardiovascular disease risk and mortality, offering valuable prognostic information in patient care.^[1]Large meta-analyses of prospective studies involving millions of adults have demonstrated the age-specific relevance of usual blood pressure, including MAP, to vascular mortality.^[21] In individuals with left ventricular dysfunction, MAP provides prognostic insights independent of other blood pressure components.^[19]Furthermore, Mendelian randomization studies provide strong evidence for a causal association between higher MAP and an increased risk of several major cardiovascular diseases, including ischaemic stroke, intracerebral haemorrhage, major coronary events, and carotid plaque.^[8]For instance, a 5 mmHg increase in MAP has been causally linked to elevated odds of ischaemic stroke (Odds Ratio [OR] 1.23, 95% CI: 1.16, 1.29) and major coronary events (OR 1.30, 95% CI: 1.21, 1.40).^[8] This causal evidence underscores MAP’s utility in identifying high-risk individuals and informing personalized prevention strategies.

Clinical Assessment and Therapeutic Monitoring

In clinical practice, MAP is a fundamental metric for diagnostic assessment and monitoring of therapeutic interventions. Blood pressure measurements, including SBP and DBP, are routinely taken, and for patients on anti-hypertensive medications, values are often adjusted (e.g., adding 10-15 mmHg to SBP and 5-10 mmHg to DBP) before MAP calculation to reflect underlying hypertension more accurately.^[4]This careful adjustment is critical for assessing true blood pressure status and guiding treatment selection. Additionally, long-term average MAP (LTA MAP) is calculated by averaging blood pressure residuals over multiple follow-up visits, adjusted for confounding factors like age, gender, and body mass index.^[2]This approach provides a more stable and representative measure of an individual’s blood pressure over time, aiding in the long-term monitoring of disease progression and the effectiveness of sustained treatment regimens. To enhance data quality and clinical accuracy, extreme blood pressure values are often Winsorized, typically at 4 or 6 standard deviations from the mean, to minimize the impact of outliers.^[2]

Associations with Cardiovascular Morbidity

Elevated MAP is causally and significantly associated with a range of cardiovascular morbidities, making it a critical indicator for assessing overall cardiovascular health.^[8] Research indicates that higher MAP causally increases the risk of both ischaemic and intracerebral haemorrhagic strokes.^[8]Moreover, it is strongly linked to major coronary events and the development of carotid plaque, a marker of subclinical atherosclerosis.^[8] For instance, multivariable Mendelian randomization analyses have shown that a 1-standard deviation higher MAP is causally associated with increased odds of major coronary events (OR 2.40, 95% CI: 1.92, 3.00) and carotid plaque (OR 1.91, 95% CI: 1.56, 2.34).^[8]These findings underscore MAP’s comprehensive role as a predictor and an independent causal factor in the etiology of widespread cardiovascular complications, thus emphasizing its importance in patient management and public health initiatives aimed at reducing global mortality from hypertension.

Frequently Asked Questions About Mean Arterial Pressure

These questions address the most important and specific aspects of mean arterial pressure based on current genetic research.

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1. Will I likely get high MAP if my parents have it?

Yes, there’s a significant chance. Mean Arterial Pressure (MAP) has an established heritability, meaning a substantial part of its variability is due to genetics. If your parents have high MAP, you might have inherited some of the genetic variants that predispose you to it. However, your lifestyle choices also play a crucial role in whether that genetic predisposition is expressed.

2. Why do some people have great MAP despite their diet?

It’s often due to their genetic makeup. Some individuals inherit genetic variants that provide a natural protective effect or better regulation of blood pressure, even with less-than-ideal environmental factors. While diet is important, their genetic predisposition helps them maintain a healthy MAP more easily than others. This highlights the strong genetic component influencing MAP variability.

3. Can I outrun my family’s high MAP with exercise?

You can significantly influence it, even with a family history. While you might have genetic predispositions for higher MAP, regular exercise is a powerful environmental factor that can help counteract these genetic influences. Adopting a healthy lifestyle, including physical activity, is essential for managing your blood pressure and reducing your risk, even if you carry some genetic risk factors.

4. Does my ethnic background change my MAP risks?

Yes, your ancestral background can play a role. Large-scale genetic studies have shown that genetic risk factors for MAP can differ across various ethnic groups, such as East Asian, European, or Hispanic/Latino populations. This means your specific genetic predispositions related to MAP might be influenced by your heritage, making ancestry-specific research important for understanding these differences.

5. My MAP is high; does stress affect me more due to genetics?

It’s possible that genetics influence how you respond to stress regarding MAP. Blood pressure regulation involves a complex interplay of genetic factors and environmental stressors like work stress. Your individual genetic makeup can influence how your body’s systems, including arterial function, react to chronic stress, potentially leading to higher MAP for some individuals.

6. Why does healthy eating work for others but not my MAP?

Your genetic makeup might be influencing your response. While healthy eating is universally beneficial, genetic predispositions can affect how effectively your body processes nutrients, regulates blood pressure, or responds to dietary interventions. For some, specific genetic variants might make it harder to achieve optimal MAP levels through diet alone, requiring a more comprehensive or tailored approach.

7. Could a genetic test predict my future high MAP?

Currently, genetic tests are not typically used to predict an individual’s precise future MAP. While research identifies many genetic variants associated with MAP risk in populations, these findings mostly help us understand the general biological mechanisms. They are primarily used for population-level risk assessment and developing better prevention strategies, rather than precise personal predictions for clinical use.

8. My sibling’s MAP is fine; why is mine a concern?

Even within families, genetic inheritance isn’t identical, and lifestyle choices differ. While you share genes with your sibling, you each inherit a unique combination of genetic variants from your parents that influence MAP. Combined with individual environmental exposures, diet, and exercise habits, these differences can lead to varying MAP levels between siblings.

9. Does my average blood pressure just naturally worsen with age?

While blood pressure can tend to increase with age for many, genetic factors also play a role in this progression. Research suggests there can be gene-age interactions that influence blood pressure regulation. This means your genetic predispositions might affect how your MAP changes over time, making some individuals more susceptible to age-related increases than others.

10. Can small daily habits truly affect my MAP long-term?

Absolutely, small daily habits can significantly influence your MAP over time. Mean Arterial Pressure is a complex trait influenced by both genetics and environmental factors, including your daily routines. Consistent healthy choices in diet, exercise, and stress management can positively impact your blood pressure regulation, even if you have a genetic predisposition for higher MAP.

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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] Kelly, T. N., et al. “Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci.”Hypertension, vol. 62, no. 5, 2013, pp. 830–838.

[2] Li, C, et al. “Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.” Circ Cardiovasc Genet, vol. 10, no. 2, 2017.

[3] Takeuchi, F, et al. “Interethnic analyses of blood pressure loci in populations of East Asian and European descent.” Nat Commun, vol. 9, no. 1, 2018, p. 4924.

[4] Sofer, T, et al. “Genome-Wide Association Study of Blood Pressure Traits by Hispanic/Latino Background: the Hispanic Community Health Study/Study of Latinos.” Sci Rep, vol. 7, no. 1, 2017, p. 10328.

[5] Sesso, H.D., et al. “Systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure as predictors of cardiovascular disease risk in Men.”Hypertension, vol. 36, no. 5, 2000, pp. 801-807. PMID: 11075764.

[6] Wain, L. V., et al. “Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.”Nat Genet, vol. 43, no. 10, 2011, pp. 1005-1011.

[7] Simino, J, et al. “Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9.” Front Genet, vol. 4, 2013, p. 272.

[8] Pozarickij, A, et al. “Causal relevance of different blood pressure traits on risk of cardiovascular diseases: GWAS and Mendelian randomisation in 100,000 Chinese adults.”Nat Commun, vol. 15, no. 1, 2024, p. 6265.

[9] Singh, S, et al. “Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study.”Nat Commun, vol. 14, no. 1, 2023, p. 8056.

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