Mean Arterial Pressure
Mean arterial pressure (MAP) represents the average arterial blood pressure during a single cardiac cycle. It is a critical physiological parameter reflecting the perfusion pressure experienced by organs in the body. Typically calculated using systolic blood pressure (SBP) and diastolic blood pressure (DBP), MAP provides a more comprehensive assessment of arterial pressure than SBP or DBP alone, as it accounts for the longer duration of diastole compared to systole.
Biologically, MAP is a key indicator of the force exerted by blood against the arterial walls and is primarily determined by cardiac output (the volume of blood pumped by the heart per minute) and systemic vascular resistance (the resistance to blood flow in the circulatory system). Maintaining MAP within a healthy range is essential for ensuring adequate blood flow to vital organs. Genetic factors contribute significantly to the variation in MAP among individuals. Research, including genome-wide association studies (GWAS), has identified multiple genetic loci that influence mean arterial pressure[1]. These studies often analyze MAP as a phenotype, alongside other blood pressure traits like SBP and DBP, adjusting for covariates such as age, sex, body mass index (BMI), height, and weight [2].
Clinically, MAP is a vital metric for evaluating cardiovascular health. Deviations from a healthy MAP range can indicate various underlying health conditions, including hypertension (high blood pressure) or hypotension (low blood pressure). MAP is frequently studied in conjunction with SBP and DBP to assess overall blood pressure regulation[3]. Elevated blood pressure, including MAP, is a major risk factor for cardiovascular diseases and stroke[4]. For individuals receiving antihypertensive therapies, blood pressure values are often adjusted in studies to account for the medication’s effects, for example, by adding 10-15 mm Hg to observed SBP and 5-10 mm Hg to DBP [3]. Large-scale research initiatives, such as the Framingham Heart Study, have utilized MAP to investigate its genetic associations with blood pressure and arterial stiffness [2].
The social importance of understanding mean arterial pressure stems from its profound impact on public health. Cardiovascular diseases, often linked to abnormal blood pressure, are leading causes of morbidity and mortality worldwide. By identifying genetic and environmental factors that influence MAP, researchers aim to develop improved strategies for the prevention, diagnosis, and treatment of these widespread conditions. Genetic variants, even those with small individual effects on blood pressure, can have an aggregate impact that leads to meaningful population-level changes in the risk of cardiovascular events and stroke[4].
Limitations
Section titled “Limitations”Understanding the genetic underpinnings of mean arterial pressure (MAP) is complex, and current research faces several inherent limitations that impact the interpretation and generalizability of findings. These limitations span study design, population diversity, and the intricate nature of blood pressure regulation.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Genetic association studies for mean arterial pressure often rely on large sample sizes to detect the subtle effects of individual genetic variants othelial function, indirectly influencing mean arterial pressure.
Variations near genes like PRDM8 and FGF5, exemplified by rs16998073 , rs10857147 , and rs13125101 , may be associated with mean arterial pressure. PRDM8 (PR/SET Domain 8) is a transcription factor involved in neurodevelopment, while FGF5 (Fibroblast Growth Factor 5) is a signaling protein with diverse biological functions, including roles in metabolism and cell growth. Although their direct mechanisms for blood pressure regulation are complex, these genes can influence pathways that indirectly affect cardiovascular function or systemic metabolic processes, both of which are known determinants of blood pressure. The region encompassing BLK (B-lymphoid tyrosine kinase) and LINC00208 (a long intergenic non-coding RNA), including variantrs899366 , may also contribute to blood pressure variability. BLK is involved in immune cell signaling, and immune responses can impact vascular inflammation and health. LINC00208, as a lncRNA, likely plays a regulatory role in gene expression, potentially affecting cardiovascular pathways. NAA25 (N-alpha-acetyltransferase 25), with variants like rs116873087 and rs17696736 , is part of a protein complex that performs N-terminal acetylation, a fundamental post-translational modification that can influence protein stability and function across numerous cellular processes, including those relevant to cardiovascular regulation. Similarly, LINC02227, another long intergenic non-coding RNA, represented by rs4371736 , may exert regulatory effects on gene expression that are pertinent to vascular function or systemic physiology, thereby influencing mean arterial pressure.
Classification, Definition, and Terminology of Mean Arterial Pressure
Section titled “Classification, Definition, and Terminology of Mean Arterial Pressure”Mean arterial pressure (MAP) is a fundamental physiological parameter reflecting the average pressure in the arteries during one cardiac cycle. Its precise definition, measurement, and clinical relevance are crucial for understanding cardiovascular health and disease.
Definition and Core Concepts
Section titled “Definition and Core Concepts”Mean arterial pressure (MAP) represents the average pressure exerted by blood within the arteries, reflecting the perfusion pressure of organs. It is a critical physiological parameter, often studied as a quantitative phenotype in genetic research[2]. MAP is intrinsically linked to other key blood pressure components, including systolic blood pressure (SBP), which is the peak pressure during heart contraction, and diastolic blood pressure (DBP), the minimum pressure when the heart rests between beats[2]. Additionally, pulse pressure (PP), the difference between SBP and DBP, is another related concept frequently analyzed alongside MAP [1]. Genetic studies have successfully identified specific genomic loci that influence MAP, underscoring its complex genetic architecture and its role as an intermediate phenotype in cardiovascular health [1].
Operational Definitions and Measurement Approaches
Section titled “Operational Definitions and Measurement Approaches”In research, mean arterial pressure is operationally defined as a derived metric from measured blood pressure values. For robust analysis, especially in large-scale epidemiological and genetic studies, MAP values undergo rigorous adjustments for various covariates. These adjustments commonly include demographic factors such as age and sex, and anthropometric measures like height, weight, and body mass index (BMI)[2]. These covariates are often incorporated into multivariable regression models, sometimes specific to study cohorts or examination cycles, to account for their influence on blood pressure phenotypes [2]. Furthermore, when analyzing constituent blood pressure components like SBP and DBP, a common practice in research is to adjust for antihypertensive medication use by adding a fixed increment (e.g., 10 mmHg to SBP and 5 mmHg to DBP) to observed values, thereby standardizing measurements across individuals with and without treatment [3].
Clinical Relevance and Associated Terminology
Section titled “Clinical Relevance and Associated Terminology”The clinical relevance of mean arterial pressure is profound, as it directly influences organ perfusion and is a key indicator of cardiovascular function, even though specific diagnostic thresholds for MAP itself are not universally established for disease classification in the provided context. MAP is considered alongside systolic and diastolic blood pressure in the assessment of cardiovascular risk and in the context of vascular diseases[5]. Hypertension, a major risk factor for cardiovascular disease-related mortality, is commonly defined by specific thresholds for SBP (≥140 mmHg) or DBP (≥90 mmHg), or by the use of antihypertensive medication[3]. Similarly, blood pressure thresholds (e.g., SBP ≥130 mmHg or DBP ≥85 mmHg, or medication use) are integral diagnostic criteria for conditions such as metabolic syndrome [6]. Thus, MAP forms an essential part of the broader terminology used in cardiovascular medicine, contributing to a comprehensive understanding of blood pressure dynamics and their implications for health.
Genetic Predisposition
Section titled “Genetic Predisposition”Mean arterial pressure (MAP) is significantly influenced by inherited genetic factors, with numerous loci identified through genome-wide association studies (GWAS). Research has uncovered multiple genetic variants that contribute to blood pressure regulation, including six new loci specifically influencing MAP and pulse pressure[1]. These studies utilize additive genetic models to assess the impact of allele dosages on blood pressure, indicating a polygenic architecture where many genes with small effects collectively determine an individual’s MAP [3]. The aggregate effect of these identified genetic variants, even those with small individual contributions (e.g., approximately 1 mm Hg/allele for SBP or 0.5 mm Hg/allele for DBP), can lead to meaningful population-level changes in cardiovascular and stroke risk[4].
Specific genetic variants have been found to influence blood pressure and cardiovascular disease risk by acting through novel pathways[7]. Additionally, certain loci associated with erythrocyte phenotypes have also shown associations with blood pressure and hypertension, highlighting potential shared genetic pathways or pleiotropic effects[5]. The heritability of blood pressure and arterial stiffness phenotypes further underscores the substantial role of genetic factors in determining an individual’s MAP [2].
Demographic and Lifestyle Influences
Section titled “Demographic and Lifestyle Influences”Beyond genetics, various demographic and lifestyle factors play a crucial role in shaping mean arterial pressure. Age is a significant determinant, with blood pressure frequently adjusted for age and age-squared in analytical models, indicating a complex, non-linear relationship where MAP tends to change with advancing years[2]. Biological sex also influences MAP, necessitating adjustments for this variable in population studies [2].
Body Mass Index (BMI) is another key factor, consistently included as a covariate in studies of blood pressure, reflecting the well-established link between body weight and cardiovascular health [2]. Furthermore, broader environmental and geographic covariates are recognized as influential, requiring study-specific adjustments to account for population stratification and regional differences that can impact blood pressure levels [4]. These factors collectively contribute to the variability of MAP across individuals and populations.
Clinical and Acquired Factors
Section titled “Clinical and Acquired Factors”Several clinical and acquired factors also contribute to variations in mean arterial pressure. Hypertension itself, defined as elevated systolic or diastolic blood pressure or the need for drug treatment, directly impacts MAP and is a major comorbidity associated with adverse cardiovascular outcomes[5]. Vascular diseases, which can affect arterial stiffness and blood vessel function, are also linked to MAP regulation, with specific genetic associations for arterial stiffness being identified [5].
The use of antihypertensive medications significantly alters observed blood pressure readings. Studies often account for this by adding a fixed increment to the measured systolic and diastolic blood pressure values of treated individuals (e.g., 10-15 mm Hg for SBP and 5-10 mm Hg for DBP) to better estimate their underlying untreated pressure, highlighting the substantial impact of pharmacological interventions on MAP[3]. These clinical considerations are essential for understanding the full spectrum of factors influencing an individual’s mean arterial pressure.
Physiological Role and Regulation of Mean Arterial Pressure
Section titled “Physiological Role and Regulation of Mean Arterial Pressure”Mean arterial pressure (MAP) represents the average pressure in a person’s arteries during one cardiac cycle, playing a critical role in tissue perfusion and overall cardiovascular health. It is a key indicator of the force driving blood through the circulatory system and delivering oxygen and nutrients to organs[2]. The body maintains MAP within a narrow range through a complex interplay of systemic mechanisms, including cardiac output, total peripheral resistance, and blood volume. Dysregulation of MAP can significantly impact the function of vital organs, highlighting its importance as a fundamental physiological parameter [8].
Regulation of MAP involves intricate neural and hormonal feedback loops that continuously monitor and adjust cardiovascular function. Baroreceptors, specialized stretch receptors located in the walls of major arteries, detect changes in blood pressure and send signals to the brainstem, which then modulates sympathetic and parasympathetic nervous system activity to alter heart rate, contractility, and vascular tone. Hormonal systems, such as the renin-angiotensin-aldosterone system (RAAS), also contribute to long-term MAP control by influencing fluid balance and vascular constriction [9]. These regulatory networks ensure that blood flow remains adequate to meet metabolic demands while preventing excessive strain on the vascular system.
Molecular and Cellular Underpinnings of Vascular Control
Section titled “Molecular and Cellular Underpinnings of Vascular Control”At the molecular and cellular levels, the regulation of mean arterial pressure relies on a diverse array of critical proteins, enzymes, receptors, and signaling pathways that control vascular tone and fluid homeostasis. Vascular smooth muscle cells, for instance, express various receptors that respond to circulating hormones and neurotransmitters, leading to contraction or relaxation and thus modulating arterial diameter and peripheral resistance. Key biomolecules involved include angiotensin-converting enzyme (ACE) and its product angiotensin II, which is a potent vasoconstrictor and stimulates aldosterone release, impacting both vascular resistance and blood volume[9].
Cellular functions such as ion transport across kidney tubule cells are also crucial for maintaining blood volume and, consequently, MAP. Genes involved in renal salt handling, which encode transporters and channels responsible for reabsorbing sodium and water, directly influence blood pressure variation [10]. Furthermore, the structural integrity and elasticity of arterial walls are maintained by extracellular matrix components, such as collagen. For example, variations in genes like COL4A1, which encodes a component of type IV collagen, are associated with arterial stiffness, a factor that contributes to altered blood pressure dynamics [11]. These molecular and cellular processes collectively dictate the mechanical properties of blood vessels and the body’s fluid balance, both of which are central to MAP regulation.
Genetic Architecture of Mean Arterial Pressure
Section titled “Genetic Architecture of Mean Arterial Pressure”Genetic mechanisms play a significant role in determining an individual’s mean arterial pressure, with numerous common genetic variants contributing to its variation within the general population. Genome-wide association studies (GWAS) have been instrumental in identifying multiple genetic loci associated with blood pressure phenotypes, including MAP[2]. These studies analyze common genetic variants across the entire human genome to uncover associations without prior assumptions about biological pathways [2]. The heritability of blood pressure and arterial stiffness phenotypes underscores the substantial genetic influence on these traits [2].
Several genes and regulatory elements have been implicated through these genetic investigations. For instance, haplotypes of the WNK1 gene have been found to associate with blood pressure variation, particularly in hypertensive populations [12]. While rare mutations are known to cause Mendelian forms of blood pressure disorders, common variants, often with small individual effects, collectively account for a greater proportion of blood pressure variation in the broader population [2]. The identification of these genetic regions provides insights into novel biological pathways and regulatory networks that contribute to the complex inheritance of MAP.
Pathophysiological Consequences and Clinical Relevance
Section titled “Pathophysiological Consequences and Clinical Relevance”Disruptions in the homeostatic regulation of mean arterial pressure are central to several pathophysiological processes, most notably hypertension, a major global health burden. Hypertension is defined by persistently elevated blood pressure, often exceeding 140/90 mm Hg, and is a significant risk factor for cardiovascular diseases[3]. Elevated MAP, along with systolic and diastolic blood pressure, serves as a strong predictor of cardiovascular disease risk[1]. The long-term consequences of uncontrolled hypertension include damage to various organs, such as the heart, kidneys, and brain.
Arterial stiffness, a condition where arteries lose their elasticity and become rigid, is a closely related pathophysiological process that significantly impacts MAP and cardiovascular risk, especially in older patients [13]. Stiffer arteries contribute to increased pulse pressure and can lead to higher MAP, placing greater strain on the heart and vasculature. The body often exhibits compensatory responses to these disruptions, such as cardiac hypertrophy or renal adjustments to fluid balance, but prolonged stress can overwhelm these mechanisms, leading to progressive organ damage and the development of severe vascular diseases [5]. Understanding these interconnected processes is crucial for effective prevention and treatment strategies for hypertension and its associated morbidities.
Mean arterial pressure (MAP) is a critical physiological parameter, reflecting the average pressure in a person’s arteries during one cardiac cycle. Its maintenance involves complex interplay across various biological pathways and regulatory mechanisms, influenced significantly by genetic factors. Research has identified multiple genetic loci associated with blood pressure, hypertension, and MAP itself, pointing to the molecular underpinnings of its regulation .
Prognostic Significance and Cardiovascular Risk Stratification
Section titled “Prognostic Significance and Cardiovascular Risk Stratification”Mean arterial pressure provides independent prognostic information, particularly in patients with specific cardiovascular conditions such as left ventricular dysfunction[14]. It serves as a vital indicator, alongside systolic and diastolic blood pressure, in the comprehensive prediction of cardiovascular disease risk[8]. Extensive meta-analyses involving a vast number of adults have highlighted the age-specific relevance of usual blood pressure, including the steady component represented by MAP, to vascular mortality, underscoring its long-term implications for patient health[15].
The value of MAP is also significant in risk stratification, aiding clinicians in identifying individuals at higher risk for adverse cardiovascular events and disease progression. Understanding the interplay between the steady (MAP) and pulsatile components of blood pressure is crucial for a complete assessment of cardiovascular mortality risk[16]. Emerging genetic studies, including genome-wide association studies, are uncovering specific genetic loci that influence MAP, paving the way for more personalized risk assessment and the development of targeted prevention strategies [1].
Diagnostic Utility and Guiding Treatment Strategies
Section titled “Diagnostic Utility and Guiding Treatment Strategies”Mean arterial pressure is a fundamental physiological parameter routinely measured and utilized in clinical practice for diagnostic purposes and for informing therapeutic interventions. As it represents the overall systemic perfusion pressure, MAP provides critical insights into the adequacy of blood flow to vital organs[2]. Its measurement is an integral part of the initial assessment of blood pressure phenotypes in a wide range of clinical scenarios, from routine check-ups to acute care settings.
In the management of hypertension and other cardiovascular conditions, a thorough understanding of MAP contributes to comprehensive blood pressure assessment, which is essential for selecting appropriate treatments and designing effective monitoring strategies. While specific MAP-targeted therapies are not explicitly detailed in all contexts, the broader evidence supporting blood pressure-lowering drugs to reduce major cardiovascular events underscores the importance of managing all blood pressure components, including MAP, for optimal patient outcomes[17], [18]. Regular monitoring of MAP, in conjunction with other blood pressure parameters, allows clinicians to evaluate treatment efficacy and make necessary adjustments to achieve desired hemodynamic targets.
Associations with Arterial Stiffness and Comorbidities
Section titled “Associations with Arterial Stiffness and Comorbidities”Mean arterial pressure is intrinsically linked to arterial stiffness, a significant marker of vascular health and a predictor of cardiovascular events. Research, including that from the Framingham Heart Study, has explored genome-wide associations between blood pressure phenotypes and arterial stiffness, emphasizing their interconnectedness[2], [11]. Elevated arterial stiffness, as indicated by measures such as aortic pulse wave velocity, independently predicts cardiovascular events, suggesting that conditions influencing MAP often have broader implications for the structural and functional integrity of the vasculature [19], [20].
Furthermore, MAP is closely associated with prevalent comorbidities, most notably hypertension, which is clinically defined by elevated systolic or diastolic blood pressure or the use of antihypertensive medication[3]. The complex interplay between MAP, large-artery stiffness, and hypertension significantly escalates overall cardiovascular risk, particularly in aging populations[13]. Ongoing genetic studies continue to identify novel loci that influence both blood pressure and cardiovascular disease risk, thereby elucidating shared biological pathways and potential overlapping phenotypes that are critical for understanding the pathophysiology and improving the clinical management of these conditions[7].
Key Variants
Section titled “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 |
Frequently Asked Questions About Mean Arterial Pressure
Section titled “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.
1. My parents have high blood pressure; will I definitely get it too?
Section titled “1. My parents have high blood pressure; will I definitely get it too?”While genetic factors significantly influence mean arterial pressure, it’s not a guarantee. You might inherit a predisposition from your family, but many genes contribute, each with a small effect. Your individual risk depends on a complex interplay between these genetic factors and your lifestyle choices.
2. I’m not European; does my ethnic background affect my MAP risk?
Section titled “2. I’m not European; does my ethnic background affect my MAP risk?”Yes, it can. Many foundational genetic studies on blood pressure have predominantly focused on populations of European descent. This means that genetic risk factors identified may not exert the same influence or even be present with similar allele frequencies in other ethnic groups, like Hispanic populations, highlighting the need for broader research.
3. Can eating healthy and exercising truly overcome my family’s MAP history?
Section titled “3. Can eating healthy and exercising truly overcome my family’s MAP history?”Lifestyle factors like dietary sodium and potassium intake, alcohol consumption, and regular exercise are very powerful influences on mean arterial pressure. While you might have a genetic predisposition, a healthy lifestyle can significantly mitigate these risks and help maintain your MAP within a healthy range, even with a family history.
4. My MAP is only slightly high; is that really a big deal for me?
Section titled “4. My MAP is only slightly high; is that really a big deal for me?”Even small genetic influences on mean arterial pressure, when combined, can contribute to your overall risk over time. While a single genetic variant might alter MAP by an amount difficult to detect individually, the aggregate impact of many genetic and environmental factors can increase your long-term risk for cardiovascular issues.
5. Does stress or just getting older always make my MAP worse?
Section titled “5. Does stress or just getting older always make my MAP worse?”Mean arterial pressure is a dynamic biological characteristic influenced by numerous physiological processes. While age is a known factor that can influence blood pressure, and stress can cause temporary spikes, it’s not a definite outcome. Your body’s genetic makeup and other lifestyle choices interact with these factors.
6. If I take blood pressure medication, does that hide my true genetic MAP risk?
Section titled “6. If I take blood pressure medication, does that hide my true genetic MAP risk?”Medications effectively lower your blood pressure to help manage health, but they don’t change your underlying genetic predisposition. While your observed MAP will be lower on medication, understanding your genetic risk factors can still be valuable for a more complete picture of your long-term health profile.
7. My doctor’s MAP reading was different last time; is it even reliable?
Section titled “7. My doctor’s MAP reading was different last time; is it even reliable?”Blood pressure measurements, including mean arterial pressure, naturally carry some inherent variability. Factors like the time of day, your activity level, or even slight differences in measurement technique can cause readings to fluctuate. Doctors often look at trends over multiple readings rather than relying on a single measurement.
8. My sibling has lower MAP than me, even though we live similar lives; why the difference?
Section titled “8. My sibling has lower MAP than me, even though we live similar lives; why the difference?”Even within families, individual genetic variations contribute significantly to differences in mean arterial pressure. While you share many genes, unique combinations of genetic variants, along with subtle differences in lifestyle or environmental exposures, can explain why your MAP differs from your sibling’s.
9. Does cutting out salt really help my MAP if genetics are involved?
Section titled “9. Does cutting out salt really help my MAP if genetics are involved?”Yes, absolutely. Dietary factors like sodium intake are known environmental contributors to mean arterial pressure. Even if you have genetic predispositions that make you more susceptible, reducing salt can still have a positive impact on your MAP by influencing how your body regulates blood volume and pressure.
10. Knowing my family’s history, what can I do to protect my MAP from getting too high?
Section titled “10. Knowing my family’s history, what can I do to protect my MAP from getting too high?”Understanding your family history is a great first step. Focus on a heart-healthy lifestyle: regular exercise, a balanced diet low in sodium and high in potassium, maintaining a healthy weight, and managing stress effectively. These actions can significantly influence your mean arterial pressure, regardless of inherited predispositions.
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
Section titled “References”[1] Wain, L. V., et al. “Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.”Nat Genet, 2011.
[2] Levy, D. et al. “Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness.” BMC Medical Genetics, vol. 8, suppl. 1, 2007, p. S3.
[3] Levy, D. et al. “Genome-wide association study of blood pressure and hypertension.”Nature Genetics, vol. 41, no. 6, 2009, pp. 677-687.
[4] Newton-Cheh, C., et al. “Genome-wide association study identifies eight loci associated with blood pressure.” Nat Genet, 2009.
[5] Ganesh, S. K. et al. “Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.” Nature Genetics, vol. 41, no. 12, 2009, pp. 1191-1198.
[6] Kraja, A. T., et al. “A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium.” Diabetes, vol. 60, no. 5, 2011, pp. 1629-39.
[7] Ehret, G. B., et al. “Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.”Nature, 2011.
[8] 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. 801–07.
[9] Lifton, R. P., A. G. Gharavi, and D. S. Geller. “Molecular mechanisms of human hypertension.”Cell, vol. 104, no. 4, 2001, pp. 545–56.
[10] Ji, W., et al. “Rare independent mutations in renal salt handling genes contribute to blood pressure variation.” Nature Genetics, vol. 40, no. 5, 2008, pp. 592–99.
[11] Tarasov, K. V., et al. “COL4A1 is associated with arterial stiffness by genome-wide association scan.” Circ Cardiovasc Genet, 2010.
[12] Newhouse, S. J., et al. “Haplotypes of the WNK1 gene associate with blood pressure variation in a severely hypertensive population from the British Genetics of Hypertension study.”Human Molecular Genetics, vol. 14, no. 13, 2005, pp. 1805–14.
[13] Blacher, J., and M. E. Safar. “Large-artery stiffness, hypertension and cardiovascular risk in older patients.”Nature Clinical Practice Cardiovascular Medicine, vol. 2, no. 9, 2005, pp. 450–55.
[14] Domanski, Michael J., et al. “Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction.”J Am Coll Cardiol, vol. 33, no. 4, 1999, pp. 951–8.
[15] Lewington, Sarah, et al. “Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.”Lancet, vol. 360, no. 9349, 2002, pp. 1903–13.
[16] Darne, B., et al. “Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis on cardiovascular mortality.”Hypertension, vol. 13, no. 4, 1989, pp. 392–400.
[17] Turnbull, Fiona, et al. “Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials.” BMJ, vol. 336, no. 7653, 2008, pp. 1121–3.
[18] Law, Malcolm R., et al. “Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies.”BMJ, vol. 338, 2009, b1665.
[19] Sutton-Tyrrell, Kathleen, et al. “Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults.” Circulation, vol. 111, no. 25, 2005, pp. 3384–90.
[20] Willum-Hansen, Thorkild, et al. “Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population.” Circulation, vol. 113, no. 5, 2006, pp. 664–70.