Lifestyle management of hypertension : International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension
- Charchar, Fadi, Prestes, Priscilla, Mills, Charlotte, Ching, Siew, Neupane, Dinesh, Marques, Francine, Sharman, James, Vogt, Liffert, Burrell, Louise, Korostovtseva, Lyudmila, Zec, Manja, Patil, Mansi, Schultz, Martin, Wallen, Matthew, Renna, Nicolás, Islam, Sheikh, Hiremath, Swapnil, Gyeltshen, Tshewang, Chia, Yook-Chin, Gupta, Abhinav, Schutte, Aletta, Klein, Britt, Borghi, Claudio, Browning, Colette, Czesnikiewicz-Guzik, Marta, Lee, Hae-Young, Itoh, Hiroshi, Miura, Katsuyuki, Akinnibosun, Olutope, Shane Thomas
- Authors: Charchar, Fadi , Prestes, Priscilla , Mills, Charlotte , Ching, Siew , Neupane, Dinesh , Marques, Francine , Sharman, James , Vogt, Liffert , Burrell, Louise , Korostovtseva, Lyudmila , Zec, Manja , Patil, Mansi , Schultz, Martin , Wallen, Matthew , Renna, Nicolás , Islam, Sheikh , Hiremath, Swapnil , Gyeltshen, Tshewang , Chia, Yook-Chin , Gupta, Abhinav , Schutte, Aletta , Klein, Britt , Borghi, Claudio , Browning, Colette , Czesnikiewicz-Guzik, Marta , Lee, Hae-Young , Itoh, Hiroshi , Miura, Katsuyuki , Akinnibosun, Olutope , Shane Thomas
- Date: 2024
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 42, no. 1 (2024), p. 23-49
- Full Text:
- Reviewed:
- Description: Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliates “Fadi Charchar, Priscilla Prestes, Britt Klein, Colette Browning, Olutope Akinnibosun and Shane Thomas” are provided in this record**
- Description: Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliates “Fadi Charchar, Priscilla Prestes, Britt Klein, Colette Browning, Olutope Akinnibossun and Shane Thomas” are provided in this record**
- Authors: Charchar, Fadi , Prestes, Priscilla , Mills, Charlotte , Ching, Siew , Neupane, Dinesh , Marques, Francine , Sharman, James , Vogt, Liffert , Burrell, Louise , Korostovtseva, Lyudmila , Zec, Manja , Patil, Mansi , Schultz, Martin , Wallen, Matthew , Renna, Nicolás , Islam, Sheikh , Hiremath, Swapnil , Gyeltshen, Tshewang , Chia, Yook-Chin , Gupta, Abhinav , Schutte, Aletta , Klein, Britt , Borghi, Claudio , Browning, Colette , Czesnikiewicz-Guzik, Marta , Lee, Hae-Young , Itoh, Hiroshi , Miura, Katsuyuki , Akinnibosun, Olutope , Shane Thomas
- Date: 2024
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 42, no. 1 (2024), p. 23-49
- Full Text:
- Reviewed:
- Description: Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliates “Fadi Charchar, Priscilla Prestes, Britt Klein, Colette Browning, Olutope Akinnibosun and Shane Thomas” are provided in this record**
- Description: Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliates “Fadi Charchar, Priscilla Prestes, Britt Klein, Colette Browning, Olutope Akinnibossun and Shane Thomas” are provided in this record**
Kidney omics in hypertension: from statistical associations to biological mechanisms and clinical applications
- Tomaszewski, Maciej, Morris, Andrew, Howson, Joanna, Franceschini, Nora, Eales, James, Xu, Xiaoguang, Dikalov, Sergey, Guzik, Tomasz, Humphreys, Benjamin, Harrap, Stephen, Charchar, Fadi
- Authors: Tomaszewski, Maciej , Morris, Andrew , Howson, Joanna , Franceschini, Nora , Eales, James , Xu, Xiaoguang , Dikalov, Sergey , Guzik, Tomasz , Humphreys, Benjamin , Harrap, Stephen , Charchar, Fadi
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Kidney International Vol. 102, no. 3 (2022), p. 492-505
- Full Text:
- Reviewed:
- Description: Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage. © 2022 International Society of Nephrology
- Authors: Tomaszewski, Maciej , Morris, Andrew , Howson, Joanna , Franceschini, Nora , Eales, James , Xu, Xiaoguang , Dikalov, Sergey , Guzik, Tomasz , Humphreys, Benjamin , Harrap, Stephen , Charchar, Fadi
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Kidney International Vol. 102, no. 3 (2022), p. 492-505
- Full Text:
- Reviewed:
- Description: Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage. © 2022 International Society of Nephrology
Stage 1 hypertension and risk of cardiovascular disease mortality in United States adults with or without diabetes
- Authors: Wang, Yutang
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 40, no. 4 (2022), p. 794-803
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
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- Description: Objective: This study aimed to investigate the association of S1 hypertension, classified according to the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline, with cardiovascular disease (CVD) mortality in adults with or without diabetes from the general United States population.Methods:This cohort study included 40 518 United States adults (including 3555 with diabetes) naive to antihypertensive drugs who attended the National Health and Nutrition Examination Surveys from 1988 to 2014.Results:Participants were followed up for 489 679 person-years (mean follow-up, 12.1 years) with 1569 CVD deaths being recorded. S1 hypertension was neither associated with an increased CVD mortality risk in the whole cohort nor in participants with or without diabetes after full adjustment. In age-stratified analyses, compared with normal BP, S1 hypertension was associated with increased CVD mortality in young adults, unrelated to CVD mortality in midlife, and associated with lower CVD mortality in the elderly. In older participants (
- Authors: Wang, Yutang
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 40, no. 4 (2022), p. 794-803
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Objective: This study aimed to investigate the association of S1 hypertension, classified according to the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline, with cardiovascular disease (CVD) mortality in adults with or without diabetes from the general United States population.Methods:This cohort study included 40 518 United States adults (including 3555 with diabetes) naive to antihypertensive drugs who attended the National Health and Nutrition Examination Surveys from 1988 to 2014.Results:Participants were followed up for 489 679 person-years (mean follow-up, 12.1 years) with 1569 CVD deaths being recorded. S1 hypertension was neither associated with an increased CVD mortality risk in the whole cohort nor in participants with or without diabetes after full adjustment. In age-stratified analyses, compared with normal BP, S1 hypertension was associated with increased CVD mortality in young adults, unrelated to CVD mortality in midlife, and associated with lower CVD mortality in the elderly. In older participants (
Deficiency of MicroRNA-181a results in transcriptome-wide cell-specific changes in the kidney and increases blood pressure
- Paterson, Madeleine, Jackson, Kristy, Dona, Malathi, Farrugia, Gabriella, Visniauskas, Bruna, Watson, Anna, Johnson, Chad, Prieto, Minolfa, Evans, Roger, Charchar, Fadi, Pinto, Alexander, Marques, Francine, Head, Geoffrey
- Authors: Paterson, Madeleine , Jackson, Kristy , Dona, Malathi , Farrugia, Gabriella , Visniauskas, Bruna , Watson, Anna , Johnson, Chad , Prieto, Minolfa , Evans, Roger , Charchar, Fadi , Pinto, Alexander , Marques, Francine , Head, Geoffrey
- Date: 2021
- Type: Text , Journal article
- Relation: Hypertension Vol. 78, no. 5 (Nov 2021), p. 1322-1334
- Full Text:
- Reviewed:
- Description: MicroRNA miR-181a is downregulated in the kidneys of hypertensive patients and hypertensive mice. In vitro, miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here, we determined whether deletion of miR-181a/b-1 in vivo changes BP and the molecular mechanisms involved at the single-cell level. We developed a KO (knockout) mouse model lacking miR-181a/b-1 genes using CRISPR/Cas9 technology. Radiotelemetry probes were implanted in 12-week-old C57BL/6J WT (wild type) and miR-181a/b-1 KO mice. Systolic and diastolic BP were 4- to 5-mm Hg higher in KO compared with WT mice over 24 hours (P<0.01). Compared with WT mice, renal renin was higher in the juxtaglomerular cells of KO mice. BP was similar in WT mice on a high- (3.1%) versus low- (0.3%) sodium diet (+0.4 +/- 0.8 mm Hg), but KO mice showed salt sensitivity (+3.3 +/- 0.8 mm Hg; P<0.001). Since microRNAs can target several mRNAs simultaneously, we performed single-nuclei RNA sequencing in 6699 renal cells. We identified 12 distinct types of renal cells, all of which had genes that were dysregulated. This included genes involved in renal fibrosis and inflammation such as Stat4, Col4a1, Cd81, Flt3l, Cxcl16, and Smad4. We observed upregulation of pathways related to the immune system, inflammatory response, reactive oxygen species, and nerve development, consistent with higher tyrosine hydroxylase in the kidney. In conclusion, downregulation of the miR-181a gene led to increased BP and salt sensitivity in mice. This is likely due to an increase in renin expression in juxtaglomerular cells, as well as microRNA-driven pleiotropic effects impacting renal pathways associated with hypertension.
- Authors: Paterson, Madeleine , Jackson, Kristy , Dona, Malathi , Farrugia, Gabriella , Visniauskas, Bruna , Watson, Anna , Johnson, Chad , Prieto, Minolfa , Evans, Roger , Charchar, Fadi , Pinto, Alexander , Marques, Francine , Head, Geoffrey
- Date: 2021
- Type: Text , Journal article
- Relation: Hypertension Vol. 78, no. 5 (Nov 2021), p. 1322-1334
- Full Text:
- Reviewed:
- Description: MicroRNA miR-181a is downregulated in the kidneys of hypertensive patients and hypertensive mice. In vitro, miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here, we determined whether deletion of miR-181a/b-1 in vivo changes BP and the molecular mechanisms involved at the single-cell level. We developed a KO (knockout) mouse model lacking miR-181a/b-1 genes using CRISPR/Cas9 technology. Radiotelemetry probes were implanted in 12-week-old C57BL/6J WT (wild type) and miR-181a/b-1 KO mice. Systolic and diastolic BP were 4- to 5-mm Hg higher in KO compared with WT mice over 24 hours (P<0.01). Compared with WT mice, renal renin was higher in the juxtaglomerular cells of KO mice. BP was similar in WT mice on a high- (3.1%) versus low- (0.3%) sodium diet (+0.4 +/- 0.8 mm Hg), but KO mice showed salt sensitivity (+3.3 +/- 0.8 mm Hg; P<0.001). Since microRNAs can target several mRNAs simultaneously, we performed single-nuclei RNA sequencing in 6699 renal cells. We identified 12 distinct types of renal cells, all of which had genes that were dysregulated. This included genes involved in renal fibrosis and inflammation such as Stat4, Col4a1, Cd81, Flt3l, Cxcl16, and Smad4. We observed upregulation of pathways related to the immune system, inflammatory response, reactive oxygen species, and nerve development, consistent with higher tyrosine hydroxylase in the kidney. In conclusion, downregulation of the miR-181a gene led to increased BP and salt sensitivity in mice. This is likely due to an increase in renin expression in juxtaglomerular cells, as well as microRNA-driven pleiotropic effects impacting renal pathways associated with hypertension.
May measurement month 2019 the global blood pressure screening campaign of the International Society of Hypertension
- Beaney, Thomas, Schutte, Aletta, Stergiou, George, Borghi, Claudio, Burger, Dylan, Charchar, Fadi, Cro, Suzie, Diaz, Alejandro, Damasceno, Albertino, Espeche, Walter, Jose, Arun, Khan, Nadia, Kokubo, Yoshihiro, Maheshwari, Anuj, Marin, Marcos, More, Arun, Neupane, Dinesh, Nilsson, Peter, Patil, Mansi, Prabhakaran, Dorairaj, Ramirez, Agustin, Rodriguez, Pablo, Schlaich, Markus, Steckelings, Ulrike, Tomaszewski, Maciej, Unger, Thomas, Wainford, Richard, Wang, Jiguang, Williams, Bryan, Poulter, Neil, M. M. M. Investigators
- Authors: Beaney, Thomas , Schutte, Aletta , Stergiou, George , Borghi, Claudio , Burger, Dylan , Charchar, Fadi , Cro, Suzie , Diaz, Alejandro , Damasceno, Albertino , Espeche, Walter , Jose, Arun , Khan, Nadia , Kokubo, Yoshihiro , Maheshwari, Anuj , Marin, Marcos , More, Arun , Neupane, Dinesh , Nilsson, Peter , Patil, Mansi , Prabhakaran, Dorairaj , Ramirez, Agustin , Rodriguez, Pablo , Schlaich, Markus , Steckelings, Ulrike , Tomaszewski, Maciej , Unger, Thomas , Wainford, Richard , Wang, Jiguang , Williams, Bryan , Poulter, Neil , M. M. M. Investigators
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Vol. 76, no. 2 (Aug 2020), p. 333-341
- Full Text:
- Reviewed:
- Description: Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (>= 18 years) recruited through opportunistic sampling were screened at sites in 92 countries during May 2019. Ideally, 3 blood pressure readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic blood pressure >= 140 mm Hg, or a diastolic blood pressure >= 90 mm Hg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants' mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1 508 130 screenees 482 273 (32.0%) had never had a blood pressure measurement before and 513 337 (34.0%) had hypertension, of whom 58.7% were aware, and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to <140/90 mm Hg, and 28.9% to <130/80 mm Hg. Of all those with hypertension, 31.7% were controlled to <140/90 mm Hg, and 350 825 (23.3%) participants had untreated or inadequately treated hypertension. Of those taking antihypertensive medication, half were taking only a single drug, and 25% reported using aspirin inappropriately. This survey is the largest ever synchronized and standardized contemporary compilation of global blood pressure data. This campaign is needed as a temporary substitute for systematic blood pressure screening in many countries worldwide.
- Authors: Beaney, Thomas , Schutte, Aletta , Stergiou, George , Borghi, Claudio , Burger, Dylan , Charchar, Fadi , Cro, Suzie , Diaz, Alejandro , Damasceno, Albertino , Espeche, Walter , Jose, Arun , Khan, Nadia , Kokubo, Yoshihiro , Maheshwari, Anuj , Marin, Marcos , More, Arun , Neupane, Dinesh , Nilsson, Peter , Patil, Mansi , Prabhakaran, Dorairaj , Ramirez, Agustin , Rodriguez, Pablo , Schlaich, Markus , Steckelings, Ulrike , Tomaszewski, Maciej , Unger, Thomas , Wainford, Richard , Wang, Jiguang , Williams, Bryan , Poulter, Neil , M. M. M. Investigators
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Vol. 76, no. 2 (Aug 2020), p. 333-341
- Full Text:
- Reviewed:
- Description: Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (>= 18 years) recruited through opportunistic sampling were screened at sites in 92 countries during May 2019. Ideally, 3 blood pressure readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic blood pressure >= 140 mm Hg, or a diastolic blood pressure >= 90 mm Hg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants' mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1 508 130 screenees 482 273 (32.0%) had never had a blood pressure measurement before and 513 337 (34.0%) had hypertension, of whom 58.7% were aware, and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to <140/90 mm Hg, and 28.9% to <130/80 mm Hg. Of all those with hypertension, 31.7% were controlled to <140/90 mm Hg, and 350 825 (23.3%) participants had untreated or inadequately treated hypertension. Of those taking antihypertensive medication, half were taking only a single drug, and 25% reported using aspirin inappropriately. This survey is the largest ever synchronized and standardized contemporary compilation of global blood pressure data. This campaign is needed as a temporary substitute for systematic blood pressure screening in many countries worldwide.
May measurement month 2018 : A pragmatic global screening campaign to raise awareness of blood pressure by the international society of hypertension
- Beaney, Thomas, Burrell, Louise, Castillo, Rafael, Charchar, Fadi, Cro, Suzie, Damasceno, Albertino, Kruger, Ruan, Nilsson, Peter, Prabhakaran, Dorairaj, Ramirez, Agustin, Schlaich, Markus, Schutte, Aletta, Tomaszewski, Maciej, Touyz, Rhian, Wang, Ji-Guang, Weber, Michael, Poulter, Neil
- Authors: Beaney, Thomas , Burrell, Louise , Castillo, Rafael , Charchar, Fadi , Cro, Suzie , Damasceno, Albertino , Kruger, Ruan , Nilsson, Peter , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Schutte, Aletta , Tomaszewski, Maciej , Touyz, Rhian , Wang, Ji-Guang , Weber, Michael , Poulter, Neil
- Date: 2019
- Type: Text , Journal article , Review
- Relation: European Heart Journal Vol. 40, no. 25 (2019), p. 2006-2017
- Full Text:
- Reviewed:
- Description: Aims: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.
- Authors: Beaney, Thomas , Burrell, Louise , Castillo, Rafael , Charchar, Fadi , Cro, Suzie , Damasceno, Albertino , Kruger, Ruan , Nilsson, Peter , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Schutte, Aletta , Tomaszewski, Maciej , Touyz, Rhian , Wang, Ji-Guang , Weber, Michael , Poulter, Neil
- Date: 2019
- Type: Text , Journal article , Review
- Relation: European Heart Journal Vol. 40, no. 25 (2019), p. 2006-2017
- Full Text:
- Reviewed:
- Description: Aims: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.
Singlet molecular oxygen regulates vascular tone and blood pressure in inflammation
- Stanley, Christopher, Maghzal, Ghassan, Ayer, Anita, Talib, Jihan, Giltrap, Andrew, Shengule, Sudhir, Wolhuter, Kathryn, Wang, Yutang, Chadha, Preet, Suarna, Cacang, Prysyazhna, Oleksandra, Scotcher, Jenna, Dunn, Louise, Prado, Fernanda, Nguyen, Nghi, Odiba, Jephthah, Baell, Johathan, Stasch, Johannes-Peter, Yamamoto, Yorihiro, Di Mascio, Paolo, Eaton, Philip, Payne, Richard, Stocker, Roland
- Authors: Stanley, Christopher , Maghzal, Ghassan , Ayer, Anita , Talib, Jihan , Giltrap, Andrew , Shengule, Sudhir , Wolhuter, Kathryn , Wang, Yutang , Chadha, Preet , Suarna, Cacang , Prysyazhna, Oleksandra , Scotcher, Jenna , Dunn, Louise , Prado, Fernanda , Nguyen, Nghi , Odiba, Jephthah , Baell, Johathan , Stasch, Johannes-Peter , Yamamoto, Yorihiro , Di Mascio, Paolo , Eaton, Philip , Payne, Richard , Stocker, Roland
- Date: 2019
- Type: Text , Journal article , Letter
- Relation: Nature Vol. 566, no. 7745 (2019), p. 548-552
- Full Text:
- Reviewed:
- Description: Singlet molecular oxygen (O-1(2)) has well-established roles in photosynthetic plants, bacteria and fungi(1-3), but not in mammals. Chemically generated O-1(2) oxidizes the amino acid tryptophan to precursors of a key metabolite called N-formylkynurenine(4), whereas enzymatic oxidation of tryptophan to N-formylkynurenine is catalysed by a family of dioxygenases, including indoleamine 2,3-dioxygenase 1(5). Under inflammatory conditions, this haem-containing enzyme is expressed in arterial endothelial cells, where it contributes to the regulation of blood pressure(6). However, whether indoleamine 2,3-dioxygenase 1 forms O-1(2) and whether this contributes to blood pressure control have remained unknown. Here we show that arterial indoleamine 2,3-dioxygenase 1 regulates blood pressure via formation of O-1(2). We observed that in the presence of hydrogen peroxide, the enzyme generates O-1(2) and that this is associated with the stereoselective oxidation of L-tryptophan to a tricyclic hydroperoxide via a previously unrecognized oxidative activation of the dioxygenase activity. The tryptophan-derived hydroperoxide acts in vivo as a signalling molecule, inducing arterial relaxation and decreasing blood pressure; this activity is dependent on Cys42 of protein kinase G1 alpha. Our findings demonstrate a pathophysiological role for O-1(2) in mammals through formation of an amino acid-derived hydroperoxide that regulates vascular tone and blood pressure under inflammatory conditions.
- Authors: Stanley, Christopher , Maghzal, Ghassan , Ayer, Anita , Talib, Jihan , Giltrap, Andrew , Shengule, Sudhir , Wolhuter, Kathryn , Wang, Yutang , Chadha, Preet , Suarna, Cacang , Prysyazhna, Oleksandra , Scotcher, Jenna , Dunn, Louise , Prado, Fernanda , Nguyen, Nghi , Odiba, Jephthah , Baell, Johathan , Stasch, Johannes-Peter , Yamamoto, Yorihiro , Di Mascio, Paolo , Eaton, Philip , Payne, Richard , Stocker, Roland
- Date: 2019
- Type: Text , Journal article , Letter
- Relation: Nature Vol. 566, no. 7745 (2019), p. 548-552
- Full Text:
- Reviewed:
- Description: Singlet molecular oxygen (O-1(2)) has well-established roles in photosynthetic plants, bacteria and fungi(1-3), but not in mammals. Chemically generated O-1(2) oxidizes the amino acid tryptophan to precursors of a key metabolite called N-formylkynurenine(4), whereas enzymatic oxidation of tryptophan to N-formylkynurenine is catalysed by a family of dioxygenases, including indoleamine 2,3-dioxygenase 1(5). Under inflammatory conditions, this haem-containing enzyme is expressed in arterial endothelial cells, where it contributes to the regulation of blood pressure(6). However, whether indoleamine 2,3-dioxygenase 1 forms O-1(2) and whether this contributes to blood pressure control have remained unknown. Here we show that arterial indoleamine 2,3-dioxygenase 1 regulates blood pressure via formation of O-1(2). We observed that in the presence of hydrogen peroxide, the enzyme generates O-1(2) and that this is associated with the stereoselective oxidation of L-tryptophan to a tricyclic hydroperoxide via a previously unrecognized oxidative activation of the dioxygenase activity. The tryptophan-derived hydroperoxide acts in vivo as a signalling molecule, inducing arterial relaxation and decreasing blood pressure; this activity is dependent on Cys42 of protein kinase G1 alpha. Our findings demonstrate a pathophysiological role for O-1(2) in mammals through formation of an amino acid-derived hydroperoxide that regulates vascular tone and blood pressure under inflammatory conditions.
Blood pressure response to interrupting workplace sitting time with non-exercise physical activity: Results of a 12-month cohort study
- Mainsbridge, Casey, Ahuja, Kiran, Williams, Andrew, Bird, Marie-Louise, Cooley, Dean, Pedersen, Scott
- Authors: Mainsbridge, Casey , Ahuja, Kiran , Williams, Andrew , Bird, Marie-Louise , Cooley, Dean , Pedersen, Scott
- Date: 2018
- Type: Journal article
- Relation: Journal of Occupational and Environmental Medicine Vol. 60, no. 9 (2018), p. 769-774
- Full Text:
- Reviewed:
- Description: OBJECTIVE:To evaluate the blood pressure (BP) effects of a yearlong e-health solution designed to interrupt prolonged occupational sitting time. METHODS:BP data of 228 desk-based employees (45.1 ± 10.5 years) were analyzed at baseline, 3, 6, 9, and 12 months. RESULTS:Systolic BP significantly reduced from baseline for the first 9 months (1.0 to 3.4 mmHg P < 0.01) while diastolic and mean arterial pressure decreased for the full 12-months (4 to 5 mmHg for diastolic pressure and 3.6 to 4.2 mmHg for MAP all P < 0.01).Participants used the e-health solution 5.5 ± 2.0 times/day in the first 3 months which reduced to 4.2 ± 2.5 times/day by the end of the study (P < 0.05). CONCLUSIONS:An e-health solution designed to increase non-exercise physical activity by interrupting sitting time in the workplace is feasible and produced long-term reductions in blood pressure.
- Authors: Mainsbridge, Casey , Ahuja, Kiran , Williams, Andrew , Bird, Marie-Louise , Cooley, Dean , Pedersen, Scott
- Date: 2018
- Type: Journal article
- Relation: Journal of Occupational and Environmental Medicine Vol. 60, no. 9 (2018), p. 769-774
- Full Text:
- Reviewed:
- Description: OBJECTIVE:To evaluate the blood pressure (BP) effects of a yearlong e-health solution designed to interrupt prolonged occupational sitting time. METHODS:BP data of 228 desk-based employees (45.1 ± 10.5 years) were analyzed at baseline, 3, 6, 9, and 12 months. RESULTS:Systolic BP significantly reduced from baseline for the first 9 months (1.0 to 3.4 mmHg P < 0.01) while diastolic and mean arterial pressure decreased for the full 12-months (4 to 5 mmHg for diastolic pressure and 3.6 to 4.2 mmHg for MAP all P < 0.01).Participants used the e-health solution 5.5 ± 2.0 times/day in the first 3 months which reduced to 4.2 ± 2.5 times/day by the end of the study (P < 0.05). CONCLUSIONS:An e-health solution designed to increase non-exercise physical activity by interrupting sitting time in the workplace is feasible and produced long-term reductions in blood pressure.
Epigenetic modifications in essential hypertension
- Authors: Wise, Ingrid
- Date: 2018
- Type: Text , Thesis , PhD
- Full Text:
- Description: Background: Hypertension (HTN) is a complex, multifactorial, quantitative trait under polygenic control that affects more than one billion people globally. Despite advances in our understanding of the pathophysiology of HTN and the implementation of more effective treatment and prevention strategies, HTN remains one of the world’s great public health problems. The accepted inference from genome-wide association studies (GWAS) is that the genetic code lays the foundation for transcriptomic changes and in turn physiological change. On the other side of the coin, environmental factors (smoking, diet, chemical exposure) can in turn affect DNA itself in genes relevant to blood pressure (BP). Variation in epigenetic forms of modification may thus explain additional phenotypic variation in BP and provide new clues to the physiological processes influencing its regulation. DNA methylation is one of these epigenetic mechanisms responsible for changes to gene expression, activated by interaction with environmental triggers. DNA methylation is a reversible epigenetic modifier of specific dinucleotide sites called CpGs, which consists of a transfer of a methyl group derived from S-adenosyl-L-methionine to position five of a cytosine ring, forming 5mC. Pathophysiologically, the kidney is known as the key organ of BP regulation and one of the most important contributors to HTN. According to the hypothesis put forward by Guyton, over 40 years ago, the control of BP in the steady-state and longer-term is critically dependent on renal mechanisms. In fact, almost all monogenic forms of HTN are driven by rare mutations in genes involved in salt handling in the distal nephron. It is therefore crucial to understand kidney DNA methylation changes that may drive gene expression in kidney and lead to HTN. Hypothesis: The central hypothesis underpinning this PhD thesis is that alterations in kidney specific DNA methylation plays a fundamental role in modulating gene expression changes involved in the regulation of BP and pathophysiology of EH. Aims: This PhD thesis focuses on characterising the role of DNA methylation in the hypertensive kidney using array and RNA-sequencing methods. Three major aims are addressed: • Aim 1: To characterise blood and kidney global DNA methylation dynamics and its functional role in the hypertensive population (Chapter 3). • Aim 2: To determine the role of genome-wide, loci specific DNA methylation in the hypertensive human kidney (Chapter 4). • Aim 3: To understand the relationship between DNA methylation and differential expression of genes associated with BP and HTN in the human kidney (Chapter 5). Results: In Aim 1 global DNA methylation changes were characterised in peripheral blood leukocyte and kidney DNA of the hypertensive (HT) population using he ELISA method. We found no association between HTN diagnosis and global methylation percentage in either peripheral blood leukocytes or kidney DNA. However, a negative correlation was found between global methylation and diastolic blood pressure (DBP), yet this relationship was not evident after adjustment for the effect of antihypertensive medication. Furthermore, we investigated the sensitivity of ELISA-based global methylation detection by calculating the percentage of global methylation in kidney using array based methods; the results were similar, demonstrating no association between HTN diagnosis and median kidney methylation
- Description: Doctor of Philosophy
- Authors: Wise, Ingrid
- Date: 2018
- Type: Text , Thesis , PhD
- Full Text:
- Description: Background: Hypertension (HTN) is a complex, multifactorial, quantitative trait under polygenic control that affects more than one billion people globally. Despite advances in our understanding of the pathophysiology of HTN and the implementation of more effective treatment and prevention strategies, HTN remains one of the world’s great public health problems. The accepted inference from genome-wide association studies (GWAS) is that the genetic code lays the foundation for transcriptomic changes and in turn physiological change. On the other side of the coin, environmental factors (smoking, diet, chemical exposure) can in turn affect DNA itself in genes relevant to blood pressure (BP). Variation in epigenetic forms of modification may thus explain additional phenotypic variation in BP and provide new clues to the physiological processes influencing its regulation. DNA methylation is one of these epigenetic mechanisms responsible for changes to gene expression, activated by interaction with environmental triggers. DNA methylation is a reversible epigenetic modifier of specific dinucleotide sites called CpGs, which consists of a transfer of a methyl group derived from S-adenosyl-L-methionine to position five of a cytosine ring, forming 5mC. Pathophysiologically, the kidney is known as the key organ of BP regulation and one of the most important contributors to HTN. According to the hypothesis put forward by Guyton, over 40 years ago, the control of BP in the steady-state and longer-term is critically dependent on renal mechanisms. In fact, almost all monogenic forms of HTN are driven by rare mutations in genes involved in salt handling in the distal nephron. It is therefore crucial to understand kidney DNA methylation changes that may drive gene expression in kidney and lead to HTN. Hypothesis: The central hypothesis underpinning this PhD thesis is that alterations in kidney specific DNA methylation plays a fundamental role in modulating gene expression changes involved in the regulation of BP and pathophysiology of EH. Aims: This PhD thesis focuses on characterising the role of DNA methylation in the hypertensive kidney using array and RNA-sequencing methods. Three major aims are addressed: • Aim 1: To characterise blood and kidney global DNA methylation dynamics and its functional role in the hypertensive population (Chapter 3). • Aim 2: To determine the role of genome-wide, loci specific DNA methylation in the hypertensive human kidney (Chapter 4). • Aim 3: To understand the relationship between DNA methylation and differential expression of genes associated with BP and HTN in the human kidney (Chapter 5). Results: In Aim 1 global DNA methylation changes were characterised in peripheral blood leukocyte and kidney DNA of the hypertensive (HT) population using he ELISA method. We found no association between HTN diagnosis and global methylation percentage in either peripheral blood leukocytes or kidney DNA. However, a negative correlation was found between global methylation and diastolic blood pressure (DBP), yet this relationship was not evident after adjustment for the effect of antihypertensive medication. Furthermore, we investigated the sensitivity of ELISA-based global methylation detection by calculating the percentage of global methylation in kidney using array based methods; the results were similar, demonstrating no association between HTN diagnosis and median kidney methylation
- Description: Doctor of Philosophy
Genetics of blood pressure : Time to curate the collection
- Harrap, Stephen, Charchar, Fadi
- Authors: Harrap, Stephen , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article , Editorial
- Relation: Journal of Hypertension Vol. 35, no. 7 (2017), p. 1360-1362
- Full Text: false
- Reviewed:
- Description: The genetics of blood pressure (BP) is all about discovery and understanding, but it is certainly not for the faint hearted. Despite heroic effort, the question we posed nearly 15 years ago [1] regarding the whereabouts of BP genes remains largely unanswered.
High intensity interval training (HIIT) improves resting blood pressure, metabolic (MET) capacity and heart rate reserve without compromising resting myocardial function in sedentary aging men
- Grace, Fergal, Herbert, Peter, Elliott, Adrian, Beaumont, Alexander, Richards, Jo, Sculthorpe, Nicholas
- Authors: Grace, Fergal , Herbert, Peter , Elliott, Adrian , Beaumont, Alexander , Richards, Jo , Sculthorpe, Nicholas
- Date: 2017
- Type: Text , Journal article
- Relation: Experimental Gerontology Vol.109, no. (2018), p.75-81
- Full Text:
- Reviewed:
- Description: Background This study examined a programme of pre-conditioning exercise with subsequent high intensity interval training (HIIT) on blood pressure, echocardiography, cardiac strain mechanics and maximal metabolic (MET) capacity in sedentary (SED) aging men compared with age matched masters athletes (LEX). Methods Using a STROBE compliant observational design, 39 aging male participants (SED; n = 22, aged 62.7 ± 5.2 yrs) (LEX; n = 17, aged = 61.1 ± 5.4 yrs) were recruited to a study that necessitated three distinct assessment phases; enrolment (Phase A), following pre-conditioning exercise in SED (Phase B), then following 6 weeks of HIIT performed once every five days by both groups before reassessment (Phase C). Hemodynamic, echocardiographic and cardiac strain mechanics were obtained at rest and maximal cardiorespiratory and chronotropic responses were obtained at each measurement phase. Results The training intervention improved systolic, mean arterial blood pressure, rate pressure product and heart rate reserve (each P < 0.05) in SED and increased MET capacity in both SED and LEX (P < 0.01) which was amplified by HIIT. Echocardiography and cardiac strain measures were unremarkable apart from trivial increase to intra-ventricular septum diastole (IVSd) (P < 0.05) and decrease to left ventricular internal dimension diastole (LVId) (P < 0.05) in LEX following HIIT. Conclusions A programme of preconditioning exercise with HIIT induces clinically relevant improvements in blood pressure, rate pressure product and encourages recovery of heart rate reserve in SED, while improving maximal MET capacity in both SED and LEX without inducing any pathological cardiovascular remodeling. These data add to the emerging repute of HIIT as a safe and promising exercise prescription to improve cardiovascular function and metabolic capacity in sedentary aging.
- Authors: Grace, Fergal , Herbert, Peter , Elliott, Adrian , Beaumont, Alexander , Richards, Jo , Sculthorpe, Nicholas
- Date: 2017
- Type: Text , Journal article
- Relation: Experimental Gerontology Vol.109, no. (2018), p.75-81
- Full Text:
- Reviewed:
- Description: Background This study examined a programme of pre-conditioning exercise with subsequent high intensity interval training (HIIT) on blood pressure, echocardiography, cardiac strain mechanics and maximal metabolic (MET) capacity in sedentary (SED) aging men compared with age matched masters athletes (LEX). Methods Using a STROBE compliant observational design, 39 aging male participants (SED; n = 22, aged 62.7 ± 5.2 yrs) (LEX; n = 17, aged = 61.1 ± 5.4 yrs) were recruited to a study that necessitated three distinct assessment phases; enrolment (Phase A), following pre-conditioning exercise in SED (Phase B), then following 6 weeks of HIIT performed once every five days by both groups before reassessment (Phase C). Hemodynamic, echocardiographic and cardiac strain mechanics were obtained at rest and maximal cardiorespiratory and chronotropic responses were obtained at each measurement phase. Results The training intervention improved systolic, mean arterial blood pressure, rate pressure product and heart rate reserve (each P < 0.05) in SED and increased MET capacity in both SED and LEX (P < 0.01) which was amplified by HIIT. Echocardiography and cardiac strain measures were unremarkable apart from trivial increase to intra-ventricular septum diastole (IVSd) (P < 0.05) and decrease to left ventricular internal dimension diastole (LVId) (P < 0.05) in LEX following HIIT. Conclusions A programme of preconditioning exercise with HIIT induces clinically relevant improvements in blood pressure, rate pressure product and encourages recovery of heart rate reserve in SED, while improving maximal MET capacity in both SED and LEX without inducing any pathological cardiovascular remodeling. These data add to the emerging repute of HIIT as a safe and promising exercise prescription to improve cardiovascular function and metabolic capacity in sedentary aging.
Renal denervation promotes atherosclerosis in hypertensive apolipoprotein E-Deficient mice infused with angiotensin II
- Wang, Yutang, Dinh, Tam, Nield, Alex, Krishna, Smriti, Denton, Kate, Golledge, Jonathan
- Authors: Wang, Yutang , Dinh, Tam , Nield, Alex , Krishna, Smriti , Denton, Kate , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Frontiers in Physiology Vol. 8, no. (2017), p. 1-9
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Objective: To determine the effect of renal denervation (RDN) on the severity of atherosclerosis and aortic aneurysm in hypertensive mice. Methods: Hypertension, atherosclerosis and aortic aneurysm were induced by subcutaneous infusion of angiotensin II (1 μg/kg/min) for 28 days in apolipoprotein E-deficient mice. RDN was conducted using combined surgical and local chemical denervation. The norepinephrine concentration in the kidney was measured by high-performance liquid chromatography. Blood pressure was measured by the tail-cuff method. Atherosclerosis was assessed by Sudan IV staining of the aortic arch. The aortic diameter was measured by the morphometric method. The mRNA expression of genes associated with atherosclerosis and aortic aneurysm were analyzed by quantitative PCR. Results: RDN decreased the median norepinephrine content in the kidney by 93.4% (n = 5-7, P = 0.003) 5 days after the procedure, indicating that the RDN procedure was successful. RDN decreased systolic blood pressure in apolipoprotein E-deficient mice. Mice that had RDN had more severe aortic arch atherosclerosis (median percentage of Sudan IV positive area: 13.2% in control mice, n = 12, and 25.4% in mice having RDN, n = 12, P = 0.028). The severity of the atherosclerosis was negatively correlated with the renal norepinephrine content (spearman r = -0.6557, P = 0.005). RDN did not affect the size of aortic aneurysms formed or the incidence of aortic rupture in mice receiving angiotensin II. RDN significantly increased the aortic mRNA expression of matrix metalloproteinase-2 (MMP-2). Conclusion: RDN promoted atherosclerosis in apolipoprotein E-deficient mice infused with angiotensin II associated with upregulation of MMP-2. The higher MMP-2 expression could be the results of the greater amount of atheroma in the RDN mice. The findings suggest further research is needed to assess potentially deleterious effects of RDN in patients. © 2017 Wang, Dinh, Nield, Krishna, Denton and Golledge.
- Authors: Wang, Yutang , Dinh, Tam , Nield, Alex , Krishna, Smriti , Denton, Kate , Golledge, Jonathan
- Date: 2017
- Type: Text , Journal article
- Relation: Frontiers in Physiology Vol. 8, no. (2017), p. 1-9
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Objective: To determine the effect of renal denervation (RDN) on the severity of atherosclerosis and aortic aneurysm in hypertensive mice. Methods: Hypertension, atherosclerosis and aortic aneurysm were induced by subcutaneous infusion of angiotensin II (1 μg/kg/min) for 28 days in apolipoprotein E-deficient mice. RDN was conducted using combined surgical and local chemical denervation. The norepinephrine concentration in the kidney was measured by high-performance liquid chromatography. Blood pressure was measured by the tail-cuff method. Atherosclerosis was assessed by Sudan IV staining of the aortic arch. The aortic diameter was measured by the morphometric method. The mRNA expression of genes associated with atherosclerosis and aortic aneurysm were analyzed by quantitative PCR. Results: RDN decreased the median norepinephrine content in the kidney by 93.4% (n = 5-7, P = 0.003) 5 days after the procedure, indicating that the RDN procedure was successful. RDN decreased systolic blood pressure in apolipoprotein E-deficient mice. Mice that had RDN had more severe aortic arch atherosclerosis (median percentage of Sudan IV positive area: 13.2% in control mice, n = 12, and 25.4% in mice having RDN, n = 12, P = 0.028). The severity of the atherosclerosis was negatively correlated with the renal norepinephrine content (spearman r = -0.6557, P = 0.005). RDN did not affect the size of aortic aneurysms formed or the incidence of aortic rupture in mice receiving angiotensin II. RDN significantly increased the aortic mRNA expression of matrix metalloproteinase-2 (MMP-2). Conclusion: RDN promoted atherosclerosis in apolipoprotein E-deficient mice infused with angiotensin II associated with upregulation of MMP-2. The higher MMP-2 expression could be the results of the greater amount of atheroma in the RDN mice. The findings suggest further research is needed to assess potentially deleterious effects of RDN in patients. © 2017 Wang, Dinh, Nield, Krishna, Denton and Golledge.
The association between serum uric acid and blood pressure in different age groups in a healthy Chinese cohort
- Cheng, Wenjuan, Wen, Shiling, Wang, Yutang, Qian, Zhiping, Tan, Yuyao, Li, Hongying, Hou, Yueli, Hu, Haiyang, Golledge, Jonathan, Yang, Guang
- Authors: Cheng, Wenjuan , Wen, Shiling , Wang, Yutang , Qian, Zhiping , Tan, Yuyao , Li, Hongying , Hou, Yueli , Hu, Haiyang , Golledge, Jonathan , Yang, Guang
- Date: 2017
- Type: Text , Journal article
- Relation: Medicine (United States) Vol. 96, no. 50 (2017), p.1-6
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: High serum uric acid (sUA) has been reported to be a risk factor for hypertension however, whether this is the case for all age groups is not clear. We examined the association between sUA concentrations and systolic and diastolic blood pressure (SBP and DBP) in different age groups in a cohort of healthy Chinese participants. A total of 1082 healthy participants aged from 41 to 70 years were included. sUA concentration was measured by the uricase-peroxidase method. SBP and DBP were assessed using mercury sphygmomanometry. Hypertension was defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Hyperuricemia (HUA) was defined as sUA concentration of >7 mg/dL in men and >6 mg/dL in women. The association between sUA concentration and SBP and DBP was examined using Pearson's correlation test, multivariate linear regression, and logistic regression analysis. The prevalence of hypertension and HUA increased with age (P < .001). Hypertension was more common in participants that had HUA than in those that did not (38.95% vs 30.16%, P = .02). Higher sUA was significantly associated with higher SBP and DBP in the 41- to 50-year-old participants (SBP, β = 0.35, P < .001; DBP, β = .29, P < .001; after adjustment for age, sex, total cholesterol, estimated glomerular filtration rate, and fasting plasma glucose). HUA was also a risk factor for hypertension in this age group (odds ratio 1.425, 95% confidence interval, 1.217-1.668, P < .001). There was no association between sUA concentration and SBP and DBP in the other age groups. In this population of healthy Chinese participants, sUA concentration was positively associated with hypertension only in the 41- to 50-year-old group. Lowering uric acid in this age group may help to reduce the incidence of hypertension.
- Authors: Cheng, Wenjuan , Wen, Shiling , Wang, Yutang , Qian, Zhiping , Tan, Yuyao , Li, Hongying , Hou, Yueli , Hu, Haiyang , Golledge, Jonathan , Yang, Guang
- Date: 2017
- Type: Text , Journal article
- Relation: Medicine (United States) Vol. 96, no. 50 (2017), p.1-6
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: High serum uric acid (sUA) has been reported to be a risk factor for hypertension however, whether this is the case for all age groups is not clear. We examined the association between sUA concentrations and systolic and diastolic blood pressure (SBP and DBP) in different age groups in a cohort of healthy Chinese participants. A total of 1082 healthy participants aged from 41 to 70 years were included. sUA concentration was measured by the uricase-peroxidase method. SBP and DBP were assessed using mercury sphygmomanometry. Hypertension was defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Hyperuricemia (HUA) was defined as sUA concentration of >7 mg/dL in men and >6 mg/dL in women. The association between sUA concentration and SBP and DBP was examined using Pearson's correlation test, multivariate linear regression, and logistic regression analysis. The prevalence of hypertension and HUA increased with age (P < .001). Hypertension was more common in participants that had HUA than in those that did not (38.95% vs 30.16%, P = .02). Higher sUA was significantly associated with higher SBP and DBP in the 41- to 50-year-old participants (SBP, β = 0.35, P < .001; DBP, β = .29, P < .001; after adjustment for age, sex, total cholesterol, estimated glomerular filtration rate, and fasting plasma glucose). HUA was also a risk factor for hypertension in this age group (odds ratio 1.425, 95% confidence interval, 1.217-1.668, P < .001). There was no association between sUA concentration and SBP and DBP in the other age groups. In this population of healthy Chinese participants, sUA concentration was positively associated with hypertension only in the 41- to 50-year-old group. Lowering uric acid in this age group may help to reduce the incidence of hypertension.
MicroRNAs in essential hypertension and blood pressure regulation
- Marques, Francine, Charchar, Fadi
- Authors: Marques, Francine , Charchar, Fadi
- Date: 2015
- Type: Text , Book chapter
- Relation: Advances in Experimental Medicine and Biology p. 215-235
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text: false
- Reviewed:
- Description: Unravelling the complete genetic predisposition to high blood pressure (BP) has proven to be challenging. This puzzle and the fact that coding regions of the genome account for less than 2 % of the entire human DNA support the hypothesis that mechanisms besides coding genes are likely to contribute to BP regulation. Non-coding RNAs, especially microRNAs, are emerging as key players of transcription regulation in both health and disease states. They control basic functions in virtually all cell types relevant to the cardiovascular system and, thus, a direct involvement with BP regulation is highly probable. Here we review the literature about microRNAs associated with regulation of BP and hypertension, highlighting investigations, methodology and difficulties arising in the field. These molecules are being studied for exploitation in diagnostics, prognostics and therapeutics in many diseases. There have been some studies that examined biological fl uid microRNAs as biomarkers for hypertension, but most remain inconclusive due to the small sample sizes and differences in methodological standardisation. Fewer studies have analysed tissue microRNA levels in vascular smooth muscle cells and the kidney. Others focused on the interaction between single nucleotide polymorphisms and microRNA binding sites. Studies in animals have shown that angiotensin II, high- salt diet and exercise change microRNA levels in hypertension. Treatment of spontaneously hypertensive rats with a miR-22 inhibitor and treatment of hypertensive Schlager BPH/2J mice with a miR-181a mimic decreased their BP. This supports the use of microRNAs as therapeutic targets in hypertension, and future studies should test the use of other microRNAs found in human association studies. In conclusion, there is a clear need of increased pace of human, animal and functional studies to help us understand the multifaceted roles of microRNAs as critical regulators of the development and physiology of BP. © Springer International Publishing Switzerland 2015. Funding Details: APP1052659, NHMRC, National Heart Foundation of Australia Funding Details: PF12M6785, National Heart Foundation of Australia
Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure
- Tomaszewski, Maciej, Eales, James, Denniff, Matthew, Myers, Stephen, Chew, Guatsiew, Nelson, Christopher, Christofidou, Paraskevi, Desai, Aishwarya, Büsst, Cara, Wojnar, Lukasz, Musialik, Katarzyna, Jozwiak, Jacek, Debiec, Radoslaw, Dominiczak, Anna, Navis, Gerjan, van Gilst, Wiek, van der Harst, Pim, Samani, Nilesh, Harrap, Stephen, Bogdanski, Pawel, Zukowska-Szczechowska, Ewa, Charchar, Fadi
- Authors: Tomaszewski, Maciej , Eales, James , Denniff, Matthew , Myers, Stephen , Chew, Guatsiew , Nelson, Christopher , Christofidou, Paraskevi , Desai, Aishwarya , Büsst, Cara , Wojnar, Lukasz , Musialik, Katarzyna , Jozwiak, Jacek , Debiec, Radoslaw , Dominiczak, Anna , Navis, Gerjan , van Gilst, Wiek , van der Harst, Pim , Samani, Nilesh , Harrap, Stephen , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 26, no. 12 (2015), p. 3151-3160
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65 x10(-5)) and diastolic BP (P=7.61 x10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0x10(-3)). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, reninangiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.
- Authors: Tomaszewski, Maciej , Eales, James , Denniff, Matthew , Myers, Stephen , Chew, Guatsiew , Nelson, Christopher , Christofidou, Paraskevi , Desai, Aishwarya , Büsst, Cara , Wojnar, Lukasz , Musialik, Katarzyna , Jozwiak, Jacek , Debiec, Radoslaw , Dominiczak, Anna , Navis, Gerjan , van Gilst, Wiek , van der Harst, Pim , Samani, Nilesh , Harrap, Stephen , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of the American Society of Nephrology Vol. 26, no. 12 (2015), p. 3151-3160
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65 x10(-5)) and diastolic BP (P=7.61 x10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0x10(-3)). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, reninangiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.
Signatures of miR-181a on the renal transcriptome and blood pressure
- Marques, Francine, Romaine, Simon, Denniff, Matthew, Eales, James, Dormer, John, Garrelds, Ingrid, Wojnar, Lukasz, Musialik, Katarzyna, Duda-Raszewska, Barbara, Kiszka, Bartlomiej, Duda, Magdalena, Morris, Brian, Samani, Nilesh, Jan Danser, Jan, Bogdanski, Pawel, Zukowska-Szczechowska, Ewa, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Marques, Francine , Romaine, Simon , Denniff, Matthew , Eales, James , Dormer, John , Garrelds, Ingrid , Wojnar, Lukasz , Musialik, Katarzyna , Duda-Raszewska, Barbara , Kiszka, Bartlomiej , Duda, Magdalena , Morris, Brian , Samani, Nilesh , Jan Danser, Jan , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2015
- Type: Text , Journal article
- Relation: Molecular Medicine Vol. 21, no. (2015), p. 739-748
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- Description: MicroRNA-181a binds to the 3’ untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a. Elevated miR-181a levels correlated positively with systolic and diastolic blood pressure in TRANSLATE, and this association was independent of circulating renin. The association between serum miR-181a and systolic blood pressure was replicated in 199 subjects from the Genetic Regulation of Arterial Pressure of Humans In the Community (GRAPHIC) study. Renal immunohistochemistry and in situ hybridization showed that colocalization of miR-181a and renin was most prominent in collecting ducts where renin is not released into the systemic circulation. Analysis of 69 human kidneys characterized by RNA sequencing revealed that miR-181a was associated with downregulation of four mitochondrial pathways and upregulation of 41 signaling cascades of adaptive immunity and inflammation. We conclude that renal miR-181a has pleiotropic effects on pathways relevant to blood pressure regulation and that circulating levels of miR-181a are both a measurable proxy of renal miR-181a expression and a novel biochemical correlate of blood pressure.
- Authors: Roberts, Evan , Wood, Pamela
- Date: 2014
- Type: Text , Journal article
- Relation: Social Science and Medicine Vol. 107, no. (2014), p. 154-161
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- Description: We provide new historical evidence on the developmental origins of health and disease in a cohort of boys born between 1907 and 1922 in Wellington, New Zealand. Using a dataset of 1523 birth records that include birth weight and length we find 852 (58%) of the adult cohort in World War II records measuring stature, body mass and blood pressure. On average, the boys weighed 3.5kg at birth, similar to Australian and American babies of the era, and nearly identical to full-term New Zealand babies in the 1990s. Using OLS regression models we estimate the effect of birth weight on adult stature and systolic blood pressure. We find an increase in birth weight of 1kg is associated with an increase in stature of 2.6cm (95% confidence interval [CI] 1.6cm-3.6cm), and a decrease in systolic blood pressure of 2.1mm/Hg (95% CI - 5.00 to 0.67). This is the earliest cohort by fifty years for whom the fetal origins hypothesis has been examined in early adulthood. Our estimates of the effect of birth weight on blood pressure are towards the upper end of the range of published estimates in modern cohorts. © 2014 Elsevier Ltd.
Ethnicity and sympathetic tone: predictors of the blood-pressure response to renal denervation?
- Authors: Wang, Yutang
- Date: 2014
- Type: Text , Letter
- Relation: Nature Reviews Cardiology Vol. 11, no. 638 (2014), p.
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
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Is isolated systolic hypertension an indication for renal denervation?
- Authors: Wang, Yutang
- Date: 2014
- Type: Text , Commentary
- Relation: Frontiers in Physiology Vol. 5, no. 505 (2014), p. 1-2
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
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- Description: Ewen et al. recently reported in the journal Hypertension that they investigated, for the first time, the effect of renal denerva tion on blood pressure in 63 patients with isolated systolic hypertension (Ewen et al., 2014). The authors concluded that renal denervation reduced office and ambula- tory blood pressure in patients with iso- lated systolic hypertension (Ewen et al., 2014). However, this conclusion may not be drawn, as renal denervation may not decrease ambulatory blood pressure in these patients. The potential risk of renal denervation may overweigh its benefit in patients with isolated systolic hypertension. Therefore, adjusted drug treatment may be recommended to these patients before renal denervation.
- Authors: Wang, Yutang
- Date: 2014
- Type: Text , Commentary
- Relation: Frontiers in Physiology Vol. 5, no. 505 (2014), p. 1-2
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
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- Description: Ewen et al. recently reported in the journal Hypertension that they investigated, for the first time, the effect of renal denerva tion on blood pressure in 63 patients with isolated systolic hypertension (Ewen et al., 2014). The authors concluded that renal denervation reduced office and ambula- tory blood pressure in patients with iso- lated systolic hypertension (Ewen et al., 2014). However, this conclusion may not be drawn, as renal denervation may not decrease ambulatory blood pressure in these patients. The potential risk of renal denervation may overweigh its benefit in patients with isolated systolic hypertension. Therefore, adjusted drug treatment may be recommended to these patients before renal denervation.
Measurement of absolute copy number variation reveals association with essential hypertension
- Marques, Francine, Prestes, Priscilla, Pinheiro, Leonardo, Scurrah, Katrina, Emslie, Kerry, Tomaszewski, Maciej, Harrap, Stephen, Charchar, Fadi
- Authors: Marques, Francine , Prestes, Priscilla , Pinheiro, Leonardo , Scurrah, Katrina , Emslie, Kerry , Tomaszewski, Maciej , Harrap, Stephen , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Medical Genomics Vol. 7, no. (2014), p. 1-8
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- Description: Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
- Authors: Marques, Francine , Prestes, Priscilla , Pinheiro, Leonardo , Scurrah, Katrina , Emslie, Kerry , Tomaszewski, Maciej , Harrap, Stephen , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Medical Genomics Vol. 7, no. (2014), p. 1-8
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- Description: Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.