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Sundström, Johan, ProfessorORCID iD iconorcid.org/0000-0003-2247-8454
Alternative names
Publications (10 of 259) Show all publications
Beijer, K., Sundström, J., Arnlöv, J., Fall, T., Ingelsson, E. & Lind, L. (2018). A targeted proteomic profile of prevalent diabetes in a population-based sample. Paper presented at 54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY. Diabetologia, 61, S252-S252
Open this publication in new window or tab >>A targeted proteomic profile of prevalent diabetes in a population-based sample
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2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S252-S252Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-367122 (URN)000443556003105 ()
Conference
54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY
Available from: 2018-11-30 Created: 2018-11-30 Last updated: 2018-11-30Bibliographically approved
Figarska, S. M., Gustafsson, S., Sundström, J., Ärnlöv, J., Mälarstig, A., Elmstahl, S., . . . Ingelsson, E. (2018). Associations of Circulating Protein Levels With Lipid Fractions in the General Population. Arteriosclerosis, Thrombosis and Vascular Biology, 38(10), 2505-2518
Open this publication in new window or tab >>Associations of Circulating Protein Levels With Lipid Fractions in the General Population
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2018 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 38, no 10, p. 2505-2518Article in journal (Refereed) Published
Abstract [en]

Objective: Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population.

Approach and Results: We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate <0.05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima-Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels.

Conclusions: Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
Keywords
cholesterol, humans, proteomics, triglycerides
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363206 (URN)10.1161/ATVBAHA.118.311440 (DOI)000445750500026 ()
Funder
Knut and Alice Wallenberg Foundation, 2013.0126
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2018-10-18Bibliographically approved
Karmali, K. N., Lloyd-Jones, D. M., van der Leeuw, J., Goff, D. C. ., Yusuf, S., Zanchetti, A., . . . Sundström, J. (2018). Blood pressure-lowering treatment strategies based on cardiovascular risk versus blood pressure: A meta-analysis of individual participant data. PLoS Medicine, 15(3), Article ID e1002538.
Open this publication in new window or tab >>Blood pressure-lowering treatment strategies based on cardiovascular risk versus blood pressure: A meta-analysis of individual participant data
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2018 (English)In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 15, no 3, article id e1002538Article in journal (Refereed) Published
Abstract [en]

Background: Clinical practice guidelines have traditionally recommended blood pressure treatment based primarily on blood pressure thresholds. In contrast, using predicted cardiovascular risk has been advocated as a more effective strategy to guide treatment decisions for cardiovascular disease (CVD) prevention. We aimed to compare outcomes from a blood pressure-lowering treatment strategy based on predicted cardiovascular risk with one based on systolic blood pressure (SBP) level.

Methods and findings: We used individual participant data from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) from 1995 to 2013. Trials randomly assigned participants to either blood pressure-lowering drugs versus placebo or more intensive versus less intensive blood pressure-lowering regimens. We estimated 5-y risk of CVD events using a multivariable Weibull model previously developed in this dataset. We compared the two strategies at specific SBP thresholds and across the spectrum of risk and blood pressure levels studied in BPLTTC trials. The primary outcome was number of CVD events avoided per persons treated. We included data from 11 trials (47,872 participants). During a median of 4.0 y of follow-up, 3,566 participants (7.5%) experienced a major cardiovascular event. Areas under the curve comparing the two treatment strategies throughout the range of possible thresholds for CVD risk and SBP demonstrated that, on average, a greater number of CVD events would be avoided for a given number of persons treated with the CVD risk strategy compared with the SBP strategy (area under the curve 0.71 [95% confidence interval (CI) 0.70-0.72] for the CVD risk strategy versus 0.54 [95% CI 0.53-0.55] for the SBP strategy). Compared with treating everyone with SBP >= 150 mmHg, a CVD risk strategy would require treatment of 29% (95% CI 26%-31%) fewer persons to prevent the same number of events or would prevent 16% (95% CI 14%-18%) more events for the same number of persons treated. Compared with treating everyone with SBP >= 140 mmHg, a CVD risk strategy would require treatment of 3.8% (95% CI 12.5% fewer to 7.2% more) fewer persons to prevent the same number of events or would prevent 3.1% (95% CI 1.5%-5.0%) more events for the same number of persons treated, although the former estimate was not statistically significant. In subgroup analyses, the CVD risk strategy did not appear to be more beneficial than the SBP strategy in patients with diabetes mellitus or established CVD.

Conclusions: A blood pressure-lowering treatment strategy based on predicted cardiovascular risk is more effective than one based on blood pressure levels alone across a range of thresholds. These results support using cardiovascular risk assessment to guide blood pressure treatment decision-making in moderate- to high-risk individuals, particularly for primary prevention.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2018
National Category
Cardiac and Cardiovascular Systems Geriatrics
Identifiers
urn:nbn:se:uu:diva-351756 (URN)10.1371/journal.pmed.1002538 (DOI)000428983600026 ()29558462 (PubMedID)
Available from: 2018-05-31 Created: 2018-05-31 Last updated: 2018-05-31Bibliographically approved
Andersen, K., Rasmussen, F., Neovius, M., Tynelius, P. & Sundström, J. (2018). Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men. Journal of Internal Medicine, 283(4), 346-355
Open this publication in new window or tab >>Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men
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2018 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 346-355Article in journal (Refereed) Published
Abstract [en]

Background: Whilst tall stature has been related to lower risk of vascular disease, it has been proposed as a risk factor for atrial fibrillation. Little is known about other anthropometric measures and their joint effects on risk of atrial fibrillation.

Objectives: We aim to investigate associations and potential joint effects of height, weight, body surface area (BSA) and body mass index (BMI) with risk of atrial fibrillation.

Methods: In a cohort covering 1 153 151 18-year-old men participating in the Swedish military conscription (1972-1995), Cox regression was used to investigate associations of height, weight, BSA and BMI with risk of atrial fibrillation.

Results: During a median of 26.3 years of follow-up, higher height was associated with higher risk of atrial fibrillation (hazard ratio [HR] 2.80; 95% CI 2.63-2.98; for 5th vs. 1st quintile) and so was larger BSA (HR 3.05; 95% CI 2.82-3.28; for 5th vs. 1st quintile). Higher weight and BMI were to a lesser extent associated with risk of atrial fibrillation (BMI: 1.42; 95% CI 1.33-1.52, for 5th vs. 1st quintile). We found a multiplicative joint effect of height and weight. Adjusting for muscle strength, exercise capacity and diseases related to atrial fibrillation attenuated these measures.

Conclusions: Higher height and weight are strongly associated with higher risk of atrial fibrillation. These associations are multiplicative and independent of each other and are summarized in a strong association of body surface area with risk of atrial fibrillation. The mechanisms remain unknown but may involve increased atrial volume load with larger body size.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
atrial fibrillation, body mass Index, body surface area, height, weight
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-353116 (URN)10.1111/joim.12717 (DOI)000428438600002 ()29178512 (PubMedID)
Funder
Swedish Research Council, 2007-5942]Swedish Research Council, 2010-1078]
Available from: 2018-06-11 Created: 2018-06-11 Last updated: 2018-06-11Bibliographically approved
Lind, L., Ingelsson, E., Ärnlöv, J., Sundström, J., Zethelius, B. & Reaven, G. M. (2018). Can the Plasma Concentration Ratio of Triglyceride/High-Density Lipoprotein Cholesterol Identify Individuals at High Risk of Cardiovascular Disease During 40-Year Follow-Up?. Metabolic Syndrome and Related Disorders, 16(8), 433-439
Open this publication in new window or tab >>Can the Plasma Concentration Ratio of Triglyceride/High-Density Lipoprotein Cholesterol Identify Individuals at High Risk of Cardiovascular Disease During 40-Year Follow-Up?
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2018 (English)In: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 16, no 8, p. 433-439Article in journal (Refereed) Published
Abstract [en]

Background: The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) is a simple way to estimate insulin resistance. We aimed to evaluate the TG/HDL-C ratio as a simple clinical way to identify apparently healthy individuals with insulin resistance and enhanced risk of future cardiovascular disease (CVD).

Methods: One thousand seven hundred twenty men, aged 50 years, free from diabetes and CVD when evaluated at baseline in 1970-1974 were followed for 40 years regarding incident CVD (myocardial infarction and/or ischemic stroke, n=576).

Results: Participants with a high TG/HDL-C ratio (highest quartile >1.8) at baseline were more insulin resistant, with a significantly more adverse cardiometabolic risk profile (P<0.001) at baseline, compared with those with a lower ratio. This group also showed an increased risk of CVD [hazard ratio, HR 1.47 (95% confidence interval 1.26-1.93) P<0.001]. Fourteen percent of subjects with metabolic syndrome, in whom insulin resistance is increased, were also at enhanced CVD risk [HR 1.75 (1.42-2.16) P<0.001].

Conclusions: Twenty-five percent of apparently healthy 50-year-old men with the highest TG/HDL-C plasma concentration ratio had a significantly more adverse cardiometabolic profile at baseline, and developed more CVD over the next 40 years, compared with those not meeting this cut point. Determining the TG/HDL-C ratio in middle-aged men provided a simple and potentially clinically useful way to identify increased risk of developing CVD in persons free of diabetes or manifest CVD.

Place, publisher, year, edition, pages
MARY ANN LIEBERT, INC, 2018
Keywords
HDL-cholesterol, triglycerides, metabolic syndrome, cardiovascular disease, prospective
National Category
Endocrinology and Diabetes Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-368757 (URN)10.1089/met.2018.0058 (DOI)000446027200007 ()30183521 (PubMedID)
Available from: 2018-12-07 Created: 2018-12-07 Last updated: 2018-12-07Bibliographically approved
Stenemo, M., Nowak, C., Byberg, L., Sundström, J., Giedraitis, V., Lind, L., . . . Ärnlöv, J. (2018). Circulating proteins as predictors of incident heart failure in the elderly. European Journal of Heart Failure, 20(1), 55-62
Open this publication in new window or tab >>Circulating proteins as predictors of incident heart failure in the elderly
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2018 (English)In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, no 1, p. 55-62Article in journal (Refereed) Published
Abstract [en]

Aims

To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology.

Methods and results

Proteomic profiling (proximity extension assay) was performed in two community‐based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0–70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9–78.1) years, 90 events]. Twenty‐nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF‐15), T‐cell immunoglobulin and mucin domain 1 (TIM‐1), tumour necrosis factor‐related apoptosis‐inducing ligand receptor 2 (TRAIL‐R2), spondin‐1 (SPON1), matrix metalloproteinase‐12 (MMP‐12), follistatin (FS), urokinase‐type plasminogen activator surface receptor (U‐PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF‐15, U‐PAR, MMP‐12, TRAIL‐R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM‐1 was positively associated with worsened diastolic function (P < 0.02 for all).

Conclusion

Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

Keywords
Biomarkers, Epidemiology, Heart failure, Left ventricular dysfunction, Proteomics, Risk prediction
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-334416 (URN)10.1002/ejhf.980 (DOI)000423809700007 ()28967680 (PubMedID)
Funder
EU, Horizon 2020, 634869Swedish Research Council, 2012-2215; 2015-03477; 221-2013-1673Marianne and Marcus Wallenberg Foundation, 2012.0082Swedish Heart Lung Foundation, 20140422; 20150429; 20120169Knut and Alice Wallenberg Foundation, 2013.0126Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of Technology, 1637
Note

Tove Fall och Johan Ärnlöv delar på sistaförfattarskapet.

Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-08-24Bibliographically approved
Zhou, B., Bentham, J., Di Cesare, M., Bixby, H., Danaei, G., Hajifathalian, K., . . . Cisneros, J. Z. (2018). Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: a pooled analysis of 1018 population-based measurement studies with 88.6 million participants. International Journal of Epidemiology, 47(3), 872-883i
Open this publication in new window or tab >>Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: a pooled analysis of 1018 population-based measurement studies with 88.6 million participants
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2018 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 47, no 3, p. 872-883iArticle in journal (Refereed) Published
Abstract [en]

Background

Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure.

Methods

We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20–29 years to 70–79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure.

Results

In 2005–16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association.

Conclusions

Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
Blood pressure, hypertension, population health, global health, non-communicable disease
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-361286 (URN)10.1093/ije/dyy016 (DOI)000438342200023 ()29579276 (PubMedID)
Funder
Wellcome trust, 101506/Z/13/Z
Note

NCD Risk Factor Collaboration (NCD-RisC) Members are listed at the end of the paper

Available from: 2018-09-27 Created: 2018-09-27 Last updated: 2018-11-15Bibliographically approved
Lampa, E., Arnlöv, J., Sundström, J., Risérus, U. & Lind, L. (2018). Diabetes increases the mortality in myocardial infarction, heart failure and stroke: results from a longitudinal study over 40 years. Paper presented at 54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY. Diabetologia, 61, S178-S178
Open this publication in new window or tab >>Diabetes increases the mortality in myocardial infarction, heart failure and stroke: results from a longitudinal study over 40 years
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2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S178-S178Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-367128 (URN)000443556002149 ()
Conference
54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY
Available from: 2018-11-30 Created: 2018-11-30 Last updated: 2018-11-30Bibliographically approved
Cars, T., Lindhagen, L., Malmström, R. E., Neovius, M., Schwieler, J., Wettermark, B. & Sundström, J. (2018). Effectiveness of Drugs in Routine Care: A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example. Clinical Pharmacology and Therapeutics, 103(3), 493-501
Open this publication in new window or tab >>Effectiveness of Drugs in Routine Care: A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example
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2018 (English)In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 103, no 3, p. 493-501Article in journal (Refereed) Published
Abstract [en]

Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different fromthose treated in clinical practice. Therefore, it is important to optimize real-time post-marketing evaluation of the effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases froma well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care. We chose the antiarrhythmic agent dronedarone as the study drug and flecainide as the comparator drug for illustration of the model. We demonstrate that this model produces consistent results with increasing precision over time as data accumulates in the clinical systems. We believe that use of this model at the introduction of new drugs can provide complementary evidence, especially in settings of adaptive licensing of new drugs.

Place, publisher, year, edition, pages
WILEY, 2018
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-348840 (URN)10.1002/cpt.751 (DOI)000424520000030 ()28560722 (PubMedID)
Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-04-23Bibliographically approved
Evangelou, E., Warren, H. R., Mosen-Ansorena, D., Mifsud, B., Pazoki, R., Gao, H., . . . Caulfield, M. J. (2018). Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.. Nature Genetics, 50(10), 1412-1425
Open this publication in new window or tab >>Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
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2018 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 10, p. 1412-1425Article in journal (Refereed) Published
Abstract [en]

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-367084 (URN)10.1038/s41588-018-0205-x (DOI)000446047000013 ()30224653 (PubMedID)
Funder
EU, European Research CouncilNovo Nordisk, NNF15CC0018486EU, FP7, Seventh Framework Programme, HEALTH-F2-2013-601456Wellcome trust, RE/13/1/30181Wellcome trust, WT098051
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2018-12-05Bibliographically approved
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