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Sundström, Johan, ProfessorORCID iD iconorcid.org/0000-0003-2247-8454
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Publications (10 of 413) Show all publications
Gustafsson, S., Lampa, E., Jensevik, K., Butterworth, A. S., Elmståhl, S., Engström, G., . . . Sundström, J. (2024). Markers of imminent myocardial infarction. Nature Cardiovascular Research
Open this publication in new window or tab >>Markers of imminent myocardial infarction
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2024 (English)In: Nature Cardiovascular Research, E-ISSN 2731-0590Article in journal (Refereed) Epub ahead of print
Abstract [en]

Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case–cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-523069 (URN)10.1038/s44161-024-00422-2 (DOI)
Note

These authors contributed equally: Stefan Gustafsson, Erik Lampa

Available from: 2024-02-13 Created: 2024-02-13 Last updated: 2024-02-13Bibliographically approved
Engström, G., Lampa, E., Dekkers, K., Lin, Y.-T., Ahlm, K., Ahlström, H., . . . Sundström, J. (2024). Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications. Eur J Epidemiol
Open this publication in new window or tab >>Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications
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2024 (English)In: Eur J Epidemiol, ISSN 1573-7284 Electronic 0393-2990 LinkingArticle in journal (Refereed) Published
Abstract [en]

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Keywords
Atherosclerosis Coronary heart disease Emphysema Spirometry
National Category
Health Sciences
Identifiers
urn:nbn:se:uu:diva-520136 (URN)10.1007/s10654-023-01088-z (DOI)
Note

Engstrom, Gunnar Lampa, Erik Dekkers, Koen Lin, Yi-Ting Ahlm, Kristin Ahlstrom, Hakan Alfredsson, Joakim Bergstrom, Goran Blomberg, Anders Brandberg, John Caidahl, Kenneth Cederlund, Kerstin Duvernoy, Olov Engvall, Jan E Eriksson, Maria J Fall, Tove Gigante, Bruna Gummesson, Anders Hagstrom, Emil Hamrefors, Viktor Hedner, Jan Janzon, Magnus Jernberg, Tomas Johnson, Linda Lind, Lars Lindberg, Eva Mannila, Maria Nilsson, Ulf Persson, Anders Persson, Hans Lennart Persson, Margaretha Ramnemark, Anna Rosengren, Annika Schmidt, Caroline Skoglund Larsson, Linn Skold, C Magnus Swahn, Eva Soderberg, Stefan Toren, Kjell Waldenstrom, Anders Wollmer, Per Zaigham, Suneela Ostgren, Carl Johan Sundstrom, Johan eng ERC-2018-STG-801965/ERC_/European Research Council/International Netherlands 2024/01/02 Eur J Epidemiol. 2024 Jan 2. doi: 10.1007/s10654-023-01088-z.

Available from: 2024-01-11 Created: 2024-01-11 Last updated: 2024-01-11
Lundberg, J., Cars, T., Lööv, S.-Å., Söderling, J., Sundström, J., Tiihonen, J., . . . Hellner, C. (2023). Association of Treatment-Resistant Depression With Patient Outcomes and Health Care Resource Utilization in a Population-Wide Study.. JAMA psychiatry, 80(2), 167-175
Open this publication in new window or tab >>Association of Treatment-Resistant Depression With Patient Outcomes and Health Care Resource Utilization in a Population-Wide Study.
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2023 (English)In: JAMA psychiatry, ISSN 2168-6238, Vol. 80, no 2, p. 167-175Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE: The totality of the societal and individual impact of treatment-resistant depression (TRD) is unknown, as is the potential to prognosticate TRD. The generalizability of many observational studies on TRD is limited.

OBJECTIVE: To estimate the burden of TRD in a large population-wide cohort in an area with universal health care by including data from both health care types (psychiatric and nonpsychiatric) and, further, to develop a prognostic model for clinical use.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study, a population-based observational study, assessed data from the Stockholm MDD Cohort for episodes of major depressive disorder (MDD) between 2010 and 2017 that fulfilled predefined criteria for TRD (≥3 consecutive antidepressant treatments). Data analysis was performed from August 2020 to May 2022.

MAIN OUTCOMES AND MEASURES: Outcomes were psychiatric and nonpsychiatric comorbid conditions, antidepressant treatments, health care resource utilization, lost workdays, all-cause mortality, and intentional self-harm and, in the prognostic model, TRD.

RESULTS: A total of 158 169 unipolar MDD episodes (in 145 577 patients) were identified between January 1, 2012, and December 31, 2017 (64.7% women; median [IQR] age, 42 years [30-56]). Of these, 12 793 episodes (11%) fulfilled criteria for TRD. The median (IQR) time from the start of MDD episode to TRD was 552 days (294-932). Selective serotonin reuptake inhibitor was the most common class of antidepressant treatment in all treatment steps, and 5907 patients (46.2%) received psychotherapy at some point before initiation of the third pharmacological antidepressant treatment. Compared with matched non-TRD episodes, TRD episodes had more inpatient bed-days (mean, 3.9 days; 95% CI, 3.6-4.1, vs 1.3 days; 95% CI, 1.2-1.4) and more lost workdays (mean, 132.3 days; 95% CI, 129.5-135.1, vs 58.7 days; 95% CI, 56.8-60.6) 12 months after the index date. Anxiety, stress, sleep disorder, and substance use disorder were all more common comorbid conditions in TRD episodes. Intentional self-harm was more than 4 times more common in TRD episodes. The all-cause mortality rate for patients with MDD with TRD episodes was 10.7/1000 person-years at risk, compared with 8.7/1000 person-years at risk for patients with MDD without TRD episodes (hazard ratio, 1.23; 95% CI, 1.07-1.41). Median time from start of the first antidepressant treatment to start of the second, and from start of the second antidepressant treatment to start of the third, was 165 and 197 days, respectively. The severity of MDD, defined using the self-rating Montgomery-Åsberg Depression Rating Scale (MADRS-S) at time of MDD diagnosis, was found to be the most important prognostic factor for TRD (C index = 0.69).

CONCLUSIONS AND RELEVANCE: In this cohort study, TRD was a common variant of MDD when including patients from both health care types, which is associated with a high disease burden for both patients and society. The median time between initiation of new antidepressant treatments was longer than recommended in current treatment guidelines, suggesting room for more structured and timely depression care.

Place, publisher, year, edition, pages
American Medical Association (AMA), 2023
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-491430 (URN)10.1001/jamapsychiatry.2022.3860 (DOI)000898105200004 ()36515938 (PubMedID)
Available from: 2022-12-21 Created: 2022-12-21 Last updated: 2024-01-26Bibliographically approved
Bergstrom, G., Rosengren, A., Brolin, E. B., Brandberg, J., Cederlund, K., Engstrom, G., . . . Lind, L. (2023). Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS. Atherosclerosis, 373, 46-54
Open this publication in new window or tab >>Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS
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2023 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 373, p. 46-54Article in journal (Refereed) Published
Abstract [en]

Background and aims: Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.

Methods: We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomog-raphy angiography (CCTA) and expressed as segment involvement score (SIS).

Results: The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.

Conclusions: Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.

Place, publisher, year, edition, pages
Elsevier BV, 2023
Keywords
Weight, Weight gain, Midlife, Coronary artery calcium score, Sex
National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-508445 (URN)10.1016/j.atherosclerosis.2023.01.024 (DOI)001010662800001 ()36813601 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationVinnovaKarolinska InstituteSwedish Heart Lung Foundation, 20180324Swedish Research Council, 2019-01140University of GothenburgLinköpings universitetLund UniversityUmeå UniversityUppsala UniversityAfa Sjukförsäkringsaktiebolag, 160334Swedish Research Council, 2018–02527
Available from: 2023-08-02 Created: 2023-08-02 Last updated: 2023-08-02Bibliographically approved
Simon, T. G., Roelstraete, B., Alkhouri, N., Hagström, H., Sundström, J. & Ludvigsson, J. F. (2023). Cardiovascular disease risk in paediatric and young adult non-alcoholic fatty liver disease. Gut, 72(3), 573-580
Open this publication in new window or tab >>Cardiovascular disease risk in paediatric and young adult non-alcoholic fatty liver disease
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2023 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 72, no 3, p. 573-580Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Longitudinal evidence is lacking regarding the long-term risk of major adverse cardiovascular events (MACE) in children and young adults with non-alcoholic fatty liver disease (NAFLD).

DESIGN: This nationwide cohort study included all Swedish children and young adults ≤25 years old with histologically confirmed NAFLD and without underlying cardiovascular disease (CVD) at baseline (1966-2016; n=699). NAFLD was defined from prospectively recorded histopathology, and further categorised as simple steatosis or non-alcoholic steatohepatitis (NASH). NAFLD patients were matched to ≤5 population controls without NAFLD or CVD (n=3353). Using Cox proportional hazards modelling, we calculated multivariable-adjusted HRs (aHRs) and 95% CIs for incident MACE (ie, ischaemic heart disease, stroke, congestive heart failure or cardiovascular mortality). In secondary analyses, we also explored rates of incident cardiac arrhythmias.

RESULTS: Over a median follow-up of 16.6 years, incident MACE was confirmed in 33 NAFLD patients and 52 controls. NAFLD patients had significantly higher rates of MACE than controls (3.1 vs 0.9/1000 person-years (PY); difference=2.1/1000 PY; aHR=2.33, 95% CI=1.43 to 3.78), including higher rates of ischaemic heart disease (difference=1.4/1000 PY; aHR=3.07, 95% CI 1.62 to 5.83) and congestive heart failure (difference=0.5/1000 PY; aHR=3.89, 95% CI=1.20 to 12.64). Rates of incident MACE outcomes appeared to be further augmented with NASH (aHR=5.27, 95% CI=1.96 to 14.19). In secondary analyses, NAFLD patients also had significantly higher rates of cardiac arrythmias (aHR=3.16, 95% CI=1.49 to 6.68).

CONCLUSION: Compared with matched population controls, children and young adults with biopsy-proven NAFLD had significantly higher rates of incident MACE, including ischaemic heart disease and congestive heart failure. Research to better characterise cardiovascular risk in children and young adults with NAFLD should be prioritised.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2023
Keywords
CARDIOVASCULAR COMPLICATIONS, CARDIOVASCULAR DISEASE, FATTY LIVER, HEPATIC FIBROSIS
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-491427 (URN)10.1136/gutjnl-2022-328105 (DOI)000899672000001 ()36522149 (PubMedID)
Available from: 2022-12-21 Created: 2022-12-21 Last updated: 2023-05-26Bibliographically approved
Hagström, H., Thiele, M., Sharma, R., Simon, T. G., Roelstraete, B., Söderling, J., . . . Ludvigsson, J. F. (2023). Cardiovascular Outcomes in Patients With Biopsy-proven Alcohol-related Liver Disease. Clinical Gastroenterology and Hepatology, 21(7), 1841-1853.e12
Open this publication in new window or tab >>Cardiovascular Outcomes in Patients With Biopsy-proven Alcohol-related Liver Disease
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2023 (English)In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 21, no 7, p. 1841-1853.e12Article in journal (Refereed) Published
Abstract [en]

BACKGROUND & AIMS: Patients with alcohol-related liver disease (ALD) frequently have risk factors for cardiovascular disease (CVD), but their long-term risk of CVD is not well-known, especially considering the competing risk of death from liver-related causes. It is further unknown if any excess risk varies across histological subgroups.

METHODS: We investigated the risk of CVD outcomes in 3488 persons with ALD and an available liver biopsy in Sweden between 1969 and 2016, compared with a matched reference population (n = 15,461). Administrative coding from national diagnostic and histopathology registers were used to define exposures and outcomes. Competing risk regression, taking non-CVD death into account and adjusting for potential confounders, was used to estimate subdistribution hazard ratios for incident CVD up until Dec 31, 2019.

RESULTS: At baseline, patients with ALD had a median age of 58 years, 64% were men, and 2039 (58%) had cirrhosis on histology. The incidence rate of CVD was 35.6 per 1000 person-years in ALD compared with 19.0 per 1000 person-years in reference individuals. ALD was associated with a 2-fold increased short-term risk for CVD compared with matched reference individuals (subdistribution hazard ratio during the first year after diagnosis, 2.29; 95% confidence interval, 1.79-2.95), but this risk decreased with time. Incidence rates of CVD were comparable across histological subgroups (ranging from 27.4 CVD cases per 1000 person-years in those with normal histology to 39.2 cases per 1000 person-years in those with cirrhosis).

CONCLUSIONS: Persons with biopsy-proven ALD have increased rates of CVD across histological subgroups compared with matched reference individuals, particularly just after ALD diagnosis. Active surveillance of modifiable CVD risk factors should be considered by clinicians treating patients with ALD.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Alcoholic Liver Disease, Epidemiology, Ethanol, Prognosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-491431 (URN)10.1016/j.cgh.2022.10.022 (DOI)001034486100001 ()36332805 (PubMedID)
Available from: 2022-12-21 Created: 2022-12-21 Last updated: 2023-08-15Bibliographically approved
Figtree, G. A., Vernon, S. T., Harmer, J. A., Gray, M. P., Arnott, C., Bachour, E., . . . Nicholls, S. J. (2023). Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors JACC State-of-the-Art Review. Journal of the American College of Cardiology, 82(13), 1343-1359
Open this publication in new window or tab >>Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors JACC State-of-the-Art Review
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2023 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 82, no 13, p. 1343-1359Article, review/survey (Refereed) Published
Abstract [en]

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed. (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2023
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-523066 (URN)10.1016/j.jacc.2023.06.045 (DOI)001144453900001 ()37730292 (PubMedID)
Available from: 2024-02-13 Created: 2024-02-13 Last updated: 2024-02-13Bibliographically approved
Malinovschi, A., Zhou, X., Andersson, A., Backman, H., Bake, B., Blomberg, A., . . . Engvall, J. E. (2023). Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry. American Journal of Respiratory and Critical Care Medicine, 208(4), 461-471
Open this publication in new window or tab >>Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry
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2023 (English)In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 208, no 4, p. 461-471Article in journal (Refereed) Published
Abstract [en]

RATIONALE: Post-bronchodilator (BD) spirometry is used for diagnosis of chronic obstructive pulmonary disease (COPD). However, pre-BD reference values are used for spirometry interpretation.

OBJECTIVES: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or post-BD reference values generated within the Swedish CArdioPulmonary bioImage Study (SCAPIS) when interpreting post-BD spirometry in a general population.

METHODS: SCAPIS reference values for post-BD and pre-BD spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or post-BD reference values, with respiratory burden in the SCAPIS general population (28,851 individuals).

MEASUREMENTS AND MAIN RESULTS: Bronchodilation resulted in higher predicted median and lower limit of normal (LLN) for FEV1/FVC ratio. The prevalence of post-BD FEV1/FVC < pre-bronchodilator LLN was 4.8% and that of post-BD FEV1/FVC < post-bronchodilator LLN was 9.9% for the general population. An additional 5.1% was identified as having an abnormal post-BD FEV1/FVC ratio and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%, p<0.001) and self-reported physician-diagnosed COPD (2.8% vs. 0.5%, p<0.001) than subjects with post-BD FEV1/FVC ratio > LLN for both pre- and post-bronchodilation).

CONCLUSIONS: Pre- and post-bronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of post-bronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using post-bronchodilator reference values when interpreting post-bronchodilator spirometry might enable identification of individuals with mild disease and be clinically relevant.

Place, publisher, year, edition, pages
American Thoracic Society, 2023
Keywords
COPD, post-bronchodilator, pre-bronchodilator, reference values, spirometry
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine; Physiology
Identifiers
urn:nbn:se:uu:diva-507832 (URN)10.1164/rccm.202212-2341OC (DOI)001055487600023 ()37339507 (PubMedID)
Funder
Swedish Heart Lung FoundationKnut and Alice Wallenberg FoundationSwedish Research CouncilVinnovaUniversity of GothenburgKarolinska InstituteLinköpings universitetLund UniversityUmeå UniversityUppsala University
Available from: 2023-07-13 Created: 2023-07-13 Last updated: 2023-10-25Bibliographically approved
Mishra, A., Lin, Y.-T., Lind, L., Sundström, J., Yngve, A. & Ezzati, M. (2023). Diminishing benefits of urban living for children and adolescents' growth and development. Nature, 615(7954), 874-883
Open this publication in new window or tab >>Diminishing benefits of urban living for children and adolescents' growth and development
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2023 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 615, no 7954, p. 874-883Article in journal (Refereed) Published
Abstract [en]

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1,2,3,4,5,6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Pediatrics Human Geography Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-509449 (URN)10.1038/s41586-023-05772-8 (DOI)001023407200001 ()36991188 (PubMedID)
Funder
EU, Horizon 2020, 774548Wellcome trust, 209376/Z/17/ZAstraZeneca
Note

For complete list of authors see http://dx.doi.org/10.1038/s41586-023-05772-8

Available from: 2023-08-18 Created: 2023-08-18 Last updated: 2023-08-18Bibliographically approved
van de Vegte, Y., Eppinga, R. P., van der Ende, M. Y., Hagemeijer, Y., Mahendran, Y. V., Salfati, E. Y., . . . van der Harst, P. (2023). Genetic insights into resting heart rate and its role in cardiovascular disease. Nature Communications, 14(1), Article ID 4646.
Open this publication in new window or tab >>Genetic insights into resting heart rate and its role in cardiovascular disease
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2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 4646Article in journal (Refereed) Published
Abstract [en]

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Cardiac and Cardiovascular Systems Medical Genetics
Identifiers
urn:nbn:se:uu:diva-511622 (URN)10.1038/s41467-023-39521-2 (DOI)001042222000014 ()37532724 (PubMedID)
Funder
Wellcome trust, 202802/Z/16/Z
Available from: 2023-09-15 Created: 2023-09-15 Last updated: 2023-10-03Bibliographically approved
Projects
Diabetes complications - causes and preventive treatment [2010-01078_VR]; Uppsala UniversityDiabetes complications - causes and preventive treatment [2010-07530_VR]; Uppsala UniversityPersonalized HYpertenSIon Care (PHYSIC) [2014-07126_VR]; Uppsala UniversityMetaHealth - A Swedish Cohort Collaboration for identifying risk factors for uncommon diseases [2014-02249_VR]; Uppsala UniversityThe Swedish Cohort Consortium (COHORTS.SE) [2015-05995_VR]; Uppsala UniversityMarkers of Imminent Myocardial Infarction (MIMI) [2016-01065_VR]; Uppsala UniversitySGLT2-hämmare eller metformin för primärprevention av kardiovaskulära komplikationer vid tidig typ 2-diabetes? SMART-studien. [20190403_HLF]; Uppsala University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2247-8454

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