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Sundström, Johan, ProfessorORCID iD iconorcid.org/0000-0003-2247-8454
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Publications (10 of 277) Show all publications
Cars, T., Lindhagen, L. & Sundström, J. (2019). A framework for monitoring of new drugs in Sweden. Upsala Journal of Medical Sciences, 124(1), 46-50
Open this publication in new window or tab >>A framework for monitoring of new drugs in Sweden
2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 46-50Article in journal (Refereed) Published
Abstract [en]

In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Comparative effectiveness research, pharmacoepidemiology, propensity score, real-world evidence, sequential monitoring
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-381208 (URN)10.1080/03009734.2018.1550454 (DOI)000461811100011 ()30689485 (PubMedID)
Available from: 2019-04-09 Created: 2019-04-09 Last updated: 2019-04-09Bibliographically approved
Marklund, M., Wu, J. H. Y., Imamura, F., Del Gobbo, L. C., Fretts, A., de Goede, J., . . . Risérus, U. (2019). Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies. Circulation, 139(21), 2422-2436
Open this publication in new window or tab >>Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies
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2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 21, p. 2422-2436Article in journal (Refereed) Published
Abstract [en]

Background:

Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

Methods:

We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

Results:

In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15198 incident cardiovascular events occurred among 68659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

Conclusions:

In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Keywords
arachidonic acid, biomarkers, cardiovascular diseases, diet, epidemiology, linoleic acid, primary prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-387592 (URN)10.1161/CIRCULATIONAHA.118.038908 (DOI)000469018300011 ()30971107 (PubMedID)
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved
Lind, L. & Sundström, J. (2019). Change in left ventricular geometry over 10 years in the elderly and risk of incident cardiovascular disease. Journal of Hypertension, 37(2), 325-330
Open this publication in new window or tab >>Change in left ventricular geometry over 10 years in the elderly and risk of incident cardiovascular disease
2019 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, no 2, p. 325-330Article in journal (Refereed) Published
Abstract [en]

Objective: Left ventricular hypertrophy (LVH) is related to a poor prognosis. We aimed to determine how left ventricular (LV) geometry changes over time, and how this relates to future cardiovascular disease.

Methods: In the Prospective Study of the Vasculature in Uppsala Seniors study, 1016 individuals were investigated with echocardiography at age 70. This was repeated after 5 and 10 years. Incident cardiovascular disease (myocardial infarction, stroke, and heart failure, n = 163) was recorded over 10 years.

Results: LV mass index (LVMI) and LV end-diastolic diameter (LVEDD) progressively increased over 10 years, while LV thickness declined (P< 0.0001 for all). Adjusting for traditional cardiovascular risk factors, LVMI at baseline, but not LVEDD, was significantly associated with incident cardiovascular disease [hazard ratio (HR) 1.02, 95% confidence interval 1.003-1.03, P = 0.019]. When adding the change in LVMI, or change in LVEDD, between ages 70 and 75 years to the models and using the time between 75 and 80 as follow-up (in total 82 incident cases), neither the change in LVMI nor the change in LVEDD were significant. Using updated information on LV geometric groups, an increased risk was seen for concentric LVH as compared with the normal group following adjustment for traditional risk factors (HR 2.29, P = 0.0014, 95% confidence interval 1.38-3.82). Eccentric LVH and concentric remodeling were not associated with a statistically significant increased risk of cardiovascular disease.

Conclusion: In elderly individuals without myocardial infarction, a progressive dilatation of the LV was seen over 10 years. However, the LV dilation seen over time in this age group was not associated with a major increase in risk of future cardiovascular disease.

Keywords
cardiovascular risk, epidemiology, left ventricular geometry
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-383890 (URN)10.1097/HJH.0000000000001897 (DOI)000467336700013 ()30113528 (PubMedID)
Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-05-28Bibliographically approved
Mubanga, M., Byberg, L., Egenvall, A., Sundström, J., Magnusson, P. K., Ingelsson, E. & Fall, T. (2019). Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study. BMJ Open, 9, Article ID e023447.
Open this publication in new window or tab >>Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study
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2019 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, article id e023447Article in journal (Refereed) Submitted
Abstract [en]

Objective To study the association between dog ownership and cardiovascular risk factors.

Design A nationwide register–based cohort study and a cross-sectional study in a subset.

Setting A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use.

Participants All Swedish residents aged 45–80 years on 1 October, 2006.

Main outcome measures Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus.

Results After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45–60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status.

Conclusions In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.

Keywords
cardiovascular risk, hypertension, dog ownership, diabetes, registers
National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-357625 (URN)10.1136/bmjopen-2018-023447 (DOI)000471144900063 ()30850401 (PubMedID)
Funder
Swedish Research Council, 2017-00641Swedish Research Council Formas, 2013-1673Göran Gustafsson Foundation for Research in Natural Sciences and Medicine
Available from: 2018-08-19 Created: 2018-08-19 Last updated: 2019-07-22Bibliographically approved
Salam, A., Atkins, E., Sundström, J., Hirakawa, Y., Ettehad, D., Emdin, C., . . . Rodgers, A. (2019). Effects of blood pressure lowering on cardiovascular events, in the context of regression to the mean: a systematic review of randomized trials. Journal of Hypertension, 37(1), 16-23
Open this publication in new window or tab >>Effects of blood pressure lowering on cardiovascular events, in the context of regression to the mean: a systematic review of randomized trials
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2019 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, no 1, p. 16-23Article, review/survey (Refereed) Published
Abstract [en]

Objective: To assess the clinical relevance of regression to the mean for clinical trials and clinical practice. Methods: MEDLINE was searched until February 2018 for randomized trials of BP lowering with over 1000 patient-years follow-up per group. We estimated baseline mean BP, follow-up mean (usual) BP amongst patients grouped by 10 mmHg strata of baseline BP, and assessed effects of BP lowering on coronary heart disease (CHD) and stroke according to these BP levels. Results: Eighty-six trials (349 488 participants), with mean follow-up of 3.7 years, were included. Most mean BP change was because of regression to the mean rather than treatment. At high baseline BP levels, even after rigorous hypertension diagnosis, downwards regression to the mean caused much of the fall in BP. At low baseline BP levels, upwards regression to the mean increased BP levels, even in treatment groups. Overall, a BP reduction of 6/3 mmHg lowered CHD by 14% (95% CI 11-17%) and stroke by 18% (15-22%), and these treatment effects occurred at follow-up BP levels much closer to the mean than baseline BP levels. In particular, more evidence was available in the SBP 130-139 mmHg range than any other range. Benefits were apparent in numerous high-risk patient groups with baseline mean SBP less than 140 mmHg. Conclusion: Clinical practice should focus less on pretreatment BP levels, which rarely predict future untreated BP levels or rule out capacity to benefit from BP lowering in high cardiovascular risk patients. Instead, focus should be on prompt, empirical treatment to maintain lower BP for those with high BP and/or high risk.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
Keywords
antihypertensive therapy, blood pressure, coronary heart disease, regression to the mean, stroke, systematic review
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-384093 (URN)10.1097/HJH.0000000000001994 (DOI)000467336300007 ()30499920 (PubMedID)
Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2019-06-12Bibliographically approved
Pennells, L., Kaptoge, S., Wood, A., Sweeting, M., Zhao, X., White, I., . . . Geleijnse, J. M. (2019). Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies. European Heart Journal, 40(7), 621-+
Open this publication in new window or tab >>Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies
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2019 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, no 7, p. 621-+Article in journal (Refereed) Published
Abstract [en]

Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.

Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.

Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

Keywords
Cardiovascular disease, Risk prediction, Risk algorithms, Calibration, Discrimination
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-378995 (URN)10.1093/eurheartj/ehy653 (DOI)000459342100017 ()30476079 (PubMedID)
Funder
EU, European Research Council, 268834EU, FP7, Seventh Framework Programme, HEALTH-F2-2012-279233
Available from: 2019-03-19 Created: 2019-03-19 Last updated: 2019-03-19Bibliographically approved
Lind, L., Sundström, J., Larsson, A., Lampa, E., Ärnlov, J. & Ingelsson, E. (2019). Longitudinal effects of aging on plasma proteins levels in older adults - associations with kidney function and hemoglobin levels. PLoS ONE, 14(2), Article ID e0212060.
Open this publication in new window or tab >>Longitudinal effects of aging on plasma proteins levels in older adults - associations with kidney function and hemoglobin levels
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 2, article id e0212060Article in journal (Refereed) Published
Abstract [en]

Background A targeted proteomics chip has been shown to be useful to discover novel associations of proteins with cardiovascular disease. We investigated how these proteins change with aging, and whether this change is related to a decline in kidney function, or to a change in hemoglobin levels. Material and methods In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, including 1,016 participants from the general population aged 70 at baseline, 84 proteins were measured at ages 70, 75, 80. At these occasions, glomerular filtration rate (eGFR) was estimated and the hemoglobin levels were measured. Results Sixty-one of the 84 evaluated proteins changed significantly during the 10-year follow-up (multiple testing-adjusted alpha = 0.00059), most showing an increase. The change in eGFR was inversely related to changes of protein levels for the vast majority of proteins (74%). The change in hemoglobin was significantly related to the change in 40% of the evaluated proteins, with no obvious preference of the direction of these relationships. Conclusion The majority of evaluated proteins increased with aging in adults. Therefore, normal ranges for proteins might be given in age-strata. The increase in protein levels was associated with the degree of reduction in eGFR for the majority of proteins, while no clear pattern was seen for the relationships between the proteins and the change in hemoglobin levels. Studies on changes in urinary proteins are warranted to understand the association between the reduction in eGFR and increase in plasma protein levels.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2019
National Category
Gerontology, specialising in Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-379592 (URN)10.1371/journal.pone.0212060 (DOI)000459710700009 ()30802263 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2013.0126
Available from: 2019-03-18 Created: 2019-03-18 Last updated: 2019-03-18Bibliographically approved
Lind, L., Sundström, J., Ärnlöv, J. & Ingelsson, E. (2019). Proteomic profiling of endothelium-dependent vasodilation. Journal of Hypertension, 37(1), 216-222
Open this publication in new window or tab >>Proteomic profiling of endothelium-dependent vasodilation
2019 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, no 1, p. 216-222Article in journal (Refereed) Published
Abstract [en]

Objective: As endothelial dysfunction is an early event in atherosclerosis formation, we investigated if proteins previously related to cardiovascular disease also were related to endothelial function using a novel targeted proteomics approach.

Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 850970, all aged 70 years), endothelium-dependent vasodilation (EDV) in the forearm was assessed by intraarterial infusion of acetylcholine. Flow-mediated vasodilation (FMD) was investigated in the brachial artery by ultrasound. The same investigations were carried out in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 375-461, all aged 50 years). After strict quality control, 84 cardiovascular-related proteins measured by the proximity extension assay were studied in relation to EDV and FMD in PIVUS (discovery sample) and POEM (validation sample).

Results: Of the 15 proteins being significantly related to EDV in PIVUS (false discovery rate < 0.025), seven could be replicated in POEM at nominal significance and same effect direction when adjusted for sex and storage time. Of those, only cathepsin D remained significant following further adjustment for traditional cardiovascular risk factors (beta, -0.08; 95% confidence interval, -0.16, -0.01; P = 0.033; change in ln-transformed EDV per 1-SD increase in protein level). No protein was significantly related to FMD.

Conclusion: Using a discovery/validation approach in two samples, our results indicate an inverse association between plasma cathepsin D levels and endothelial-dependent vasodilation.

Keywords
cathepsin D, endothelium, epidemiology, proteomics, vasodilation
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-383894 (URN)10.1097/HJH.0000000000001863 (DOI)000467336300031 ()30339551 (PubMedID)
Available from: 2019-05-24 Created: 2019-05-24 Last updated: 2019-05-24Bibliographically approved
Sundström, J., Björkelund, C., Giedraitis, V., Hansson, P.-O., Högman, M., Janson, C., . . . Svennblad, B. (2019). Rationale for a Swedish cohort consortium. Upsala Journal of Medical Sciences, 124(1), 21-28
Open this publication in new window or tab >>Rationale for a Swedish cohort consortium
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2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 21-28Article in journal (Refereed) Published
Abstract [en]

We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Common infrastructure, epidemiological research, pilot study, rare outcomes, Swedish cohort consortium
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-381205 (URN)10.1080/03009734.2018.1556754 (DOI)000461811100006 ()30618330 (PubMedID)
Available from: 2019-04-10 Created: 2019-04-10 Last updated: 2019-04-10Bibliographically approved
Bixby, H., Lind, L., Lytsy, P., Sundström, J., Yngve, A. & Ezzati, M. (2019). Rising rural body-mass index is the main driver of the global obesity epidemic in adults [Letter to the editor]. Nature, 569(7755), 260-264
Open this publication in new window or tab >>Rising rural body-mass index is the main driver of the global obesity epidemic in adults
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2019 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 569, no 7755, p. 260-264Article in journal, Letter (Other academic) Published
Abstract [en]

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
International Health; Nutrition
Identifiers
urn:nbn:se:uu:diva-383181 (URN)10.1038/s41586-019-1171-x (DOI)000467473600049 ()31068725 (PubMedID)
Funder
Wellcome trust
Note

NCD Risk Factor Collaboration (NCD-RisC)

For a complete list of all 1155 authors see https://doi.org/10.1038/s41586-019-1171-x

Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-06-19Bibliographically approved
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