Published in 2021

Vitamin D concentrations from neonatal dried blood spots and the risk of early-onset type 2 diabetes in the Danish D-tect case-cohort study

Keller, A., Thorsteinsdottir, F., Stougaard, M., Cardoso, I., Frederiksen, P., Cohen, A. S., Vaag, A., Jacobsen, R. & Heitmann, B. L., jul. 2021, I: Diabetologia. 64, 7, s. 1572-1582 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

AIMS/HYPOTHESIS: The aim of this study was to examine the influence of neonatal vitamin D concentration on the development of early-onset type 2 diabetes in a large population sample.

METHODS: We conducted a case-cohort study utilising data from the Danish biobank and registers. Neonatal vitamin D was assessed measuring 25-hydroxyvitamin D3 [25(OH)D3] concentrations on the dried blood spot samples from the Biological Specimen Bank for Neonatal Screening. Cases of type 2 diabetes (n = 731) were retrieved from the Danish National Patient Register for all individuals born in Denmark between 1 May 1981 and 31 December 1992. The sub-cohort (n = 1765) was randomly selected from all children born in the same period. We used a weighted Cox proportional hazard model assessing the hazard of first type 2 diabetes diagnoses by quintiles of 25(OH)D3 and restricted cubic spline.

RESULTS: The median 25(OH)D3 concentration (IQR) among cases was 21.3 nmol/l (13.3-34.1) and 23.9 nmol/l (13.7-35.7) in the sub-cohort. There was no indication of a potential lower risk of early-onset type 2 diabetes among individuals in the higher quintile of vitamin D concentration compared with the lowest (HRcrude 0.97 [95% CI 0.71, 1.33] p = 0.85; HRadjusted 1.29 [95% CI 0.92, 1.83] p = 0.14).

CONCLUSIONS/INTERPRETATION: The results of this study do not support the hypothesis that higher neonatal vitamin D concentrations are associated with a lower risk of early-onset type 2 diabetes in adulthood.

Originalsprog Engelsk
Tidsskrift Diabetologia
Vol/bind 64
Udgave nummer 7
Sider (fra-til) 1572-1582
Antal sider 11
ISSN 0012-186X
DOI
Status Udgivet - jul. 2021

VP10.02: The prenatal detection rate of orofacial clefts in Denmark from 2009–2018

Petersen, OB., 14 okt. 2021, I: Abstracts of the 31st World Congress on Ultrasound in Obstetrics and Gynecology. 58, 1, s. 130-131

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

VP21.03: Neurodevelopmental outcome in children with a congenital heart defect compared to healthy children

Petersen, OB., 14 okt. 2021.

Publikation: KonferencebidragKonferenceabstrakt til konferenceFormidling

Published in 2020

3-D synthetic aperture high volume rate tensor velocity imaging using 1024 element matrix probe

Makouei, F., Asl, B. M., Jorgensen, L. T., Tomov, B. G., Stuart, M. B. & Jensen, J. A., 7 sep. 2020, IUS 2020 - International Ultrasonics Symposium, Proceedings. IEEE Computer Society Press, 9251377. (IEEE International Ultrasonics Symposium, IUS, Bind 2020-September).

Publikation: Bidrag til bog/antologi/rapportKonferencebidrag i proceedingsForskningpeer review

A Comparison of Tenocyte Populations from the Core and Periphery of Equine Tendon

Yeung, C.-Y. C., 21 aug. 2020, I: Journal of Proteome Research. doi.org/10.1021/acs.jproteome.0c00591.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

A novel scaling methodology to reduce the biases associated with missing data from commercial activity monitors

O'Driscoll, R., Turicchi, J., Duarte, C., Michalowska, J., Larsen, S. C., Palmeira, A. L., Heitmann, B. L., Horgan, G. W. & Stubbs, R. J., 24 jun. 2020, I: PLoS One. 15, 6, s. e0235144 e0235144.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Commercial physical activity monitors have wide utility in the assessment of physical activity in research and clinical settings, however, the removal of devices results in missing data and has the potential to bias study conclusions. This study aimed to evaluate methods to address missingness in data collected from commercial activity monitors.

METHODS: This study utilised 1526 days of near complete data from 109 adults participating in a European weight loss maintenance study (NoHoW). We conducted simulation experiments to test a novel scaling methodology (NoHoW method) and alternative imputation strategies (overall/individual mean imputation, overall/individual multiple imputation, Kalman imputation and random forest imputation). Methods were compared for hourly, daily and 14-day physical activity estimates for steps, total daily energy expenditure (TDEE) and time in physical activity categories. In a second simulation study, individual multiple imputation, Kalman imputation and the NoHoW method were tested at different positions and quantities of missingness. Equivalence testing and root mean squared error (RMSE) were used to evaluate the ability of each of the strategies relative to the true data.

RESULTS: The NoHoW method, Kalman imputation and multiple imputation methods remained statistically equivalent (p<0.05) for all physical activity metrics at the 14-day level. In the second simulation study, RMSE tended to increase with increased missingness. Multiple imputation showed the smallest RMSE for Steps and TDEE at lower levels of missingness (<19%) and the Kalman and NoHoW methods were generally superior for imputing time in physical activity categories.

CONCLUSION: Individual centred imputation approaches (NoHoW method, Kalman imputation and individual Multiple imputation) offer an effective means to reduce the biases associated with missing data from activity monitors and maximise data retention.

Originalsprog Engelsk
Artikelnummer e0235144
Tidsskrift PLoS One
Vol/bind 15
Udgave nummer 6
Sider (fra-til) e0235144
ISSN 1932-6203
DOI
Status Udgivet - 24 jun. 2020

A pilot study examining patient preference and satisfaction for ava®, a reusable electronic injection device to administer certolizumab pegol

Pouls, B. P. H., Kristensen, L. E., Petersson, M., van den Bemt, B. J. F., Ballerini, L., Bruggraber, R., Karlen, H., Mountian, I., van Bracht, E., Wiegratz, S. & Jørgensen, T. S., maj 2020, I: Expert Opinion on Drug Delivery. 17, 5, s. 705-711 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Acoustic Myography in Assessment of Isokinetic and Isometric Muscle Strength in a Healthy Danish Population

Bartels, E. M., 2020, I: Journal of Biomedical Science and Engineering.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Dansk
Tidsskrift Journal of Biomedical Science and Engineering
ISSN 1937-6871
Status Udgivet - 2020

Adaptive transverse blood velocity estimation in medical ultrasound: A simulation study

Makouei, F. & Asl, B. M., dec. 2020, I: Ultrasonics. 108, s. 106209

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Adoptive cell therapy in combination with checkpoint inhibitors in ovarian cancer

Kverneland, A. H., Pedersen, M., Wulff Westergaard, M. C., Nielsen, M., Borch, T. H., Olsen, L. R., Aasbjerg, G., Santegoets, S. J., van der Burg, S. H., Milne, K., Nelson, B. H., Met, Ö., Donia, M. & Svane, I. M., 1 jun. 2020, I: Oncotarget. 11, 22, s. 2092-2105 14 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Adrenal insufficiency in prednisolone-treated patients with polymyalgia rheumatica or giant cell arteritis-prevalence and clinical approach

Borresen, S. W., Thorgrimsen, T. B., Jensen, B., Hilsted, L., Bartels, E. M., Feldt-Rasmussen, U. & Locht, H., 1 okt. 2020, I: Rheumatology (Oxford, England). 59, 10, s. 2764-2773 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Glucocorticoid treatment is fundamental in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), but carries a risk of glucocorticoid-induced adrenal insufficiency. Adrenal insufficiency can cause reluctance to stop glucocorticoid treatment after disease remission as symptoms can resemble PMR/GCA flare. We aimed to determine the prevalence of adrenal insufficiency in prednisolone-treated patients with PMR/GCA. Methods: We included 47 patients with PMR (n = 37), GCA (n = 1) or both (n = 9), treated with prednisolone for ≥5.4 months, current dose 2.5-10 mg/day. Adrenal function was evaluated using a corticotropin (Synacthen®) stimulation test following 48 h prednisolone pause. Two years' clinical follow-up data are provided. Results: Seven patients (15%) had adrenal insufficiency, 4 (11%) of the 37 patients with PMR alone, and 3 (30%) of the 10 patients with GCA. Corticotropin-stimulated P-cortisol was significantly associated with current prednisolone dose, mean daily dose the last 3 and 6 months before testing, and basal P-cortisol, but not with total dose or treatment duration. Adrenal insufficiency occurred with all current prednisolone doses (2.5-10 mg/day). Five (71%) of the glucocorticoid-insufficient patients could discontinue prednisolone treatment; two of them recovered glucocorticoid function, whereas three still needed hydrocortisone replacement 2 years later. Two patients experienced in total four acute hospital admissions with symptoms of adrenal crises. Conclusion: Glucocorticoid-induced adrenal insufficiency occurred in 15% of patients with PMR/GCA. Mean prednisolone dose the last 3 months and basal P-cortisol were the best and simplest predictors of adrenal function. Most of the glucocorticoid-insufficient patients could discontinue prednisolone with appropriate treatment for adrenal insufficiency.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 59
Udgave nummer 10
Sider (fra-til) 2764-2773
Antal sider 10
ISSN 1462-0324
DOI
Status Udgivet - 1 okt. 2020

Bibliografisk note

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

An update on unconjugated neonatal hyperbilirubinaemia in Denmark

Donneborg, M. L., Hansen, B. M., Petersen, J. P., Vandborg, P. K. & Ebbesen, F., 30 mar. 2020, I: Ugeskrift for Laeger. 182, 14

Publikation: Bidrag til tidsskriftReviewpeer review

Antibiotic containing bone cement in prevention of hip and knee prosthetic joint infections: A systematic review and meta-analysis

Sebastian, S., Liu, Y., Christensen, R., Raina, D. B., Tägil, M. & Lidgren, L., jul. 2020, I: Journal of orthopaedic translation. 23, s. 53-60 8 s.

Publikation: Bidrag til tidsskriftReviewpeer review

Background: Prosthetic joint infection (PJI) is the most serious total joint arthroplasty (TJA) complication despite several aseptic and antiseptic preventive measures. There is no clear evidence or even consensus, whether antibiotic-loaded bone cement (ALBC) should be used, in addition to systemic short-term routine antibiotic prophylaxis, to reduce the risk of PJI in primary TJA. We aimed to analyze the efficacy of ALBC for prevention of PJI in patients undergoing primary TJA.

Methods: We searched systematically for randomized controlled trials (RCTs) in PubMed, Scopus, Embase, Web of Science and Cochrane library. Two reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. PJI was prespecified as the primary outcome of interest. The meta-analyses were based on risk ratios using random-effects model per default. For the purpose of sensitivity, the corresponding fixed effects model odds ratios were calculated with the use of the Peto method as well. To evaluate a potential difference in effect sizes using different types (subgroups) of antibiotics used in bone cement, and at different follow-up periods, we performed stratified meta-analyses.

Results: Thirty-seven studies were eligible for the systematic review and qualitative synthesis, and 9 trials (6507 total joint arthroplasties) were included in this meta-analysis. Overall ALBC significantly reduced the risk of PJI following primary TJAs (RRs, 0.36; 95% CIs, 0.16 to 0.80; P = 0.01) with a moderate degree of inconsistency (I2 = 47%). Based on stratified meta-analyses the use of gentamicin appeared to have a better effect (P = 0.0005) in the total hip arthroplasty. Pooled data of different antibiotics used in knee arthroplasties showed a significant association of cefuroxime (RRs, 0.08; 95% CIs, 0.01 to 0.63; P = 0.02). Further, ALBCs significantly reduced the PJI at one and two years of follow-up (P = 0.03 and P = 0.005 respectively).

Conclusions: The evidence suggests that ALBCs are effective in reducing the PJI following primary TJA; i.e. between 20 and 84% reduced risk. However, the clear limitations of the available trial evidence highlight the need for joint-specific confirmatory trials, that will need to be designed as cluster-randomized trials of clinics in countries with well-functioning arthroplasty registries.The translational potential of this article: This meta-analysis highlights the prophylactic potential of ALBCs in lowering the risk of infection following primary hip or knee arthroplasties but emphasizes the need for more recent confirmatory trials.

Originalsprog Engelsk
Tidsskrift Journal of orthopaedic translation
Vol/bind 23
Sider (fra-til) 53-60
Antal sider 8
ISSN 2214-031X
DOI
Status Udgivet - jul. 2020

Bibliografisk note

© 2020 The Author(s).

Assessing the effect of interventions for axial spondyloarthritis according to the endorsed ASAS/OMERACT core outcome set: a meta-research study of trials included in Cochrane reviews

Andreasen, R. A., Kristensen, L. E., Baraliakos, X., Strand, V., Mease, P. J., de Wit, M., Ellingsen, T., Hansen, I. M. J., Kirkham, J., Wells, G. A., Tugwell, P., Maxwell, L., Boers, M., Egstrup, K. & Christensen, R., 25 jul. 2020, I: Arthritis Research & Therapy. 22, 1, s. 177

Publikation: Bidrag til tidsskriftReviewpeer review

The Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) disease-controlling anti-rheumatic therapy (DC-ART). These include the following domains for all three core sets: "physical function," "pain," "spinal mobility," "spinal stiffness," and "patient's global assessment" (PGA). The core set for clinical record keeping further includes the domains "peripheral joints/entheses" and "acute phase reactants," and the core set for DC-ART further includes the domains "fatigue" and "spine radiographs/hip radiographs." The Outcome Measures in Rheumatology (OMERACT) endorsed the core sets in 1998.Using empirical evidence from axSpA trials, we investigated the efficacy (i.e., net benefit) according to the ASAS/OMERACT core outcome set for axSpA across all interventions tested in trials included in subsequent Cochrane reviews. For all continuous scales, we combined data using the standardized mean difference (SMD) to meta-analyze outcomes involving the same domains. Also, through meta-regression analysis, we examined the effect of the separate SMD measures (independent variables) on the primary endpoint (log [OR], dependent variable) across all trials.Based on 11 eligible Cochrane reviews, from these, 85 articles were screened; we included 43 trials with 63 randomized comparisons. Mean (SD) number of ASAS/OMERACT core outcome domains measured for SM-ARD/physical therapy trials was 4.2 (1.7). Six trials assessed all proposed domains. Mean (SD) for number of core outcome domains for DC-ART trials was 5.8 (1.7). No trials assessed all nine domains. Eight trials (16%) were judged to have inadequate (i.e., high risk of) selective outcome reporting bias. The most responsible core domains for achieving success in meeting the primary objective per trial were pain, OR (95% CI) 5.19 (2.28, 11.77), and PGA, OR (95% CI) 1.87 (1.14, 3.07). In conclusion, selective outcome reporting (and "missing data") should be reduced by encouraging the use of the endorsed ASAS/OMERACT outcome domains in clinical trials. Overall outcome reporting was good for SM-ARD/physical therapy trials and poor for DC-ART trials. Our findings suggest that both PGA and pain provide a valuable holistic construct for the assessment of improvement beyond more objective measures of spinal inflammation.

Originalsprog Engelsk
Tidsskrift Arthritis Research & Therapy
Vol/bind 22
Udgave nummer 1
Sider (fra-til) 177
ISSN 1478-6354
DOI
Status Udgivet - 25 jul. 2020

OBJECTIVE: To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse.

METHODS: Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n = 70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests.

RESULTS: Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P < .01), independent of clinical and radiographic measures, and was also associated with most of the hand-related HAQ items (P < .03). In multivariate models including MRI, SvH scores were not associated with PROs. MRI-assessed inflammation was not associated with PROs at remission or relapse.

CONCLUSION: Magnetic resonance imaging-assessed wrist/hand damage, but not inflammation, in patients with established RA is associated with patient-reported physical impairment at remission and relapse. The amount of damage in the wrist/hand is associated with reduced hand function.

Originalsprog Engelsk
Tidsskrift International Journal of Rheumatic Diseases
Vol/bind 23
Udgave nummer 4
Sider (fra-til) 488-498
Antal sider 10
ISSN 1756-1841
DOI
Status Udgivet - apr. 2020

Bibliografisk note

COPECARE

Association between objectively measured sleep duration, adiposity and weight loss history

Larsen, S. C., Horgan, G., Mikkelsen, M-L. K., Palmeira, A. L., Scott, S., Duarte, C., Santos, I., Encantado, J., Driscoll, R. O., Turicchi, J., Michalowska, J., Stubbs, J. & Heitmann, B. L., jul. 2020, I: International journal of obesity (2005). 44, 7, s. 1577-1585 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: An association between sleep and obesity has been suggested in several studies, but many previous studies relied on self-reported sleep and on BMI as the only adiposity measure. Moreover, a relationship between weight loss history and attained sleep duration has not been thoroughly explored.

DESIGN: The study comprised of 1202 participants of the European NoHoW trial who had achieved a weight loss of ≥5% and had a BMI of ≥25 kg/m2 prior to losing weight. Information was available on objectively measured sleep duration (collected during 14 days), adiposity measures, weight loss history and covariates. Regression models were conducted with sleep duration as the explanatory variable and BMI, fat mass index (FMI), fat-free mass index (FFMI) and waist-hip ratio (WHR) as response variables. Analyses were conducted with 12-month weight loss, frequency of prior weight loss attempts or average duration of weight maintenance after prior weight loss attempts as predictors of measured sleep duration.

RESULTS: After adjusting for physical activity, perceived stress, smoking, alcohol consumption, education, sex and age, sleep duration was associated to BMI (P < 0.001), with the highest BMI observed in the group of participants sleeping <6 h a day [34.0 kg/m2 (95% CI: 31.8-36.1)]. Less difference in BMI was detected between the remaining groups, with the lowest BMI observed among participants sleeping 8-<9 h a day [29.4 kg/m2 (95% CI: 28.8-29.9)]. Similar results were found for FMI (P = 0.008) and FFMI (P < 0.001). We found no association between sleep duration and WHR. Likewise, we found no associations between weight loss history and attained sleep duration.

CONCLUSION: In an overweight population who had achieved a clinically significant weight loss, short sleep duration was associated with higher BMI, with similar associations for fat and lean mass. We found no evidence of association between weight loss history and attained sleep duration.

Originalsprog Engelsk
Tidsskrift International journal of obesity (2005)
Vol/bind 44
Udgave nummer 7
Sider (fra-til) 1577-1585
Antal sider 9
ISSN 0307-0565
DOI
Status Udgivet - jul. 2020

Association Between Participant Retention and the Proportion of Included Elderly People in Rheumatology Trials: Results From a Series of Exploratory Meta-Regression Analyses

Palmowski, A., Nielsen, S. M., Buttgereit, T., Palmowski, Y., Boers, M., Christensen, R. & Buttgereit, F., okt. 2020, I: Arthritis Care & Research. 72, 10, s. 1490-1496 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The elderly, a population defined by an age of ≥65 years, are underrepresented in rheumatology trials, possibly due to investigators' concerns of increased premature discontinuations in higher age groups. The present study was undertaken to evaluate whether the proportion of included elderly individuals (PE) is independently associated with participant retention in rheumatology trials.

METHODS: Medline was searched for randomized controlled trials (RCTs) in rheumatoid arthritis (RA) and osteoarthritis (OA) of any intervention (years 2016 and 2017). PE was either extracted from the research manuscript or estimated from an assumed (truncated) normal distribution. We used mixed-effects meta-regression models including several covariates to assess whether there is an independent association between PE and participant retention. Using sensitivity analyses, we evaluated whether associations were connected to attrition due to lack of efficacy (LoE) or adverse events (AE).

RESULTS: In total, 243 RCTs comprising >48,000 participants were included. Pooled participant retention was 88%. PE was not associated with retention in the unadjusted (P = 0.97) or adjusted (all: P ≥ 0.14) models. Of all covariates, only study duration and type of intervention were associated with retention (both: P < 0.001). Post hoc analyses allowing for interaction revealed a small but statistically significant positive association between PE and retention in pharmacologic interventions and a negative association in physical/physiotherapeutic interventions (overall P for interaction = 0.05). No associations were found for PE and attrition due to LoE or AE.

CONCLUSION: Participant retention in RA and OA trials is high and not associated with PE. These findings should motivate investigators to include more elderly participants in rheumatology trials.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
Vol/bind 72
Udgave nummer 10
Sider (fra-til) 1490-1496
Antal sider 7
ISSN 2151-464X
DOI
Status Udgivet - okt. 2020

Bibliografisk note

© 2019 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Association Between Reproductive Life Span and Incident Nonfatal Cardiovascular Disease: A Pooled Analysis of Individual Patient Data From 12 Studies

Mishra, S. R., Chung, H-F., Waller, M., Dobson, A. J., Greenwood, D. C., Cade, J. E., Giles, G. G., Bruinsma, F., Simonsen, M. K., Hardy, R., Kuh, D., Gold, E. B., Crawford, S. L., Derby, C. A., Matthews, K. A., Demakakos, P., Lee, J. S., Mizunuma, H., Hayashi, K., Sievert, L. L., & 4 flereBrown, D. E., Sandin, S., Weiderpass, E. & Mishra, G. D., 1 dec. 2020, I: JAMA Cardiology. 5, 12, s. 1410-1418 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Importance: Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD.

Objective: To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause.

Design, Setting, and Participants: Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019.

Exposures: Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older.

Main Outcomes and Measures: First nonfatal CVD event, including coronary heart disease and stroke events.

Results: A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (<30 years) were at 1.71 (95% CI, 1.58-1.84) times higher risk of incident CVD events than women with a reproductive life span of 36 to 38 years after adjustment for covariates. This association remained unchanged when adjusted for age at menarche but was attenuated to 1.26 (95% CI, 1.09-1.46) when adjusted for age at menopause. There was a significant interaction between reproductive life span and age at menarche associated with CVD risk (P < .001). Women who had both short reproductive life span (<33 years) and early menarche (age ≤11 years) had the highest risk of CVD (hazard ratio, 2.06; 95% CI, 1.76-2.41) compared with those with a reproductive life span of 36 to 38 years and menarche at age 13 years.

Conclusions and Relevance: Short reproductive life span was associated with an increased risk of nonfatal CVD events in midlife, and the risk was significantly higher for women with early age at menarche.

Originalsprog Engelsk
Tidsskrift JAMA Cardiology
Vol/bind 5
Udgave nummer 12
Sider (fra-til) 1410-1418
Antal sider 9
ISSN 2380-6583
DOI
Status Udgivet - 1 dec. 2020

Pages