Elevated HbA1c is not associated with recurrent venous thromboembolism in the elderly, but with all-cause mortality– the SWEETCO 65+ study

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Abstract

The association of glycated hemoglobin (HbA1c) with venous thromboembolism (VTE) and death in the elderly is unknown. In the SWEETCO 65+ study we analyzed prospectively a Swiss Cohort of Elderly Patients with Venous Thromboembolism (SWITCO 65+). 888 patients were enrolled for the SWEETCO 65+ analysis. HbA1c was determined at baseline and divided into three categories (HbA1c < 5.7%, normal range; 5.7–6.49%, pre-diabetic range; and >6.5%, diabetic range). Median follow-up was 2.5 years. The primary endpoint was recurrent VTE. Secondary endpoints included all-cause mortality and major bleeds. The total prevalence of diabetes was 22.1%. The risk of recurrent VTE was similar in patients with HbA1c with pre-diabetes (adjusted subhazard ratio (aSHR) 1.07 [0.70 to 1.63]) and diabetes (aSHR 0.73 [0.39 to 1.37]) as compared to those with a HbA1c in the normal range. However, a HbA1c ≥ 6.5% (median IQ range 7.0 [6.70;7.60]) was significantly associated with a higher risk of all-cause mortality (adjusted hazard ratio [aHR] 1.83 [1.21 to 2.75]). In summary we found no association between HbA1c and major bleeding. Elevated HbA1c levels are not associated with recurrent VTE but with increased all-cause mortality in an elderly population with acute VTE.

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Cardiovascular risk factors and venous thromboembolism: a meta-analysis.

Walter Ageno, Cecilia Becattini, Timothy Brighton … (2008)

The concept that venous thromboembolism (VTE) and atherosclerosis are 2 completely distinct entities has recently been challenged because patients with VTE have more asymptomatic atherosclerosis and more cardiovascular events than control subjects. We performed a meta-analysis to assess the association between cardiovascular risk factors and VTE. Medline and EMBASE databases were searched to identify studies that evaluated the prevalence of major cardiovascular risk factors in VTE patients and control subjects. Studies were selected using a priori defined criteria, and each study was reviewed by 2 authors who abstracted data on study characteristics, study quality, and outcomes. Odds ratios or weighted means and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of chi2 and I2 statistics. Twenty-one case-control and cohort studies with a total of 63 552 patients met the inclusion criteria. Compared with control subjects, the risk of VTE was 2.33 for obesity (95% CI, 1.68 to 3.24), 1.51 for hypertension (95% CI, 1.23 to 1.85), 1.42 for diabetes mellitus (95% CI, 1.12 to 1.77), 1.18 for smoking (95% CI, 0.95 to 1.46), and 1.16 for hypercholesterolemia (95% CI, 0.67 to 2.02). Weighted mean high-density lipoprotein cholesterol levels were significantly lower in VTE patients, whereas no difference was observed for total and low-density lipoprotein cholesterol levels. Significant heterogeneity among studies was present in all subgroups except for the diabetes mellitus subgroup. Higher-quality studies were more homogeneous, and significant associations remained unchanged. Cardiovascular risk factors are associated with VTE. This association is clinically relevant with respect to individual screening, risk factor modification, and primary and secondary prevention of VTE. Prospective studies should further investigate the underlying mechanisms of this relationship.

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Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk.

Kay-Tee Khaw, Nicholas J. Wareham, Sheila Bingham … (2004)

Increasing evidence suggests a continuous relationship between blood glucose concentrations and cardiovascular risk, even below diagnostic threshold levels for diabetes. To examine the relationship between hemoglobin A1c, cardiovascular disease, and total mortality. Prospective population study. Norfolk, United Kingdom. 4662 men and 5570 women who were 45 to 79 years of age and were residents of Norfolk. Hemoglobin A1c and cardiovascular disease risk factors were assessed from 1995 to 1997, and cardiovascular disease events and mortality were assessed during the follow-up period to 2003. In men and women, the relationship between hemoglobin A1c and cardiovascular disease (806 events) and between hemoglobin A1c and all-cause mortality (521 deaths) was continuous and significant throughout the whole distribution. The relationship was apparent in persons without known diabetes. Persons with hemoglobin A1c concentrations less than 5% had the lowest rates of cardiovascular disease and mortality. An increase in hemoglobin A1c of 1 percentage point was associated with a relative risk for death from any cause of 1.24 (95% CI, 1.14 to 1.34; P < 0.001) in men and with a relative risk of 1.28 (CI, 1.06 to 1.32; P < 0.001) in women. These relative risks were independent of age, body mass index, waist-to-hip ratio, systolic blood pressure, serum cholesterol concentration, cigarette smoking, and history of cardiovascular disease. When persons with known diabetes, hemoglobin A(1c) concentrations of 7% or greater, or a history of cardiovascular disease were excluded, the result was similar (adjusted relative risk, 1.26 [CI, 1.04 to 1.52]; P = 0.02). Fifteen percent (68 of 521) of the deaths in the sample occurred in persons with diabetes (4% of the sample), but 72% (375 of 521) occurred in persons with HbA1c concentrations between 5% and 6.9%. Whether HbA1c concentrations and cardiovascular disease are causally related cannot be concluded from an observational study; intervention studies are needed to determine whether decreasing HbA1c concentrations would reduce cardiovascular disease. The risk for cardiovascular disease and total mortality associated with hemoglobin A1c concentrations increased continuously through the sample distribution. Most of the events in the sample occurred in persons with moderately elevated HbA1c concentrations. These findings support the need for randomized trials of interventions to reduce hemoglobin A1c concentrations in persons without diabetes.

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The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients.

Paolo Prandoni, Franco Noventa, Angelo Ghirarduzzi … (2007)

While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence. We followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion. After a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5-12.5) after 1 year, 19.6% (17.5-21.7) after 3 years, 29.1% (26.3-31.9) after 5 years, and 39.9% (35.4-44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82-2.90) in patients whose first VTE was unprovoked, 2.02 (1.52-2.69) in those with thrombophilia, 1.44 (1.03-2.03) in those presenting with primary DVT, 1.39 (1.08-1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06-1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change. Besides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age.

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Author and article information

Contributors

Juerg H. Beer: hansjuerg.beer@ksb.ch

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 12 February 2020

Publication date PMC-release: 12 February 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 2495

Affiliations

[1 ]DiaMon Institute, Baden-Dättwil, Switzerland

[2 ]Department of Internal Medicine, Cantonal Hospital of Baden, Baden, Switzerland

[3 ]ISNI 0000 0004 1937 0650, GRID grid.7400.3, Center for Molecular Cardiology, , University of Zurich, ; Schlieren, Switzerland

[4 ]Central Laboratory, Cantonal Hospital of Baden, Baden, Switzerland

[5 ]ISNI 0000 0001 0726 5157, GRID grid.5734.5, CTU Bern, and Institute of Social and Preventive Medicine (ISPM), , University of Bern, ; Bern, Switzerland

[6 ]Division of General Internal Medicine, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland

[7 ]ISNI 0000 0001 0423 4662, GRID grid.8515.9, Division of Internal Medicine, , Lausanne University Hospital, ; Lausanne, Switzerland

[8 ]ISNI 0000 0001 0726 5157, GRID grid.5734.5, Institute of Primary Health Care (BIHAM), , University of Bern, ; Bern, Switzerland

[9 ]Department of Hematology and Central Hematology Laboratory, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland

[10 ]ISNI 0000 0001 0726 5157, GRID grid.5734.5, Department of Bio Medical Research, , University of Bern, ; Bern, Switzerland

[11 ]ISNI 0000 0001 0721 9812, GRID grid.150338.c, Division of Angiology and Hemostasis, , Geneva University Hospital, ; Geneva, Switzerland

[12 ]GRID grid.410567.1, Division of Angiology, , Basel University Hospital, ; Basel, Switzerland

[13 ]Department of Internal Medicine, Cantonal Hospital of Frauenfeld, Frauenfeld, Switzerland

[14 ]ISNI 0000 0001 2294 4705, GRID grid.413349.8, Cantonal Hospital of St. Gallen, ; St. Gallen, Switzerland

[15 ]ISNI 0000 0004 0478 9977, GRID grid.412004.3, Division of Angiology, , Zurich University Hospital, ; Zurich, Switzerland

[16 ]ISNI 0000 0004 0478 9977, GRID grid.412004.3, Department for Cardiology, , University Heart Center, Zurich University Hospital, ; Zurich, Switzerland

[17 ]ISNI 0000 0000 8587 8621, GRID grid.413354.4, Division of Angiology, , Cantonal Hospital of Lucerne, ; Lucerne, Switzerland

[18 ]ISNI 0000 0001 0423 4662, GRID grid.8515.9, Emergency Department, , Lausanne University Hospital, ; Lausanne, Switzerland

Author information

Simona Stivala http://orcid.org/0000-0003-1549-8932

Oliver Hugli http://orcid.org/0000-0003-2312-1625

Article

Publisher ID: 59173

DOI: 10.1038/s41598-020-59173-2

PMC ID: 7016100

PubMed ID: 32051462

SO-VID: 960ea244-2fae-4828-affc-9016e2076118

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 13 December 2018

Date accepted : 21 January 2020

Funding

Funded by: Foundation Kardio Baden, Switzerland The Swiss National Science Foundation, grant. no 33CSCO-122659/139470 for the Switco 65+ study and grant no. 310030_144152/1 to Prof. HJ Beer for the substudy Sweetco 65+

Funded by: JHB has received research grant support by the Swiss National Fondation of Science and educational grants and honoraria from Bayer HealthCare, BMS, Boehringer Ingelheim and Daiichi Sankyo outside this study

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Keywords: endocrinology,medical research

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ScienceOpen disciplines: Uncategorized

Keywords: endocrinology, medical research

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Elevated HbA1c is not associated with recurrent venous thromboembolism in the elderly, but with all-cause mortality– the SWEETCO 65+ study

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Most cited references 47

Cardiovascular risk factors and venous thromboembolism: a meta-analysis.

Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk.

The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients.

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