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Arefalk, Gabriel
Publications (8 of 8) Show all publications
Arefalk, G. (2018). Smokeless Tobacco (Snus) and Cardiovascular Disease: Associations with Heart Failure and Prognosis after Myocardial Infarction. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Smokeless Tobacco (Snus) and Cardiovascular Disease: Associations with Heart Failure and Prognosis after Myocardial Infarction
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Previous investigations of snus use (oral moist snuff, a Swedish form of smokeless tobacco) and cardiovascular disease have generally focused on atherosclerotic events such as myocardial infarction and stroke, likely because smoking is such a well-established risk factor for atherosclerotic disease. Smokeless administration of tobacco circumvents most of the atherogenic effects of the combusted products from smoked tobacco, but it is possible that the potent autonomic and hemodynamic effects of snus and nicotine per se are detrimental for cardiovascular tissues.

The aim of this thesis was to investigate if snus is associated with development of heart failure and the prognosis after myocardial infarction. We used data from Swedish cohort studies and the national quality register for myocardial infarctions (SWEDEHEART), with linkages to national registers.

Snus use was associated with a higher risk of heart failure in a dose-response manner. This association was specific to non-ischemic heart failure, implying a direct myocardial effect, rather than an atherogenic effect (papers I and II).

Acute, short-term or long-term outcomes following a myocardial infarction were not consistently worse among snus users relative to snus non-users, although snus use was associated with an increased risk of death after myocardial infarction among never-smokers (paper III).

Discontinuation of snus use after a myocardial infarction was associated with an almost halved mortality risk, similar to the benefit associated with smoking cessation (paper IV).

Although smoking was consistently stronger related to all adverse outcomes, and with reservations due to the observational design, the findings from this thesis indicate that snus should not be regarded as harmless. Snus use was associated with a higher risk of heart failure and post-myocardial infarction mortality, which may have public health implications for the risk assessment of snus, and potentially other modes of smokeless nicotine.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 67
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1445
Keywords
Snus, smokeless tobacco, nicotine, cardiovascular disease, heart failure, myocardial infarction, mortality, prognosis, epidemiology
National Category
Clinical Medicine Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Epidemiology
Identifiers
urn:nbn:se:uu:diva-345869 (URN)978-91-513-0283-6 (ISBN)
Public defence
2018-05-09, Enghoffsalen, Akademiska Sjukhuset, ingång 50 BV, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2018-04-18 Created: 2018-03-18 Last updated: 2018-10-08
Hofmann, R., James, S. K., Jernberg, T., Lindahl, B., Erlinge, D., Witt, N., . . . Svensson, L. (2017). Oxygen Therapy in Suspected Acute Myocardial Infarction. New England Journal of Medicine, 377(13), 1240-1249
Open this publication in new window or tab >>Oxygen Therapy in Suspected Acute Myocardial Infarction
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2017 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 13, p. 1240-1249Article in journal (Refereed) Published
Abstract [en]

BACKGROUND The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P = 0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P = 0.33). The results were consistent across all predefined subgroups. CONCLUSIONS Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality.

Place, publisher, year, edition, pages
MASSACHUSETTS MEDICAL SOC, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-337093 (URN)10.1056/NEJMoa1706222 (DOI)000411838100007 ()28844200 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research CouncilSwedish Foundation for Strategic Research AstraZeneca
Available from: 2018-01-08 Created: 2018-01-08 Last updated: 2018-01-08Bibliographically approved
Arefalk, G., Hambraeus, K., Lind, L., Michaëlsson, K., Lindahl, B. & Sundström, J. (2015). Response to Letter Regarding Article, "Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction" [Letter to the editor]. Circulation, 131(17), E423-E423
Open this publication in new window or tab >>Response to Letter Regarding Article, "Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction"
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2015 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 131, no 17, p. E423-E423Article in journal, Letter (Refereed) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-257116 (URN)10.1161/CIRCULATIONAHA.114.014029 (DOI)000353560600002 ()25918045 (PubMedID)
Available from: 2015-06-30 Created: 2015-06-30 Last updated: 2018-11-30
Arefalk, G., Hambraeus, K., Lind, L., Michaëlsson, K., Lindahl, B. & Sundström, J. (2014). Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction. Circulation, 130(4), 325-323
Open this publication in new window or tab >>Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction
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2014 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 130, no 4, p. 325-323Article in journal (Refereed) Published
Abstract [en]

Background-Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and Results-All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). Conclusions-In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

Keywords
mortality, myocardial infarction, prognosis, risk factors, smokeless tobacco
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-230084 (URN)10.1161/CIRCULATIONAHA.113.007252 (DOI)000339392300009 ()24958793 (PubMedID)
Available from: 2014-09-03 Created: 2014-08-19 Last updated: 2018-03-18
Arefalk, G., Hergens, M.-P., Ingelsson, E., Ärnlöv, J., Michaëlsson, K., Lind, L., . . . Sundström, J. (2012). Smokeless Tobacco (Snus) and Risk of Heart Failure: Results from Two Swedish Cohorts. European Journal of Cardiovascular Prevention & Rehabilitation, 19(5), 1120-1127
Open this publication in new window or tab >>Smokeless Tobacco (Snus) and Risk of Heart Failure: Results from Two Swedish Cohorts
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2012 (English)In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 19, no 5, p. 1120-1127Article in journal (Refereed) Published
Abstract [en]

Background:

Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.

Design:

Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers.

Methods:

Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

Results:

In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.

Conclusion:

Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-164695 (URN)10.1177/1741826711420003 (DOI)000309527700022 ()21828223 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2011-12-22 Created: 2011-12-22 Last updated: 2018-03-22
Arefalk, G., Hergens, M. P., Ingelsson, E., Ärnlöv, J., Michaëlsson, K., Lind, L., . . . Sundström, J. (2010). Smokeless Tobacco (Snus) And Risk Of Heart Failure In Two Swedish Cohorts. Journal of Hypertension, 28, E48-E49
Open this publication in new window or tab >>Smokeless Tobacco (Snus) And Risk Of Heart Failure In Two Swedish Cohorts
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2010 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, p. E48-E49Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-140936 (URN)000283023402015 ()
Available from: 2011-01-10 Created: 2011-01-10 Last updated: 2017-12-11Bibliographically approved
Arefalk, G., Svennblad, B., Andersen, K., James, S. K., Varenhorst, C. & Sundström, J.Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART Study.
Open this publication in new window or tab >>Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART Study
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background

Based on effects of nicotine and snus (a smokeless tobacco) on hemodynamics, pro-arrhythmia and remodelling, in combination with indications of increased risk for fatal myocardial infarction (MI) in snus users; we hypothesised that the outcome of an MI may be worse in snus users.

Methods

Data was extracted from the SWEDEHEART registry for all patients who underwent coronary angiography in Sweden due to MI between December 2009 and December 2014. In snus users (n=4,950) relative to snus non-users (n=55,412), we compared risks of a large MI (defined as hs-cTnT of  > 10,000 ng/L, cTnT > 10 μg/L or cTnI > 10 μg/L) and death in the acute (in-hospital) setting, and death+HF (a combined endpoint of all-cause death or hospitalization for heart failure) and all-cause death at short- (<28 days) and long-term follow-up. Relations of snus use to outcomes were also analysed in pre-specified subgroups of never, previous and current smokers.

Results

A large MI was diagnosed in 10,975 patients. During long-term follow-up (median 1.9 years), 7,758 either died (n=6,044) or were hospitalized due to heart failure (n=1,714). In models adjusting for age, gender, smoking, previous MI and occupational classification (employed, unemployed/sick leave and retired), snus use was not associated with risk of large MI (odds ratio 1.01; 95% confidence interval (CI) 0.93-1.09) or death+HF (long-term Cox proportional hazard ratio (HR) 0.99; 95% CI 0.90-1.10). Nonetheless, among never-smokers snus use was associated with an increased risk for death+HF (long-term HR 1.26, 95% CI 1.03-1.55), driven by a higher mortality risk (long-term HR for death of any cause 1.29, 95% CI 1.02-1.64).

Conclusions

In this study, snus use was unrelated to acute, short-term or long-term adverse outcomes after an MI. Among never-smokers, snus use was associated with an increased risk of post-MI death.

National Category
Medical and Health Sciences Cardiac and Cardiovascular Systems
Research subject
Cardiology; Epidemiology; Medical Science
Identifiers
urn:nbn:se:uu:diva-342247 (URN)
Available from: 2018-03-18 Created: 2018-03-18 Last updated: 2018-06-26
Arefalk, G., Galanti, R., Lundberg, M., Ye, W., Norberg, M., Lindmark, K., . . . Magnusson, C.Smokeless Tobacco (Snus) and Risk of Heart Failure of Ischemic and Non-Ischemic Origin: a Pooled Analysis of Eight Prospective Cohort Studies.
Open this publication in new window or tab >>Smokeless Tobacco (Snus) and Risk of Heart Failure of Ischemic and Non-Ischemic Origin: a Pooled Analysis of Eight Prospective Cohort Studies
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background

Snus, a Swedish type of smokeless tobacco, has potent acute hemodynamic effects, which could provoke stress on the cardiovascular system, including the myocardium. Snus has, however, not been linked to risk of ischemic heart disease. Therefore, we hypothesized that snus use increases the risk for heart failure of non-ischemic origin.

Methods

We conducted a pooled analysis of eight Swedish prospective cohort studies involving individual participant data from 350,711 men. Shared frailty models with random effects at the cohort level, were used to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs) of heart failure in relation to snus use. We investigated dose-response associations, and association with ischemic and non-ischemic heart failure in separate. For positive control purposes, we also investigated associations between smoking and risk of heart failure.

Results

During a median follow-up time of 16 years, 5,404 men were hospitalized for heart failure. In models adjusting for age, smoking, previous myocardial infarction and educational level, current snus use was associated with a higher risk of heart failure (HR 1.27, 95 % CI 1.07-1.50), relative to non-current snus use. A dose-response pattern was observed, with higher risk with more snus cans used per week. We observed an association of snus use with non-ischemic heart failure, HR 1.34 (95 % CI 1.11-1.63), but not with ischemic heart failure, HR 1.01 (95 % CI 0.72-1.42). Smoking was more strongly associated with heart failure, particularly of ischemic origin, than snus use.

Conclusions

Snus use was associated with a modestly increased risk for heart failure of non-ischemic origin in a dose-response manner. This finding has public health implications for the risk assessment of snus use, and potentially other modes of smokeless use of nicotine.

National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Cardiology; Epidemiology
Identifiers
urn:nbn:se:uu:diva-345868 (URN)
Available from: 2018-03-18 Created: 2018-03-18 Last updated: 2018-03-22
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