Review
Fish Intake and Venous Thromboembolism: A Systematic Literature Review
Clinical and Applied Thrombosis/Hemostasis 1-5 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1076029615585992 cat.sagepub.com
Camilla Mattiuzzi, MD1, Gianfranco Cervellin, MD2, Massimo Franchini, MD3, and Giuseppe Lippi, MD4
Abstract Diet plays an important role in modulating the risk of arterial and venous thrombosis. Several lines of evidence attest that consumption of fish and its compounds, especially omega-3 fatty acids, may be effective to decrease the cardiovascular risk. Since the pathogenesis of arterial and venous thrombosis share some common aspects, we performed a systematic review of published clinical studies that investigated the association between fish intake and venous thrombosis. An electronic search was carried out in Medline, Scopus, and ISI Web of Science using the key words ‘‘fish’’ OR ‘‘seafood’’ AND ‘‘venous thromboembolism’’ OR ‘‘deep vein thrombosis’’ OR ‘‘pulmonary embolism’’, with no language or date restriction. Overall, 6 studies (5 prospective and 1 case– control) were finally identified. In only 1 small case–control study, a larger intake of total fish was found to be negatively associated with the risk of venous thromboembolism. No association was found in 4 large prospective studies, whereas a positive association was observed in the remaining. No substantial difference was also noticed between intake of fatty or lean fish. Taken together, the current epidemiological evidence does not support the existence of a significant effect of total fish consumption on the risk of venous thromboembolism. Keywords venous thromboembolism, thrombosis, fish, seafood, risk
Introduction Venous thromboembolism (VTE), which conventionally entails deep vein thrombosis and/or pulmonary embolism, is a relatively frequent disorder, whose prevalence approximates 422 per 100 000 in the general population.1 The frequency of VTE is even higher in hospitalized patients (ie, *3.8%) and represents the leading cause of morbidity and death in these patients.2 The pathogenesis of VTE is clearly multifaceted and multifactorial, wherein several acquired prothrombotic conditions interplay with a discrete number of genetic abnormalities.3,4 Among the various risk factors, diet seems to play a noticeable role, in that a number of nutrients and dietary supplements interplay with primary and secondary hemostasis, thus exerting a positive or negative influence on platelet biology and blood coagulation.5 Several lines of evidence now attest that fish consumption may be associated with a lower risk of cardiovascular disease. A recent meta-analysis including 11 prospective cohort and 8 case–control studies totaling 408 305 participants proved the existence of an inverse association between fish intake and risk of acute coronary syndrome, since an additional 100 g serving of fish per week was found to be associated with a 5% (95% confidence interval CI, 3%-8%) reduced risk of coronary heart disease.6 A modest and inverse association between fish intake and cerebrovascular disease was also reported in
another recent meta-analysis of 26 prospective cohort and 12 randomized trials totaling 794 000 participants,7 in which total fish consumption of 5 servings per week was associated with a 12% (95% CI, 4%-19%) lower cerebrovascular risk compared to the intake of 1 serving per week. The beneficial influence of fish consumption on cardiovascular risk has been mostly attributed to the presence of omega-3 fatty acids, which are seemingly effective to produce a wide spectrum of favorable effects, including reduction in total and low-density lipoprotein cholesterol and increase in highdensity lipoprotein cholesterol and platelet inhibition.8 Since the pathogenesis of arterial and venous thrombosis share some common and partially overlapping aspects (eg, thrombophilia, age, obesity, diabetes, and smoking),9 we performed a systematic
1
Service of Clinical Governance, General Hospital of Trento, Trento, Italy Emergency Department, Academic Hospital of Parma, Parma, Italy 3 Department of Hematology and Transfusion Medicine, C. Poma Hospital, Mantova, Italy 4 Laboratory of Clinical Chemistry and Hematology, Academic Hospital of Parma, Parma, Italy 2
Corresponding Author: Giuseppe Lippi, U.O. Diagnostica Ematochimica, Azienda OspedalieroUniversitaria di Parma, Via Gramsci, 14, 43126, Parma, Italy. Email: [email protected], [email protected]
Downloaded from cat.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 19, 2015
2
Clinical and Applied Thrombosis/Hemostasis
Electronic search (Medline, Scopus and ISI Web of Science)
Keywords: - “fish” OR “seafood” AND - “venous thromboembolism” OR “deep vein thrombosis” OR “pulmonary embolism”
26 documents identified after exclusion of replicates
6 documents selected
Excluded after title, abstract or full-text reading (n. 20) - n. 11: No data on the association between VTE and fish intake - n. 3: Review articles - n. 3: Letter or commentary - n. 2: Case reports - n. 1: Duplicate study
- n. 5: Prospective studies - n. 1: Case-control study
Figure 1. Description of results of the search methodology.
review of published clinical studies that investigated the association between fish intake and VTE.
Search Methodology An electronic search was performed in Medline (with PubMed interface), Scopus, and ISI Web of Science using the key words ‘‘fish’’ OR ‘‘seafood’’ AND ‘‘venous thromboembolism’’ OR ‘‘deep vein thrombosis’’ OR ‘‘pulmonary embolism’’ in ‘‘Title/Abstract/Keywords’’, with no language or date restriction. All articles identified according to the search criteria were systematically reviewed by 2 authors (GL and CM). The references of selected articles were also hand-searched to identify other pertinent documents.
Results A total number of 26 publications could be identified after elimination of replicate documents among the 3 scientific databases. Twenty documents were excluded after accurate reading of title, abstract, and full text (when available; Figure 1). Therefore, 6 studies (5 prospective and 1 case–control) were finally
selected for this systematic literature review (Table 1).10-15 Interrater agreement was absolute (k statistics, 1.00). Steffen et al carried out a prospective trial including 14 962 middle-aged participants (8253 women and 6709 men) of the Atherosclerosis Risk in Communities study, who were followed up for 12.5 years.10 Overall, 197 VTE events were recorded during follow-up (VTE rate: 1.3%). After classification of the study population in quintiles of daily food intake, the VTE risk of participants in the highest quintile of total fish intake was not significantly different from that of participants in the lowest quintile (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.44-1.10). A larger consumption of omega-3 fatty acids was also found to be ineffective for lowering the risk of VTE (HR of highest vs lowest quintile of intake: 0.70; 95% CI, 0.43-1.13). Results were similar after excluding idiopathic VTE from analysis. Lutsey et al carried out a prospective study including 37 393 women aged 55 to 69 years who participated in the Iowa Women’s Health Study and were followed up for 19 years.11 A total number of 1950 cases with VTE were recorded during follow-up (VTE rate: 5.2%). Women consuming 2.5 servings per week of total fish exhibited a significantly higher risk of
Downloaded from cat.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 19, 2015
Mattiuzzi et al
3
Table 1. Description of Prospective and Case–Control Studies Investigating the Association Between Fish Intake and Risk of VTE. Authors
Setting
Study Design Study Population
End Point
Results
Incident VTE (1.3%) HR of total fish intake: 14 962 participants (8253 women and 0.70; 95% CI, 6709 men) aged 45-64 years, followed 0.44-1.10 up for 12.5 years Lutsey et al, United Prospective 37 393 women aged 55-69 years, followed Incident VTE (5.2%) HR of total fish intake: 2009 States up for 19 years 1.22; 95% CI, 1.03-1.46 Prevalence of VTE OR of total fish intake: Bhoopat et al, Thailand Case–control 97 Patients with VTE (68 women and (32.5%) 0.24; 95% CI, 2010 29 men; age 17-93 years) and 0.10-0.56 195 matched controls (136 women and 59 men; age 22-88 years) Varraso et al, United Prospective 129 430 participants (80 192 women and Incident VTE (2.2%) RR of total fish intake in men: 0.96; 95% 2012 States 49 238 men) aged 40-75 years, followed CI, 0.80-1.14 up for 24 years RR of total fish intake in women: 0.95; 95% CI, 0.80-1.11 Hansen-Krone Norway Prospective 23 621 participants (12 381 women and Incident VTE (2.3%) HR of total fish intake: 0.78; 95% CI, et al, 2014 11 240 men) aged 25-97 years, followed 0.60-1.01 up for 15.8 years HR of total fish and fish oil supplements in take: 0.52; 95% CI, 0.34-0.79 Severinsen Denmark Prospective 57 054 participants (29 876 women and Incident VTE (1.1%) HR of total fish intake in men: 0.98; 95% et al, 2014 27 178 men) aged 50-64, followed up CI, 0.64-1.2.8 for 10.2 years HR of total fish intake in women: 1.19; 95% CI, 0.77-1.83 Steffen et al, 2007
United States
Prospective
Reference 10
11
12
13
14
15
Abbreviations: HR, hazard ratio; OR, odds ratio; VTE, venous thromboembolism; RR, relative risk.
VTE compared to those reporting an intake 2.64 servings per day of total fish compared to those reporting an intake
Fish Intake and Venous Thromboembolism: A Systematic Literature Review
Clinical and Applied Thrombosis/Hemostasis 1-5 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1076029615585992 cat.sagepub.com
Camilla Mattiuzzi, MD1, Gianfranco Cervellin, MD2, Massimo Franchini, MD3, and Giuseppe Lippi, MD4
Abstract Diet plays an important role in modulating the risk of arterial and venous thrombosis. Several lines of evidence attest that consumption of fish and its compounds, especially omega-3 fatty acids, may be effective to decrease the cardiovascular risk. Since the pathogenesis of arterial and venous thrombosis share some common aspects, we performed a systematic review of published clinical studies that investigated the association between fish intake and venous thrombosis. An electronic search was carried out in Medline, Scopus, and ISI Web of Science using the key words ‘‘fish’’ OR ‘‘seafood’’ AND ‘‘venous thromboembolism’’ OR ‘‘deep vein thrombosis’’ OR ‘‘pulmonary embolism’’, with no language or date restriction. Overall, 6 studies (5 prospective and 1 case– control) were finally identified. In only 1 small case–control study, a larger intake of total fish was found to be negatively associated with the risk of venous thromboembolism. No association was found in 4 large prospective studies, whereas a positive association was observed in the remaining. No substantial difference was also noticed between intake of fatty or lean fish. Taken together, the current epidemiological evidence does not support the existence of a significant effect of total fish consumption on the risk of venous thromboembolism. Keywords venous thromboembolism, thrombosis, fish, seafood, risk
Introduction Venous thromboembolism (VTE), which conventionally entails deep vein thrombosis and/or pulmonary embolism, is a relatively frequent disorder, whose prevalence approximates 422 per 100 000 in the general population.1 The frequency of VTE is even higher in hospitalized patients (ie, *3.8%) and represents the leading cause of morbidity and death in these patients.2 The pathogenesis of VTE is clearly multifaceted and multifactorial, wherein several acquired prothrombotic conditions interplay with a discrete number of genetic abnormalities.3,4 Among the various risk factors, diet seems to play a noticeable role, in that a number of nutrients and dietary supplements interplay with primary and secondary hemostasis, thus exerting a positive or negative influence on platelet biology and blood coagulation.5 Several lines of evidence now attest that fish consumption may be associated with a lower risk of cardiovascular disease. A recent meta-analysis including 11 prospective cohort and 8 case–control studies totaling 408 305 participants proved the existence of an inverse association between fish intake and risk of acute coronary syndrome, since an additional 100 g serving of fish per week was found to be associated with a 5% (95% confidence interval CI, 3%-8%) reduced risk of coronary heart disease.6 A modest and inverse association between fish intake and cerebrovascular disease was also reported in
another recent meta-analysis of 26 prospective cohort and 12 randomized trials totaling 794 000 participants,7 in which total fish consumption of 5 servings per week was associated with a 12% (95% CI, 4%-19%) lower cerebrovascular risk compared to the intake of 1 serving per week. The beneficial influence of fish consumption on cardiovascular risk has been mostly attributed to the presence of omega-3 fatty acids, which are seemingly effective to produce a wide spectrum of favorable effects, including reduction in total and low-density lipoprotein cholesterol and increase in highdensity lipoprotein cholesterol and platelet inhibition.8 Since the pathogenesis of arterial and venous thrombosis share some common and partially overlapping aspects (eg, thrombophilia, age, obesity, diabetes, and smoking),9 we performed a systematic
1
Service of Clinical Governance, General Hospital of Trento, Trento, Italy Emergency Department, Academic Hospital of Parma, Parma, Italy 3 Department of Hematology and Transfusion Medicine, C. Poma Hospital, Mantova, Italy 4 Laboratory of Clinical Chemistry and Hematology, Academic Hospital of Parma, Parma, Italy 2
Corresponding Author: Giuseppe Lippi, U.O. Diagnostica Ematochimica, Azienda OspedalieroUniversitaria di Parma, Via Gramsci, 14, 43126, Parma, Italy. Email: [email protected], [email protected]
Downloaded from cat.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 19, 2015
2
Clinical and Applied Thrombosis/Hemostasis
Electronic search (Medline, Scopus and ISI Web of Science)
Keywords: - “fish” OR “seafood” AND - “venous thromboembolism” OR “deep vein thrombosis” OR “pulmonary embolism”
26 documents identified after exclusion of replicates
6 documents selected
Excluded after title, abstract or full-text reading (n. 20) - n. 11: No data on the association between VTE and fish intake - n. 3: Review articles - n. 3: Letter or commentary - n. 2: Case reports - n. 1: Duplicate study
- n. 5: Prospective studies - n. 1: Case-control study
Figure 1. Description of results of the search methodology.
review of published clinical studies that investigated the association between fish intake and VTE.
Search Methodology An electronic search was performed in Medline (with PubMed interface), Scopus, and ISI Web of Science using the key words ‘‘fish’’ OR ‘‘seafood’’ AND ‘‘venous thromboembolism’’ OR ‘‘deep vein thrombosis’’ OR ‘‘pulmonary embolism’’ in ‘‘Title/Abstract/Keywords’’, with no language or date restriction. All articles identified according to the search criteria were systematically reviewed by 2 authors (GL and CM). The references of selected articles were also hand-searched to identify other pertinent documents.
Results A total number of 26 publications could be identified after elimination of replicate documents among the 3 scientific databases. Twenty documents were excluded after accurate reading of title, abstract, and full text (when available; Figure 1). Therefore, 6 studies (5 prospective and 1 case–control) were finally
selected for this systematic literature review (Table 1).10-15 Interrater agreement was absolute (k statistics, 1.00). Steffen et al carried out a prospective trial including 14 962 middle-aged participants (8253 women and 6709 men) of the Atherosclerosis Risk in Communities study, who were followed up for 12.5 years.10 Overall, 197 VTE events were recorded during follow-up (VTE rate: 1.3%). After classification of the study population in quintiles of daily food intake, the VTE risk of participants in the highest quintile of total fish intake was not significantly different from that of participants in the lowest quintile (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.44-1.10). A larger consumption of omega-3 fatty acids was also found to be ineffective for lowering the risk of VTE (HR of highest vs lowest quintile of intake: 0.70; 95% CI, 0.43-1.13). Results were similar after excluding idiopathic VTE from analysis. Lutsey et al carried out a prospective study including 37 393 women aged 55 to 69 years who participated in the Iowa Women’s Health Study and were followed up for 19 years.11 A total number of 1950 cases with VTE were recorded during follow-up (VTE rate: 5.2%). Women consuming 2.5 servings per week of total fish exhibited a significantly higher risk of
Downloaded from cat.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 19, 2015
Mattiuzzi et al
3
Table 1. Description of Prospective and Case–Control Studies Investigating the Association Between Fish Intake and Risk of VTE. Authors
Setting
Study Design Study Population
End Point
Results
Incident VTE (1.3%) HR of total fish intake: 14 962 participants (8253 women and 0.70; 95% CI, 6709 men) aged 45-64 years, followed 0.44-1.10 up for 12.5 years Lutsey et al, United Prospective 37 393 women aged 55-69 years, followed Incident VTE (5.2%) HR of total fish intake: 2009 States up for 19 years 1.22; 95% CI, 1.03-1.46 Prevalence of VTE OR of total fish intake: Bhoopat et al, Thailand Case–control 97 Patients with VTE (68 women and (32.5%) 0.24; 95% CI, 2010 29 men; age 17-93 years) and 0.10-0.56 195 matched controls (136 women and 59 men; age 22-88 years) Varraso et al, United Prospective 129 430 participants (80 192 women and Incident VTE (2.2%) RR of total fish intake in men: 0.96; 95% 2012 States 49 238 men) aged 40-75 years, followed CI, 0.80-1.14 up for 24 years RR of total fish intake in women: 0.95; 95% CI, 0.80-1.11 Hansen-Krone Norway Prospective 23 621 participants (12 381 women and Incident VTE (2.3%) HR of total fish intake: 0.78; 95% CI, et al, 2014 11 240 men) aged 25-97 years, followed 0.60-1.01 up for 15.8 years HR of total fish and fish oil supplements in take: 0.52; 95% CI, 0.34-0.79 Severinsen Denmark Prospective 57 054 participants (29 876 women and Incident VTE (1.1%) HR of total fish intake in men: 0.98; 95% et al, 2014 27 178 men) aged 50-64, followed up CI, 0.64-1.2.8 for 10.2 years HR of total fish intake in women: 1.19; 95% CI, 0.77-1.83 Steffen et al, 2007
United States
Prospective
Reference 10
11
12
13
14
15
Abbreviations: HR, hazard ratio; OR, odds ratio; VTE, venous thromboembolism; RR, relative risk.
VTE compared to those reporting an intake 2.64 servings per day of total fish compared to those reporting an intake
