Caroline Lind

Impact of incident venous thromboembolism on risk of arterial thrombotic diseases

Background— Growing evidence supports an association between venous thromboembolism (VTE) and arterial thrombotic diseases (ie, myocardial infarction and ischemic stroke). We aimed to study the association between VTE and future arterial events and to determine the population attributable risk of arterial events by VTE in a large prospective cohort recruited from the general population. Methods and Results— In 1994 to 1995 and 1993 to 1997, 81 687 subjects were included in the Tromsø Study and in the Diet, Cancer and Health Study and followed up to the date of incident venous and arterial events (myocardial infarction or ischemic stroke), death or migration, or to the end of the study period (2010 and 2008, respectively). There were 1208 cases of VTE and 90 subsequent arterial events during a median follow-up of 12.2 years. An association between VTE and future arterial events was found in all women and men aged <65 years but not in men aged >65 years. Women <65 years old with VTE had 3.3-fold higher risk of arterial disease (adjusted hazard ratio, 3.28; 95% confidence interval, 1.69–6.35) compared with women of the same age without VTE. The corresponding hazard ratio in men aged <65 years was 2.06 (95% confidence interval, 1.32–3.20). Only 0.9% of the arterial events were attributed to VTE, and the VTE explained 63.8% of the risk of arterial events among VTE patients. Conclusions— Our findings imply that women and young men with VTE have higher risk of arterial thrombotic disease than those without VTE. However, only 1% of the arterial thrombotic events in the population are attributed to VTE.

Family History of Myocardial Infarction and Cause-Specific Risk of Myocardial Infarction and Venous Thromboembolism - The Tromsø Study

Background—A family history of myocardial infarction (FHMI) has been shown to increase the risk of venous thromboembolism (VTE). The mechanism underlying the association remains unclear. Therefore, we aimed to determine the risks of MI and VTE by FHMI using a cause-specific model and to explore whether atherosclerotic risk factors could explain the association between FHMI and VTE in a population-based cohort. Methods and Results—The study included 21 624 subjects recruited from the Tromsø Study in 1994 to 1995 and 2001 to 2002. Incident MI and VTE events were registered from date of enrollment to end of follow-up, December 31, 2010. There were 1311 MIs and 428 VTEs during a median follow-up of 15.8 years. FHMI was associated with a 52% increased risk of MI (adjusted hazard ratio, 1.52; 95% confidence interval, 1.35–1.70) and a 26% increased risk of VTE (adjusted hazard ratio, 1.26; 95% confidence interval, 1.02–1.55) in the cause-specific Cox model. Similar results were found using the traditional Cox model. The risk estimates by status of FHMI were highest for unprovoked deep vein thrombosis (adjusted hazard ratio, 1.69; 95% confidence interval, 1.12–2.56), and the risk increased with increasing number of affected relatives. Modifiable atherosclerotic risk factors slightly altered the association between FHMI and MI but had a negligible effect on the association between FHMI and VTE. Conclusions—FHMI was associated with increased risk of both MI and VTE in a cause-specific model. Apparently, the association between FHMI and VTE applied to unprovoked deep vein thrombosis and was not explained by modifiable atherosclerotic risk factors.

Impact of incident myocardial infarction on the risk of venous thromboembolism: the Tromsø Study

Essentials Registry‐based studies indicate a link between arterial‐ and venous thromboembolism (VTE). We studied this association in a cohort with confounder information and validated outcomes. Myocardial infarction (MI) was associated with a 4.8‐fold increased short‐term risk of VTE. MI was associated with a transient increased risk of VTE, and pulmonary embolism in particular.

Impact of Venous Thromboembolism on the Formation and Progression of Carotid Atherosclerosis: The Tromsø Study

Venous thromboembolism (VTE) is associated with increased risk of arterial cardiovascular diseases (CVD), and development of atherosclerosis secondary to VTE may be an intermediate between VTE and CVD. Therefore, we aimed to investigate whether incident VTE was associated with subsequent carotid atherosclerosis formation and progression in a population-based observational study. Subjects attending two or more ultrasound examinations of the right carotid artery, with measurement of total plaque area (TPA), in the Tromsø Study in 1994–1995, 2001–2002, and/or 2007–2008 were eligible. We identified 150 subjects diagnosed with first-lifetime VTE between the initial and follow-up visit, and randomly selected 600 age- and sex-matched subjects without VTE between the visits. Subjects with VTE and carotid plaque(s) at the first visit had 4.1 mm 2 (β: 4.13, 95% CI: −1.72 to 9.98) larger change in TPA between the first and second visit compared with subjects without VTE after adjustment for change in high-sensitivity C-reactive protein (hs-CRP) and traditional atherosclerotic risk factors. The association remained after restricting the analyses to VTE events diagnosed in the first half of the time interval between the carotid ultrasounds (β: 4.02, 95% CI: −3.66 to 11.70), supporting that the change in TPA occurred subsequent to the VTE. No association was found between VTE and novel carotid plaque formation. In conclusion, we found a possible association between VTE and atherosclerosis progression in those with already established carotid plaques, but not between VTE and novel plaque formation. The association between VTE and carotid plaque progression was not mediated by low-grade inflammation assessed by hs-CRP.

Family History of Myocardial Infarction and Cause-Specific Risk of Myocardial Infarction and Venous ThromboembolismCLINICAL PERSPECTIVE

Background—A family history of myocardial infarction (FHMI) has been shown to increase the risk of venous thromboembolism (VTE). The mechanism underlying the association remains unclear. Therefore, we aimed to determine the risks of MI and VTE by FHMI using a cause-specific model and to explore whether atherosclerotic risk factors could explain the association between FHMI and VTE in a population-based cohort. Methods and Results—The study included 21 624 subjects recruited from the Tromsø Study in 1994 to 1995 and 2001 to 2002. Incident MI and VTE events were registered from date of enrollment to end of follow-up, December 31, 2010. There were 1311 MIs and 428 VTEs during a median follow-up of 15.8 years. FHMI was associated with a 52% increased risk of MI (adjusted hazard ratio, 1.52; 95% confidence interval, 1.35–1.70) and a 26% increased risk of VTE (adjusted hazard ratio, 1.26; 95% confidence interval, 1.02–1.55) in the cause-specific Cox model. Similar results were found using the traditional Cox model. The risk estimates by status of FHMI were highest for unprovoked deep vein thrombosis (adjusted hazard ratio, 1.69; 95% confidence interval, 1.12–2.56), and the risk increased with increasing number of affected relatives. Modifiable atherosclerotic risk factors slightly altered the association between FHMI and MI but had a negligible effect on the association between FHMI and VTE. Conclusions—FHMI was associated with increased risk of both MI and VTE in a cause-specific model. Apparently, the association between FHMI and VTE applied to unprovoked deep vein thrombosis and was not explained by modifiable atherosclerotic risk factors.

Family History of Myocardial Infarction and Cause-Specific Risk of Myocardial Infarction and Venous ThromboembolismCLINICAL PERSPECTIVE: The Tromsø Study

Background—A family history of myocardial infarction (FHMI) has been shown to increase the risk of venous thromboembolism (VTE). The mechanism underlying the association remains unclear. Therefore, we aimed to determine the risks of MI and VTE by FHMI using a cause-specific model and to explore whether atherosclerotic risk factors could explain the association between FHMI and VTE in a population-based cohort. Methods and Results—The study included 21 624 subjects recruited from the Tromsø Study in 1994 to 1995 and 2001 to 2002. Incident MI and VTE events were registered from date of enrollment to end of follow-up, December 31, 2010. There were 1311 MIs and 428 VTEs during a median follow-up of 15.8 years. FHMI was associated with a 52% increased risk of MI (adjusted hazard ratio, 1.52; 95% confidence interval, 1.35–1.70) and a 26% increased risk of VTE (adjusted hazard ratio, 1.26; 95% confidence interval, 1.02–1.55) in the cause-specific Cox model. Similar results were found using the traditional Cox model. The risk estimates by status of FHMI were highest for unprovoked deep vein thrombosis (adjusted hazard ratio, 1.69; 95% confidence interval, 1.12–2.56), and the risk increased with increasing number of affected relatives. Modifiable atherosclerotic risk factors slightly altered the association between FHMI and MI but had a negligible effect on the association between FHMI and VTE. Conclusions—FHMI was associated with increased risk of both MI and VTE in a cause-specific model. Apparently, the association between FHMI and VTE applied to unprovoked deep vein thrombosis and was not explained by modifiable atherosclerotic risk factors.

Response to Letter Regarding Article, “Impact of Incident Venous Thromboembolism on Risk of Arterial Thrombotic Diseases”

We thank Dr Chaix and colleagues for their interest in our publication.1 In their letter to the editor, they question whether the higher prevalence of important atherosclerotic risk factors in those with venous thromboembolism (VTE) who subsequently developed arterial thrombotic disease (ATD) compared with the VTE-only group could be partially responsible for the ATD. First, we want to remind the readers that the aim of the present study was to investigate whether subjects with VTE had higher risk of ATD compared with those without VTE. Thus, with regard to confounding, the interrogating question would be whether a higher prevalence of atherosclerotic risk factors in the VTE group overall compared with those …