Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome

Abstract

G lobally, cardiovascular diseases (CVDs) are the leading cause of death and a major source of disability. The majority of these are caused by ischemic heart disease such as acute myocardial infarction (AMI), stroke, and other cerebrovascular diseases.1 Several factors, including infectious diseases, have been associated with increased risk for CVD. [2][3][4][5][6] The host inflammatory response to infection often results in release of proinflammatory cytokines and activation of platelets, leukocytes, and endothelial cells that can activate procoagulant pathways and can inhibit anticoagulant pathways. 2,3 This can tip the balance of hemostasis toward a prothrombotic state, laying the foundation for acute cardiovascular events such as AMI and stroke. 2,3 Clinical Perspective on p 1302Viral hemorrhagic fevers are characterized by fever, hemorrhages, and shock. Abnormal coagulation and vascular dysfunction are common observations during viral hemorrhagic fevers, 7 which could be risk factors for CVD. Four viral families contain members that cause viral hemorrhagic fevers: Bunyaviridae, Flaviviridae, Filoviridae and Arenaviridae. Pathogenic hantaviruses in the Bunyaviridae family cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome in the Americas.8 HFRS caused by Puumala virus is considered a mild viral hemorrhagic fever 7 characterized by thrombocytopenia, enhanced coagulation and fibrinolysis, 9 and disseminated intravascular coagulopathy. 10In a highly endemic area for Puumala virus in Northern Sweden, we observed a tendency of HFRS patients to develop acute cardiovascular events. Furthermore, we have recently shown that CVD is a common cause of death during acute HFRS in Sweden.11 Together, these findings suggest a possible association between acute HFRS and CVD. Therefore, we decided to investigate in more detail whether HFRS is a risk factor for CVD. To test this, we compared the incidence of AMI and stroke Background-We recently observed that cardiovascular causes of death are common in patients with hemorrhagic fever with renal syndrome (HFRS), which is caused by hantaviruses. However, it is not known whether HFRS is a risk factor for the acute cardiovascular events of acute myocardial infarction (AMI) and stroke. Methods and Results-Personal identification numbers from the Swedish HFRS patient database (1997-2012; n=6643) were cross-linked with the National Patient Register from 1987 to 2011. Using the self-controlled case series method, we calculated the incidence rate ratio of AMI/stroke in the 21 days after HFRS against 2 different control periods either excluding (analysis 1) or including (analysis 2) fatal AMI/stroke events. The incidence rate ratios for analyses 1 and 2 for all AMI events were 5.53 (95% confidence interval [CI], 2.6-11.8) and 6.02 (95% CI, 2.95-12.3) and for first AMI events were 3.53 (95% CI, 1.25-9.96) and 4.64 (95% CI, 1.83-11.77). The incidence rate ratios for analyses 1 and 2 for all stroke events were 12.93 (95% CI, 5.62-29.74)...

Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus‐associated syndromes

“…A Swedish study addressing the causes of death during and after HFRS concluded that cardiovascular disorders were the cause of death in more than half of patients who died in Sweden during the first year after HFRS . Corroborating this study, a related report demonstrated a significantly increased risk of acute myocardial infarction and stroke during HFRS . More recently, risk of thromboembolism following HFRS has also been addressed where a significantly increased risk of venous thromboembolism was observed early after on onset of HFRS .…”

Risk of stroke in retinal vein occlusion

“…[28][29][30][31][32] Although the association between the retinal vasculature and cardiovascular diseases is not entirely clear, emerging evidence suggests that changes in the retinal microvasculature might be a sign or clue of cerebral small vessel disease, 28,29,31 which is characterized by lacunar infarcts and white matter lesions. In addition, numerous studies have previously verified the methodology of a claims database, 6,9,10,15,16,18,21,24 and we also attempted to verify the incident patients with retinal diseases in our previous studies. 30 RVO; of these, occurrence of RVO at the point of the arteriovenous nipping (crossing) and adjacent retinal hemorrhage is a pathognomonic feature of RVO.…”

Sex and Gender Differences in Infection and Treatments for Infectious Diseases

“…During and soon after HFRS, there is an increased risk of cardiovascular complications, such as stroke and myocardial infarction (Connolly-Andersen et al 2014). Some people suffer from long-lasting fatigue.…”