Venous thromboembolic disease (VTE) is a complex condition with a multifactor aetiology in which both the clinical history of the patient and the genetic and environmental factors play a role.

Survival rate after VTE is worse than expected and it is even worse after pulmonary embolism (PE) than after deep venous thrombosis (DVT) alone1. Mortality during follow-up of patients with VTE has been the topic of several research studies and it ranges from 12.5%2 to 37%3. VTE recurrence is so often that, about 30% of patients, present recurrences in the following 10years4.

Patients with VTE show several variables associated to a decreased survival rate. From a clinical point of view, it is interesting to which those aspects can be treated.

Patients with non treated dyslipidemia have a global mortality rate a year of 9.7%5. As shown by several double-blind placebo-controlled studies, the use of statins to reduce cholesterol levels significantly decrease cardiovascular risk6. Lower levels of cholesterol achieved by the administration of statins may reduce the incidence of ictus in high risk populations and in patients with ictus or transient ischemic attack7.

Although we have found some studies which associate dyslipidemia with a higher risk of VTE8–12, none of these works has documented the prognostic role dyslipidemia may play in this type of patients.

In this paper, we present a long-term study of a series of consecutive patients diagnosed with PE aiming to analyse the main complications of such condition and their distribution in time and to establish the factors associated with a lower survival rate.

The sample obtained in our cohort was 148 patients. Half of the patients (n=74) were male. Mean age of patients was 64.2±17.2 yrs. During the two-year follow-up period 34 patients died (23%). The causes of death were: cancer (n=20), acute coronary syndrome (n=6), sudden death with dyspnoea (n=4), major bleeding in the digestive tract (n=1), non hemorrhagic acute cerebrovascular stroke (n=1) and unknown causes (n=2). Accumulated mortality rate reached 19.2% after one year and 29.6% after two years.

Patients (272 patients/year) were followed up for a period of 24±23.8 (median±range). 73.6% of the sample (23% dead and 3.4% lost) was followed up for 24 months.

Table (table 1) shows those variables whose possible association with less survival rate at two years has been analysed. Independent variables associated to less survival rate were: creatinine levels > 2 (OR, 8.8; 95% CI, 1.1 – 70.87), previous neoplasm (OR, 8.8; 95% CI, 3.69 – 20.98), dementia (OR, 6.85; 95% CI, 2.1 – 22.33) and dyslipidemia (OR, 5.07; 95% CI, 1.92 – 13.44).

The 44.45% of patients with dyslipidemia died vs. 20.8% of patients who did not show such condition (Figure 1). No significant differences were observed in relation to mean age (63.8 vs. 68.7) or gender between patients with and without dyslipidemia.

Figure 1.

Cumulative survival in patients with and without dyslipidemia.

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One of the most relevant data obtained in the present study, and which contributes to its seriousness and external accuracy, is the appropriate two-year follow-up of 97% of the sample made up only of patients with PE who were consecutively and prospectively enrolled in the study.

The sample of patients was homogeneous and its distribution between genders was similar to that observed in other studies13,14. Patient age was similar to that reported by different series in the United States13, Spain2 and other European studies15–17.

Reported survival rate after VTE varies widely17,18. Such variability is probably the result of the shortcomings observed in study design: patients with negative clinical evolution19–21, patients diagnosed in residences15–22, age > 65years15,22, patients admitted to tertiary level hospitals23,24 or patients from clinical trials25,26. As a result, an accurate estimate of global survival rate associated to VTE cannot be obtained. Anyway mortality observed in our study is similar to other series2,3.

The factors associated to a lower survival rate mentioned in our study had already been analysed in previous studies, as in the case of neoplasm, dementia and renal insufficiency27–29. Dementia is considered a negative prognostic factor in new prognostic scales29,30, but at present dyslipidemia is not included in any scale.

High serum cholesterol and LDL cholesterol levels, and low HDL cholesterol levels are considered risk factors for atherothrombosis31. Despite their potent effect on atherogenesis, lipids and lipoproteins could affect haemostasis by modulating the procoagulant and fibrinolytic expression and function32. Doggen et al.9 have shown that elevated triglycerides levels pose a higher risk (twofold) for venous thrombosis. A case-control study10 also reported the fact that hypercholesterolemia is associated with a higher risk of DVT. As regards hypertriglyceridemia, results are controversial: some studies associate it with venous thrombosis9–12, but others do not report such interplay33. It is important to carry out the measurements prior to the onset of therapy, because it is known that lipid levels diminish in the event of an acute vascular episode34. Finally, Tsai et al.8, in their analysis of cardiovascular risk factors and incidence of a first episode of VTE, concluded that some arterial risk factors, including dyslipidemia, were not associated with VTE.

All the above mentioned studies establish the association of dyslipidemia with a first episode of VTE, but we report the association of dyslipidemia, as an independent risk factor, with lower long-term survival rate in patients with PE.

The interplay between dylipidemia and PE in this sense has not been thoroughly analysed yet. In our series, long-term mortality rate due to vascular reasons in patients with dyslipidemia who have suffered PE is sevenfold greater than mortality in untreated dyslipidemic patients5. Moreover, the mortality rate observed in our patients with PE is more than twofold greater in patients with dylipidemia than in those without this condition. We do not know for sure whether the fact of having suffered an episode of PE boosts the effect of dyslipidemia as a prognostic factor for lower survival. Nor do we know whether patients with dyslipidemia who suffer PE are those with a more advanced or difficult to manage metabolic disease. Other questions we should answer would be: which parameters defined as dyslipidemia are considered more determinant and whether the prognosis of these patients may improve with statin therapy. This last question would have significant practical implications as we already know that statin therapy in dyslipidemic patients reduces mortality in 12.37% a year, disregard of the cause of death5.This work has several limitations. Firstly, the sample of patients included in our study is not large but the results get at hypothetical new factor related to a poor survival. Further studies with larger samples and primarily focused on this issue could answer many of the above mentioned questions. Secondly, other data not available and would be interesting to contrast with the results obtained are quantitative results of total cholesterol, LDL-cholesterol, HDL cholesterol, triglycerides, duplication of tests and if the analytical was fasting or not, and whether the patient was taking statins. Individuals treated with lipid-lowering drugs should be excluded or taking into account, because treatment could affect lipid levels. Several studies, including ours, did not make such exclusion10,35. These data were not considered when designing the study. The development of prospective studies should collect these data.

We think that this finding also becomes more important due mainly to two recently published papers. Khemasuwan et al. suggest that the use of statins is associated with a significant reduction in the occurrence of venous thromboembolism in patients with cancer36. Glynn et al. in a randomized trial of apparently healthy persons found that rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism37. These previous results in addition to our work open a field of research on whether this type of Venous Thromboembolism patients may benefit from treatment with statins.

We could summarize that in our study, patients with dyslipidemia who suffered PE showed worse survival rate. The role dyslipidemia may have as a vascular risk factor especially in patients with PE and the possibility to improve survival rates warrants further investigation.

Authors declare that they don’t have any conflict of interests.