LDL cholesterol: a new risk factor for the onset of venous thromboembolic disease?

Cholesterol and Thromboembolism Over Time

For some time now, there have been voices suggesting that one of the beneficial effects of the most widespread hypolipidemic drugs – statins – might also be the reduction of thromboembolic disease (TED) risk. For instance, a meta-analysis from 2017 spoke about a reduction in this risk ranging between 15–25% compared to patients who did not use statins. Recently, American geneticists reached a conclusion that may carry very similar information, although they approached the issue from a completely different angle. Preliminary results of their extensive study were presented in May 2019 at the American Heart Association's Vascular Discovery: From Genes to Medicine conference.

Hundreds of Thousands of Genomes

The study, which utilized data from two large patient registries, aimed to identify genes and proteins associated with the onset of TED (defined as deep vein thrombosis, pulmonary embolism, or unspecified thromboembolism). The analysis included a total of 26,066 patients with a history of TED and over 624,000 controls.

Risk Factors Old and New

Several previously undescribed loci were identified that may contribute to a higher risk of TED. Most of them were associated with already described risk factors, such as body mass index (BMI) or hypercoagulability. In 4 risky variants, increased expression of plasma proteins inducing a hypercoagulable state was directly described, including the well-known factor Xa or plasminogen activator inhibitor 1 (PAI-1), which is a potential new therapeutic target. The study authors also noted a higher risk of TED in connection with higher levels of LDL cholesterol (LDL-c), which could be a causal risk factor (odds ratio [OR] 1.17 for an increase in LDL-c level by 1 standard deviation [SD]; p = 0.003).

Another Step Towards Personalized Medicine

According to one of the study's authors, Dr. Scott Damrauer, this study suggests that the treatment of elevated LDL cholesterol levels might indeed lead to a reduction in TED risk. This disease ranks among the most common hereditary cardiovascular diseases and is also one of the most common preventable causes of death in hospitalized patients. Overall, the study's results may help to uncover genetically conditioned increased risk of TED. They are another drop in the growing sea of knowledge that helps bring us closer to true personalized medicine.

(luko)

Sources:
1. Kunutsor S. K., Seidu S., Khunti K. Statins and primary prevention of venous thromboembolism: a systematic review and meta-analysis. Lancet Haematol 2017; 4 (2): e83–e93, doi: 10.1016/S2352-3026(16)30184-3.
2. Klarin D., Busenkell E., Judy R. et al. Genetic analysis implicates LDL cholesterol reduction and plasminogen activator-inhibitor 1 antagonism as therapeutic interventions for venous thromboembolism. Arteriosclerosis, Thrombosis, and Vascular Biology 2019; 39: A110. 
3. AHA News. Dangerous blood clots may be the latest risk from 'bad' cholesterol. American Heart Association, 2019 May 14. Available at: www.heart.org/en/news/2019/05/14/dangerous-blood-clots-may-be-the-latest-risk-from-bad-cholesterol