Patients who suffer from a blood clot in the leg, called a deep vein thrombosis (DVT), are more likely to die from heart attacks or stroke compared with the general population but the reasons for this association remain unknown. We hypothesise that one reason for this association could be because DVT directly accelerates a change in the blood vessels supplying the heart and brain by a process called atherosclerosis, which we have previously shown to be important in experimental models. Symptoms of atherosclerosis include: chronic heart problems causing chest pain or shortness of breath when walking or at rest; leg pain when walking or at rest, which can lead to amputation, and; mini strokes that cause no long-lasting symptoms. Together, these conditions are termed cardiovascular disease (CVD) and are commonly managed in primary care. We would now like to investigate if patients with DVT are more likely to complain of symptoms associated with CVD over time when compared with the general population. If a relationship were to be demonstrated, a closer surveillance of DVT patients and/or interventions to reduce the risk of atherosclerosis would be supported, which has the potential to save many lives.
Major cardiovascular events (e.g. myocardial infarction (MI), coronary heart disease (CHD), angina, stroke, transient ischemic attack (TIA), and peripheral artery disease (PAD)) occur more frequently in deep vein thrombosis (DVT) patients than in the general population, but the cause of this association remains unknown. Our pre-clinical experimental data suggests that this connection could be because DVT directly accelerates atherosclerotic plaque growth. The aim of this study is to investigate whether a similar relationship exists in patients. Patients who suffer MACE often have demonstrable evidence of increased cardiovascular risk prior to their MACE, including hypertension, hypercholesterolemia, obesity, and smoking. Long term management of these conditions commonly occurs in primary care. We now would like to investigate whether patients who suffer from a DVT go on to experience more MACE secondary to atherosclerosis. We propose to carry out a prospective matched control study, comparing the risk of future MACE among patients with a DVT event with a comparison group of those who never had a DVT. We will also consider several secondary outcome measures, including all-cause mortality, QRISK score, and benefits/harms associated with blood pressure and cholesterol-based therapy. The study participants will include patients aged 40 years and over at the time of first DVT diagnosis between January 2005 and December, 2020. Patients will be stratified by their baseline cardiovascular risk based on their age, sex and recognised risk factors including smoking history, hypertension, hypercholesterolemia and family history. Data will be analysed in a time to event framework (e.g. Cox regression), adjusting for baseline confounders using competing risk analysis. If there is an association between DVT and atherosclerosis, it would lead to a change in clinical practice to modify vascular risk factors in patients following DVT with the potential to save many lives.
The main outcome measure of the study is major cardiovascular events including myocardial infarction (MI), coronary heart disease (CHD), angina, stroke, transient ischaemic attack (TIA), and peripheral artery disease (PAD) identified using SNOMED-CT medical codes. Several secondary outcome will be investigated to include All-cause mortality; QRisk score; Blood pressure and/or total cholesterol treatment associated benefits/harms (e.g., hypotension, syncope, acute kidney injury).
Prakash Saha - Chief Investigator - King's College London (KCL)
Alex Dregan - Corresponding Applicant - King's College London (KCL)
Clemens Gutmann - Collaborator - King's College London (KCL)
Xiaohui Sun - Collaborator - King's College London (KCL)