European Journal of Cardiovascular Medicine

Deep vein thrombosis (DVT) is a significant health concern affecting approximately 1 in 1000 individuals annually in high-income countries.[1,2] This condition, along with venous thromboembolism (VTE), which includes DVT and pulmonary embolism (PE), increases markedly with age. VTE prevalence is particularly high among hospitalized patients and nursing home residents due to immobility and underlying health issues. In Western countries, up to 900,000 VTE cases are reported annually, contributing substantially to morbidity and mortality despite advanced healthcare systems. The burden is exacerbated by an aging population and prevalent risk factors such as obesity, cancer, and prolonged immobility.[3-7]

In India, postoperative DVT often goes undiagnosed until it leads to severe conditions like PE, highlighting the need for better awareness and management.[4,7-10] Hyperhomocysteinemia, characterized by elevated homocysteine levels, is a significant DVT risk factor due to its association with vascular diseases and blood clots. Monitoring homocysteine levels is crucial, especially in colorectal cancer surgery patients who are particularly vulnerable to DVT.[1]

This study aims to explore homocysteine metabolism and lipid profile as biomarkers for early DVT detection. By investigating the association between homocysteine and cholesterol levels with DVT, and comparing hyperhomocysteinemia in mild and extensive DVT cases, the study seeks to improve preventive and management strategies for high-risk populations.

This prospective observational study was conducted in the Department of Surgery at D.Y. Patil Hospital and Research Institute, Kolhapur, over a period of two years. The study aimed to investigate the significance of homocysteine levels and lipid profiles in patients diagnosed with deep vein thrombosis (DVT). Written informed consent was obtained from all patients participating in the study. The inclusion criteria encompassed all diagnosed DVT patients older than 18 years, while the exclusion criteria included patients who did not provide consent, those undergoing steroid treatment, and patients with DVT secondary to catheter insertion.

Upon admission, patients with symptoms of DVT underwent a thorough clinical examination and laboratory investigations. Data were collected on various parameters, including demographic details (name, age, sex, occupation), body mass index (BMI), presence of malignancy, hormone use (for women), history of varicose veins, significant family history, and history of comorbid conditions such as COVID-19, hypertension, or diabetes mellitus. Blood samples were collected to measure pre- and post-prandial blood sugar levels, HbA1c, homocysteine levels, and lipid profile parameters including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides.

Radiological investigations, including Doppler studies (with or without venogram), were performed to determine the extent of thrombosis. Homocysteine levels were measured using high-performance liquid chromatography (HPLC) following the derivatization of plasma samples with a fluorescent reagent to ensure precise quantification. Lipid profile parameters were determined through enzymatic colorimetric assays, with each lipid component quantified using automated analyzers calibrated with standard reference materials. Quality control protocols, including the use of control samples and regular calibration of equipment, were rigorously adhered to throughout the process to maintain the consistency and validity of the biochemical measurements.

The study also considered additional factors such as the patient's history of surgery, ICU stay, and vitamin supplementation. All data were meticulously recorded in an Excel master sheet for analysis. The sample size was calculated based on the expected prevalence of DVT, accounting for a 10% dropout rate, resulting in a minimum required sample size of 63 patients. Statistical analysis was performed using SPSS software. Descriptive statistics, such as mean, median, and standard deviation, were calculated for continuous variables, while frequencies and percentages were used for categorical variables. Comparative analysis between DVT patients with normal and elevated homocysteine levels was performed using the chi-square test for categorical variables and the t-test for continuous variables. Multivariate logistic regression was employed to identify independent predictors of DVT severity, adjusting for potential confounders such as age, sex, BMI, and comorbid conditions. A p-value of <0.05 was considered statistically significant.

Ethical considerations were strictly followed, with the study commencing only after obtaining clearance from the internal ethical committee. The study aimed to provide comprehensive data on the role of homocysteine and lipid profiles in the early detection and management of DVT, potentially informing future preventive strategies and improving patient outcomes.

Table 1: Demographic and Clinical Characteristics of Study Participants

The table describes the characteristics of a sample population. Age groups are distributed as follows: 21 to 30 years (14 individuals, 20%), 31 to 40 years (34 individuals, 48.57%), 41 to 50 years (20 individuals, 28.57%), and 51 to 60 years (2 individuals, 2.86%). Gender distribution shows 31 females (44.29%) and 39 males (55.71%). Surgical history indicates that 21 individuals (30%) have a history of surgery, while 49 (70%) do not. Risk factors among the population include smoking (23 individuals, 32.86%), obesity/overweight (16 individuals, 22.86%), trauma (10 individuals, 14.29%), NSAID use (8 individuals, 11.43%), hormone replacement therapy (8 individuals, 25.81% of females), OCP intake (3 individuals, 9.68% of females), hospitalization (6 individuals, 8.57%), and ischemic heart disease (5 individuals, 7.14%).

Table 2: Site and Extent of DVT

The table describes the site, extent, and side of Deep Vein Thrombosis (DVT) in a sample population. The distribution of DVT sites includes femoral (32 cases, 45.71%), iliac (18 cases, 25.71%), popliteal (12 cases, 17.14%), and tibial (8 cases, 11.43%). The extent of DVT is categorized into complete (41 cases, 58.57%) and partial (29 cases, 41.43%). Regarding the side of DVT, 49 cases (70%) are on the right side, while 21 cases (30%) are on the left side.

Table 3: Association of Homocysteine and Cholesterol levels in DVT

Table 3 compares homocysteine and cholesterol levels. In the mild category, 16 patients (22.86%) have normal cholesterol and 19 patients (27.14%) have raised cholesterol, totaling 35 patients (50%). In the normal homocysteine category, 12 patients (17.14%) have normal cholesterol and 23 patients (32.86%) have raised cholesterol, also totaling 35 patients (50%). Overall, there are 28 patients (40%) with normal cholesterol and 42 patients (60%) with raised cholesterol, totalling 70 patients. The P value is 0.329, suggesting no significant association between homocysteine and cholesterol levels.

The study aimed to assess the values of homocysteine levels and lipid profiles in the early detection of deep vein thrombosis (DVT) and to examine the role of vitamin supplementation and dietary modifications in lowering homocysteine levels. The findings of this study provide significant insights into the risk factors and biomarkers associated with DVT.

The majority of DVT patients in this study were between 31-40 years old (48.57%) with a mean age of 46.43 years, and there was a slight male predominance (55.71% male, 44.29% female). This differs from other studies, such as Dai et al.(11) (2019), which reported a mean age of 67.36 years for DVT patients following total knee arthroplasty (TKA), with a higher incidence in females (85.3%). These discrepancies in age distribution may be attributable to differences in the populations studied. The higher mean age in Dai et al.'s study could be due to the specific surgical population they investigated, where older adults are more likely to undergo knee arthroplasty.[11]

Seventy percent of the participants in our study had never had surgery, highlighting the importance of considering comorbid conditions and lifestyle factors as significant risk factors. The two main risk factors identified were obesity (22.86%) and smoking (32.86%). These findings align with Mouravas et al. [12] (2014), who emphasized the significant role of lifestyle factors, including smoking, in the development of DVT. Smoking increases thrombin production and decreases fibrinolysis, promoting thrombosis. Similarly, obesity is associated with higher levels of adipokines and pro-inflammatory cytokines, which can induce a pro-thrombotic condition.

Our study did not find a significant association between elevated homocysteine levels and DVT occurrence, similar to Mouravas et al. (2014).[12] However, Ekim et al. [13] (2013) suggested that hyperhomocysteinemia could be a potential risk factor for DVT, especially in women over 40 years. The role of homocysteine in thrombosis remains contentious, with some studies indicating that high homocysteine levels can lead to endothelial dysfunction, increased oxidative stress, and enhanced platelet activation, while others have not found a direct causal relationship.

Our study’s lack of significant findings regarding homocysteine may also be influenced by confounding factors such as vitamin B12 and folate levels, which were not extensively controlled for. These vitamins are crucial in the metabolism of homocysteine, and deficiencies can lead to elevated levels. Future research should consider these nutritional factors to clarify the relationship between homocysteine and DVT.

Our findings indicated a significant association between dyslipidemia and DVT, with 97.14% of DVT patients showing deranged lipid profiles. This aligns with Ray and Rosendaal (2001), who reviewed evidence linking dyslipidemia with venous thromboembolism (VTE) and suggested that LDL-C and lipoprotein(a) [Lp (a)] might be important risk factors. Dyslipidemia, marked by high LDL-C levels and low HDL-C levels, contributes to atherosclerosis and endothelial dysfunction, fostering conditions that favor thrombosis.[11,14]

The high prevalence of dyslipidemia among DVT patients in our study highlights the importance of effective lipid management for reducing thrombotic risk. Given the strong link between dyslipidemia and DVT, addressing lipid abnormalities could be crucial in preventing thrombotic events. Statins, which lower LDL-C and have anti-inflammatory effects, may offer benefits in DVT prevention.

The study underscores the need for comprehensive assessment and management of risk factors associated with DVT. While homocysteine levels did not show a significant association with DVT in our study, the high prevalence of dyslipidemia among DVT patients highlights the importance of lipid management in preventing thrombotic events. Future research should explore the specific mechanisms by which dyslipidemia contributes to DVT and identify effective interventions. Implementing routine screening and management of lipid profiles, along with considering nutritional factors, can enhance preventive strategies and improve patient outcomes in those at risk of DVT.

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