European Journal of Cardiovascular Medicine

Hypertension, a major contributor to cardiovascular morbidity and mortality, continues to pose significant global health challenges. As of recent estimates, nearly 1.3 billion adults worldwide are affected by hypertension, with its prevalence steadily increasing in both developed and developing countries [1]. Beyond traditional risk factors such as age, obesity, and sedentary lifestyle, emerging evidence highlights the role of metabolic disturbances, including lipid abnormalities and hyperhomocysteinemia, in the pathogenesis of hypertension [2]. These revelations highlight how crucial it is to understand how lipid metabolism and homocysteine levels interact in hypertension individuals.

Elevated plasma homocysteine levels, or hyperhomocysteinemia, have been identified as a separate risk factor for hypertension and other cardiovascular conditions. Mechanistically, homocysteine aggravates hypertension by promoting vascular remodeling, oxidative stress, and endothelial dysfunction [3]. Research has indicated that increasing homocysteine levels are linked to reduced nitric oxide bioavailability and increased arterial stiffness, both of which raise blood pressure [4]. Furthermore, hyperhomocysteinemia has been linked to dysregulation of lipid metabolism, particularly involving (VLDL) particles.

VLDL, a key lipoprotein responsible for transporting triglycerides, plays a crucial role in cardiovascular health. Elevated serum VLDL levels are associated with atherogenic processes, including lipid deposition and inflammation [5]. According to recent research, hyperhomocysteinemia and serum VLDL levels may be related in hypertensive individuals. For example, a 2020 study demonstrated that hypertensive individuals with hyperhomocysteinemia had significantly higher serum VLDL levels than their normohomocysteinemic counterparts, suggesting a synergistic impact on cardiovascular risk [6]. Additionally, experimental evidence indicates that homocysteine may influence VLDL metabolism by altering hepatic lipid synthesis and secretion pathways [7].

Understanding the correlation between serum VLDL levels and hyperhomocysteinemia in hypertensive patients is crucial for developing targeted therapeutic strategies. Addressing both lipid abnormalities and elevated homocysteine levels may yield synergistic benefits in reducing cardiovascular risk. Current guidelines emphasize the importance of integrated management approaches that include lifestyle modifications and pharmacological interventions to mitigate these metabolic disturbances [8]. The aim of the study is to investigate the correlation between serum VLDL levels and hyperhomocysteinemia in hypertensive patients.

Study Design

This is a retrospective cross-sectional observational study.

Study Setting

The study was carried out at the VSS Institute of Medical Sciences and Research (VIMSAR), Burla, Sambalpur, Odisha. The research spanned 12 months, from February 1, 2023, to January 31, 2024.

Participants

The study included 100 hypertensive patients attending the outpatient or inpatient departments of VIMSAR. Participants were enrolled based on predefined inclusion and exclusion criteria to ensure the homogeneity and reliability of the study population.

Inclusion Criteria:

1. Patients aged 30–65 years diagnosed with hypertension.
2. Individuals willing to provide informed consent.
3. Patients with no recent acute illnesses or infections.

Exclusion Criteria:

• Patients with diabetes mellitus, renal impairment, or hepatic dysfunction.
• Pregnant or lactating women.
• Individuals on lipid-lowering therapy or vitamin supplements affecting homocysteine levels.
• Patients with secondary hypertension.

Bias

To minimize selection bias, random sampling methods were used to enroll participants. By using qualified employees to collect data, observer bias was minimized and accuracy and consistency were assured. Additionally, laboratory analyses were performed in a blinded manner.

Data Collection

Data were collected through structured questionnaires, clinical examinations, and laboratory investigations. Data on lifestyle factors, medical history, and demographics were documented. Serum VLDL levels and homocysteine levels were measured using standardized biochemical techniques.

Procedure

Eligible participants were screened, and their consent was obtained. After an overnight fast, blood samples were extracted and prepared for biochemical examination. Serum VLDL levels were assessed using enzymatic colorimetric assays, while serum homocysteine levels were determined through high-performance liquid chromatography (HPLC). Blood pressure was measured using a calibrated sphygmomanometer, following standard guidelines.

Statistical Analysis

SPSS software, version 23.0, was used to analyze the data. Clinical and demographic data were summarized using descriptive statistics. The correlation between serum VLDL levels and hyperhomocysteinemia was assessed using correlation analysis. When applicable, independent t-tests and chi-square tests were used for group comparisons. P-values less than 0.05 were regarded as statistically significant.

The study included 100 hypertensive patients, with 60% being male and 40% female. The mean age of the participants was 50.2 years. Among the participants, 55 (55%) were classified as having hyperhomocysteinemia (serum homocysteine levels >15 µmol/L), while 45 (45%) had normal homocysteine levels.

Table 1: Demographic and Clinical Characteristics

Serum VLDL levels, homocysteine levels, and systolic and diastolic blood pressures (SBP and DBP) were all considerably higher in those with hyperhomocysteinemia than in those with normal homocysteine levels (p<0.05).

Correlation Analysis

Correlation analysis was performed to evaluate the relationships between serum VLDL levels, homocysteine levels, and blood pressure. The results revealed strong and statistically significant correlations.

Table 2: Correlation Analysis Results

The correlation analysis demonstrated a strong positive relationship between serum VLDL and homocysteine levels (r=0.72, p<0.001). Additionally, both systolic and diastolic blood pressures showed moderate positive correlations with homocysteine levels, indicating a potential interplay between lipid and homocysteine metabolism in hypertensive patients.

Statistical Comparison of Variables

To compare the mean values of serum VLDL and homocysteine levels between the groups, independent t-tests were conducted.

Table 3: Group Comparisons

This table highlights the statistically significant differences in serum VLDL and homocysteine levels between participants with hyperhomocysteinemia and those with normal homocysteine levels (p<0.001). The higher levels in the hyperhomocysteinemia group underscore the potential relationship between these variables.

Key Findings

• Prevalence: Hyperhomocysteinemia was present in 55% of the participants.
• Blood Pressure: Participants with hyperhomocysteinemia had significantly higher SBP and DBP levels.
• Serum VLDL and Homocysteine Levels: Strong positive correlations were observed, with hyperhomocysteinemia associated with elevated serum VLDL levels.
• Implications: These findings suggest a link between lipid metabolism and homocysteine levels in hypertensive patients, which warrants further investigation.

The study investigated the correlation between serum (VLDL) levels and hyperhomocysteinemia in hypertensive patients. Among the 100 participants, 55% were identified as having hyperhomocysteinemia (serum homocysteine levels >15 µmol/L), while 45% had normal levels. Participants with hyperhomocysteinemia had significantly higher systolic and diastolic blood pressures, serum VLDL levels, and homocysteine levels compared to those with normal homocysteine levels. These findings emphasize the interplay between lipid metabolism and homocysteine levels in hypertensive patients.

Serum VLDL and homocysteine levels showed a substantial positive connection (r=0.72, p<0.001), suggesting that elevated VLDL levels are linked to elevated homocysteine levels.  This suggests a potential metabolic linkage, where disruptions in lipid metabolism might contribute to elevated homocysteine levels or vice versa. Furthermore, systolic and diastolic blood pressures showed moderate correlations with serum homocysteine levels, with statistical significance (p<0.05), underscoring the influence of hyperhomocysteinemia on blood pressure regulation.

Significant variations in blood VLDL and homocysteine levels between persons with hyperhomocysteinemia and those with normal levels were also shown by group comparisons. Participants with hyperhomocysteinemia had markedly higher serum VLDL levels (45 ± 8 mg/dL) compared to the normal group (35 ± 7 mg/dL; p<0.001). Similarly, serum homocysteine levels were significantly elevated in the hyperhomocysteinemia group (25 ± 5 µmol/L) compared to the normal group (12 ± 3 µmol/L; p<0.001).

Recent studies have extensively examined the relationship between serum VLDL levels and hyperhomocysteinemia in hypertensive and cardiovascular patients. Chen et al. conducted a cross-sectional study and found a significant association between elevated VLDL levels and hyperhomocysteinemia in hypertensive patients. They reported that individuals in the highest quartile of VLDL levels had a 3.8-fold increased risk of hyperhomocysteinemia, independent of other variables such as triglycerides and age [9]. Similarly, Wang et al. demonstrated that elevated uric acid, which is closely related to lipid abnormalities like increased VLDL, was a strong predictor of hyperhomocysteinemia in hypertensive adults. They suggested that these biochemical markers could serve as independent indicators of cardiovascular risk [10]. In coronary artery disease patients, Wu et al. observed a significant relationship between hyperhomocysteinemia and an atherogenic lipid profile, including higher levels of VLDL. They concluded that hyperhomocysteinemia exacerbates lipid imbalance, which could further contribute to disease progression [11]. Furthermore, Guo et al. pointed out that hypertension patients with hyperhomocysteinemia had worse oxidative stress biomarkers than those without, which subtly implies that elevated VLDL levels may contribute to cardiovascular impairment brought on by oxidative stress [12].

These findings suggest that hyperhomocysteinemia may be a critical factor in hypertensive patients, influencing both lipid profiles and blood pressure. The strong association between VLDL and homocysteine levels highlights a potential area for therapeutic interventions. Addressing both lipid and homocysteine abnormalities could improve clinical outcomes in hypertensive patients.

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