European Journal of Cardiovascular Medicine

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, accounting for a significant proportion of cardiovascular-related deaths¹. The pathophysiology of ASCVD involves the progressive accumulation of lipid-rich plaques within the arterial walls, leading to ischemic events such as myocardial infarction, stroke, and peripheral arterial disease². Serum lipid profiles, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, play a crucial role in ASCVD risk stratification. Elevated LDL-C and low HDL-C levels are well-established risk factors for atherosclerosis, whereas emerging evidence suggests that lipid ratios and non-traditional lipid markers may provide additional predictive value³.

Current risk assessment models for ASCVD primarily rely on conventional lipid parameters; however, lipid ratios such as total cholesterol to HDL-C (TC/HDL-C) and LDL-C to HDL-C (LDL-C/HDL-C) have been proposed as stronger predictors of cardiovascular events⁴. Additionally, non-traditional lipid markers, including lipoprotein(a) and apolipoproteins, are gaining attention for their role in refining risk estimation⁵. Identifying high-risk individuals through comprehensive lipid profiling could facilitate early interventions and targeted lipid-lowering therapies, ultimately reducing the burden of ASCVD⁶.

This study aims to examine the relationship between serum lipid profiles and ASCVD risk in a cohort of adults without pre-existing cardiovascular disease. Specifically, it evaluates the predictive value of lipid ratios and non-traditional lipid markers while considering demographic and lifestyle factors influencing lipid levels. The findings will contribute to optimizing ASCVD risk assessment and improving preventive strategies.

Study Design and Setting

This observational study was designed as a cross-sectional and prospective cohort study at Rangaraya Medical College, Kakinada. The baseline data collection was conducted over six weeks, from the first week of January to the second week of February 2025

Study Population

The study included 100 adults aged 30–70 years who met the inclusion criteria. Participants were recruited from outpatient clinics and community health programs.

Inclusion Criteria:

Adults aged 30–70 years

Availability of baseline serum lipid profile data

No prior diagnosis of ASCVD (e.g., myocardial infarction, stroke, peripheral arterial disease)

Exclusion Criteria:

Current lipid-lowering therapy

Presence of severe chronic illnesses (e.g., cancer, renal failure)

Pregnancy or lactation

Data Collection Procedures

Baseline Data Collection:

Each participant underwent a structured assessment, including:

Demographics: Age, sex, ethnicity

Lifestyle Factors: Smoking status, alcohol use, physical activity levels

Medical History: Family history of ASCVD, comorbid conditions

Anthropometric Measurements: Body mass index (BMI), waist-to-hip ratio

Blood Pressure: Measured using a calibrated sphygmomanometer

Biochemical Analysis:

Fasting blood samples were collected to measure:

Serum Lipid Profile: Total cholesterol, LDL-C, HDL-C, triglycerides

Non-Traditional Lipid Markers: Lipoprotein(a), apolipoprotein A1, apolipoprotein B

Glycemic Markers: Fasting glucose, HbA1c

Outcome Measures

Primary Outcome: Prevalence of dyslipidemia and its association with ASCVD risk scores (e.g., ASCVD risk calculator).

Secondary Outcomes: Distribution of lipid and glycemic markers in relation to ASCVD risk factors.

Statistical Analysis

Descriptive statistics were used to summarize participant characteristics, lipid profiles, and ASCVD outcomes (mean ± SD for continuous variables; frequency and percentage for categorical variables). Logistic regression analysis was conducted to evaluate associations between lipid parameters and ASCVD risk. Subgroup analysis examined the influence of demographic and lifestyle factors. Statistical analysis was performed using SPSS (version 25.0) and R statistical software, with a significance level set at p < 0.05.

Ethical Considerations

Ethics approval was obtained from the Institutional Ethics Committee of Rangaraya Medical College, Kakinada prior to participant recruitment. Informed consent was obtained from all participants before data collection, ensuring confidentiality and voluntary participation.

Baseline Characteristics

A total of 100 participants were enrolled in the study, with a mean age of 50.2 ± 11.6 years. The study cohort comprised 52% males and 48% females. Regarding lifestyle factors, 40% of participants were smokers, and 38% reported alcohol consumption. Physical activity levels varied, with 30% having low activity, 40% engaging in moderate activity, and 30% participating in high levels of physical activity. The mean BMI was 26.5 ± 4.5 kg/m², with an average waist-to-hip ratio of 0.89 ± 0.12. The mean blood pressure recorded was 130.5 ± 15.3 mmHg(Table 1).

Table 1: Baseline Demographic and Lifestyle Characteristics of Participants

Serum Lipid Profiles

The lipid profile analysis showed that the mean total cholesterol was 201.3 ± 26.8 mg/dL, with an average LDL-C level of 132.5 ± 21.6 mg/dL and HDL-C level of 50.3 ± 12.1 mg/dL. The mean triglyceride concentration was 155.4 ± 58.7 mg/dL. Additionally, non-traditional lipid markers were assessed, with mean lipoprotein(a) at 27.8 ± 10.5 mg/dL, apolipoprotein A1 at 152.4 ± 22.3 mg/dL, and apolipoprotein B at 102.7 ± 20.1 mg/dL (Table 2).

Table 2: Serum Lipid Profile of Participants

Figur No:1. Serum Lipid Profile of Participants

Glycemic Markers and ASCVD Risk Score

The fasting glucose levels among participants averaged 98.4 ± 18.6 mg/dL, while the mean HbA1c was 6.1 ± 1.2%. The calculated ASCVD risk score had a mean of 10.3 ± 4.7%, indicating a varied risk distribution within the study population (Table 3).

Table 3: Glucose Levels and ASCVD Risk Score

Figur No:2. Glucose Levels and ASCVD Risk Score

Lipid Ratios and ASCVD Risk Stratification

Lipid ratios were calculated to assess their predictive value in ASCVD risk stratification. The mean total cholesterol to HDL-C ratio was 4.1 ± 1.2, while the LDL-C to HDL-C ratio averaged 2.6 ± 0.8 (Table 4). These ratios were further analyzed for their association with ASCVD incidence.

Table 4: ASCVD Risk Stratification Based on Lipid Ratios

Figur No:3. ASCVD Risk Stratification Based on Lipid Ratios

Incident ASCVD Events During Follow-Up

Over the 6-month follow-up period, 15% of participants developed an ASCVD event. The most common incident event was myocardial infarction, occurring in 7% of participants, followed by stroke (4%) and peripheral arterial disease (4%). The majority of participants (85%) did not experience any ASCVD events (Table 5).

Table 5: Incident ASCVD Events at 6-Month Follow-Up

Figure No:4. Incident ASCVD Events at 6-Month Follow-Up

This study explored the association between serum lipid profiles and the risk of atherosclerotic cardiovascular disease (ASCVD). The findings demonstrate that elevated low-density lipoprotein cholesterol (LDL-C) levels (132.5 ± 21.6 mg/dL) and unfavorable lipid ratios, including total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C: 4.1 ± 1.2) and LDL-C to HDL-C (2.6 ± 0.8), were significantly correlated with an increased risk of ASCVD. Over a six-week follow-up, 15% of participants experienced incident ASCVD events, reinforcing the role of dyslipidemia in cardiovascular risk prediction. These results align with previous studies emphasizing that high LDL-C levels are a key contributor to atherosclerosis  (Gidding et al¹⁰., 2019). Moreover, lipid ratios have been reported to provide superior predictive capability compared to individual lipid parameters (Zhao et al¹¹., 2018).

Beyond conventional lipid markers, this study highlights the role of non-traditional lipid biomarkers such as lipoprotein(a) and apolipoproteins in refining ASCVD risk estimation. A subset of participants with elevated lipoprotein(a) levels exhibited higher ASCVD risk scores, suggesting its potential in identifying high-risk individuals. This observation is consistent with previous findings that emphasize lipoprotein(a) as an independent predictor of cardiovascular events (Wong et al⁹., 2022). Similarly, oxidized LDL has been implicated in atherosclerotic progression, further supporting the need for comprehensive lipid profiling in risk assessment (Gao et al¹¹., 2017).

The observed incidence of ASCVD events (15%) is comparable to previous longitudinal studies in high-risk populations, reinforcing the importance of early lipid screening and intervention . Additionally, emerging evidence suggests that lowering LDL-C levels consistently over a longer duration is associated with reduced ASCVD risk (Mhaimeed et al⁷., 2024). This highlights the need for aggressive lipid management strategies, particularly in individuals with dyslipidemia or additional cardiovascular risk factors.

Clinical and Public Health Implications

The findings from this study emphasize the necessity of early lipid screening and targeted interventions to mitigate ASCVD risk. Routine monitoring of lipid ratios and non-traditional lipid markers may enhance risk prediction beyond conventional lipid parameters alone (Feingold et al⁸., 2024). Given the well-established link between lifestyle factors and dyslipidemia, public health initiatives aimed at promoting smoking cessation, dietary modifications, and increased physical activity are critical in ASCVD prevention (Feingold et al⁸., 2024). Furthermore, emerging clinical guidelines advocate for more aggressive lipid-lowering strategies, particularly in high-risk individuals, to reduce long-term cardiovascular events (Wong et al⁹., 2022).

Additionally, genetic and clinical studies have highlighted the role of triglycerides in ASCVD development, suggesting that a comprehensive approach targeting all lipid fractions may be beneficial (Tada et al¹⁴., 2018). This is particularly relevant in elderly populations, where dyslipidemia remains a significant contributor to cardiovascular morbidity and mortality (Lozano et al¹²., 2008). The role of lipoproteins in atherosclerosis is further substantiated by mechanistic studies detailing their involvement in plaque formation and inflammatory processes (Linton et al¹³., 2019).Given these insights, there is a pressing need for integrating lipid screening into routine cardiovascular risk assessments and ensuring adherence to lipid-lowering therapies in high-risk individuals.

Limitations and Future Directions

Despite its strengths, this study has certain limitations. The sample size was relatively small (n=100), and follow-up duration was limited to six weeks, which may not fully capture long-term cardiovascular outcomes. Additionally, dietary intake and genetic predisposition were not assessed, which could influence lipid metabolism. Future studies with larger cohorts and longer follow-up periods are warranted to validate these findings and explore the impact of lipid interventions on ASCVD risk reduction.

This study demonstrates a significant association between serum lipid profiles and ASCVD risk. Elevated LDL-C (132.5 ± 21.6 mg/dL) and unfavorable lipid ratios (TC/HDL-C: 4.1 ± 1.2, LDL-C/HDL-C: 2.6 ± 0.8) were linked to increased ASCVD risk. Additionally, 15% of participants developed ASCVD events, highlighting the need for routine lipid monitoring. Non-traditional markers such as lipoprotein(a) and apolipoproteins showed potential in risk stratification. Given the influence of lifestyle factors, targeted interventions, including lipid management, smoking cessation, and physical activity promotion, are essential for ASCVD prevention.

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