European Journal of Cardiovascular Medicine

Hypertension is a leading cause of cardiovascular diseases and significantly contributes to morbidity and mortality worldwide¹. Chronic hypertension causes structural and functional changes in the microvasculature, including the retinal vessels, which are particularly sensitive to elevated blood pressure^2,3. Retinal microvascular changes, such as arteriolar narrowing, venular dilation, and the development of microaneurysms, are commonly observed in hypertensive patients and are associated with an increased risk of systemic vascular complications, including stroke and cardiovascular events^4,5.

In addition to hypertension, dyslipidemia is another major cardiovascular risk factor that plays a crucial role in vascular pathology. Elevated levels of serum lipids, such as total cholesterol, low-density lipoprotein (LDL), and triglycerides, have been linked to atherosclerosis and endothelial dysfunction⁶. High-density lipoprotein (HDL), on the other hand, is known to have protective effects on the vasculature. Despite well-established relationships between dyslipidemia and large vessel diseases, the impact of abnormal lipid levels on the retinal microvasculature in hypertensive patients remains understudied⁷.

Understanding the correlation between serum lipid profiles and retinal microvascular changes is of clinical importance, as the retina provides a unique, non-invasive window into the microvascular health of the body. Identifying such associations may help clinicians detect early vascular damage and optimize preventive strategies.

This study aims to investigate the relationship between serum lipid levels and retinal microvascular measurements, including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR), in hypertensive patients. By exploring these associations, we hope to shed light on the role of lipid management in preventing microvascular complications in hypertension.

Study Design and Setting: This cross-sectional study was conducted at the Department of Ophthalmology, Government Medical College and Hospital, Suryapet. The study was carried out over a one-year period from March 2023 to February 2024.

Study Population: The study included 100 hypertensive patients attending the outpatient clinic during the study period. Participants were selected based on the following inclusion and exclusion criteria:

Inclusion Criteria:

Patients aged between 35 and 75 years diagnosed with essential hypertension (blood pressure ≥140/90 mmHg), either untreated or on antihypertensive medication.

Patients with a known duration of hypertension for at least 1 year.

Patients willing to provide informed consent.

Exclusion Criteria:

Patients with diabetes mellitus, known retinal diseases, or ocular conditions such as glaucoma and macular degeneration.

Patients with a history of ocular surgery or trauma.

Patients on lipid-lowering therapy.

Individuals with systemic diseases other than hypertension, such as renal or liver dysfunction.

Data Collection: After obtaining informed consent, detailed demographic and clinical data were collected, including age, gender, body mass index (BMI), duration of hypertension, smoking status, and current antihypertensive treatment. Blood pressure was measured using a standardized protocol. Blood samples were collected to assess serum lipid profiles, including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and very low-density lipoprotein (VLDL) cholesterol.

Ophthalmic Examination: All participants underwent a comprehensive ophthalmic examination, including visual acuity testing, intraocular pressure measurement, and fundus photography. Retinal microvascular parameters were assessed using digital fundus photographs. The central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR) were calculated using a standardized imaging software.

Statistical Analysis: Descriptive statistics were used to summarize demographic and clinical characteristics of the participants. Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were presented as frequencies and percentages. Pearson correlation analysis was performed to assess the relationship between serum lipid levels and retinal microvascular parameters. A multivariate regression analysis was conducted to evaluate the association of lipid parameters with retinal measurements, adjusting for potential confounders such as age, gender, BMI, and blood pressure. Statistical significance was set at p < 0.05. All analyses were conducted using SPSS software (version 25.0).

Ethical Considerations: The study protocol was reviewed and approved by the Institutional Ethics Committee of Government Medical College and Hospital, Suryapet. Written informed consent was obtained from all participants prior to enrollment in the study. The study was conducted in accordance with the principles of the Declaration of Helsinki.

A total of 100 hypertensive patients were included in this study. The baseline demographic and clinical characteristics of the participants are shown in Table 1. The mean age of participants was 55.2 ± 10.5 years, with 56% being male. The average duration of hypertension was 8.5 ± 4.6 years, and 34% of the participants were current smokers. The mean body mass index (BMI) was 27.8 ± 4.2 kg/m², while the mean systolic and diastolic blood pressures were 145.4 ± 16.2 mmHg and 92.8 ± 10.4 mmHg, respectively. The mean HbA1c level in this cohort was 5.8 ± 1.2%.

Table 1: Baseline Demographic and Clinical Characteristics of Study Participants

The lipid profiles of the participants are presented in Table 2. The mean total cholesterol was 192.3 ± 34.5 mg/dL, with LDL cholesterol levels averaging 122.5 ± 28.6 mg/dL. HDL cholesterol levels were 47.3 ± 10.2 mg/dL, while triglycerides and VLDL cholesterol levels were 168.9 ± 40.1 mg/dL and 33.8 ± 9.1 mg/dL, respectively(Figure No:1).

Table 2: Serum Lipid Profiles of Study Participants

Figure No:1 Serum Lipid Profiles of study Participants

Retinal microvascular measurements are displayed in Table 3. The mean central retinal arteriolar equivalent (CRAE) was 147.6 ± 11.3 µm, and the central retinal venular equivalent (CRVE) was 212.8 ± 19.4 µm. The arteriovenous ratio (AVR) was 0.69 ± 0.08, and the mean number of retinal microaneurysms was 2.5 ± 1.7(Figure No:2).

Table 3: Retinal Microvascular Measurements in Study Participants

Figure No:2 Retinal Microvascular Measurements in Study Participants

Pearson correlation analysis revealed significant associations between lipid parameters and retinal microvascular changes (see Table 4). Total cholesterol was negatively correlated with CRAE (r = -0.32, p = 0.002) and positively correlated with CRVE (r = 0.28, p = 0.006). Similarly, LDL cholesterol was inversely correlated with CRAE (r = -0.29, p = 0.005) and positively correlated with CRVE (r = 0.34, p = 0.001). HDL cholesterol showed a positive correlation with CRAE (r = 0.35, p = 0.001) and a negative correlation with CRVE (r = -0.21, p = 0.03). Triglycerides were inversely correlated with CRAE (r = -0.26, p = 0.01) and positively correlated with CRVE (r = 0.30, p = 0.004). Furthermore, LDL cholesterol was negatively correlated with AVR (r = -0.38, p = 0.0005), while HDL cholesterol showed a positive correlation with AVR (r = 0.29, p = 0.005).

Multivariate regression analysis, adjusted for age, gender, BMI, and blood pressure, confirmed these associations (see Table 5). Total cholesterol and LDL cholesterol were independently associated with a reduction in CRAE (β = -0.21, 95% CI: -0.35, -0.07, p < 0.05 and β = -0.22, 95% CI: -0.37, -0.08, p < 0.05, respectively) and an increase in CRVE (β = 0.19, 95% CI: 0.05, 0.33, p < 0.05 and β = 0.28, 95% CI: 0.14, 0.42, p < 0.05, respectively). HDL cholesterol was associated with an increase in CRAE (β = 0.25, 95% CI: 0.11, 0.39, p < 0.05) and AVR (β = 0.21, 95% CI: 0.07, 0.35, p < 0.05). Conversely, triglycerides were negatively associated with CRAE (β = -0.19, 95% CI: -0.33, -0.05, p < 0.05) and AVR (β = -0.16, 95% CI: -0.30, -0.03, p < 0.05), while being positively associated with CRVE (β = 0.24, 95% CI: 0.10, 0.38, p < 0.05).

Table 5: Multivariate Regression Analysis: Association of Lipid Parameters with Retinal Microvascular Changes (Adjusted for Age, Gender, BMI, and Blood Pressure)

*Statistical significance at p < 0.05

This study explored the correlation between serum lipid profiles and retinal microvascular changes in hypertensive patients, an important area of research given the intertwined roles of hypertension and dyslipidemia in microvascular health. The findings demonstrate that dyslipidemia, particularly elevated levels of total cholesterol, LDL cholesterol, and triglycerides, is significantly associated with adverse retinal microvascular changes, while higher HDL cholesterol appears to have a protective effect.

Association Between Serum Lipids and Retinal Microvascular Changes: We observed a significant negative correlation between total cholesterol and LDL cholesterol levels with central retinal arteriolar equivalent (CRAE), suggesting that higher lipid levels are associated with narrower retinal arterioles. This narrowing is consistent with previous studies that have linked dyslipidemia to increased systemic vascular resistance and endothelial dysfunction, contributing to early microvascular damage in hypertension (Alattas et al⁸., 2022; Liu et al¹⁰., 2022). Dyslipidemia-induced oxidative stress and inflammation may promote arteriolar narrowing, as previously noted by Xiao et al⁹. (2017).

Conversely, we found a positive correlation between total cholesterol, LDL cholesterol, and central retinal venular equivalent (CRVE). Wider venules have been associated with chronic inflammation, impaired vascular autoregulation, and increased cardiovascular risk (Prakash et al¹³., 2017; Liu et al¹⁰., 2022). The mechanisms underlying this may involve lipid-induced inflammatory responses that promote endothelial dysfunction and venular dilation, a finding consistent with Xiao et al⁹. (2017), who demonstrated a similar relationship between dyslipidemia and venular widening in children and adolescents.

In contrast to the adverse effects of elevated LDL and total cholesterol, HDL cholesterol was positively correlated with CRAE and arteriovenous ratio (AVR), indicating its protective role in maintaining retinal microvascular health. This aligns with findings from Alattas et al⁸. (2022), where HDL was shown to counteract the negative effects of other lipid abnormalities by preserving endothelial function and preventing oxidative stress. The anti-inflammatory and endothelial protective properties of HDL suggest that adequate HDL levels could mitigate retinal microvascular damage caused by dyslipidemia (Chua et al¹²., 2019). This study's results are in line with Li et al¹⁴. (2023), who found a link between hypertensive retinopathy and albuminuria, highlighting the role of microvascular changes in hypertension.

Clinical Implications: These findings highlight the potential role of lipid management in preventing retinal microvascular damage in hypertensive patients. Elevated LDL cholesterol, total cholesterol, and triglycerides may accelerate the progression of hypertensive retinopathy, while maintaining higher HDL levels could provide a protective effect (Joshi & Adatiya¹¹, 2023). Given the non-invasive nature of retinal imaging, retinal microvascular measurements such as CRAE, CRVE, and AVR can serve as valuable biomarkers for assessing systemic vascular health, offering clinicians insights into early microvascular damage associated with dyslipidemia and hypertension (Prakash et al¹³., 2017; Xiao et al⁹., 2017).

Moreover, regular monitoring of serum lipid profiles in hypertensive patients may help identify those at higher risk for retinal microvascular complications, potentially guiding early interventions with lipid-lowering therapies. Previous studies have demonstrated the benefit of lipid-lowering interventions in reducing the risk of diabetic retinopathy and other vascular complications (Liu et al¹⁰., 2022), suggesting a similar benefit for hypertensive retinopathy.

Study Strengths and Limitations: A key strength of this study is the focus on a well-defined population of hypertensive patients, with comprehensive data collection and standardized retinal imaging. The use of multivariate regression analysis allowed for the control of potential confounders, enhancing the robustness of the observed associations between lipid levels and retinal microvascular changes

However, there are limitations to consider. The cross-sectional nature of this study restricts our ability to establish causality between dyslipidemia and retinal microvascular changes. Longitudinal studies are needed to confirm whether dyslipidemia directly contributes to the progression of retinal microvascular changes over time. Additionally, the exclusion of patients on lipid-lowering therapy may limit the generalizability of the findings, as lipid-lowering interventions could influence retinal microvascular outcomes. Other factors, such as genetic predisposition and lifestyle habits, which were not assessed in this study, may also play a role in the observed associations

Our study demonstrates a significant correlation between dyslipidemia and retinal microvascular changes in hypertensive patients. Elevated levels of total cholesterol, LDL cholesterol, and triglycerides were associated with narrower arterioles (lower CRAE) and wider venules (higher CRVE), indicating adverse retinal microvascular alterations. In contrast, higher HDL cholesterol levels showed a protective effect, correlating positively with CRAE and arteriovenous ratio (AVR). These findings underscore the importance of managing lipid levels in hypertensive patients to mitigate microvascular damage, potentially reducing the risk of hypertensive retinopathy. Further longitudinal studies are necessary to confirm these associations and establish causality.

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