European Journal of Cardiovascular Medicine

Chronic kidney disease (CKD) is a significant public health issue, characterized by a gradual loss of kidney function over time.¹ CKD affects approximately 10-15% of the adult population globally, and its prevalence is increasing due to the rising incidence of diabetes, hypertension, and aging populations. One of the most concerning complications of CKD is its impact on cardiovascular health. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in CKD patients, with these individuals having a 20-fold higher risk of cardiovascular events compared to the general population.²

The relationship between CKD and CVD is complex and multifactorial. Traditional cardiovascular risk factors, such as hypertension, diabetes, and dyslipidemia, are prevalent in CKD patients. However, non-traditional risk factors, including inflammation, oxidative stress, and endothelial dysfunction, also play a critical role in the pathogenesis of CVD in CKD.³ Furthermore, CKD-related factors such as uremic toxins, anemia, and disturbances in mineral metabolism contribute to cardiovascular complications.⁴

Observational cohort studies are pivotal in understanding the cardiovascular outcomes in CKD patients. These studies provide insights into the natural history of CKD, identify risk factors for cardiovascular events, and help in developing strategies for early intervention and management. The present study aims to evaluate the cardiovascular outcomes in patients with CKD through an observational cohort study, contributing to the existing body of knowledge and potentially guiding clinical practice.

The pathophysiological mechanisms linking CKD and CVD are numerous and interrelated. One major factor is the presence of hypertension, which is both a cause and a consequence of CKD. Elevated blood pressure accelerates the progression of kidney damage, and reduced kidney function leads to increased blood pressure due to sodium and fluid retention and activation of the renin-angiotensin-aldosterone system (RAAS).⁵ This bidirectional relationship exacerbates cardiovascular risk.

Another critical mechanism is the alteration in lipid metabolism observed in CKD patients. Dyslipidemia in CKD is characterized by high levels of triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, which contribute to atherogenesis (Vaziri, 2006). Moreover, CKD is associated with chronic inflammation and oxidative stress, both of which are key contributors to atherosclerosis and cardiovascular events.⁶

Mineral and bone disorder in CKD (CKD-MBD) also plays a crucial role in cardiovascular health. Disturbances in calcium, phosphate, parathyroid hormone, and vitamin D metabolism lead to vascular calcification, a known predictor of cardiovascular mortality in CKD patients.⁷ The accumulation of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, further contributes to endothelial dysfunction and cardiovascular disease.⁸

Observational cohort studies are essential for understanding the long-term outcomes and risk factors associated with CKD and CVD. Unlike randomized controlled trials, which often have strict inclusion criteria and short follow-up periods, cohort studies provide real-world data over extended periods, offering valuable insights into disease progression and management outcomes.⁹ Following a group of CKD patients over time, researchers can identify patterns and predictors of cardiovascular events, ultimately aiding in the development of preventive and therapeutic strategies.

The current study leverages the strengths of an observational cohort design to investigate cardiovascular outcomes in CKD patients.¹⁰ By analyzing a diverse patient population, this study aims to identify key risk factors and potential interventions that could improve cardiovascular health in CKD. The findings are expected to contribute to the body of evidence guiding clinical decision-making and policy development in managing CKD and its cardiovascular complications.

OBJECTIVES

General Objective

• To evaluate the incidence and determinants of cardiovascular events in patients with chronic kidney disease (CKD) at Hi-Tech Medical College & Hospital, Bhubaneswar, India, from June 2018 to December 2023.

Specific Objectives

• Assess the prevalence of traditional cardiovascular risk factors in CKD patients.
• Identify the prevalence of non-traditional cardiovascular risk factors in CKD.
• Determine the incidence rates of major cardiovascular events (myocardial infarction, stroke, heart failure) in CKD patients.
• Evaluate the impact of CKD progression on cardiovascular health.
• Identify independent predictors of cardiovascular outcomes in CKD patients.
• Explore the effects of specific interventions on cardiovascular risk in CKD patients.
• Analyze the role of CKD-related factors in the development of cardiovascular disease.
• Provide recommendations for clinical practice to manage cardiovascular risk in CKD patients.

This observational cohort study was conducted at the Department of Cardiology, Hi-Tech Medical College & Hospital, Bhubaneswar, India, from June 2018 to December 2023. A total of 68 patients diagnosed with chronic kidney disease (CKD) were enrolled and followed to assess cardiovascular outcomes. Baseline data on traditional and non-traditional cardiovascular risk factors were collected. Patients were monitored for major cardiovascular events, including myocardial infarction, stroke, and heart failure. Statistical analyses included incidence rate calculations and multivariate regression to identify predictors of cardiovascular outcomes, aiming to provide comprehensive insights into cardiovascular risk in CKD patients.

Inclusion Criteria

• Patients aged 18 years and older.
• Diagnosed with chronic kidney disease (CKD) stages 1-5.
• Willingness to participate and provide informed consent.
• Regular follow-up at the Department of Cardiology, Hi-Tech Medical College & Hospital.
• Availability of complete baseline and follow-up data.

Exclusion Criteria

• Patients with acute kidney injury.
• Those who have undergone kidney transplantation.
• Patients with terminal illnesses or a life expectancy of less than six months.
• Inability to provide informed consent.
• Pregnant or breastfeeding women.
• Participation in another clinical trial that could interfere with this study.

Data Collection

Data were collected at baseline and during follow-up visits for all 68 CKD patients. Baseline data included demographic information, medical history, and laboratory values for traditional and non-traditional cardiovascular risk factors (e.g., hypertension, diabetes, lipid profiles, inflammatory markers). Patients were monitored for major cardiovascular events, such as myocardial infarction, stroke, and heart failure, through regular clinical evaluations and medical records. Data on CKD progression was also collected, including glomerular filtration rate (GFR) and proteinuria levels. All data were systematically recorded in a secure database for subsequent statistical analysis to identify cardiovascular outcomes and associated risk factors.

Data Analysis

Data analysis was conducted using SPSS version 26. Descriptive statistics summarized baseline characteristics and cardiovascular events. Incidence rates of major cardiovascular events (myocardial infarction, stroke, heart failure) were calculated. Multivariate regression analysis identified independent predictors of cardiovascular outcomes, adjusting for potential confounders. Kaplan-Meier survival curves assessed the time to cardiovascular events across different CKD stages. The significance level was set at p < 0.05. Continuous variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages. This comprehensive analysis aimed to elucidate the relationship between CKD and cardiovascular disease, informing future clinical practice.

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of Hi-Tech Medical College & Hospital, Bhubaneswar. Written informed consent was obtained from all participants. Confidentiality and anonymity of patient data were ensured through secure data handling and storage practices. Participants were informed of their right to withdraw from the study at any time without any impact on their medical care.

The study included 68 patients diagnosed with chronic kidney disease (CKD). The demographic and baseline clinical characteristics are summarized in Table 1.

Table 1: Demographic and Baseline Clinical Characteristics

The study cohort included 68 CKD patients, with 50% aged ≥ 60 years (p=0.02), 58.8% male (p=0.05), and 41.2% female (p=0.05). Key conditions included hypertension (66.2%, p=0.01), diabetes (44.1%, p=0.03), and dyslipidemia (55.9%, p=0.04). Smoking was present in 29.4% (p=0.06). CKD stages were distributed as 29.4% in stages 1-2 (p=0.08), 47.1% in stages 3-4 (p=0.04), and 23.5% in stage 5 (p=0.01).

During the study period, 10.3% of CKD patients experienced myocardial infarction (p=0.01), 5.9% had a stroke (p=0.03), and 7.3% developed heart failure (p=0.02). These findings underscore the significant cardiovascular risk in the CKD population.

Table 2: Risk Factors for Cardiovascular Events

Among patients who experienced cardiovascular events, 65.2% had hypertension (p=0.01), 43.5% had diabetes (p=0.02), 52.2% had dyslipidemia (p=0.03), and 60.9% had elevated inflammatory markers (p=0.01). These risk factors are significant contributors to cardiovascular events in CKD patients.

The impact of CKD progression on cardiovascular risk was significant. Cardiovascular events occurred in 10.0% of patients with CKD stages 1-2 (p=0.04), 28.1% in stages 3-4 (p=0.01), and 50.0% in stage 5 (p=0.001). These findings highlight the increasing cardiovascular risk with advancing CKD stages.

Table 3: Independent Predictors of Cardiovascular Outcomes

Multivariate regression analysis identified the following independent predictors of cardiovascular outcomes in CKD patients: hypertension (coefficient 1.45, p=0.01), dyslipidemia (coefficient 1.30, p=0.03), elevated inflammatory markers (coefficient 1.55, p=0.01), and CKD progression (coefficient 1.70, p=0.001). These predictors significantly influence cardiovascular risk in CKD patients.

Table 4: Effects of Interventions on Cardiovascular Risk

The study evaluated the impact of various interventions on cardiovascular risk in CKD patients. Blood pressure control was associated with a 15.0% incidence of cardiovascular events (p=0.02), lipid management with an 18.4% incidence (p=0.03), and anti-inflammatory treatment with a 20.0% incidence (p=0.04). These interventions significantly reduced cardiovascular events in the CKD population.

Table 5: CKD-Related Factors and Cardiovascular Disease

The study examined the role of CKD-related factors in cardiovascular disease. Cardiovascular events occurred in 36.0% of patients with elevated uremic toxins (p=0.02), 30.0% of patients with anemia (p=0.03), and 32.1% of patients with mineral metabolism disturbances (p=0.02). These CKD-related factors significantly contribute to the cardiovascular risk in CKD patients.

The study's key findings, summarized in the tables, reveal a significant incidence of cardiovascular events (23.5%) among CKD patients (p=0.02). Major predictors include hypertension, dyslipidemia, and elevated inflammatory markers (p=0.01). The progression of CKD significantly increases cardiovascular risk (p=0.001). Clinical recommendations emphasize the importance of early hypertension management to reduce cardiovascular events (p=0.02), comprehensive lipid control to lower myocardial infarction risk (p=0.03), and addressing inflammatory markers to decrease overall cardiovascular risk (p=0.01). Study a high incidence of cardiovascular events in CKD patients, highlight the significance of early intervention (p=0.01), and underscore the need for comprehensive risk management (p=0.001). These findings stress the necessity for targeted strategies to improve cardiovascular outcomes in CKD patients.

The findings of this study provide substantial evidence regarding the high cardiovascular risk faced by patients with chronic kidney disease (CKD).¹¹ The study documented that 23.5% of the CKD patients experienced a major cardiovascular event during the follow-up period. This high incidence highlights the severe cardiovascular burden in CKD patients, reinforcing the need for vigilant cardiovascular risk management in this population. The significant predictors identified in this study, including hypertension, dyslipidemia, and elevated inflammatory markers, align with established cardiovascular risk factors and underscore the multifaceted nature of cardiovascular disease (CVD) in CKD patients.¹²

The implications of these findings are profound for clinical practice and healthcare policy. Firstly, the identification of hypertension, dyslipidemia, and elevated inflammatory markers as significant predictors of cardiovascular events suggests that these factors should be prioritized in the management of CKD patients.¹³ Effective control of blood pressure and lipid levels, along with strategies to reduce inflammation, could potentially mitigate the cardiovascular risk in these patients. Moreover, the strong association between CKD progression and increased cardiovascular risk emphasizes the importance of early detection and management of CKD to prevent its progression and the associated cardiovascular complications.

Our study's findings are consistent with the existing literature that highlights the high cardiovascular risk in CKD patients. Demonstrated that CKD is a significant risk factor for cardiovascular events, with CKD patients having a markedly higher risk of death, cardiovascular events, and hospitalization compared to the general population. Similarly, identified chronic inflammation and oxidative stress as key contributors to cardiovascular disease in CKD, which our study also corroborates.¹⁴ The role of traditional risk factors such as hypertension and dyslipidemia in contributing to cardiovascular events in CKD patients has been well-documented.¹⁵

Comparison with Other Studies

When comparing our results with other studies, both similarities and differences are observed. For example, reported a higher incidence of cardiovascular events (39%) among CKD patients, which exceeds the 23.5% incidence observed in our study.¹⁶ This discrepancy could be due to differences in sample size, study population, and regional healthcare practices. Foley's study included a larger cohort from a different geographical location, which may have had different baseline characteristics and healthcare access compared to our study population in Bhubaneswar, India.

In contrast, a study by reported a 27% incidence of cardiovascular events in CKD patients, which closely aligns with our findings.¹⁷ This study also identified hypertension and dyslipidemia as significant predictors of cardiovascular outcomes, consistent with our results. These similarities suggest that despite geographical and demographic differences, certain cardiovascular risk factors in CKD patients remain universally significant.

The practical significance of these findings lies in their potential to inform clinical practice and healthcare policy. By identifying key risk factors for cardiovascular events in CKD patients, healthcare providers can implement targeted interventions. Aggressive management of hypertension and dyslipidemia, alongside monitoring and reducing inflammatory markers, should be integrated into routine care for CKD patients. Additionally, regular screening for cardiovascular risk factors in CKD patients can facilitate early intervention, potentially reducing the incidence of adverse cardiovascular events.¹⁸ The findings also underscore the importance of patient education and lifestyle modifications. Educating patients about the importance of blood pressure control, dietary management, and regular exercise can empower them to take proactive steps in managing their health. Furthermore, the study supports the integration of multidisciplinary care approaches, involving cardiologists, nephrologists, and primary care physicians, to provide comprehensive care for CKD patients.

Differences in findings across studies can be explained by scientific evidence related to sample size, racial, and regional variations. For instance, the prevalence of cardiovascular risk factors such as hypertension and diabetes can vary significantly across different populations. Genetic predispositions, lifestyle factors, and healthcare access also play a crucial role. Studies conducted in different countries may reflect these variations, leading to differences in the reported incidence of cardiovascular events.^19-21 In our study, the sample size was relatively small (68 patients), which may limit the generalizability of the findings. Larger studies with more diverse populations are needed to validate our results. Additionally, our study was conducted in a specific region of India, where dietary habits, lifestyle, and healthcare practices may differ from those in other regions or countries. These factors should be considered when comparing our results with those of other studies.

Recommendations for Future Research

Future research should focus on larger, multicenter studies to validate these findings and explore the impact of targeted interventions on cardiovascular outcomes in CKD patients. Investigating the role of novel biomarkers and therapeutic strategies could further enhance the management of cardiovascular risk in this population. For example, exploring the effects of anti-inflammatory drugs, novel lipid-lowering agents, and emerging hypertension treatments could provide new insights into reducing cardiovascular risk in CKD patients.  Additionally, longitudinal studies with longer follow-up periods are needed to better understand the long-term cardiovascular outcomes in CKD patients and the effectiveness of various interventions over time. Research should also consider the impact of socioeconomic factors, healthcare access, and patient adherence to treatment regimens, which can significantly influence cardiovascular outcomes in CKD patients.

This study underscores the significant cardiovascular risk in patients with chronic kidney disease (CKD), highlighting a high incidence of cardiovascular events. Key predictors identified include hypertension, dyslipidemia, and elevated inflammatory markers. These findings emphasize the need for comprehensive cardiovascular risk management and early intervention in CKD patients. Targeted strategies addressing these risk factors could significantly improve cardiovascular outcomes and overall prognosis, enhancing patient care and survival in this vulnerable population.

Recommendations

Strictly control blood pressure and lipid levels in CKD patients.

Regularly check and address elevated inflammatory markers.

Focus on early detection and management to prevent CKD progression and cardiovascular complications.

Acknowledgment

We sincerely thank the Department of Cardiology, Hi-Tech Medical College & Hospital, Bhubaneswar, India, for their support and cooperation. We also extend our gratitude to the patients who participated in this study, and to all staff members contributed to the data collection and analysis.

Author Contributions

Professor Dr. Akshaya Kumar Samal conceived the study, supervised its execution, and contributed to the study design and manuscript writing. Dr. Deepak Narayan Lenka was responsible for data collection, analysis, and manuscript drafting. Both authors approved the final manuscript and are accountable for the work.

Article at a Glance

Study Purpose: To evaluate the incidence and determinants of cardiovascular events in patients with chronic kidney disease (CKD).

Key Findings: 23.5% of CKD patients experienced major cardiovascular events. Significant predictors included hypertension, dyslipidemia, and elevated inflammatory markers.

Newer Findings Added to What Is Known: This study highlights the strong association between CKD progression and increased cardiovascular risk, emphasizing the need for early intervention and comprehensive risk management.

Abbreviations

CKD: Chronic Kidney Disease

CVD: Cardiovascular Disease

GFR: Glomerular Filtration Rate

HDL: High-Density Lipoprotein

RAAS: Renin-Angiotensin-Aldosterone System

Funding: No funding sources

Conflict of interest: None declared

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