European Journal of Cardiovascular Medicine

Heart failure is a clinical syndrome resulting from structural or functional cardiac disorder that impairs the ability of ventricles to fill with or eject blood leading to inadequate perfusion of tissues with oxygenated blood. This clinical syndrome is characterized by symptoms like breathlessness, pedal edema, fatigue, exercise intolerance, signs of elevated jugular venous pressure (JVP), pulmonary crackles, and peripheral edema. Heart failure and renal dysfunction are closely interlinked due to their common underlying risk factors like hypertension, diabetes mellitus and age. Reduced cardiac output and congestion lead to a decrease in renal perfusion, activating the compensatory neurohormonal system and sympathetic nervous system.

Cardiovascular diseases (CVDs) are the foremost cause of death and disability in India, accounting for approximately 14.1% of disability-adjusted life years. CVDs, including heart failure (HF), are major contributors to mortality and morbidity in both urban and rural regions of India. The prevalence of HF is estimated to range from 1.3 million to 22.7 million, with an annual incidence of 0.5 to 1.8 million cases. ^[2,3]

Dyslipidemia characterized by abnormal levels of cholesterol and triglycerides are prevalent in patients with heart failure due to shared risk factors like obesity, diabetes mellitus, and metabolic syndrome. Dyslipidemia contributes to the progression of atherosclerosis and cardiovascular disease which can lead to coronary artery disease and subsequent heart failure. Dyslipidemia contributes to endothelial dysfunction and oxidative stress, which can affect renal function with inflammation and vascular damage. Renal dysfunction and dyslipidemia in heart failure patients is a complex interaction due to risk factors.^[4]

Renal dysfunction is a broad term encompassing impaired kidney function, characterized by reduced glomerular filtration rate (GFR), electrolyte imbalances, and abnormalities in urine composition.^[5] Hypertension and dyslipidemia are well-established risk factors for cardiovascular disease and have also been linked to adverse effects on kidney function. While hypertension is strongly associated with the initiation and accelerated loss of kidney function, dyslipidemia may contribute to the accelerated development of renal insufficiency.^[6]

This was a single centered and cross-sectional study conducted among 168 patients of freshly diagnosed heart failure who came to the outpatient department (OPD) or were admitted to the medicine wards at GMERS Medical College and Hospital, Gotri, Vadodara, Gujarat, over 2 years from the date of approval, Written informed consent was obtained from patients or their relatives before enrolling patients in the study. We were enrolling 168 patients were taken into the study based on using the Daniel Formula we considered 69% prevalence according to previous studies.

Predefined proforma was used to collect data of each individual participant. A thorough medical history was obtained to determine when the symptoms first appeared, how long they have persisted, and any changes that have occurred over time and detailed history, clinical examination, routine blood investigations, and other investigations provisional diagnosis was made in this study.

Patients were divided into two groups based according to renal dysfunction [normal and renal dysfunction]. Renal dysfunction was defined as an eGFR < 90 mL/min·1.73 m² according to the formula given by the Cockcroft-Gault equation: Enrolled patients evaluated for dyslipidaemia, dyslipidaemia defined as total cholesterol [TC] more than 200mg/dl, serum triglycerides [TG] more than 150mg/dl, HDL cholesterol less than 40mg/dl, LDL cholesterol more than 100mg/dl.^[7]

The data collected was recorded in an MS Excel data collection sheet format. Continuous variables were presented as mean ± SD or median (IQR) for non-normally distributed data. Categorical variables were expressed as frequencies and percentages with a 95% Confidence interval. Statistical testing was conducted with the Statistical Package for the Social Sciences software (SPSS trial version). Student t-tests and Chi-Squared tests were used to compare the continuous and categorical data, respectively. A two-sided P value of <0.05 was considered statistically significant. We predicted a finding of 50% with heart failure having renal dysfunction based on previous data.

The table 1 displays demographic details of subjects in a study. It reveals that a small portion, 2.38%, of the participants are between 18 to 35 years old, totaling 4 subjects. Those aged 36 to 45 years comprise 10.71% of the sample, amounting to 18 individuals. The age group of 46 to 55 years is the second-largest, making up 28.57% with 48 subjects. Slightly fewer participants, 46 individuals or 27.38%, fall into the 56 to 65 years category. The largest group, consisting of 52 subjects or 30.95%, is over 65 years old. Out of a total of 168 participants, males constitute a majority, with 98 individuals representing 58.33% of the sample. Females, on the other hand, make up 41.67% of the participants, totaling 70 individuals.

The table 2 presents the distribution of subjects according to their Body Mass Index (BMI). Among the 168 participants, 21 individuals, or 12.50%, are classified as underweight. A larger portion, 52 subjects or 30.95%, fall within the normal weight range. Overweight individuals constitute 25.00% of the sample, with 42 subjects. The largest category is obese, with 53 participants representing 31.55% of the total.

The table 3 outlines the clinical presentations observed among the subjects in the study. Pedal edema was the most common symptom, affecting 57 individuals, or 33.93% of the sample. Fatigue is also highly prevalent, reported by 68 subjects, which represents 40.48% of the participants. Orthopnea is experienced by 31 individuals, accounting for 18.45%. Paroxysmal nocturnal dyspnea affects 36 subjects, making up 21.43% of the sample. Chest pain is reported by 41 participants or 24.40%, and abdominal distension is observed in 32 individuals, representing 19.05%. Out of 168 participants, 36 individuals, or 21.43%, have Diabetes Mellitus. Hypertension is the most prevalent comorbidity, affecting 59 subjects, which constitutes 35.12% of the sample. Chronic Obstructive Pulmonary Disease (COPD) is present in 18 participants, accounting for 10.71%.

The table 4 presents the New York Heart Association (NYHA) classification of subjects in the study, indicating the severity of heart failure symptoms among the participants. There are no subjects classified as Class I, representing 0.00% of the total, which indicates no limitation of physical activity. Class II includes 79 individuals, making up 47.02% of the sample, who experience slight limitation of physical activity. Class III encompasses 53 subjects, or 31.55%, who have marked limitation of physical activity. Class IV, the most severe classification, includes 36 individuals, accounting for 21.43% of the participants, who are unable to carry out any physical activity without discomfort.

The table 5 summarizes the mean lipid profile levels and dyslipidemia  of subjects in the study, indicating their cholesterol and triglyceride levels. The mean total cholesterol level is 174.10 mg/dl with a standard deviation of 13.2, suggesting a relatively moderate average within the population. High-Density Lipoprotein Cholesterol (HDL-C), known as "good" cholesterol, has a mean level of 40.92 mg/dl with a standard deviation of 4.79. Low-Density Lipoprotein Cholesterol (LDL-C), often referred to as "bad" cholesterol, shows a higher mean level of 135.46 mg/dl with a standard deviation of 21.3. The mean triglyceride level is 121.2 mg/dl, also with a standard deviation of 21.3. Dyslipidemia, a condition characterized by abnormal lipid levels in the blood, is present in 87 individuals, accounting for 51.79% of the sample. In contrast, 81 subjects, representing 48.21%, do not exhibit dyslipidemia.

The table 6 illustrates the occurrence of renal dysfunction among the subjects in the study. Renal dysfunction, indicating impaired kidney function, is present in 79 individuals, which constitutes 47.02% of the sample. Conversely, 89 subjects, or 52.98%, do not exhibit renal dysfunction.

The table 7 represents examines the association between renal dysfunction and dyslipidemia among heart failure patients. Out of 79 subjects with renal dysfunction, 57 also have dyslipidemia, while 22 do not. In contrast, among the 89 subjects without renal dysfunction, 30 have dyslipidemia and 59 do not. This indicates that dyslipidemia is more prevalent in patients with renal dysfunction compared to those without. The chi-square statistic for this association is 24.7731, with a p-value of less than 0.00001, indicating a statistically significant association at the p < 0.05 level. This suggests a significant relationship between renal dysfunction and the presence of dyslipidemia in heart failure patients.

Heart failure (HF) is frequently accompanied by renal dysfunction, a relationship that has been extensively studied. Cole RT et al. reported that 20% to 57% of patients with chronic, stable HF and 30% to 67% of those with acutely decompensated HF exhibit varying levels of renal dysfunction. A recent large-scale UK study involving 50,114 heart failure patients found that the prevalence of chronic kidney disease (CKD) in the HF community was 63%, which led to an 11% increase in hospitalizations and a 17% rise in mortality among these patients. The primary pathophysiological mechanism is believed to be the reduction in cardiac output and subsequent decrease in renal perfusion, driving renal dysfunction in HF.

These significant findings underscore the importance of addressing renal dysfunction in heart failure patients to reduce prevalence, hospitalizations, and mortality. Dyslipidemia has emerged as a notable risk factor for renal dysfunction in heart failure. Recent studies indicate that managing dyslipidemia could influence renal outcomes. For instance, a study involving 188,577 CKD patients demonstrated that a 17 mg/dL increase in HDL cholesterol concentration was associated with a 0.8% increase in eGFR and a lower risk for eGFR < 60 mL/min·1.73 m², though no causal relationship was found between LDL cholesterol, triglyceride levels, and kidney disease measures.

The heart and kidneys are closely linked in the context of heart failure. Previous studies have shown a high prevalence of renal dysfunction among heart failure patients. A recent UK national study found that the prevalence of chronic kidney disease (CKD) (eGFR < 60 ml/min·1.73m²) in the heart failure community is 63%. This high prevalence is consistent with findings from hospital and other specialist care settings. Given the high prevalence of CKD among heart failure patients and the significant associated morbidity and mortality, it is crucial to investigate whether lipid profiles are linked to renal dysfunction in this population. This understanding could inform better management strategies and improve patient outcomes.^[7]

The primary objective of this study was to explore the association between serum lipid profiles and renal dysfunction in patients with heart failure. The study involved a diverse group of 168 subjects with varying ages, gender, body mass index (BMI), comorbidities, and clinical presentations, offering a comprehensive understanding of the interplay between lipid levels and renal function in this patient population.

The age distribution showed a predominance of older adults, with 30.95% of the subjects being over 65 years old and another 27.38% aged between 56 to 65 years. This is consistent with the higher prevalence of heart failure in older populations. Males constituted 58.33% of the study sample, reflecting a slight male predominance in heart failure prevalence.Putra GBGP et al.^[9] reported in their study that out of the total subjects, 22 were female, accounting for 31.4%, and 48 were male, making up 68.6%, with a combined total of 70 participants. Similar results were found in previous epidemiological data that show the incidence of dyslipidemia is more common in men.In their study, Jarab AS et al.^[10] found that the average age of participants was 63 ± 12 years. The majority of participants were male, comprising 63.8% of the sample.

The BMI distribution indicated that a significant proportion of the subjects were either overweight (25.00%) or obese (31.55%), which are known risk factors for both heart failure and renal dysfunction. The presence of underweight individuals (12.50%) also highlights the variability in the nutritional and health status of the participants.In their study, Jarab AS et al.^[9] observed the body mass index (BMI) distribution of the participants as follows: 90 participants (21.8%) had a normal BMI (≤24.9 kg/m²), 161 participants (39%) were overweight (25-29.9 kg/m²), and 162 participants (39.2%) were obese (≥30 kg/m²).

Comorbid conditions were common, with hypertension (35.12%) and diabetes mellitus (21.43%) being the most prevalent. Chronic Obstructive Pulmonary Disease (COPD) was present in 10.71% of the subjects. These comorbidities are significant as they can exacerbate both heart failure and renal dysfunction.In their study, Zhang H et al.^[10] observed that 116 participants, or 63.7%, had hypertension, while 52 participants, representing 28.6%, had diabetes mellitus.In their study, Jarab AS et al.^[10] noted that the most prevalent comorbidities among the participants were hypertension (77.1%), type 2 diabetes (61.2%), and ischemic heart disease (IHD) (64.3%). Additionally, the majority of patients, 69.6%, were classified as group III/IV according to the NYHA classification.

The most frequently reported symptoms were fatigue (40.48%), and pedal edema (33.93%). These symptoms are indicative of the advanced stage of heart failure in many subjects. The NYHA classification further corroborates this, with a majority of patients falling into Class II (47.02%) and Class III (31.55%), signifying mild to marked limitations in physical activity.In their study, Zhang H et al.^[11] observed that 242 patients, or 72.0%, were classified as NYHA class II. Additionally, 70 patients, representing 20.8%, were classified as NYHA class III, while 24 patients, accounting for 7.1%, were classified as NYHA class IV.

The mean lipid profile values suggest a moderate level of dyslipidemia among the subjects, with mean total cholesterol at 174.10 mg/dl, HDL-C at 40.92 mg/dl,   LDL-C at 135.46 mg/dl, and triglycerides at 121.2 mg/dl. Dyslipidemia was present in 51.79% of the participants, underscoring its prevalence in the heart failure population.Jarab AS et al in their study observed that the means of TGs, TC, LDL, and HDL were 1.96 (±1.169), 4.18 (±1.288), 2.47 (±1.12), and 0.993 (±0.316) mmol/L, respectively.^[9]In their study, Putra GBGP et al. found that 59 participants, or 84.3%, had dyslipidemia, while 11 participants, representing 15.7%, did not. The total number of subjects was 70, accounting for 100%.^[9]

Epidemiological studies in humans have shown a significant association between dyslipidemia and a higher risk of renal dysfunction in chronic kidney disease (CKD) populations. Animal studies further support that hyperlipidemia contributes to kidney damage, leading to increased glomerulosclerosis and tubulointerstitial damage. In the current study, renal dysfunction was observed among 47.02% of the subjects with heart failure.In the current study, the association analysis between renal dysfunction and dyslipidemia revealed that 57 out of 79 heart failure patients with renal dysfunction also had dyslipidemia, compared to 30 out of 89 heart failure without renal dysfunction. The chi-square statistic of 24.7731 and a p- value of less than 0.00001 indicate a highly significant association between renal dysfunction and dyslipidemia in heart failure patients. In their study, Putra GBGP et al. noted that 62 participants, constituting 88.6%, experienced acute renal failure, whereas 8 participants, or 11.4%, did not. The total number of subjects was 70, representing 100%.^[12]

Another study conducted by Farhan et al^[13] aimed to examine the correlation between stages 4 and 5 of chronic kidney disease and the incidence of dyslipidemia at Fatmawati Central General Hospital in Jakarta during 2016. This cross-sectional study used a simple randomized technique, collecting data from patients' medical records. The study included 80 subjects, all patients with chronic renal failure at the hospital in 2016. The results indicated that the majority of subjects with stage 4 chronic kidney disease (22 subjects, 73.33%) had low levels of LDL, whereas those with stage 5 chronic kidney disease (36 subjects, 72%) had high levels of LDL. The bivariate analysis using the Chi-square test revealed a significant correlation between stages 4 and 5 of chronic renal failure and the incidence of dyslipidemia (p=0.002).^[13]Similarly, Pritee et al.⁵⁸ conducted research on the prevalence of dyslipidemia in patients with acute renal failure. The study found that individuals with acute renal failure had significantly higher levels of total cholesterol,triglycerides(TG),andvery-low-density

lipoprotein           (VLDL) (p<0.05) compared to those without acute renal failure. Additionally, patients with acute heart failure exhibited extremely low levels of high-density lipoprotein (HDL). The study also discovered that acute renal failure was associated with high levels of total cholesterol and LDL, and low levels of HDL.^[13]

This study shows the association between serum lipid profiles and renal dysfunction in patients with heart failure. The findings reveal several important aspects of this relationship. The lipid profile shows moderate average levels within the population, with mean total cholesterol at 174.10 mg/dl, HDL-C at 40.92 mg/dl, LDL-C at 135.46 mg/dl, and triglycerides at 121.2 mg/dl. Dyslipidemia is present in 51.79% of the participants. Renal dysfunction affects 47.02% of the subjects, indicating a high prevalence among heart failure patients. The study identifies a significant association between renal dysfunction and dyslipidemia. Among the 79 subjects with renal dysfunction, 57 (72.15%) also have dyslipidemia, compared to 30 (33.71%) out of 89 subjects without renal dysfunction. The chi-square statistic of 24.7731 and a p-value of less than 0.00001 indicate a highly significant relationship between these conditions.

Limitation:

This research was conducted at a single center and therefore had challenges in reaching a suitable number and geographic variety of participants.

The patients for this study were recruited from a tertiary care hospital, which generally caters to more severe cases compared to the community; thus, the general applicability of these results is a concern.

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