Ischemic heart disease (IHD), or coronary artery disease (CAD), is a predominant source of morbidity and mortality globally. It is defined by a disparity between myocardial oxygen supply and demand, typically resulting from atherosclerotic constriction of the coronary arteries.1 Urbanization, sedentary habits, and escalating incidence of risk factors such as diabetes, hypertension, dyslipidemia, obesity, and smoking are contributing to the growing burden of IHD in developing nations, including India.2 The prompt identification of persons at risk is essential for diminishing cardiovascular incidents and enhancing long-term results.3 Rheumatoid factor (RF) is an autoantibody that targets the Fc region of immunoglobulin G (IgG). Historically, RF has been regarded as a serological indicator for the diagnosis and prognosis of rheumatoid arthritis.4 Nonetheless, high RF levels are not exclusive to rheumatoid arthritis and may occur in other circumstances, including persistent infections, autoimmune diseases, pulmonary abnormalities, and a minor percentage of healthy elderly adults. In addition to its diagnostic utility, RF has been increasingly examined for its potential involvement in systemic inflammation and vascular pathology.5 Increasing data indicates that systemic inflammation is pivotal in the pathogenesis of atherosclerosis. Chronic inflammatory mediators expedite endothelial dysfunction, enhance lipid accumulation, and enable plaque formation and rupture, which are essential factors underlying IHD. Considering that RF indicates a persistent inflammatory condition, researchers have investigated its correlation with cardiovascular illnesses.6,7 The exact mechanism connecting RF to IHD remains incompletely elucidated. It is postulated that RF and other autoantibodies may induce vascular damage via immune complex deposition, complement activation, and the enhancement of inflammatory cascades.8 These processes can expedite atherosclerosis, resulting in a heightened occurrence of myocardial infarction, unstable angina, and other indications of IHD.9 In India, the incidence of IHD is increasing, especially among middle-aged individuals. Notwithstanding progress in diagnostic and treatment techniques, a considerable number of patients appear late with severe disease. Recognizing supplementary signals like RF may enhance the risk categorization of patients who could be overlooked by conventional risk factors alone. Moreover, because to its simplicity, cost-effectiveness, and widespread accessibility, RF estimate can be incorporated into standard clinical practice in resource-constrained environments.10,11 This study seeks to elucidate the association between RF and cardiovascular risk within a hospital-based context. Establishing this association may have substantial consequences in preventive cardiology, particularly for high-risk populations. AIMS AND OBJECTIVES • To study the correlation between Rheumatoid Factor and Ischemic Heart Disease

This observational study was undertaken in the Inpatient Department of General Medicine at Sree Mookambika Institute of Medical Sciences, Kulasekharam, spanning eight months. The research cohort comprised 80 patients admitted with a clinical suspicion of IHD. I ndividuals aged 18 years and older were deemed eligible for participation if they had symptoms indicative of IHD, including chest discomfort, dyspnea, or syncope, and given informed consent to participate. Individuals with diagnosed rheumatoid arthritis, other recognized connective tissue illnesses, chronic infections such as tuberculosis or hepatitis, or chronic pulmonary conditions that are known to increase RF levels were excluded from the study. Individuals who declined to provide informed consent were likewise eliminated. Following recruitment, each patient received a comprehensive clinical history and an exhaustive physical examination. Demographic information and risk variables, including smoking, alcohol consumption, diabetes, hypertension, dyslipidemia, and familial history of IHD, were documented in a structured style. Standard investigations were conducted, encompassing electrocardiography (ECG) to detect ischemia alterations, echocardiography to evaluate regional wall motion abnormalities and left ventricular function, and serum cardiac enzymes, including troponins and CK-MB, to confirm acute coronary syndromes. Furthermore, biochemical measures such as fasting blood glucose, renal function assessments, and lipid profiles were evaluated. Serum RF levels were assessed in all individuals utilizing the latex agglutination technique. A result exceeding 20 IU/ml was deemed positive. Patients were classified into two groups based on the test results: those with a positive RF and those with a negative RF. The diagnosis of IHD was validated using a synthesis of clinical observations, electrocardiogram alterations, cardiac enzyme concentrations, and echocardiographic data. All collected data were assembled and analyzed with SPSS software (version 20.0). Continuous variables were presented as mean ± standard deviation, whereas categorical variables were represented as percentages. The Chi-square test was employed to compare categorical variables, whilst Pearson’s correlation coefficient was utilized to evaluate the association between RF and IHD. A p-value below 0.05 was considered to be statistically significant.

The mean age of the study population was 49.6 ± 12.7 years. Male predominance was noted (65%), with the majority of patients belonging to the 41–60 years age group, consistent with the known epidemiology of IHD. (Table 1) Table 1: Age and Sex Distribution of Study Population Age Group (years) Male (n=52) Female (n=28) Total (n=80) Percentage (%) 18–30 6 3 9 11.3 31–40 10 6 16 20.0 41–50 14 6 20 25.0 51–60 12 7 19 23.8 >60 10 6 16 20.0 Hypertension (42.5%) and diabetes (37.5%) were the most common comorbidities observed among the study population, reflecting their established role in the pathogenesis of IHD. Among 80 patients, 28 (35.0%) were RF positive (>20 IU/ml), while 52 (65.0%) were negative (≤20 IU/ml), indicating moderate seropositivity in the cohort. 46 (57.5%) were diagnosed with IHD, confirming the high burden of CAD in this patient group. A statistically significant association was found between RF positivity and the presence of IHD. Patients with elevated RF had a higher prevalence of IHD compared to those with normal RF levels. (Table 3) Table 3: Correlation between Rheumatoid Factor and Ischemic Heart Disease Rheumatoid Factor Status IHD Present (n=46) IHD Absent (n=34) p value Positive (n=28) 20 (71.4%) 8 (28.6%) 0.042 Negative (n=52) 26 (50.0%) 26 (50.0%) Patients with IHD had significantly higher mean RF levels compared to those without IHD, reinforcing the positive correlation (p < 0.05).(Table 4) Among IHD patients (n=46), 30 were troponin positive and 16 were troponin negative. The mean RF level was 29.4 ± 11.8 IU/ml, and the difference was statistically significant (p = 0.027) indicating a notable association between elevated RF levels and troponin positivity in IHD patients. Table 4: Mean Rheumatoid Factor Levels in Patients with and without IHD Group Mean RF (IU/ml) ± SD p-value IHD Present (n=46) 27.8 ± 12.6 0.031* IHD Absent (n=34) 19.6 ± 10.4 RF positive patients had significantly higher total cholesterol, triglycerides, and LDL-C levels with lower HDL-C values. A moderate positive correlation existed between RF and dyslipidemia, supporting the role of inflammation in atherogenesis. Table 5: Correlation between Rheumatoid Factor Levels and Serum Lipid Profile Parameter RF Positive (n=28) Mean ± SD RF Negative (n=52) Mean ± SD p-value Total Cholesterol (mg/dl) 212.4 ± 28.6 190.8 ± 26.2 0.008* Triglycerides (mg/dl) 182.4 ± 40.2 164.6 ± 35.7 0.021* LDL-C (mg/dl) 136.2 ± 24.1 120.8 ± 20.6 0.014* HDL-C (mg/dl) 38.6 ± 6.4 44.2 ± 7.2 0.016* The mean left ventricular ejection fraction (LVEF) among RF positive patients with IHD was 44.2 ± 7.5%, while for RF negative patients with IHD, it was 50.6 ± 6.8%. The difference between the two groups was statistically significant (p = 0.031), indicating that higher RF levels were associated with reduced LVEF.

The mean age of the participants was 49.6 ± 12.7 years, with 65% being male and most of them being between 41 and 60 years old. This demographic distribution corresponds with the recognized epidemiology of IHD, predominantly impacting middle-aged and older individuals, with a higher prevalence in males presumably attributable to variations in hormonal protection and exposure to risk factors. Hypertension and diabetes mellitus were the predominant comorbidities, occurring in 42.5% and 37.5% of patients, respectively, followed by smoking, dyslipidemia, and alcohol consumption. These findings align with the conventional comprehension of cardiovascular risk factors and their role in the progression of atherosclerosis. A considerable percentage of individuals with IHD lacked these traditional risk factors, indicating that supplementary indicators, such as RF, may independently contribute to cardiovascular risk assessment. RF positive was detected in 35% of the research cohort. In RF-positive individuals, 71.4% had IHD, whereas 50% of RF-negative patients did, indicating a statistically significant correlation (p = 0.042). Furthermore, mean RF levels were markedly elevated in individuals with IHD (27.8 ± 12.6 IU/ml) compared to those without IHD (19.6 ± 10.4 IU/ml, p = 0.031), hence substantiating the association between RF and the existence of CAD. Levi EH et al.12 noted that the prevalence of IHD in patients with rheumatoid arthritis (RA) was elevated compared to controls (16.6% versus 12.8%, P < 0.001). Lee TH et al.13 also noted that the prevalence of CAD in patients with rheumatoid arthritis (RA) was markedly elevated compared to the general population. Following propensity score matching to equilibrate confounding variables, rheumatoid arthritis had a substantial association with CAD. Prasad KSJ et al.14 conducted a study involving 50 patients with RF positive, of whom 18 (36%) were male and 32 (64%) were female. Eight patients exhibited ischemia alterations on their ECG, comprising six males (75%) and two females (25%). Of the 8 individuals exhibiting ischemia alterations, 6 presented with conventional risk factors, comprising 4 males (75%) and 2 females (25%). The positive relationship between RF and troponin levels (p = 0.027) suggests that increased RF may be associated with heightened myocardial damage and disease severity. These data substantiate the concept that RF, as an indicator of systemic inflammation, may have a role in atherogenesis and the pathogenesis of IHD. The study revealed substantial correlations between RF positive and dyslipidemia. Patients with RF positivity demonstrated elevated levels of total cholesterol, triglycerides, and LDL-C, accompanied by reduced HDL-C, with correlation values between 0.28 and 0.34. This indicates that systemic inflammation, shown by increased RF, may worsen lipid irregularities, facilitating the formation of atherosclerotic plaques. Chronic inflammation is recognized to disrupt lipid metabolism, elevate oxidative modification of LDL, and diminish protective HDL function, hence increasing cardiovascular risk. Li L et al.15 noted that participants in higher RF quartiles exhibited an elevated BMI (P for trend < 0.001). The levels of BP, FBG, HDL-C, and TG exhibited an upward trend in participants with elevated RF quartiles (all P for trends < 0.01). The LVEF was influenced by RF status. Patients with IHD and positive RF exhibited a significantly reduced LVEF of 44.2 ± 7.5% compared to RF-negative IHD patients, who had an LVEF of 50.6 ± 6.8% (p = 0.031), demonstrating a negative association (r = –0.33). This result indicates that elevated RF levels may correlate with compromised heart function, possibly resulting from inflammation-induced myocardial damage and detrimental ventricular remodelling. It emphasizes the possible use of RF as both an indicator of illness existence and a measure of disease severity. In the study conducted by Faxen J et al.16 rheumatoid arthritis was found to be more prevalent among individuals with heart failure, especially those with an LVEF of 40% or greater. Although RA did not correlate with cardiovascular outcomes among LVEF categories, it was associated with heightened all-cause mortality among patients with LVEF <40%, indicating a possible influence on survival in this category. The study indicates that RF may function as an independent indicator of IHD, in addition to conventional cardiovascular risk factors. The identified correlations between RF and the prevalence of IHD, troponin increase, dyslipidemia, and diminished ejection fraction collectively substantiate its involvement in systemic inflammation and atherogenesis. Although conventional risk variables are fundamental in cardiovascular evaluation, integrating RF assessment may improve risk categorization, especially in individuals lacking evident traditional risk markers.

The positivity of RF was substantially correlated with both the prevalence and severity of IHD. Patients with RF positivity had a greater incidence of IHD, increased troponin concentrations, unfavourable lipid profiles, and reduced LVEF in comparison to RF-negative patients. These data indicate that RF may function as an independent indicator of systemic inflammation and cardiovascular risk. Integrating RF assessment with traditional risk indicators may enhance the early detection and risk categorization of patients predisposed to IHD. FINANCIAL SUPPORT AND SPONSORSHIP: Nil. CONFLICTS OF INTEREST: There are no conflicts of interest

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