European Journal of Cardiovascular Medicine

Metabolic syndrome (MetS) is defined by a cluster of risk factors, including obesity, dyslipidemia, and hypertension and insulin resistance [1]. When occurring together, they increase the risk of developing cardiovascular disease (CVD) and diabetes [2]. Previous studies have shown that the defined MetS risk factors cannot explain all CVD events observed in these subjects. Therefore, several other risk factors such as inflammatory markers, microalbuminuria, hyperuricemia and disorders of coagulation have been debated to be included in the MetS definition [3–6]. The prevalence of MetS is increasing worldwide including Asian countries [7], and a high prevalence of MetS (30.1 %) has been reported in Iran [8]. Serum uric acid is a final enzymatic product of purine metabolism in humans, and it is suggested that hyperuricemia is associated with MetS, and they may have common pathophysiology [9]. In addition to MetS, elevated concentrations of uric acid are associated with a variety of cardiovascular conditions [10].

Micro albuminuria represents an abnormally elevated urine albumin level that cannot be detected with the use of a urinalysis dipstick and is defined as urinary albumin excretion between 30mg to 300mg over a 24 hour period. Micro albuminuria is present in very early stages of Diabetes Mellitus (DM) at a time when GFR may be normal and when there is no evidence of abnormal glomerular filtration. Micro albuminuria is a marker of endothelial dysfunction and is considered a prognostic marker of kidney damage. Studies have shown that prevalence of micro albuminuria increases with increase in duration of the disease in both Diabetes Mellitus (DM) and Non-Diabetic hypertension (NDH). Positivity of micro albuminuria reveals higher range of urea and creatinine in DM and NDH patients. Many studies have concluded that micro albuminuria is essential for early detection of diabetic and hypertensive nephropathy. Therefore, it is recommended that micro albuminuria test should be done at regular intervals for both DM and NDH patients.

Hyperuricemia is an excess of uric acid in the blood. It is defined as serum uric acid level ≥ 7 mg/dl (in men) or ≥ 6.0 mg/dl (in women). It can be a consequence of increased uric acid production and/or decreased renal capacity to excrete uric acid. Abnormal renal hemodynamic commonly seen in initial stages of the disease account for the increased serum urate concentration. Uric acid is the end product of purine metabolism in human and great apes. The enzyme uricase catalyzes the degradation of uric acid to the readily excretable compound allantoin. Increased serum urate may be defined by the solubility of urate, and this is preferable to population defined hyperuricemia (men greater or less than 7.0 mg/dl and women greater or less than 6.0 mg/dl). Hyperuricemia was found to be an independent predictor for the development of newly diagnosed CKD in non CKD patients. This association increases with increasing length of follow up. Increasing evidence suggest that hyperuricemia may be a pathogenic factor for the development of CKD rather than just a marker of decreased renal uric acid excretion. Several potential mechanisms have been suggested to explain the casual relationship between hyperuricemia and CKD including vascular smooth cell proliferation, endothelial dysfunction, and increased synthesis of interleukin-6, impaired endothelial nitric oxide production and insulin resistance. Hyperuricemia may also reflect an unhealthy lifestyle such as smoking, obesity and hyperlipidaemia. Thus risk factors have been confirmed to play a pathogenic role in diabetes, hypertension and metabolic syndrome which also contributes to renal dysfunction.

The metabolic syndrome is a clustering of hyperglycaemia/insulin resistance, obesity and dyslipidaemia. It identifies patients who are at high risk of developing cardiovascular diseases (CVD) and type 2 diabetes mellitus. Metabolic syndrome according to NCEP ATP 3:

Any three of the five criteria: 

Waist circumference: >40 inches (M), >35 inches (F)

Fasting glucose :> /=100mg/dl or Rx

TG :> /=150mg/dl or Rx

HDL cholesterol :< 40mg/dl (M), <50mg/dl (F) or Rx

BP>130mmHg Systole or >85mmHg Diastolic or Rx

Hyperuricemia is an independent risk factor for kidney dysfunction. Various findings suggest that uric acid is an inflammatory factor and may have a role in endothelial dysfunction and act as a mediator of diabetic nephropathy. On the other hand, Micro albuminuria is a well-known early marker of early stages of diabetic nephropathy. In this present study, we want to evaluate the association between hyperuricemia and albuminuria in patients with Metabolic Syndrome.

Study area: The study was conducted in N.R.S Medical College and Hospital (Dept of General Medicine), Kolkata

Study period: February 2023 to May 2024.

Study population: Patients who attended OPD and also from Indoor wards (IPD) of General Medicine and Cardiology Department, N.R.S Medical College & Hospital, Kolkata and those who fulfilled inclusion and exclusion criteria of the study.

Sample Size: 100 both male and female.

Study Design: The study design used here in this study was a clinical, prospective, hospital based single centre observational study.

Inclusion Criteria: Patients fulfilling criteria of metabolic syndrome are to be included in the study.

Exclusion Criteria:

1. Patients with overt nephropathy or diagnosed Chronic Kidney Diseases or Glomerular Filtration Rate (GFR) < 60 ml/min
2. Conditions leading to Albuminuria like pregnancy, urinary tract infections, congestive cardiac failure and acute stressful illness like fever due to any cause.
3. Myeloproliferative or lymph proliferative disorders.
4. Patients on Uric acid lowering agents.
5. History of talking medications which may increase the serum uric acid levels like diuretics, etambutol, pyrazinamide, levodopa, nicotinic acid, cyclosporine and alcohol.
6. Very sick/critically ill patients.

METHOD OF DATA COLLECTION:

1. Interview / History taking
2. Physical examination

• Laboratory examination,

1. Record analysis.

LABORATORY INVESTIGATIONS:-

1. Complete haemogram
2. Fasting Blood Glucose

• Serum electrolytes – Sodium, potassium, chloride etc.

1. Serum uric acid
2. Blood urea & creatinine
3. Urine RE/ME and ACR

• Lipid profile: TC, LDL, HDL.
• ECG in all leads

PARAMETERS AND PROCEDURES:

1. Detailed History: Particularly Alcohol Consumption and use of certain drugs.
2. Clinical Examination:
3. Measurement of Blood Pressure
4. Weight was taken in kilogram by standard weighing machine
5. Height was taken in centimetre with the help of stadiometer
6. BMI was calculated by standard equation. The equation used is as follows: BMI =Weight(Kg)/[Height(Metre)]²
7. Thorough general survey and systemic evaluation was done.
8. Hematological and Biochemical investigations:
9. Haemoglobin, total leucocyte count, differential leucocyte count, platelet count, ESR.
10. Fasting blood glucose (FBG). FBG was estimated by GOD / POD (glucose oxidase-peroxidase) method
11. Serum urea, creatinine
12. Fasting lipid profile: fasting serum total cholesterol, low density lipoprotein cholesterol(LDL), high density lipoprotein cholesterol(HDL), Triglycerides (TGL)
13. Estimation of total cholesterol- Total serum cholesterol was estimated by “CHOD – POD” (cholesterol oxidase - peroxidase method) enzymatic photometric test.
14. Estimation of HDL – Phosphotungstate / Mg2+ precipitates chylomicrons, LDL, VLDL fractions. HDL fraction remains unaffected in supernatant fluid which is measured by absorbance of light at 510 nm.
15. Estimation of triglyceride – by colorimetric enzymatic test using glycerol 3 phosphate oxidase.
16. LDL cholesterol – was calculated by the formula: total cholesterol – [triglyceride /5+HDL].
17. Urine R/E M/E
18. ECG in all leads
19. Specific investigation:
    1. Urinary creatinine was measured by colorimetry. Urinary albumin was measured by immunoturbidimetry. Urinary albumin creatinine ratio (ACR) was calculated by dividing the urinary albumin concentration in micrograms by the urinary creatinine concentration in milligrams.
    2. Serum uric acid level was measured in standardised auto analyser with appropriate quality control sera.
20. Other necessary investigations as and when required. GFR was calculated using Cockroft-Gault formula. Patients enrolled in the study were recommended not to have heavy excersise 24 hours before examination. Urine sample consisted of mid stream urine spot test. Blood samples were collected after 10 hours of fasting.

SCHEDULE OF DATA COLLECTION:

Selected patients were subjected to detailed history taking & clinical examination. They were investigated for base line parameters as outlined above, within the selected study duration & subsequently data were subjected to appropriate stastical analysis.

STUDY TOOLS:

1. Proforma for case records
2. Bedside clinical instruments
3. Standard and modern pathological and biochemical laboratory instruments.

Table 1: shows the distribution of HU/NU of the study population

Table 2: shows the Mean, SD, Median and IQR of different parameters of Study population

In our study, from the above table no.1, the patients Hyperuricemia percentage is 44 %, Normouricemia percentage is 56 %. From the above table no.2, it is revealed that the mean age of the study population is 56.58 years with standard deviation 9.8383, median is 55.5 years with Inter quartile range 15.75 years. For Waist Cir (inch), the mean and SD  are 34.960 inches & 2.1126 inches respectively, median is 35.000 inches, with Inter quartile range 2.00 inches . The average BMI of the study population with standard deviation 25.277 ± 2.1477 with median 25.220 (kg/m2), Inter quartile range 2.862 (kg/m2). The average fasting blood glucose with variation (SD) is 160.030 ± 56.997 with median 146.500 and Inter quartile range is 89.000. The mean Urinary ACR is 143.321 with high variation among study population (SD = 178.68) and Inter quartile range is 170.45 whereas the average Sr. Uric Acid with SD  is 5.777 ± 1.6470 with median 5.750 and Inter quartile range 3.100 . In lipid profile, the variation in TG is more than LDL & HDL.

This study is a hospital-based, observational (cross-sectional) study to evaluate serum uric acid level & urinary Albumin Creatinine Ratio (ACR) in patients of Metabolic Syndrome in both younger & older age group (40 to 80 years). The study also Evaluated the relation between normo albuminuria (ACR <30 ug/ mg), micro albuminuria (ACR between 30 ug/mg & 299 ug/mg) & macro albuminuria (ACR ≥ 300ug/mg) with serum uric acid levels. Although we have contemplated a study both in younger & older age group but eventually this was not done as the number of patients with Metabolic Syndrome in younger age group was inadequate and those who are younger than 40 years were excluded.

A total of 100 patients in the age group of 40-80 yrs. with Metabolic Syndrome who satisfied the inclusion criteria were selected.

In the present study, the correlation and association was studied between micro albuminuria and asymptomatic hyperuricemia in patients with metabolic syndrome.    The clinical parameters examined   included a detailed anthropometry (weight, Height, waist circumference, BMI) and other vital parameters (blood pressure, Hypertension, fasting blood glucose etc.) in addition to detailed systematic examination.

In our study, it is revealed that most of the patient’s age are in the age group 50-70 yrs., (60%), followed by less than 50 yrs. (31 %).

Chin-Hsiao Tseng et al ¹ (2005) reported that mean age in study population was 62.8±10.8 years.

Bonakdaran S, Hami M et al ² (2011) showed mean age in the study population was 52.45 ±10.11 years.

In the present study, it is revealed that most of the patient’s Sex are Female (53 %), followed by Male (47 %). The slightly increased number of females could be explained by the fact that women come more to the health care set up. Another cause may be that our study was hospital based not population based and the disorder (Metabolic Syndrome) is more common in women.

Chin-Hsiao Tseng et al [11] (2005) reported that in study population 42% were Male & 58% were Female.

Bonakdaran S, Hami M et al ² (2011) reported that in study population 43.53% were Male&56.47% were Female.

We found in our present study, most of the patient’s BMI are overweight (51 %), followed by NORMAL (45 %) and obese is 4%.

Chin-Hsiao Tseng et al [11] (2005) reported that in study population mean BMI was 24.6 ±3.5 kg/ m².

Bonakdaran S, Hami M et al ² (2011) reported that in study population mean BMI was 28.24±4.42 kg/m².

The difference in the BMI with our study is probably due to the Indian population inclusion in our study.

We found that, most of the patient’s Waist Cir are not in the group > 40 inches (M), &>35 inches (F)    (71 %), followed by > 40 inches (M), &>35 inches (F) (29 %).

We observed that, it is revealed that most of the patient’s Blood Pressure are not in the group >130mmHg Systole or > 85mmHg Diastolic (34% %), followed by <130mmHg Systole or <80mmHg Diastolic (66 %).

Proportion of Hypertension patients are 50 %, Anti-Hypertensive Therapy (AHT) in 43 % of the patients are present. From the table 8 it is revealed that the patients Macro albuminuria percentage is 19%, Micro albuminuria percentage is 32 % and Normo albuminuria percentage is 49 %. Hyperuricemia percentage is 44 %, Normouricemia percentage is 56 % .Anti-lipid therapy (ALT) in 48 % of the patients. Regarding Inferential statistics, From the table 11,  it is revealed that there is statistically no significant relation/ association between Hyperuricemia / Normouricemia with   Anti lipid therapy as the p-value is >0.05, at 5 % level of significance and the Prevalence of Anti lipid therapy in presence of HU/NU is 48 % . From the table 12, there is statistically significant relation/ association between Hyperuricemia / Normouricemia with   Macro albuminuria /Micro albuminuria / Norm albuminuria as the p-value is < 0.05, at 5 % level of significance. Which shows the same result in various previous study. From the table 13,  it is revealed that there is statistically no significant relation/ association between Hyperuricemia / Normouricemia with   ADT as the p-value is >0.05, at 5 % level of significance and the  Prevalence of ADT in presence of HU/NU is 73 % .From the table 14,  there is statistically no significant relation/ association between Hyperuricemia /

Normouricemia with   AHT as the p-value is > 0.05, at 5 % level of significance and the Prevalence of AHT in presence of HU/NU is 43 % .From table 15 there is statistically no significant relation/ association between Hyperuricemia / Normouricemia with   HTN as the p-value is >0.05, at 5 % level of significance and the Prevalence of HTN in presence of HU/NU is 50 % .From the table 16,  it is revealed that there is statistically  significant relation/ association between Hyperuricemia / Normouricemia with   FBG as the p-value is  <0.05 and the  Prevalence of FBG in presence of HU/NU is 73 %.From the table 17,  it is revealed that there is statistically  significant relation/ association between Hyperuricemia / Normouricemia with   BP as the p-value is <0.05, at 5 % level of significance and the  Prevalence of  BP (dyslipidaemias)  in presence of HU/NU is 34 % .From the table 18 ,  there is statistically no significant relation/ association between Hyperuricemia / Normouricemia with   HDL cholesterol as the p-value is >0.05, at 5 % level of significance and the  Prevalence of HDL cholesterol   in presence of HU/NU is 43 %.From the table19 , it is revealed that the mean age of the study population is   56.58 years with standard deviation  9.8383 , median is 55.5 years with Inter quartile range 15.75 years . For Waist Cir (inch), the mean and SD  are 34.960 inches & 2.1126 inches respectively, median is 35.000 inches, with Inter quartile range 2.00 inches . The average BMI of the study population with standard deviation 25.277 ± 2.1477 with median 25.220 (kg/m2), Inter quartile range 2.862 (kg/m2). The average fasting blood glucose with variation (SD) is 160.030 ± 56.997 with median.146.500 And Inter quartile range is 89.000. The mean Urinary ACR is 143.321 with high variation among study population ( SD = 178.68 ) and Inter quartile range is 170.45 whereas the average Sr. Uric Acid with SD  is 5.777 ± 1.6470 with median 5.750 and Inter quartile range 3.100 . In lipid profile, the variation in TG is more than LDL & HDL.

Serum Uric Acid level in the study:

The mean of the serum Uric Acid in patients with Metabolic Syndrome in our study population was 5.8 ± 1.65 mg/dl (maximum=8.8 mg/dl, minimum= 3.2mg/dl).

Chin-Hsiao Tseng et al [11] (2005) reported that the mean of the Uric Acid in patients with T2DM in study population was 5.6 ± 1.9 mg/dl.

Bonakdaran S, Hami M et al ² (2011) observed that the mean of the serum Uric Acid in patients with T2DM in study population was 5.55 ± 1.47 mg/dl.

Mean serum Uric Acid levels in patients with metabolic syndrome in our study population for normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 4.64 ± 1.07 mg/dL, 6.38± 1.3 mg/dL, and 7.68 ± 1.0 mg/dL respectively.

Chin-Hsiao Tseng et al [11] (2005) reported that the mean serum Uric Acid levels in patients with T2DM in study population for normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 5.2 ± 1.6 mg/dL, 5.6± 1.9 mg/dL, and 6.7 ± 2.1 mg/dL respectively.

Bonakdaran S, Hami M et al ² (2011) observed that the mean serum Uric Acid levels in patients with T2DM in study population for normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 4.49 ± 1.22 mg/dL, 4.84± 1.52 mg/dL, and 6.15 ± 1.68 mg/dL respectively.

Urinary ACR in the study:

Mean urinary ACR levels in patients with Metabolic Syndrome in our study population for normouricemic & hyperurecimic patients were 59.99±101.05 μg/mg, and 249.38±199.75 μg/mg, Mean urinary ACR levels in patients with Metabolic in our study population for normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 22.28 ± 4.09 μg/mg, 134.79±70.65 μg/mg, and 469.83 ± 120.14μg/mg respectively.

Bonakdaran S, Hami M et al ² (2011) observed that the mean urinary ACR in patients with T2DM in study population was 32.52±54.96μg/mg.

Relation of serum Uric Acid level with urinary ACR:

There is significant correlation between serum Uric acid & urinary ACR in our study. Pearson correlation coefficient r = 0.675 (P value <0.001). Spearman’s coefficient of rank correlation (rho)   = 0.731 (P value <0.001).

Chin-Hsiao Tseng et al [11] (2005) reported that there is significant correlation between serum Uric Acid & urinary ACR. Pearson correlation coefficient r   between serum uric acid & natural logarithmic urinary ACR =0.168(P value <0.05).

Bonakdaran S, Hami M et al [12] (2011) observed that there is significant correlation between serum Uric Acid & urinary ACR. Pearson correlation coefficient r   between serum uric acid & urinary ACR =0.097(P value <0.05).

Hyperuricemia correlated positively with FBG, LDL & Triglycerides in patients with Metabolic Syndrome. No significant correlation was found between Hyperuricemia and Age, Sex, Weight, Height, BMI, Hypertension & HDL. Urinary ACR correlated positively with FBG, LDL & Triglycerides in patients with Metabolic Syndrome. No significant correlation found between urinary ACR and Age, Sex, Weight, Height, BMI, Hypertension & HDL. In patients with Metabolic Syndrome, serum uric acid level correlated positively with urinary albumin creatinine ratio. This study showed that Hyperuricemia was associated with a greater probability of Albuminuria in patients with Metabolic Syndrome, Serum uric acid is an independent correlate of urinary ACR in patients with type 2 diabetes mellitus.

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