BIBLIOGRAPHY

Clinical assessment of chronic heart failure patients has been helpful in determining severity of disease using measures such as six minutes walk test, NYHA functional class, AHA staging of heart failure and measurement of peak oxygen consumption with maximum bicycle or treadmill exercise. In addition, several biomarkers have been evaluated for use in diagnosis, monitoring and prognostication of chronic heart failure.^114-119

Although high serum uric acid level has been established to be associated with chronic heart failure from several works19,88,120,121 there is need to define clearly the pattern of changes in the serum level to aid its application in patient management, especially in resource limited countries like Nigeria.

In this study of 90 patients and 90 controls, there was no statistically significant difference in the sex and age of the subjects. There were 30 (33.3%) males and 60 (66.7%) females.

The high percentage of females is a reflection of the hospital visits for female patients and the high prevalence of peripartum cardiomyopathy (PPCM) in Zaria. ^121,122The mean age of patients was 40.69±15.46 years with a significant difference in the male (51.43± 12.84 years) and female (35.32±13.84 years) mean ages. Hypertension was the commonest cause of heart failure (44.4%) consistent with findings in other parts of Nigeria and Africa 36,45-47,123 as against ischaemic heart disease seen among the elderly in developed countries 44,124,125

The overall prevalence of hyperuricaemia among chronic heart failure patients was 67.8%

which is 3.5 times the prevalence among controls (18.9%). This finding is similar to the prevalence reported by Anker SD et al¹⁶ in two separate studies of 112 (derivation study) and 182 (validation study) patients, and other studies.^87,126,127Lower prevalences of 56% and 40% were reported in studies done by Yamaguchi et al and Jankowska et al. ^128,129The prevalence of 56% may be due to the use of all classes of heart failure patients. Similarly, class IV patients were excluded from the study with a prevalence of 40%. The range of uric acid levels among patients in this study showed a lower limit similar to that observed in the derivation study but differ in the highest value obtained. Values obtained from the validation study were different from both the derivation study and the current study.¹⁶ This is because values used to define range of data may be isolated and thus can vary widely.¹⁰⁷

Mean serum uric acid level in patients was markedly different when compared with the mean value in controls (51.2% higher). This is similar to the 56.8% higher value reported by Leyva et al²⁸ thereby supporting the role of chronic heart failure in the generation of high uric acid levels. In this study the mean uric acid level was well above the cut-off for hyperuricaemia²⁹ and only slightly short of the value validated in studies to be associated with worsened outcome.¹⁵ In the study of 59 chronic heart failure patients by Leyva et al²⁸ the mean UA level was 488.9µmol/L as compared to the higher value of 543.03µmol/L in this study. This may be due to the fact that NYHA II-IV patients were used in this study compared to NYHA I-IV used for that study.

There was also an increasing trend in the mean serum UA levels with increasing NYHA class which represents worsening functional status and thus severity of cardiac failure.⁵² In previous studies, increasing NYHA class and worse cardiac function have been associated with higher UA levels.28,95,127,130,131 There was statistically significant difference between the mean UA level of each NYHA class (ρ=0.001) which suggests a distinct rise in serum UA levels as patients’ functional status deteriorate. Contrary to the finding of rising UA level

with increasing NYHA Class, the levels of serum UA did not rise with duration of heart failure. The highest mean serum UA level was found among patients with heart failure for

<1 year. This is consistent with several reports of high serum UA levels even among patients with new onset or acute heart failure.^132-134 Although heart failure is likely to progress with time, functional status (NYHA Class) can vary considerably thereby serving as a basis for changes in the serum UA levels rather than the duratiion.

Diastolic function had a weak positive correlation (r=0.143) with UA levels. The weak coefficient of correlation in this study may be due to the presence of combined systolic and diastolic dysfunction in most (68.9%) of the patients studied . These findings are similar to those in other studies where a positive correlation between UA levels and severity of diastolic dysfunction were found.28,95,135,136 Although combined diastolic and systolic dysfunction showed highest serum UA levels compared to other forms of left ventricular dysfunction, there was no statistically significant difference between them. Also the difference in UA levels observed between patients with normal and abnormal diastolic function (524µmol/L versus 547µmol/L) was not statistically significant.

The left ventricular ejection fraction had moderate negative correlation (r= -0.315) with UA levels. Simple linear regression showed that the LVEF significantly predicted UA level.

Similarly, fractional shortening (FS) showed significant negative correlation (r=-0.297) with serum UA levels while all other measures of LV systolic functions assessed (LVIDD, LVIDS, ESV, EDV) showed significant positive correlation with serum UA levels. These agree with a study by Yazicioglu MV et al¹³⁷ where serum UA negatively correlated with LVEF (r=-0.334) and positively correlated with left ventricular volume. Also, in the study by Jankowska et al¹²⁹ LVEF had a moderate negative correlation with serum UA levels. The fact that LVEF and UA levels have been demonstrated separately to correlate with worsening heart failure are supportive evidences to the findings in this study.28,127,135

In a multiple regression analysis (F= 2.865, ρ= 0.012), LVEF best predicted serum UA level independent of LVIDD, duration of heart failure, BMI, and E/A ratio. This finding may be important in providing insight on how depressed LVEF may be especially in areas where echocardiography facility or skilled manpower are not available.

Age of patients was found to correlate positively with serum UA levels similar to findings in normal subjects however, the age could not significantly predict UA levels. Based on gender, the UA level was found to be higher in males compared to female patients. This is a reflection of the established fact that higher UA levels are found in males while the levels remain low in females untill after menopause.^2,138 In this study, 57.8% of patients were less than 45 years of which 82.7% were females suggesting a high proportion of premenopausal women in this study.

Mean UA levels for different aetiologies of heart failure had no statistically significant difference. This was also shown by other studies^16,28,77 because once heart failure is established it causes similar metabolic, functional and immunologic derrangement irrespective of aetiology. Further evidence in support of this fact is that although some cardiovascular diseases have long been associated with raised serum UA, other eatiologies such as rheumatic valve disease have not untill the onset of heart failure.¹³⁹ Cardiovascular diseases including obesity, stroke, diabetes occured as co-morbidities in 23.3% of patients, however the mean uric acid level was not significantly different from those without comorbidities. A cummulative effect from presence of multiple cardiovascular diseases is therefore not likely.