April 1987, Volume 37, Issue 4

Original Article


Akhtar Parvaiz  ( Department of Medicine, Allama Iqbal Medical College, Lahore. )
Akhtar Parvaiz  ( National Institute of Child Health, Jinnah Postgraduate Medical Centre, Karachi. )
Hasan Aziz  ( National Institute of Child Health, Jinnah Postgraduate Medical Centre, Karachi. )
Nargis Rehman  ( Department of Neuropsychiatry Jinnah Postgraduate Medical Centre, Karachi. )


Serum Uric Acid (SUA), cholesterol, Ponderal Index (P1) and smoking behaviour were studied in 27 patients with coronary heart disease (CHD) and 30 sex, physique and ethnic group matched controls. Mean SUA was significantly raised (P < 0.01) in the coronary grolup. Mean serum cholesterol, although within normal range in both the groups, was higher in the coronary group than in controls (P < 0.05). The difference of P1’ was also highly significant (P <0.001) indicating preponderance of obesity in the coronary group. No correlation, was found between SUA and either cholesterol or ponderal index. (JPMA 37 90, 1987).


The association between hyperuricemia and accelerated atherosclerotic arterial disease is well known 1-3 Many epidemiological studies have shown significantly raised SUA levels in CHD patients than in controls4 1 0 Coronary Drug Project Group’’ reported twice as higher a risk of early coronary mortality in hyperuricemic CHD patients as compared to normouricemies. Davis’ reported urate deposits on heart valves in rare cases of gout. Later, urate crystal induced endothelial injury was reported to initiate coronary artery thrombosis 2 Since then many studies have demonstrated platelet stimulation and activation of initial coagulation pathways by hyperuricemia both in-vivo and in vitro and reversal of these changes by lowering SUA with uricosuric agents’4’1 9 The object of the present study was to assess the status of SUA in coronary risk profile and to study its correlation with other risk factors as obesity and hyper­cholesterolemia in our population.


A total of 30 patients of CHD admitted during the year 1983-84 to the Department of Medicine, UnitIV of Allama lqbal Medical College, Lahore could fulfil all criteria laid down below and qualified for the study. Thirty age, sex, phy­sique and ethnic group matched controls were selected from the patients Aattendants or hospital employees. Data of three coronary patients on final analysis was found incomplete hence statisti­cal analysis in coronary group was reduced to 27 patients only.


CHD patients with typical history and ECG changes and raised cardiac enzymes in cases of myocardial infarction were included in the study. Those with atypical history and the ones with non-specific ST-T changes, Left Bundle Branch Block or Left ventricular hypertrophy were excluded. Patients having any of the conditions known to be associated with hyperuricemia like myelo and lymphoproliferative disorders, mali­gnancy, psoriasis, sarcoidosis, chronic renal failure, congestive cardiac failure or on drugs as diuretics, methyldopa, reserpine, low dose salicylates, ethambutol, pyrazinamide were excluded from the study.

A questionnaire was given to each subject which also included items on educational and vocational achievements, smoking, alcoholism and high purine dietary fads etc. A complete history was taken and general and systemic examination done on each subject. Height was recorded in inches (without shoes) and weight in pounds (ibs). Ponderal Index was calculated for each subject, which is a quotient of height in inches to cube root of weight in lbs.
Related inversely to body physique, P1’ is a measure of body build. A value approaching 10 reflects laterality of build or obesity while a figure approaching 14 indicates linearity of build or leanness4. Haemoglobin, urinalysis and total and differential white cell count were obtained in each subject. An X-Ray chest, P.A.view, was taken in all coronary patients for the evidence of cardio­megaly and wherever indicated in control group. A resting 12 lead ECG was recorded in each subject and whenever necessary ‘Master’s Double Step Stress Test’ was administered. Sera of all the cases was immediately refrigerated for the deter­mination of SUA, creatinine and cholesterol. Hemolysed sera were discarded. SUA was deter­mined by uricase enzyme spectro -photometric method2 0 and serum cholesterol by ‘Abell Kendal Method21. Fasting and 2 hours post prandial blood glucose was determined in all on capillary blood by Ferricyanide Method. All laboratory determinations except fasting blood glucose were done within a week of drawing blood.
Statistical analysis was done by student’s ‘t’ test and 2 tailed test of significance. Taking SUA, a dependent variable, its correlation with Serum Cholesterol and Ponderal Index was deter­mined by calculating its correlation co-efficient vis-a-vis, the other 2 independent study variables.


For statistical analysis subjects were divided into Coronary and control groups. Coron­ary group consisted of 19 males and 8 females (sex ratio 2.37:1) against 21 males and 9 females in the control group (sex ratio 2.33:1). Age ± SD for all the study groups is summarized in table I.

Table II sums up means ± SD of the 3 study variables i.e., SUA, P1 and S. Cholesterol (sexwise and pooled figures) in different groups. Frequency distribution of SUA arranged in in­crements of 1 against percentage of study subjects falling in each range is shown in Figure 1 for all the study groups.

There was a preponderance of smokers in the coronary group as compared to the controls. While 36.84% of coronary males smoked 20 or more cigarettes a day, only 12.5% of control males smoked that heavily. Among males 43.75% controls and 15.78% patients were non smokers (Figure 2).

None of the control females smoked so their data is not shown in the figure 2.
There was a significant difference in mean SUA levels and P1 in control and coronary groups (Table III).

Cholesterol was normal in both groups.


Many diverse conditions influence SUA either by increasing uric acid synthesis (over­production - hyperuricemia) or by decreasing its renal excretion (under-excretion -hyperuri- cemia). Examples of the former include all myelo and lyrnphoproliferative disorders, malignancies, sarcoidosis, psoriasis, cytotoxic agents, radio­therapy etc., (i.e. all conditions characterized by increased cell turn-over), while examples of the latter include all types of acidosis, chronic renal insufficiency, all oedematous conditions, diabetes, CCF, most diuretics, low dose salicylates,methyl­dopa, reserpine, guanethedine, suiphinpyrazone, ethambutol, pyrazinamide, alcohol. A sizeable percentage of coronary patients would have one or the other of above mentioned associates on admission. All these for obvious reasons had to be excluded, making patient selection very difficult.
Mean age in coronary females (52.50. ± 5.97) was slightly higher than their male counter parts (50.89 ± 11.68) indicating possibly a slight cardioprotective role of female sex hormones at least until menopause. Mean SUA in the present study was 7.40 ± 2.61 for coronary males and 6.9 ± 1.73 for coronary females. Com­parable figure of Mc-Ewin and colleagues9 in a study of 300 Australian patients with myocardial infarction was 7.24 ± 1.18 mg/dl and 6.60± 2.01 for males and females respectively. In the control group mean SUA was 5.43 ± 2.51 in males and 4.89 ± 1.78 in females. A comparable figure in Evan County study23 was 5.7 ± 1.2 and 4.8 ± 1 .2 for males and females respectively. Figures of Framingham study5, Yano and associates7 and Haider et al 26 were similar. Lower means for SUA in females of both the study groups indicate presumably a depresarit effect of eostrogens on SUA. Frequency distribution of SUA and ponderal index did not reveal any consistent trend what­soever except that 37.5% of coronary females had ‘P1’ 10 and below vis-a-vis 22.22% of control females, indicating a preponderance of obesity in former compared to the later notwithstanding the fact that females in both the groups were bulkier as compared to males.
‘SUA’ has been reported to be dependent on age, ponderal index, serum cholesterol, fasting blood glucose and social status5 ,27 In the present study no correlation was found between SUA and age or social status. These findings are in agreement with those of Yano and associates7 No regular association between SUA and educa­tional or vocational achievements was found in the present and other study” while a positive corre­lation between SUA and vocational and/or educational achievement was found by them24’25 As diabetics were excluded from the present study hence effect of blood glucose on SUA could not be studied. As for influence of serum cholesterol and ponderosity on SUA, correlation-co-efficient of each of these 2 variables with ‘SUA’ was calculated, and represented as an ‘r’ value (Table IV) An ‘r’ value

approaching zero indicates no correlation, while a value of +1 indicates a direct positive and 1 a direct negative one. In this study SUA vs ‘P1’ had an ‘r’ value of —0.02 and is in complete harmony with many other epidemio­logical studies5 ,2 2,2 6 while other studies showed a positive correlation4 27; A similar comment applies to the correlation between SUA and cholesterol (r—0 003) and is in agreement with many similar studies.2,9- 1 Many other studies have reported a direct positive correlation between SUA and cholesterol7 ,22 ,23 In Framingham study5 this correlation could not reach statistical signi­ficance. Contrary to the controversial association between SUA and cholesterol an association between SUA and triglycerides is clearly defined and is a real one. Halparn et al12 2 reported a direct positive correlation between SUA and tri­glycerides. Many other epidemiological studies corroborate this point.32’7 It appears that the association between SUA and triglycerides is a direct and true one, that between cholesterol and SUA is uncertain and needs further work. Findings of this study suggest hyperuricemia to be a risk factor on its own merits in CHD, not being interdependent on obesity or hypercholestero lemia.


The author wishes to convey special thanks to Mr. Manzar Saleem, ex-Statistical Officer Services Hospital, Lahore for his expert help in statistical analysis of the study.


1. Davis, N.S. The cardiovascular and renal relations and manifestation of gout. JAMA., 1897;29 :261.
2. Huchard. Traite Clinique des maladies due coeur et de I’aorta. Paris, G.Doin, 1899; P. 174.
3. Futcher, T.B., Osler, W. and McCrae, T. Modern medicine, Philadelphia, Lea Bros., 1907; vol. 1, p. 808.
4. Gertler, M.M., Garn, S. and Levine, S.A. Serum uric acid in relation to age and physique in health and in coronary heart disease. Ann. Intern. Med., 1951; 34:1421.
5. Kennel, W.B. Some lessons in cardiovascular epidemiology from Framingham. Am.J. Cardiol., 1976; 37 :269.
6. Rakic, M.T., Valkenburg, H.A., Davidson, R.T., Engels, J. P., Mikkelsen, W.M., Neel, J.V. and Duff, i.F. Observations on the natural history of hyperuricemia and gout. I. An eighteen years follow-up of Nineteen Gouty families. Am. J. Med., 1964; 37 : 862.
7. Yano, K., Rhoads, G.G. and Kagan, A. Epi­demiology of serum uric acid among 8000 Japanese American men in Hawai. J. Chronic Dis., 1977; 30 : 171.
8. Myers, A.R., Epstein, FE-I., Dodge, H.J. and Mikkelsen, W.M. The relationship of serum uric acid to risk factors in coronary heart disease. Am.J.Med.,1968;45 :520.
9. Jacobs, D.Hyperuricemia in myocardial infarc­tion. S. Afr. Med. J., 1972; 46: 367.
10. Mathieu, L., Colleson, L. and Hedal Infants do myocardia etc goutte articulaire. Rheum., 1952; 19 : 722
11. Coronary Drug Project Research Group Serum uric acid; its association with other risk factors and with mortality in coronary heart disease. J.Chronic Dis., 1976;29: 557.
12. Traut, E.F., Knight, A.A., Szanto, P.B. and Passerelli, E.W. Specific vascular changes in gout. JAMA., 1954; 156: 591.
13. Bluhm, G.B. and Riddle, J.M. Vascular disease in gout. Prim.Cardiol., 1978;26.
14. Smythe, H.A., et al. Platelet economy & blood coagulation in gout. Arthritis Rheum., 1962; 5:322.
15. Mustard, J.F., et al. Blood coagulation and platelet economy in subjects with primary gout. Edited by Mario, C. Beldini. New York, Crone & Stratton, 1974; p. 265.
16. Viozzi, F.J., Bluhm, B.J. and Riddle, J.M. Gout and arterialtthrombosis. Henry Ford Hosp. Med. J., 1972;   20: 119.
17. Winocour, P.D., Turner, M.R., Taylor, T.G. and Munday, K.A. Gout and cardiovascular disease. Lancet, 1977; 1: 959.
18. Talbott, J.H. Gouty arthritis & hyperuricemia. Hosp. Med., 1977; 13: 44.
19  Riddle, J.M., Bradshaw, D.L. and Bluhm, G.B. Platelet ultrastructure in primary gout. Arthritis Rheum.,1968; 11: 113.
20. Wells, M.G. Improved method for the determi­nation of uric acid in blood and urine. clin. Chim. Acta,1968;22: 379.
21. Abell, L.L., Levy, B.B.,Brodie,B.B. and Kendall, F.E. A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J.Biol. Chem., 1952; 195:357.
22. Fessel, W.J., Siegelaub, A.B. and Johnson, E.S. Correlates and consequences of asymptomatic hyperuricemia. Arch. Intern. Med., 1973; 132: 44.
23. Klein, R., Klein, B.E., Cornoni. J.C. Serum Uric Acid, its relationship to coronary heart disease, risk factors and cardiovascular disease, Evans County, Georgia. Arch. Intern. Med., 1973; 132:401.
24. KasI, S.V., Brooks, G.W. and Rodgers, W.L. Serum uric acid, cholesterol in achievement behaviour and motivation. I. The relationship to ability, grades, test performance and motivation. JAMA., 1970;213: 1158.
25. KasI, S.V., Brooks, G.W. and Rodgers, W.L. Serum uric acid cholesterol in achievement, behaviour and   motivation. II. The relationship to college attendance, extracurricular and social activities, and vocational    aspirations. JAMA., 1970;213: 1291.
26. Haider, Z., Bano, K.A., Usman, S., Maqbool, K. and Saleem, M. Serum uric acid values in hypertension. JPMA., 1979; 29:234.
27. Fessel, WJ. Hyperuricemia in Health and Disease. Seminar. Arthritis Rheum., 1972; 1 : 275.
28  Berkowitz, D. Gout, hyperlipidemia, and diabetes interrelationships. JAMA., 1966; 197:77.
29. Benedek, T.G. Correlations of serum uric acid and lipid concentrations in normal, gouty, and  atherosclerotic men. Ann. Intern. Med., 1967; 66 : 851.
30. Dunn, J.P. and Moses, C. Correlation of serum lipids with uric acid and blood sugar in normal males. Metabolism, 1965; 14: 788.
31. Halpern, M.J. and Pereira, Miguel, M.S. Uric acid and coronary heart disease. J.Am. Geriatr. Soc., 1974;22: 86.
32. Zalokar, J., Lellouch, J., Claude, J.R. and Kuntz, D. Epidemiology of serum uric acid and gout in  Frenchmen. J. Chronic Dis., 1974; 27: 59.

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