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Hyperuricemia as a risk factor for cardiovascular Disease: A Prospectivestudy of patients attending A tertiary hospital in North- Eastern Nigeria.

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Akande T,

            Dept. of Chemical Pathology, Bingham University, Jos Campus

Olusanya T, Mamza Y.

            Dept. of Medical Laboratory Science, University of Maiduguri

All correspondence to: Akande T. Dept. of Chemical Pathology, Bingham University, Jos Campus

ABSTRACT

Background- Elevated serum uric acid concentration is strongly associated with increased cardiovascular risk and poor outcome. Objective:This study aimed to determine whether hyperuricemia is an independent risk factor of cardiovascular disease. Methods – A total of 100 patients with mean age 45 ±14.3 diagnosed with cardiovascular disease attending the university of Maiduguri Teaching hospital were examined and compared with 50 healthy individuals as control. The serum uric acid was estimated by the uricase enzymatic method. Results– The result showed a mean concentration of serum uric acid of 431± 160 µmol/L in thecardiovascular subjects was significantly higher (P<0.05) than (318 ±57) µmol/L in the control. The data also revealed that 57% of the patients had an incidence of hyperuricemia. Conclusion – hyperuricemia was associated with cardiovascular disease independently of conventional cardiovascular disease risk factors.

Key words: Hyperuricemia, Cardiovascular disease, Risk factors

INTRODUCTION

Uric acid is the metabolic acid product of Purine metabolism. Previous studies have demonstrated a strong relationship between serum uric acid level and coronary heart disease (CHD) and some studies suggested that uric acid may be an independent risk factor for cardiovascular disease [1-9]. Recently, a meta-analysis showed that hyperuricemia may increase the risk of CHD events, independently of traditional CHD risk factors [10]. However, the nature of relationship between uric acid and cardiovascular disease remain a subject of debate [11-13].

Epidemiological studies have reported relationship between serum uric acid level and a wide variety of cardiovascular conditions, including hypertension metabolic syndrome [14] Coronary artery disease [15]. Cardiovascular disease is the number one global cause of death. An estimated 17.3 million people died from cardiovascular disease CVDs in 2008; representing 30% of all global death [16] CVDs are projected to remain the single leading cause of death [17]. Presently there is paucity of epidemiological data on serum uric acid level in cardiovascular disease in this environment and even with long standing awareness of this association, little attention has been paid to its potential significance, hence the need for this study.

 

Materials and Method

The study group comprised 100 consecutive cardiovascular disease patients attending the medical clinic at the university of Maiduguri teaching hospital, a referral center for North-eastern states of Nigeria and neighbouring countries e.g. Chad and Cameroon.

The patient recruited were seen in the medical clinics, reviewed by the physicians and provisionally diagnosed of cardiovascular disease. Control subjects, 50 apparently healthy individuals without signs of cardiovascular disorder were recruited. Patients with associated cases of kidney dysfunction and gout were excluded.

 

Data Collection

A standard questionnaire was used to collect information such as age, sex, medications, education level. The history of chronic disease and current use of medication were recorded.

In all study patents, a complete clinical work was done including height, weight and body mass index. The body mass index was calculated and expressed as Kg/m2. The blood pressure was recorded in the right upper arm in the sitting posture after a five-minute rest. Patient were categorized as being hypertensive if they were on antihypertensive treatment or if they had a systolic blood pressure >140mmHgand /or diastolic blood pressure >90mmHg [18].

 

Biochemical Measurements

Peripheral various blood samples were collected after an overnight fast and the following investigations were done: plasma glucose, serum cholesterol, and serum triglyceride high density lipoprotein-cholesterol and serum uric acid. Biochemical analyses were done spectrophotometrically using reagents supplied by Randox UK). Serum uric acid using Uricase enzymatic method, were estimated in all samples.

Statistical analysis

Statistical analysis was performed with the SPSS statistical package (version 11.0). Student’t’ test was used to compare the means of variables. The level of significance was set at p-value of <0.05.

 

Results

The study included a total population of 150 subjects, 100 of which were patients with confirmed cases of cardiovascular disease and 50 control individuals. Among the test individual’s females represented 66% of the total population while males represented a portion of 34%.

Table 1. Shows the mean distribution of the age, blood pressure, and body mass index of test and control individuals by sex. There was a significant difference (P<0.05) between the test and control for all characteristics. The total mean age for test individuals was 45.9±15.4 with the males (mean=54.7±14.3) averagely older than the female patients (mean=41.5±14.2). Table 2 shows a mean distribution of biochemical parameters.

Table 3: represent the percentage distribution of serum uric acid levels stratified by age group and sex. The total percentage incidence of hyperuricemia in the CVD patients was 57% among all the age groups and gender. There was a significant level of occurrence of hyperuricemia among all the age and sex. Few of the patients fell between the age group 0 – 19 (4%) and highest was 40 – 59 (54%) having an incidence of 56%.

Table 4: shows the relationship that exists between serum uric acid levels and cardiovascular disease in the presence and absence of individual CVD risk factors. The result revealed that hyperuricemia still persisted even in the absence of individual CVD risk factors. It shows that 54.5% of patients with normal BMI were hyperuricemic as well as 58% of non diabetic patients, 62% of patients with normal serum cholesterol levels and 63% of patients with normal blood pressure all of which were significantly higher than those of patients with one or more CVD risk factors.Table 5: shows the association of serum uric acid level and CVD after categorizing the test individually into diuretic users. The result shows a frequency of 39% diabetics as against 61% of those whose indication does not include diuretic. The incidence of hyperuricemic was substantially higher among persons on diuretic use (64%). However, the association of hyperuricemia with CVD was still maintained as a significant 52.5% of the non-diuretic

DISCUSSION

In this representative general population, hyperuricemia bore a continuous, independent, specific, and significant positive relationship to cardiovascular disease. This association was true for both men and women. The impact of hyperuricemia on cardiovascular disease was positive at all age groups but this influence was strongly observed from those aged 20-59 and above 80.

These data are consistent with a variety of other studies suggesting that an elevated serum uric acid level is an independent risk factor for cardiovascular disease [19, 20, 21, 22].

Furthermore, after controlling for potential risk factors, it was observed that the presence or absence of individual CVD risk factors did not generally alter the positive relation of hyperuricemia to cardiovascular disease as the association of increased serum uric acid level still persisted even among subjects with low cardiovascular risk (i.e. those without an increased cholesterol level, hypertension, diabetes, or obesity). On other hand, hyperuricemia was not strongly associated with CVD in diabetic and patients with elevated cholesterol. In adult, serum uric acid levels vary with height, body weight, blood pressure, alcohol intake and diuretic use [23, 24, 25]. The influence of diuretic therapy on serum uric acid is of particular note and potential importance [26, 27]. To check this influence on the study subjects, patients were stratified based on diuretic and non-diuretic users. In this group, diuretic therapy did appear to modestly increase serum uric acid level. However, the serum uric acid to CVD relation was independently of the effect of diuretics as a higher percentage of the non-diuretic users still had a hyperuricemic state.

The results of this study are not in agreement with that of Culleton etal [11]which reported that an elevated serum uric acid level at baseline was not independently associated with increased risk of cardiovascular mortality. They concluded that the apparent association of serum uric acid to cardiovascular events was probably due to the effect of other cardiovascular risk factors, particularly by diuretic use. The different results seen in these two studies may be due to difference in the population studied (i.e. population from their study was almost exclusively white while those in this study were all black). But considering the vast reports that favor the results of this study, it suggested that theirs may however be an exception, rather than the rule.

The vital question is whether increased serum uric acid is a casual factor for cardiovascular disease. Observational data alone cannot answer that question. It is not possible to determine here whether hyperuricemia is a marker, a co- morbid or intervening factor, or a direct cause of CVD.

In any event, however, hyperuricemia has been shown to meet conventional criteria for a cardiovascular risk factor. The association of increased serum uric acid to cardiovascular disease events is significant, is independent of other known CVD risk factors, is specific and has substantial effect size.

Conclusion

Hyperuricemia was associated with cardiovascular disease independently of conventional cardiovascular disease risk factors and may be considered a risk factor for cardiovascular disease.

 

  1. Neogi T, Ellison RC, Hunt S, Terkeltamb R, Felson DT, Zhang Y: Serum Uric Acid is associated with carotid plaques : the National Heart, Lung and blood Institute family Heart Study. Rheumatol 2009, 36: 378-384.

 

  1. Bos MJ, Kondstaal PJ, Hofman A, Witteman JC, BretelerMM : Uric acid is a risk factor for myocardial infarction and stroke : Rottedam study . stroke 2006, 37 :1503-1507

 

  1. Franse LV, PahorM, Di Bari M, Shorr RI, Wan JY, Somes GW, Applegate WB : Serum Uric acid, diuretic treatment and risk of cardiovascular events in the systolic Hypertension in the Elderly program (SHEP). J Hypertens 2000, 18 : 1149-1154.

 

  1. Juraschek SP, Turistall-pedoe H, Woodward M : Serum Uric acid and the risk of mortality during 23 years follow up in the Scottish Heart Health Extended cohort study Atherosclerosis 2014; 233 :623-629

 

  1. Ito H, Abe M, Mifure M, Oshikiri K, Antoku S, Takenchi Y, TaganeM : Hyper uricemia is independently associated with coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus PLOS one 2011, 6: e27817.

 

  1. Freedman DS, Williamson DF, Gunter EW, Byers T: Relation of serum Uric acid to mortality and lschemic heart disease. The NHANES 1 Epidemiologic follow-up study Am J Epidemiol 19995, 141 : 637-644

 

  1. Krishnan E, Baker JF, Furst DE, Schnmacher HR: Gout and the risk of acute myocardial infarction
  2. Verdechia P, Schillaci G, Reboldi G, Santeusanio F, Porcellati C, Brunetti P, Relation between serum acid and risk of cardiovascular disease in essential hypertension. The  PIUMA study: Hypertension 2000, 36 :1072-1078.

 

  1. Li Q, Yang Z, LuB Wen J, Ye Z, Chen L, He M, Tao X, Zhang W, Huang Y, Zhang Z, Qu S, Hu R serum Uric acid level and its association with metabolic syndrome and carotid atherosclerosis in patients with type 2 diabetes cardiovascular Diabetol 2011, 10 : 72.

 

  1. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, AlbertDA , Hyper uricemia and coronary heart disease : a systematic review and meta –analysis :  Arthritis care Res (Hoboken) 2010, 62 : 170-180

 

  1. Culleton BF, Larson MG, Kannel WB, Levy D : Serum uric acid and risk factor for cardiovascular disease and death : The Framingham Heart study. Ann intern med 1999, 131 : 7-13

 

  1. Brand FN, McGee DL, Kannel WB stokes J 3rd,CatelliWP : Hyper uricemia as a risk factor of coronary heart disease : The Framingham study . Ann J Epidemiol 1985, 121: 11-18.

 

  1. Morianty JT, Folsom AR, Lumbaren C, Nieto FJ, Rosamond WD :serum uric acid risk of coronary heart disease : Atherosclerosis Risk in communities (ARIC) Study Ann Epidemiol2000, 10 : 136-143

 

  1. Ford ES, Lic, cook S serum concentrations of Uric acid and the metabolic syndrome among US children and adolescents. Circulation, 2007,115, 2526-2532

 

  1. Lebto S, Niskanen L, Ronnema T, LaaksoM : serum Uric acid is a strong predictor of stroke in patients with non-insulin dependent diabetes mellitus . Stroke 1998, 29: 635-639.

 

  1. Global status report on non-communicable diseases 2010. Geneva. World Health Organization 2011.

 

  1. Matters CD, Loncar D. projections of Global mortality and burden of disease from 2002 -2030 PLos Med, 2006, 3(11) e 442.

 

  1. Joint National committee on Detection, Evaluation and Treatment of high blood pressure. The fifth report of the Joint National Committee on Detection, Evaluation and treatment of high blood pressure (JNC-V) . Arch intern med. 1993, 153 : 154-183

 

  1. Klein R, Klem BE, comoni J, Maready J, Cassel JC, Tyroler HA. Serum Uric acid. Arch intern Med 1973, 132 : 401-410

 

  1. Bengtsson C, Lapidus L, Stendahal C, Walden storm J. Hyperuricemia and risk of cardiovascular diseases and over all death. Acta Med Scand 1988 224: 549-555.

 

  1. Freedman DS, Williamson DF, Gunber EW, Byers T. Relation of serum uric acid to mortality and ischemic heart diseases. Ann JEpidemiol1995 141 : 637-644

 

  1. Hunt SC, Stephanson SH, Aopkinas PN, Williams RR. Predictors of an increased risk of future hypertension in Utah: a screening analysis Hypertension, 1991, 17: 969-976.

 

  1. Nishioka K, Mikanagi K. Hereditary and environmental factor influencing the serum uric acid throughout ten years population study in Japan Adv Exp Med Biol. 1980, 24 : 631-633

 

  1. Gutman AB, YU TF. Gout: a derangement ofpurine metabolism. Adv. Intern Med 5 : 227-302

 

  1. Steele TH, Oppenheimer S. Factors affecting urate excretion following diuretic administration in man Am J Med 1969, 47 : 564-574

 

  1. Cameron JC, Moro F, Simmods, HA. Uric acid and the kidney In Davison A, Cameron JS, Grunfield JP, Kevv D (leds). The oxford textbook of clinical nephrology. Oxford Medical publication 1998, 825-837

 

27.          Bengtson C, Elavated serum uric acid levels during treatment with anti-hypertensive drugs Acta Med ScandSuppl 1979,628: 69