BMC Public Health BioMed Central

Research article Open Access
Prevalence of hyperuricemia and relation of serum uric acid with
cardiovascular risk factors in a developing country
D Conen1, V Wietlisbach2, P Bovet2,3, C Shamlaye3, W Riesen4, F Paccaud2
and M Burnier*1

Address: 1Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland, 2University Institute of Social and Preventive Medicine,
Lausanne, Switzerland, 3Ministry of Health, Republic of Seychelles and 4Kantonalspital St Gallen, Switzerland
Email: D Conen - conend@uhbs.ch; V Wietlisbach - vincent.wietlisbach@inst.hospvd.ch; P Bovet - pbovet@seychelles.net;
C Shamlaye - shamlaye@seychelles.net; W Riesen - walter.riesen@ikch.ch; F Paccaud - fred.paccaud@inst.hospvd.ch;
M Burnier* - michel.burnier@chuv.hospvd.ch
* Corresponding author

Published: 25 March 2004 Received: 30 December 2003
Accepted: 25 March 2004
BMC Public Health 2004, 4:9
This article is available from: http://www.biomedcentral.com/1471-2458/4/9
© 2004 Conen et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all
media for any purpose, provided this notice is preserved along with the article's original URL.

Serum uric acidblood pressuretriglyceridescholesterolweightpopulation study

Abstract
Background: The prevalence of hyperuricemia has rarely been investigated in developing
countries. The purpose of the present study was to investigate the prevalence of hyperuricemia
and the association between uric acid levels and the various cardiovascular risk factors in a
developing country with high average blood pressures (the Seychelles, Indian Ocean, population
mainly of African origin).
Methods: This cross-sectional health examination survey was based on a population random
sample from the Seychelles. It included 1011 subjects aged 25 to 64 years. Blood pressure (BP),
body mass index (BMI), waist circumference, waist-to-hip ratio, total and HDL cholesterol, serum
triglycerides and serum uric acid were measured. Data were analyzed using scatterplot smoothing
techniques and gender-specific linear regression models.
Results: The prevalence of a serum uric acid level >420 µmol/L in men was 35.2% and the
prevalence of a serum uric acid level >360 µmol/L was 8.7% in women. Serum uric acid was strongly
related to serum triglycerides in men as well as in women (r = 0.73 in men and r = 0.59 in women,
p < 0.001). Uric acid levels were also significantly associated but to a lesser degree with age, BMI,
blood pressure, alcohol and the use of antihypertensive therapy. In a regression model,
triglycerides, age, BMI, antihypertensive therapy and alcohol consumption accounted for about 50%
(R2) of the serum uric acid variations in men as well as in women.
Conclusions: This study shows that the prevalence of hyperuricemia can be high in a developing
country such as the Seychelles. Besides alcohol consumption and the use of antihypertensive
therapy, mainly diuretics, serum uric acid is markedly associated with parameters of the metabolic
syndrome, in particular serum triglycerides. Considering the growing incidence of obesity and
metabolic syndrome worldwide and the potential link between hyperuricemia and cardiovascular
complications, more emphasis should be put on the evolving prevalence of hyperuricemia in
developing countries.

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More recently. the 20% disorders which characterize the so-called metabolic syn. studies have explored the relationship of serum uric acid with cardiovascular risk factors in a bi-racial community Alcohol habits [16. hyperinsulinemia. cardiovascular disease accounted for 37% of all deaths in 2003.m. Hip and waist were measured to hyperuricemia in all race-sex groups. two the nearest 1 cm. did never smoke. the Seychelles. A simple age. elevated serum uric acid lev- els have been linked to hypertension. The study was conducted between July and Decem- Elevated serum uric acid levels are commonly seen in ber 1994. a levels [16]. Those declaring a consumption of at least one The purpose of the present study was to investigate the drink per week were further questioned about their prevalence and the clinical correlates of hyperuricemia in weekly average consumption of the different alcohol bev- a developing country. persons were categorised according to frequency of alence of hyperuricemia has rarely been investigated in alcohol drinking: never. principal island (89% of the total population) was lin to decrease the clearance of uric acid in the renal included. there is still no well-established pathophysio. Among the initial group of 1280 persons. a group of confounding factors such as obesity. 1226 proximal tubule resulting in an increase in serum uric acid were eligible and a total of 1059 participated the study. every other day and almost every day.17].m. About 65% of the population of the Seychelles association with glucose intolerance. ease has been recognized since the 1950s and has been confirmed by numerous epidemiological studies since Methods then [1-7].16-22]. increased body mass index. currently smoking at least one cigarette per day. occasional smokers referred to persons reporting white populations of North America and Europe or non-daily consumption of cigarettes and regular smokers. dyslipidemia. use of diuretics and insulin resistance [8-10]. The study was designed as a cross- drome [11-15]. A population-based health examination Page 2 of 9 (page number not for citation purposes) . 10% of predominantly Caucasian and dyslipidemia. a population mainly erages available. a cluster of metabolic and hemodynamic 5% of predominantly Indian or Chinese descent. whether uric acid is an independent The Seychelles Heart Study II risk factor for cardiovascular mortality is still disputed as The Seychelles Heart Study II was a second survey to assess several studies have suggested that hyperuricemia is the cardiovascular risk factors and selective cardiovascular merely associated with cardiovascular diseases because of outcomes in the population of the Seychelles. However.BMC Public Health 2004. It has been described in as well as in subjects with asymptomatic hyperuricemia detail before [24]. 115 islands lying in the Indian Ocean with a relatively tension. Klein et al studied a multiracial community in Evans County. once or twice a week. Thus. Several population-based studies have also response rate of 86%. In 1973. standing without shoes and heavy outer garments. hypertension and is of black descent. in order to examine the frequency distri. statistics. Smoking habits were classified as followed: persons who lesterol [11. Weight and height and body mass index bution of serum uric acid and the relationship of serum Height and body weight were measured with participants uric acid levels with known coronary risk factors [23]. Alcohol consumption was assessed in two stages.biomedcentral. of African origin. occasionally but less than once a developing countries. week. The prev. which are based on death certificates established logical link between hyperuricemia and the development by a doctor for all fatalities in the country. high cardiovascular morbidity and mortality [24]. 4 http://www.com/1471-2458/4/9 Background survey was conducted recently in this country. Smoking increased alcohol consumption and decreased HDL cho. Studies performed in healthy volunteers section of the general population. remaining being mixed. The study The positive association between serum uric acid and car. population including elderly subjects. entirely black populations from South Africa. ex-smokers designated persons who reported no current smoking but regular smoking in the Most studies on uric acid have been performed in selected past. However. Measures and cut-off points reduced physical activity. sample of the residents aged 25–64 years living on the drome and serum uric acid is related to the ability of insu. these latter investigations were con. indicate that of cardiovascular complications. population represents a complete sample of the general diovascular diseases such as stroke or ischemic heart dis. Indeed Moreover. and 10 a.13. In the ducted essentially in children and young adults.and sex-stratified random have suggested that the link between the metabolic syn. hyper. All participants have been submit- examined the influence of a number of cardiovascular risk ted to a detailed questionnaire and a medical examination factors or components of the metabolic syndrome on in the study centre between 8 a.14. serum uric acid levels. Georgia. Body They found that the prevalence of hypertension was mass index (BMI) was calculated as weight divided by greater in hyperuricemic as compared to subjects without height squared (kg/m2). first.

The characteristics of the participants are presented in tory in the University Policlinic. significant correlations (p < 0.e. Total cholesterol was As shown in this table and in Figure 1. Chemistry.com/1471-2458/4/9 Blood pressure Statistical analysis Blood pressure (BP) was measured three times consecu. The statistically significant covariates were second urine sample a few hours later and. i. determined as the mean of the last were used to determine the independent predictors of two measurements. data regarding the relationship of uric acid to cardiovascu- lar disease is lacking in developing countries. shows the simple correlation coefficients between serum ing laboratory with the average of the results from all the uric acid levels and the various cardiovascular risk factors participating laboratories. Hypertension was defined as a diastolic BP ≥ 95 and/ potential explanatory variables in these models. Switzerland. L in men and >360 µmol/L in women [3]. 7. in the urine was tested in all participants using dipsticks (Glukotest. the subject being in a sitting position after at least 30 Station. The analyses were performed at a labora. For continuous variables. no instruction on the need to be square test respectively. Boehringer. and readings based on Korotkoff first and fifth base ous components of the metabolic syndrome. alcohol consumption and high triglyc- and at the Canton Institute of Haematology and Clinical erides levels were more common in men than in women. In this analysis. and centrifugation took place within 2 hours of drawing and serum was kept Results frozen at -20°C. When using the commonly accepted cut-off values tion with magnesium phosphotungstate.6 % in women [25]. 0. In women. the prevalence gal analyser (Wako Chemicals. using the Stata Software 6. Values of The diagnosis of diabetes mellitus was considered when uric acid above the sex-specific percentile 75 (i. provide only approximate estimates of diabetes preva. model predicting high uric acid was developed resorting pants actually reported fasting. cients with uric acid were first calculated and tested betes were invited to have glycosuria re-checked on a against zero. we have used laboratory determinations were regularly performed at the sex-specific 75th percentile which gives a cut-off at 460 the Swiss-Centre for Quality Control. Nevertheless most of the partici.0 (Stata Corporation. Smoking.m. in the population.7% in ured on a standard autoanalyzer. of hyperuricemia would be 35. For categorical and binary variables. the prevalence of diabetes evaluated Robust estimators of the regression coefficients. were considered as tion.e. the linear correlation coeffi- sons who tested positive and were unaware of having dia. St. College eter.01). Age. External controls for the women (p < 0. Mannheim. Linear and logistic regression techniques minutes of rest. Yet. In both sexes. the strength of association with high uric acid was measured using the Biochemical analyses Mantel-Haenszel test for linear trend and the Pearson chi- On the inviting letter. serum triglycerides and serum uric acid levels were strongly correlated (p < 0. Texas). body mass index and alcohol consumption were retained lence as both a few false negative and false positive cases in the final parsimonious regression model for both sexes. Gallen.01) were also found with almost all metabolic parameters except for Page 3 of 9 (page number not for citation purposes) . All per. then included in a multivariate linear regression model in a urine sample collected on the next morning after an and a stepwise backward selection procedure was used to overnight fast (the later result was considered in such determine which covariates contributed to the variation of cases). els were significantly higher in men than in women (p < HDL-cholesterol was measured similarly after precipita. Uric acid was meas.BMC Public Health 2004. The vari- Hg.e a serum uric acid >420 µmol/ were analysed enzymatically using a Cobas-Mira centrifu. use of diuretics. was obtained from 8 a. may be included.01). Participants were asked if they had taken drugs for other established risk factors of uric acid (alcohol con- high blood pressure within 2 weeks prior to the examina. triglycerides. 4 http://www. Lausanne.1% in men and 8. >460 individuals reported to have been told by a doctor to have µmol/L for men and >296 µmol/L for women) were diabetes or tested positive for glycosuria. Presence of sugar defined as high.m. Switzerland Table 1. based on with this approach was very close to the figure obtained the command "rreg" in the Stata software. chelles. if still positive. A multivariate logistic regression fasting was mentioned. Germany). and 2 p. USA). All statistical analyses were carried out separately by sex tively on the right arm with a standard sphygmomanom. were recorded to the nearest 2 mm serum uric acid and hyperuricemia respectively. This simple screening procedure was expected to uric acid independently of the others. sumption. Because or current intake of antihypertensive medication.). etc. serum uric acid lev- determined enzymatically using a Boehringer test kit. were used with the measurement of fasting glucose in 1994 i.001).8% because of some very high values of acid uric in the Sey- in men and 4. Values. Table 1 also result of the analysis of a sample obtained in the request. however.biomedcentral. ad-hoc crite- Diabetes ria for hyperuricemia were adopted in this study. Triglycerides for serum uric acid levels. A venous blood sample to the same stepwise method of variable selection. by comparing the µmol/L for men and 296 µmol/L for women. as well as the sounds.

1 0. - SD: standard-deviation.40 -0.3 0.2 0.7 24.4 1.3 .0 . The respective figures in women were : 215 µmol/L.528 Weight kg 70.06 0.5 23.290 Body mass index kg/m2 24. Page 4 of 9 (page number not for citation purposes) .8 1.254 68.228 1.80 0.319 Diastolic BP mmHg 90.7 11.8 14.6 0.306 0.biomedcentral.3 0.53 0.000 264.5 11.0 12.215 85. 6.2 0. .0 . 4 http://www.357 Systolic BP mmHg 139.295 Total cholesterol mmol/l 5.286 27.1 0. 253 µmol/L and 296 µmol/L.373 Alcohol intake ml/day 59.5 0.3 80. BP: blood pressure Corr: correlation coefficient with serum uric acid Frequency (%) 35 30 25 20 15 10 5 0 25 75 125 175 225 275 325 375 425 475 525 575 625 675 725 775 800. In men. the 25th percentile of serum uric acid was 305 µmol/L.3 13. White bars represent the distribution in men and black bars distribution in women. the 50th percentile 374 µmol/L and the 75th percentile 460 µmol/L.87 0.06 0. 13.734 1.2 4. .com/1471-2458/4/9 Table 1: Mean levels.8 21.2 0.48 1.2 0.142 44.2 12. standard deviations and correlations with uric acid for selected cardiovascular risk factors by sex Men (n = 482) Women (n = 529) Risk factor unit Mean SD Corr Mean SD Corr Serum uric acid µmol/l 408.5 0.410 Waist-to-hip ratio 0. - History of diabetes % 5.152 Triglycerides mmol/l 1.7 175.1 10.0 .0 0.0 .7 105. .172 3.3 1.138 5.68 0.BMC Public Health 2004.54 0.5 0.317 82.> 1200 1200 Serum uric acid in µmol (center of class) Figure 1 of serum uric acid by sex Distribution Distribution of serum uric acid by sex. - Treatment for hypertension % 9.1 5.16 0.242 132.370 HDL-cholesterol mmol/l 1.000 Age years 44.339 Waist cm 84.17 0.134 Smoking % 39. 7.0 0.0 15.50 -0.6 0.2 .9 0.0 1.

a high triglycerides level and the pres- Table 2 shows the multivariate model linear regression ence of hypertensive therapy was associated with a signif- model. In men. As shown in this table.4% 55–64 124 26. triglycerides. the odd abolic parameters were strongly associated with serum ratio decreasing from 37.004 Triglycerides mmol/l 99.38 0.0% Page 5 of 9 (page number not for citation purposes) . exclusion. The effect of age was particularly promi.040 0.040 2. of triglycerides in the logistic regression for men.001 Total cholesterol <5.000 46. Smoking had no effect on serum between a high triglyceride and a high uric acid level in uric acid levels.94 0.83 0.001 97 40.54 3.7% 460 20.01 0.2–6.5 before exclusion to 21.8% <0. The most sub- acid in sex-specific highest quartiles according to selected stantial change was found relative to the highest category cardiovascular risk factors.21 0.66 0.1% 165 23. serum uric acid correlated Table 4 shows the odds ratio for high uric acid levels with blood pressure.23 0.08 1. As mentioned above.biomedcentral. Table 2: Parsimonious robust multivariate linear regression model on serum uric acid by sex.000 Alcohol intake ml/day 0. alcohol consumption and treatment of hypertension.009 125 40. Men (n = 482) Women (n = 529) Explanatory variables unit Coeff SD P Coeff SD P Age years 0. by sex Men Women n % P n % P Age group 25–34 115 13.9% 139 8. waist according to different levels of age.com/1471-2458/4/9 alcohol consumption.000 % variation explained (R2) 0.18 12.001 35.4% yes 44 56. waist.1% <0.9% 209 30.001 Treatment for hypertension no 438 21.041 Treatment for hypertension 0/1 45.6% 0. 4 http://www.000 Body mass index (BMI) kg/m2 2.6% >160/100 mmHg 142 35.000 0. When excluding all subjects on anti- of the variations in serum uric acid levels in both sexes. alcohol consumption and icant odd ratio of having an elevated serum uric acid level a treatment for hypertension were the major determinants in this population.34 3. all met.9% <0.e.21 0. Age. and waist to hip ratio (p < 0.2% <0.96 7. in sex-specific highest quartile) according to selected cardiovascular risk factors.000 95. only small changes were observed Table 3 presents the proportion of persons with high uric in the values of the regression coefficients.471 Table 3: Proportion of persons with high uric acid (i. body weight.01). hypertensive therapy.56 0.3 after uric acid levels.8% 134 17. BMI.16 0.34 0.8% <0.488 0. triglycerides.001 Blood pressure <130/85 mmHg 117 15.000 Intercept 160. men.0% 197 13.73 0. This suggests that antihypertensive therapy and nent in women and the effect of alcohol consumption was particularly diuretics play a role in the association more marked in men. total cholesterol.0% >130/85 mmHg 223 22.6% 35–44 113 24.0 27.4% 223 13.BMC Public Health 2004.10 0.9% 45–54 130 33.41 0.2 mmol/l 231 19.1% 131 34.70 0.04 0.62 0.93 13.2 mmol/l 135 28.2% 5.001 69 55.

4% <0.001 Triglycerides <1.134 45–54 2. -- 35–44 1.4% <1. in sex-specific highest quartile) according to selected cardiovascular risk factors. -.9% 498 24.007 >1.0–1.03–1.012 Treatment for hypertension no 1.051 30 50.83 4.6% 25–30 147 32.11 1.001 88 61.com/1471-2458/4/9 Table 3: Proportion of persons with high uric acid (i.e.128 37 35.7 mmol/l 157 17.5% 273 11.4% 248 20.00 -.6% <0.005 2.11 0.4% 240 25.00 5.61 0.86 0.18 0.001 Body mass index <25 288 18.0% 168 23.001 Total 482 24.7 mmol/l 37.43 1.0% >1.001 Waist <77 cm 124 6.50 0.0% 0.2% <0.5% 202 7.e. -.00 -. -.00 -.878 1.8% >=30 43 46.1% 0.001 154 44.BMC Public Health 2004.6% <0.46 2.163 History of diabetes no 458 24.47 0.09 87.98 2.001 Regular cigarette smoking no 293 27. -.9% 77–88 cm 177 24.biomedcentral.36 6.12 11.6% 0.001 HDL-Cholesterol >1.000 Page 6 of 9 (page number not for citation purposes) .3% 492 24.3% >0 ml/j 248 28.0–1.63 0.00 -.0% P Mantel-Haenszel test for linear association Table 4: Parsimonious multivariate logistic regression model for predicting high uric acid (i. -.7 mmol/l 3.5% <0.31 4.3% 152 25. -- yes 4.7% <0.0 mmol/l 199 4. -.1% 207 11.2% yes 189 21.8% 168 28.50 3.24 1.71 1.00 -. 4 http://www. -.810 2.0% <0.001 167 40.000 2.006 55–64 1.45 7.33 0.000 7.03 mmol/l 73 46.07 0.05 0.001 41 51.2 mmol/l 116 32.23 0.0% >88 cm 179 38.24 5.47 2.7% 0. -.0 mmol/l 1.005 Triglycerides <1.96 1.001 171 45. in sex-specific highest quartile) by sex Men Women OR 95% CI P OR 95% CI P Age group 25–34 1.051 2.0% 499 23. by sex (Continued) >6.00 -.31 1.138 Alcohol consumption 0 ml/j 234 20.49 16.8% <0. -. -- 1. 1. 1.91 0.7 mmol/l 126 65.95 14.2% <0.55 0.2% 0.051 31 35.55 mmol/l 208 26. 1.55 mmol/l 201 15.2% 1.68 0.4% yes 24 41.23 3.5% 0.51 0.4% 1.9% <0.9% 529 25.

27 0.37-41] including in patients with primary diuretics which are known to increase serum uric acid lev.152 4.00 -. Interestingly the association elevated uric acid levels [29].00 -. blood pressure The main observations of the present study are the follow.55 0. partially corrected correlations.002 >88 cm 1. -. In the Seychelles. 4 http://www. Thirdly. with higher corre- tion. In our robust Significant correlations were found between serum uric multivariate linear regression model. the prevalence of hyperuricemia is high in our eral possible pathophysiological mechanisms have been group of male Black subjects from the Seychelles. Yet the strong by confounding factors such as the BMI or other associ- association between serum uric acid and triglycerides per. n = 44) was els [30. gout where a strong correlation (r = 0.27]. Insulin resistance may increase blood pressure uric acid levels are higher in men than in women. These sex differences of serum uric tem [36]. -- >0 ml/day 1.90 0. -. waist-to-hip-ratio.17. -. directly via enhanced proximal tubular sodium reabsorp- although uric acid levels in women tend to increase above tion [34. lycerides. evoked to explain these associations including insulin ondly. age combined with acid and several components of the metabolic syndrome.113 2. Alcohol consumption is significantly associated with lation levels in Black males. triglycerides and anti-hypertensive therapy Page 7 of 9 (page number not for citation purposes) . diuretics belong to the most found between urinary uric acid excretion and serum trig- frequently prescribed first line therapy of essential hyper. higher than those found in tainly the close relationship between serum triglycerides previous studies including Black populations [16. significant relationships between serum uric and resistance [13. Hence.68.33]. In our multivariate linear was obtained even within the normal range of serum trig- regression model. -.com/1471-2458/4/9 Table 4: Parsimonious multivariate logistic regression model for predicting high uric acid (i. a particularly Indeed the kidney seems to play an important role in the strong association was found between serum uric acid lev.00 -. high insulin levels by decreasing uric acid clearance. Thereby.023 2. the kidney has been implicated as the acid levels and the increase after the menopause in potential link between muscle insulin resistance and com- females have been reported previously and attributed to pensatory hyperinsulinemia and the development of the influence of sexual hormones [29]. Black men in our study had unusually ele.BMC Public Health 2004. 1.90 1. Another important has been found previously in several groups of patients factor may be the use of antihypertensive agents such as [11. The correlation of triglycerides with uric acid nificantly to uric acid levels in men.46 5. The most striking association found in our study is cer- vated serum uric acid levels.38 0.00 -.31] or impaired the various components of the metabolic syndrome were renal function accompanying hypertension [32. male subjects have a higher prevalence of hyperuricemia than women. Sev- ing: firstly. observations were made in both sexes.85 0.biomedcentral.68 0. alcohol consumption contributes sig.17]. Insulin- els and triglycerides.18 8.24 2. lycerides particularly among non-drinkers. or indirectly by the sympatho-adrenal sys- the age of 50 [8. and lower HDL-cholesterol in both men and women. in sex-specific highest quartile) by sex Waist <77 cm 1.541) has even been reported in healthy therapy contributes significantly to the variations in subjects [38].90 2. prob- ably linked to insulin-induced urinary sodium retention In accordance with previous studies.23 0.16. the use of diuretics [30. -.14]. it is not surprising that anti-hypertensive lation (r = 0. However.059 Discussion such as a higher BMI. A strong corre- tension.31].35].000 Alcohol consumption 0 ml/day 1. Sec. cance persisted although the coefficients were lower prob- ably under the influence of age and BMI. -- 77–88 cm 2.e. We also found that hyperuricemia and eventually hypertension.87 1.97 5. These partial explanation for this could be the alcohol consump.13. we found that serum [15]. This association persisted after full resistant individuals secrete larger amounts of insulin in adjustment in a multiple logistic model suggesting a close order to maintain an adequate glucose metabolism. A and serum uric acid levels and hyperuricemia. found in men as well as in women.96 0. BMI.63 0.78 4. in our sisted even after exclusion of all subjects receiving antihy. ated variables as suggested previously. -. 1.16 7. the high statistical signifi- pertensive therapies. development of the metabolic syndrome [15]. The link between serum uric acid and serum triglycerides kidney which is not insulin-resistant responds to these levels.26. This association could have been explained serum uric acid in men as well as in women.

even lycerides values and serum uric acid levels are still not elu. Staessen J: Prognostic significance of renal function in elderly patients with isolated systolic hypertension: results Our results also provide some insights on the possible from the Syst-Eur Trial. Although. Mazza S. have found that uric acid is a prognostic marker for cardi. Rodicio JL. Garn SM. Kannel WB. Delsignore R. 131:7-13. Zenere MB. 3. obesity and metabolic syndrome around the World and for the Systollic Hypertension in China (Syst-China) Trial Collabora- tive Group: Hypertension 2001. VW and MB have written the paper. Whincup PH: Serum urate and the risk of major coronary heart disease events. Staessen JA. Birkenhäger WH. Verdecchia P. Birkenhäger WH. is also closely linked to the various components of the 6. role of hyperuricemia as a risk factor in the development 10. 121:11-18. 37:1069-1074. 13:2213-2222. the potential link between hyperuricemia and coronary 8. However. Epidemiology 1999. Kannel WB. 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