From the Department of Medicine, University of Kuopio (Finland) (S.L.,
L.N., M.L.), the Department of Medicine, University of Turku (T.R.), and The
Social Insurance Institution (T.R.), Turku, Finland.
Correspondence to Markku Laakso, MD, Professor and Chair, Department of Medicine, University of Kuopio, SF-70210 Kuopio, Finland. E-mail markku.laakso{at}uku.fi
Methods—In this population-based study,
cardiovascular risk factors were determined in 1017
patients (551 men and 466 women) with NIDDM, aged 45 to 64 years at
baseline. The patients were followed up for 7 years with respect to
stroke events.
Results—During the follow-up period, 31 NIDDM patients (12
men [2.2%] and 19 women [4.1%]) died from stroke and 114 NIDDM
patients (55 men [10.0%] and 59 women [12.7%]) had a fatal or
nonfatal stroke. The incidence of stroke increased significantly by
quartiles of serum uric acid levels (P<.001). High uric
acid level (above the median value of >295 µmol/L) was
significantly associated with the risk of fatal and nonfatal stroke by
Cox regression analysis (hazard ratio, 1.93 [1.30 to 2.86];
P=.001). This association remained statistically
significant even after adjustment for all
cardiovascular risk factors (hazard ratio, 1.91 [1.24
to 2.94[; P=.003).
Conclusions—Our results indicate that hyperuricemia is a
strong predictor of stroke events in middle-aged patients with NIDDM
independently of other cardiovascular risk factors.
Serum uric acid (or more correctly, its monoanion uric acid at
physiological pH values) has been thought to be in
humans a metabolically inert end product of purine
metabolism without physiological
significance (except gouty diathesis). However, serum uric acid has
been recently associated with insulin
resistance.6 7 Furthermore, in nondiabetic
subjects an elevated level of uric acid has been shown to be an
independent predictor of coronary heart disease and total
mortality.8 9 10 11 Therefore, we examined serum uric
acid as a risk factor for stroke in a prospective population-based
study that included a large number of patients with NIDDM.
Study Program and Methods at Baseline Examination in
1982–1984
Blood pressure was measured with the patients in a sitting position
after a 5-minute rest with use of a mercury sphygmomanometer and read
to the nearest 2 mm Hg. Subjects were classified as having
hypertension if they were receiving drug treatment for hypertension or
had systolic blood pressure of at least 160 mm Hg or
diastolic blood pressure of at least 95 mm Hg. Body
mass index was calculated by weight (kilograms) divided by height
(meters) squared.
Biochemical Methods
Research Design and Methods of Follow-up Study
As in the baseline study, WHO criteria for verified and possible stroke
were used in the ascertainment of a new stroke event (ie, a clinical
syndrome consisting of a neurological deficit and persisting more than
24 hours [nonfatal stroke]), without other diseases explaining the
symptoms.16 Death from stroke included ICD9 codes
431 through 434. Thus, thromboembolic and hemorrhagic strokes but not
subarachnoid hemorrhage, were included in the diagnosis
of stroke. If a subject had more than one stroke during the follow-up,
only the first stroke event was included in statistical
analyses.
Statistical Methods
Approval of Ethics Committee
Table 1
At baseline, serum uric acid level was significantly correlated with
the components of the insulin resistance syndrome, body mass index
(r=0.26, P<.001), total triglycerides (r=0.14,
P<.001), and HDL cholesterol (-0.25,
P<.001). No significant correlation between hyperuricemia
and total cholesterol levels was observed.
Fig 1
The role of hyperuricemia (>295 versus
Previous studies have indicated that hyperuricemia predicts
ischemic heart disease in nondiabetic
subjects,9 10 24 25 26 and one cross-sectional
study has suggested that this may apply also to patients with
NIDDM.27 However, data relating the risk of
hyperuricemia to cerebrovascular disease are limited. In the study of
Bansal et al,28 serum uric acid levels were
measured in 50 patients with ischemic thrombotic
cerebrovascular disease. Hyperuricemia was more frequent in those with
abnormal angiograms, and uric acid levels were related to lipoprotein
abnormalities. Moreover, studies performed with carotid
ultrasound29 or
angiography30 31 have suggested that there is a
linear relationship between carotid atherosclerosis and
hyperuricemia.
The mechanism(s) via which hyperuricemia is associated with
atherosclerotic vascular disease remain(s) unexplained. Hyperuricemia
could be an "innocent bystander," a nonspecific marker of adverse
pattern of risk factors. However, we do not exclude the possibility
that hyperuricemia could play a role in the pathogenesis of
atherosclerosis. Overwhelming evidence suggests that
hyperuricemia is linked to obesity,32
hypertension,33 reduced HDL
cholesterol,34
hypertriglyceridemia,35
hyperinsulinemia and reduced insulin
sensitivity,6 7 components of the
metabolic syndrome. We also observed this association and
the presence of multiple risk factors is likely to explain a
substantial part of increased risk of stroke. However, even after
extensive adjustment for cardiovascular risk factors,
serum uric acid remained an independent risk factor for stroke.
Elevated levels of serum uric acid are due to either an increase in
uric acid production or a decrease in its excretion.
Differences in dietary purine intake are unlikely to explain the
association of hyperuricemia with stroke, although this was not
directly assessed in our study. However, there are other
physiological and pathological factors that
influence serum uric acid levels. Ferris and
Gorden36 demonstrated in normal subjects that
sympathetic nervous system stimulation induced by
norepinephrine or angiotensin II infusion
caused a simultaneous increase in serum uric acid levels
and blood pressure. These changes were reversible after the
discontinuation of the pressor agent. Serum uric acid levels have been
reported to be inversely related to renal blood flow and directly to
renal vascular resistance in both normotensive and hypertensive
humans.37 38 Cappuccio et
al39 demonstrated that high uric acid levels were
independently associated with increased proximal tubular sodium
reabsorption in men. This association is strikingly similar to the
ability of insulin to promote renal sodium reabsorption that has been
suggested to be one of the reasons for the high frequency of
hypertension in metabolic syndrome and
NIDDM.40 In insulin-resistant states the
vasodilatory effect of insulin mediated by nitric oxide is blunted,
leading to disturbances in arterial blood
flow.41 On the other hand, hyperuricemia has been
associated with elevated circulating endothelin
levels,42 and one of the major sites of the
production of uric acid in the cardiovascular
system is the vessel wall and particularly the
endothelium.43 Recently, we have
demonstrated that cardiac autonomic neuropathy is an
independent predictor of stroke in patients with
NIDDM.44 Taken together, these findings suggest
that high uric acid could also be a marker of sodium retention coupled
with impaired hemodynamic reserves and/or disturbed
blood flow.
Uric acid is one of the major endogenous water-soluble
antioxidants of the body.43 There is accumulating
evidence that increased oxidative stress is closely related to diabetes
and its vascular complications.45 Thus, high
circulating uric acid levels may be an indicator that the body is
trying to protect itself from the deleterious effects of free radicals
by increasing the products of endogenous antioxidants,
eg, uric acid. Interestingly, uric acid prevents oxidative modification
of endothelial enzymes and preserves the ability of
endothelium to mediate vascular dilatation in the face
of oxidative stress.43 There is also some
evidence that uric acid may have a direct role in the atherosclerotic
process, because human atherosclerotic plaque contains more uric acid
than do control arteries.46 Inflammation is one
of the features of
atherosclerosis,47 and uric acid
crystals may induce inflammatory responses that are reduced by
lipoproteins which have an ability to bind uric acid
crystals.48 Hyperuricemia via purine
metabolism may also promote thrombus
formation.49 50 Serum uric acid was measured only
once, and we therefore have no information on the stability of uric
acid levels over time. However, a single measurement of a
parameter usually weakens the associations observed.
In conclusion, our results suggest that hyperuricemia is a strong
predictor of stroke events in middle-aged patients with NIDDM, and this
association is independent of other cardiovascular risk
factors. The mechanisms through which hyperuricemia increases the risk
of stroke should be the focus of further research.
Received September 22, 1997;
revision received December 9, 1997;
accepted December 9, 1997.
© 1998 American Heart Association, Inc.
Original Contributions
Serum Uric Acid Is a Strong Predictor of Stroke in Patients With Non–Insulin-Dependent Diabetes Mellitus
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and
Purpose—Patients with non–insulin-dependent diabetes mellitus
(NIDDM) are at increased risk for stroke. Hyperuricemia is a common
finding in NIDDM, but its significance as an independent risk factor
for cardiovascular disease has remained uncertain.
Therefore, we investigated serum urate as a predictor of stroke in
NIDDM patients free of clinical nephropathy (ie, with a
serum creatinine level of 
120 µmol/L).
Key Words: diabetes mellitus • mortality • uric acid • stroke onset
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Several
population-based studies1 2 3 have shown that
subjects with NIDDM have a twofold to fourfold greater risk of all
manifestations of atherosclerotic vascular disease, including stroke,
compared with nondiabetic subjects. The increased risk of stroke
is only partly explained by the adverse effects of NIDDM on classic
risk factors1 4 or risk factors clustering with
hyperinsulinemia (elevated levels of total
triglycerides, decreased HDL cholesterol,
hypertension, and glucose intolerance).5
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Research Design and Methods at the Baseline Study
All diabetic patients in Finland who need antidiabetic drug
therapy receive it free of charge according to the Sickness Insurance
Act. The Social Insurance Institution maintains a central register of
diabetic subjects who receive drug reimbursement. Based on this
register, we identified all diabetic patients aged 45 to 64 years who
were born and living in the Kuopio University Hospital district (East
Finland) and in the Turku University Central Hospital district (West
Finland). The formation of the final patient population, consisting of
510 diabetic subjects (253 men and 257 women) who participated in this
study in East Finland (participation rate, 83%) and 549 diabetic
subjects (328 men and 221 women) who participated in the study in West
Finland (participation rate, 79%), has been previously described in
detail.12 Insulin-dependent diabetes was excluded
in all insulin-treated NIDDM patients by C-peptide
measurements.13 None of the patients classified
as having NIDDM according to the World Health Organization (WHO)
criteria14 and included in the final study
population had a history of ketoacidosis. Thirty-three patients (23 men
and 10 women) with elevated serum creatinine levels of
>120 µmol/L and 9 patients (7 men and 2 women) for whom serum
uric acid measurement was not available were excluded from statistical
analyses. Of the 1017 NIDDM patients, 88 men and 54 women were
treated with diet only, 393 men and 345 women with oral hypoglycemic
drugs, and 70 men and 67 women with insulin. The proportion of
diet-treated patients in our study was 16.5% in East Finland and
11.5% in West Finland. It is unlikely, however, that the
underrepresentation of diet-treated diabetic patients in our
series could influence our results concerning the main study objective
(the evaluation of risk factors for stroke in patients with NIDDM),
because the mode of treatment of diabetes appeared to be quite similar
in both study areas. The mean±SD age of diabetic men was 57.2±0.2
years and that of diabetic women 59.0±0.2 years.
The study program was carried out during one outpatient visit at
the Clinical Research Unit of the University of Kuopio or the
Rehabilitation Research Center of the Social Insurance Institution in
Turku. These methods have been previously described in
detail.12 The visit included an interview on the
history of chest pain symptoms suggestive of coronary heart
disease, smoking, alcohol intake, physical activity, and use of drugs.
All medical records of those subjects who reported on the interview
that they had been admitted to the hospital on the basis of chest pain
or symptoms suggestive of stroke were reviewed. Review of the medical
records was performed by two of the authors (M.L. in Kuopio and
T.R. in Turku) after a careful standardization of the methods between
the reviewers. The WHO criteria for verified definite or possible MI,
based on chest pain symptoms, electrocardiographic changes, and
enzymatic determinations, were used to ascertain the diagnosis of
previous MI.15 The WHO criteria for verified
definite or possible stroke were used to ascertain the diagnosis of
previous stroke, which was defined as a clinical syndrome consisting of
neurological symptoms persisting for >24
hours.16 Thromboembolic and hemorrhagic
strokes, but not subarachnoid hemorrhage, were included
in the diagnosis of stroke.
All laboratory specimens were drawn at 8 AM, after a
12-hour fast. All analyses except that for glycohemoglobin
A1 (GHbA1) were performed
in duplicate. Fasting plasma glucose was determined by the glucose
oxidase method (Boehringer). GHbA1 was
determined by affinity chromatography (Isolab). The
plasma C-peptide response to glucagon was assessed according to the
method of Faber and Binder.17 Plasma C-peptide
was determined by radioimmunoassay (antiserum M 1230,
Novo).18 Serum lipids and lipoproteins were
determined from fresh serum samples drawn after a 12-hour overnight
fast. Serum total cholesterol and triglycerides
were assayed by automated enzymatic methods
(Boehringer).19 Serum HDL
cholesterol was determined enzymatically after
precipitation of low-density and very-low-density lipoproteins with
dextran sulfate MgCl2.20
Serum uric acid was measured with use of an enzymatic calorimetric
method (Amer Division, Miles Laboratories).21 The
subjects were classified into two categories, according to the median
of serum uric acid: low uric acid (295 µmol/L) and high uric
acid (>295 µmol/L) groups.
Collection of Follow-up Data
In 1990 a postal questionnaire containing questions about
hospitalization because of acute chest pain and symptoms suggestive of
stroke was sent to every surviving participant of the original study
cohort. All medical records of the subjects who died between
baseline examination and December 31, 1989, or who reported in the
questionnaire that they had been admitted to the hospital on the basis
of symptoms suggestive of stroke between the baseline examination and
December 31, 1989, were reviewed by one of us (S.L.). To ensure that
the data collection was complete, a computerized hospital discharge
register was used to check hospital admissions of all participants of
the baseline study, and in cases of hospitalization for stroke the
medical records were checked. Copies of death certificates for the
patients who had died were obtained from the files of the Central
Statistical Office of Finland. In the final classification of the
causes of death, hospital records and autopsy records were used
if available. Causes of deaths were coded according to the ninth
revision of the International Classification of Diseases,
Clinical Modification (ICD-9-CM).22
Data analyses were conducted with the SPSSX and SPSS/PC+
programs (SPSS Inc). The results for continuous variables are given
as mean±SEM and proportions as percentages. The differences between
the groups were assessed by the 
2 test or the
Student two-tailed t test for independent samples when
appropriate. A univariate and multivariate
Cox regression model23 was used to investigate
the association of cardiovascular risk factors with the
incidence of stroke events.
This study was approved by the Ethics Committees of the Kuopio
University Central Hospital and the Turku University Central Hospital.
All subjects gave their informed consent for participation in the
study.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
During the 7-year follow-up (mean follow-up was 7.2 years in men
and women), 31 patients (12 men [2.2%] and 19 women [4.1%]) with
NIDDM died of stroke. Altogether, 114 patients (55 men [10.0%] and
59 women [12.7%]) had a fatal or nonfatal stroke event. 
presents clinical
characteristics of NIDDM patients by the median value of serum uric
acid at baseline in the whole study population by gender. Data from
East and West Finland were combined because no significant differences
existed between these areas in the levels of
cardiovascular risk factors with respect to stroke. Men
with high uric acid levels (
295 µmol/L) were more obese and
hypertensive and were more likely to receive treatment with
diuretics and have a history of MI. Furthermore, men with high
uric acid level had higher levels of serum creatinine and
total triglycerides and lower levels of HDL
cholesterol, plasma glucose, and
GHbA1 than men with low (<295 µmol/L)
levels. Women with high uric acid levels were older and more obese,
more likely to have a history of MI and hypertension, and more likely
to receive treatment with diuretics than those with low levels.
Furthermore, women with high uric acid levels had higher serum
creatinine and total triglyceride levels as
well as lower LDL cholesterol, plasma glucose, and
GHbA1 levels than those with low uric acid
levels.
View this table:
[in a new window]
Table 1. Characteristics of the Study Population According to
the Median Value of Serum Uric Acid ( 295 µmol/L=low uric acid,
>295 µmol/L=high uric acid) shows the incidence of stroke
events (men and women combined) by quartiles of serum uric acid.
Incidence of stroke increased with increased serum uric acid levels
(P<.001), and the threshold for increased risk was close to
the median value (295 µmol/L). The results were essentially
similar when the data were analyzed separately for men and
women (data not shown).
View larger version (48K):
[in a new window]
Figure 1. Seven-year incidence (%) of stroke events (fatal or nonfatal
stroke) with respect to the quartiles of serum uric acid concentration
(expressed as micromoles per liter) (quartile limits: <243, 243 to
295, 296 to 357, and >357). ***P<.001. 295 µmol/L) as a risk
factor for fatal or nonfatal stroke in NIDDM patients was investigated
by Cox regression analysis (Table 2). Hazard ratios were calculated for the
whole study population, as the interpretation of the results was
essentially similar in men and women (data not shown). Hyperuricemia
increased the risk of stroke by approximately twofold. This association
remained essentially unchanged, even after adjustment for age, gender,
smoking, total cholesterol, hypertension, body mass index,
serum total triglycerides, HDL cholesterol,
plasma glucose, previous history of stroke, use of diuretics,
and known duration of diabetes. Further adjustment for serum
creatinine did not affect the interpretation of the
findings (note that subjects with serum creatinine
>120 µmol/L were excluded). The results remained essentially
similar when only the incident strokes were included in regression
analysis. Moreover, exclusion of patients who used
diuretics did not abolish the statistical significance of uric
acid as an independent risk factor for stroke.
View this table:
[in a new window]
Table 2. Adjusted Hazard Ratios and 95% CIs for
Hyperuricemia (serum uric acid >295 µmol/L) to Increase the
Risk of Stroke during 7-year Follow-up in Patients with NIDDM (Cox
Regression Model)
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Our population-based 7-year follow-up study is the first to
demonstrate the independent role of hyperuricemia as a predictor of
fatal and nonfatal stroke events in patients with NIDDM. In
univariate analysis the risk of stroke was
increased twofold among NIDDM patients with high uric acid (>295
µmol/L) compared with those with low uric acid. The predictive value
of hyperuricemia remained statistically significant even after
adjustment for all major cardiovascular risk factors
measured in our study.
Selected Abbreviations and Acronyms
GHbA1
=
glycohemoglobin A1
MI
=
myocardial infarction
NIDDM
=
non–insulin-dependent diabetes mellitus
WHO
=
World Health Organization
Acknowledgments
This study was supported by grants from the Academy of Finland,
the Aarne and Aili Turunen Foundation, and the Finnish Heart
Research Foundation.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
This article has been cited by other articles:
 |
|
 |
|
  C. Meisinger, W. Koenig, J. Baumert, and A. Doring Uric Acid Levels Are Associated With All-Cause and Cardiovascular Disease Mortality Independent of Systemic Inflammation in Men From the General Population: The MONICA/KORA Cohort Study Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1186 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Schretlen, A. B. Inscore, T. D. Vannorsdall, M. Kraut, G. D. Pearlson, B. Gordon, and H. A. Jinnah Serum uric acid and brain ischemia in normal elderly adults Neurology, October 2, 2007; 69(14): 1418 - 1423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Baker, H. R. Schumacher, and E. Krishnan Serum Uric Acid Level and Risk for Peripheral Arterial Disease: Analysis of Data From the Multiple Risk Factor Intervention Trial Angiology, September 1, 2007; 58(4): 450 - 457. [Abstract] [PDF]
|
|
|
|
 |
|
 V. F. Panoulas, H. J. Milionis, K. M. J. Douglas, P. Nightingale, M. D. Kita, R. Klocke, M. S. Elisaf, and G. D. Kitas Association of serum uric acid with cardiovascular disease in rheumatoid arthritis Rheumatology, September 1, 2007; 46(9): 1466 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Alderman Podagra, Uric Acid, and Cardiovascular Disease Circulation, August 21, 2007; 116(8): 880 - 883. [Full Text] [PDF]
|
|
|
|
 |
|
 V. G. Athyros, D. P. Mikhailidis, E. N. Liberopoulos, A. I. Kakafika, A. Karagiannis, A. A. Papageorgiou, K. Tziomalos, E. S. Ganotakis, and M. Elisaf Effect of statin treatment on renal function and serum uric acid levels and their relation to vascular events in patients with coronary heart disease and metabolic syndrome: A subgroup analysis of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study Nephrol. Dial. Transplant., January 1, 2007; 22(1): 118 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Papazafiropoulou, N. Tentolouris, I. Moyssakis, D. Perrea, and N. Katsilambros The Potential Effect of Some Newer Risk Factors for Atherosclerosis on Aortic Distensibility in Subjects With and Without Type 2 Diabetes Diabetes Care, August 1, 2006; 29(8): 1926 - 1928. [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Bos, P. J. Koudstaal, A. Hofman, J. C.M. Witteman, and M. M.B. Breteler Uric Acid Is a Risk Factor for Myocardial Infarction and Stroke: The Rotterdam Study Stroke, June 1, 2006; 37(6): 1503 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zoccali, R. Maio, F. Mallamaci, G. Sesti, and F. Perticone Uric Acid and Endothelial Dysfunction in Essential Hypertension J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1466 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kikura, T. Takada, and S. Sato Preexisting Morbidity as an Independent Risk Factor for Perioperative Acute Thromboembolism Syndrome Arch Surg, December 1, 2005; 140(12): 1210 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Suresh Diagnosis and management of gout: a rational approach Postgrad. Med. J., September 1, 2005; 81(959): 572 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Milionis, E. Rizos, J. Goudevenos, K. Seferiadis, D. P. Mikhailidis, and M. S. Elisaf Components of the Metabolic Syndrome and Risk for First-Ever Acute Ischemic Nonembolic Stroke in Elderly Subjects Stroke, July 1, 2005; 36(7): 1372 - 1376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ishizaka, Y. Ishizaka, E.-I. Toda, R. Nagai, and M. Yamakado Association Between Serum Uric Acid, Metabolic Syndrome, and Carotid Atherosclerosis in Japanese Individuals Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 1038 - 1044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Viazzi, D. Parodi, G. Leoncini, A. Parodi, V. Falqui, E. Ratto, S. Vettoretti, G. P. Bezante, M. Del Sette, G. Deferrari, et al. Serum Uric Acid and Target Organ Damage in Primary Hypertension Hypertension, May 1, 2005; 45(5): 991 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. K. Niskanen, D. E. Laaksonen, K. Nyyssonen, G. Alfthan, H.-M. Lakka, T. A. Lakka, and J. T. Salonen Uric Acid Level as a Risk Factor for Cardiovascular and All-Cause Mortality in Middle-aged Men: A Prospective Cohort Study Arch Intern Med, July 26, 2004; 164(14): 1546 - 1551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-P. Hsu, M.-F. Pai, Y.-S. Peng, C.-K. Chiang, T.-I Ho, and K.-Y. Hung Serum uric acid levels show a 'J-shaped' association with all-cause mortality in haemodialysis patients Nephrol. Dial. Transplant., February 1, 2004; 19(2): 457 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W S Waring, S H Adwani, O Breukels, D J Webb, and S R J Maxwell Hyperuricaemia does not impair cardiovascular function in healthy adults Heart, February 1, 2004; 90(2): 155 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chamorro, A. M. Planas, C. J. Weir, S. W. Muir, M. R. Walters, and K. R. Lees Yin and Yang of Uric Acid in Patients With Stroke * Response Stroke, January 1, 2004; 35 (1): e11 - e12. [Full Text] [PDF]
|
|
|
|
|
|
J. Kanellis and R. J. Johnson Editorial Comment--Elevated Uric Acid and Ischemic Stroke: Accumulating Evidence That It Is Injurious and Not Neuroprotective Stroke, August 1, 2003; 34(8): 1956 - 1957. [Full Text] [PDF]
|
|
|
|
|
|
R. J. Johnson, D.-H. Kang, D. Feig, S. Kivlighn, J. Kanellis, S. Watanabe, K. R. Tuttle, B. Rodriguez-Iturbe, J. Herrera-Acosta, and M. Mazzali Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease? Hypertension, June 1, 2003; 41(6): 1183 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.S. WARING Uric acid: an important antioxidant in acute ischaemic stroke QJM, October 1, 2002; 95(10): 691 - 693. [Full Text] [PDF]
|
|
|
|
|
|
G. Seghieri, D. Moruzzo, S. Fascetti, C. Bambini, R. Anichini, A. De Bellis, L. Alviggi, and F. Franconi Increase in Serum Uric Acid Is Selectively Associated With Stroke in Type 2 Diabetes Diabetes Care, June 1, 2002; 25(6): 1095 - 1095. [Full Text] [PDF]
|
|
|
|
 |
|
 K.Y.K. Wong, R.S. Macwalter, H.W. Fraser, I. Crombie, S.A. Ogston, and A.D. Struthers Urate predicts subsequent cardiac death in stroke survivors Eur. Heart J., May 2, 2002; 23(10): 788 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chamorro, V. Obach, A. Cervera, M. Revilla, R. Deulofeu, and J. H. Aponte Prognostic Significance of Uric Acid Serum Concentration in Patients With Acute Ischemic Stroke Stroke, April 1, 2002; 33(4): 1048 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-G. Wang, J. A. Staessen, R. H. Fagard, W. H. Birkenhager, L. Gong, and L. Liu Prognostic Significance of Serum Creatinine and Uric Acid in Older Chinese Patients With Isolated Systolic Hypertension Hypertension, April 1, 2001; 37(4): 1069 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. McFarlane, M. Banerji, and J. R. Sowers Insulin Resistance and Cardiovascular Disease J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 713 - 718. [Full Text]
|
|
|
|
|
|
P. Verdecchia, G. Schillaci, G. Reboldi, F. Santeusanio, C. Porcellati, and P. Brunetti Relation Between Serum Uric Acid and Risk of Cardiovascular Disease in Essential Hypertension : The PIUMA Study Hypertension, December 1, 2000; 36(6): 1072 - 1078. [Abstract] [Full Text] [PDF]
|
|
|