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Abstract

  1. Top of page
  2. Abstract
  3. SUA AND CV EVENTS
  4. SUA AND RENAL EVENTS
  5. IS SUA A PROMOTER OF CV AND RENAL DAMAGE?
  6. ROLE OF SUA IN THE PATHOGENESIS OF VASCULAR DAMAGE
  7. SUA AS A POTENTIAL TARGET FOR TREATMENT
  8. CONCLUSIONS
  9. References

Hyperuricemia is commonly associated with traditional risk factors such as abnormalities in glucose metabolism, dyslipidemia, and hypertension. Recent studies have revived the controversy over the role of serum uric acid as an independent prognostic factor for cardiovascular mortality. The authors review clinical and experimental evidence concerning the role of serum uric acid in the development of cardiovascular and renal damage. Results of trials suggesting that serum uric acid variations over time may have a prognostic impact are also discussed.

Considerable experimental evidence suggests a causal role for serum uric acid (SUA) in the pathogenesis of hypertension.1–4 Furthermore, the link between SUA levels and traditional metabolic risk factors is well known, and several large clinical studies have shown that asymptomatic hyperuricemia is associated with cardiovascular (CV) and renal complications. Whether SUA is just an innocent bystander in proximity to unfavorable events or whether it plays a mechanistic role in the development of CV damage is still under debate.

SUA AND CV EVENTS

  1. Top of page
  2. Abstract
  3. SUA AND CV EVENTS
  4. SUA AND RENAL EVENTS
  5. IS SUA A PROMOTER OF CV AND RENAL DAMAGE?
  6. ROLE OF SUA IN THE PATHOGENESIS OF VASCULAR DAMAGE
  7. SUA AS A POTENTIAL TARGET FOR TREATMENT
  8. CONCLUSIONS
  9. References

Several reports indicate that SUA is independently associated with adverse events, especially in women (Table I). This finding has been confirmed by most, although not all,11 studies among subjects at higher CV risk, such as those with hypertension8 and diabetes.6 Gueyffier et al.21 analyzed the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) database and found that the prevalence of CV events associated with increased SUA levels is similar to what is attributable to blood pressure (BP) and total cholesterol. The association of SUA with cerebrocardiovascular disease is even stronger in well-treated hypertensive patients and endures after successful BP control.8

Table I. Studies on the Association Between Serum Uric Acid (SUA) and Cardiovascular (CV) Events
StudyPopulation (M/W)Age (yr)*Follow-Up (yr)**EventsComparisonAdjusted Risk EstimateIndependent Role of SUA
Wannamethee et al.57688 men40–5916.8Fatal or nonfatal CHDHighest vs. lowest quintile1.55No
Lehto et al.61017 patients with T2DM (551/466)587.2Fatal or nonfatal strokeSUA >5.0 mg/dL1.91Yes
Culleton et al.76763 subjects from general population (3075/3688)474(c)1) Overall mortality 2) CV diseases 3) CHDHighest vs. lowest quintile1) ns (M); 3.63 (W) 2) ns (M); 5.69 (W) 3) ns(M); 4.11 (W)No
Liese et al. Epidemiology. 19991044 men from general population45–648(c)1) All-cause mortality 2) CV mortality 3) Myocardial infarctionSUA >6.3 mg/dL vs. <5.4 mg/dL1) 2.8 2) 2.2 (ns) 3) 1.7 (ns)1)Yes 2) No 3) No
Alderman et al.87978 mild-to-moderate hypertensives (4883/3095)536.6CV eventsSUA ≥7.6 mg/dL (M); ≥6.3 mg/dL (W) vs. lowest quartile1.48Yes
Moriarity et al. Ann Epidemiol. 200013,504 healthy subjects (5904/7645–648(c)CHDSUA ≥7.6 mg/dL (M); ≥6.3 mg/dL (W) vs. lowest quartile1.02 (ns) (M) 1.18 (ns) (W)No
Fang and Alderman. JAMA. 20005926 subjects from general population4816.4CV mortalitySUA ≥7 mg/dL (M); ≥5.6 mg/dL (W) vs. lowest quartile1.77 (M) 3.0 (W)Yes
Franse et al.94327 patients with hypertension (1860/2467)715(c)1) CV mortality 2) CHD 3) Stroke 4) All-cause mortalitySUA ≥6.7 mg/dL (M); ≥5.8 mg/dL (W) vs. lowest quartile1) 1.32 2) 1.43 3) 0.85 (ns) 4) 1.05 (ns)1)Yes 2) Yes 3) No 4) No
Verdecchia et al. Hypertension. 20001720 patients with primary hypertension (920/800)5141) CV events 2) Fatal CV events 3) All-cause mortalitySUA ≥6.2 mg/dL (M) ≥4.6 mg/dL (W) vs. second quartile1) 1.73 2) 1.96 3) 1.63Yes
Sakata et al.108172 subjects from general population (3596/4576)4914 (c)All-cause mortalitySUA ≥6.6 mg/dL (M) ≥5.0 mg/dL (W) vs. lowest quartileNS (M) 2.25 (W)No
Mazza et al. Eur J Epidemiol. 20013282 elderly subjects from genera population (1281/2001)7414 (c)StrokeSUA >6.5 mg/dL1.61Yes
Wang et al. Hypertension. 20011873 elderly Chinese patients wit ISH (1207/666)6631) CV mortality 2) Fatal strokePer additional SUA 0.8 mg/dL1) 1.14 2) 1.34Yes
De Leeuwet al.114556 elderly patients with ISH (1500/3056)7021) Overall mortality 2) CV mortality 3) CV eventsPer additional SUA 0.8 mg/dL1) ns 2) ns 3) 1.09No
Bickel et al. Am J Cardiol. 20021017 patients with angiographically defined coronary artery disease (747/270)622.2Overall mortalitySUA >7.1 mg/dL vs. lowest quartile2.71Yes
Wong et al.12354 stroke survivors692.81) CV mortality 2) All-cause mortalitySUA >5.4 mg/dL1) 3.1 2) ns1) Yes 2) No
Weir et al.132498 stroke survivors (1199/1299)722.7Major vascular eventsPer additional SUA 1.68 mg/dL1.27Yes
Anker et al.141) 112 patients with chronic HF (101/11) 2) 182 patients with chronic HF (149/33)595(c)Overall mortality (in 12 months)SUA ≥9.5 mg/dL1) 3.9 2) 7.14Yes
Niskanen et al. Arch Intern Med. 20041423 healthy Finnish men5211.9CV mortalitySUA ≥5.9 mg/dL4.77Yes
Hoieggen et al.159193 hypertensive patients with LVH (4230/4963)674.8 (c)Major vascular eventsPer additional SUA 0.17 mg/dL1.006 (ns) (all) 1.006 (ns) (M) 1.013Yes(W)
Athyros et al.161600 patients with established CHD (1256/344)593CV eventsPer additional SUA 1 mg/dL1.29Yes
Hsu et al.17146 hemodialysis patients (68/78)601All-cause mortality≥80th percentile vs. lower levels5.67Yes
Hakoda et al. J Rheumatol. 200510615 Japanese atomic bomb survivors (3860/6755)4924.91) All-cause mortality 2) CV mortalitySUA ≥8.0 mg/dL (M) ≥7.0 mg/dL (W) vs. lower levels1) 1.22 (M); 1.63 (W) 2) ns (M); 1.79 (W)1) Yes 2) Yes (W)
Simon et al.182763 postmenopausal women664.1 (c)CHDPer additional SUA 1.3 mg/dL1.05No
Madsen et al.191596 patients with angiographically defined coronary artery disease (1245/351)652.6All-cause mortalityHighest vs. lowest quintile1.5Yes: patients not using diuretics No: diuretics users
Kojima et al.201124 consecutive patients hospitalized within 48 hours of onset of symptoms of AMI (800/324)6730 daysAll-cause mortalitySUA ≥6.8 mg/dL vs. lowest quartile3.7Yes
M=men; W=women; CHD=coronary heart disease; T2DM=type 2 diabetes mellitus; ISH=isolated systolic hypertension; HF=heart failure; LVH=left ventricle hypertrophy; AMI=acute myocardial infarction; *expressed as mean or range; **expressed as mean except where expressed as cumulative (c) years; each report is statistically significant except when noted as nonsignificant (ns)

A relationship between SUA and events has been observed in patients with overt CV disease. Anker et al.14 reported that high SUA levels predict unfavorable outcome in patients with moderate-to-severe chronic heart failure, a finding that has also been confirmed in patients with angiographically proven coronary artery disease19,22 or with previous acute myocardial infarction20 or stroke.12,13 Although an increase in SUA could be at least partly due to a subtle impairment of renal function, the association between SUA and CV events seems to be independent of serum creatinine.8,12–14,21 Preliminary observations suggest that, even in patients on hemodialysis therapy, increased CV risk has been observed in patients with higher SUA levels.17

On the other hand, several studies, especially those performed on the general population, have failed to prove the independent nature of these associations, further highlighting the complex relationship between SUA levels and CV outcome.5,7,10

SUA AND RENAL EVENTS

  1. Top of page
  2. Abstract
  3. SUA AND CV EVENTS
  4. SUA AND RENAL EVENTS
  5. IS SUA A PROMOTER OF CV AND RENAL DAMAGE?
  6. ROLE OF SUA IN THE PATHOGENESIS OF VASCULAR DAMAGE
  7. SUA AS A POTENTIAL TARGET FOR TREATMENT
  8. CONCLUSIONS
  9. References

Elevated SUA is a frequent finding in patients with kidney disease and may be the direct consequence of decreased renal clearance. However, hyperuricemia per se may be involved in the induction or aggravation of renal dysfunction.23 Acute renal failure caused by marked hyperuricosuria, as observed in patients with tumor lysis syndrome, is a well recognized clinical entity. Moreover, subjects with recurrent gout attacks may develop chronic kidney disease, but the coexistence of vascular disease and age are better predictors of reduction in renal function.24 A causal role for uric acid in renal disease is still under debate (Table II).

Table II. Studies on the Association Between Serum Uric Acid (SUA) and Renal Events
StudyPopulation (M/W)Age (yr)*Follow-Up (yr)**Definition of Renal EventsComparisonAdjusted Risk EstimateIndependent Role of SUA
Tomita et al.2549,413 Japanese workers (M)25–605.4Renal failureSUA ≥8.5 mg/dL vs. >5.0–6.4 mg/dL8.52No
Syrjanen et al.261) 223 patients with IgAN (141/82) 2) Subgroup: 181 patients with IgAN with normal renal function4110 (c)SCr ≥1.4 mg/dL (M); ≥1.2 mg/ dL (W) at follow-up; >20% elevation from baselineSUA >7.5 mg/dL (M); >5.7 mg/dL (W) vs. lower1) 2.2 (ns) 2) 4.61) No 2) Yes
Iseki et al.276210 Japanese from general population with normal SCr levels (4047/2163)482(c)SCr ≥1.4 mg/dL (M); ≥1.2 mg/ dL (W) at follow-upSUA ≥8 mg/dL vs. <5 mg/dL2.91 (M) 10.39 (W)Yes
Iseki et al.2848,117 Japanese from general population (22,949/25,228)527(c)End-stage renal diseaseSUA ≥7 mg/dL (M); ≥6 mg/dL (W) vs. lower2.0 (M) (ns) 5.8 (W)Yes (W)
Domrongkitchaiporn et al.293499 Thai subjects35–5512 (c)1) GFR <60 mL/min at follow-up 2) SCr ≥1.49 mg/dL (M); ≥1.13 mg/dL (W) at follow-upSUA >6.3 mg/dL vs. <4.5 mg/dL1) 1.82 2) 1.75Yes
M=men; W=women; IgAN=IgA nephropathy;SCr=serum creatinine; GFR=glomerular filtration rate; *expressed as mean or range; **expressed as mean or cumulative (c) years; xach report is statistically significant except when noted as nonsignificant (ns)

Recent epidemiologic studies have demonstrated that uric acid is an independent risk factor for the deterioration of glomerular filtration rate in the general population27–29 as well as in patients with glomerulonephritis.26,27 SUA levels proved to be a predictor of end-stage renal disease in a prospective cohort of 48,117 Japanese subjects, after adjusting for common confounding variables such as proteinuria, high BP, and dyslipidemia.28 On the basis of multivariate analysis, Domrongkitchaiporn et al.29 identified systolic hypertension, hyperuricemia (>6.3 mg/dL), and high body mass index as promoters of the development of chronic kidney disease over a 12-year follow-up period.29 Increased uric acid levels are also believed to contribute to the deterioration of glomerular filtration rate in IgA nephropathy; hyperuricemia increased the risk of progression of kidney disease 4.6-fold after adjusting for proteinuria, hypertension, diabetes, dyslipidemia, age, gender, and body mass index.26 At variance with these results, hyperuricemia was not found to predict renal deterioration in the Modification of Diet in Renal Disease (MDRD) study30 or in other more recent studies in Japanese cohorts.25,31

Altogether these findings suggest, but do not offer definitive proof of, the role of SUA as an independent renal risk factor, especially in women and in patients who initially have normal renal function.27,28

IS SUA A PROMOTER OF CV AND RENAL DAMAGE?

  1. Top of page
  2. Abstract
  3. SUA AND CV EVENTS
  4. SUA AND RENAL EVENTS
  5. IS SUA A PROMOTER OF CV AND RENAL DAMAGE?
  6. ROLE OF SUA IN THE PATHOGENESIS OF VASCULAR DAMAGE
  7. SUA AS A POTENTIAL TARGET FOR TREATMENT
  8. CONCLUSIONS
  9. References

The relationship between SUA and the development of subclinical CV and renal damage has been under investigation for several years. In several cross-sectional and prospective reports, SUA levels were found to be associated with carotid intima-media thickening and/or carotid plaque (Table III), but in some studies an independent correlation was observed only in a subset of patients34,35 or could not be confirmed at all.39

Table III. Studies on the Association Between Serum Uric Acid (SUA) and Target Organ Damage (TOD)
StudyPopulation (M/W)Age (yr)*TODCorrelation Between SUA and TODIndependent Role of SUA
Persky et al.3224,997 subjects18–64ECG abnormalitiesYesYes (W)
Mazza et al. Metabolism. 2000130 T2DM patients (60/70)53Carotid abnormalitiesYesYes (W)
Bo et al. Eur J Clin Invest. 20011186 T2DM patients (628/558)651) Microalbuminuria by UAE 2) Macroalbuminuria by UAEYes1) No 2) Yes
Tuttle et al.33277 patients admitted for elective coronary angiography (195/82)62Angiographically defined coronary artery disease severityYes (W)No
Ishizaka et al.348141 general population (5470/2671)571) Carotid plaque 2) Carotid IMTYes1) Yes (M without MS) 2) No
Kawamoto et al. Intern Med. 2005919 elderly persons (398/521)75Carotid IMTYesYes
Tsioufis et al.35842 patients with HTN (406/436)531) LVH (echo) 2) Microalbuminuria by UAE1) No 2) Yes1) No 2) Yes
Viazzi et al.36425 patients with HTN (265/160)471) LVH (echo) 2) Carotid abnormalities 3) Microalbuminuria by ACR1) Yes (W) 2) Yes (W) 3) No1) Yes (W) 2) Yes (W) 3) No
Tseng Kidney Int. 2005343 patients with T2DM (144/199)63Albuminuria by ACRYesYes (patients without HTN)
Wu et al.371005 IgA nephropathy31Arterial-arteriolar lesions (light microscopy semiquantitative scoring)YesYes
Myllymaki et al.38202 patients with IgA nephropathy41Tubular atrophy (light microscopy semiquantitative scoring)YesYes
Iribarren et al.3911,488 subjects free of cardiovascular disease (4966/6522)45–64Carotid abnormalitiesYes (W, white M)No
M=men; W=women; ECG=electrocardiographic; T2DM=type 2 diabetes mellitus; UAE=urinary albumin excretion; IMT=intima-media thickness;MS=metabolic syndrome; HTN=hypertension; LVH (echo)=left ventricular hypertrophy assessed by echocardiogram; ACR=albumin/creatinine ratio; *expressed as mean or range

As for cardiac end points, a link between SUA levels and electrocardiographic abnormalities,32 left ventricular hypertrophy,28,35 and coronary artery disease33 has been reported. It is noteworthy that this association was found to be stronger in women than in men.32,33,36 The lack of relationship between left ventricular hypertrophy and SUA reported by Tsioufis et al.35 may have been due to the failure to stratify patients by gender.

SUA has also been described as an independent correlate of the urinary albumin excretion rate both in patients with type II diabetes (Table III) and with primary hypertension.35,36 Moreover, in patients with IgA nephropathy, the severity of intrarenal arterial lesions37 and of tubular atrophy,38 as assessed at biopsy, were closely correlated with SUA levels, regardless of other well known markers of adverse renal outcome.

In a recent cross-sectional study on untreated patients with primary hypertension,36 we observed an independent association between the presence and degree of early signs of subclinical organ damage and SUA in women (Figure). These findings provide information relating to the association of SUA to CV events and renal progression. Subclinical organ damage represents an intermediate step between exposure to risk factors and occurrence of overt disease and has previously been shown to be a potent predictor of major CV and renal events. The correlation between SUA and target organ damage that we and others have observed in women compared with men (Table III) may account for the previously reported CV and renal predictive power of uric acid in women (Tables I and II).

image

Figure Figure. Relative risk in women (with 95% confidence interval [CI]) for left ventricular hypertrophy (LVH), carotid atherosclerosis (ATS), and early signs of sub clinical target organ damage (TOD) in at least one organ, for each mg/dL rise in serum uric acid (SUA)

Download figure to PowerPoint

ROLE OF SUA IN THE PATHOGENESIS OF VASCULAR DAMAGE

  1. Top of page
  2. Abstract
  3. SUA AND CV EVENTS
  4. SUA AND RENAL EVENTS
  5. IS SUA A PROMOTER OF CV AND RENAL DAMAGE?
  6. ROLE OF SUA IN THE PATHOGENESIS OF VASCULAR DAMAGE
  7. SUA AS A POTENTIAL TARGET FOR TREATMENT
  8. CONCLUSIONS
  9. References

Although experimental evidence supports a role for SUA in the pathogenesis of vascular damage,23 the issue remains controversial. SUA may exert its detrimental effects by entering vascular smooth muscle cells via an organic anion transport system,40 and thus activating mitogen-activated protein kinases3,41,42 and nuclear transcription factors.3 Subsequently, cyclooxygenase-2,37 platelet-derived growth factor,3,43 and various inflammatory mediators, including C-reactive protein42 and monocyte chemoattractant protein-144 are stimulated. The complex of these events may lead to vascular smooth muscle cell hypertrophy. Uric acid may also be implicated in the development of endothelial dysfunction and atherosclerosis by inactivating NO and arresting the proliferation of endothelial cells.42,45 Hyperuricemic rats have been reported to show a decrease in serum nitrites, a reflection of NO production. The combination of a proliferative effect on vascular smooth muscle cells and an inhibitory effect on endothelial cells may account for the ability of SUA to induce small-vessel disease in experimental models.

Some human studies have investigated the relationship between SUA levels and endothelial damage. In high-risk patients with46 or without47 CV disease, some studies have shown a relationship between hyperuricemia and impaired flow-mediated vasodilation, a measurement of in vivo vascular NO activity. These findings, however, have not been confirmed in a recent study, which failed to show any effect of acute IV infusion of uric acid on endothelial function.48 Thus, there is also some debate regarding the exact role of elevated SUA in the pathogenesis of renal and cardiac disease.49

Although renin is increased in the kidney of the hyperuricemic rat and angiotensin-converting enzyme inhibition ameliorates renal injury,2 the mechanism by which uric acid increases renin-angiotensin system activity is not clear. It should be noted that uric acid may also act as an antioxidant,50 due to its ability to preferentially react with peroxynitrite, thus leading to stabilization of endothelial NO synthase activity.51 Uric acid has also been shown to stimulate the expression of extracellular superoxide dismutase, thereby conferring antioxidant activity.52

In summary, SUA plays several pathophysiologic roles both at the cellular and tissue level. The net balance of these contrasting mechanisms may result in adverse vascular effects.

SUA AS A POTENTIAL TARGET FOR TREATMENT

  1. Top of page
  2. Abstract
  3. SUA AND CV EVENTS
  4. SUA AND RENAL EVENTS
  5. IS SUA A PROMOTER OF CV AND RENAL DAMAGE?
  6. ROLE OF SUA IN THE PATHOGENESIS OF VASCULAR DAMAGE
  7. SUA AS A POTENTIAL TARGET FOR TREATMENT
  8. CONCLUSIONS
  9. References

Available data on the prognostic impact of the pharmacologic lowering of SUA are scanty, and to date, only a few randomized studies have described any CV benefits related to SUA changes (Table IV).

Table IV.  Drugs With Proven or Potential Serum Uric Acid-Lowering Effect
Drug(s)Mechanism (s) of ActionReference (s)Effect*
AllopurinolXanthine oxidase inhibitionJohnson et al.53Yes
  Rashid and William-Olsson 54 
  Tabayashi et al.55 
  Gavin and Struthers 56No
LosartanUricosuricHoieggen et al.15Yes
 Insulin-sensitizing  
Estrogen + progestinUricosuricSimon et al.18No
AtorvastatinUricosuricAthyros et al.16Yes
 Insulin-sensitizingMilionis et al.58 
Sulfinpyrazone (antiplatelet)UricosuricThe Anturane Reinfarction Trial. N Engl J Med. 1978Yes
Cilostazol (antiplatelet)UricosuricMitsuhashi et al. Endocr J. 2004Yes
Fenoflbrate (PPAR-α)UricosuricElisaf et al. J Cardiovasc Pharmacol. 1999?
 PPAR agonistSeber et al. Diabetes Res Clin Pract. 2005 
 Insulin-sensitizing  
Rosiglitazone (PPAR-γ)PPAR agonistTsunoda et al. Am J Hypertens. 2002?
 Insulin-sensitizing  
MetforminInsulin-sensitizingGokcel et al. Diabetes Obes Metab. 2002?
Sibutramine-orlistat (weight loss)Insulin-sensitizingGokcel et al. Diabetes Obes Metab. 2002?
Low-energy dietInsulin-sensitizingTsunoda et al. Am J Hypertens. 2002?
AmlodipineUricosuricSennesael et al. Am J Kidney Dis. 1996?
  Chanard et al. Nephrol Dial Transplant. 2003 
PPAR=peroxisome proliferator-activated receptors; ?=potential, but still unproven; *attributed effect on renal and cardiovascular disease

Allopurinol

Small studies have suggested that allopurinol, a widely used uric acid production blocker that inhibits xanthine oxidase activity, can improve endothelial function in patients with heart failure.59,60 There are data suggesting that lowering uric acid levels did not result in improvement in outcome in patients with heart failure.53–57

Losartan

This angiotensin II receptor blocker lowers SUA by interfering with urate reabsorption in the renal proximal tubule.61 This effect has been credited with at least some of the benefit in stroke outcome in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study,15 which compared an angiotensin receptor blocker with an atenolol-based treatment program.

Hormones

Estrogens have been reported to lower SUA levels in hyperuricemic patients.62 Although the exact mechanism is unclear, it has been suggested that they might increase uric acid renal clearance.63 Recent studies with estrogen and progestin reported lowered SUA (−0.2 mg/dL) regardless of baseline levels, but lowering did not affect overall risk for CV events.18 Thus, this issue cannot be considered settled.

Atorvastatin

In one study,16 treatment with atorvastatin was associated with a 24% reduction in coronary heart disease-related events for each mg/dL decrease in SUA levels, regardless of changes in low- or high-density lipoprotein cholesterol.16 The pathophysiologic mechanisms underlying the hypouricemic effect of atorvastatin are a matter of speculation; whether this effect is specific for this molecule or whether it is a class effect remains unclear. It has been hypothesized that uric acid production may be reduced by effects on carbohydrate metabolism; improvements in insulin sensitivity have been observed with atorvastatin in elderly patients with dyslipidemia and non-insulin-dependent diabetes.64 It has been reported that the hypouricemic action of atorvastatin is, at least in part, mediated by an increase in the fractional excretion of uric acid.58

An interesting finding regarding the possible prognostic role of SUA comes from the Systolic Hypertension in the Elderly Program (SHEP).9 After 1 year of treatment with 12.5–25 mg chlorthalidone, the benefits of the diuretic on coronary events were offset in patients who experienced an increase in SUA ≥1 mg/dL.9 However, over a 5-year follow-up, diuretic treatment was associated with significantly fewer CV events compared with placebo.65 To date, analyses of data on changes in SUA over the entire study period have not been published; the issue remains controversial. Furthermore, in the context of a decline in age-adjusted CV mortality, recent speculations about the effects of diuretic use and end-stage renal disease incidence are unproven.66 Recent data67 from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicate that CV events in diuretic-treated subjects were adversely affected in patients with varying degrees of renal impairment. Based on these data, there appears to be little reason to withhold the use of these agents in hypertensive patients if they are required to lower BP.

CONCLUSIONS

  1. Top of page
  2. Abstract
  3. SUA AND CV EVENTS
  4. SUA AND RENAL EVENTS
  5. IS SUA A PROMOTER OF CV AND RENAL DAMAGE?
  6. ROLE OF SUA IN THE PATHOGENESIS OF VASCULAR DAMAGE
  7. SUA AS A POTENTIAL TARGET FOR TREATMENT
  8. CONCLUSIONS
  9. References

At present, there is insufficient evidence to recommend the routine use of SUA-lowering therapies in patients at high CV risk with asymptomatic hyperuricemia. Large-scale, prospective intervention trials are warranted, however, to ascertain the exact role that reducing SUA levels will play in reducing CV risk.

References

  1. Top of page
  2. Abstract
  3. SUA AND CV EVENTS
  4. SUA AND RENAL EVENTS
  5. IS SUA A PROMOTER OF CV AND RENAL DAMAGE?
  6. ROLE OF SUA IN THE PATHOGENESIS OF VASCULAR DAMAGE
  7. SUA AS A POTENTIAL TARGET FOR TREATMENT
  8. CONCLUSIONS
  9. References
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