Serum uric acid is associated with microalbuminuria in prehypertension

Serum uric acid is associated with cardiovascular disease. However, the independent role of uric acid in the development of cardiovascular disease is uncertain. This study examined the cross-sectional association of serum uric acid level with microalbuminuria among 6771 subjects without diabetes or hypertension. Blood pressure was categorized as prehypertension (systolic blood pressure, 120 to 140 mm Hg or diastolic blood pressure, 80 to 90 mm Hg) and normotension (systolic blood pressure, <120 mm Hg and diastolic blood pressure, <80 mm Hg). Microalbuminuria was found in 4.0% of normotensive subjects (n=4819) and in 7.9% of prehypertensive subjects (n=1952). Prehypertensive subjects with microalbuminuria had higher uric acid level than those with normoalbuminuria (men, 387 [68] mmol/L versus 371 [69] mmol/L; P=0.017; women 286 [56] mmol/L versus 262 [54] mmol/L; P=0.006). However, the difference in serum uric acid level according to the presence or absence of microalbuminuria was not found in the normotensive group. Multiple logistic regression models showed that, in the prehypertensive group, after adjustment for other cardiovascular risk factors, the highest uric acid quartile entailed >2 times greater risk for microalbuminuria than the lowest quartile in both men (odds ratio, 2.12; 95% CI, 1.16 to 3.87) and women (odds ratio, 3.36; 95% CI, 1.17 to 9.69). In the normotensive group, serum uric acid quartile did not show the independent association with microalbuminuria. In conclusion, serum uric acid level was strongly associated with microalbuminuria in prehypertensive subjects.     

Serum uric acid is positively associated with pulmonary function in Korean health screening examinees

Objectives: To determine whether level of serum uric acid (SUA) is linked to pulmonary function in health screening examinees without overt medical conditions.

Methods: We performed a cross-sectional study on 69,928 Koreans that participated in an annual health check.

Results: Percent predicted forced vital capacity (FVC%) and forced expiratory volume in 1?s (FEV1%) were positively correlated with SUA in both genders (FVC%: r?=?.361; FEV1%: r?=?.314 in males and FVC%: r?=?.413; FEV1%: r?=?.382 in females, all p?p for trend <.001). Similarly, the adjusted OR of having hyperuricemia in females decreased significantly across FEV1% and FVC% quartile groups compared to the reference.

Conclusions: Hyperuricemia may have a positive effect on pulmonary function in middle aged healthy population.     

Serum uric acid in hypertensive patients.

Both the average serum uric acid and annual increment were determined in 250 treated patients attending a hypertension clinic. The average serum uric acid was greater in men compared with women, in patients receiving a thiazide diuretic and in patients with a high average plasma urea. The mean annual increment in uric acid was close to zero (0.0017 mmol/litre per year) and was not related to sex, age, blood pressure control, diuretic therapy, or plasma urea. There was an unexplained positive association between annual increment and methyldopa therapy though this drug was not associated with a significantly high average serum uric acid. A table is presented giving the theoretical upper limits for average serum uric acid according to sex, plasma urea concentration, and whether or not a thiazide diuretic has been prescribed. It is hoped that this table will be of assistance in assessing the normality or otherwise of a high serum uric acid found in a hypertensive patient.     

Serum uric acid in hypertensive patients.

Both the average serum uric acid and annual increment were determined in 250 treated patients attending a hypertension clinic. The average serum uric acid was greater in men compared with women, in patients receiving a thiazide diuretic and in patients with a high average plasma urea. The mean annual increment in uric acid was close to zero (0.0017 mmol/litre per year) and was not related to sex, age, blood pressure control, diuretic therapy, or plasma urea. There was an unexplained positive association between annual increment and methyldopa therapy though this drug was not associated with a significantly high average serum uric acid. A table is presented giving the theoretical upper limits for average serum uric acid according to sex, plasma urea concentration, and whether or not a thiazide diuretic has been prescribed. It is hoped that this table will be of assistance in assessing the normality or otherwise of a high serum uric acid found in a hypertensive patient.     

Higher serum uric acid is associated with increased arterial stiffness in Japanese individuals

Hyperuricemia is postulated to be a risk factor for atherosclerotic diseases, although whether it is independent of classical atherogenic risk factors is controversial. The automatic computer-assisted measurement of brachial-ankle pulse wave velocity (baPWV) is a valid and reproducible method by which to assess arterial stiffness, a potential surrogate marker of early atherosclerosis. By analyzing cross-sectional data from 982 individuals who underwent health screening, we have investigated whether serum uric acid is associated with high baPWV, which was determined as the highest quartile of baPWV values, in a sex-specific manner. Multivariate analysis showed that the odds ratios (95% CI) of the highest baPWV quartile across the sex-specific quartiles of serum uric acid were 1.0, 2.80 (0.93-8.40), 2.13 (0.74-6.19), and 2.76 (1.01-7.55) in women, and 1.0, 1.10 (0.55-2.20), 1.97 (1.04-3.75), and 2.24 (1.10-4.56) in men after adjusting for age, total and HDL-cholesterol, BMI, systolic blood pressure, triglycerides, fasting glucose and smoking status. The association between uric acid and high baPWV was observed in both subjects with metabolic syndrome and those without. These data suggest that in both genders, serum uric acid level is associated with increased baPWV, a marker of arterial stiffness, and is in part independent of other conventional risk factors for atherosclerosis and metabolic syndrome.     

Serum leptin is associated with serum uric acid concentrations in humans.

This cross-sectional study aimed to evaluate the relationship between leptin and the cluster of abnormalities often referred to as the metabolic syndrome. The serum leptin concentration, body mass index (BMI), percent body fat, total fat mass (FM), waist and hip circumference, waist to hip ratio (WHR), prevalence of hypertension, and triglyceride (TG), lipoprotein, and uric acid concentration were determined in 86 type 2 diabetic (n = 59) and healthy (n = 27) subjects. Multiple regression analyses showed that the estimates of total body obesity (BMI, percent body fat, and total FM), sex, and serum uric acid concentration are independently associated with the serum leptin concentration. The finding of a positive correlation between serum leptin and uric acid levels suggests that leptin could be a pathogenic factor responsible for hyperuricemia in obesity.     

Serum uric acid is independently associated with hypertension in patients with rheumatoid arthritis

Hypertension (HT) is highly prevalent in rheumatoid arthritis (RA). Serum uric acid (SUA) has been associated with HT in the general population. The mutual exclusion of gout and RA, and the systemic inflammatory component of RA may alter this association in this patient population. We explored a potential association between SUA levels and HT in RA and evaluated whether this association is independent of HT risk factors, RA characteristics and relevant drugs. A total of 400 consecutive RA patients were assessed. SUA and complete biochemical profile were measured. Demographic, HT-related factors, RA characteristics and drugs were assessed as potential covariates. Results were analysed using binary logistic models to test the independence of the association between SUA and HT. SUA levels were higher in hypertensive compared to normotensive RA patients (5.44+/-1.6 mg dl(-1) (323.57+/-95.17 micromol l(-1)) vs 4.56+/-1.1 mg dl(-1) (271.23+/-65.43 micromol l(-1)), P<0.001). When adjusted for HT risk factors, renal function, RA characteristics, non-steroidal anti-inflammatory drugs, oral prednisolone, cyclosporine, leflunomide and low-dose aspirin, the odds of being a hypertensive RA patient per 1 mg dl(-1)(59.48 micromol l(-1)) SUA increase were significantly increased: OR=1.59 (95% CI: 1.21-2.1, P=0.001). This was also significant for the subgroup of patients who were not on diuretics (OR=1.5, 95% CI: 1.1-2.05; P=0.011). This cross-sectional study suggests that SUA levels are independently associated with HT in RA patients. Prospective longitudinal studies are needed to confirm and further explore the causes and implications of this association.     

血尿酸与多发性肌炎患者肺动脉压力的相关性研究

目的:探讨血尿酸与多发性肌炎(PM)患者肺动脉收缩压之间的关系。方法:纳入2005年至2014年,我院收治的PM患者62例。采用超声心动图检测肺动脉收缩压,肺动脉收缩压≥40mm Hg(1mm Hg=0.133k Pa)被定义为肺动脉高压PAH,应用多因素分析评估血尿酸与多发性肌炎患者肺动脉收缩压之间的关系。结果:多发性肌炎患者的8.1%(5/62)存在PAH,平均肺动脉收缩压为(50.75±9.74)mm Hg,平均血尿酸值为(428.20±204.40)μmol/L;肺动脉收缩压与血尿酸水平直线正相关(R2=0.132,P=0.034);多元线性回归提示矫正多个混杂因素后,血尿酸水平与肺动脉收缩压密切相关(P=0.030)。结论:多发性肌炎患者PAH比例较高,且血尿酸水平与肺动脉收缩压密切相关,但具体机制仍然需要进一步研究。     

Serum uric acid is independently associated with hypertension in patients with polymyositis and dermatomyositis

Serum uric acid (UA), as an antioxidant, has been associated with hypertension in the general population. Hypertension is highly prevalent in patients with polymyositis and dermatomyositis (PM/DM). Owning elevated levels of reactive oxygen species, patients with PM/DM have lower concentrations of UA in comparison with healthy people. We explored a potential association between UA levels and hypertension in PM/DM and evaluated whether this association is independent of hypertension risk factors, PM/DM characteristics and relevant drugs. A total of 472 PM/DM patients were assessed. UA and related laboratory data were measured. Demographic, hypertension-related factors, PM/DM characteristics and drug use were assessed as potential covariates. Results were analyzed using logistic models to test the independence of the association between UA and hypertension. UA levels were higher in hypertension subjects compared to non-hypertensive PM/DM patients [284.70 (239.93-357.38) vs 264.00(222.50-322.75), p = .017]. When adjusted for hypertension risk factors, PM/DM characteristics and drugs, the odds of being a hypertensive PM/DM patient per 1 μmol/L UA increase were significantly increased: odds ratio = 1.473 (95% confidence interval:1.063-2.042, p = .020). This cross-sectional study suggests that UA levels are independently associated with hypertension in PM/DM patients.     

Serum uric acid levels are associated with lupus nephritis in patients with normal renal function

Uric acid has been recognised as a potential marker of endothelial dysfunction and kidney disease but there are scarce data about its importance in systemic lupus erythematosus (SLE) nephritis. This study aimed to evaluate serum uric acid (UA) levels in lupus nephritis (LN), by comparing SLE patients with normal renal function, with and without nephritis. Forty-six female SLE patients were consecutively selected and divided in two groups according to renal activity at the evaluation: presence of a recently diagnosed lupus nephritis (LN+, n?=?18) and absence of lupus nephritis (LN?, n?=?28). Age-matched healthy women were selected (CONTROL, n?=?28). Patients with gout, creatinine clearance lower than 80 ml/min and use of drugs that interfere in UA were excluded. Laboratory and clinical data were analysed by appropriate tests. A multivariate analysis was performed, and a receiver operating characteristic (ROC) curve was plotted, and the area under the curve was calculated to assess the diagnostic strength of UA in LN. The mean age was similar among LN+, LN? and CONTROL groups (32.44?±?6.09 vs. 30.68?±?5.36 vs. 30.86?±?5.00 years, p?=?0.52). UA was significantly higher in LN+ compared to LN? (5.54?±?1.67 vs. 3.65?±?1.090 mg/dL, p?<?0.001) and CONTROL (5.54?±?1.67 vs. 3.92?±?0.95 mg/dL p?<?0.001). Multivariate analysis confirmed that high UA was an independent variable related to LN (p?<?0.001). The cut-off value for UA using the ROC curve was 4.47 mg/dL (AUC 0.86, p?=?0.00004, CI 95% 0.75–0.96). Lupus nephritis was associated with higher UA. Hyperuricemia as a predictor of renal damage in SLE needs to be evaluated in further studies.     

Serum uric acid is associated with incident metabolic syndrome independent of body shape index and body roundness index in healthy individuals

Background and aimsElevated serum uric acid (SUA) levels, body shape index (BSI) and body roundness index (BRI) were associated with incident metabolic syndrome (MetS). We aimed to investigate the relationship among the SUA level, BSI, and BRI on the incidence of MetS.Methods and resultsWe retrospectively included 6221 healthy individuals from annual health exams at our hospital between 2016/1/1 and 2016/12/31. We defined hyperuricemia as SUA levels greater than 7 mg/dl in men and 6 mg/dl in women and MetS according to the contemporary definition. The study cohort included 6221 healthy individuals with an overall incidence rate of MetS of 9.8%. Compared with the normouricemic group, the hyperuricemic group had a greater incidence of MetS (17.2% vs. 9.6%, P < 0.001). After full adjustment for confounders, the SUA level was significantly associated with incident MetS in addition to body mass index (BMI) (adjusted OR [aOR]: 1.161, 95% CI: 1.071–1.259, P < 0.001), BRI (aOR: 1.196, 95% CI: 1.104–1.296, P < 0.001), and BSI (aOR: 1.297, 95% CI: 1.200–1.403, P < 0.001). Regarding the anthropometric indices, BMI and BRI were independent predictors of incident MetS, but the BSI lost its significant association in multivariate logistic regression analyses. In sensitivity analyses, various thresholds of elevated SUA levels remained associated with incident MetS.ConclusionWe showed a dose-response effect of SUA on incident MetS independent of BMI, BRI and BSI in healthy individuals. Future studies can use SUA levels to stratify cardiometabolic risk in healthy individuals.Clinical trialsClinicalTrials.gov with the identification number NCT03473951.     

Serum uric acid in hypertensive patients with and without peripheral arterial disease

BACKGROUND: Uric acid is frequently elevated in hypertension. In addition to renal and metabolic disturbances, lower limb ischemia might contribute to hyperuricemia among hypertensives complicated by peripheral arterial disease (PAD). OBJECTIVE: To test the hypothesis that uric acid status is related to lower limb function in hypertensives with PAD. METHODS: Serum and 24-h urine uric acid levels and other risk factors were examined in 145 hypertensives free of PAD and 166 hypertensives with PAD. Ankle/brachial index (ABI) and absolute claudication distance (in PAD) on a treadmill test (ACD) were assessed. RESULTS: In multiple regression analysis for serum uric acid in the total group, PAD emerged as an independent determinant (P=0.03) next to age (P=0.005), triglycerides (P=0.04), and insulin (P=0.02). Serum uric acid concentrations were higher in hypertensives with PAD (404+/-101 vs. 347+/-80 micromol/l, P<0.001) independent of components of the metabolic syndrome (body mass index, triglycerides, insulin) and of age, gender, diabetes mellitus, pulse pressure, cholesterol, C-reactive protein, and treatment. After adjustment for kidney function by uric acid/creatinine ratio, values remained higher in hypertensives with PAD (P=0.01). Uric acid excretion was higher in the PAD group (P<0.001), whereas uric acid clearance was comparable between both groups. In multiple regression analysis for ACD (357+/-183 m) in the PAD group, serum uric acid (P=0.02), C-reactive protein (P<0.0001), age (P=0.02), and smoking (P=0.004) were independently associated. ABI (0.62+/-0.17) was not related to uric acid in PAD patients. CONCLUSION: Hyperuricemia is more pronounced in hypertensives complicated by PAD and is associated with worse functional status of the peripheral circulation.     

Serum uric acid is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus

Hyperuricemia has been reported to be associated with increased risk of renal insufficiency as well as cardiovascular events. The aim of this study was to evaluate the relationships between serum uric acid concentration and degree of urinary albumin excretion as well as markers of subclinical atherosclerosis in men with type 2 diabetes mellitus. Serum uric acid concentrations were measured in 343 men with type 2 diabetes mellitus. We then evaluated relationships of serum uric acid concentrations to degree of urinary albumin excretion as well as to major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, and glycemic control (hemoglobin A1c). The relationships between serum uric acid concentration and pulse wave velocity or ankle-brachial index (n=236) and between serum uric acid concentration and carotid intima-media thickness or plaque score (n=125) were investigated additionally in a subgroup of patients. Serum uric acid concentration correlated positively with logarithm of urinary albumin excretion (r=0.302, P<.0001). Positive correlation was found between serum uric acid concentration and intima-media thickness (r=0.233, P=.0087), whereas inverse correlation was found between serum uric acid concentration and ankle-brachial index (r=-0.150, P=.0207). Multiple regression analysis demonstrated that serum uric acid concentration (beta=.281, P<.0001), duration of diabetes (beta=.253, P<.0001), hemoglobin A1c (beta=.166, P=.0034), serum triglyceride concentration (beta=.125, P=.0472), and systolic blood pressure (beta=.275, P=.0013) were independent determinants of logarithm of urinary albumin excretion. In conclusion, serum uric acid concentration is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus.     

Acute angiotensin II receptor blockade improves insulin-induced microvascular function in hypertensive individuals

Objective

An effect of insulin that is crucial for stimulating glucose uptake is its ability to increase the number of perfused capillaries, and thereby enhance its own delivery, and that of glucose, to muscle cells. To unravel possible mechanisms involved in the insulin-sensitizing effects of angiotensin II receptor blockers (ARBs) in hypertensive individuals we investigated the effect of single-dose ARB administration on insulin-mediated microvascular perfusion in hypertensive individuals.

Methods

We examined the effects of ARB administration on hyperinsulinemia-associated capillary density by measuring baseline skin capillary density, capillary density during reactive hyperemia (hyperemic capillary recruitment), and capillary density during venous congestion in 17 hypertensive individuals in the basal state, during a hyperinsulinemic euglycemic clamp, and during a hyperinsulinemic clamp with acute ARB administration (600 mg irbesartan), acute calcium channel blockade (CCB; 10 mg felodipine ER), as a control for the reduction in blood pressure, or placebo. In addition, insulin sensitivity and blood pressure were measured.

Results

Compared to the basal state, hyperinsulinemia increased baseline capillary density (57.3 ± 6.8 vs. 60.3 ± 7.9 n/mm², P < 0.01), but not hyperemic capillary recruitment. ARB and CCB treatment induced similar blood pressure reductions. Compared to placebo, ARB, but not CCB, increased hyperinsulinemia-associated baseline capillary density (+ 2.3 ± 3.4 (P = 0.02) and − 0.4 ± 4.4 n/mm², respectively). Hyperinsulinemia-associated hyperemic capillary recruitment was not altered by either treatment. Compared to placebo, neither ARB nor CCB treatment enhanced insulin sensitivity.

Conclusions

Acute ARB administration increases insulin-induced microvascular perfusion in mildly hypertensive individuals; this beneficial effect on microvascular perfusion was however not associated with increased insulin-mediated glucose uptake.     

Serum gamma-glutamyltransferase is associated with arterial stiffness in healthy individuals

Objective Gamma‐glutamyltransferase (GGT) has been reported to be useful in predicting cardiovascular disease. Arterial stiffness measured by brachial‐ankle pulse wave velocity (baPWV) is not only a marker of vascular damage but a significant predictor of cardiovascular events. Gender difference has been reported in the association between GGT and baPWV. We assessed, therefore, the association between GGT and baPWV in a large population and determined whether there was gender difference. Design This cross‐sectional study was conducted at the Asan Medical Centre, Seoul, Republic of Korea. Subjects and measurements Serum GGT, baPWV and conventional risk factors were measured in 10 988 apparently healthy subjects (7248 men, 3740 women) who participated in a routine health screening examination. Results In both men and women, we observed positive linearity between GGT quartiles and body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, LDL cholesterol, triglycerides, uric acid, high‐sensitive C‐reactive protein (hsCRP) and homeostatic model assessment of insulin resistance (HOMA‐IR) score (P for trends < 0·001). The proportion of individuals with diabetes, hypertension increased as the GGT quartile increased (P for trends < 0·001). Age‐adjusted mean baPWV increased gradually in both males and females according to GGT quartiles (P for trends < 0·001 in both genders). The odds for higher baPWV (i.e. >75th percentile in each sex) were significantly higher in the highest compared with the lowest GGT quartiles, after adjustment for confounding variables, in both men [odds ratio (OR) = 1·63, 95% CI = 1·21–2·20] and women (OR = 1·56, 95% CI = 1·08–2·27). Conclusions These results suggest that GGT is independently associated with the increased level of arterial stiffness both in men and in women and the association between them appears to be stronger in men compared to women.     

Serum uric acid and cardiovascular events in successfully treated hypertensive patients.

To determine whether pretreatment and/or in-treatment serum uric acid (SUA) is independently and specifically associated with cardiovascular events in hypertensive patients, we examined the 20-year experience of 7978 mild-to-moderate hypertensive participants in a systematic worksite treatment program. Clinical evaluation and treatment were protocol-directed. SUA was measured at entry and annually thereafter. Subjects were stratified according to gender-specific quartile of baseline SUA. Blood pressures at entry and in-treatment were, respectively, 152.5/95.6 and 138.9/85.4 mm Hg. SUA was normally distributed with a mean of 0.399+/-0.0893 and 0. 321+/-0.0833 mmol/L for men and women, respectively. Subjects with highest SUA were heavier, had greater evidence of cardiovascular disease (CVD), higher systolic blood pressure, higher creatinine, more frequent diuretic use, and lower prevalence of diabetes. During an average follow-up of 6.6 years (52 751 patient-years), 548 CVD events (183 mortal) and 116 non-CVD events occurred. In bivariate analysis, the association of SUA to CVD was more robust in nonwhites than whites and in patients at low versus high CVD risk. In multivariate analysis, CVD incidence was significantly associated with SUA with a hazard ratio of 1.22 (95% confidence interval 1.11 to 1.35), controlling for other known cardiovascular risk factors, including serum creatinine, body mass index, and diuretic use. Despite blood pressure control, SUA levels increased during treatment and were significantly and directly associated with CVD events, independently of diuretic use and other cardiovascular risk factors.     

Elevated serum uric acid levels impair coronary microvascular function in patients with idiopathic dilated cardiomyopathy

In patients with idiopathic dilated cardiomyopathy (IDC), attenuated coronary flow reserve (CFR) and elevated serum uric acid levels have been reported. In this study, we investigated whether increased uric acid levels correlate with the degree of coronary microvascular dysfunction. Serum uric acid levels were measured in 29 patients with IDC (mean age: 57.0+/-10.8 years, 10 female), and each patient also underwent transthoracic echocardiographic examination including CFR measurement. The study population was divided into two groups according to the median CFR value (lower CFR group and higher CFR group). Uric acid levels were significantly higher in the lower CFR group than in the higher CFR group (7.59+/-2.56 vs 4.80+/-0.80 mg/dL, P=0.000). CFR correlated significantly and inversely to serum uric acid (r=-0.570, P=0.001). Logistic regression analysis revealed that uric acid level was the only independent predictor of CFR (B=-1080, P=0.015). We found a possibly clinically important negative association between serum uric acid levels and CFR in patients with IDC.