A Randomized Study of Allopurinol on Endothelial Function and Estimated Glomular Filtration Rate in Asymptomatic Hyperuricemic Subjects with Normal Renal Function

Summary

Background and objectives

Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease. Recent studies have implicated hyperuricemia as a risk factor for cardiovascular disease. We hypothesized that lowering uric acid in subjects with asymptomatic hyperuricemia with allopurinol might improve endothelial dysfunction, BP, estimated GFR (eGFR), and inflammatory markers.

Design, setting, participants, & measurements

Subjects with asymptomatic hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month randomized prospective study. Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups. Flow-mediated dilation (FMD), eGFR, ambulatory BP monitoring, spot urine protein-creatine ratio, and highly sensitive C-reactive protein were measured at baseline and at 4 months.

Results

Age, gender, lipid profile, eGFR, hemoglobin, glucose, and level of proteinuria were similar in hyperuricemic subjects and controls at baseline. As expected, hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients. Allopurinol treatment resulted in a decrease in serum uric acid, a decrease in systolic BP, an increase in FMD, and an increase in eGFR compared with baseline. No significant difference was observed in the control hyperuricemic and normouricemic groups. In a multiple regression analysis, FMD levels were independently related to uric acid both before (beta = −0.55) and after (beta = −0.40) treatment.

Conclusions

Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia.     

Effect of hyperuricemia upon endothelial function in patients at increased cardiovascular risk

The aim of the present study was to evaluate the effect of increased serum uric acid (UA) levels and their therapeutic reduction with allopurinol on endothelium-dependent dilation in subjects with a high cardiovascular (CV) risk but who were free from clinical CV disease. Patients with hyperuricemia had impaired flow-mediated dilation (FMD) compared with matched controls with normal UA levels and elevated CV risk. Three-month therapy with allopurinol improved FMD in hyperuricemic subjects, showing an intrinsic negative effect of elevated UA levels on the arterial wall; conversely, FMD remained unchanged in controls, thus suggesting that the reduction of UA to less than a certain value does not affect endothelial function.     

Impaired systemic endothelial function in patients with pseudoexfoliation syndrome

Pseudoexfoliation syndrome (PEX) is the most common clinical precursor of open-angle glaucoma. Recent studies have shown that pseudoexfoliative material is widely distributed throughout the body, including blood vessels. The aim of our study was to evaluate endothelial function in the brachial artery of patients with pseudoexfoliation syndrome. We prospectively examined 23 patients with PEX (mean age, 70 +/- 8 years) and 20 healthy age- and sex-matched individuals (mean age, 68 +/- 9 years) as a control group. Brachial artery endothelial function was assessed by vascular response to reactive hyperemia (flow-mediated dilation (FMD) and sublingual nitroglycerin (NTG-mediated dilation) using high-resolution ultrasound. Flow-mediated and NTG-induced dilation were expressed as the percent change in diameter after reactive hyperemia and after NTG administration relative to the baseline value, respectively. Patients with cardiovascular disease and other conditions associated with endothelial dysfunction were excluded. When compared with controls, patients with PEX had significantly lower flow-mediated dilation (4.5 +/- 2.8 versus 8.2 +/- 3.7, P = 0.01) and NTG-mediated dilation (10.9 +/- 3.1 versus 15.8 +/- 3.8, P = 0.0001). Flow-mediated dilation and NTG-mediated dilation were similar in PEX patients with glaucoma (n = 11) and without glaucoma (n = 12). Flow-mediated and NTG-mediated dilation did not correlate with any measured parameter in any patient or control subject. The findings indicate that systemic endothelial function is impaired in PEX syndrome patients.     

Endothelium-dependent and -independent functions are impaired in patients with coronary heart disease

Endothelium plays a pivotal role in the development of atherosclerosis. Endothelial dysfunction participates in the course of acute coronary event. Using high-resolution ultrasound technique, endothelial dysfunction has been demonstrated in patients with atherosclerosis and risk factors for coronary disease, such as hypertension, diabetes mellitus, hypercholesterolemia and being smokers. In the present study, using this non-invasive method, the endothelial function of the brachial artery of patients with coronary heart disease (CHD) (n = 71) and control subjects (n = 34) was investigated. The results showed that endothelium-dependent and -independent vasodilatation were impaired in patients with CHD (2.61+/-2.91 vs. 8.10+/-7.81%, 17.20+/-7.93 vs. 23.19+/-8.89%, respectively) (P<0.001). Flow-mediated dilation (FMD) was significantly positively correlated with nitroglycerine-induced dilation (P<0.001). On univariate and multivariate analysis, the extent of FMD was significantly correlated with serum HDL-C levels (P<0.01). In conclusion, our study indicates both endothelial and underlying smooth muscle functions were impaired in patients with CHD. Decreased HDL-C levels may impair endothelial function.     

Vascular endothelial function and oxidative stress mechanisms in patients with Behçet's syndrome

OBJECTIVES: We sought to test the hypothesis that vascular endothelial function is impaired in Beh?et's syndrome and reflects increased levels of oxidative stress. BACKGROUND: Beh?et's syndrome is a multisystem inflammatory disorder commonly complicated by vascular thrombosis and arterial aneurysm formation. The precise mechanisms underlying vascular disease in Beh?et's syndrome are not known. METHODS: We studied 19 patients with Beh?et's syndrome (18 to 50 years old, 9 men) and 21 healthy volunteers (18 to 50 years old, 10 men). Brachial artery flow-mediated dilation (endothelium-dependent), and nitroglycerin (NTG)-induced dilation (endothelium-independent) were measured. To investigate oxidative stress mechanisms, vascular studies were repeated 1 h after administration of vitamin C (1 g, intravenous) in 12 patients and 12 control subjects. RESULTS: Flow-mediated dilation was reduced in patients with Behcet's syndrome as compared with control subjects (0.7 +/- 0.9% vs. 5.7 +/- 0.9%, p = 0.001). In contrast, there were no significant differences in the brachial artery diameter (4.2 +/- 0.2 vs. 4.0 +/- 0.2 mm, p = 0.47) or NTG-induced dilation (19.7 +/- 1.9% vs. 19.7 +/- 1.2%, p = 0.98). In regression analysis, Beh?et's syndrome was associated with impaired flow-mediated dilation independent of age, gender, brachial artery diameter, blood pressure, cholesterol and glucose. Vitamin C increased flow-mediated dilation in Beh?et's syndrome (0.2 +/- 0.7% to 3.5 +/- 1.0%, p = 0.002), but not in control subjects (4.3 +/- 0.6% to 4.7 +/- 0.4%, p = 0.51). In both groups, NTG-induced dilation and brachial artery diameter were unchanged after vitamin C treatment. CONCLUSIONS: Vascular endothelial function is impaired in Behcet's syndrome and can be rapidly improved by vitamin C treatment. Our results support a role for oxidative stress in the pathophysiology of Beh?et's syndrome and provide a rationale for therapeutic studies aimed at reducing vascular complications in this disorder.     

Hyperuricemia as a risk factor for contrast-induced nephropathy in patients with chronic kidney disease.

OBJECTIVES: Hyperuricemia as a risk factor for contrast-induced nephropathy (CIN) has not been studied. BACKGROUND: The aim of the present study was to assess the influence of hyperuricemia on the development of CIN in patients undergoing coronary angiography. METHODS: This was a prospective cohort study. A total of 266 patients with a mean age of 58.33 +/- 7.85 years and serum creatinine > or = 1.2 mg/dl were divided into two groups (hyperuricemic, n = 126, and normouricemic, n = 140). CIN was defined as an increase of > or = 25% in creatinine over baseline within 48 hr of angiography, and hyperuricemia as serum uric acid > or = 7 mg/dl in males and > or = 6.5 mg/dl in females. RESULTS: CIN occurred in 15.1% of the hyperuricemic group and 2.9% of the normouricemic group (P < 0.001). Serum creatinine increased from 1.45 +/- 0.20 to 1.67 +/- 0.45 mg/dl in the hyperuricemic group and from 1.42 +/- 0.16 to 1.56 +/- 0.23 mg/dl in the normouricemic group (P < 0.001). Hyperuricemia [odds ratio (OR) 4.71; 95% confidence interval (95% CI) 1.29-17.21; P = 0.019] and a high incidence of multi-vessel coronary involvement (OR 3.59; 95% CI 1.12-11.48; P = 0.032) in the hyperuricemic group were predictors of CIN. Hypoalbuminemia (P = 0.001) and age > or = 70 years (P = 0.023) were other risk indicators of CIN. Length of hospital stay (P < 0.001) and CIN requiring renal replacement therapy (P = 0.017) were significantly higher in hyperuricemic group. Serum uric acid level > or = 7 mg/dl in males and > or = 5.9 mg/dl in females were found to be the best cut-off value for prediction of CIN. CONCLUSION: Our data support the hypothesis that patients with hyperuricemia are at risk of developing CIN.     

Left ventricular hypertrophy and endothelial functions in patients with essential hypertension

OBJECTIVE: In this study, we used a non-invasive method in patients with essential hypertension and without any overt clinical evidence of atherosclerosis to investigate the role of left ventricular hypertrophy (LVH) in endothelial functions. METHODS: We assessed endothelial function in 32 hypertensive patients with LVH (group 1), 28 hypertensive patients without LVH (group 2) and 29 normotensive subjects (control group). Flow-mediated (endothelium-dependent) and nitrate induced (endothelium-independent) dilatation of the brachial artery was evaluated in all groups. RESULTS: Flow-mediated dilatation was considerably higher in the control group than in group 1 and 2 (13.98 +/- 2.92%, 4.67 +/- 1.09% and 7.02 +/- 1.79% respectively, p < 0.001). In addition, endothelium-dependent dilatation was significantly lower in group 1 than in group 2 (p < 0.001), whereas nitrate induced changes were similar in all groups. CONCLUSION: Vascular endothelial functions are impaired in hypertensive patients. There may be heterogeneity of endothelial dysfunction among patients with hypertension. Presence of LVH has an additional negative effect on endothelial function in hypertensive patients.     

Anti-cardiolipin antibodies and endothelial function in patients with coronary artery disease

Endothelial dysfunction is considered an important marker in atherosclerosis, having a prognostic value. Antiphospholipid antibodies are considered prothrombotic and have recently been reported to be associated also with atherosclerosis. This study was conducted to investigate a possible association of endothelial dysfunction with various antiphospholipid autoantibodies in healthy subjects and patients with cardiovascular disease. In a single-center, prospective study, 2 groups were included. The study group included patients with cardiovascular diseases (coronary disease and/or cerebrovascular disease) and healthy subjects without apparent heart disease who were referred to the endothelial function laboratory for the assessment of endothelial function. Flow-mediated dilatation, which indicates endothelial function, and nitroglycerin-mediated vasodilatation, which indicates smooth-muscle function, were measured. The 2 groups were evaluated for autoantibodies, including anticardiolipin (aCL; immunoglobulin G [IgG], immunoglobulin M [IgM], and immunoglobulin A [IgA]), antinuclear antibody, anti-beta2-glycoprotein I (IgG, IgM, and IgA), and oxidized low-density lipoprotein. One hundred seven subjects were included in the study: 45 patients (42%) and 62 healthy controls (58%). Flow-mediated dilatation was significantly lower in patients compared with healthy controls (8.0 +/- 9.5% vs 8.0 +/- 13.5%, p = 0.012). In addition, nitroglycerin-mediated vasodilatation was nonsignificantly lower in patients than in healthy controls (8.0 +/- 13.4% vs 11.0 +/- 16.7%, p = 0.084). The mean levels of anti-beta2-glycoprotein I (IgG, IgM, and IgA), aCL (IgM and IgA), antinuclear antibody, and oxidized low-density lipoprotein were not different between groups. However, the mean level of IgG aCL was significantly higher in patients than in healthy controls. In conclusion, in accordance with previous reports of an association between aCL and atherosclerosis, patients with cardiovascular disease had endothelial dysfunction and elevated levels of aCL.     

Serum uric acid correlates with extracellular superoxide dismutase activity in patients with chronic heart failure

Increased serum uric acid has been identified as an independent risk factor for cardiovascular disease. However, because of its antioxidant capacity, uric acid may play a beneficial role in endothelial function. This paradoxical relationship between uric acid and endothelial function in chronic heart failure patients remains poorly understood. Thirty-eight chronic heart failure patients (New York Heart Association functional class II-III, mean age 58+/-10 years and mean left ventricular ejection fraction 25+/-8%) and twelve age-and-sex-matched healthy controls were studied. Chronic heart failure patients showed higher uric acid levels (7.3+/-2.3 mg/dL vs. 6.1+/-0.2 mg/dL, p<0.05) and lower extracellular superoxide dismutase activity (136+/-36 U ml(-1) min(-1) vs. 203+/-61 U ml(-1) min(-1), p<0.01) and endothelium-dependent vasodilatation (4.0+/-1.6% v. 9.1+/-3.0%, p<0.01) when compared with control subjects. In chronic heart failure patients, correlations between both uric acid levels and extracellular superoxide dismutase activity (r=0.45; p<0.01), and uric acid and endothelium-dependent vasodilatation (r=0.35; p=0.03) were detected. These correlations were not observed in healthy individuals, suggesting a positive effect of uric acid on endothelial function partially mediated by modulation of extracellular superoxide dismutase activity in chronic heart failure.     

高尿酸血症与心血管疾病

目的了解心血管疾病患者中高尿酸血症的发病情况,以及血尿酸水平与心血管疾病各相关因素之间的关系。方法连续入选2006年1～10月因心血管疾病住院的患者,测定血尿酸水平,分析患者高尿酸血症发病率,并从性别、年龄等方面进行对比。结果入选的722例40～89岁心血管疾病患者中,男性高尿酸血症患病率为32.27%(111/344)、女性为30.16%(114/378),高尿酸血症的相关危险因素有冠心病、高血压、糖尿病、高甘油三酯血症、血肌酐增高,在男性患者还有高胆固醇血症,女性患者还有年龄。高尿酸血症患者合并有3种及以上危险因素的比例明显高于无高尿酸血症者,男性为38.74%比22.75%,女性为45.61%比28.03%。结论心血管疾病患者中高尿酸血症发病率高,高尿酸血症患者的心血管疾病的危险因素具有聚集性,女性患者绝经前高尿酸血症发病率低于男性、绝经后与男性无明显差别,女性高尿酸血症发病率随年龄增长而上升。     

Studies on flow-mediated vasodilation and intima-media thickness of the brachial artery in patients with primary hyperparathyroidism

The endothelium is a newly recognized target organ of parathyroid hormone (PTH) and may contribute to its effects on vascular tone and blood pressure regulation. Flow-mediated vasodilation (FMD), brachial and carotid intima-media thickness (IMT) were studied in patients with primary hyperparathyroidism (pHPT) and controls to evaluate endothelial function and structural arterial vessel wall alterations. Sixteen patients with pHPT (mean +/- SEM, age 44 +/- 5 years; PTH 229 +/- 72 ng/L; serum calcium 3.0 +/- 0.06 mmol/L; serum phosphate 2.0 +/- 0.2 mg/L) and 16 normocalcemic control subjects matched for age, sex, and blood pressure were included. Diabetes, hypertension, and vascular disease were excluded in both groups. End-diastolic diameter, flow-mediated (FMD) and nitroglycerin-mediated (NMD) dilation of the brachial artery were measured by a multigate pulsed Doppler system (echo-tracking). IMT was determined using automatic analysis of the M-line signal. Endothelium-dependent FMD was impaired in patients compared to controls (4.6 +/- 1.6% v 19.2 +/- 3.9%, P < .001). NMD (23.8 +/- 3.1% v. 22.4 +/- 2.8%, P = NS), carotid and brachial IMT (0.60 +/- 0.04 mm v 0.64 +/- 0.06 mm, P = NS, and 0.46 +/- 0.04 mm v 0.47 +/- 0.08 mm, P = NS, respectively) and artery diameters were not different. Endothelium-dependent vasodilation is impaired in patients with primary hyperparathyroidism despite normal IMT. Endothelial dysfunction may contribute to increased cardiovascular morbidity and mortality in pHPT.     

Oral L-arginine improves endothelial function in healthy individuals older than 70 years

Ageing is associated with progressive endothelial dysfunction in normal humans. Flow-mediated dilation (FMD) of the brachial artery is impaired in elderly individuals with cardiovascular disease and vascular nitric oxide (NO) bioavailability is reduced. We investigated whether oral L-arginine, the substrate for NO synthesis, can improve impaired FMD in healthy very old people. In a prospective, double-blind, randomized crossover trial, 12 healthy old subjects (age 73.8 +/- 2.7 years) took L-arginine (8 g p.o. two times daily) or placebo for 14 days each, separated by a wash-out period of 14 days. FMD was determined by high-resolution ultrasound in the brachial artery during reactive hyperaemia. Baseline artery diameter was 3.88 +/- 0.18 mm. L-Arginine significantly improved FMD (to 5.7 +/- 1.2%, p < 0.0001), whereas placebo had no effect (-0.25 +/- 0.7%; n.s.). After L-arginine, plasma levels of L-arginine increased significantly (114.9 +/- 11.6 versus 57.4 +/- 5.0 micromol/l), but placebo had no effect. As NO synthesis can be antagonized by its endogenous inhibitor asymmetric dimethyl L-arginine (ADMA), we determined ADMA plasma concentrations, which were elevated at baseline in comparison to healthy middle-aged individuals (3.9 +/- 0.2 versus 1.0 +/- 0.1 micromol/l; p < 0.0001). ADMA remained unchanged during treatment, but L-arginine supplementation normalized the L-arginine/ADMA ratio (p < 0.05). We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation, probably due to normalization of the L-arginine/ADMA ratio.     

Hyperuricemia and cardiovascular risk factor clustering in a screened cohort in Okinawa, Japan.

The relation between serum uric acid level and cardiovascular risk factors is complex and has been investigated mainly in men. We examined the correlation between serum uric acid level and obesity, hypertension, dyslipidemia, and diabetes mellitus (DM) in both men and women of a screened cohort in Okinawa, Japan. A total of 9,914 individuals (6,163 men and 3,751 women ranging in age from 18 to 89 years) who were screened at Okinawa General Health Maintenance Association were subjects in this study. Hyperuricemia was defined as a serum uric acid level > or = 7.0 mg/dl in men and > or = 6.0 mg/dl in women. The odds ratios (95% confidence intervals) for the presence of hyperuricemia in men were 1.75 (1.56-1.97) for obesity, 1.42 (1.25-1.62) for hypertension, 1.16 (1.02-1.30) for hypercholesterolemia, 1.80 (1.60-2.03) for hypertriglyceridemia, 1.19 (1.02-1.40) for hypo-high density lipoprotein (HDL) cholesterolemia, and 0.61 (0.49-0.75) for DM; in women, they were 2.02 (1.62-2.53) for obesity, 1.64 (1.29-2.10) for hypertension, 1.31 (1.04-1.65) for hypercholesterolemia, 1.95 (1.51-2.51) for hypertriglyceridemia, 1.53 (0.96-2.44) for hypo-HDL cholesterolemia, and 1.20 (0.76-1.90) for DM. Hyperuricemic subjects had higher rates of coexistence of two or more of these cardiovascular risk factors than non-hyperuricemic subjects (63.8% vs. 43.2% in men; 58.9% vs. 27.6% in women). The present study revealed that hyperuricemia is positively associated with obesity, hypertension, and dyslipidemia in both men and women, and that hyperuricemic subjects tend to have a clustering of these cardiovascular risk factors.     

The impact of heavy passive smoking on arterial endothelial function in modernized Chinese

OBJECTIVES: The study evaluated whether heavy exposure to environmental tobacco smoke (passive smoking) might damage arterial function in modernized Chinese. BACKGROUND: Heavy passive smoking is associated with arterial endothelial dysfunction in Caucasian, but not rural Chinese, subjects. METHODS: We studied 20 young (mean age 36.6 +/- 7.0 years) nonsmoking asymptomatic casino workers (9 men) in Macau who were exposed to environmental tobacco smoke for over 8 h/day for at least two years and 20 normal subjects (control subjects). These two groups were carefully matched for age, gender, body mass index (BMI), blood pressure, vessel diameter, cholesterol and glucose levels. Brachial artery diameter was measured by high-resolution B-mode ultrasound at rest, after flow increase (causing flow-mediated endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator). RESULTS: Flow-mediated dilation (mean +/- SD% of diameter changes) was significantly lower in passive smokers (6.6 +/- 3.4%) compared with the controls (10.6 +/- 2.3%) (p < 0.0001). Nitroglycerin-induced dilation of the two groups were similar. Upon multivariate analysis, passive smoking exposure was the strongest independent predictor (beta = -0.59; p = 0.0001) for impaired flow-mediated endothelium-dependent dilation (model R2 = 0.75, F value = 6.1, p = 0.0001). CONCLUSIONS: In modernized Chinese, as in Caucasians, exposure to heavy environmental tobacco smoke causes arterial endothelial dysfunction, a key early event in atherosclerosis. This may have serious implications for cardiovascular health in China, currently in a process of rapid modernization.     

Effect of folic acid on endothelial function following acute myocardial infarction

The aim of this study was to test the influence of high-dose folic acid (10 mg/d) on endothelial function in patients referred for coronary intervention after an acute myocardial infarction (AMI) and determine its relation to homocysteine levels. Flow-mediated dilation (FMD) of the brachial artery was performed in 40 patients after AMI (16 with normal homocysteine levels and 24 patients with elevated levels [>11 micromol/L]). Subjects were randomized to receive first folic acid (10 mg/day; group A) or placebo (group B) for 6 weeks in a double-blind crossover trial with a 2-week washout. Plasma folate, total homocysteine and its subtypes (oxidized, reduced, and protein-bound), FMD, and nitroglycerin-mediated dilation were assessed at baseline and at 6 and 14 weeks. In group A, folic acid improved FMD from 3.98 +/- 0.35% to 6.44 +/- 0.56% (p <0.001). This effect persisted after the crossover with placebo (5.42 +/- 0.59, p = 0.13). In group B, placebo did not increase FMD (4.01 +/- 0.34% vs 4.46 +/- 0.38, p = 0.38); however, a significant increase was observed in the second active treatment period (6.49 +/- 0.56%, p = 0.005). In both groups, improved FMD neither correlated with basal levels of homocysteine and its subtypes nor with changes induced during the folate treatment. Nitroglycerin-mediated dilation did not change significantly in either group. Folic acid increased FMD in both normo- and hyperhomocysteinanemic groups (p = 0.006 and p <0.001). In conclusion, 6-week treatment with high-dose folic acid improves endothelial function in post-AMI patients, independent from homocysteine status. Folic acid can be recommended to improve postinfarction endothelial dysfunction in patients with normo- and hyperhomocysteinemia.     

Impaired endothelial function following a meal rich in used cooking fat

OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.     

Community based epidemiological study on hyperuricemia and gout in Kin-Hu, Kinmen

OBJECTIVE: This is a population survey conducted in 1991-92 among residents aged > or =30 years in Kin-Hu, Kinmen, with a 77.7% response rate to study the prevalence of hyperuricemia and hyperuricemia associated gout. A stratified analysis based on sex and age was used to assess the interaction and analyze the associated risk factors for hyperuricemia and gout. METHODS: Hyperuricemia was defined as uric acid > or =7.0 mg/dl for men and > or =6.0 mg/dl for women. Gout was clinically diagnosed by a senior rheumatologist based on patient's history and examination according to the clinical criteria of Wallace. Basic demographic and lifestyle variables as well as biochemical data were collected. RESULTS: The prevalence of hyperuricemia was 25.8% (391/1515) in men and 15.0% (250/1670) in women. The prevalence of gout among hyperuricemic subjects was 11.5% for men and 3% for women. According to age spectrum, the risk factor for hyperuricemia was hyperlipidemia in young adults (30-39 yrs); lifestyle and some clinical syndromes played a significant role in middle aged persons (40-59 yrs). The different risk factors between the sexes in middle age were alcohol consumption effect in men and menopause effect in women. Impaired renal function and use of diuretics became the important factors in the elderly (> or =60 yrs). The risk factors for gout among either the general population or subjects with hyperuricemia were concentration of serum uric acid, alcohol consumption, and central obesity. CONCLUSION: Risk factors for hyperuricemia tended to be different with respect to sex and age. Alcohol consumption and central obesity were independent predictors of gout among hyperuricemic subjects irrespective of uric acid level.     

Hyperuricemia and its association with carotid intima-media thickness in hypertensive and non hypertensive patients

Carotid intima-media thickness (C-IMT) measured noninvasively by ultrasonography is widely used as a marker for increased risk of cardiovascular disease. Also hyperuricemia (HU) is a well recognized risk factor for cardiovascular diseases. The study was designed to assess the relation between hyperuricemia and carotid intima-media thickness C-IMT in patients with and without hypertension (HTN).This study included 126 patients divided into four groups: (1) Group A, included 59 hypertensive patients with hyperuricemia. (2) Group B, included 29 hypertensive patients without hyperuricemia. (3) Group C, included 17 patients with hyperuricemia and normal blood pressure without history of hypertension. (4) Group D, included 21 control subjects.We measured carotid intima-media thickness by B-mode ultrasound in the common carotid and internal carotid artery. Routine echocardiography and uric acid level was assessed for all patients.We found that C-IMT was significantly higher in group A, B and C than group D; and it was significantly higher in group A than B. This means that C-IMT is significantly higher in all hypertensive groups than control group but it was significantly higher in hypertensive hyperuricemia (group A) than those hypertensives without hyperuricemia. We also observed a higher C-IMT in hyperuricemic non hypertensive patients than control group this means that hyperuricemia per se could be a risk factor for atherosclerosis.Uric acid levels among the whole number of patients included in the study and among the groups with hyperuricemia (group A and C) were positively correlated with the intimal-media thickness (IMT) while there were no correlations in the other two groups without hyperuricemia.We found that left ventricular hypertrophy (LVH) was significantly higher in hypertensive patients (group A&B) than normotensives (group C&D) either with or without hyperuricemia and this was evident in the hypertensive hyperuricemic patients (group A); but unexpectedly we observed the presence of LVH in the hyperuricemic non hypertensive patients (group C) which was significantly higher than the control group (group D). This means that hyperuricemia is a risk factor for development of LVH hypertrophy independently of hypertension.Therefore, higher serum uric acid levels are associated with increased C-IMT and left ventricular hypertrophy in hypertensive and even non hypertensive patients. So, early screening for hyperuricemia and lowering serum uric acid levels might be beneficial in slowing progression of atherogenesis.     

Effects of oral niacin on endothelial dysfunction in patients with coronary artery disease: results of the randomized, double-blind, placebo-controlled INEF study

High-density-lipoproteins-cholesterol (HDL-C) is invertedly related to the incidence of cardiovascular events. Recent studies suggest that HDL-C directly improves endothelial function. Nicotinic acid (niacin) effectively raises serum HDL-C. We therefore hypothesized that treatment with niacin improves endothelial dysfunction in patients with coronary artery disease (CAD). One hundred seven patients with CAD were randomly assigned to double-blinded treatment for 12 weeks with extended-release (ER)-niacin 1000 mg/day (N) or placebo (C), respectively. Flow-mediated dilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent dilation (NMD) and serum lipid concentrations were measured before and after treatment. Triglycerides (P=0.013), low-density-lipoprotein-cholesterol (LDL-C) (P=0.013) and HDL-C (P<0.0001) were altered by N compared to C. Niacin treatment was without effect on FMD or NMD, respectively, compared to placebo. However, post-hoc subgroup analysis revealed an improvement in FMD in patients with low HDL-C at baseline (absolute change in FMD (mean+/-S.D.) N: +3.25+/-3.88%, C: +1.03+/-2.71% in low tertile HDL-C 相似文献   

Concomitant impairment in endothelial function and neural cardiovascular regulation in offspring of type 2 diabetic subjects

Endothelial function is impaired in first-degree relatives (FDRs) of patients with type 2 diabetes. Many states characterized by endothelial dysfunction are associated with increased cardiovascular sympathetic outflow. In this study, we investigated endothelial and autonomic nervous system (ANS) functioning in FDRs and tested the hypothesis that in basal condition, impaired endothelial function is associated with impaired cardiovascular ANS regulation. Flow-mediated endothelium-dependent and -independent vasodilation of the brachial artery was measured with high-resolution ultrasound in 27 otherwise healthy FDRs (14 men and 13 women; mean age 32 years) with normal oral glucose tolerance and in 15 age- and gender-matched control subjects. Cardiovascular ANS regulation was investigated by means of spectral analysis of heart rate and systolic blood pressure (SBP) variability. Baroreflex sensitivity was assessed by the spontaneous baroreflex sequences technique. Flow-mediated endothelium-dependent vasodilation was 9.4+/-1.0% in FDRs and 17.0+/-2.3% in control subjects (P=0.001). Low-frequency oscillations in SBP variability were 8.6+/-2.8 and 2.8+/-0.6 mm Hg in FDRs and controls, respectively (P=0.04). Baroreflex sensitivity was significantly less in FDRs than controls (22.8+/-2.7 versus 37.0+/-5.8, respectively; P=0.01). Change in vessel diameter was inversely correlated with the low-frequency component of SBP variability (r=-0.40; P=0.014). In healthy FDRs of diabetic patients there is a concomitant, possibly related, impairment in endothelial and ANS functioning, which manifests, indirectly, with increase in vascular sympathetic outflow and a depressed baroreflex, vagal, control of heart rate.