Impaired arterial responsiveness in untreated gout patients compared with healthy non-gout controls: association with serum urate and C-reactive protein

To determine whether arterial responsiveness is impaired among patients with gout, and whether arterial responsiveness inversely correlates with serum urate and inflammatory measures. This is a cross-sectional study of untreated gout subjects (n?=?34) and non-gout healthy controls (n?=?64). High-resolution dynamic ultrasound-measured flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent arterial responsiveness respectively. Serum urate (sUA) and high-sensitivity C-reactive protein (hsCRP) were measured in the gout group, and correlated with FMD and NMD responses. Both FMD (2.20?±?0.53 vs 3.56?±?0.31, p?=?0.021) and NMD (16.69?±?1.54 vs 24.51?±?0.90, p?=?0.00002) were impaired in the gout versus control group. Stratification for individual comorbidities suggested that no single risk factor accounted for impaired FMD/NMD in the gout subjects. However, the degree of association between gout and FMD, but not NMD impairment, was dampened after multivariable adjustment (FMD unadjusted beta?=???1.36 (SE 0.58), p?=?0.02; adjusted beta?=???1.16 (SE 0.78), p?=?0.14 and NMD unadjusted beta?=???7.68 (SE 1.78), p?<?0.0001; adjusted beta?=???5.33 (SE 2.46), p?=?0.03). Within the gout group, there was an inverse correlation between FMD and sUA (R?=???0.5, p?=?0.003), and between FMD and hsCRP (R?=???0.42, p?=?0.017), but not between NMD and sUA or hsCRP. Compared with healthy controls, subjects with gout have reduced arterial function. Individual comorbidities are insufficient to account for differences between gout and control groups, but multiple comorbidities may collectively contribute to impairment in endothelium-dependent arterial responsiveness. Endothelial impairment is also related to sUA and hsCRP, markers of gout severity and inflammation respectively. Studies to determine whether gout therapy may improve arterial responsiveness are warranted.     

Determinants of vascular function in patients with chronic gout

Epidemiologic studies have proposed a relationship between hyperuricemia and cardiovascular (CV) risk. However, it is unclear whether uric acid (UA) is an independent risk factor for CV disease (CVD) after controlling for other predisposing conditions. Gout patients might have persistent systemic inflammation, which, in addition to hyperuricemia, may potentiate CVD. This study examined vascular function and markers of CV damage in gout patients when compared with healthy controls. Brachial artery flow-mediated dilatation, arterial compliance, and microvascular function were measured. Circulating apoptotic endothelial cells and endothelial progenitor cells were quantified by FACS and circulating biomarkers of CVD by enzyme-linked immunosorbent assay. Gout patients displayed significant increases in body mass index, C-reactive protein, UA, and triglycerides and decreases in high-density lipoprotein. There were no significant differences in other CV traditional risk factors, adhesion molecules, or chemokines. Gout patients did not differ from controls in vascular function. In univariate and multivariate analysis, UA was not associated with the quantified CV risk parameters. Despite an increase in several CV risk factors, inflammation, and UA, gout patients display normal endothelial function and no increases in biomarkers of CVD. These results do not support the notion that gout is an independent risk factor for premature CVD.     

An immunohistochemical study of renal vascular lesions in hypertensive patients

This study examined the immunohistochemical findings in renal arterioles from biopsy specimens, and related the findings to those of light and electron microscopy. The renal biopsy specimens were obtained from 57 normotensive patients with primary glomerular diseases or idiopathic hematuria, 14 hypertensive patients with associated primary glomerular diseases, 4 patients with essential hypertension and 1 with primary aldosteronism. The tissue slices for the immunohistochemical study were processed with FITC-labelled rabbit antihuman immunoglobulin antisera. Deposits of IgM were detected on the renal arterioles in 16 of the hypertensive patients (84%), but in only 7 of the normotensive patients (12%). The difference in incidence was significant (p less than 0.005). C3 was almost always deposited in the renal arterioles regardless of whether the patient was hypertensive or normotensive. IgG, IgA or fibrinogen were demonstrated only in a few cases, and albumin in no cases. When sections stained with horseradish peroxidase-conjugated anti-IgM antibody were compared under a light microscope with the adjacent PAS-stained sections, it was demonstrated that IgM was deposited only in the portions of the arteriolar walls which showed hyalinotic changes. Electron microscopic examination demonstrated that electron-dense deposits in the subendothelial or intercellular spaces of arteriolar walls were more frequent in the hypertensive patients (11 of 14 cases, 79%) than in the normotensive patients (5 of 18 cases, 28%, p less than 0.05). The deposits appeared to be similar to those which are often found in the glomeruli of patients with glomerulonephritis and which are considered to be immune complexes. These findings suggest that some immunologic mechanism mediated by IgM antibody might be a factor in the development of hypertensive vascular lesions.     

Comorbidities and factors influencing frequent gout attacks in patients with gout: a cross-sectional study

Clinical Rheumatology - The objective was to identify the comorbidities of gout, to compare gender difference and independent factors of frequent gout attacks (&gt; 20 times). Demographic,...     

Objectifying exercise ischemia in peripheral vascular disease: a study in 120 patients

This study presents the results of transcutaneous oxygen pressure (TcPO2) monitoring during a treadmill test walk performed in the early stages of peripheral obliterative vascular disease. The study population consisted of a first group of 50 known arteriopathic patients presenting, on questioning, with intermittent claudication; a second group of 50 known arteriopathic patients void of any symptoms of intermittent claudication; and a third group, which was a control cohort of 20 nonarteriopathic, nonclaudicating patients. Though resting TcPO2 cannot be used to aid the clinical diagnosis of exercise ischemia it may be useful in revealing asymptomatic chronic resting ischemia (9% of cases in this series). On the other hand, a posteffort (recovery phase) fall in TcPO2 had a predictive positive diagnostic accuracy for ischemia on exercise in 99% of the cases reported here versus 87% for clinical appraisal. In the light of these results, TcPO2 measurements coupled to a treadmill test walk perfectly ascertain exercise ischemia in arteriopathic patients, whether asymptomatic or not, and avoid the false-positive results obtained by clinical evaluation.     

Platelets and vascular disease in gout

Vascular complications appear to have more than a coincidental occurrence in primary gout. The presence in gout of hypertension, renal disease, diabetes mellitus, and hyperlipidemia (accepted factors of risk for arterial lesions) may influence onset of atheromas. However, additional data are presented from patients with primary gout, and secondary hyperuricemia, to support the thesis that an elevated serum uric acid level is an increased risk for arterial disease. New data are presented that hyperactive platelet populations occur in at least 51 % of the patients with primary gout. The activation status of the platelet population may relate to the serum uric acid level.It is proposed that the platelet may be a prime reactant linking hyperuricemia (a documented thrombotic risk factor) with the greater incidence of arterial disease in primary gout. Uricosuric drugs can be separated into two classes: those which produce only an indirect inhibitory potential on platelet surface activation by lowering the level of serum uric acid and those which, in addition, possess a direct inhibitory action on platelet surface activation. Halofenate and allopurinol were found to be potent direct inhibitors of platelet activation in both ex vivo and in vivo studies.     

Surgical revascularization versus amputation for peripheral vascular disease in dialysis patients: a cohort study

Background

Surgical treatment of peripheral vascular disease (PVD) in dialysis patients is controversial.

Methods

We examined the post-operative morbidity and mortality of surgical revascularization or amputation for PVD in a retrospective analysis of United States Renal Data System. Propensity scores for undergoing amputation were derived from a multivariable logistic regression model of amputation.

Results

Of the Medicare patients initiated on dialysis from Jan 1, 1995 to Dec 31, 1999, patients underwent surgical revascularization (n = 1,896) or amputation (n = 2,046) in the first 6 months following initiation of dialysis were studied. In the logistic regression model, compared to claudication, presence of gangrene had a strong association with amputation [odds ratio (OR) 19.0, 95% CI (confidence interval) 13.86–25.95]. The odds of dying within 30 days and within1 year were higher (30 day OR: 1.85, 95% CI: 1.45–2.36; 1 yr OR: 1.46, 95% CI: 1.25–1.71) in the amputation group in logistic regression model adjusted for propensity scores and other baseline factors. Amputation was associated with increased odds of death in patients with low likelihood of amputation (< 33^rd percentile of propensity score) and moderate likelihood of amputation (33^rd to 66^th percentile) but not in high likelihood group (>66^th percentile). The number of hospital days in the amputation and revascularization groups was not different.

Conclusion

Amputation might be associated with higher mortality in dialysis patients. Where feasible, revascularization might be preferable over amputation in dialysis patients.     

Demographic and clinical features of gout patients in Turkey: a multicenter study

Gout results from multifactor interactions between gender, age, genetic and environmental factors. Environmental factors underlying gout and precipitating factors triggering acute attacks might vary in different populations with different lifestyles. In this study, we aimed to collect data regarding the demographic and clinical features, comorbid factors, and precipitating factors associated with the initiation of acute attacks in gout patients in Turkey. A total of 312 patients were included in this study (mean age, 58.8 ± 13.8 years; female/male ratio, 55/257). The demographic features, alcohol intake, clinical and laboratory features, and comorbid conditions including obesity, diabetes mellitus, hyperlipidemia, hypertension, and coronary heart disease were noted in a standard questionnaire. Precipitating factors initiating acute attacks (if any) were also noted. The patients were divided into 4 groups according to the region of location as central Anatolian region, southeast Anatolian region, Aegean region, and Trakya region. Our results were compared according to the gender and the location of the patients. The mean age at the start of the symptoms was 10 years higher in women (60.4 ± 14.8 and 50.6 ± 13.5 years in women and men, respectively, p < 0.001).Obesity was present in 40.1 %, diabetes mellitus in 17.9 %, hyperlipidemia in 30.1 %, hypertension in 53.5 %, coronary artery disease in 17 %, and nephrolithiasis in 21.8 % of patients. Precipitating factors triggering gout flares were as follows: diet (high consumption of meat or fish) in 46.5 %, alcohol consumption in 15.7 %, diuretics in 8.3 %, diet or diuretics in 5.1 %, diet or alcohol in 4.5 %, diet or alcohol or diuretics in 1.6 %, others in 4.2 %, and none in 14.1 %. The presence of diabetes and diuretic use was more common among women. Use of diuretics is a more common trigger for gout flares among women. On the other hand, various comorbid conditions, such as obesity and hypertension, and triggers for gout flares may differ between patients living in different geographic regions. In summary, we reported the first data regarding clinical and demographic characteristics of gout in Turkey. The majority of our patients could describe at least one “trigger” that initiated gout flare. Both comorbid conditions and triggers of attack might differ between men and women, and in different geographic areas. Better knowledge of the modifiable risk factors can be useful for the management strategy to optimize long-term patient outcomes in local clinics.     

Identification of peripheral vascular disease with real-time ultrasonic imaging

Real-time ultrasonic imaging can provide useful clinical information in subjects with peripheral vascular disease. This report outlines the technique of imaging the extracranial arterial system and arterial segments that supply the lower extremities. It describes our interpretation of the ultrasonic image as it relates to the pathology of fatty streaks, smooth and complex plaques, occlusions and thrombus formations. Our experience consists of in excess of 2700 patients who were evaluated with real-time ultrasonic imaging in conjunction with noninvasive functional studies over 4 1/2 years. In our hands, real-time ultrasonic imaging performed in conjunction with functional noninvasive studies plays a more important role in the management of patients with cerebrovascular disease than in lower extremity vascular disease.     

Family study of lipid and purine levels in gout patients.

A family study was performed to determine whether the hypertriglyceridaemia associated with gout is present in families of gout patients or due to the life style of the patient himself. The study revealed the expected hypertriglyceridaemia in gout patients; this was reflected by elevated serum levels of prebetalipoproteins and with reduction in the proportion of beta-lipoprotein. None of these abnormalities were seen in the first-degree relatives. Furthermore, the proportion of high-density lipoproteins was not significantly raised in gout patients.