Content uploaded by Vishal Singh
Author content
All content in this area was uploaded by Vishal Singh on Jun 16, 2018
Content may be subject to copyright.
A preview of the PDF is not available
Aeromedical Decision Making: Approach to a case of hyperuricemia
ResearchGate has not been able to resolve any citations for this publication.
The release of human platelet constituents by the etiologic agent of gout, the monosodium urate crystal, is described here. In suspensions of washed platelets, response to urate crystals proceeded in two phases: A secretory phase involved the rapid active release of serotonin, ATP, and ADP with little loss of lactic dehydrogenase or beta-glucuronidase. A lytic phase involved the slower loss of all platelet constituents. Both phases were inhibited by iodoacetate plus dinitrophenol, suggesting an energy requirement. In ultrastructural studies, lysis of washed platelets which appeared to contain crystals was seen. Urate crystals were also shown to induce serotonin release and platelet lysis in citrated platelet-rich plasma. Since urate crystals are deposited at a variety of sites, urate crystal-platelet interaction in vivo is a possibility. Such interactions, leading to release of platelet constituents, might contribute to gouty inflammation or to enhanced atherogenesis.
Increased oxidative stress in chronic heart failure is thought to contribute to endothelial dysfunction. Xanthine oxidase produces oxidative stress and therefore we examined whether allopurinol improved endothelial dysfunction in chronic heart failure.
We performed a randomized, placebo-controlled, double-blind crossover study on 11 patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (1 month) versus placebo. Endothelial function was assessed by standard forearm venous occlusion plethysmography with acetylcholine, nitroprusside, and verapamil. Plasma malondialdehyde levels were also compared to assess significant changes in oxidative stress. Allopurinol significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean+/-SEM]: 181+/-19% versus 120+/-22% allopurinol versus placebo; P=0.003). There were no significant differences in the forearm blood flow changes between the placebo and allopurinol treatment arms with regard to sodium nitroprusside or verapamil. Plasma malondialdehyde was significantly reduced with allopurinol treatment (346+/-128 nmol/L versus 461+/-101 nmol/L, allopurinol versus placebo; P=0.03), consistent with reduced oxidative stress with allopurinol therapy.
We have shown that allopurinol improves endothelial dysfunction in chronic heart failure. This raises the distinct possibility that allopurinol might reduce cardiovascular events and even improve exercise capacity in chronic heart failure.
Serum uric concentration was determined in a series of 1462 women, aged 38-60 when first examined in 1968-69, as the first phase of a longitudinal population study in Gothenburg, Sweden. Serum uric acid concentration was positively correlated to the 12-year overall mortality in univariate analysis. No relationship was observed between initial serum uric acid values and incidence of myocardial infarction, angina pectoris, ECG changes indicating ischaemic heart disease or stroke. The association between serum uric acid concentration and mortality was independent of age, body mass index, systolic blood pressure, adipose tissue distribution, smoking habits, serum cholesterol concentration, serum triglyceride concentration, serum creatinine concentration, serum calcium concentration, use of diuretics, and haematological disease. The increased mortality could not be explained by any increase in malignant neoplastic disease.
In a study of male Israeli civil service workers, five-year incidence rates of hypertension (using the WHO definition) were found to increase with age and were higher for European-born subjects. Data are presented in support of a hypothesis that the size of the family group living together is inversely related to the risk of developing hypertension. Other factors found associated (at p <0.01 level) with hypertension incidence (all positively) were weight/height ratio, skinfolds, serum uric acid, pulse rate, cigarette smoking, and prolongation and suppression of feelings following conflicts in certain life situations. Other associated variables between the <0.01 and <0.05 levels are recorded and the fact is stressed that we are only at the beginning of an understanding of factors associated with hypertension incidence.
Although hyperuricemia is frequently found among persons with ischemic heart disease, its importance as a risk factor remains uncertain. The authors examined this relation among 5,421 persons in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study; baseline data were collected in 1971-1975 and follow-up was through 1987. No associations were seen among men, but, among women, the serum uric acid level was predictive of mortality from all causes and from ischemic heart disease. These associations persisted even after excluding the first 10 years of follow-up and were independent of use of antihypertensive agents and diuretics, diastolic blood pressure, overweight, and other characteristics. A dose-response relation was evident for mortality from ischemic heart disease: each 1-mg/dl change in uric acid (about two thirds of the standard deviation) among women increased the rate by 1.48 (95% confidence interval 1.3-1.7). Furthermore, as compared with women who had a uric acid level < 4 mg/dl, those with a level > or = 7 mg/dl had a 4.8-fold (95% confidence interval 1.9-12) higher rate of ischemic heart disease mortality. In contrast, the uric acid level showed a weaker relation with disease incidence among women, with a rate ratio of 1.14 for each 1-mg/dl change. Although the biologic mechanism is unclear, further investigation into the possible role of uric acid in the development of ischemic heart disease is needed.
A subsample of 147 Chinese subjects from a population-based study of cardiovascular diseases (Cardiovascular Disease Risk Factor Two-Township Study) participated in an ancillary study on extracranial carotid color duplex ultrasonography that aimed to assess the relations of coagulation factors to stroke and carotid atherosclerosis.
Logistic models were used to study the associations between cardiovascular disease risk factors and stroke/carotid atherosclerosis, controlling for the effects of age and sex.
Stroke was significantly associated with hypertension and high values of plasma glucose but not with fibrinogen, factor VIIc, or factor VIIIc. Carotid plaques identified in this study were mostly mild and moderate. The presence of these mild and moderate carotid plaques was significantly associated with high values of factor VIII activity, hypercholesterolemia, hypertriglyceridemia, and hypertension. The highest tertile of factor VIIIc (> 1.53) was associated with an odds ratio of 3.35 for carotid atherosclerosis when compared with the lowest tertile (< 1.20). A multiple logistic regression including all significant risk factors showed that the degree of association between factor VIIIc and atherosclerosis was attenuated to an odds ratio of 2.65 (P = .061).
In the present study, the roles of hypertension, hypercholesterolemia, and hypertriglyceridemia have been implicated in the pathogenesis of carotid atherosclerosis, and roles for hypertension and hyperglycemia in stroke were indicated. A positive association between factor VIIIc and carotid atherosclerosis in this Chinese population was found. Whether this association is independent of the effect of other cardiovascular risk factors awaits further study.
Although many epidemiological studies have suggested that increased serum uric acid levels are a risk factor for cardiovascular mortality, this relationship remains uncertain.
To determine the association of serum uric acid levels with cardiovascular mortality.
Cross-sectional population-based study of epidemiological follow-up data from the First National Health and Nutrition Examination Survey (NHANES I) from 1971-1975 (baseline) and data from NHANES I Epidemiologic Follow-up Study (NHEFS).
A total of 5926 subjects who were aged 25 to 74 years and had serum uric acid level measurements at baseline.
Ischemic heart disease mortality, total cardiovascular mortality, and all-cause mortality, compared by quartiles of serum uric acid level.
In an average of 16.4 years of follow-up, 1593 deaths occurred, of which 731 (45.9%) were ascribed to cardiovascular disease. Increased serum uric acid levels had a positive relationship to cardiovascular mortality in men and women and in black and white persons. Deaths due to ischemic heart disease in both men and women increased when serum uric acid levels were in the highest quartile compared with the lowest quartile (men, >416 vs <321 micromol/L; risk ratio, 1.77 [95% confidence interval [CI], 1.08-3.98]; women, >333 vs <238 micromol/l; risk ratio, 3.00 [95% CI, 1.45-6.28]). Cox regression analysis showed that for each 59.48-micromol/L increase in uric acid level, cardiovascular mortality and ischemic heart disease mortality increased. Hazard ratios for men were 1.09 (95% CI, 1.02-1.18) and 1.17 (95% CI, 1.06-1.28), and for women were 1.26 (95% CI, 1.16-1.36) and 1.30 (95% CI, 1.17-1.45), respectively, after adjustment for age, race, body mass index, smoking status, alcohol consumption, cholesterol level, history of hypertension and diabetes, and diuretic use. Further analysis, stratifying by cardiovascular risk status, diuretic use, and menopausal status, confirmed a significant association of uric acid and cardiovascular mortality in all subgroups except among men using diuretics (n=79) and men with 1 or more cardiovascular risk factors (n=1140).
Our data suggest that increased serum uric acid levels are independently and significantly associated with risk of cardiovascular mortality.
Hyperuricemia and hyperinsulinemia/insulin resistance are commonly seen in obese subjects and hypertensive patients. To clarify whether the insulin resistance plays a role in hyperuricemia, we investigated alterations in serum uric acid (UA) concentrations during treatment with a low-energy diet or an insulin-sensitizing agent in overweight hypertensive patients.
Twenty-eight overweight hypertensive patients (14 men and 14 women, mean age 61 +/- 2 years) were assigned to a weight reduction program with a low-energy diet (3360 kJ/day for 3 weeks, n = 14) and to treatment with troglitazone (200 mg twice daily for 8 weeks, n = 14). Measurements of body weight, blood pressure (BP), serum UA, and a 75-g oral glucose tolerance test were performed at baseline and the end of the intervention periods.
Body weight and BP decreased significantly in the diet group but not in the troglitazone group at the end of the intervention periods. Levels of blood glucose, plasma insulin, and homeostasis model assessment-insulin resistance index (HOMA-R) improved similarly in the two groups. Serum UA concentration decreased by treatment both in the diet (0.4 +/- 0.2 mg/dL, P < .05) and troglitazone groups (1.0 +/- 0.2 mg/dL, P < .001).
The amelioration of insulin resistance by either a low-energy diet or troglitazone decreased the serum UA level in overweight hypertensive patients. Insulin resistance or hyperinsulinemia, independent of body weight and BP, may play an important role in UA metabolism in multiple risk factor syndrome.
The association between alcohol consumption and risk of gout has been suspected since ancient times, but has not been prospectively confirmed. Additionally, potential differences in risk of gout posed by different alcoholic beverages have not been assessed.
Over 12 years (1986-98) we used biennial questionnaires to investigate the relation between alcohol consumption and risk of incident gout in 47?150 male participants with no history of gout at baseline. We used a supplementary questionnaire to ascertain whether reported cases of gout met the American College of Rheumatology survey gout criteria.
We documented 730 confirmed incident cases of gout. Compared with men who did not drink alcohol, the multivariate relative risk (RR) of gout was 1.32 (95% CI 0.99-1.75) for alcohol consumption 10.0-14.9 g/day, 1.49 (1.14-1.94) for 15.0-29.9 g/day, 1.96 (1.48-2.60) for 30.0-49.9 g/day, and 2.53 (1.73-3.70) for > or =50 g/day (p for trend <0.0001). Beer consumption showed the strongest independent association with the risk of gout (multivariate RR per 12-oz serving per day 1.49; 95% CI 1.32-1.70). Consumption of spirits was also significantly associated with gout (multivariate RR per drink or shot per day 1.15; 95% CI 1.04-1.28); however, wine consumption was not (multivariate RR per 4-oz serving per day 1.04; 95% CI 0.88-1.22).
Alcohol intake is strongly associated with an increased risk of gout. This risk varies substantially according to type of alcoholic beverage: beer confers a larger risk than spirits, whereas moderate wine drinking does not increase the risk.