Podagra, Uric Acid, and Cardiovascular Disease

Abstract

Hippocrates would not be surprised to read that persons with gout had higher mortality, and particularly cardiovascular-related mortality, than persons without gout. 1 On the other hand, he might well have been bemused, nearly 2500 years after he described the syndrome, that this made news. Article p 894He should not have been. All too often, rigorous examination debunks conventional wisdom. Reassuringly, in this case, Drs Choi and Curhan found evidence to support long-standing belief. These dedicated and productive students of the pathogenesis and natural history of gout have here reported empiric data from the 51 000 male nonphysician health professionals who participated in the Health Professions Follow-up Study. From initial examination in 1986 through nearly 600 000 person-years of follow-up, 5825 deaths occurred, of which 2132 were cardiovascular and 1576 were ascribed to coronary heart disease, rates that attest to the generally good health of the group.The Ϸ6% prevalence of gout, at baseline, in men in their mid-50s, who mirror the general US population in body mass index, reported history of hypertension, hypercholesterolemia, and diabetes mellitus, was higher than expected. Interim biennial questionnaires identified incident cases of gout. Participants with gout were both more likely to report coronary heart disease (CHD) at baseline and, regardless of CHD status, more likely than gout-free persons to have cardiovascular disease (CVD) risk factors. Results were presented after stratification by CHD status at baseline. As expected, the incidence of all-cause and CHD mortality was much greater in those with than in those without prevalent CHD. The adjusted increased relative risk of those with gout (compared with those without) for all-cause, CVD, and CHD mortality was Ϸ25%. The single exception was a near doubling of increased relative risk of CHD mortality among those free of CHD at baseline. Neither the inclusion of incident cases of gout nor stratification by CVD risk factors yielded significantly different results. In fact, inclusion of incident cases actually increased the relative risk of those with gout. The relation of gout to stroke was not reported.The report assessed mortality for persons with prevalent gout at baseline and also for the combination of incident and prevalent cases. The actual incidence of gout was not reported. However, the comparison of deaths in the 2 analyses is puzzling. Total deaths among participants with gout at baseline for no CHD and CHD cases were 410 and 235, respectively. The inclusion of incident gout cases increased those figures to 451 and 456, respectively. If my understanding is correct, this means that a remarkable number of incident cases must have occurred over 10 years among the CHD group to generate the additional 221 deaths.In any event, like Hippocrates, most present-day clinicians would be surprised that this is the first prospective study linking gout to mortality. As coronary artery disease has become more prevalent and its behavioral characteristics...

Serum Uric Acid As An Independent Predictor of Cardiovascular Event In Patients With Acute ST Elevation Myocardial Infarction

“…All of these actions are believed to contribute to the development of degenerative vascular disease [7], and might have role in worsening the acute thrombosis. Furthermore, uric acid is a general marker of cell death [14] and elevated serum uric acid is linked with obesity, dyslipidemia [15], hypertension, insulin resistance [16], male gender, aging, menopause [17], excessive alcohol intake and diuretic use [18]. Moreover, uric acid level may reflect xanthine oxidase pathway activity, which has the potential to contribute in to the progression of left ventricular dysfunction by interfering with myocardial energetics and myofilament calcium sensitivity [10].…”

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

“…There is evidence that elevated uric acid levels correlate with the increase in blood pressure in rats (Mazzali et al, 2001). Furthermore, elevated serum uric acid levels are associated with increased cardiovascular risk in hypertensive patients (Alderman, 1999;Alderman et al, 1999). Hyperuricemia-induced Allopurinol 3-month therapy with allopurinol improved impaired endotheliumdependent flow-mediated dilation in hyperuricemic subjects Mercuro et al (2004) In mild gestational hypertension, an indirect measure of XO was increased (Nemeth et al, 2002), and in mild hypertension associated with type II diabetes, chronic treatment with allopurinol improved peripheral vascular function (Butler et al, 2000).…”

Hyperuricemia and associated factors: a cross-sectional study of Japanese-Brazilians

“…According to previous studies, some foods can help increase or decrease the serum uric acid levels 6,7,8 , depending on their purine content. There is still little information on the exact amount of purines contained in foods, since their content and availability depend on the food processing procedures, among other factors 4,9,10 .…”

“…The relationship between excess plasma uric acid and gout is described in the literature, but despite all the studies and technological advances, there is still limited evidence to show a direct relationship between hyperuricemia and cardiovascular diseases 3,4,5 .According to previous studies, some foods can help increase or decrease the serum uric acid levels 6,7,8 , depending on their purine content. There is still little information on the exact amount of purines contained in foods, since their content and availability depend on the food processing procedures, among other factors 4,9,10 .…”