Uric Acid , and Cardiovascular Disease

He 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 6% 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 25%. 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 and risk factors identified, most clinicians, and probably the general public, have assumed that gout adversely affected survival. Choi and Curhan have now successfully exploited a large, well-conducted observational study to identify a hypothesis. Epidemiology, as William Kannel liked to remind us, is the attempt to prove guilt by association. The robust findings here are evidence that long-term cohort studies, despite their well-known limitations, can identify associations (new and old) that can then be tested experimentally. The size and composition of the study group lend credibility to the conclusions drawn. However, information based on patient report does not have the same reliability as that directly obtained from patients and validated. Nevertheless, it seems reasonable to accept that the observed association is genuine and that the magnitude of that association is clinically important. Despite the absence of women and the narrow professional range of the men studied, there is little reason to quibble with the assertion that the biological impact of gout is probably similar in other groups as well. Gout is a clinical syndrome whose pathophysiological construct is characterized by the deposition of urate crystals that provoke this common form of inflammatory arthritis. Wide geographic variation exists in the prevalence of gout. Approximately 5% of Maoris in New Zealand and 1% of adult Americans are affected. From the 1970s to 1990s, the annual incidence of gout in the United States has more than doubled from 20.2/100 000 to 45.9/100 000.2 Notably, the incidence of gout secondary to thiazide diuretic use did not increase during that time. Gout not only pains the patient but also burdens the healthcare system in general and employers in particular. A diagnosis of gout nearly doubles ($6870 versus $3705) the healthcare expenditures for employed persons. Most of that is consumed by “circulatory system” conditions.3 Age is the most important risk factor for gout, and the condition is rare in premenopausal women. A variety of lifestyle-related factors, including obesity, alcohol consumption, high purine (primarily meat) intake, and medical The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY. Correspondence to Dr Michael H. Alderman, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461. E-mail alderman@ aecom.yu. edu (Circulation. 2007;116:880-883.) © 2007 American Heart Association, Inc.