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Objective: Experimental studies indicate that patients with Wegener's granulomatosis (WG) experience accelerated atherosclerosis. The purpose of this study was to investigate whether the occurrence of overt ischemic heart disease (IHD) is increased in WG., Methods: A total of 293 WG patients were included in the study. Information on all hospitalizations for IHD in Denmark from 1977 to 2006 was obtained from the Danish National Hospital Register. The WG patients were compared with the Danish background population with respect to rates of hospitalization for clinical manifestations of IHD after the date of vasculitis diagnosis by calculating standardized ratios of observed to expected (O:E) events., Results: Sixty-three first IHD events were registered in the WG group during the 2,482 patient-years of followup, corresponding to a significantly increased O:E ratio for IHD of 1.9 (95% confidence interval [95% CI] 1.4-2.4). A significantly increased risk was found for acute myocardial infarction (MI) (O:E ratio 2.5 [95% CI 1.6-3.7]), but not for angina pectoris (O:E ratio 1.3 [95% CI 0.7-2.1]). In analyses stratified according to the time between the diagnosis of vasculitis and the cardiovascular event, increased O:E ratios were found for IHD and acute MI occurring <5.0 years after WG diagnosis (2.1 [95% CI 1.4-3.0] for IHD and 3.6 [95% CI 2.0-5.9] for acute MI) and for IHD occurring > or =10.0 years after WG diagnosis (2.2 [95% CI 1.3-3.4]). Significantly increased O:E ratios for IHD and acute MI were found in patients who were > or =50.0 years of age at the time of diagnosis of WG, in male patients, and in patients who received high cumulative doses of cyclophosphamide., Conclusion: Compared with the background population, WG patients seem to experience an increased number of both early and late cardiovascular events due to IHD.

Objective: To investigate whether patients with WG have an increased risk of malignancies prior to and/or around the time of the vasculitis diagnosis, as suggested by previous studies., Methods: A total of 293 WG patients were included in the study. Ten gender- and age-matched controls were selected randomly for each patient from the Danish Central Population Register. Information on malignancies was obtained through the Danish Cancer Registry. Occurrence of malignancies before WG diagnosis among patients and before WG diagnosis of their matched case among controls (reference date) was compared by calculation of prevalence odds ratios (OR)., Results: Twenty-six patients were diagnosed with cancer before WG, while 194 controls were diagnosed with cancer before the reference date (OR 1.4; 95% CI 0.9, 2.2). Among specific malignancies, a significantly increased prevalence was found for testis cancer (OR 6.4; 95% CI 1.1, 38) based on two patients, who developed testis cancer >10 years before WG. The overall prevalence of malignancies diagnosed <2 years before WG was not significantly increased (OR: 1.6; 95% CI: 0.8, 3.4), but non-melanoma skin cancer occurred with an increased prevalence within this time interval (OR 4.0; 95% CI 1.4, 12)., Conclusions: We did not find clear evidence of an increased prevalence of preceding cancer in our WG cohort, indicating that shared risk factors are of minor importance for the excess of malignancies that occur in WG patients after the vasculitis diagnosis. Furthermore, our current and previously reported latency analyses do not substantiate that serious malignancies play a significant role in the pathogenic events that trigger development of WG.

Objective: To describe the incidence of malignancies in a cohort of Danish patients with Wegener's granulomatosis (WG) and to investigate the cancer risk associated with cyclophosphamide (CYC) -therapy in WG., Methods: In total, 293 patients diagnosed with WG between 1973 and 1999 were studied. Cancer incidence in the cohort was assessed through 2003 by linkage to the Danish Cancer Registry and compared to that of the general population by calculation of standardized incidence ratios (SIR). Analyses were stratified according to treatment with low cumulative CYC doses (< or = 36 g) and high doses (> 36 g, corresponding to treatment with 100 mg CYC/day for > 1 year)., Results: Fifty cancers occurred during 2121 person-years of followup (SIR of cancer of 2.1, 95% CI 1.5-2.7). Significantly increased SIR were observed for acute myeloid leukemia (AML; SIR 19.6, 95% CI 4.0-57), bladder cancer (SIR 3.6, 95% CI 1.2-8.3), and non-melanoma skin cancers (SIR 4.7, 95% CI 2.8-7.3). Leukemias and bladder cancers were diagnosed 6.9-18.5 years after initiation of CYC therapy. The risk of these malignancies was not increased for patients who never received CYC or for patients treated with cumulative CYC doses < or = 36 g. In contrast, high risks of AML (SIR 59.0, 95% CI 12-172) and bladder cancer (SIR 9.5, 95% CI 2.6-24) were observed for patients treated with cumulative CYC doses > 36 g., Conclusion: Treatment with high cumulative CYC doses implies a substantial risk of late-occurring, serious malignancies in WG. Patients with WG should be monitored for development of cancer for several decades after cessation of CYC therapy. These findings emphasize the need for development of new treatment regimens in WG.