In this large nationally representative cohort of men with gout with more than 10 years of follow-up, we have provided contemporary, generalisable and population-based estimates of the absolute risk of ED reporting in England. Overall we found the risk of ED post-diagnosis to be 2% per year. Whilst those with gout were 31% more likely to consult their general practitioner for ED compared to those without gout, the excess absolute risk was 0.6% per year. The risk of pharmacologically treated ED was not statistically different between cases and controls among the younger population (<45 years) or those with a recorded diagnosis of diabetes or chronic renal failure. Having more than 6 months of ULT within 1 and 3 years from initial gout diagnosis had no impact ED reporting. The risk of consulting a GP for ED was also higher within the year preceding the initial gout diagnosis.
We have conducted one of the largest studies to precisely determine the risk of ED among men with gout. Our study used an open cohort approach, with prospectively recorded data utilising information from primary care from across England, covering 3% of the total UK population with similar age and sex distribution to the population as a whole. Thus these findings are not only generalisable to England but also to other developed nations with comparable health care systems. Our use of primary care data allowed us to adjust our estimates for important confounding factors such as smoking status, alcohol consumption and BMI, which had not been done in previous studies on the subject. Furthermore, prospective data allowed us to look at the timing of ED in relation to gout diagnosis, which also has not been previously demonstrated.
A potential limitation is the use of anonymised data with no direct link to the patient record and our reliance on general practitioners entering data accurately. However, gout diagnosis has been externally validated in CPRD with a high degree of accuracy [10] so it is unlikely that there is any major error in our study due to the misclassification of gout diagnosis. Similarly, validity and under-reporting of ED due to the reluctance of patients to seek medical advice may be a concern, however, our study provides estimates which reflect contemporary ED reporting and screening practices in primary care, which form the basis of management. Nonetheless, our absolute rates of ED are much higher compared to most studies on the subject [6, 7].
There may be potential ascertainment bias as gout patients may be more aware of associated comorbidities and consequently, report more ED compared to those without gout. However, we believe the impact of this may be minimal as higher relative risk of ED was also observed among those with pharmacologically treated ED and also within the year preceding gout diagnosis. We also acknowledge the lack of complete data on BMI which could bias our estimates. Nonetheless, we treated patients with missing data as a separate category and included them in our analysis. The fact that we were able to adjust for BMI and other lifestyle-related characteristics is an advantage over other large studies on the topic. Finally, the use of 1- and 3-year landmarks for our ULT analysis means that our findings are only generalisable to those alive and contributing data at those landmark points and prescribed at least 6 months of ULT after their initial gout diagnosis.
The absolute rate of ED reporting among gout patients in our cohort was calculated to be 2% per year. This is much higher than the rate previously reported by two large registry-based studies from Taiwan (0.1–0.2% per year) utilising Health Insurance Research Database [6, 7]. This may be because treatment for ED in Taiwan is not covered by their National Health Insurance program leading to under-ascertainment of ED. Furthermore, differences in study population and cultural norms may also have contributed to ED under-reporting. Overall we observed a 31% increased relative risk of ED among gout patients compared to controls. Whilst these estimates are in line with those reported in Southeast Asian studies [6, 7], a US-based study reported around threefold higher risk of ED among gout cases [5]. The latter study was based on a cross-sectional survey of men aged 18–89 years attending a rheumatology clinic with any form of arthritis, which may be prone to selection and recall bias. Furthermore, the finding of this previous study may not be generalisable to the majority of patients with gout who are managed exclusively in primary care.
Whilst our study supports most of the findings from the Taiwanese studies, it is important to note that the excess absolute risk of ED among gout patients compared to controls is less than 0.6%. Furthermore, we reported no increased risk of ED reporting among those with diabetes and chronic renal disease, which suggests stronger influence of those conditions on ED than gout. Our findings support the likely physiological influence of hyperuricaemia on vasculature including induction of vascular smooth muscle proliferation, oxidative stress, and activation of the renin-angiotensin axis in vascular beds [14] which begins in asymptomatic hyperuricaemia before the clinical diagnosis of gout.