This study was undertaken to augment the limited data available on the epidemiology of gout and its management in practice in Europe. The study dealt exclusively with patients with a clinical diagnosis of gout but not patients with asymptomatic hyperuricaemia. The overall prevalence of gout of 1.4% was remarkably similar in two large IMS databases, each containing about 2.5 million patient records from the years 2000–5 in Germany and the UK. The overall prevalence was also remarkably similar to that found previously by Mikuls et al10
in the records of 1.8 million patients in the UK General Practice Research Database (GPRD) for the years 1990–9, using similar case definitions.10
The consistency of these observations on the prevalence of gout consultations in Germany and the UK would seem to provide a measure of confidence in the robustness of estimates of the true prevalence of gout in primary care settings in Northern Europe. It is noteworthy, however, that the prevalence of gout was not greater in the current study, than in the UK GPRD for 1990–9,10
despite the fact that the mean ages of the patients with gout in the UK and German databases for 2000–5 were 6 years and 3 years older, respectively. The prevalence rates observed are, however, slightly higher than those found by Harris et al
(0.95%) in 40 UK general practices in 199312
and fivefold higher than those observed (0.26%) in the survey by Currie in UK general practices 30 years ago.13
There are other data which suggest that the prevalence of gout might have increased over the past 30 years. The annual prevalence of self-reported gout in the National Health Interview Survey in the USA trebled between 1969 and 1996,14
and the prevalence of gout and hyperuricaemia requiring urate-lowering drug treatment was observed to have increased by 80% between 1990 and 1999 in a managed-care population in the USA.15
However, Mikuls et al
showed that the overall incidence of consultations for gout remained relatively stable throughout the 1990s,10
suggesting that any increase in prevalence might be largely attributable to the changing age structure of the population. Nevertheless, gout is the most common cause of inflammatory arthritis in men over the age of 40 years,16
and the overall prevalence of gout is notably higher than that of rheumatoid arthritis, which was recently estimated to be 1.16% in women and 0.44% in men across the UK population.17
As expected, the prevalence of comorbidities was high among patients with gout in both the UK and Germany. The comorbidities found to be most commonly associated with gout in this study were obesity in the UK and diabetes in Germany. Obesity was twice as common (27.7%) in UK patients as in German patients (13.3%), while diabetes was recorded as a comorbid diagnosis three times as often in the German patients (25.9%) as in those in the UK GPRD (8.3%). Similar prevalence rates of obesity have been estimated previously in the UK and Germany,18
and the somewhat surprising difference reported in this study may be attributable, in part, to the use of the IMS Disease Analyzer database. In the UK, GPs in the IMS Disease Analyzer panel can record items such as BMI in addition to using ICD-10 codes for obesity, but in Germany only the ICD-10 codes were considered in the study definition of obesity as there was no other electronically coded way for a GP to record obesity. Therefore, it is possible that British GPs were more likely to capture information electronically about obesity than those in Germany. The greater frequency with which diabetes was recorded in Germany is consistent with previous estimates of prevalence rates in Europe, which were more than twice as high in Germany as those in the UK.19
Over 60 years ago, Brochner-Mortensen observed that 78% of a group of 100 Scandinavian patients with gout were more than 10% overweight and 57% were more than 30% overweight.20
Grahame and Scott found that 48% of a UK cohort of 354 patients with gout attending a hospital clinic were more than 15% overweight.21
Obesity was not recorded as a specific comorbidity in the study by Mikuls et al
However, recently published data demonstrated that the prevalence of abdominal obesity and metabolic syndrome is as high as 62.9% in people with gout identified in the US Third National Health and Nutrition Survey (NHANES III),22
and diabetes was a comorbid diagnosis in 19.9% of 9482 patients with gout in a North American study of patients in a managed-care setting.23
It is therefore interesting and surprising that Mikuls et al
also found the prevalence of diabetes to be remarkably low (6.4%) in patients with gout in their analysis from the UK GPRD for 1990–9.10
In that study, it was found that coronary artery disease and hypertension were the most common comorbidities in patients with gout (24.9% and 23.9%, respectively).10
The prevalence of hypertension among patients with gout was found to be as high as 59.7% in the North American managed-care population.23
There is some evidence to suggest that gout and hyperuricaemia may be independent risk factors for cardiovascular disease.24 25
The clinical data demonstrating the association of gout with obesity, hypertension, excessive alcohol consumption and metabolic syndrome is now overwhelming and incontrovertible.22 23 25 26
As these comorbidities are themselves major risk factors for cardiovascular disease, every diagnosis of gout should act as a “red flag” to alert doctors to assess patients for cardiovascular risk.7 22 27
A similar proportion of patients were found to be receiving prescriptions for diuretic drugs in the UK and Germany in this study (~ 30%), and by Mikuls et al
Diuretics, especially thiazide diuretics, can increase the sUA level as a consequence of volume depletion, increased renal tubular reabsorption of urate, stimulation of the urate-anion exchanger (URAT-1) and a decrease in renal urate excretion.28
Diuretic use has been found to be a risk factor for incident gout (relative risk (RR)
1.77; 95% confidence interval 1.42 to 2.20) which is apparently independent of hypertension in the 12 years of follow-up of a cohort of men who had no previous history of gout in the health professionals follow-up study.26
However, a recent case–control study found no evidence that diuretics were a risk factor for the development of gout, and suggested that the cardiovascular conditions for which they were prescribed, which are themselves risk factors for gout, might have confounded previous inferences.29
This would imply that continuing flares of gout in these patients were not primarily attributable to continuing treatment with diuretics, but rather were a consequence of failure to treat hyperuricaemia adequately.
Allopurinol was by far the most commonly used drug for treating patients with chronic and interval gout in both the UK and Germany, accounting for about 90% of all such medication. However, despite the clear preference for allopurinol as the preferred uric acid lowering drug, the findings from the current study show that the management of patients with gout is suboptimal. A large proportion of patients with gout continued to have raised sUA levels and recurrent gout flares. Persistence of treatment with allopurinol was remarkably low in both the UK and Germany, but this study provides no information about why this should have been the case.
Until recently, the importance of follow-up sUA testing to guide treatment decisions in patients diagnosed with gout has not been emphasised or well defined by research evidence. However, there is now evidence from comparative randomised controlled trials,3 30
and from an observational study in a managed-care setting,1
that fewer than 50% of patients receiving allopurinol, in the most commonly prescribed dose of 300 mg daily, achieve optimum reductions in plasma urate concentrations. Recent evidence-based, consensus guidelines from EULAR7
emphasise the importance of ensuring that the sUA level is maintained below 360 μmol/l (6 mg/dl), but those from the British Society for Rheumatology27
recommend maintaining the sUA level below 300 μmol/l (5 mg/dl). Despite a lack of evidence for the optimum frequency for monitoring the sUA level, recent guidelines recommend 3-monthly measurements of sUA in the first year after the start of treatment with uric acid lowering drug treatment followed by annual measurements.27
The frequency of sUA testing was found to be extremely low in this study; sUA evaluation was performed in only 14% of the UK and 9% of the German study populations, and fewer than 5% of patients had two sUA tests performed in the observation period in either country. It might be argued that it is acceptable for the sUA level to be monitored less frequently in patients with good symptomatic control; however, the study clearly showed that even patients who continued to experience gout flares were not having regular sUA checks.
Seventy-two percent of the patients with gout in the UK, and over 40% of those in Germany, experienced at least one gout flare, and the frequency of gout flares was significantly correlated with sUA levels.
Previous studies have demonstrated the presence of urate crystals in the joints of patients with asymptomatic gout,31
but reduction of the sUA below 360 μmol/l (6 mg/dl) leads to decreased intra-articular crystal deposition8
and more rapid reduction of tophi3
as well as a reduction in the frequency of gout flares.9
This suggests that maintaining the sUA level below 360 μmol/l (6 mg/dl) could prevent recurrent attacks of acute gout in the long term.1 9
Indeed, it would be of interest to undertake further research to investigate the possibility of a continuous relationship between sUA levels and the risk of crystal deposition, analogous to the relationship that has been demonstrated between cardiovascular risk and measures such as serum cholesterol levels and blood pressure.
This study has some limitations. Although the primary care consultation data provided by the IMS databases are an important source of information on the prevalence of gout, associated comorbidities and treatment, and can provide age and sex standardised estimates of the number of new consultations, the IMS Disease Analyzer does not contain community-based data that would allow for the measurement of population-wide incidence rates of gout in different countries. Although the IMS database populations in Germany and the UK closely mirror the populations at large in their male to female ratio, social class and geographical distribution, it is possible that not all practice types are represented.
Possibly, the study might have underestimated the prevalence of gout in Germany, as several patients in the German database were excluded from the analysis because they only had a single recording of gout in their notes. Second attacks might have been under-recorded in the German database because of the free choice of healthcare that operates in Germany, where the doctor responsible for the patient’s records might not be the doctor consulted for a subsequent gout flare. There is also the possibility that the study underestimated the frequency of gout flares, because the option to self-medicate means not all gout flares would necessarily have been detailed in a patient’s records. Any such effect did not, however, prevent the study from demonstrating a correlation between sUA level and gout flares.
Another important question that was not dealt with was whether the doses of allopurinol were optimum in those patients with gout found to have a high sUA level and frequent gout flares. The study showed that 97.9% of patients prescribed allopurinol in the UK and 96.6% of those in Germany received doses of
300 mg/day (), but how this was related to outcomes was not investigated. Neither did the study evaluate whether allopurinol doses were adjusted according to renal function to minimise the risk of toxicity in patients with renal impairment.27 32
The relationship between flares and the recommended7 27
prophylactic use of low-dose colchicine or NSAIDs to minimise the risk of gout flares following the initiation of urate-lowering treatment was not investigated.
In conclusion, this study has shown that the prevalence of gout in practice in the UK and Germany in the years 2000–5 was 1.4%, a figure that is consistent with previous UK data for 1990–9. Patients with gout had a high frequency of chronic comorbidities, several of which are associated with an increased risk of cardiovascular disease. Allopurinol was the preferred urate-lowering drug for the management of interval and chronic gout in both countries studied, but persistence with treatment was poor and gout flares were frequent despite urate-lowering treatment.
Evaluation of sUA levels to guide treatment was not undertaken sufficiently. The importance of regular monitoring of sUA levels and adjustment of treatment to optimise sUA was highlighted by data from this study, showing that the prevalence of comorbidities among patients with gout was directly related to sUA levels, and that patients with sUA levels >360 μmol/l (>6 mg/dl) had an increased risk of gout flares.