Gout in women: Differences in risk factors in young and older women

Article (PDF Available)inThe New Zealand medical journal 125(1363):39-45 · November 2012with23 Reads
Source: PubMed
Abstract
To describe the clinical characteristics of female patients with gout, assess risk factors in this group and to identify any differences between pre- and postmenopausal women with this diagnosis. We retrospectively reviewed the case records of all women who were seen with gout in a secondary care setting (inpatient and outpatient) at Counties Manukau District Health Board between July 2007 and July 2008. Demographic data, risk factors for gout and information on urate-lowering therapy was collected. A cut-off of less than and equal to 50 years was used to estimate pre-menopausal status. 122/509 (24%) of patients seen with gout were female. Fourteen female patients were less than or equal to 50 years of age; all of these patients were either Maori (43%) or of Pacific Island ethnicity (57%). Comorbidities in those =50 years old were renal impairment (78.6%), hypertension (64.3%), congestive heart failure (43%) and diabetes mellitus (42.9%). Comorbidities in women >50 years old were similar: hypertension (77%), renal impairment (70%), dyslipidemia (53%) and diabetes mellitus (50%). Ischemic heart disease was more common in older women (43% vs 7%), P<0.01. Mean body mass index (BMI) was significantly higher in the younger women (43.5 vs 33.1), P<0.01. Half of all the female patients were on diuretics, and medication used to lower uric acid level was prescribed in 35.7% of women less than and equal to 50 years of age, and 42.59% of women >50 years of age. Women who develop gout are more likely to be over the age of 50, have other comorbidities and be on diuretics. In comparison, younger women who develop gout have similar risk factors but tended to have a higher body mass index and are more likely to be of Maori or Pacific Island ethnicity.
THE NEW ZEALAND
MEDICAL JOURNAL
Journal of the New Zealand Medical Association
NZMJ 12 October 2012, Vol 125 No 1363; ISSN 1175 8716 Page 1 of 7
URL: http://www.nzma.org.nz/journal/125-1363/5373/ ©NZMA
Gout in
women: differences in risk factors in young and
older women
Sunil Kumar, Rajiv Gupta, Ravi Suppiah
Abstract
Aim To describe the clinical characteristics of female patients with gout, assess risk
factors in this group and to identify any differences between pre- and postmenopausal
women with this diagnosis.
Methods We retrospectively reviewed the case records of all women who were seen
with gout in a secondary care setting (inpatient and outpatient) at Counties Manukau
District Health Board between July 2007 and July 2008. Demographic data, risk
factors for gout and information on urate-lowering therapy was collected. A cut-off of
50 years was used to estimate pre-menopausal status.
Results 122/509 (24%) of patients seen with gout were female. Fourteen female
patients were 50 years of age; all of these patients were either Maori (43%) or of
Pacific Island ethnicity (57%). Comorbidities in those 50 years old were renal
impairment (78.6%), hypertension (64.3%), congestive heart failure (43%) and
diabetes mellitus (42.9%). Comorbidities in women >50 years old were similar:
hypertension (77%), renal impairment (70%), dyslipidemia (53%) and diabetes
mellitus (50%). Ischemic heart disease was more common in older women (43% vs
7%), P<0.01. Mean body mass index (BMI) was significantly higher in the younger
women (43.5 vs 33.1), P<0.01. Half of all the female patients were on diuretics, and
medication used to lower uric acid level was prescribed in 35.7% of women 50 years
of age, and 42.59% of women >50 years of age.
Conclusion Women who develop gout are more likely to be over the age of 50, have
other comorbidities and be on diuretics. In comparison, younger women who develop
gout have similar risk factors but tended to have a higher body mass index and are
more likely to be of Māori or Pacific Island ethnicity.
Gout is a form of inflammatory arthritis caused by uric acid precipitation in and
around joints. This painful condition was first identified in ancient times by Egyptians
around 2640 BC. Hippocrates first wrote about this disorder in 400 BC.
1,2
Prolonged
hyperuricemia is the main risk factor for gout.
Hyperuricemia can be caused by either excessive intake of a purine rich diet or
inadequate excretion of uric acid by the kidneys. Human beings lack the enzyme
uricase which converts uric acid into water soluble allantoin which is more readily
excreted.
3
Genetic studies have identified association between polymorphism in the
GLUT9 (SLC2A9) gene and URAT1 (SLC22CA12) gene to be key regulators and
transporters of uric acid.
Genetic variations in these enzymes are identified as risk factors for hyperuricemia
and gout.
4,5
Other well recognised associations for hyperuricemia and gout include
NZMJ 12 October 2012, Vol 125 No 1363; ISSN 1175 8716 Page 2 of 7
URL: http://www.nzma.org.nz/journal/125-1363/5373/ ©NZMA
age, diabetes mellitus, hypertension, metabolic syndrome, renal disease,
cardiovascular diseases and medications like diuretics.
Gout is predominantly a disease of males, but in recent times, there has been an
increase in prevalence in women. The reported male to female ratio is approximately
7:1 to 9:1 but in people over the age of 65 this ratio is reduced to 3:1.
6–8
Gout is
considered rare in premenopausal women as the estrogenic hormones have a mild
uricosuric effect and therefore protective against hyperuricemia and gout. During
menopause the estrogen levels drop and women with risk factors become more likely
to develop hyperuricemia and gout.
9
However, in our clinical practice we have
noticed an increasing frequency of young women presenting with acute flares of gout.
The objective of this study was to describe the clinical characteristics of female
patients with gout, assess risk factors for gout in this cohort and identify any
differences between pre- and postmenopausal women with this diagnosis who present
to secondary care in South Auckland.
Methods
We retrospectively reviewed the records of female patients with a diagnosis of gout using the
International Classification of Diseases-9 (ICD-9 codes 274.0, 274.8, 274.9), who were seen at
Counties Manukau District Health Board (CMDHB), South Auckland, New Zealand, between July
2007 and July 2008.
Demographic data, information on relevant comorbidities and diuretic use were collected.
Comorbidities of interest were obesity, hypertension, congestive heart failure, dyslipidemia, diabetes
mellitus and renal impairment. Obesity was defined as body mass index (BMI) >30kg/m
2
; renal
impairment was defined as estimated glomerular filtration rate (eGFR) of <60mls/min using the
Modification of Diet in Renal Disease (MDRD) formula.
10
The menstrual status of women was not usually recorded in the hospital medical charts therefore we
used an age cut-off of 50 years (average age of menopause in our population) as a surrogate marker for
pre-and postmenopausal status.
We collected laboratory data on lipid levels, serum urate and glomerular filtration rate. The use of
urate-lowering therapy was determined from the electronic medical records.
Statistical analysis—Statistical analysis was conducted using OpenEpi (version 2.3.1) software. Paired
t-test (2 sided) was used to compare differences among means. Chi-squared was used to compare
differences in proportions. One-way ANOVA used to compare differences in means when there were
more than 2 samples. All reported p values less than 0.05 were considered statistically significant.
Results
Between 1 July 2007 and 31 July 2008, 509 patients presented to CMDHB for
management of gout. This included inpatient as well as outpatient visits. Table 1
shows the gender and ethnic distribution of the study population. Among the 509
patients, 122 (24%) were female.
Fourteen female patients (11.5%) were either 50 years or younger and 108 (88.5%)
were over 50 years of age. Table 2 shows a comparison of the ethnicity, the traditional
risk factors and prescribed treatment between the two age groups.
NZMJ 12 October 2012, Vol 125 No 1363; ISSN 1175 8716 Page 3 of 7
URL: http://www.nzma.org.nz/journal/125-1363/5373/ ©NZMA
Table1. Gender and ethnic distribution of patients with gout presenting to
secondary care at Counties Manukau District Health Board in the period 1 July
2007 and 31 July 2008
Ethnicity Total
n (%)
Males
n (%)
Females
n (%)
M:F ratio
Māori
Pacific people
Europeans
Others
129 (25)
237 (47)
115 (23)
28 (6)
87 (22)
190 (49)
86 (22)
24 (6)
42(34)
47 (39)
29 (24)
4 (3)
2:1
4:1
3:1
6:1
Total n (%) 509 (100) 387 (100) 122 (100) 3:1
Table 2. Description of women with gout stratified by age
Characteristics Age 50 years
(n=14)
Age >50
(n=108)
P value
Mean age (range)
41 (23–50) 71.5 (51–95)
Ethnicity
Māori n (%) 6 (43) 36 (33.3) 0.67
Pacific n (%) 8 (57) 39 (36.1) 0.22
European n (%) 0 (0) 29 (26) 0.035
Others n (%) 0 (0) 4 (3.7) 1.00
Risk factors
Mean BMI
Hypertension no (%)
Diabetes mellitus
Renal impairment
CHF
Dyslipidemia
Ischemic heart disease
Three or more comorbidities
43.5
9 (64.3)
6 (42.9)
11 (78.6)
6 (43)
5 (35.7)
1 ( 7.0)
9 (64)
33.1
83 (77)
54 (50)
76 (70)
40 (37)
60 (55)
46 (43)
70 (64.8)
0.002
0.24
0.41
0.39
0.44
0.13
0.01
0.97
SUA mean (range)
0.54 (0.4–0.8) 0.48 (0.22–0.92) 0.17
Treatment
Allopurinol no (%)
Uricosuric agent
3 (21.4)
2 (14.3)
45 (42)
1 (1.0)
0.12
0.03
Table 3. Risk factors for the three major ethnic groups
Characteristics European Māori Pacific people P value
Numbers (%)
29 (24.58) 42 (35.59) 47 (39.83)
Average age (range)
78.9 (52–95) 60.5 (23–85) 60.93 (27–83) 0.10
Mean BMI (range)
31.6 (20.6–40) 34.1 (24–51.2) 37.1 (21–77) <0.001
Hypertension No. (%)
19 (65.5) 33 (78.6) 35 (74.5) 0.47
Diabetes mellitus No. (%)
7 (24.14) 21 (50) 23 (48.90) 0.06
Renal impairment No. (%)
18 (62) 27 (64.3) 39 (83) 0.07
CHF no (%)
11 (37.9) 18 (42.9) 17 (36.2) 0.80
IHD no (%)
16 (55) 17 (40.5) 13 (27.7) 0.06
Dyslipidemia No. (%)
20 (69) 19 (45.2) 25 (53.2) 0.14
Diuretic use No. (%)
16 (55) 23 (54.8) 20 (42.6) 0.42
Mean SUA (range)
0.45 (0.22–0.71) 0.51 (0.28–0.92) 0.50 (0.27–0.81) 0.42
Treatment
Allopurinol No (%) 10 (34.5) 16 (38) 21 ( 44.7) 0.65
Uricosuric agent No (%) 0 (0) 0 (0) 3 ( 6.4) 0.10
NZMJ 12 October 2012, Vol 125 No 1363; ISSN 1175 8716 Page 4 of 7
URL: http://www.nzma.org.nz/journal/125-1363/5373/ ©NZMA
In the ‘pre-menopausal’ age group ( 50 years), 43% were Māori and 57% were
Pacific people. There was no European or people of other ethnic group represented in
this age group. In the older age group (> 50 years), 26% of the population were
Europeans, 33.3% were Māori, 36.1% were Pacific People and 4% were of other
ethnic group (predominantly Asian).
Every patient in the ‘pre-menopausal’ age group had a comorbidity that predisposed
them to gout. Renal impairment (78.6%) and hypertension (64.3%) were the two most
common co morbidities in the 50 age group. Renal impairment was attributed to
hypertensive disease in 57% and glomerulonephritis in 21%.
Congestive heart failure and diabetes mellitus were present in 43% of patients who
were 50 years old. The underlying cause for congestive heart failure was either
rheumatic valvular heart disease or non-ischemic cardiomyopathy.
Comorbidities seen in the older age group were hypertension (77%), renal impairment
(70%), dyslipidemia (55%), diabetes mellitus (42.95%) and ischemic heart disease
(43%). The presence of ischemic heart disease was more common in older women
(43% vs 7%, P<0.01), whereas the mean BMI was significantly higher in the younger
age group (BMI 43.5 vs. 33.1, P<0.01).
Diuretic use was similar between the age groups (approximately 50% in both groups).
The mean serum uric acid was not statistically different between the 2 age groups.
Medication to lower uric acid was prescribed in 5 (35.7%) of patients in the younger
age group and 46 (42.59%) of patients in the older age group. Allopurinol was the
drug of choice and only 3 (2.68%) received uricosuric agents.
When risk factors for different ethnic groups were compared, statistically significant
difference was noted in the mean BMI. Obesity, defined as a BMI of greater than 30
was noted in 64 % of the less than 50 age group and 39% in the older age group, with
the Pacific People having highest mean BMI (37.1) followed by Māori (34.1) and
European (31.6). There was a suggestion that European women were older (mean age
78.9 years) compared to Māori and Pacific women (60.52 and 60.93 years
respectively), but this did not reach statistical significance.
Hypertension and renal impairment were the two most common comorbidities in all
three ethnicities. Diabetes mellitus occurred more commonly in Māori (50%) and
Pacific people (48.9%) compared with European (24%), P=0.06. The mean serum uric
acid (SUA) concentration and diuretic use was similar in all three ethnic groups.
Therapy to lower uric acid levels was similar in all three ethnicities with no
significant statistical difference noted.
Discussion
The Counties Manukau District Health Board (CMDHB) has an estimated population
of 464,000 of which 46% are Europeans, 21% Pacific people, 17% Māori and 16%
Asians. It has the third highest district health board (DHB) population in New Zealand
and has the highest number of Māori and Pacific people. Gout is a common metabolic
condition present in this DHB population (11).
NZMJ 12 October 2012, Vol 125 No 1363; ISSN 1175 8716 Page 5 of 7
URL: http://www.nzma.org.nz/journal/125-1363/5373/ ©NZMA
This study shows that 24% of patients presenting with gout to secondary care in South
Auckland are women, giving an overall male to female ratio of 3:1. The ratio for
Māori was 2:1, European 3:1 and Pacific people 4:1. This compares to
epidemiological survey conducted by Klemp and colleagues in 1996 which showed
that the sex ratio of Māori men to women with gout was 5:1 and European men to
women were 8:1.
12
A potential reason for this discrepancy between our findings and Klemp could be that
women are more likely to seek medical attention and attend appointments in
secondary care, but alternatively it could mean that the prevalence of gout in women
is rising.
Approximately 89% of women with gout in our study were over 50 years of age,
confirming that this disease that mainly affects postmenopausal women, but a
significant number of women under the age of 50 are now presenting with gout.
Māori and Pacific women have a higher prevalence of gout, similar to their male
counterparts, suggesting genetic factors to be involved. Genetic variation in SLC2A9
is shown to increase the risk of gout by 500% in New Zealand Māori and Pacific
Island Polynesians as shown in a study by Hollis-Moffatt et al.
13
European women with gout in our study were on average eighteen years older than
Māori and Pacific women. The main traditional risk factors identified for gout were
obesity, hypertension, renal impairment and diuretic use similar to those identified in
other studies.
14,15
All the women in the ‘pre-menopausal’ age group had at least one risk factor for gout
and 64% had more than three comorbidities. Similar finding were also noted in
women over 50 years of age. The main differences between the risk factors for gout
between young and older women were increased body mass index (BMI) in the
younger age group and Māori and Pacific Island ethnicity. The Nurses health study
showed that women with BMI between 23 and 24.9 kg/m2 had a 1.55 relative risk of
gout.
The risk continued to increase with increasing BMI, so that RR was 2.86 for those
with BMI of 25-29.9 kg/m
2
, RR of 4.69 for BMI of 30 to 43.9 kg/m
2
, and RR of 7.25
for BMI exceeding 35kg/m
2
.The same study showed hypertension was associated
with a RR of 2.26 and diuretic use had a RR of 2.63.
14
Other important risk factors identified in the women population with gout were
diabetes mellitus, congestive cardiac failure and to a lesser extent, ischemic heart
disease. A study to determine the prevalence of gout in patients with diabetes mellitus
showed a high prevalence (22%) in patients with Type 2 diabetes.
16
Our study showed that 50% of Māori and Pacific, and 25% of European women with
gout had diabetes mellitus. This study highlighted that treatment to lower uric acid
was inadequately administered in women with only 40% receiving any form of
therapy. This would explain why the mean serum uric acid was elevated in all the
study groups.
There are limitations to this study. Firstly only patients who presented to secondary
care were included. A large percentage of patients with gout are cared for by their
NZMJ 12 October 2012, Vol 125 No 1363; ISSN 1175 8716 Page 6 of 7
URL: http://www.nzma.org.nz/journal/125-1363/5373/ ©NZMA
primary care physicians and it is likely that patients with difficult to treat gout or with
multiple comorbidities were more likely to be referred to secondary care.
The prevalence of comorbidities in our study may not be the true reflection of our
wider gout population. We only had a small number of patients in the young age
group which makes it difficult to interpret the risk factors in this subgroup. Menstrual
data was not available and therefore we used an age cut-off as a surrogate marker for
menopause. Alcohol and diet history was not reliably recorded, hence the influence of
these important risk factors were not included in the study.
In conclusion, women who develop gout are more likely to be over the age of 50 (i.e.
postmenopausal), have one or more comorbidity and are more likely to use diuretics.
In comparison, younger women who develop gout have similar risk factors but tended
to have a higher body mass index and are more likely to be of Māori or Pacific Island
ethnicity.
Women with gout seem to be under-treated despite being seen in secondary care. This
study highlights important demographic feature of women with gout which can be
used as a starting point for larger epidemiological studies and also provides valuable
information which can be used in power calculations for future interventional studies
to test preventative or therapeutic strategies.
Competing interests: None known.
Author information: Sunil Kumar, Rheumatologist, Department of Rheumatology,
Counties Manukau District Health Board, Auckland; Rajiv Gupta, Rheumatologist,
Department of Rheumatology, Counties Manukau District Health Board, Auckland;
Ravi Suppiah, Rheumatologist, Department of Rheumatology, Auckland City
Hospital and Middlemore Hospital, Auckland
Correspondence: Dr Sunil Kumar, Department of Rheumatology, Counties Manukau
District Health Board, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand.
Email: skumar@middlemore.co.nz
References:
1. Benedek TG, Rodnan GP. A brief history of the rheumatic disease. Bull Rheum Dis
1982;32(6):59–68.
2. Nuki G, Simkin PA. A concise history of gout and hyperuricemia and their treatment. Arthritis
Res Ther 2006;8(suppl 1):S1.
3. Vogt B. Urate oxidase (rasburicase) for treatment of severe tophaceous gout. Nephrol Dial
Transplant 2005;20:431–433.
4. Brandstatter A, Kiechl S, Kollerits, et al. Sex-specific association of the putative fructose
transporter SLC2A9 variants with uric acid levels is modified by BMI. Diabetes care: Aug
2008;31(8):1662–1667.
5. Richette, Pascal; Bardin, Thomas. Gout. Lancet 2010;375(9711):318–328.
6. Mahajan A, Tandon VR, Sharma S, Jandial C. Gout and menopause. J K Science
2007;9(1):50–51.
7. Souza AWS, Fernandes V, Ferrari AJL. Female gout: Clinical and laboratory features. J.
Rheumatol 2005; 32 (11):2186–2188.
8. Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in
US women – The Third National Health and Nutrition Examination Survey. Arthritis Res
Ther. 2008;10(5):120.
NZMJ 12 October 2012, Vol 125 No 1363; ISSN 1175 8716 Page 7 of 7
URL: http://www.nzma.org.nz/journal/125-1363/5373/ ©NZMA
9. Harrold LR, Yood RA, Mikuls TR, et al. Sex differences in gout epidemiology: evaluation
and treatment. Ann Rheum Dis 2006;65:1368–1372.
10. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular
filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal
Disease Study Group. Ann Int Med 1999;130(6):461–70.
11. Wong K, Jackson G. The changing demography of Counties Manukau District health.
http://www.cmdhb.org.nz/About_CMDHB/Planning/Health-
Status/Population/2008/changing-demography-report.pdf
12. Klemp P, Stansfield SA, Castle B, Robertson MC. Gout is on the increase in New Zealand.
Ann Rheum Dis. 1997;56(1):22–6.
13. Hollis-Moffatt JE, Xu X, Dalbeth N, et al. A role for the urate transporter SLC2A9 gene in
susceptibility to gout in New Zealand Maori, Pacific Island and Caucasian case-control
cohorts. Arthritis Rheum 2009;60:3485–92.
14. Choi H, Curhan G. Adiposity, hypertension, diuretic use and risk of incident gout in women-
The Nurses Health Study. ACR Annual scientific meeting 2005; Abstract 1977.
15. Lally EV, Ho G Jr, Kaplan SR. The clinical spectrum of gouty arthritis in women. Arch Intern
Med. 1986 Nov;146(11):2221–5.
16. Suppiah R, Dissanayake A, Dalbeth N. High prevalence of gout in patients with Type 2
diabetes: male sex, renal impairment, and diuretic use are major risk factors N Z Med J.
2008;121 (1283). http://journal.nzma.org.nz/journal/121-1283/3293/
  • [Show abstract] [Hide abstract] ABSTRACT: About 2500 years ago, gout was observed by Hippocrates and many people suffered severe pain and deformity. Lifestyle and diet play a significant role in gout and serum uric acid levels. Epidemiological and research studies have supported this evidence. Many recommendations and guidelines from different parts of the world mention the impact of diet on gout. Recently, new research has shown associations between vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and the risk of gout. Our review summarizes recently published research regarding dietary impact on the risk of gout and serum uric acid levels. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
    Article · Jun 2015
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: The objective of this study was to assess the real-world comparative effectiveness of continuing on allopurinol versus switching to febuxostat. Methods: In a retrospective claims data study of enrollees in health plans affiliated with Optum, we evaluated patients from February 1, 2009, to May 31, 2012, with a gout diagnosis, a pharmacy claim for allopurinol or febuxostat, and at least 1 serum uric acid (SUA) result available during the follow-up period. Univariate and multivariable-adjusted analyses (controlling for patient demographics and clinical factors) assessed the likelihood of SUA lowering and achievement of target SUA of less than 6.0 mg/dL or less than 5.0 mg/dL in allopurinol continuers versus febuxostat switchers. Results: The final study population included 748 subjects who switched to febuxostat from allopurinol and 4795 continuing users of allopurinol. The most common doses of allopurinol were 300 mg/d or less in 95% of allopurinol continuers and 93% of febuxostat switchers (prior to switching); the most common dose of febuxostat was 40 mg/d, in 77% of febuxostat switchers (after switching). Compared with allopurinol continuers, febuxostat switchers had greater (1) mean preindex SUA, 8.0 mg/dL versus 6.6 mg/dL (P < 0.001); (2) likelihood of postindex SUA of less than 6.0 mg/dL, 62.2% versus 58.7% (P = 0.072); (3) likelihood of postindex SUA of less than 5.0 mg/dL, 38.9% versus 29.6% (P < 0.001); and (4) decrease in SUA, 1.8 (SD, 2.2) mg/dL versus 0.4 (SD, 1.7) mg/dL (P < 0.001). In multivariable-adjusted analyses, compared with allopurinol continuers, febuxostat switchers had significantly higher likelihood of achieving SUA of less than 6.0 mg/dL (40% higher) and SUA of less than 5.0 mg/dL (83% higher). Conclusions: In this "real-world" setting, many patients with gout not surprisingly were not treated with maximum permitted doses of allopurinol. Patients switched to febuxostat were more likely to achieve target SUA levels than those who continued on generally stable doses of allopurinol.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
    Full-text · Article · Nov 2015