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      Comorbidity in gout at the time of first diagnosis: sex differences that may have implications for dosing of urate lowering therapy

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          Abstract

          Background

          The aim of this study is to examine the occurrence of comorbidities at the time of first diagnosis of gout compared with matched population controls, overall and by sex, as well as to examine the crude and age-standardized prevalence of these comorbidities in men and women with gout at first diagnosis.

          Methods

          A population-based study used data from Swedish national and regional registers, including 14,113 gout patients aged ≥ 20 years, with a first recorded diagnosis of gout between 1 January 2006 and 31 December 2012, and 65,782 population controls, matched by age, sex and county. Prevalence ratios (95% confidence intervals) comparing gout cases and controls were calculated, overall and by sex. Crude and age-standardized prevalence (95% confidence interval) of all comorbidities in gout patients were calculated, to show differences between sexes, taking also the higher age at diagnosis in women into account.

          Results

          All examined comorbidities were 1.2–2.5-fold more common in gout patients at diagnosis than in population controls in both sexes. Women with gout were on average 6 years older than men at first gout diagnosis and most comorbidities, including obesity and diuretic use, were or tended to be more frequent in women than in men. When standardizing for age, women had a higher prevalence of thromboembolism (6.6% vs 5.2%) and chronic obstructive pulmonary disease (3.1% vs 2.4%). Men, on the other hand, had a higher prevalence of coronary heart disease (9.4% vs 6.4%), atrial fibrillation (9.0% vs 6.0%), congestive heart failure (7.7% vs 6.6%) and stroke (4.1% vs 3.3%).

          Conclusions

          The occurrence of most comorbidities was significantly increased at first diagnosis of gout in both sexes. Women were older at diagnosis and had higher occurrence of most comorbidities, including obesity and diuretic use, factors that increase serum urate, and this needs to be taken into account when starting and optimizing urate lowering therapy. These sex differences were attenuated when standardizing for age and the occurrence of cardiovascular diseases was actually higher in men.

          Electronic supplementary material

          The online version of this article (10.1186/s13075-018-1596-x) contains supplementary material, which is available to authorized users.

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          Most cited references41

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          Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study.

          The role of uric acid as a risk factor for myocardial infarction is controversial, and little is known about its role as a risk factor for stroke. Recent evidence suggests that uric acid may be an important causal agent in cardiovascular disease, for example, by inducing renal disease and hence hypertension. We investigated the association between serum uric acid and coronary heart disease and stroke in a large prospective population-based study. The study was based on 4385 participants of the Rotterdam Study who, at baseline (1990 to 1993), were > or =55 years of age, free from stroke and coronary heart disease, and had blood taken. Follow-up for incident stroke and myocardial infarction was complete until January 1, 2002. Data were analyzed with Cox proportional hazards models with adjustment for relevant confounders. Average follow-up was 8.4 years. High serum uric acid levels were associated with risk of myocardial infarction and stroke; age- and sex-adjusted hazard ratios (95% CIs) for highest versus lowest quintile of uric acid were 1.68 (1.24 to 2.27) for cardiovascular disease (515 cases), 1.87 (1.12 to 3.13) for myocardial infarction (194 cases), 1.57 (1.11 to 2.22) for stroke (381 cases), 1.77 (1.10 to 2.83) for ischemic stroke (205 cases), and 1.68 (0.68 to 4.15) for hemorrhagic stroke (46 cases). Adjustment for other vascular risk factors only slightly attenuated these associations. Associations were stronger in persons without hypertension than in those with hypertension. Uric acid is a strong risk factor for myocardial infarction and stroke.
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            Independent impact of gout on mortality and risk for coronary heart disease.

            Although gout and hyperuricemia are related to several conditions that are associated with reduced survival, no prospective data are available on the independent impact of gout on mortality. Furthermore, although many studies have suggested that hyperuricemia is associated with cardiovascular disease (CVD), limited data are available on the impact of gout on CVD. Over a 12-year period, we prospectively examined the relation between a history of gout and the risk of death and myocardial infarction in 51,297 male participants of the Health Professionals Follow-Up Study. During the 12 years of follow-up, we documented 5825 deaths from all causes, which included 2132 deaths from CVD and 1576 deaths from coronary heart disease (CHD). Compared with men without history of gout and CHD at baseline, the multivariate relative risks among men with history of gout were 1.28 (95% confidence interval [CI], 1.15 to 1.41) for total mortality, 1.38 (95% CI, 1.15 to 1.66) for CVD deaths, and 1.55 (95% CI, 1.24 to 1.93) for fatal CHD. The corresponding relative risks among men with preexisting CHD were 1.25 (95% CI, 1.09 to 1.45), 1.26 (95% CI, 1.07 to 1.50), and 1.24 (95% CI, 1.04 to 1.49), respectively. In addition, men with gout had a higher risk of nonfatal myocardial infarction than men without gout (multivariate relative risk, 1.59; 95% CI, 1.04 to 2.41). These prospective data indicate that men with gout have a higher risk of death from all causes. Among men without preexisting CHD, the increased mortality risk is primarily a result of an elevated risk of CVD death, particularly from CHD.
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              Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study.

              The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality. A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels. A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.
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                Author and article information

                Contributors
                panagiota.drivelegka@vgregion.se
                valgerdur.sigurdardottir@ltdalarna.se
                anna.svard@ltdalarna.se
                lennart.jacobsson@gu.se
                mats.dehlin@vgregion.se
                Journal
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                1478-6354
                1478-6362
                1 June 2018
                1 June 2018
                2018
                : 20
                : 108
                Affiliations
                [1 ]ISNI 0000 0000 9919 9582, GRID grid.8761.8, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, , University of Gothenburg, ; Grona Straket 12, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
                [2 ]Centre of Clinical Research Dalarna, Falun, Sweden
                Article
                1596
                10.1186/s13075-018-1596-x
                5984404
                29855389
                5e379771-4fdd-4ea0-be5b-1519b75cb80d
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 7 February 2018
                : 18 April 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Orthopedics
                gout,comorbidity,epidemiology,gender,urate lowering treatment
                Orthopedics
                gout, comorbidity, epidemiology, gender, urate lowering treatment

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