Risk of Multiple Sclerosis in People Living with HIV: An International Cohort Study.

OBJECTIVE: There has been interest in a possible negative association between HIV and multiple sclerosis (MS). We aimed to compare the risk of MS in a cohort of individuals living with HIV to that in the general population. METHODS: Population-based health data were accessed for 2 cohorts of HIV-positive persons from Sweden and British Columbia, Canada. Incident MS was identified using MS registries or a validated algorithm applied to administrative data. Individuals with HIV were followed from 1 year after the first clinical evidence of HIV or the first date of complete administrative health data (Canada = April 1, 1992 and Sweden = January 1, 2001) until the earliest of incident MS, emigration, death, or study end (Canada = March 31, 2020 and Sweden = December 31, 2018). The observed MS incidence rate in the HIV-positive cohort was compared to the expected age-, sex-, calendar year-, income-specific, and region of birth-specific rates in a randomly selected sample of >20% of each general population. The standardized incidence ratio (SIR) for MS following the first antiretroviral therapy exposure ("ART-exposed") was also calculated. RESULTS: The combined Sweden-Canada cohort included 29,163 (75% men) HIV-positive persons. During 242,248 person-years of follow-up, 14 incident MS cases were observed in the HIV-positive cohort, whereas 26.19 cases were expected. The SIR for MS in the HIV-positive population was 0.53 (95% confidence interval [CI] = 0.32-0.90). The SIR for MS following the first ART exposure was 0.55 (95% CI = 0.31-0.96). INTERPRETATION: This international population-based study demonstrated a lower risk of MS among HIV-positive individuals, and HIV-positive ART-exposed individuals. These findings provide support for further exploration into the relationship among HIV, ART, and MS. ANN NEUROL 2024;95:487-494.

Interrogation of the Multiple Sclerosis Prodrome Using High-Dimensional Health Data.

BACKGROUND: There is growing evidence of a prodromal period in multiple sclerosis (MS). A better understanding of the prodrome may facilitate prompt recognition and treatment of MS as well as narrowing of the etiologically relevant -period when searching for MS risk factors. OBJECTIVES: To explore and further delineate the MS prodrome, we used statistical learning techniques to examine associations of physician-generated diagnostic codes and prescription medication classes in the 5 years before the first demyelinating-related claim for MS cases and matched population controls. METHODS: In this matched cohort study, we accessed data from linked health administrative hospital, physician, and prescription databases from British Columbia, Canada, between 1996 and 2013. We focused on 7 medication classes previously identified as associated with the MS prodrome: urinary anti-spasmodics, glucocorticoids, muscle relaxants, anti-epileptics, dopa-derivatives, benzodiazepine, and antivertigo preparations. Diagnostic codes associated with the use of each medication class were first identified using LASSO logistic regression analyses in two-thirds of the cohort and then validated using multivariate logistic regressions in the remaining cohort. RESULTS: Our analyses included 4,862 MS cases and 22,649 controls. Although the identified diagnostic codes showed fair to good predictive performance in 6 medication classes (C-index = 0.712-0.858), these codes failed to fully explain the higher usage of these medications by the MS cases. Compared to controls of the same age, sex, and diagnostic codes, MS cases had higher odds of filling a prescription for antivertigo preparations (adjusted OR [aOR] 2.48; 95% CI 1.92-3.19), anti-epileptics (aOR 2.34; 1.90-2.90), glucocorticoids (aOR 1.76; 1.52-2.03), urinary anti-spasmodics (aOR 1.72; 1.20-2.46), and muscle relaxants (aOR 1.33; 1.13-1.56). CONCLUSIONS: We observed markedly higher use of specific medications in MS cases in the 5 years before the first demyelinating claim. The overrepresentation of specific medications in MS cases, which was not fully explained by the physician diagnoses, may represent a signature of the MS prodrome.

Content and construct validity of the Rheumatic Diseases Comorbidity Index in patients with gout.

OBJECTIVE: Gout has been associated with a large number of co-morbidities. As yet, no co-morbidity measure has been validated for use in clinical studies in gout. This study aims to evaluate the content and construct validity of the Rheumatic Diseases Comorbidity Index (RDCI) and a gout-specifically modified RDCI (mRDCI) in patients with gout. METHODS: In a cross-sectional sample of 122 patients with gout, data on co-morbidities were obtained during an interview, chart review and clinical examination. The data were used to compute the RDCI/mRDCI, a simple co-morbidity count, the Charlson Comorbidity Index (CCI) and the Functional Comorbidity Index (FCI). Content and construct validity was explored by assessing Spearman correlations between the two RDCI versions and between RDCI/mRDCI and the other co-morbidity indices, as well as demographic and clinical outcomes. In addition, we assessed the independent association between the RDCI/mRDCI and physical functioning (HAQ disability index), physical health (36-Item Short Form Health Survey) and direct health care and non-health care costs using multivariable regression analyses. RESULTS: The correlation between the RDCI and mRDCI was 0.86. Correlations between the RDCI/mRDCI and simple co-morbidity count, CCI or FCI varied between 0.72 and 0.88. Correlations with generic and gout-specific health outcomes were moderate and weak, respectively, with slightly better results for the mRDCI. Multivariable analyses showed that both the RDCI and mRDCI contributed to the variation in physical functioning, physical health and direct health care and non-health care costs. CONCLUSION: Both the RDCI and mRDCI have appropriate content and construct validity to evaluate the influence of co-morbidity on outcome in patients with gout.

Determinants of the prevalence of gout in the general population: a systematic review and meta-regression.

Studies on the occurrence of gout show a large range in estimates. However, a clear insight into the factors responsible for this variation in estimates is lacking. Therefore, our aim was to review the literature on the prevalence and incidence of gout systematically and to obtain insight into the degree of and factors contributing to the heterogeneity. We searched MEDLINE, EMBASE, and Web of Science (January 1962 to July 2012) to identify primary studies on the prevalence and incidence of gout in the general population. Data were extracted by two persons on sources of clinical heterogeneity, methodological heterogeneity, and variation in outcome reporting. Meta-analysis and meta-regression analysis were performed for the prevalence of gout. Of 1,466 articles screened, 77 articles were included, of which 71 reported the prevalence and 12 the incidence of gout. The pooled prevalence (67 studies; N = 12,226,425) based on a random effects model was 0.6% (95% CI 0.4; 0.7), however there was a high level of heterogeneity (I(2) = 99.9%). Results from a mixed-effects meta-regression model indicated that age (p = 0.019), sex (p < 0.001), continent (p < 0.001), response rate (p = 0.016), consistency in data collection (p = 0.002), and case definition (p < 0.001) were significantly associated with gout prevalence and jointly accounted for 88.7% of the heterogeneity. The incidence in the total population ranged from 0.06 to 2.68 per 1,000 person-years. In conclusion, gout is a common disease and the large variation in the prevalence data on gout is explained by sex, continent on which the study was performed, and the case definition of gout.

The cross-sectional association between uric acid and atherosclerosis and the role of low-grade inflammation: the CODAM study.

OBJECTIVES: The aims of this study were to investigate (i) associations between uric acid and prevalent cardiovascular disease (CVD), ankle-arm blood pressure index (AAIx) and carotid intima-media thickness (CIMT) in the total population and in predefined subgroups according to glucose metabolism status and (ii) the extent to which these associations are explained by low-grade inflammation. METHODS: Cross-sectional analyses were conducted among 530 individuals [60.6% men, mean age 58.9 years (s.d. 6.9), 52.6% normal glucose metabolism (NGM)] at increased risk of CVD from the Cohort of Diabetes and Atherosclerosis Maastricht study. A low-grade inflammation score was computed by averaging the z-scores of eight inflammation markers [CRP, TNF-α, IL-6, IL-8, serum amyloid A, intercellular adhesion molecule 1 (ICAM-1), ceruloplasmin and haptoglobin]. RESULTS: After adjustment for traditional CVD risk factors, plasma uric acid (per s.d. of 81 µmol/l) was associated with CVD in individuals with NGM [odds ratio (OR) = 1.66, 95% CI 1.06, 2.58] but not with disturbed glucose metabolism (DGM) (OR = 0.81, 95% CI 0.55, 1.19, P interaction = 0.165). Uric acid was associated with CIMT in the total population (ß = 0.024, 95% CI 0.007, 0.042) and slightly more strongly in individuals with NGM (ß = 0.030, 95% CI 0.006, 0.054) than DGM (ß = 0.018, 95% CI -0.009, 0.044, P interaction = 0.443). There was no association between uric acid and AAIx in any group (P interaction = 0.058). Uric acid was associated with low-grade inflammation in the total population (ß = 0.074, 95% CI 0.013, 0.134, P interaction = 0.737). Adding low-grade inflammation to the models did not attenuate any of the associations. CONCLUSION: The associations for uric acid with CIMT, and with CVD in NGM only, were not explained by low-grade inflammation. A difference in the strength of the associations between individuals with NGM and DGM was suggested.

Multiple sclerosis disease-modifying drug use by immigrants: a real-world study.

Little is known about disease-modifying drug (DMD) initiation by immigrants with multiple sclerosis (MS) in countries with universal health coverage. We assessed the association between immigration status and DMD use within 5-years after the first MS-related healthcare encounter. Using health administrative data, we identified MS cases in British Columbia (BC), Canada. The index date was the first MS-related healthcare encounter (MS/demyelinating disease-related diagnosis or DMD prescription filled), and ranged from 01/January/1996 to 31/December/2012. Those included were ≥ 18 years old, BC residents for ≥ 1-year pre- and ≥ 5-years post-index date. Persons becoming permanent residents 1985-2012 were defined as immigrants, all others were long-term residents. The association between immigration status and any DMD prescription filled within 5-years post-index date (with the latest study end date being 31/December/2017) was assessed using logistic regression, reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We identified 8762 MS cases (522 were immigrants). Among immigrants of lower SES, odds of filling any DMD prescription were reduced, whereas they did not differ between immigrants and long-term residents across SES quintiles (aOR 0.96; 95%CI 0.78-1.19). Overall use (odds) of a first DMD within 5 years after the first MS-related encounter was associated with immigration status.

Sex and age differences in the Multiple Sclerosis prodrome.

Background and objectives: Little is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome. Methods: This was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event ("administrative cohort;" n = 6,863) or MS symptom onset ("clinical cohort;" n = 966) were compared to age-, sex- and geographically-matched controls (n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (< 30, 30-49, ≥50 years). Results: In the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P < 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries < 30/30-49/≥50: aRR = 1.16/1.39/2.12, P < 0.01; infections 30-49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30-49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular < 30/30-49/≥50: aRR = 1.56/1.39/1.18, P < 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P < 0.01) and ≥50-year-olds (< 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, < 50-years-old (< 30/30-49/≥50: aRR = 2.25/2.20/1.55, P < 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance (P ≥ 0.05). Discussion: Sex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation.

Large epidemiologic studies of gout: challenges in diagnosis and diagnostic criteria.

Large epidemiologic studies of gout can improve insight into the etiology, pathology, impact, and management of the disease. Identification of monosodium urate monohydrate crystals is considered the gold standard for diagnosis, but its application is often not possible in large studies. Therefore, under such circumstances, several proxy approaches are used to classify patients as having gout, including ICD coding in several types of databases or questionnaires that are usually based on the existing classification criteria. However, agreement among these methods is disappointing. Moreover, studies use the terms acute, recurrent, and chronic gout in different ways and without clear definitions. Better definitions of the different manifestations and stages of gout may provide better insight into the natural course and burden of disease and can be the basis for valid approaches to correctly classifying patients within large epidemiologic studies.

A systematic review of morbidities suggestive of the multiple sclerosis prodrome.

INTRODUCTION: The identification of a prodromal phase in multiple sclerosis (MS) could have major implications for earlier recognition and management of MS. The authors conducted a systematic review assessing studies of morbidities before, or at, MS onset or diagnosis.Areas covered: Two independent reviewers searched Medline, Embase, Psycinfo and CINAHL from inception to February 8th, 2019. To be eligible, studies had to be published in English and report the relative occurrence of at least one morbidity or symptom before, or at, MS onset or diagnosis among MS cases in comparison to a control group not known to have MS. Findings were narratively synthesized. Study quality was assessed using the Newcastle-Ottawa scale (NOS, maximum score 9).Expert opinion: Twenty-nine studies were included, which comprised 83,590 MS cases and 396,343 controls. Most were case-control studies (25/29), 8/29 were of high quality (NOS≥8) and 19/29 examined the period before MS symptom onset. Most studies assessing anxiety, depression, migraine and lower cognitive performance found these conditions to be more prevalent before MS onset or diagnosis relative to controls. There was limited evidence to implicate other conditions. Thus, there is evidence that anxiety, depression, migraine and lower cognitive performance form part of the MS prodrome.

MRI utilization during the diagnostic and post-diagnostic phases in multiple sclerosis.

BACKGROUND: Magnetic resonance imaging (MRI) plays an important role in the diagnosis and monitoring of people with multiple sclerosis (MS). MRI rates in MS populations are poorly understood. Although Canada has universal health care, socioeconomic status (SES) is associated with MRI use. It is unknown if such disparities persist for specific conditions such as MS when care is managed centrally, or how disease-specific characteristics may affect MRI use. OBJECTIVE: To assess magnetic resonance imaging (MRI) use in MS and control participants and its association with participant characteristics. METHODS: Using administrative and clinical data from Manitoba, Canada, we assessed MRI use in MS and control participants during the five years pre-index (first demyelinating claim in the administrative cohort or symptom onset in the clinical cohort), between index and diagnosis (third demyelinating claim in the administrative cohort or diagnosis date in the clinical cohort), and the five years post-diagnosis. Using zero-inflated Poisson regression, we assessed associations between participant characteristics and index year, and MRI use during these three phases. RESULTS: We included 2,763 MS cases and 13,815 controls in the administrative cohort, and 961 MS cases in the clinical cohort. MRI use increased over time, but more in cases than in controls. Pre-index, individuals aged <50 years at the index date had lower MRI rates than those aged ≥50 years. Sex, socioeconomic status and region were not associated with MRI use. Disease-modifying therapy use was associated with 25% more MRIs post-diagnosis (adjusted rate ratio: 1.25; 95%CI:1.09-1.43) in the clinical cohort. CONCLUSION: Our findings suggest equity of access to MRI across sex, region and socioeconomic status in MS.

Higher health care use before a clinically isolated syndrome with or without subsequent MS.

BACKGROUND: To establish whether a unique multiple sclerosis (MS) prodrome exists by comparing health care utilization in the five-year period before initial presentation with optic neuritis (ON) or transverse myelitis (TM) among those who were and were not subsequently diagnosed with MS. METHODS: Using population-based administrative health data we conducted a retrospective cohort study in three Canadian provinces. We identified individuals with a clinically isolated syndrome (ON or TM), who were eventually diagnosed with MS (CIS-MS) or not (CIS-non MS), and a control cohort matched on age, sex and region without a CIS. We compared rates of hospitalization, physician services use and prescription drug use in the five years before the first ON or TM claim (labeled years -1,-2,-3,-4,-5) using negative binomial regression models adjusted for age, sex, socioeconomic status and index year. RESULTS: We identified 1,155 CIS-MS cases, 20,638 CIS-non MS cases, and 108,726 matched controls. Compared to matched controls, the CIS-MS cohort had a higher hospitalization rate (years -5 and -1), physician visits (all years) and prescription drug use (years -4 and -1). Compared to matched controls, the CIS-non MS cohort had a higher rate of hospitalizations (all years), physician visits (all years) and prescription drug use (all years). CONCLUSION: Health care use was higher in individuals with a CIS than without a CIS in the five years before an incident demyelinating event, regardless of whether they were subsequently diagnosed with MS. This suggests that there is a prodromal period before CIS which is not unique to MS.

Mining healthcare data for markers of the multiple sclerosis prodrome.

BACKGROUND: Previous studies suggest the existence of a prodromal period in multiple sclerosis, but little is known about the phenotypic characteristics. This study aims to characterize the multiple sclerosis (MS) prodrome using data mining analytics in the healthcare setting. METHODS: We identified people with MS and matched general population controls using health administrative data in two Canadian provinces (British Columbia and Saskatchewan). Using a training dataset (66.6% of British Columbia's cohort), L1 penalized logistic regression models were fitted to predict MS from physician and hospital encounters (via International Classification of Diseases [ICD] codes) and prescriptions filled (as drug classes) during the five years before the MS case's first demyelinating event. Internal and external validation of identified predictors was performed using logistic regression on the remaining British Columbia (33.4%) and Saskatchewan data. Adjusted odds ratios (aORs) and Area under the Curve (AUC) metrics for the models' predictive performance were reported. RESULTS: We identified 8,669 MS cases and 40,867 controls. Good predictive performance was observed for physician data (internal/external validation AUC = 0.81/0.79). Physician-generated ICD codes that were associated with MS and validated in both provinces included disorders of the central and peripheral nervous system, disorders of the eye, and cerebrovascular disease (aOR = 1.3-7.0). Overall, hospital and prescription data showed very poor and poor predictive performance (internal/external validation AUCs = 0.54/0.55 and 0.66/0.61, respectively). However, hospitalizations related to the urinary system or spinal cord diseases, or prescriptions for urinary antispasmodics or anti-vertigo preparations, were associated with 2 to 3-fold higher odds of MS (aOR = 2.3-3.3). CONCLUSIONS: Findings provide insight into the clinical characteristics of the MS prodrome. Diagnostic codes from physician encounters were capable of differentiating between MS cases and controls.

Identifying optic neuritis and transverse myelitis using administrative data.

OBJECTIVE: We aimed to validate administrative case definitions to identify individuals with optic neuritis (ON) or transverse myelitis (TM), and to distinguish which of these individuals had a monophasic presentation versus multiple sclerosis (MS). METHODS: Using population-based administrative (health claims) data from Manitoba, Canada, we developed case definitions for ON and TM, and distinguished individuals who had monophasic presentations (ON-nonMS, TM-nonMS) versus those later diagnosed with MS (ON-MS, TM-MS). We compared performance of these case definitions to diagnoses based on medical records review in a reference cohort (n = 1251) using sensitivity, specificity, positive predictive value and negative predictive value. We estimated the annual incidence of these conditions for a three-year period (2011-2013). RESULTS: When compared to medical records, using ≥1 physician visit, the case definition for ON had good sensitivity (88.5%), and specificity (82.7%) whereas the case definition for TM had low sensitivity (25.9%) and higher specificity (89.0%). Findings for the other case definitions tested were: ON-MS (sensitivity: 84.1%, specificity: 83.9%), ON-nonMS (sensitivity: 66.7%, specificity 98.5%), TM-MS (sensitivity: 22.2%, specificity: 90.4%), and TM-nonMS (sensitivity: 3.7%, specificity: 99.7%). After applying the ON and TM case definitions to administrative data, the average annual incidence of ON over the period 2011-2013 was 75.9 per 100,000 person-years (95%CI: 72.8, 79.1) and of TM was 18.3 per 100,000 person-years (95%CI: 16.8, 19.8). CONCLUSION: Administrative data can be used to identify individuals with incident ON and TM, and to distinguish those with monophasic syndromes from those with an incident presentation of MS.

Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study.

BACKGROUND: Degenerative processes in neurodegenerative diseases can start years before clinical manifestation. We aimed to establish whether a multiple sclerosis prodromal period exists by examining patterns of health-care use before a first demyelinating event. METHODS: In this matched cohort study, we used data from linked health administrative and clinical databases from four Canadian provinces (British Columbia, Saskatchewan, Manitoba, and Nova Scotia) to compare hospital, physician, and prescription use data from people with multiple sclerosis and matched general population controls in the 5 years before the first demyelinating disease claim (health administrative index date) or clinically reported symptom onset (clinical index date). Rate ratios (RRs) were estimated using negative binomial regression and combined across provinces using random effect models. The primary outcome was all-cause use of health care during each of the 5 years before the health administrative or clinical index date. FINDINGS: The health administrative cohort included 14 428 multiple sclerosis cases and 72 059 matched controls for whom data were available between April, 1984, and April, 2014. Annual health-care use increased steadily between 5 years and 1 year before the first demyelinating disease claim in people with multiple sclerosis compared with controls (from RR 1·26 [95% CI 1·16-1·36] to 1·78 [1·50-2·10] for hospital admissions; from 1·24 [1·16-1·32] to 1·88 [1·72-2·07] for physician claims; and from 1·23 [1·06-1·41] to 1·49 [1·41-1·59] for prescriptions, assessed as drug classes). Similar patterns for physician claims and prescriptions were observed in the cohort with available clinical symptom onset (3202 individuals with multiple sclerosis and 16 006 controls), although the differences in use in each of the 5 years mostly did not reach statistical significance. INTERPRETATION: More frequent use of health care in patients with multiple sclerosis than in controls in the 5 years before a first demyelinating event, according to health administrative data, suggests the existence of a measurable multiple sclerosis prodrome. These findings have clinical and research implications, including the establishment of an earlier window of opportunity to identify and potentially treat multiple sclerosis. FUNDING: National Multiple Sclerosis Society.

Cost of illness and determinants of costs among patients with gout.

OBJECTIVE: To estimate costs of illness in a cross-sectional cohort of patients with gout attending an outpatient rheumatology clinic, and to evaluate which factors contribute to higher costs. METHODS: Altogether, 126 patients with gout were clinically assessed. They completed a series of questionnaires. Health resource use was collected using a self-report questionnaire that was cross-checked with the electronic patient file. Productivity loss was assessed by the Work Productivity and Activity Impairment Questionnaire, addressing absenteeism and presenteeism. Resource use and productivity loss were valued by real costs, and annual costs per patient were calculated. Factors contributing to incurring costs above the median were explored using logistic univariable and multivariable regression analysis. RESULTS: Mean (median) annual direct costs of gout were €5647 (€1148) per patient. Total costs increased to €6914 (€1279) or €10,894 (€1840) per patient per year when adding cost for absenteeism or both absenteeism and presenteeism, respectively. Factors independently associated with high direct and high indirect costs were a positive history of cardiovascular disease, functional limitations, and female sex. In addition, pain, gout concerns, and unmet gout treatment needs were associated with high direct costs. CONCLUSION: The direct and indirect costs-of-illness of gout are primarily associated with cardiovascular disease, functional limitations, and female sex.

Association between serum uric acid, aortic, carotid and femoral stiffness among adults aged 40-75 years without and with type 2 diabetes mellitus: The Maastricht Study.

OBJECTIVE: Arterial stiffness may be a mechanism to explain the association between uric acid and cardiovascular disease. We aimed to analyse associations between serum uric acid and regional and local arterial stiffness, and assess potential differences related to sex and glucose metabolism status. METHODS: A cross-sectional study was performed in 614 adults [52.6% men; mean age 58.7 ±â€Š8.5 years; 23.2% type 2 diabetes mellitus (by design)] from The Maastricht Study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), distensibility, and compliance coefficient of the carotid and femoral artery, and carotid artery Young's elastic modulus. RESULTS: Higher uric acid (per SD of 74 µmol/l) was associated with greater stiffness indicated by a significantly higher cfPWV [ß = 0.216 (95% confidence interval 0.061, 0.372); P = 0.006] and lower carotid distensibility coefficient [ß = -0.633 (95% confidence interval -1.099, -0.166); P = 0.008] after adjustment for sex, age, and glucose metabolism status. Associations lost significance after adjusting for mean arterial pressure, BMI, waist, smoking status, heart rate, total : high-density lipoprotein cholesterol ratio, triglycerides, estimated glomerular filtration rate, use of lipid-lowering, antihypertensive, and diabetes medication, and use of secondary uricosurics. No associations were found between uric acid and carotid compliance coefficient, carotid Young's elastic modulus, or stiffness of the femoral artery. A significant interaction (P < 0.10) with glucose metabolism status was found for cfPWV. However, none of the stratified associations were significant. There was no interaction with sex. CONCLUSION: Uric acid was not significantly associated with stiffness of the aorta, or the carotid or femoral artery among adults aged 40-75 years without and with type 2 diabetes mellitus.

Uric acid and skin microvascular function: the Maastricht study.

OBJECTIVE: Microvascular dysfunction has been suggested as a possible underlying mechanism for the association between uric acid and various diseases, such as hypertension, renal disease and cardiomyopathies. We therefore analysed the association between serum uric acid and skin microvascular function, a model of generalized microvascular function. METHODS: A cross-sectional study was performed in 610 individuals [51.8% men; mean age 58.7 ±â€Š8.6 years; 23.6% with type 2 diabetes (by design)] from The Maastricht Study. We assessed skin capillary density (capillaries/mm) by capillaroscopy at baseline, after 4 min of arterial occlusion, and after 2 min of venous congestion. Capillary recruitment after arterial occlusion and during venous congestion was expressed as the absolute change in capillary density after recruitment and as the percentage change in capillary density from baseline. RESULTS: Crude linear regression analyses showed that serum uric acid [per +1 standard deviation (SD) of 74 µmol/l] was not associated with baseline capillary density [ß = -0.21 (95% confidence interval, 95% CI -1.61 to 1.19) P = 0.765], while an inverse association was found between uric acid and absolute change in capillary density after arterial occlusion [ß = -1.15 (95% CI -2.36 to 0.06) P = 0.062] and during venous congestion [ß = -1.41 (95% CI -2.68 to -0.14) P = 0.029]. However, after adjustment for sex, age and glucose metabolism status, these associations were no longer statistically significant. In addition, we found no association between uric acid and percentage capillary recruitment after arterial occlusion [ß = -1.66 (95% CI -3.97 to 0.65) P = 0.159] or during venous congestion [ß = -2.02 (95% CI -4.46 to 0.42) P = 0.104] in unadjusted analyses; multivariable analyses gave similar results. CONCLUSION: These results do not support the hypothesis that generalized microvascular dysfunction (as estimated in skin microcirculation) is the underlying mechanism for the association between uric acid and cardiovascular and renal diseases. The possibility that uric acid is associated with microvascular dysfunction in specific end-organs, for example heart or kidney, needs further investigation.