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Repeated measurements of serum urate and mortality: a prospective cohort study of 152,358 individuals over 8 years of follow-up.

ABSTRACT: BACKGROUND:Longitudinal evidence on change of serum urate level with mortality risk is limited as prior studies have a measurement of serum urate at a single time point. Further, the combined effect of serum urate and systemic inflammation on mortality is unknown. METHODS:We conducted a prospective cohort study of 152,358 participants (122,045 men and 30,313 women) with repeated measurements of serum urate in 2006, 2008, 2010, and 2012 (107,751 participants had all four measurements of serum urate). We used the Cox proportional hazard model to examine the association between cumulative average and changes in serum urate with mortality. The combined effect of serum urate and systemic inflammation was determined by testing the interaction of serum urate and high-sensitive C-reactive protein (hs-CRP) in relation to mortality risk. RESULTS:During a median follow-up of 8.7 (interquartile range 6.3-9.2) years, we identified 7564 all-cause deaths, 1763 CVD deaths, 1706 cancer deaths, and 1572 other deaths. We observed U-shaped relationships of cumulative average serum urate with all-cause mortality, cardiovascular mortality, and other mortalities. Compared with participants with stable serum urate, those with greater increases in serum urate had a 1.7-fold elevated mortality (hazard ratio (HR) = 1.66, 95% confidence interval (CI) = 1.49-1.84), and those with decreased serum urate had a 2-fold elevated mortality risk (HR = 2.14, 95% CI 1.93-2.37). Participants with both hyperuricemia and hs-CRP had 1.6 times higher mortality, compared with those with low serum urate and hs-CRP levels (HR = 1.56, 95% CI 1.37-1.76). CONCLUSIONS:We observed a U-shaped relationship of long-term cumulative average serum urate with all-cause mortality, cardiovascular mortality, and other mortalities. Compared with participants with relatively stable serum urate levels, a greater increase or decrease in serum urate was associated with elevated mortality. Participants with both hyperuricemia and high systemic inflammation had the greatest mortality risk compared with those with low serum urate and low hs-CRP levels.

SUBMITTER: Li S

PROVIDER: S-EPMC7160947 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Socioeconomic inequalities in mortality can be explained by different groups of risk factors. However, little is known whether repeated measurement of risk factors can provide better explanation of socioeconomic inequalities in health. Our study examines the extent to which relative educational and income inequalities in mortality might be explained by explanatory risk factors (behavioral, psychosocial, biomedical risk factors and employment) measured at two points in time, as compared to one measurement at baseline.From the Norwegian total county population-based HUNT Study (years 1984-86 and 1995-1997, respectively) 61 513 men and women aged 25-80 (82.5% of all enrolled) were followed-up for mortality in 25 years until 2009, employing a discrete time survival analysis. Socioeconomic inequalities in mortality were observed. As compared to their highest socioeconomic counterparts, the lowest educated men had an OR (odds ratio) of 1.41 (95% CI 1.29-1.55) and for the lowest income quartile OR = 1.59 (1.48-1.571), for women OR = 1.35 (1.17-1.55), and OR = 1.40 (1.28-1.52), respectively. Baseline explanatory variables attenuated the association between education and income with mortality by 54% and 54% in men, respectively, and by 69% and 18% in women. After entering time-varying variables, this attainment increased to 63% and 59% in men, respectively, and to 25% (income) in women, with no improvement in regard to education in women. Change in biomedical factors and employment did not amend the explanation.Addition of a second measurement for risk factors provided only a modest improvement in explaining educational and income inequalities in mortality in Norwegian men and women. Accounting for change in behavior provided the largest improvement in explained inequalities in mortality for both men and women, as compared to measurement at baseline. Psychosocial factors explained the largest share of income inequalities in mortality for men, but repeated measurement of these factors contributed only to modest improvement in explanation. Further comparative research on the relative importance of explanatory pathways assessed over time is needed.

Project description:Background and aimsThe concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0-10, 10-20, 20-30 and >30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD.MethodsData was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time.ResultsSubjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7-17; 25-75 percentiles, minimum 2), with median 6 (4-9; 25-75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age.ConclusionOur study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.

Project description:PurposeTo assess longer-term patterns of glaucoma medication adherence and identify whether patterns established during the first year of medication use persist during 3 subsequent years of follow-up.DesignRetrospective, longitudinal cohort analysis.ParticipantsBeneficiaries aged ≥40 years who were enrolled in a United States (US)-managed care plan for ≥7 years between 2001 and 2012 and newly diagnosed and treated for open-angle glaucoma.MethodsFor each enrollee, we quantified medication adherence using the medication possession ratio. Group-based trajectory modeling (GBTM) was applied to identify patterns of adherence for 1 and 4 years of follow-up. The percent of beneficiaries who remained in the same trajectory group in the 1- and 4-year models was tabulated to evaluate group stability. Factors impacting adherence at 1 and 4 years were identified using regression analyses.Main outcome measuresPatterns of glaucoma medication adherence.ResultsOf the 1234 eligible beneficiaries, GBTM identified 5 distinct glaucoma medication adherence patterns in both the 1-year and 4-year follow-up periods. These groups were as follows: (1) never adherent after their index prescription fill (7.5% and 15.6% of persons in the 1- and 4-year models, respectively); (2) persistently very poor adherence (14.9% and 23.4% of persons in the 1- and 4-year models, respectively); (3) declining adherence (9.5% and 9.1% of persons in the 1- and 4-year models, respectively); (4) persistently moderate adherence (48.1% and 37.0% of persons in the 1- and 4-year models, respectively); and (5) persistently good adherence (20.0% and 15.0% of persons in the 1- and 4-year models, respectively). More than 90% of beneficiaries in the 4 groups with the worst and best adherence patterns (groups 1, 2, 3, 5) maintained their patterns from their first year throughout their 4 years of follow-up. Those with persistently moderate adherence (group 4), the largest group, were most likely to change groups from 1 to 4 years of follow-up. Persons with the best adherence over 4 years were more likely to be white, to be older, to earn >$60 000/year, and to have more eye care visits (P < 0.05 for all comparisons). Those with a higher initial copayment cost had lower adherence rates (β = -0.06/dollar, P = 0.03).ConclusionsFor most patients who were newly prescribed glaucoma medications, adherence patterns observed in the first year of treatment reflect adherence patterns over the subsequent 3 years. Investing resources in both identifying and helping patients with suboptimal adherence patterns over the first year may have a large impact on longer-term adherence.

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Repeated measurements of serum urate and mortality: a prospective cohort study of 152,358 individuals over 8 years of follow-up.

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