Hyperuricaemia-associated all-cause mortality risk effect is increased by non-impaired kidney function - Is renal hyperuricaemia less dangerous?

BACKGROUND: Both hyperuricaemia and chronic kidney disease are known mortality risk factors. This study examined the modifying effect of renal function on hyperuricaemia-associated mortality risk, which is an issue that has not been studied before. METHODS: Data on levels of serum uric acid (SUA), creatinine, cystatin C and other variables of persons aged 52-76 years were collected. Persons with SUA >410 µmol/L (75th percentile) were classified as clearly hyperuricaemic and persons with eGFR of ≤67 ml/min (25th percentile) as having reduced kidney function. RESULTS: Reduced kidney function was associated with higher mortality in both SUA groups. When compared to individuals with SUA ≤410 µmol/L and eGFR >67 ml/min the hazard ratio (HR) for all-cause mortality was 1.53 (95 % CI: 1.26-1.84) in clearly hyperuricaemic persons with reduced kidney function, 1.26 (95 % CI: 1.02-1.55) in clearly hyperuricaemic persons with eGFR of >67 ml/min and 1.15 (95 % CI: 0.96-1.39) in persons with SUA ≤410 µmol/L and reduced kidney function. The HR for hyperuricaemia-related premature death was lowest in individuals with reduced eGFR, and it rose strikingly as the eGFR increased above 90 ml/min. CONCLUSIONS: Reduced kidney function is a risk factor for mortality both in individuals with normal and elevated SUA. The hyperuricaemia-associated mortality risk is remarkably higher in individuals with normal kidney function than in individuals with reduced kidney function. Presumably overproduction of uric acid (metabolic hyperuricaemia) is a separate and more deleterious entity than hyperuricaemia resulting from reduced renal excretion of uric acid (renal hyperuricaemia).

Hyperuricaemia: prevalence and association with mortality in an elderly Finnish population.

OBJECTIVE: To establish the prevalence of hyperuricaemia in an elderly Finnish cohort and to assess its association with comorbidities and mortality. DESIGN: Prospective cohort study. SETTING: Good Ageing in Lahti Region study, Finland 2002-2012 (mortality data analysed until 2018). PARTICIPANTS: 2673 participants (mean age 64 years; 47% men). PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of hyperuricaemia in the study population was detected. Associations between hyperuricaemia and mortality were assessed using multivariable adjusted Cox proportional hazards models. METHODS: Data from a prospective, population-based study of elderly people (52-76 years) in the Lahti region, Finland, were used. Information on serum uric acid (SUA) levels as well as several other laboratory variables, comorbidities, lifestyle habits and socioeconomic factors was collected, and the association between SUA level and mortality in a 15-year follow-up period was analysed. RESULTS: Of 2673 elderly Finnish persons included in the study 1197 (48%) were hyperuricaemic. Hyperuricaemia was extremely prevalent in men (60%). There was an association between elevated SUA and mortality which remained after adjustment for potential confounding factors (age, gender, education, smoking status, body mass index, hypertension and dyslipidaemia). The adjusted HR for all-cause mortality among clearly hyperuricaemic individuals with SUA≥420 µmol/L compared with normouricaemic individuals (SUA<360 µmol/L) was 1.32 (95% CI 1.05 to 1.60) in women and 1.29 (95% CI 1.05 to 1.60) in men. In slightly hyperuricaemic individuals (SUA 360-420 µmol/L) the corresponding HRs were 1.03 (95% CI 0.78 to 1.35) and 1.11 (95% CI 0.89 to 1.39). CONCLUSIONS: Hyperuricaemia is very prevalent in the elderly Finnish population and is independently associated with increased mortality.

Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Impact of Inflammation and Antirheumatic Treatment.

Patients with rheumatoid arthritis (RA) are at approximately 1.5-fold risk of atherosclerotic cardiovascular disease (CVD) compared with the general population, a phenomenon resulting from combined effects of traditional CVD risk factors and systemic inflammation. Rheumatoid synovitis and unstable atherosclerotic plaques share common inflammatory mechanisms, such as expression of proinflammatory cytokines interleukin (IL)-1, tumour necrosis factor (TNF)-α and IL-6. RA patients are undertreated in terms of CVD prevention, and structured CVD prevention programmes are warranted. Alongside management of traditional risk factors, suppressing systemic inflammation with antirheumatic medication is fundamental for the reduction of CVD risk among this high-risk patient group. Many antirheumatic drugs, especially methotrexate, TNF-α-inhibitors and IL-6-inhibitors are associated with reduced risk of CVD in observational studies among RA patients, but randomised controlled trials with hard CVD endpoints are lacking. In patients without rheumatic disease, anti-inflammatory therapies targeting nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin domain-containing protein 3 inflammasome and the IL-1/IL-6 pathway arise as potential therapies after an atherosclerotic CVD event.