1,720,999 research outputs found
Uric Acid and Estimate of Renal Function. Let's Stick Together
No full textHyperuricaemia refers to an abnormally high concentration of uric acid in serum [ 1
], typically defined as >7 mg/dL (416 μmol/L) in men and >6 mg/dL in women [ 1
]. Mean serum uric acid has increased progressively over the last century in many populations and the prevalence of hyperuricemia increases with age and is higher in men than premenopausal women [ 1
], as oestrogen increases urate excretion by the kidneys. Hyperuricaemia is usually discussed in the context of gout, but it is increasingly recognised that serum uric acid values >5.0 mg/dL (men) or 4.5 mg/dL (postmenopausal women) are clinically relevant markers of other diseases including hypertension, chronic kidney disease (CKD), hypertriglyceridemia, obesity, atherosclerotic heart disease, and metabolic syndrome [ 1
, 2
]. The threshold of uric acid associated with the risk of cardiovascular and renal disease is significantly lower than that suggested for the diagnosis of gout [ 3
] while only slight increases in the levels of serum uric acid are associated with poorer blood pressure control [ 4
] and an increase RR of cardiovascular disease beyond the SCORE risk calculation [ 5
]. However, a large body of evidence links hyperuricaemia with the decline in renal function and to the increase in serum creatinine. The uric acid produced by the body is largely excreted by the kidney and any abnormality in the renal function can result in a significant reduction in urate excretion with a consequent increase in serum urate levels [ 6
]. This would clearly support the hypothesis that the plasma levels of uric acid are directly related to serum creatinine and the negative prognostic impact described for hyperuricemia is actually an indirect effect of renal dysfunction/CKD, a well-known risk factor for cardiovascular diseases. This could explain the unfavourable effects of hyperuricemia in patients with heart failure where the decline in cardiac function and the extensive use of diuretics would results in a decrease in GFR with the consequent development of hyperuricemia. This elementary sequence is contradicted by the “paradoxical” results of a couple of large clinical trials in patients with heart failure [ 7
, 8
] where the hazard ratio of all-cause and cardiovascular mortality is significantly higher in patients with preserved renal function. This evidence clearly supports the importance of uric acid production over under excretion for cardiovascular risk and clearly emphasizes the possibility that the prognostic meaning of hyperuricemia can be actually estimated by considering also renal function. An increase in uric acid levels associated with normal or slightly impaired renal function is highly suggestive of abnormalities in the urate production or tubular re-absorption that can directly and indirectly contribute to the dangerous vascular effects of hyperuricemia
Does gouty nephropathy exist, and is it more common than we think?
No full textGout is present in one third of subjects with CKD but is usually an exclusion criterion in clinical trials investigating the role of uric acid in kidney disease. Bardin et al. report that one third of gouty subjects have hyperechoic medullas by ultrasound (consistent with crystalline deposits) that correlates with increased risk for hypertension and kidney dysfunction and which were not observed in >500 controls. If validated, a "gouty nephropathy" from microcrystalline deposits could be an important, unrecognized cause of CKD
Advances in pharmacotherapies for hyperuricemia
No full textIntroduction: Hyperuricemia is an overlooked cardiovascular and renal risk factor. Epidemiological and genetic studies have shown an independent role of uric acid in the risk of coronary artery disease, heart failure, chronic kidney disease, and cardiovascular mortality. Treatment options include xanthine oxidase inhibitors, uricosuric medications, and the recombinant uricases. Whether to treat asymptomatic hyperuricemia, and to which target, remains debated. However, the results of recent trials and meta-analysis seem to support this therapeutic strategy. Areas covered: In the present review, we summarized current therapeutic indications and options for the treatment of symptomatic and asymptomatic hyperuricemia. Furthermore, we searched the recent literature (last 5 years: 2018 to 2022) to report the results of randomized controlled trials and meta-analysis on cardiovascular and nephroprotective effects of hypouricemic agents. Expert opinion: Future large well-designed clinical trials on the role of hypouricemic agents in nephroprotection and cardiovascular prevention and treatment are warranted and may extend their indications and use, with a direct impact on morbidity and mortality. Differentiating between hyperproducing and hypoexcreting phenotypes may help designing future trials improving the consistency of results. Finally, medications with cardio and nephroprotective properties have shown to reduce serum uric acid levels and may be used in patients with hyperuricemia and other cardiovascular complications
Uric Acid and Hypertension: Prognostic Role and Guide for Treatment
Full text linkThe relationship between serum uric acid (SUA) and hypertension has been a subject of increasing interest since the 1870 discovery by Frederick Akbar Mahomed. Several epidemiological studies have shown a strong association between high SUA levels and the presence or the development of hypertension. Genetic analyses have found that xanthine oxidoreductase (XOR) genetic polymorphisms are associated with hypertension. However, genetic studies on urate transporters and Mendelian randomization studies failed to demonstrate a causal relationship between SUA and hypertension. Results from clinical trials on the role of urate-lowering therapy in the management of patients with hypertension are not uniform. Our study sought to analyze the prognostic and therapeutic role of SUA in the hypertensive disease, from uric acid (UA) biology to clinical trials on urate-lowering therapies
Gender-Specific Medicine in the European Society of Cardiology Guidelines from 2018 to 2023: Where Are We Going?
Full text linkBackground/Objectives: Evidence-based medicine (EBM) shapes most clinical guidelines. Although the advent of EBM marked a significant advancement, failure to include sex differences in the study design and analysis of most trials leads to an under-representation of gender-specific medicine (GM) in EBM-directed guidelines. In this review, we evaluated how the topic of GM was developed in the guidelines produced by the European Society of Cardiology (ESC) from 2018 to 2023. Methods: Two independent reviewers evaluated 24 ESC guidelines. Significant mentions of GM were counted and divided between epidemiology, diagnosis, and therapeutics. The qualitative and semi-quantitative analysis of information relating to GM was performed. Data on the number of citations of papers with a title concerning GM and the prevalence and role of women in guidelines’ authorship were also analyzed. Results: Less than 50% of guidelines had a section dedicated to GM. Only nine guidelines were led by a woman, and 144/567 authors were female. In the most recent guidelines and in those with at least 30% of female authors, there was an increased mention of GM. On average, guidelines had four significant mentions of GM regarding epidemiology, two regarding diagnosis, and one regarding therapy. Articles with titles concerning GM made up, on average, 1.5% of the total number of citations. Conclusions: Although sex differences play a significant role in most clinical scenarios, ESC guidelines still do not sufficiently account for this. The problem does not seem to solely lie in the guidelines, but in the lack of attention to GM in research needed for their preparation
The Role of Xanthine Oxidase in Pregnancy Complications: A Systematic Review
Full text linkXanthine oxidoreductase (XOR) is an enzyme involved in the oxidation of hypoxanthine and xanthine to uric acid. XOR has two isoforms: xanthine dehydrogenase and xanthine oxidase (XO). XO plays a major role in oxidative stress, causing the formation of reactive oxygen species. In the present study, we aimed to summarize the evidence on the association between XO and pregnancy complications. The PRISMA checklist guided the reporting of the data. We conducted systematic searches in the PubMed and Web of Science databases to identify all human studies investigating XO in pregnancy diseases up to June 2024. A total of 195 references have been identified and 14 studies were included. Most studies focused on women with PE and GD. Overall, all the included studies found a statistically significant increase in maternal, placental, and/or fetal XO levels, activity, or tissue expression in women with pregnancy complications, compared to those with uncomplicated pregnancies. Although promising, the quality and dimension of the included studies do not allow for a definitive answer to the question of whether XO may play a crucial role in pregnancy complications. Future studies are warranted to confirm if XO could represent a prognostic and therapeutic marker in pregnancy complications and their impact on long-term maternal and offspring cardiovascular health
The Gut Microbiota and Vascular Aging: A State-of-the-Art and Systematic Review of the Literature
Full text linkThe gut microbiota is a critical regulator of human physiology, deleterious changes to its composition and function (dysbiosis) have been linked to the development and progression of cardiovascular diseases. Vascular ageing (VA) is a process of progressive stiffening of the arterial tree associated with arterial wall remodeling, which can precede hypertension and organ damage, and is associated with cardiovascular risk. Arterial stiffness has become the preferred marker of VA. In our systematic review, we found an association between gut microbiota composition and arterial stiffness, with two patterns, in most animal and human studies: a direct correlation between arterial stiffness and abundances of bacteria associated with altered gut permeability and inflammation; an inverse relationship between arterial stiffness, microbiota diversity, and abundances of bacteria associated with most fit microbiota composition. Interventional studies were able to show a stable link between microbiota modification and arterial stiffness only in animals. None of the human interventional trials was able to demonstrate this relationship, and very few adjusted the analyses for determinants of arterial stiffness. We observed a lack of large randomized interventional trials in humans that test the role of gut microbiota modifications on arterial stiffness, and take into account BP and hemodynamic alterations
Follow-up study on the reduction of burnout levels through mindfulness meditation in health care professionals
No full textGli interventi con la meditazione mindfulness realizzati attraverso corsi di 8 settimane si sono dimostrati utili per la riduzione dei livelli di burnout legato allo stress lavorativo. Nella maggior parte della letteratura questi effetti positivi sono stati stimati con valutazioni fatte immediatamente prima e subito dopo gli interventi terapeutici. Poco si sa, invece, delle traiettorie sintomatologiche del burnout nei mesi successivi a questo tipo di interventi. Il nostro studio esplorativo ha preso in esame un gruppo di professionisti (n=19) dell’area socio-sanitaria con problematiche legate alla sindrome di burnout, valutando tramite questionari psicometrici gli effetti di un intervento standard di 8 settimane con la meditazione mindfulness; su alcuni di questi soggetti (n=8), che hanno continuato a meditare dopo il corso, è stato eseguito anche un follow-up a distanza di 9 mesi dalla seconda valutazione. Inoltre, un altro gruppo di professionisti (n=9) della stessa categoria, ma che non hanno meditato durante questa ricerca, è stato utilizzato come gruppo di controllo. La valutazione ha riguardato burnout, abilità mindfulness e soddisfazione organizzativa. Dall’analisi dei dati è emerso che gli effetti di riduzione dei livelli di burnout non sono stati avvertiti al termine delle 8 settimane del corso, quanto invece nel lungo periodo oggetto del follow-up. Ciò indica da un lato la possibilità di ottenere risultati con la meditazione mindfulness anche in soggetti che non rispondono alla terapia secondo le tempistiche normali, dall’altro l’importanza di monitorare il processo di guarigione
Is the 2020 Sampson equation the best formula for LDL-C estimation?
No full textMore than 4 million deaths in Europe are caused by cardiovascular disease (CVD) each year. Low-density lipoprotein-cholesterol (LDLC) has been demonstrated to be one of the major eterminants of atherogenesis and CVD burden, resulting the most important modifiable risk factor for CVD prevention strategies. According to the last European Guidelines, both direct and indirect assessment of LDL-C can be used in clinical practice. However, the direct measurement techniques are time consuming, expensive, not fully standardized, and not worldwide available. Thus, the most used method for LDL-C quantification continues to be the 1972 old, landmark Friedewald formula (FF): LDL-C = Total cholesterol – High-Density Lipoprotein cholesterol (HDL-C) – riglycerides/5. FF is based on the two assumptions that, in chylomicron absence, most plasma TG are contained in triglyceride-rich Very-Low Density Lipoproteins (VLDL), and the ratio of TG mass to that of VLDL is relatively constant and roughly equal to 5:1 in normal subjects as well as patients with all types of hyperlipoproteinemia, excluding the rare Type III. FF results in reasonably
approximated LDL-C estimations, however it suffers from some limitations: it is not applicable for patient with chylomicronemia, overestimates LDL-C values in patients with Type III ypercholesterolemia
and leads to LDL-C underestimation in patients with plasma TG ≥ 400
mg/dl [3,4]. Moreover, LDL-C underestimation has also been reported
for subjects with low TG levels [5]. For this reason, different research
groups have developed new equations for LDL-C estimation during the
last decades [6–8]. Although promising, the efficacy and potential
clinical role of these new formulae have not been thoroughly validated
and while one formula should be preferred to another is still being
debatin
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