The effects of cardiometabolic factors on the association between serum uric acid and risk of all-cause mortality in adults with congestive heart failure

ABSTRACT Background Serum uric acid (SUA) has been shown to increase all-cause mortality from cardiovascular disease. However, limited studies have examined the mediating effect of dyslipidemia, hyperglycemia, or hypertension on the association between SUA and all-cause mortality in patients with congestive heart failure (CHF). Methods Participants in the present investigation were 620 US adults with CHF from the NHANES database (1999–2014). The relationship between SUA and all-cause mortality was evaluated utilizing multivariable Cox proportional hazards models. Additionally, the nonlinearity between SUA and mortality was investigated utilizing Restricted Cubic Splines (RCS) and 2-piecewise Cox proportional hazards models. Finally, the mediating role of cardiometabolic factors on the relationship between SUA and all-cause mortality was investigated utilizing the mediation analysis. Results During a mean follow-up of 7.6 years, 391 (63.1%) all-cause deaths occurred. Furthermore, we found a U-shaped association between SUA and all-cause mortality. The inflection point for the RCS curve was found at a SUA level of 363 umol/L. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.998 (0.995–1.000) and 1.003 (1.002–1.005) to the left and right of the inflection point, respectively. This U-shaped association was also observed in both subgroups of sex and age. Moreover, the effect of SUA on all-cause mortality was not mediated by hypertension, hyperglycemia, or dyslipidemia (all P-values>0.05). Conclusion The association between SUA level and all-cause mortality followed a U-shaped curve, and this association was not mediated by hypertension, hyperglycemia, or dyslipidemia.

[1]  D. Shi,et al.  Serum Uric Acid and Risk of Chronic Heart Failure: A Systematic Review and Meta-Analysis , 2021, Frontiers in Medicine.

[2]  H. Kono,et al.  Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis , 2021, International journal of molecular sciences.

[3]  F. Viazzi,et al.  The Urrah study. , 2021, Panminerva medica.

[4]  Pengfei Han,et al.  U-Shaped Relationship Between Cardiovascular Mortality and Serum Uric Acid May Be Attributed to Stroke- and Heart-Specific Mortality, Respectively, Among Hypertensive Patients: A Nationally Representative Cohort Study , 2020, Medical science monitor : international medical journal of experimental and clinical research.

[5]  M. Lanaspa,et al.  Uric acid and hypertension , 2020, Hypertension Research.

[6]  A. Scuiller,et al.  La maladie goutteuse , 2020 .

[7]  G. Parati,et al.  Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project , 2020, High Blood Pressure & Cardiovascular Prevention.

[8]  H. Bao,et al.  U-Shaped Association of Serum Uric Acid with All-cause and Cause-Specific Mortality in US Adults: A Cohort Study. , 2020, The Journal of clinical endocrinology and metabolism.

[9]  G. Parati,et al.  Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years , 2019, Hypertension.

[10]  G. Ndrepepa Uric acid and cardiovascular disease. , 2018, Clinica chimica acta; international journal of clinical chemistry.

[11]  Yoosoo Chang,et al.  U‐Shaped Association Between Serum Uric Acid Level and Risk of Mortality , 2018, Arthritis & rheumatology.

[12]  N. Câmara,et al.  Soluble Uric Acid Activates the NLRP3 Inflammasome , 2017, Scientific Reports.

[13]  Anita Deswal,et al.  Contributory Risk and Management of Comorbidities of Hypertension, Obesity, Diabetes Mellitus, Hyperlipidemia, and Metabolic Syndrome in Chronic Heart Failure: A Scientific Statement From the American Heart Association. , 2016, Circulation.

[14]  Ajinkya C. Inamdar,et al.  Heart Failure: Diagnosis, Management and Utilization , 2016, Journal of clinical medicine.

[15]  J. Sandbank,et al.  Serum uric acid as a clinically useful nutritional marker and predictor of outcome in maintenance hemodialysis patients. , 2015, Nutrition.

[16]  Naoki Sato,et al.  The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. , 2014, Journal of the American College of Cardiology.

[17]  I. Piña,et al.  Forecasting the Impact of Heart Failure in the United States: A Policy Statement From the American Heart Association , 2013, Circulation. Heart failure.

[18]  H. Rakugi,et al.  Serum uric acid is an independent risk factor for cardiovascular disease and mortality in hypertensive patients , 2012, Hypertension Research.

[19]  L. Tamariz,et al.  Uric acid, heart failure survival, and the impact of xanthine oxidase inhibition. , 2012, Congestive heart failure.

[20]  B. Kestenbaum,et al.  Vitamin D, parathyroid hormone, and cardiovascular events among older adults. , 2011, Journal of the American College of Cardiology.

[21]  S. Juraschek,et al.  Effect of oral vitamin C supplementation on serum uric acid: A meta‐analysis of randomized controlled trials , 2011, Arthritis care & research.

[22]  G. Fonarow,et al.  Epidemiology and risk profile of heart failure , 2011, Nature Reviews Cardiology.

[23]  B. Álvarez-Lario,et al.  Uric acid and evolution. , 2010, Rheumatology.

[24]  Duk-Hee Kang,et al.  Oxidative stress with an activation of the renin–angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction , 2010, Journal of hypertension.

[25]  S. Semiz,et al.  Relevance of uric Acid in progression of type 2 diabetes mellitus. , 2010, Bosnian journal of basic medical sciences.

[26]  K. Tuttle,et al.  Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? , 2003, Hypertension.

[27]  A Hofman,et al.  The prognosis of heart failure in the general population: The Rotterdam Study. , 2001, European heart journal.

[28]  J. Pell,et al.  Evidence of Improving Prognosis in Heart Failure: Trends in Case Fatality in 66 547 Patients Hospitalized Between 1986 and 1995 , 2000, Circulation.

[29]  S G Thompson,et al.  Survival of patients with a new diagnosis of heart failure: a population based study , 2000, Heart.

[30]  B. Ames,et al.  Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. , 1981, Proceedings of the National Academy of Sciences of the United States of America.