The prevalence of cardiovascular disease is increasing and is now one of the leading causes of death worldwide. Inflammatory conditions like Rheumatoid Arthritis and Gout are frequently linked to an increased risk and earlier onset of this disease. Gout has been linked to an increased risk of several types of cardiovascular disease, including heart attack, heart failure, and atrial fibrillation, or an irregular heartbeat, according to research. Patients with hyperuricemia SUA are at an increased risk of cardiac, renal, and vascular damage, as well as CV events, according to epidemiological, experimental, and clinical data.
According to a 2018 Arthritis Care & Research study, adults 65 and older have at least a two-fold risk of heart attack compared to those without gout. Gout increases the risk of stroke and peripheral vascular disease. A study presented at the 2021 European Renal Association-European Dialysis and Transplant Association meeting details findings that hyperuricemia is a risk factor for cardiovascular disease and all-cause mortality, as well as an increase that occurs in tandem with a decrease in kidney function. The Uric Acid Right Heart Health (URRAH) project included 21,963 patients and resulted in 1582 cardiovascular events with 3130 deaths over a 9-year period of follow-up.
According to researcher Elisa Russo, MD of the University of Genoa, each 1/mg/dl increase in uric acid levels increases the risk of cardiovascular mortality by 21% and all-cause mortality by 10%. This is a clear and significant association. Furthermore, patients with impaired kidney function/blood filtration showed significant risk factor increases for both cardiovascular and all-cause mortality. Patients with both hyperuricemia and advanced kidney disease had a significantly higher risk of cardiovascular death than those with neither risk factor.
Because of estrogen’s protective effect, women’s cardiovascular and gout risks are lower during their premenopausal years. However, when compared to men, this protection against heart disease is lost in the postmenopausal years and essentially matches the risks for both. Smoking, diabetes, hypertension, hyperlipidemia, and a family history of heart disease are all risk factors shared by both men and women. More research is needed to investigate the gender differences in the pathogenesis of gout-associated heart disease.
Gout is linked to systemic inflammation, and other research has linked systemic inflammation to an increased risk of heart disease and other chronic inflammatory conditions. The model below depicts the mechanisms of cardiovascular disease.
Figure 1
Potential pathogenic pathways for an increased risk of cardiovascular disease in gout patients. The solid lines represent current evidence supporting the mechanism/pathway, while the dotted lines represent a potential mechanism/pathway for which more evidence is required. Several pathways from gout to the intermediate event (endothelial dysfunction, for example) may be hyperuricemia or non-hyperuricemia-mediated (eg, systemic inflammation).
Figure 2
The molecular mechanisms by which high UA activates NLRP3-inflammasomes and promotes M1/M2 polarization in macrophages. AMPK stands for AMP-activated protein kinase; HIF-1 stands for hypoxia-inducible factor-1; IL-1 stands for interleukin-1; MAPK stands for mitogen activated protein kinases; mTOR stands for mammalian target of rapamycin; NF-B stands for nuclear factor B; NLRP3, nod-like receptor protein 3; TLR stands for Toll-like receptors; UA stands for uric acid
Figure 3
High UA’s possible molecular mechanisms promote the occurrence and progression of cardiovascular diseases. High UA influences the progression and prognosis of cardiovascular diseases such as hypertension (A), atherosclerosis (B), atrial fibrillation (C), and heart failure by regulating numerous molecular signals such as inflammation, oxidative stress, insulin resistance, and endothelial dysfunction (D). AMPK stands for AMP-activated protein kinase; mROS stands for mitochondrial ROS; mTOR stands for mammalian target of rapamycin; NLRP3, nod-like receptor protein 3; RAS stands for renin-angiotensin system; and UA stands for uric acid.
