*For medical professionals only for reference
Gout is a common and recurrent acute inflammatory arthritis [1]. With the improvement of living standards and changes in dietary structure, the incidence of gout increases year by year.
gout is common in patients with cardiovascular disease. A large number of studies have proved that gout is related to cardiovascular disease , including myocardial infarction, heart failure , hypertension , etc., which are risk factors for cardiovascular disease. Colchicine was originally a common drug in gout. In recent studies, it has been found that it can be used to prevent cardiovascular events in patients with inflammatory heart diseases such as pericardial disease, coronary artery disease and atrial fibrillation, and further proves the correlation between gout and cardiovascular events [2].
However, the short-term correlation between gout attack and cardiovascular events is unknown.
Recently, the Edoardo Cipolletta team of UN of of published important research results on JAMA on the short-term correlation between gout and cardiovascular events [3]. found that gout attacks are related to the increase in the incidence of short-term cardiovascular events, providing important theoretical support for early prevention of cardiovascular events after gout attacks in clinical work.
The paper homepage screenshot
Low let’s take a look at how this retrospective observation study was carried out.
gout attacks are determined by hospitalization information, primary care clinic, prescription (nonsteroidal anti-inflammatory drugs, glucocorticoid or colchicine). Cardiovascular events are defined as acute myocardial infarction or stroke (ischemic or hemorrhagic).
study included gout patients aged ≥18 years old in the data link of clinical practice research in England from January 1, 1997 to December 31, 2020, patients who registered in the database for less than one year before the first diagnosis of gout, and patients whose first gout consultation was recorded on the same date as the cardiovascular event. The nested case-control study and self-control case series (SCCS) were used for analysis. A total of 62,574 gout patients were included in the
nest case-control study, and a total of 1,421 gout attacks and cardiovascular events were included in the self-controlled case series to evaluate whether gout attacks were related to the recent increase in the incidence of cardiovascular events.
nested case control study cohort
study results found that in the nested case control study, 10,475 patients in newly diagnosed gout patients had at least one cardiovascular event after the gout attack, while 52,099 patients did not have related cardiovascular events.
Compared with patients without cardiovascular events, patients with cardiovascular events had significantly increased their chances of gout attacks within the first 60 days (2.0% vs 1.4%; adjusted OR, 1.93). During the period 61 to 120 days before the cardiovascular event, the gout incidence rate in patients was also higher than that in patients without cardiovascular events (1.6% vs 1.2%; adjusted OR, 1.57). Time moved forward again, and 121-180 days before the cardiovascular event, no significant difference was found in the gout attack rate between the two groups. The relationship between cardiovascular events and pre-event gout attacks (Nest-style case control study) The case series of
self-controlled cases was observed for up to 720 days. Overall, the incidence of cardiovascular events after gout attacks in patients gradually decreased . On days 0-60 after gout onset, the incidence of cardiovascular events was 2.49 per 1,000 persons/day; from 61 to 120 days, the incidence was 2.16 per 1,000 persons/day; from 121 to 180 days, the incidence was 1.70 per 1,000 persons/day.
The association between gout attack and cardiovascular events gradually weakens over time . During the period from 150 days before or 181 to 540 days after the onset of gout, the incidence of cardiovascular events was 1.32 per 1,000 persons/day. The final study results show that in gout patients, gout attacks are associated with an increased short-term risk of cardiovascular events. The self-controlled case series used itself as the control to control all fixed confounding variables, further confirming the results of the nested case-control study and increasing the credibility of the results of this study.Analysis of the correlation between the first gout attack and cardiovascular events (a series of self-controlled cases)
gout attack is characterized by acute inflammation dominated by neutrophils caused by activation of NLRP3 inflammasomes [4]. Neutrophil inflammation is associated with plaque instability and rupture of atherosclerosis [5]. Activating inflammatory cells in plaques upregulate reactive proteins, including metalloproteinase and peptidase , and promotes oxidative stress , which aggravates plaque instability [6]. This may partly explain the link between gout onset and the risk of subsequent short-term cardiovascular events.
Of course, since this is an observational study of , we cannot obtain the causal relationship between gout attack and cardiovascular events. Secondly, due to the lack of clinical data, the severity of gout is not controlled in the analysis. However, this research results still provide important tips for the related research and clinical practice of gout and cardiovascular disease, emphasizing that clinicians need to pay attention to the risks of gout attacks and cardiovascular events in patients, and take preventive measures in advance. We can also optimize the patient management process based on this , and can stratify the risks of recent cardiovascular events and conduct more precise interventions based on different hierarchies.
References:
[1] Dalbeth N, Gosling AL, Gaffo A, Abhishek A. Gout [published correction appears in Lancet. 2021 May 15;397(10287):1808]. Lancet. 2021;397(10287):1843-1855. doi:10.1016/S0140-6736(21)00569-9
[2] Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383(19):1838-1847. doi:10.1056/NEJMoa2021372
[3] Cipolletta E, Tata LJ, Nakafero G, Avery AJ, Mamas MA, Abhishek A. Association Between Gout Flare and Subsequent Cardiovascular Events Among Patients With Gout. JAMA. 2022;328(5):440-450.doi:10.1001/jama.2022.11390
[4] Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237-241. doi:10.1038/nature04516
[5] Ionita MG, van den Borne P, Catanzariti LM, et al. High neutrophil numbers in human carotid atherosclerotic plaques are associated with characteristics of rupture-prone lesions. Arteriescler Thromb Vasc Biol. 010;30(9):1842-1848. doi:10.1161/ATVBAHA.110.209296
[6] Musher DM, Abers MS, Corrales-Medina VF. Acute Infection and Myocardial Infarction. N Engl J Med. 2019;380(2):171-176. doi:10.1056/NEJMra1808137
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