Smoking and coronary artery disease risk in patients with diabetes: A Mendelian randomization study

Abstract

BackgroundPrevious observational studies have shown an association between smoking and coronary artery disease (CAD) in patients with diabetes. Whether this association reflects causality remains unestablished. This study aimed to explore the causal effect of smoking on CAD in patients with diabetes.MethodsGenetic signatures for smoking were extracted from a large genome-wide association study (GWAS), consisted of up to 1.2 million participants. Four smoking phenotypes were included: smoking initiation, cigarettes per day, age at initiation of regular smoking, and smoking cessation. Genetic associations with CAD in patients with diabetes were extracted from another GWAS, which included 15,666 participants (3,968 CAD cases and 11,696 controls). The analyses were performed using the univariable and multivariable Mendelian randomization (MR) method.ResultsMR analysis revealed that smoking initiation was positively related to CAD risk in patients with diabetes (OR = 1.322, 95% CI = 1.114 – 1.568, P = 0.001), but this association was attenuated when adjusted for cardiovascular risk factors (OR = 1.212, 95% CI = 1.008 – 1.457, P = 0.041). Age at initiation of regular smoking was negatively related to CAD in patients with diabetes (OR = 0.214, 95% CI = 0.070 – 0.656, P = 0.007), but this association became insignificant when adjusted for cardiovascular risk factors.ConclusionsThis study supported the effect of smoking initiation on the risk of CAD in patients with diabetes.

Prognostic factors of MINOCA and their possible mechanisms

“…Meanwhile, the increased levels of inflammatory factors further contribute to impaired glucose uptake and metabolism in blood vessels, forming a cycle of disordered glucose metabolism. ( van Helden et al, 2020 , Songzan et al, 2023 , O'Sullivan Jack et al, 2023 , Abdu Fuad et al, 2023 , Pasquale et al, 2021 , Choo et al, 2019 , Nordenskjöld et al, 2018 , Luying et al, 2023 , Marlene et al, 2022 , Hiroaki, 2014 , Bye Bailey et al, 2023 , Paula et al, 2023 , Driskill Jordan and Duojia, 2023 , Tedy et al, 2022 , Fangdi et al, 2022 , Elias et al, 2023 , Roshanzamir and Showkathali, 2013 ) Lipid metabolism disorder Lack of research temporarily. The role of cholesterol in the pathogenesis of MINOCA is controversial; total cholesterol is a predictor of pathogenesis in patients with NSTE MINOCA; a high LDL-C level is an independent risk factor for MACE in STE MINOCA; reducing Lp[a] levels improves survival in patients with MINOCA.…”

“…Clinically important glucose metabolism disorders mainly result in too high or low blood glucose concentrations ( van Helden et al, 2020 ). Previous studies have confirmed the association between diabetes and CAD prognosis ( Songzan et al, 2023 , O'Sullivan Jack et al, 2023 ), but the effect of diabetes on cardiovascular outcomes in patients with MINOCA is unclear.…”

“…However, these lesions tend to have features of fragile plaques, such as large lipid pools and thin fibrous caps ( Montone Rocco et al, 2021 ), which can induce plaque rupture, resulting in transient local thrombosis and spontaneous fibrinolysis, causing distal coronary thromboembolism and MINOCA. Although there have been no studies concerning glucose metabolism and plaque morphology, diabetes is a risk factor for intravascular plaque formation, which may also greatly increase the incidence of MINOCA ( van Helden et al, 2020 , Songzan et al, 2023 ). Moreover, abnormal blood sugar levels can directly damage the vascular endothelium to cause arterial spasm or atherosclerotic plaque formation, mediated by non-enzymatic glycosylation of low-density lipoprotein cholesterol (LDL-C), other apolipoproteins and blood clotting factors like Apolipoprotein B, Fibrinogen, Factor V and Factor VII ( Elias et al, 2023 ).…”

Gut microbiota and autism spectrum disorders: a bidirectional Mendelian randomization study

“…If not, the IVW model with fixed effects was used ( Shi et al., 2023 ). Meanwhile, we used MR-PRESSO and MR-Egger intercept tests to detect horizontal pleiotropy ( Chen et al., 2023 ). Finally, the leave-one-out sensitivity analysis was performed to examine if one single SNP drove the causal association.…”

Association of rs5051 and rs699 polymorphisms in angiotensinogen with coronary artery disease in Iranian population: A case-control study

“…Family history is also associated with the risk of mortality of CAD. [3] The renin-angiotensin-aldosterone system (RAAS) is a key modulator of cardiovascular and renal function. Clinical trials have demonstrated that inhibiting this system would reduce the risk of coronary events.…”