Angiographic coronary atherosclerosis burden mediates a substantial part of the impact of lipids and type 2 diabetes on myocardial infarction and heart failure risk.
Does angiographic CAD burden mediate the association between traditional ASCVD risk factors and adverse cardiovascular outcomes?
Genetic analyses demonstrate that the angiographic burden of coronary atherosclerosis causally mediates the relationship between traditional risk factors (like lipids and diabetes) and cardiovascular outcomes (MI and HF).
Tasa de eventos absoluta: 0% vs 0%
BACKGROUND: Coronary artery disease (CAD) is a major contributor to cardiovascular morbidity (including myocardial infarction and heart failure) and mortality. Although the burden of CAD (number and degree of coronary artery stenosis) has been observationally linked to these outcomes, the causal contribution and independence from traditional cardiovascular risk factors have been poorly defined. METHODS: We developed a polygenic risk score for angiographic CAD burden using data from the VA Million Veteran Program (n=41 507) and validated this score using data from the Penn Medicine Biobank (n=41 660 with genotyping, N=3771 with angiogram data). We then used publicly available GWAS data and a mediation framework using Mendelian Randomization to investigate whether angiographic CAD burden contributes to adverse cardiovascular outcomes independent of traditional risk factors. RESULTS: We first demonstrated that increasing levels of the polygenic risk score were strongly associated with increased prevalence of nonobstructive and obstructive CAD on coronary angiography (odds ratio, 1.26 95% CI, 1.14–1.39; odds ratio, 2.23 95% CI, 1.94–2.55, respectively) and was associated with other forms of cardiometabolic disease including peripheral artery disease and atherosclerotic risk factors including hyperlipidemia, hypercholesterolemia and hypertension. Through Mendelian randomization analyses, we found that lipid measures (apolipoprotein B, high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides) and type 2 diabetes significantly influenced myocardial infarction risk through their effects on angiographic CAD burden. Furthermore, low-density lipoprotein and total cholesterol demonstrated significant indirect effects on heart failure through angiographic CAD burden, suggesting these lipids primarily influence heart failure through their impact on coronary atherosclerosis. CONCLUSIONS: Our findings indicate that angiographic burden of coronary atherosclerosis mediates a substantial proportion of the relationship between traditional cardiovascular risk factors and adverse outcomes. These results support prioritizing primary prevention efforts targeting modifiable risk factors to prevent the development and progression of coronary plaques before clinical disease manifestation.
Tsao et al. (Fri,) reported a other. Angiographic coronary atherosclerosis burden mediates a substantial part of the impact of lipids and type 2 diabetes on myocardial infarction and heart failure risk.