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Background: Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable‐device‐measured ST with physical activity (PA) is unknown. Objectives: To examine the associations of wearable‐device‐measured ST replaced by PA with incident CHD across strata of genetic susceptibility. Methods: This study included 77,500 White British (57% female) with valid wrist‐worn accelerometry and without prevalent CHD/stroke from UK Biobank. Genetic susceptibility to CHD was quantified through weighted polygenic risk scores for CHD based on 300 single‐nucleotide polymorphisms. Wrist‐worn accelerometer data were used to derive ST, light PA, and moderate‐to‐vigorous PA (MVPA). Results: Reallocation of 60 min/day of ST into the same amount of MVPA was associated with approximately 9% lower relative risk of CHD for all participants and across strata of genetic risk: replacement of 1 min/day of ST associated with <1% lower relative risk of CHD. No evidence of interaction (p: 0.784) was found between genetic risk and ST for CHD risk. Reallocating 60 min/day of ST into the same MVPA time was associated with greater absolute CHD risk reductions at high genetic risk (0.27%) versus low genetic risk (0.15%). Conclusions: Replacing any amount of ST with an equal amount of MVPA time is associated with a lower relative risk of CHD, irrespective of genetic susceptibility to CHD. Reductions in CHD absolute risk for replacing ST with MVPA are greater at high genetic risk versus low genetic risk. [ABSTRACT FROM AUTHOR]

Efferocytosis, the process of engulfing and removing apoptotic cells, is attenuated in vulnerable plaques of advanced atherosclerosis. T‐cell immunoglobulin and mucin domain 4 (TIMD4) is a recognition receptor protein for efferocytosis that has been implicated in atherosclerosis mouse models. However, the role of serum‐soluble TIMD4 (sTIMD4) in coronary heart disease (CHD) remains unknown. In this study, we analyzed serum samples collected from two groups: Group 1 (36 healthy controls and 70 CHD patients) and Group 2 (44 chronic coronary syndrome [CCS]) and 81 acute coronary syndrome [ACS] patients). We found that sTIMD4 levels in patients with CHD were significantly higher than those in healthy controls and were also higher in ACS than in CCS patients. The area under the receiver operating characteristic curve was 0.787. Furthermore, our in vitro results showed that low‐density lipoprotein/lipopolysaccharide activated p38 mitogen‐activated protein kinase, which in turn enhanced a disintegrin and metalloproteinase 17, resulting in increased secretion of sTIMD4. This impairment of macrophage efferocytosis promoted inflammation. Thus, this study is not only the first identification of a potential novel biomarker of CHD, sTIMD4, but also demonstrated its pathogenesis mechanism, providing a new direction for the diagnosis and treatment of CHD. [ABSTRACT FROM AUTHOR]