Abstract Background Adiposity is associated with increased risk of breast cancer in post-menopausal women, while the association appears to be the inverse among premenopausal women in Western populations, but is unclear for Chinese women. Methods Using data on 284 538 women with no history of cancer, hysterectomy, oophorectomy, or breast surgery at baseline in 2004–8 from the China Kadoorie Biobank (a prospective cohort study), Cox regression was used to estimate adjusted hazard ratios (HRs) for breast cancer and its subtypes by measured body mass index (BMI) and other adiposity measures (waist circumference, fat percentage, waist–hip ratio, fat mass) and by self-reported BMI at age 25 years. Results Mean BMI was 23.8 (3.5 SD) kg/m2 at baseline (mean age 51.4 years) and 21.9 (2.7 SD) kg/m2 at age 25 years. During 10 years of follow-up, there were 2379 incident breast cancer cases. Higher BMI was associated with a higher risk of breast cancer in women who were post-menopausal [HR = 1.35, 95% confidence interval (CI) 1.24–1.47] and premenopausal (HR = 1.13, 95% CI 1.03–1.24) at baseline, but not when censoring at age 50 years to capture mainly premenopausal cancers. Among post-menopausal women, BMI was associated with oestrogen-receptor positive (ER ) (HR = 1.47, 95% CI 1.24–1.74), but not with oestrogen-receptor negative (ER−) breast cancer (HR = 1.02, 95% CI 0.75–1.37). Waist circumference and fat percentage were associated with a higher risk of breast cancer. Conclusion In this cohort of Chinese women, higher levels of general and central adiposity were associated with a higher risk of breast cancer, in both women who were premenopausal and women who were post-menopausal at baseline. Among post-menopausal women, adiposity was associated with ER but not ER − breast cancer.
C. Kartsonaki, N. Wright, I. Millwood et al.· International Journal of Epi...· 0 citations
Although air pollution is recognized as a contributor to accelerated biological aging, its associations with clinically significant liver-related outcomes and the potential role of proteomic aging remain unclear. We aimed to evaluate the associations of key air pollutants with liver-related outcomes and the potential mediating role of proteomic aging clocks. Among 504,006 China Kadoorie Biobank participants without liver disease or cancer, we used time-varying Cox regression to assess associations of PM2.5, PM10, NO2, and warm-season O3, and their mixtures with liver-related events (LRE) and liver-related mortality (LRM), and mediation analyses to examine the role of proteomic aging clocks (i.e., ProtAge). Long-term exposure to PM2.5, PM10, NO2, and warm-season O3 showed significant positive associations with LRE, while PM2.5, PM10, and NO2 were also positively associated with LRM. A 1-unit increment in the weighted pollutant score was associated with an 81% higher risk of LRE (hazard ratio [HR]=1.81 [1.65-1.98]) and a 17% higher risk of LRM (HR=1.17 [1.05-1.31]). Acceleration in ProtAge was associated with higher risks of LRE (HR=1.86 [1.16-2.97]) and LRM (HR=4.43 [3.02-6.50]). ProtAge accounted for an estimated 7.1% and 12.5% of the associations of pollutant mixtures with LRE and LRM, respectively. Among proteins in ProtAge, CD248, GDF15, TNFRSF6B, and XG showed concordant associations in pollutant mixture-protein and protein-LRE analyses. Long-term air pollution was associated with higher risks of clinically significant liver-related outcomes. These findings suggest a possible role of proteomic aging in the association between air pollution and liver-related outcomes, warranting further investigation.
BACKGROUND
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a risk factor for cardiovascular disease (CVD). However, the risk of liver-related events (LREs) after CVD is often overlooked. We investigated the association between incident CVD and subsequent long-term LRE risk among individuals with MASLD.
METHODS
We used UK Biobank data to examine whether incident CVD (coronary heart disease [CHD], myocardial infarction [MI], heart failure [HF], or atrial fibrillation [AF]) was associated with subsequent long-term LREs (cirrhosis, decompensation, hepatocellular carcinoma, or liver-related death) in MASLD. Semi-Markov multi-state and time-dependent Cox regression models estimated transition rates and adjusted hazard ratios (aHRs). Imaging and proteomic data explored biological mechanisms.
RESULTS
Among 142,454 individuals with MASLD, 22,630 (15.9%) developed incident CVD, and 2635 (1.8%) developed subsequent LREs over a median of 15.1 years. The transition rate from CVD to LREs was higher than the direct progression from MASLD to LREs (3.56 vs. 1.08 per 1000 person-years). Time-dependent Cox regression showed that incident CVD was associated with a higher risk of subsequent LREs (aHR 1.93, 95%CI 1.73-2.14). The risk varied by CVD subtypes, with HF highest, followed by AF, CHD, and MI (all P < 0.001). Exploratory integrated multi-omics analyses revealed associations between cardiac dysfunction and hepatic parameters, and identified a shared proteomic signature enriched in immune and fibrotic pathways.
CONCLUSIONS
Individuals with MASLD who experience a CVD event have a higher subsequent risk of long-term LREs. These findings underscore the value of targeted liver monitoring for high-risk individuals after CVD and integrated heart-liver co-management.
Li-You Lian, Qin-Fen Chen, Tianyi Xia et al.· Metabolism: Clinical and Exp...· 0 citations
