韩意
中国医学科学院阜外医院
AIMS:Mortality risk assessment in patients with heart failure (HF) with preserved ejection fraction (HFpEF) presents a major challenge. We sought to construct a polygenic risk score (PRS) to accurately predict the mortality risk of HFpEF.METHODS AND RESULTS:We first carried out a microarray analysis of 50 HFpEF patients who died and 50 matched controls who survived during 1-year follow-up for candidate gene selection. The HF-PRS was developed using the independent common (MAF > 0.05) genetic variants that showed significant associations with 1-year all-cause death (P < 0.05) in 1442 HFpEF patients. Internal cross-validation and subgroup analyses were performed to evaluate the discrimination ability of the HF-PRS. In 209 genes identified by microarray analysis, 69 independent variants (r < 0.1) were selected to develop the HF-PRS model. This model yielded the best discrimination capability for 1-year all-cause mortality with an area under the curve (AUC) of 0.852 (95% CI 0.827-0.877), which outperformed the clinical risk score consisting of 10 significant traditional risk factors for 1-year all-cause mortality (AUC 0.696, 95% CI 0.658-0.734, P = 4 × 10-11), with net reclassification improvement (NRI) of 0.741 (95% CI 0.605-0.877; P < 0.001) and integrated discrimination improvement (IDI) of 0.181 (95% CI 0.145-0.218; P < 0.001). Individuals in the medium and the highest tertile of the HF-PRS had nearly a five-fold (HR = 5.3, 95% CI 2.4-11.9; P = 5.6 × 10-5) and 30-fold (HR = 29.8, 95% CI 14.0-63.5; P = 1.4 × 10-18) increased risk of mortality compared to those in the lowest tertile, respectively. The discrimination ability of the HF-PRS was excellent in cross validation and throughout the subgroups regardless of comorbidities, gender, and patients with or without a history of heart failure.CONCLUSION:The HF-PRS comprising 69 genetic variants provided an improvement of prognostic power over the contemporary risk scores and NT-proBNP in HFpEF patients.
European journal of preventive cardiology 2023
OBJECTIVE:Long-term weight loss (LTWL) has been shown to be associated with lower metabolic risk in young adults with overweight/obesity. However, the dose-response association is uncertain.METHODS:In a large-scale nationwide screening project in China, the participants aged 35 to 64 years who recalled overweight/obesity at age 25 years and experienced LTWL or maintained stable weight were included. The dose-response association between LTWL from age 25 to screening (35 to 64 years) and the odds of metabolic syndrome at screening were assessed using multivariable adjusted regression models with restricted cubic splines.RESULTS:A total of 40,150 participants (66.4% women) were included. The increment of LTWL was associated with continuously decreased odds of metabolic syndrome. The odds of metabolic syndrome were 0.64 (0.60 to 0.67), 0.42 (0.40 to 0.45), 0.27 (0.25 to 0.29), and 0.15 (0.13 to 0.17) for those with LTWL of 5% to 9.9%, 10% to 14.9%, 15% to 19.9%, and 20% or greater compared with <5% LTWL, respectively. Moreover, the incremental pattern was observed across all population subgroups.CONCLUSIONS:An incremental association between LTWL from young adulthood and odds of later-life metabolic syndrome was observed. Our findings highlight the effective ways to achieve LTWL to improve lifetime metabolic health for young adults with overweight/obesity.
Obesity (Silver Spring, Md.) 2022
