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OBJECTIVE: To prospectively evaluate the association between modifiable lifestyle factors and peripheral artery disease (PAD) among individuals with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We included 14,543 individuals with T2D from the UK Biobank. We defined a weighted healthy lifestyle score using nonsmoking, regular physical activity, high-quality diet, moderate alcohol consumption, optimal waist-to-hip ratio, and adequate sleep duration, and categorized into unfavorable, intermediate, and favorable lifestyles. We created a genetic risk score (GRS) using 19 single nucleotide polymorphisms previously found to be associated with PAD. We modeled the association between lifestyle score and PAD, overall and stratified by PAD genetic susceptibility. RESULTS: After a median 13.5 years of follow-up, 628 incident cases of PAD were documented. A linear inverse association between the weighted lifestyle score and PAD was observed, with a hazard ratio (HR) (95% CI) of 0.27 (0.19, 0.38) for favorable compared with unfavorable lifestyle (Ptrend < 0.0001). An estimated 58.3% (45.0%, 69.1%) of PAD in this population could be potentially avoidable if all participants attained a favorable lifestyle. Moreover, the PAD GRS was associated with increased PAD risk (HR [95% CI] per SD increment: 1.13 [1.03, 1.23]). A favorable lifestyle was able to partially mitigate the excess risk of PAD associated with higher GRS, albeit as a nonsignificant interaction. Several biomarkers in the lipid metabolism, hepatic/renal function, and systemic inflammation pathways collectively explained 13.3% (8.5%, 20.1%) of the association between weighted lifestyle score and PAD. CONCLUSIONS: A favorable lifestyle was associated with lower risk of PAD among individuals with T2D, independent of genetic predisposition to PAD. [ABSTRACT FROM AUTHOR]

Aims: To examine the association of Life's Essential 8 (LE8) with the risk of recurrent cardiovascular events among patients with CHD., Methods: This prospective cohort study included 11,997 patients with CHD from the UK Biobank. The LE8 score was generated using five lifestyle factors (diet, body mass index, physical activity, smoking, and sleep) and three biological factors (blood lipids, blood glucose, and blood pressure). LE8 score ranged from 0 to 100 and was categorized into quartiles. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% CI (confidence interval)., Results: During a median follow up of 12.5 years, we documented 3366 recurrent cardiovascular events, 1068 myocardial infarction, 1829 heart failure events, 703 strokes, and 934 cardiovascular deaths. The multivariable-adjusted HR (95% CI) for the highest versus the lowest quartile of LE8 score was 0.57 (0.50, 0.65) for recurrent cardiovascular events, 0.66 (0.52, 0.83) for myocardial infarction, 0.54 (0.45, 0.67) for heart failure, 0.50 (0.36, 0.68) for stroke, and 0.46 (0.37, 0.56) for cardiovascular death. Furthermore, the population attributable fraction of the lowest to the highest quartile of LE8 score were ranged from 16.2% to 32.5% for the various cardiovascular outcomes. In addition, biomarkers including renal function and inflammation collectively explained 47.6%-87.7% of the associations between the lifestyle factors and recurrent cardiovascular events., Conclusions: Better cardiovascular health as measured by LE8 was associated with significantly lower risk of recurrent cardiovascular events among patients with CHD. Clinicians should prioritize educating patients with CHD on the importance of optimal cardiovascular health for secondary prevention. In addition, our findings indicated significant mediation effect of biomarkers involving of glycemic control, renal function, liver function, lipid profile, and systemic inflammation on the associations between overall lifestyle factors and recurrent cardiovascular events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Insulin-like growth factor-1 (IGF-1) has been implicated in several malignancies, but few studies have examined multiple cancers simultaneously. We sought to conduct systematic assessments of the association between IGF-1 and cancer risk., Methods: We conducted a prospective analysis between IGF-1 and incident total and 19 site-specific cancers among 412,645 individuals enrolled in the UK Biobank with follow-up to 2016. IGF-1 was measured using blood samples provided at the baseline examination. HR and 95% confidence interval (CI) were calculated with multivariable-adjusted Cox models with IGF-1 modeled both in sex-specific quintiles and continuously., Results: Participants were followed for a median of 7.2 years. We observed positive associations between circulating IGF-1 and overall cancer risk for both men (HR = 1.03 per 5-nmol/L increment in IGF-1; 95% CI, 1.01-1.06) and women (HR = 1.03; 95% CI, 1.01-1.06). For specific sites, we observed positive associations for breast (HR = 1.10; 95% CI, 1.07-1.14), prostate (1.09; 95% CI, 1.05-1.12), colorectum (1.07; 95% CI, 1.02-1.11), melanoma (1.08; 95% CI, 1.01-1.15), kidney (1.10; 95% CI, 1.00-1.20), and thyroid (1.22; 95% CI, 1.05-1.42) and inverse associations for lung (0.91; 95% CI, 0.86-0.96), ovaries (0.86; 95% CI, 0.77-0.95), head and neck (0.90; 95% CI, 0.82-0.99), and liver (0.32; 95% CI, 0.26-0.38). The inverse association between IGF-1 and lung cancer was observed only in ever-smokers (HR ever-smoker = 0.88 vs. HR never-smoker = 1.14; P interaction = 0.0005). Analyses comparing extreme quintiles were consistent., Conclusions: IGF-1 is modestly associated with increased risk of total cancer in both men and women but demonstrated divergent associations for site-specific cancers., Impact: Our study suggests that IGF-1 could serve as a target for cancer prevention or treatment., (©2020 American Association for Cancer Research.)