Life's essential 8 factors and their impact on the risk of stroke and dementia: a Mendelian randomization study

Despite advancements in the treatment of stroke and dementia, these conditions still contribute significantly to global health and economic burdens, highlighting the need for prevention. Although these diseases are linked to modifiable lifestyle factors such as diet, physical activity, and smoking, previous studies have lacked a systematic and comprehensive framework to fully elucidate these associations. To bridge this gap, this study comprehensively evaluates the causal links between lifestyle factors in "Life's Essential 8" (LE8) and the risks of stroke and dementia, providing evidence for prevention strategies.

This study used a two-sample Mendelian randomization approach with genetic variants as instrumental variables to assess the causal effects of lifestyle factors on stroke and dementia risks. Data were sourced from large-scale GWAS and the UK Biobank, including clinical endpoints for stroke and dementia subtypes. The leading analysis utilized the inverse-variance weighted (IVW) method, supplemented by weighted mode, MR-Egger, weighted median and simple mode approaches. Sensitivity analyses included MR-Egger intercept, Cochran's Q test, leave-one-out analysis and MR-PRESSO.

Increased grain intake (OR = 0.469; 95% CI: 0.264-0.835; P = 0.010), higher HDL-C levels, and physical activity (OR = 0.927; 95% CI: 0.860-0.999; P = 0.048) reduced stroke risk. Conversely, smoking showed the strongest association with increased stroke risk (OR = 17.375; 95% CI: 1.041-289.999; P = 0.047), followed by genetically predicted high blood pressure for small-vessel stroke (OR = 7.520), prolonged sedentary behavior or TV watching (OR = 1.576), and higher salt intake (OR = 1.229; 95% CI: 1.037-2.291; P = 0.033). Genetically normal blood pressure status was associated with a lower risk of small-vessel stroke (OR = 0.132). For dementia, high salt intake and total cholesterol were associated with increased risk, whereas diastolic blood pressure showed a statistically significant inverse association with dementia risk (OR = 0.765; 95% CI: 0.617-0.949; P = 0.015).

This study emphasizes the role of lifestyle interventions, particularly dietary sodium reduction, smoking cessation, blood pressure management, and appropriate physical activity, in mitigating the risks of stroke and dementia. The findings provide strong evidence for prioritizing modifiable behaviors in public health strategies to alleviate the increasing global burden of these conditions.