BACKGROUND: The coexistence of cardiovascular disease and chronic kidney disease, termed chronic cardiovascular-kidney disorder (CCV-KD), is increasingly prevalent. However, limited studies have assessed the association between cardiovascular health (CVH), assessed by the American Heart Association\'s Life\'s Essential 8 (LE8), and CCV-KD.
METHODS: We conducted a prospective cohort study using data from UK Biobank. Participants without cardiovascular disease and chronic kidney disease at baseline and having complete data on metrics of LE8 were included (N = 125,986). LE8 included eight metrics, and the aggregate score was categorized as low (< 50 points), intermediate (50 to < 80 points), and high (≥ 80 points), with a higher score indicating better CVH health. Adjusted Cox proportional hazard models were conducted to explore the association of CVH with the risk of CCV-KD. The adjusted proportion of population attributable risk (PAR%) was used to calculate the population-level risk caused by low or intermediate CVH.
RESULTS: During a median follow-up of 12.5 years, 1,054 participants (0.8%) had incident CCV-KD. Participants with intermediate and high CVH had 54% (HR = 0.46, 95% CI: 0.40-0.54, P < 0.001) and 75% (HR = 0.25, 95% CI: 0.18-0.34, P < 0.001) lower risks of incident CCV-KD compared with those in low CVH group. There was an approximately dose-response linear relationship between the overall LE8 score and incident CCV-KD. The risk of incident CCV-KD decreased by 30% (HR = 0.70, 95% CI: 0.67-0.74, P < 0.001) for a 10-point increment of LE8 score. The adjusted PAR% of lower overall CVH was 47.4% (95% CI: 31.6%-59.8%).
CONCLUSIONS: Better CVH, assessed by using LE8 score, was strongly associated with decreased risk of incident CCV-KD. These findings imply optimizing CVH may be a preventive strategy to reduce the burden of CCV-KD.

OBJECTIVE: This study evaluates the relationship between the Life\'s Essential 8 (LE8) scoring system and all-cause and cause-specific mortality among obese individuals using NHANES data.
METHODS: Data from 9,143 obese participants (BMI ≥30 kg/m2) collected between 2005 and 2018 were analyzed. Participants were categorized based on their LE8 scores: low cardiovascular health (Low CVH, n=2264), moderate cardiovascular health (Moderate CVH, n=6541), and high cardiovascular health (High CVH, n=338). Associations between LE8 scores and mortality were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models.
RESULTS: Over a median follow-up of 7.3 years, there were 867 all-cause deaths (9.5%), including 246 cardiovascular disease (CVD) deaths (2.7%) and 621 non-CVD deaths (6.8%). In multivariable Cox regression analysis, compared to the Low CVH group, the Moderate CVH group had an adjusted hazard ratio (HR) for all-cause mortality of 0.63 (95% CI: 0.55-0.72), and the High CVH group had an HR of 0.25 (95% CI: 0.10-0.60). For CVD mortality, the HRs were 0.61 (95% CI: 0.47-0.78) for Moderate CVH and 0.19 (95% CI: 0.03-1.38) for High CVH. For non-CVD mortality, the HRs were 0.64 (95% CI: 0.54-0.75) for Moderate CVH and 0.27 (95% CI: 0.10-0.72) for High CVH. Each 10-point increase in LE8 score was associated with a 20% reduction in all-cause mortality (P<0.001), 21% reduction in CVD mortality (P<0.001), and 20% reduction in non-CVD mortality (P<0.001).
CONCLUSIONS: Higher LE8 scores are significantly associated with lower rates of all-cause, CVD, and non-CVD mortality among obese individuals. These findings support the LE8 scoring system as an effective predictor of health status and mortality risk.

UNASSIGNED: To prospectively assess the individual and joint effects of birth weight and the life\'s essential 8 (LE8)-defined cardiovascular health (CVH) on myocardial infarction (MI) risk in later life.
UNASSIGNED: In 144,803 baseline MI-free participants who were recruited in the UK Biobank cohort between 2006 and 2010, Cox proportional hazard models were used to estimate the associations of birth weight, LE8 score, and their interactions with incident MI. LE8 was defined on the basis of diet, physical activity, nicotine exposure, sleep health, body mass index, blood pressure, blood glucose, and blood lipids.
UNASSIGNED: Low birth weight was associated with higher risk of MI [hazard ratio (HR) 1.17, 95% confidence interval 1.02-1.35, P = 0.025], while no significant correlation between high birth weight and MI was observed after adjustment. Low CVH was associated with higher MI risk [HR 6.43 (3.71-11.15), P < 0.001). Participants with low birth weight and low CVH (vs. participants with normal birth weight and high CVH) had HR of 5.97 (2.94-12.14) for MI incidence. The relative excess risk due to interaction of low birth weight and low CVH on MI was -4.11 (-8.12, -0.11), indicating a negative interaction on an additive scale. A consistent decreasing trend of MI risk along with increased LE8 score was observed across all three birth weight groups.
UNASSIGNED: Low birth weight was associated with increased MI risk, emphasizing the importance of the prenatal factor in risk prediction and prevention of MI. Improving LE8 can mitigate MI risk attributed to low birth weight.

BACKGROUND: The American Heart Association recently introduced a novel cardiovascular health (CVH) metric, Life\'s Essential 8 (LE8), for health promotion. However, the relationship between LE8 and cancer mortality risk remains uncertain.
METHODS: We investigated 17,076 participants from US National Health and Nutrition Examination Survey (US NHANES) and 272,727 participants from UK Biobank, all free of cancer at baseline. The CVH score, based on LE8 metrics, incorporates four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index, lipid, blood glucose, and blood pressure). Self-reported questionnaires assessed health behaviors. Primary outcomes were mortality rates for total cancer and its subtypes. The association between CVH score (continuous and categorical variable) and outcomes was examined using Cox model with adjustments. Cancer subtypes-related polygenic risk score (PRS) was constructed to evaluate its interactions with CVH on cancer death risk.
RESULTS: Over 141,526 person-years in US NHANES, 424 cancer-related deaths occurred, and in UK Biobank, 8,872 cancer deaths were documented during 3,690,893 person-years. High CVH was associated with reduced overall cancer mortality compared to low CVH (HR 0.58, 95% CI 0.37-0.91 in US NHANES; 0.51, 0.46-0.57 in UK Biobank). Each one-standard deviation increase in CVH score was linked to a 19% decrease in cancer mortality (HR: 0.81; 95% CI: 0.73-0.91) in US NHANES and a 19% decrease (HR: 0.81; 95% CI: 0.79-0.83) in UK Biobank. Adhering to ideal CVH was linearly associated with decreased risks of death from lung, bladder, liver, kidney, esophageal, breast, colorectal, pancreatic, and gastric cancers in UK Biobank. Furthermore, integrating genetic data revealed individuals with low PRS and high CVH exhibited the lowest mortality from eight cancers (HRs ranged from 0.36 to 0.57) compared to those with high PRS and low CVH. No significant modification of the association between CVH and mortality risk for eight cancers by genetic predisposition was observed. Subgroup analyses showed a more pronounced protective association for overall cancer mortality among younger participants and those with lower socio-economic status.
CONCLUSIONS: Maintaining optimal CVH is associated with a substantial reduction in the risk of overall cancer mortality. Adherence to ideal CVH correlates linearly with decreased mortality risk across multiple cancer subtypes. Individuals with both ideal CVH and high genetic predisposition demonstrated significant health benefits. These findings support adopting ideal CVH as an intervention strategy to mitigate cancer mortality risk and promote healthy aging.

BACKGROUND: Patients with post-traumatic stress disorder (PTSD) experience higher risk of adverse cardiovascular (CV) outcomes. This study explores shared loci, and genes between PTSD and CV conditions from three major domains: CV diagnoses from electronic health records (CV-EHR), cardiac and aortic imaging, and CV health behaviors defined in Life\'s Essential 8 (LE8).
METHODS: We used genome-wide association study (GWAS) of PTSD (N=1,222,882), 246 CV diagnoses based on EHR data from Million Veteran Program (MVP; N=458,061), UK Biobank (UKBB; N=420,531), 82 cardiac and aortic imaging traits (N=26,893), and GWAS of traits defined in the LE8 (N = 282,271 ~ 1,320,016). Shared loci between PTSD and CV conditions were identified using local genetic correlations (rg), and colocalization (shared causal variants). Overlapping genes between PTSD and CV conditions were identified from genetically regulated proteome expression in brain and blood tissues, and subsequently tested to identify functional pathways and gene-drug targets. Epidemiological replication of EHR-CV diagnoses was performed in AllofUS cohort (AoU; N=249,906).
RESULTS: Among the 76 PTSD-susceptibility risk loci, 33 loci exhibited local rg with 45 CV-EHR traits (|rg|≥0.4), four loci with eight heart imaging traits(|rg|≥0.5), and 44 loci with LE8 factors (|rg|≥0.36) in MVP. Among significantly correlated loci, we found shared causal variants (colocalization probability > 80%) between PTSD and 17 CV-EHR (in MVP) at 11 loci in MVP, that also replicated in UKBB and/or other cohorts. Of the 17 traits, the observational analysis in the AoU showed PTSD was associated with 13 CV-EHR traits after accounting for socioeconomic factors and depression diagnosis. PTSD colocalized with eight heart imaging traits on 2 loci and with LE8 factors on 31 loci. Leveraging blood and brain proteome expression, we found 33 and 122 genes, respectively, shared between PTSD and CVD. Blood proteome genes were related to neuronal and immune processes, while the brain proteome genes converged on metabolic and calcium-modulating pathways (FDR p <0.05). Drug repurposing analysis highlighted DRD2, NOS1, GFAP, and POR as common targets of psychiatric and CV drugs.
CONCLUSIONS: PTSD-CV comorbidities exhibit shared risk loci, and genes involved in tissue-specific regulatory mechanisms.

BACKGROUND: The health effects of Life\'s Essential 8 (LE8) on chronic diseases have been disclosed, but its association with hypertension remains unknown. The current study aimed to explore the potential link between 10-year LE8 trajectory and the incidence of hypertension.
METHODS: LE8 was constructed from four behaviors and four metabolic factors, ranging from 0 to 100. Latent mixture models were used to identify trajectories of LE8 scores during 2006 to 2016. Incident hypertension was diagnosed based on self-reported clinical diagnoses and physical examinations from 2016 to 2020. Cox models were employed to assess the association of LE8 trajectories with hypertension. In addition to incorporating the mean hs-CRP levels from 2006 to 2016, age, sex, monthly income, educational level, and occupation at recruitment were adjusted for as confounding factors.
RESULTS: 7500 participants aged 40.28 ± 10.35 years were included in the study, of whom 2907 (38.76%) were women. Five LE8 trajectory patterns were identified. After around four-year follow-up, 667 hypertension events were observed. Compared to the Low-Stable trajectory, the hazard ratios and 95% confidence intervals for the Moderate-Increasing, Moderate-Decreasing, Moderate-Stable, and High-Stable trajectories were 0.51 (0.40, 0.65), 0.81 (0.64, 1.02), 0.45 (0.36, 0.58), 0.23 (0.16, 0.33), respectively. The risk of incident hypertension decreased as participants improved their LE8 status. The robustness of the primary results was confirmed through several sensitivity analyses.
CONCLUSIONS: LE8 trajectories were associated with the incident hypertension. People who improved their LE8 scores over time experienced a decreased risk of hypertension, even if they started with lower LE8 scores initially.

BACKGROUND: Depression is an increasing illness worldwide that severely diminishes the quality of life. The study sought to elucidate the association of the American Heart Association\'s Life\'s Essential 8 (LE8) metrics with the incidence of cardiovascular disease (CVD) among depression participants and further quantify the related theoretical reduction of long-term CVD burden.
METHODS: 20,832 participants with depression from UK-Biobank were included. LE8, including diet quality, physical activity, nicotine exposure, sleep duration, body mass index, lipids, glucose, and blood pressure, was calculated at baseline and categorized into low, medium, and high levels. Hazard ratios (HR) and 95% confidence interval (95%CI) for major cardiovascular events (MACE) was calculated using Cox models. We further quantified population attributable fractions (PAF) for CVD.
RESULTS: During a median follow-up of 12.0 years, 658 MACE were recorded. After multi-variable adjustment, compared with participants with low LE8, people with high LE8 had a decreased risk of MACE (HR, 95%CI: 0.32, 0.22-0.47), non-fatal MACE (0.39, 0.26-0.61), myocardial infarction (0.23, 0.12-0.44), and ischaemic stroke (0.52, 0.27-0.99). Overall, 50.7% (95%CI: 34.5-66.9%) of MACE and 48.0% (95%CI: 29.5-66.4%) of non-fatal MACE were attributable to the low and medium adherence to LE8 at the 5-year follow-up, respectively. Sub-optimal control of blood pressure ranked as the top contributor to all types of CVD in individuals with depression.
CONCLUSIONS: Optimal adherence to LE8 was associated with lower burden of CVD in depression. Adopting a comprehensive lifestyle intervention might help further reduce CVD burden in mental disorders.

BACKGROUND: The American Heart Association (AHA) recently defined a new concept of cardiovascular health-Life\'s Essential 8 (LE8). We sought to examine whether LE8 score is associated with a risk of all-cause and cardiovascular disease (CVD)-related mortality in individuals with hypertension.
METHODS: This longitudinal study analyzed data from the National Health and Nutrition Examination Survey from 2007 to 2018 in people 20 years or older with hypertension. LE8 score (range 0-100) was measured according to the AHA definition and divided into unweighted tertiles into groups T1 (< 50.00), T2 (50.00-61.25), and T3 (≥ 61.25). Primary outcomes included all-cause mortality and CVD-specific mortality.
RESULTS: A total of 15,318 individuals with hypertension were included in this study, with a mean ± standard error age of 55.06 ± 0.25 years. During the median follow-up period of 76 months, 2525 all-cause mortality occurred, of which 806 were due to CVD. Compared with participants with hypertension in the T1 group, those in T2 and T3 respectively had 28% (adjusted HR = 0.72, 95% CI 0.63-0.83, P < 0.001) and 39% (adjusted HR = 0.61, 95% CI 0.52-0.72, P < 0.001) lower risk of all-cause mortality, the T2 and T3 groups were associated with 32% (adjusted HR = 0.68, 95% CI 0.53-0.88, P = 0.003) and 36% (adjusted HR = 0.64, 95% CI 0.49-0.84, P = 0.001) reduced risk of CVD mortality separately.
CONCLUSIONS: A higher LE8 score is associated with a lower risk of all-cause mortality and CVD mortality, and the higher LE8 score can be maintained in the clinic to improve prognosis by modifying the diet and lifestyle habits of individuals with hypertension.

OBJECTIVE: Osteoarthritis (OA) often coexists with risk factors for cardiovascular disease (CVD), worsening symptoms and functional impairment. This cross-sectional study investigated the association between Life\'s Essential 8 (LE8) and disability in individuals with OA.
METHODS: Data from 8334 United States adults (aged ≥ 20) who participated in the 2005-2018 National Health and Nutrition Examination Survey (NHANES) with complete data on LE8 components and disability status were analyzed. LE8 components, including diet, physical activity (PA), nicotine exposure, sleep, body mass index (BMI), blood lipids, glucose, and blood pressure (BP), were scored on a 0-100 scale, categorizing cardiovascular health (CVH) as low, moderate, or high. Disability mainly caused by OA was assessed using a standardized physical functioning questionnaire. Association analyses were performed using multivariable logistic regression, adjusting for demographic, socioeconomic, lifestyle, and health-related covariates.
RESULTS: Individuals with CVH scores 10 points higher had a 15% lower prevalence of OA (95% CI 0.81-0.90). Individuals with OA were more than twice as likely to experience disability. High levels of CVH were associated with a lower prevalence of disability in various domains compared to low levels of CVH (all P < 0.05), such as in activities of daily living (OR 0.32, 95% CI 0.18-0.58). Among the LE8 components, BMI, PA, and sleep health were associated with disabilities in all domains, while blood lipid scores were not.
CONCLUSIONS: A higher adherence to LE8 is associated with a lower prevalence of different types of disability in domains of physical functioning and functional limitations in individuals with OA.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear.
METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life\'s Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values.
RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause.
CONCLUSIONS: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.