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: 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.

UNASSIGNED: The American Heart Association\'s Life\'s Essential 8 (LE8) Presidential Advisory deemed psychological health foundational for cardiovascular health (CVH) but did not include it as a CVH metric.
UNASSIGNED: The purpose of this study was to evaluate associations of a CVH construct enhanced with a ninth metric for psychological health based on readily administered depression screening with mortality risk in U.S. adults.
UNASSIGNED: Participants were 21,183 adults (mean age: 48y, 51% female, 11% Black, 15% Hispanic, 65% White) from the 2011 to 2018 National Health and Nutrition Examination Survey. The LE8 algorithm was used to assess CVH. Two enhanced CVH constructs that include a ninth psychological health metric based on depression screening using the Patient Health Questionnaires (PHQ-2 and PHQ-9) were computed. Multivariable Cox proportional hazards models compared all-cause and cause-specific mortality risk across CVH score tertiles and a priori defined categories (high: 80-100, moderate: 50-79, low: 0-49) in the overall sample and by sex and race and ethnicity.
UNASSIGNED: There were 1,397 deaths (414 cardiovascular and 329 cancer deaths). High vs low CVH scores, enhanced with PHQ-2 and PHQ-9, were associated with 69% and 70% lower mortality risk, while a high vs low LE8 score was associated with 65% lower risk (p-trend<0.001). Higher LE8 and enhanced CVH scores predicted lower mortality risk in both sexes and in Black and White but not Hispanic adults and were also associated with lower cardiovascular and cancer mortality. Both enhanced CVH scores had excellent performance for predicting mortality, similar to the LE8 score (C-statistic = 0.843 vs 0.842, P < 0.001).
UNASSIGNED: A CVH construct enhanced with psychological health strongly predicts mortality. Inclusion of psychological health as a ninth CVH metric, with depression screening as a feasible proxy in clinical and public health settings, should be considered.

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.

BACKGROUND: Accumulating evidence suggests that cardiovascular diseases and breast cancer share a number of common risk factors, however, evidence on the association between cardiovascular health (CVH) and breast cancer is limited. The present study aimed to assess the association of CVH, defined by Life\'s Essential 8 (LE8) and genetic risk with breast cancer incidence and mortality among premenopausal and postmenopausal women.
METHODS: We used data from the UK Biobank and conducted the multivariate Cox proportional-hazards models to examine associations of LE8 score and genetic risk with breast cancer incidence and mortality. Date on LE8 score was collected between 2006 and 2010 and composed of eight components, including behavioral metrics (diet, tobacco or nicotine exposure, physical activity, and sleep health), and biological metrics (body mass index, blood lipids, blood glucose, and blood pressure). The polygenic risk score (PRS) was calculated as the sum of effect sizes of individual genetic variants multiplied by the allele dosage.
RESULTS: A total of 150,566 premenopausal and postmenopausal women were included. Compared to postmenopausal women with low LE8 score, those with high LE8 score were associated with 22% lower risk of breast cancer incidence (HR: 0.78, 95% CI: 0.70-0.87) and 43% lower risk of breast cancer mortality (HR: 0.57, 95% CI: 0.36-0.90). By contrast, we did not observe the significant association among premenopausal women. Further analyses stratified by PRS categories showed that high LE8 score was associated with 28% and 71% decreased risk of breast cancer incidence (HR: 0.72, 95% CI: 0.60-0.87) and mortality (HR: 0.29, 95% CI: 0.10-0.83) compared to low LE8 score among high genetic risk groups, but no significant associations were found among low genetic risk groups. Furthermore, compared with postmenopausal women with high LE8 score and low genetic risk, those with low LE8 score and high genetic risk were associated with increased risk of breast cancer incidence (HR: 6.26, 95% CI: 4.43-8.84).
CONCLUSIONS: The present study suggests that better CVH is a protective factor for both breast cancer incidence and mortality among postmenopausal women. Moreover, the risk of developing breast cancer caused by high genetic susceptibility could be largely offset by better CVH.

UNASSIGNED: Evidence regarding the potential health effects of Life\'s Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited.
UNASSIGNED: The purpose of this study was to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality among individuals with T2D.
UNASSIGNED: We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes. Diet, lifestyle, and health conditions were repeatedly assessed every 2 years. The LE8 score (range 0-100), was calculated based on 8 components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. We used time-varying cox models to model the associations.
UNASSIGNED: During a median follow-up of 11.5 years in participants with T2D, there were 3,295 incident CVD cases and 3,123 deaths. Higher LE8 score was associated with lower risk of CVD incidence and total mortality among participants with diabetes. The multivariate-adjusted HRs for the highest quintile of LE8 score compared with the lowest quintile were 0.56 (95% CI: 0.53-0.59) for CVD, 0.57 (95% CI: 0.53-0.62) for heart disease, 0.53 (95% CI: 0.49-0.57) for stroke, and 0.73 (95% CI: 0.69-0.78) for total mortality (all P trend <0.001). Furthermore, compared with participants with stable or decreased LE8 score after diabetes diagnosis, those with increased LE8 score had 17% to 42% lower risk of CVD, heart disease, stroke, and mortality.
UNASSIGNED: A higher LE8 score was associated with a substantially lower risk of CVD incidence and total mortality among adults with T2D.

UNASSIGNED: The American Heart Association (AHA) recently introduced the Life\'s Essential 8 (LE8) to improve cardiovascular health (CVH). However, the association between LE8 and the risk of prediabetes or diabetes is not yet fully understood. Consequently, this study aims to assess the association between CVH, as evaluated by LE8, and the risk of prediabetes and diabetes.
UNASSIGNED: This cross-sectional study encompassed 7,739 participants aged ≥20 years from the 2007-2018 National Health and Nutrition Examination Surveys (NHANES). The CVH of participants was evaluated using the LE8, combining four health behaviors and three health factors. Glucose metabolic status categories included normal glucose metabolism, prediabetes including isolated impaired fasting glucose, isolated impaired glucose tolerance, both IFG and IGT, and diabetes. The associations between CVH and prediabetes and diabetes were analyzed using logistic regression, linear regression, restricted cubic splines, and subgroup analyses. Among 7,739 participants, 1,949 had iIFG, 1,165 were diagnosed with iIGT, 799 were IFG+IGT, and 537 were diagnosed with diabetes. After multivariable adjustments, CVH scores were inversely associated with prediabetes and diabetes, with the most robust inverse association observed between IFG+IGT and CVH across all prediabetes subgroups. Of all CVH components not directly in the causal pathway, body mass index (BMI) had the most robust associations with prediabetes and diabetes. Subgroup analyses indicated that the negative correlation between CVH and prediabetes was stronger among those with university or higher education.
UNASSIGNED: CVH, as defined by LE8, showed a significant negative association with prediabetes and diabetes.