Association of Life’s Essential 8 with incident atherosclerotic cardiovascular disease in cancer patients: the Kailuan prospective cohort study

Abstract

Cardiovascular disease (CVD) is now the second leading cause of morbidity and mortality amongst cancer survivors. The shared risk factors between CVD and cancer could not only increase the CVD risk per se but also increase the predisposition to anti-cancer treatment-related cardiovascular toxicities.1 Therefore, the most effective strategy for the prevention of CVD amongst cancer survivors is likely achieved through modification of traditional risk factors.2 We therefore investigated the associations between cardiovascular health (CVH) assessed by the Life’s Essential 8 (LE8)3 with risk of incident atherosclerotic CVD (ASCVD) and ASCVD-related mortality amongst cancer patients. The methodology is detailed in the Supplementary material online, Materials. This prospective study used data from the Kailuan cohort, where participants underwent health checkup surveys every 2 years.4,5 Adult participants with newly diagnosed cancer between 2006 and 2020, without prior ASCVD, were included. This study was approved by the ethics committee of the Kailuan General Hospital (trial registration number ChiCTR-TNRC-11001489). All participants signed written informed consent forms. According to the American Heart Association (AHA), eight components were used to create the LE8 score, including four health behaviours (diet, physical activity, smoking, and sleep) and four healthy factors [body mass index (BMI), non-high-density lipoprotein (HDL) cholesterol, blood glucose, and blood pressure].3 Due to the lack of detailed dietary data, the diet health was assessed according to the status of salt intake, tea consumption, and fatty food intake in this study.4 The algorithms for the LE8 in the Kailuan study are shown in Supplementary material online, Table S1. The aggregate score is scaled from 0 to 100 points, calculated as the unweighted average of 8 component metric scores.3 The same definitions were used to establish the health behaviour score (including diet, physical activity, smoking, and sleep) and health factor score (including BMI, non-HDL cholesterol, blood glucose, and blood pressure) to investigate the association between LE8 subscales and ASCVD. Health checkup data of the latest survey after cancer diagnosis were used to estimate these CVH scores. Ascertainment of cancer cases and definitions of ASCVD [including myocardial infarction (MI), ischaemic stroke (IS), heart failure (HF), and coronary revascularization] are detailed in the Supplementary material online, Materials. Multivariable competing risk analyses adjusting for age and sex (Model 1), plus education level, alcohol consumption, high-sensitivity C-reactive protein, anti-cancer therapy, and family history of CVD (Model 2) were used to investigate the relationship between tertiles of LE8 with risk of incident ASCVD. Restricted cubic spline analyses were used to explore the linearity of this relationship. Sub-group and sensitivity analyses are detailed in the Supplementary material online, Materials. A two-sided P < 0.05 was considered statistically significant. A total of 4424 cancer patients free of prior ASCVD were included in the current study. During a median follow-up of 2.89 (0.95, 6.94) years, 218 (5.0%) participants developed incident ASCVD, and 157 (3.5%) ASCVD-death were observed. The mean LE8 score of the overall cohort was 59.63 ± 11.48 points. Compared to patients in Tertile 1 of LE8, patients in Tertile 3 had 46% lower risks of developing composite ASCVD events (HR, 0.54; 95% CI, 0.39–0.75) and a 40% lower ASCVD related mortality risk (HR, 0.60; 95% CI, 0.41–0.88) (Table 1). An increase in the tertile of LE8 was significantly associated with reduced risk of ASCVD events (P for trend <0.001), and a linear association between LE8 with ASCVD (Poverall < 0.01) was observed (Figure 1A). A similar pattern was observed between higher health factor score with lower ASCVD (HR, 0.39; 95% CI, 0.28–0.56), but not for health behaviour score (HR, 0.85; 95% CI, 0.61–1.18) (see Supplementary material online, Table S2). There was a linear association between health factor scores with ASCVD (Poverall < 0.01) (Figure 1B), whereas no linear (Poverall = 0.188) or non-linear association (Pnonlinearity = 0.655) was observed between health behaviour score with ASCVD (Figure 1C). As for the individual component of ASCVD, compared to those in Tertile 1 of LE8, patients in the highest tertile had significantly reduced risks of IS and coronary revascularization, but not for MI and HF (Table 1). Dose-response relationships between Life’s Essential 8 score (A), health factor score (B), health behaviour score (C), with atherosclerotic cardiovascular diseases. Hazard ratios and 95% confidence levels were adjusted for age, sex, education level, drinking, high-sensitivity C-reactive protein level, family history of cardiovascular disease, and anti-cancer drugs use. Health factor score was calculated based on four health factor traits, including body mass index, non-high-density lipoprotein cholesterol, blood glucose, and blood pressure. Health behaviour score was calculated based on four health behaviour traits, including diet, physical activity, nicotine exposure, and sleep. Abbreviations: ASCVD, atherosclerotic cardiovascular diseases; HR, hazard ratio; LE8, Life’s Essential 8. The associations between LE8 with ASCVD and ASCVD-related mortality aIncidence rate presented as per 1000 person-years Model 1: adjusted for age and sex Model 2: Model 1 + education level, drinking, hs-CRP level, family history of CVD, and anti-cancer drugs use. Abbreviations: ASCVD, atherosclerotic cardiovascular diseases; CI, confidence interval; HR, hazard ratio; LE8, Life’s Essential 8. In sub-group analyses, the significant association between LE8 and ASCVD was observed in both male and female cancer patients but was more prominent amongst younger patients (<60 years). The association between LE8 and ASCVD was significantly stronger amongst patients with digestive cancers and respiratory cancers, but not for cancers of urologic or reproductive systems (see Supplementary material online, Table S3). The results from several sensitivity analyses are in agreement with the primary analysis (see Supplementary material online, Table S4). To the best of our knowledge, this is the first study investigating the association between CVH assessed by LE8 and incident ASCVD amongst cancer survivors. The significant association between higher LE8 score with lower ASCVD risk was in line with findings in a similar study using the Life’s Simple 7 metrics6 and previous studies conducted in other populations.4,7 In addition, our study observed a significant association between LE8 and ASCVD-related mortality in cancer survivors, which has not been addressed before. Our study adds novel evidence that the LE8 metrics could be a potentially strong risk stratification tool in the cardio-oncology field to reduce both morbidity and mortality of CVD amongst cancer survivors. Moreover, our study found an inverse linear relationship between the overall LE8 score and health factor score with ASCVD, which suggests that the higher the CVH assessed by LE8 at baseline, the lower the risk of developing ASCVD in cancer survivors. As observed elsewhere,4,8 no association between health behaviour score with ASCVD was found in this study, which might suggest that there is a disparity in the potential beneficial value of the LE8 components,8 with the health factor metrics being the main driver in reducing CVD amongst cancer patients. Intriguingly, in this study, younger cancer patients presented with a more significant association between LE8 and ASCVD risk, likely because ageing has more dominant effects on CVH in older individuals,9 which also highlights the importance of reaching a higher CVH score earlier in life to prevent ASCVD amongst cancer patients. Additionally, this study observed 46% and 80% lower risks of IS and coronary revascularization in patients with higher LE8 but failed to identify the associations between LE8 with risks of HF and MI, which may be due to the relatively small events number of MI and HF. The findings of this study have important implications for public health and cancer patient care. First, cancer patients are faced with a substantially heavy CVH burden (only 3.3% in high CVH and up to 20.7% in low CVH status in this study);3 therefore, it is imperative to pay sufficient attention to the CVH of cancer survivors. Second, the LE8 metrics could be a strong risk stratification tool to identify cancer patients with a high risk of developing ASCVD. Interventions to mitigate CVH and decisions regarding switching to alternative less cardiotoxic cancer treatments should be considered in cancer patients identified at high or very high risk of CVD by LE8 metrics. Third, primordial prevention that focuses on preventing the initial occurrence of CVD risk factors should be highly suggested in cancer patients.10 In conclusion, LE8 score was inversely associated with incident ASCVD and ASCVD-related mortality amongst cancer patients. Primordial prevention strategies to prevent the initial occurrence of risk factors and interventions to mitigate established risk factors should be strongly considered for cancer patients. Supplementary material is available at European Journal of Preventive Cardiology. The authors thank all the survey teams of the Kailuan study group for their contribution and the study participants who contributed their information. T.L. and S.W. contributed to the conception or design of the work. Z.W. and N.Z. contributed to the acquisition, analysis, or interpretation of data for the work. N.Z., Z.W., Y.Z. drafted the manuscript. Q.Z., Z.C., G.T., G.L., T.L., and S.W. critically revised the manuscript. All authors gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy. The funders had no role in the study design, data collection analysis, decision to publish, or manuscript preparation. This work was funded by the National Natural Science Foundation of China (81970270, 82170327 to T.L.), Tianjin Natural Science Foundation (20JCZDJC00340, 20JCZXJC00130 to T.L.), and Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-029A). The data in this study could be made available upon reasonable request to the corresponding authors.

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