Authors: Jing Wang, Shuilin Wu, Liuxin Li, Jing Wu, Shiqiu Meng, Xueying Qin, Xin Chen, Shoulin Wu, Jie Shi, Yanping Bao, Feng Wang
Categories: Research, Life’s essential 8, Heart failure, All-cause mortality, Hypertension, Kailuan study
Source: BMC Public Health
Authors: Jing Wang, Shuilin Wu, Liuxin Li, Jing Wu, Shiqiu Meng, Xueying Qin, Xin Chen, Shoulin Wu, Jie Shi, Yanping Bao, Feng Wang
Hypertension can lead to an increased risk of heart failure and death. The life’s essential 8 (LE8) is an eight-factor measure of cardiovascular health recently released by the American Heart Association for use in measuring cardiovascular health. However, evidence on the beneficial effects and necessity of LE8 control is still lacking, especially for hypertension.
The study population was drawn from the Kailuan cohort, hypertensive population at baseline with the non-hypertensive population matched 1 according to age and sex were involved in this analysis. The cut off value for each factor in LE8 was 50 (≥ 50 as controlled, < 50 as uncontrolled). The primary outcomes involved heart failure and all-cause mortality. Cox proportional risk regression models were used to analyze the relationship between the degree of LE8 control and the risk of heart failure and all-cause mortality among hypertensive participants. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated.
A baseline population of 69,032 Kailuan cohort with a mean age of 53.08 years (SD 10.59) was included in the study. During a mean follow-up period of 13.17 years (SD 2.57), 1308 (3.8%) heart failures and 5391 (15.6%) deaths occurred among hypertensive patients. In the hypertensive population, there was a negative dose response between the degree of LE8 control and the risk of heart failure or death (P for trend < 0.001). Compared with the group with the control less than or equal to 2 risk factors of LE8, the group with 6 or more risk factors of control had a 55% lower risk of heart failure (HR 0.45, 95% CI 0.26–0.77; P < 0.05) and a 31% lower risk of death (HR 0.69, 95% CI 0.50–0.93; P < 0.05). Compared with the non-hypertensive population, the risk of heart failure and death decreased with increasing of the number of risk factor controlled in LE8, down to a minimum of 1.27-fold (HR 1.27, 95%CI 1.13–1.42; P < 0.05) and 1.25-fold (HR 1.25, 95%CI 1.19–1.32; P < 0.05), respectively. In addition, the association between hypertension and heart failure or mortality was higher in participants aged < 60 years compared with older individuals (P for interaction < 0.05).
Enhanced control of LE8 is significantly associated with a reduced risk of heart failure and mortality in hypertensive patients, as well as a decreased likelihood of hypertension-related heart failure or mortality.
The online version contains supplementary material available at 10.1186/s12889-025-22422-y.
Hypertension is a risk factor for various diseases and is the leading cause of cardiovascular disease and death worldwide [1]. According to the 2021 Global Burden of Disease (GBD) study estimates, it ranks second in the burden of all diseases caused by risk factors [2]. Hypertension is one of the important risk factors for multiple several diseases [3–6], and it is still a serious public health problem worldwide. Although the measurement and management of hypertension have been improved with the progress of technology and economic development, and some of the disease burden caused by hypertension has been alleviated, the situation in low- and middle-income countries is still not optimistic and needs to be paid enough attention [7].
Heart failure is a common and serious clinical syndrome with heterogeneous pathophysiology and complex etiology [8, 9]. Heart failure is estimated to affect more than 56 million people worldwide, causing a substantial global health burden associated with decreased quality of life, increased medical costs, and high premature mortality [8–10]. Hypertension is one of the most common cause of heart failure, high blood pressure can make cardiac myocytes exposed to high mechanical stress and neural hormone, thereby increasing quality of myocardium, and lead to left ventricular hypertrophy, which may further progress for heart failure [11, 12]. Hypertension is also one of the most common comorbidities, and most studies have shown that the comorbidity rate of the two diseases can be as high as about 50-80% [13–16]. Therefore, it is particularly important to implement effective preventive interventions in hypertensive population.
LE8 is an update of the eight elements of cardiovascular health proposed by the American Heart Association on the basis of life’s essential 7 (LE7), with the addition of a sleep item, and it is expected to improve cardiovascular health through enhanced nursing or intervention [17]. Many studies have shown that increasing the LE8 score can reduce the risk of cardiovascular disease events, reduce mortality and improve life expectancy [18–26]. Only one study, based on the National Health and Nutrition Examination Survey (NHANES) data, found a reduced risk of all-cause mortality in adults with hypertension and a higher total LE8 score compared with a lower total LE8 score [27]. Evidence remains sparse regarding the relationship between the degree of LE8 control and future heart failure outcomes and mortality in hypertensive patients.
Therefore, to fill the gap, we used data from the Kailuan study to prospectively examine the association between the degree of LE8 control and heart failure and all-cause mortality in hypertensive patients. In addition, we investigated the association between hypertension and heart failure and all-cause mortality at different degrees of LE8 control using paired hypertensive and non-hypertensive populations.
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Our study sample was derived from the Kailuan cohort, established in the Kailuan community of Tangshan City, Hebei Province, China, and the detailed study design and procedures have been described previously [28]. Briefly, a total of 101,510 adult participants in the Kailuan community participated in the first survey between July 2006 and October 2007, and have been followed every two years since 2006. Participants with missing data on cardiovascular health behaviors and factors at baseline were excluded (n = 7051), and we excluded participants with a history of cardiovascular disease at baseline (n = 3301). Totally, 44,658 subjects with baseline hypertension and 56,852 subjects without baseline hypertension were used for further 1 matching based on age (± 2 years) and sex. Detailed procedure is shown in Fig. 1.
Fig. 1Flow chart of population inclusion and exclusion
According to the American Heart Association (AHA), the Eight Elements of LE8 include four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index (BMI), Non-high-density lipoprotein cholesterol (Non-HDL-C), blood glucose, and blood pressure) [17]. In Kailuan cohort, the total score of each factor was 100 [29], and the algorithm is shown in Supplementary Material, Table S1. The main difference between the Kailuan and American Heart Association estimates was in the estimation of dietary health. Due to the lack of detailed dietary data, the total dietary health score of the Kailuan cohort was derived from the unweighted mean of salt, high-fat foods, and tea. In this study, we considered a single item score of 50 or more for each element as control of that element according to LE8 score category including high or moderate cardiovascular health [17], and vice versa, as uncontrolled. We defined hypertension as systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg or self-reported use of antihypertensive medication in accordance with the recommendations of the Seventh Joint National Commission Report [30]. Detailed methods of blood pressure measurement have been described elsewhere [31].
Outcomes of interest included heart failure and all-cause mortality. Heart failure was first included as the end point of follow-up during the health examination in 2010, and evaluated annually during the follow-up period. The diagnostic criteria for heart failure were the European Society of Cardiology guidelines for the diagnosis of chronic heart failure [32]. The diagnosis of heart failure items (1) clinical symptoms of heart failure, such as dyspnea, fatigue, fluid retention; and New York Heart Association (NYHA) functional classification II, III, or IV, or Killip functional classification II, III, and IV; (2) left ventricular ejection fraction, measured on two-dimensional and Doppler echocardiography using the modified Simpson’s method, of ≤ 50%; and (3) a left ventricular ejection fraction > 50% but with abnormally elevated plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Heart failure was diagnosed if conditions (1) and any of (2) and (3) were met. The diagnosis of two or more times of heart failure was based on the nature and time of the first diagnosis. All-cause mortality data were collected from provincial vital statistics offices and reviewed by physicians.
Baseline characteristics, including age, sex and marital status, education level, income level, marital status, and lifestyle factors, only including alcohol drinking, and disease related factors including family history of cardiovascular disease (CVD), prevalence of chronic kidney disease (CKD) and use of antihypertensive agents, were incorporated into as confounding factors for main analysis or sensitivity analysis. We categorized education levels into illiteracy or primary school, junior high school, and senior high school or above. Income levels are divided into “<800 ¥/ month”, “800–< 1000 ¥/ month” and “≥ 1000 ¥/ month”. Alcohol drinking involved “Never”, “Current” and “Past”. The remaining factors without details were included in the analysis as continuous or binary variables.
Basic characteristics of the study population were described as mean and standard deviation (SD) for continuous variable and number with percentage for category variables. Cox proportional hazards model was used to calculate the hazard ratio (HR) and 95% confidence interval (95%CI) of the degree of control of LE8 with heart failure and all-cause mortality. The control number of LE8 in hypertensive patients was used as the independent variable, and the hypertension patients with control of LE8 less than or equal to 2 were combined into one group, and those with control of LE8 greater than or equal to 6 were combined into the other group. Group of LE8 control number less than or equal to 2 was as the reference group. Model 1 was adjusted for age and sex (male and female). Model 2 additionally adjusted for education level (illiteracy or primary school, junior high school, and senior high school or above), income (< 800, 800-< 1000, and ≥ 1000 ¥/month), marital status (yes, no), alcohol consumption (never, current and past), and family history of CVD (yes, no) on the basis of Model 1. These covariates were chosen as they are potentially causal for LE8 and outcomes. Subjects with missing key variables were eliminated and covariate missing were supplemented with Multiple Imputation. In addition, people without hypertension were included as the reference group to explore the risk of heart failure and all-cause mortality attributable to hypertension under different control degrees of LE8.
Multiplicative terms were added to Cox proportional hazards regression models to assess potential interaction associations between hypertension under LE8 control group and potential effect modifiers. Stratified analyses were performed accordingly, and subjects without hypertension were used as the reference group. To assess the stability of the results, we performed sensitivity analyses as First, we excluded cases of occurring outcomes at 2 years of follow-up. Second, a 2-year lag analysis for associations of duration of adherence was performed. Third, baseline and follow-up cancer cases were excluded. Finally, we additionally perform a model containing prevalence of CKD to Model 2. Data analyses were conducted from June 2024 through July 2024. Analyses were performed with the use of SAS software, version 9.4 (SAS Institute), and two-sided P values of less than 0.05 were considered to indicate statistical significance.
A total of 69,032 participants including hypertensive and non-hypertensive matched 1 by age and gender from Kailuan study were included. (Fig. 1) The demographic characteristics of the 69,032 participants with a mean follow-up period of 13.17 years (SD 2.57) are presented in Table 1 according to the presence or absence of hypertension and the degree of control of LE8.
Table 1Baseline characteristics of the study population. (N = 69032)Total (N = 69032)Non-hypertensive (N = 34516)Degree of Risk Factor Control among hypertensive population≤ 2 Risk Factors (N = 279)3 Risk Factors (N = 1524)4 Risk Factors (N = 5449)5 Risk Factors (N = 11630)≥ 6 Risk Factors (N = 15634)Age, years53.08 ± 10.5953.08 ± 10.5950.19 ± 9.0551.67 ± 9.5952.42 ± 10.0153.23 ± 10.3553.41 ± 11.06BMI, kg/m^2^25.22 ± 3.4524.39 ± 3.2229.32 ± 4.3928.07 ± 4.1127.12 ± 3.9916.30 ± 3.5925.21 ± 2.78 Male 58,706 (85.04)29,353 (85.04)267 (95.70)1401 (91.93)4845 (88.92)9972 (85.74)12,868 (82.31) Education level Illiteracy or primary school7727 (11.19)3683 (10.67)49 (17.56)282 (18.50)844 (15.49)1459 (12.55)1410 (9.02) Junior high school50,641 (73.36)24,766 (71.75)187 (67.03)1010 (66.27)3830 (70.29)8686 (74.69)12,162 (77.79) senior high school or above10,664 (15.45)6067 (17.58)43 (15.41)232 (15.22)775 (14.22)1485 (12.77)2062 (13.19)Income level, ¥/ month < 80060,076 (87.03)29,498 (85.46)240 (86.02)1296 (85.04)4705 (86.35)10,331 (88.83)14,006 (89.59) 800-< 10004864 (7.05)2643 (7.66)22 (7.89)119 (7.81)430 (7.89)745 (6.41)905 (5.79) ≥10004092 (5.93)2375 (6.88)17 (6.09)109 (7.15)314 (5.76)554 (4.76)723 (4.62) Alcohol drinking Never40,108 (58.10)19,536 (56.60)65 (23.30)497 (32.61)2196 (40.30)6524 (56.10)11,290 (72.21) Current26,327 (38.14)13,747 (39.83)199 (71.33)922 (60.50)2992 (54.91)4646 (39.95)3821 (24.44) Past2597 (3.76)1233 (3.57)15 (5.38)105 (6.89)261 (4.79)460 (3.96)523 (3.35) Marital status 68,650 (99.45)34,278 (99.31)277 (99.28)1514 (99.34)5417 (99.41)11,598 (99.72)15,566 (99.57) Family history of CVD 4103 (5.94)1984 (5.75)37 (13.26)159 (10.43)440 (8.07)707 (6.08)776 (4.96) Chronic kidney disease 10,823 (15.68)3745 (10.85)64 (22.94)286 (18.77)1030 (18.90)2249 (19.34)3449 (22.06) Antihypertensive agents 7701 (11.16)0 (0.00)118 (42.29)588 (38.58)1551 (28.46)2663 (22.90)2781 (17.79) Health factors control Blood glucose62,043 (89.88)31,941 (92.54)96 (34.41)857 (56.23)3848 (70.62)9922 (85.31)15,379 (98.37) Blood lipids53,000 (76.78)27,061 (78.40)40 (14.34)406 (26.64)2526 (46.36)7935 (68.23)15,032 (96.15) Body mass index63,189 (91.54)32,923 (95.38)115 (41.22)931 (61.09)3996 (73.33)9830 (84.52)15,394 (98.46) Health behaviors control Diet health17,154 (24.85)8893 (25.76)21 (7.53)215 (14.11)951 (17.45)2342 (20.14)4732 (30.27) Nicotine exposure43,873 (63.55)21,207 (61.44)29 (10.39)328 (21.52)2000 (36.70)6709 (57.69)13,600 (86.99) Physical activity62,975 (91.23)31,435 (91.07)105 (37.63)903 (59.25)4271 (78.38)10,840 (93.21)15,421 (98.64) Sleep health61,902 (89.67)30,990 (89.78)114 (40.86)922 (60.50)4131 (75.81)10,414 (89.54)15,331 (98.06)Values are mean ± SD for continuous variables or number (percentage) for categorical variablesBMI, body mass index. CVD, cardiovascular disease. SD, standard deviation
At recruitment, the mean age of total participants was 53.08 years (SD 10.59) with a mean BMI of 25.22 (SD 3.45), and the majority of them were male (85.04%). Most of the participants had junior high school education (73.36%), low income (<800 ¥/month, 87.03%), and were married (99.45%), which were basically consistent with the characteristics of non-hypertensive subjects, and similar characteristics were observed in all groups with different levels of control. However, alcohol use, family history of CVD and prevalence of CKD differed between the control groups and non-hypertensive population. Antihypertensive drugs were only used in hypertensive patients, and decreased gradually with the improvement of risk factor control. The proportion of health factors and health behaviors were higher in the group with higher control degree of LE8. It is worth noting that the proportion of healthy diet in the group with the highest degree of control was only about 30% due to the standard of never drinking tea, and the other factors were maintained at about 90%. (Table 1)
We explored the association between the degree of “Life’s Essential 8” control and heart failure or death in hypertensive patients, which of 3.8% developed heart failure and 15.6% died during follow-up, and found that risk of heart failure decreased with the increase of the number of factors controlled in the multivariate model (P for trend < 0.001). Controlling each risk factor could reduce the risk of heart failure by about 22% (HR 0.78, 95%CI 0.74–0.82; P < 0.05). Compared with control of less than or equal to 2 risk factors, control of 6 or more risk factors reduced the risk of heart failure by 55% (HR 0.45, 95%CI 0.26–0.77; P < 0.05) (Model 2). For the ending for all-cause mortality, similar results were found. Multivariable analysis showed that there was a dose-response relationship between the number of risk factor controls and all-cause mortality (P for trend < 0.001). Each risk factor control reduced the risk of all-cause mortality by 13% (HR 0.87, 95%CI 0.85–0.90; P < 0.05). The risk of all-cause mortality when controlling 6 or more risk factors was 69% of that when controlling less than or equal to 2 risk factors (HR 0.69, 95%CI 0.50–0.93; P < 0.05). (Model 2, Table 2)
Table 2Adjusted HR of incident HF and all-cause mortality according to the LE8 score control among hypertensive patients. (N = 34516)≤ 2 Risk Factors N = 2793 Risk Factors N = 15244Risk Factors N = 54495 Risk Factors N = 11,630≥ 6 Risk Factors N = 15,634Per 1 Risk-Factor ControlP for trend HF No. of case/person-years14/363080/19,664252/70,508473/151,168489/205,044 Model 1Ref.0.96 (0.55,1.70)0.81 (0.47,1.39)0.67 (0.39,1.14)0.49 (0.29,0.84)0.80 (0.75–0.82)< 0.001 Model 2Ref.0.94 (0.53,1.65)0.79 (0.46,1.35)0.63 (0.37,1.08)0.45 (0.26,0.77)0.78 (0.74,0.82)< 0.001 All-Cause Mortality No. of case/person-years46/3718246/20,060914/71,8001893/153,4452292/207,461 Model 1Ref.1.00 (0.70,1.34)0.96 (0.70,1.307)0.85 (0.63,1.16)0.72 (0.53,0.97)0.86 (0.84–0.91)< 0.001 Model 2Ref.0.95 (0.68,1.31)0.95 (0.697,1.30)0.86 (0.61,1.13)0.69 (0.50,0.93)0.87 (0.85,0.90)< 0.001Data were HR and 95% CIModel adjusted for age and sexModel model 1 + education (illiteracy or primary school, junior high school, senior high school or above), income (≤ 800, 800-<1000, ≥1000 ¥/month), marital status (yes, no), alcohol-drinking (never, past, current), family history of CVD (yes, no)CI, confidence interval. CVD, cardiovascular disease. HF, heart failure. HR, hazard ratio
When the non-hypertensive population was included in the analysis as the reference group, the results of the multivariable model showed that the risk of heart failure in the hypertensive population to control less than or equal to 2 risk factors was about 2.9 times that in the non-hypertensive group (HR 2.89, 95%CI 1.70–4.90; P < 0.05). With the increase of the degree of risk factor control in hypertensive patients, the risk decreased to about 1.3 times when controlling 6 or more risk factors (HR 1.27, 95%CI 1.13–1.42; P < 0.05). For all-cause mortality, the model after adjusting for confounding factors showed that controlling less than or equal to 2 risk factors among hypertensive individuals increased the risk of 86% compared with non-hypertensive individuals (HR 1.86, 95%CI 1.37–2.52; P < 0.05). The risk of all-cause mortality also decreased with the increase of risk factor control, and it was lowest when 6 or more risk factors were controlled, with HR of 1.25 (1.19, 1.32). (Model 2, Table 3)
Table 3Adjusted HR of incident HF and all-cause mortality according to the LE8 score control compared with matched control subjects. (N = 69032)Non-hypertensive N = 34,516≤ 2 Risk Factors N = 2793 Risk Factors N = 15244Risk Factors N = 54495 Risk Factors N = 11,630≥ 6 Risk Factors N = 15,634 HF No. of case/person-years820/459,16914/363080/19,664252/70,508473/151,168489/205,044 Model 1Ref.2.74 (1.16,4.64)2.60 (2.07,3.28)2.18 (1.89,2.51)1.78 (1.59,2.00)1.30 (1.16,1.46) Model 2Ref.2.89 (1.70,4.90)2.68 (1.13,3.38)2.24 (1.94,2.58)1.78 (1.59,2.00)1.27 (1.13,1.42) All-Cause Mortality No. of case/person-years3862/463,11146/3718246/20,060914/71,8001893/153,4452546/207,461 Model 1Ref.1.82 (1.35,2.47)1.74 (1.54,1.98)1.73 (1.61,1.86)1.53 (1.45,1.62)1.28 (1.21,1.34) Model 2Ref.1.86 (1.37,2.52)1.78 (1.53,1.98)1.75 (1.62,1.88)1.52 (1.44,1.60)1.25 (1.19,1.32)Data were HR and 95% CIModel adjusted for age and sexModel model 1 + education (illiteracy or primary school, junior high school, senior high school or above), income (< 800, 800-< 1000, ≥ 1000 ¥/month), marital status (yes, no), alcohol-drinking (never, past, current), family history of CVD (yes, no)CI, confidence interval. CVD, cardiovascular disease. HF, heart failure. HR, hazard ratio
In the interaction analysis, the results showed that only age had interaction on heart failure or all-cause mortality caused by hypertension (P for interaction < 0.05). Stratified analysis showed that the risk of heart failure due to hypertension decreased from 3.5 times (HR 3.54, 95%CI 1.94–6.46; P < 0.05) to 1.4 times (HR 1.38, 95%CI 1.18–1.61; P < 0.05) in younger adults when the number of risk factors controlled increased from “≤2” to “≥6” referenced to non-hypertension. However, the risk of heart failure due to hypertension was higher in those younger than 60 years than in those older than 60 years. For all-cause mortality, there were similar results that hypertension patient with less than or equal to 2 risk factors controlled leaded to more than two-times risk than non-hypertension (HR 2.10, 95%CI 1.44–3.06; P < 0.05), which reducing to 1.38 times (HR 1.38, 95%CI 1.28–1.50; P < 0.05) with 6 or more risk factors controlled. It is noteworthy that although there was no significant stratification effect of income, the risk of heart failure in hypertensive subjects was 3.33 times higher than that in non-hypertensive subjects when less than or equal to 2 risk factors were controlled (HR 3.33, 95%CI 1.96–5.66; P < 0.05), and the risk was significantly reduced to 1.25 times when 6 or more risk factors were controlled (HR 1.25, 95%CI 1.11–1.41; P < 0.05). (Tables 4 and 5)
Table 4Stratified HR for HF according to the LE8 score control compared with matched control subjects. (N = 69032)Non-hypertension≤ 2 Risk Factors3 Risk Factors4Risk Factors5 Risk Factors≥ 6 Risk Factors
P
interaction
Sex0.651 femaleRef.4.86 (0.68,34.94)1.40 (0.515,3.79)2.88 (2.01,4.13)2.30 (1.74,3.04)0.96 (0.69,1.32) maleRef.2.82 (1.625,4.88)2.82 (2.22,3.57)2.139 (1.83,2.50)1.69 (1.50,1.92)1.32 (1.17,1.49)Age category (y)0.001 < 60Ref.3.54 (1.94,6.46)3.17 (2.39,4.21)2.76 (2.30,3.30)2.26 (1.95,2.62)1.38 (1.18,1.61) ≥ 60Ref.1.94 (0.62,60.54)2.11 (1.40,3.17)1.64 (1.29,2.08)1.28 (1.07,1.53)1.17 (0.99,1.37)BMI category (kg/m^2^)0.596 18.5-<24Ref.1.71 (0.24,12.21)3.40 (1.98,5.85)2.17 (1.59,2.97)1.75 (1.40,2.18)1.25 (1.02,1.52) < 18.5 or ≥ 24Ref.2.78 (1.60,4.83)2.35 (1.81,3.04)2.10 (1.78,2.47)1.69 (1.47,1.93)1.22 (1.07,1.40)Income level (¥/ month)0.257 <800Ref.3.33 (1.96,5.66)2.60 (2.02,3.35)2.26 (1.94,2.63)1.71 (1.51,1.93)1.25 (1.11,1.41) 800-< 1000Ref.-4.49 (2.28,8.84)2.19 (1.29,3.73)1.93 (1.26,2.96)1.33 (0.86,2.06) ≥1000Ref.-1.68 (0.52,5.42)2.15 (1.19,3.88)2.76 (1.81,4.20)1.42 (0.89,2.28)Family history of CVD0.252 NoRef.3.05 (1.76,5.28)2.74 (2.16,3.48)2.20 (1.89,2.55)1.78 (1.59,2.00)1.25 (1.11,1.40) YesRef.2.01 (0.27,14.78)2.25 (0.87,5.77)3.04 (1.76,5.24)1.80 (1.05,3.07)1.78 (1.06,3.07)Data were HR and 95% CIModel: adjusted for age, sex, education (illiteracy or primary school, junior high school, senior high school or above), income (<800, 800-<1000, ≥1000 ¥/month), marital status (yes, no), alcohol drinking (never, past, current), and family history of CVD (yes, no)BMI, body mass index. CI, confidence interval. CVD, cardiovascular disease. HF, heart Failure. HR, hazard ratio
Table 5Stratified HR for all-cause mortality according to the LE8 score control compared with matched control subjects. (N = 69032)Non-hypertension≤ 2 Risk Factors3 Risk Factors4Risk Factors5 Risk Factors≥ 6 Risk Factors
P
interaction
Sex0.143 femaleRef.2.13 (0.30,15.17)2.51 (1.56,4.04)2.13 (1.66,2.74)1.91 (1.58,2.30)1.35 (1.12,1.32) maleRef.1.83 (1.34,2.49)1.68 (1473,1.93)1.71 (1.58,1.84)1.48 (1.40,1.57)1.25 (1.18,1.32)Age category (y)<0.001 < 60Ref.2.10 (1.44,3.06)2.18 (1.84,2.57)1.96 (1.77,2.17)1.72 (1.58,1.86)1.38 (1.28,1.50) ≥ 60Ref.1.58 (0.93,2.67)1.32 (1.07,1.62)1.57 (1.42,1.75)1.38 (1.28,1.49)1.16 (1.09,1.25)BMI category (kg/m^2^)0.722 18.5-<24Ref.2.36 (1.22,4.54)1.89 (1.42,2.52)1.84 (1.60,2.10)1.57 (1.43,1.72)1.25 (1.16,1.36) < 18.5 or ≥ 24Ref.1.82 (1.29,2.57)1.76 (1.52,2.04)1.76 (1.62,1.93)1.53 (1.42,1.64)1.27 (1.18,1.36)Income level (¥/ month)0.893 < 800Ref.1.90 (1.38,2.62)1.78 (1.55,2.04)1.76 (1.63,1.91)1.54 (1.45,1.63)1.25 (1.18,1.32) 800-<1000Ref.1.25 (0.31,5.06)1.36 (0.79,2.34)1.85 (1.40,2.44)1.40 (1.11,1.76)1.30 (1.05,1.61) ≥ 1000Ref.1.93 (0.48,7.78)1.44 (0.81,2.59)1.37 (0.98,1.91)1.24 (0.97,1.59)1.31 (1.04,1.64)Family history of CVD0.079 NoRef.1.97 (1.44,2.69)1.70 (1.49,1.95)1.72 (1.60,1.86)1.51 (1.43,1.60)1.24 (1.18,1.31) YesRef.0.95 (0.24,3.86)2.50 (1.59,3.95)2.33 (1.71,3.17)1.80 (1.36,2.38)1.50 (1.13,2.00)Data were HR and 95% CIModel: adjusted for age, sex, education (illiteracy or primary school, junior high school, senior high school or above), income (<800, 800-<1000, ≥1000 ¥/month), marital status (yes, no), alcohol drinking (never, past, current), and family history of CVD (yes, no)BMI, body mass index. CI, confidential interval. CVD, cardiovascular disease. HR, hazard ratio
In the sensitivity analysis, when we excluded outcomes within the first 2 years of follow-up, the risk of heart failure in hypertensive patients who controlled for less than or equal to 2 risk factors was 2.7 times higher than that in non-hypertensive patients (HR 2.71, 95%CI 1.53–4.80; P < 0.05). When the number of control factors increased to 6 or more, the risk decreased to 1.3 times (HR 1.29, 95%CI 1.15–1.45; P < 0.05). For all-cause mortality risk, with control of less than or equal to 2 to 6 or more factors, the risk decreased from 83% (HR 1.83, 95%CI 1.33–2.50; P < 0.05) to 26% (HR 1.26, 95%CI 1.19–1.33; P < 0.05). In addition, other sensitivity analyses were generally consistent with the main results. (Table 6)
Table 6Sensitivity analysisNon-hypertension≤ 2 Risk Factors3 Risk Factors4Risk Factors5 Risk Factors≥ 6 Risk FactorsExcluding outcomes within the first 2 years of follow-up ^^HF(n = 68460)Ref.2.71 (1.53,4.80)2.67 (2.10,3.40)2.27 (1.96,2.63)1.80 (1.60,2.02)1.29 (1.15,1.45) ^^Death(n = 68609)Ref.1.83 (1.33,2.50)1.74 (1.53,1.99)1.75 (1.63,1.89)1.53 (1.44,1.62)1.26 (1.19,1.33)A 2-year lag analysis for Associations of duration of adherence ^^HF (n = 69032)Ref.2.70 (1.52,4.78)2.67 (2.09,3.40)2.27 (1.96,2.63)1.79 (1.59,2.02)1.30 (1.15,1.46) ^^Death (n = 69032)Ref.1.83 (1.33,2.50)1.74 (1.53,1.99)1.75 (1.63,1.89)1.53 (1.44,1.62)1.26 (1.19,1.33)Excluding cancer cases at baseline and follow-up ^^HF (n = 68773)Ref.2.90 (1.70,4.92)2.70 (2.14,3.41)2.25 (1.95,2.60)1.79 (1.60,2.00)1.26 (1.12,1.41) ^^Death (n = 68773)Ref.1.86 (1.37,2.52)1.75 (1.54,2.00)1.74 (1.62,1.88)1.52 (1.44,1.60)1.24 (1.18,1.31)Additional adjustment for CKD prevalence ^†^HF (n = 69032)Ref.2.76 (1.62,4.69)2.61 (2.07,3.29)2.18 (1.89,2.52)1.74 (1.55,1.95)1.24 (1.10,1.38) ^†^Death (n = 69032)Ref.1.78 (1.32,2.42)1.70 (1.50,1.94)1.71 (1.59,1.84)1.49 (1.41,1.57)1.22 (1.16,1.29)Data were HR and 95% CI^*^ Adjusted for age, sex, education (illiteracy or primary school, junior high school, senior high school or above), income (<800, 800-<1000, ≥1000 ¥/month), marital status (yes, no), alcohol drinking (never, past, current), and family history of CVD (yes, no)^†^ Adjusted for age, sex, education (illiteracy or primary school, junior high school, senior high school or above), income (< 800, 800-< 1000, ≥ 1000 ¥/month), marital status (yes, no), alcohol drinking (never, past, current), and family history of CVD (yes, no), CKD (yes, no)CVD, cardiovascular disease. HF, Heart Failure. HR, hazard ratioCI, confidence interval. CKD, chronic kidney disease. CVD, cardiovascular disease. HF, heart failure. HR, hazard ratio
In this prospective cohort study of Chinese hypertensive patients, over half of the participants exhibited less than six factors controlled for LE8. We observed a significant association between a higher degree of LE8 control and reduced risks of heart failure and all-cause mortality. Hypertensive patients with the highest level of LE8 control had a 55% lower risk of heart failure and a 31% lower risk of all-cause mortality compared to those with the lowest level. Furthermore, the risk of heart failure and mortality associated with hypertension decrease as the level of LE8 control increases, when compared to individuals without hypertension. Additionally, we found that hypertension was more strongly associated with heart failure or mortality in participants under 60 years old compared to older age groups, while achieving LE8 control showed better effectiveness in reducing these risks.
The control of LE8 can effectively mitigate the risk of heart failure and mortality. Previous studies consistently demonstrate that higher cardiovascular fitness, evaluated by LE8, is associated with a decreased risk of heart failure and mortality in both the general population and individuals with chronic diseases [18, 20, 22, 29, 33–42]. A cross-sectional analysis conducted in the United States using NHANS data revealed that heart failure is one of the diseases most strongly linked to cardiovascular health based on LE8 [39], which was further supported by a prospective cohort analysis utilizing UK Biobank data [41]. Researchers utilizing the Kailuan cohort discovered that elevated levels of LE8 reduced the risk of heart failure by 68% compared to lower levels in patients with chronic kidney disease (CKD), underscoring the importance of employing LE8 for heart failure prevention among CKD patients [33]. By combining individual-level data from six contemporary U.S. cohorts, it was observed that each 10-point increase in overall LE8 score corresponded to a 23–38% lower risk for heart failure and a 17–21% lower risk for all-cause mortality [34]. A follow-up study conducted within the Kailuan cohort involving young adults without cardiovascular disease demonstrated that individuals with lower cardiovascular health scores faced nearly twice the risk of death compared to those with higher scores [29]. Utilizing NHANES, a nationally representative sample of U.S. adults, researchers found that individuals with high cardiovascular fitness (LE8 score ≥ 80) had an approximately nine-year longer life expectancy at age 50 than those with low fitness (LE8 score < 50) [22]. Furthermore, there existed a significant inverse curve trend between LE8 score and both all-cause and cardiovascular mortality [35]. Higher levels of LE8 were associated with reduced all-cause and cause-specific mortality among CKD patients as well [38]. In the Framingham Heart Study, participants with a LE8 of ≥ 68 (the median sample) had a 45% lower risk of death than those with a LE8 of < 68 [36], and each standard-deviation increase in the LE8 score was associated with a 29% lower risk of all-cause mortality [37]. Few studies have investigated the role of LE8 or even LE7 in assessing the risk of heart failure and all-cause mortality in hypertensive individuals. The only other study that has examined the association between the LE8 score and all-cause mortality in hypertensive individuals is largely consistent with our findings [27]. However, regrettably, it did not include a controlled group of non-hypertensive individuals to fully account for the impact of LE8, nor did it investigate the primary outcome of heart failure.
LE8 control can reduce the risk of heart failure and mortality caused by hypertension. Numerous previous studies have consistently demonstrated a positive correlation between hypertension and an elevated risk of various cardiovascular diseases as well as death. A comprehensive meta-analysis comprising 123 studies revealed that there was a corresponding 20% decrease in the risk of major cardiovascular diseases, a 28% decrease in the risk of heart failure, and a significant 13% reduction in all-cause mortality for every 10 mmHg reduction in systolic blood pressure [42]. Another meta-analysis involving 17 cohort studies encompassing 4.5 million young adults found that elevated blood pressure was linked to an increased likelihood of experiencing cardiovascular events, with evidence suggesting a graded and progressive association [43]. In addition to observational findings, another meta-analysis based on independent trials from diverse sources indicated that primary prevention strategies targeting blood pressure were significantly associated with reduced mortality rates and decreased risks of developing cardiovascular diseases among individuals with baseline systolic blood pressure levels ≥ 140 mmHg [44]. These further underscore the crucial role played by blood pressure management in preventing cardiovascular disease. However, few studies have investigated the effect of controlling health factors on the risk of cardiovascular events or death due to hypertension. A cohort based on national health screening in Korea found that the risk of cardiovascular events and death was lower in patients with uncontrolled hypertension than in those with uncontrolled hypertension and diabetes [45]. Another cohort of 450,000 male found a significant association between hypertension and lung cancer mortality only among smokers [46]. The impact of overall change in LE8 on the risk of hypertension-related heart failure and mortality was not evaluated. Our findings, making up for this defect, demonstrated a consistent association between higher levels of LE8 control and reduced risks of heart failure and all-cause mortality attributed to hypertension, aligning with the conclusion drawn from single-factor control.
Hypertension in young people is more likely to lead to the occurrence of cardiovascular events or death. This was supported by the results of our stratified analyses, in which we found stronger associations among younger participants. In another study based on the Kailuan cohort, researchers specifically examined age and found that younger individuals had a higher risk of heart failure [33]. Among young adults in the Kailuan cohort, low cardiovascular fitness was associated with a 6-fold risk of cardiovascular disease compared with high cardiovascular fitness [29]. A prospective study using the UK Biobank of 250,000 found that the LE8 score was more strongly associated with major adverse cardiovascular events in participants younger than 50 years [41]. In another previous study, using the NHANS data, researchers found a stronger association between cardiovascular fitness and the risk of death in people aged 46 to 65 years than in older people [47]. These consistent conclusions all emphasized the importance of controlling LE8 in early life. In addition, significant reductions in heart failure risk were observed with increasing degree of control of LE8 in the low-income population. This also highlights the importance of implementing health education or health promotion among low-income populations in order to prevent the onset of the disease.
The LE8 framework represents a comprehensive and holistic approach to lifestyle, which has been increasingly supported by numerous studies highlighting its inseparable association with cardiovascular disease. This underscores the significance of LE8 in evaluating and enhancing individuals’ cardiovascular health. There are some implications and recommendations for public health Firstly, at the national level, it is imperative for each country to expeditiously issue relevant guidelines or policies to ensure the authority and feasibility of universal education. Particularly, this approach has significant health economics benefits for low- and middle-income countries. Secondly. From the clinical and nursing perspective, active implementation of standardized training programs should be pursued to facilitate the application and dissemination of LE8 in clinical practice. Finally. From the standpoint of patients and general populace, LE8 should be actively embraced and flexibly adopted in real-life scenarios.
Our study has several important strengths. First, it is the first to comprehensively and prospectively examine the association of LE8 control with heart failure and all-cause mortality in Chinese hypertensive patients. Second, this study, which is based on a Chinese cohort, holds significant reference value for low- and middle-income countries. In addition, the average follow-up time of this study has been more than ten years, and have enough sample size. This study has several limitations that should be acknowledged. First, it was an observational study, and confounding factors could not be fully balanced. Therefore, no conclusive causal inferences can be drawn, which is a limitation of most cohort studies. Second, LE8 was mainly obtained through structured questionnaires, specifically collected via self-reporting, with the main potential bias being misclassification bias. Although we anticipated that this misclassification would be non-differential in our prospective study, it could still result in an underestimation of the true association. In future studies, researchers can collect some classified self-reports by means of continuous variable collection, multiple collection homogenization or quantitative device collection to achieve further accuracy of information. Thirdly, the subjects of this study were exclusively from Chinese population and most of them are male groups, which limits the extrapolation of the results; however, they hold significant reference value for developing countries or those with low-income economies, which also serves as a strength we have highlighted. Furthermore, we did not differentiate outcomes by subtype, which may have led to a reduced clinical benefit associated with these outcomes.
In conclusion, our findings suggest that enhanced control of LE8 is significantly associated with a reduced risk of heart failure and mortality in hypertensive patients, as well as a decreased likelihood of hypertension-related heart failure or mortality. These results hold substantial implications for both public health and clinical practice.
Below is the link to the electronic supplementary material.
Supplementary Material 1