| Part One The association of increased brachial-ankle pulse wave velo-city with heart failure in middle-aged and elderly peopleObjective: Studies on the associations of arterial stiffness with heart failure have been limited and inconsistent.This study aimed to identify the association between arterial stiffness and heart failure in middle-aged and elderly people,according to age-specific and sex-specific 75% values of brachial-ankle pulse wave velocity(ba PWV).Methods: A total of 28,259 participants aged ≥45 years without a history of atrial fibrillation who had synchronized ba PWV and health examination data from 2010-2018 in the Kailuan study were selected as the observation population.Then,participants without heart failure matched 3:1with participants with heart failure for age(±1 year)and sex.Multivariate logistic regression analysis was used to identify the association between arterial stiffness and heart failure.Results: There were 715 participants in the heart failure group and 2860 participants in the nonheart failure group for the final statistical analysis.Compared with the nonheart failure group,the heart failure group had a higher proportion of arterial stiffness(30.35% vs.25.63%,P=0.01).Multivariate logistic regression analysis showed that compared with participants without arterial stiffness,the odds ratio(OR)and 95% confidence interval(95% CI)of participants with arterial stiffness were 1.23(95% CI 1.01-1.51)for heart failure.A similar result was obtained in the sensitivity analysis after excluding those with a history of myocardial infarction(OR 1.31,95% CI 1.05-1.62).Summary: Arterial stiffness was positively associated with heart failure in a general middle-aged and elderly population,and this association was independent of traditional risk factors and myocardial infarction.This finding may help to design future intervention research to reduce the risk of heart failure in this populationPart Two The association between arterial stiffness andnew-onset heart failureObjective: Arterial stiffness(AS)was associated with heart failure in previous studies based on specific populations with small samples and the effects of age and blood pressure on AS were not taken into account.Whether AS was independently associated with new-onset heart failure in community dwellers has not been fully investigated so far.Methods: Individuals who participated in health evaluations and underwent synchronized brachial-ankle pulsewave velocity(ba PWV)screening in2010-2019,were included.They were free of heart failure and atrial fibrillation at baseline.The participants were allocated to three groups according to their ba PWV values.Normal AS was defined as ba PWV<1,400 cm/s,borderline AS was defined as 1,400 ≤ ba PWV< 1,800 cm/s,and elevated AS was defined as ba PWV ≥1,800 cm/s.The cumulative incidence of heart failure in the three groups was calculated by Kaplan-Meier method and compared by log-rank test.Cox proportional hazard regression was used to calculate hazard ratios(HRs)with 95% confidence intervals(CIs)of new-onset heart failure across different AS groups.Results: A total of 40064 participants were enrolled with a mean age of48.81±12.67 years.During a mean 5.53 years of follow-up,411 participants developed heart failure.The incidence densities of heart failure were 0.38 per1000 person-year,1.9 per 1000 person-year,5.83 per 1000 person-year for the normal AS group,the borderline AS group,and the elevated AS group,respectively.The cumulative incidences of heart failure were 1.02%,1.96%,2.21% for the normal AS group,the borderline AS group,and the elevated AS group,respectively.Compared with the normal AS group,the HR(95% CI)for incident heart failure was 1.97(1.36-2.86)for the borderline AS group and2.24(1.49-3.38)for the elevated AS group in the multivariable-adjusted model.For each 1 standard deviation(359cm/s)increase in ba PWV,the HR(95%CI)for new-onset heart failure was 1.10(1.02-1.20).To test the reliability of this study,another analysis was conducted across groups divided by ba PWV values at different age and blood pressure levels.Compared with the normal AS group,the HR(95%CI)for incident heart failure was 0.89(0.71-1.12)for the borderline AS group and 1.56(1.20-2.03)for the elevated AS group in the multivariable-adjusted model.Age subgroup analysis showed that the HR(95%CI)for new-onset heart failure was 1.36(0.28-6.55)and 2.26(1.47-3.47)for those younger than 45 years and 45 years and older,respectively,in the elevated AS group compared with the normal AS group.Sex subgroup analysis showed that the HR(95%CI)for new-onset heart failure was 2.56(1.57-4.19)and 1.30(0.60-2.82)for the male population and female population,respectively,in the elevated AS group compared with the normal AS group.Several sensitivity analyses showed similar results after excluding participants with a history of MI or new-onset MI during the follow-up period,anklebrachial index≤0.9,and taking antihypertensive agents at baseline.Summary: AS was positively associated with a higher risk of new-onset heart failure independently of traditional risk factors,with a dose-responsive and possibly age-and sex-dependent.This finding may help to screen people at high risk of heart failure and play an important role in the prevention of heart failure.Part Three The individual and combined effect of arterial stiffness and hypertension on incident heart failureObjective: To investigate the individual and combined effect of arterial stiffness(AS)and hypertension on incident heart failure in Kailuan community dwellers.Methods: Individuals who participated in health evaluations and underwent synchronized brachial-ankle pulse wave velocity(ba PWV)screening in2010-2019,were included.They were free of heart failure and atrial fibrillation at baseline.The participants were allocated to different groups according to their ba PWV values or blood pressure status.Non-AS group was defined as ba PWV<1,400 cm/s,AS group was defined as ba PWV≥1,400 cm/s.Nonhypertension group was defined as the participants had not hypertension at baseline,hypertension group was defined as the participants had hypertension at baseline.The participants were also been divided into 4 groups,according to their hypertension and AS status:1)ideal vascular function(IVF)group:normotension and ba PWV<1400 cm/s;2)normotension with AS(NTAS)group:normotension and ba PWV≥1400 cm/s;3)hypertension and non-AS(HTNAS)group:hypertension and ba PWV<1400 cm/s;4)hypertension and AS(HTAS)group:hypertension and ba PWV≥1400 cm/s.The cumulative incidence of heart failure in different groups was calculated by Kaplan-Meier method and compared by log-rank test.Cox proportional hazard regression was used to calculate hazard ratios(HRs)with 95%confidence intervals(CIs)of new-onset heart failure across different groups.Results: A total of 40064 participants were enrolled with a mean age of48.81±12.67 years.During a mean 5.53 years of follow-up,411 participants developed heart failure.The cumulative incidences of heart failure were0.35%,3.31%,for the non-AS group,the AS group,respectively.The cumulative incidences of heart failure were 0.68%,3.89%,for the non-hypertension group,the hypertension group,respectively.The cumulative incidences of heart failure were 0.24%,1.42%,0.95% and 4.58% for the IVF group,the NTAS group,the HTNAS group,and the HTAS group,respectively.Compared with the non-AS group,the HR(95% CI)for incident heart failure was2.03(1.40-2.93)for the AS group in the multivariable-adjusted model.Compared with the non-hypertension group,the HR(95% CI)for incident heart failure was 1.74(1.27-2.39)for the hypertension group in the multivariableadjusted model.Compared with the IVF group,the HR(95% CI)for incident heart failure was 2.38(1.41-4.01)for the NTAS group,2.39(1.23-4.65)for the HTNAS group and 3.69(2.14-6.35)for the HTAS group in the multivariableadjusted model.The results of subgroup analysis were as follows: compared with the IVF group,the HR(95% CI)for incident heart failure was 3.26(1.19-8.97)for the HTNAS group and 3.94(2.08-7.45)for the HTAS group in the multivariable-adjusted model in the isolated systolic hypertension;compared with the IVF group,the HR(95%CI)for incident heart failure was1.67(0.47-6.90)for the HTNAS group and 2.29(0.98-5.37)for the HTAS group in the multivariable-adjusted model in the isolated diastolic hypertension;compared with the IVF group,the HR(95%CI)for incident heart failure was 3.58(1.58-8.11)for the HTNAS group and 4.59(2.59-8.13)for the HTAS group in the multivariable-adjusted model in the high systolic and diastolic hypertension.The results of another subgroup analysis were as follows:compared with the IVF group,the HR(95%CI)for incident heart failure was1.29(0.25-6.30)for the HTNAS group and 4.23(1.58-11.33)for the HTAS group in the multivariable-adjusted model in the hypertensive controlled group;compared with the IVF group,the HR(95%CI)for incident heart failure was2.92(1.50-5.68)for the HTNAS group and 4.22(2.51-7.09)for the HTAS group in the multivariable-adjusted model in the hypertensive uncontrolled group.Sensitivity analysis after redefining AS and hypertension with new cut-off values yielded similar results,that was,the highest risk of new-onset heart failure in the HTAS group.Summary: AS and hypertension contributed to an increased risk of incident heart failure individually or with combined effect.Participants with AS and hypertension had the highest risk of developing heart failure.This finding may help to screen people at high risk of heart failure and play an important role in the prevention of heart failure.Conclusions:1.Arterial stiffness was positively associated with heart failure in a general middle-aged and elderly population,and this association was independent of traditional risk factors and myocardial infarction.2.Arterial stiffness was positively associated with a higher risk of newonset heart failure independently of traditional risk factors,with a doseresponsive and possibly age-and sex-dependent.3.Arterial stiffness and hypertension contributed to an increased risk of incident heart failure individually or with combined effect.Participants with AS and hypertension had the highest risk of developing heart failure. |
