Association Of Resting Heart Rate With Cardiovascular Events In The Middle-aged And Older Population

Part 1 Variables influencing heart rateObjectives: Resting heart rate reflects the balance of sympathetic and parasympathetic activity and varies under the influence of many factors.Elevated heart rate is significantly associated with risk of incident cardiovascular disease(CVD).Most studies on the correlation of resting heart rate and its influence factors were conducted in European population,and the findings were inconsistent.To investigate variables influencing heart rate in the middle-aged and older Chinese population,we conducted a correlation study in the Dongfeng-Tongji cohort.Methods: A total of 20828 participants were included in the correlation analyses,excluding participants with history of CVD or anti-hypertensive treatment.The correlations of resting heart rate and its influence factors were assessed with the Spearman rank correlation tests and generalized linear regression models.Results: Resting heart rate was negatively correlated with age(r=-0.05,P<0.01),BMI(r=-0.04,P<0.01),and positively correlated with systolic blood pressure(r=0.14,P<0.01),diastolic blood pressure(r=0.17,P<0.01),fasting blood glucose(r=0.08,P<0.01),total cholesterol(r=0.02,P=0.01),triglyceride(r=0.08,P<0.01).Participants with obesity(β=-0.98,P<0.01),exercise(β=-0.48,P<0.01)had lower mean resting heart rate.Participants with hypertension(β=3.00,P<0.01),diabetes(β=1.49,P<0.01),hyperlipidemia(β=0.40,P=0.01)had higher mean resting heart rate.Conclusions: This study suggested that resting heart rate was negatively correlated with age.Participants with obesity,exercise had lower resting heart rate.Participants with hypertension,diabetes and hyperlipidemia had higher resting heart rate.These results showed that intervention measures can be taken to control resting heart rate in a certain range and provided evidences for prevention of CVD.Part 2 Association of Resting Heart Rate and Its Change with Incident Cardiovascular Events: Prospective Cohort StudyObjectives: CVD is the major cause of disability and death.Prospective cohort studies have shown that resting heart rate is significantly associated with incident CVD.Whether heart rate change is associated with incident CVD in the general population is unclear.To investigate the associations of baseline heart rate and heart rate change with incident CVD,we conducted a prospective cohort study in the Dongfeng-Tongji cohort.Methods: A total of 20828 participants were included in the analyses of baseline heart rate and 9132 participants were included in the analyses of heart rate change,excluding participants with history of CVD or anti-hypertensive treatment.Baseline heart rate was categorized as low(<65 bpm),moderate(65 to 80 bpm),high(>80 bpm),according to integral values near 20 th and 80 th percentiles.Change of heart rate was categorized as decrease(more than 5 bpm),stable(-5 to 15 bpm),increase(more than 15 bpm),according to integral values near 20 th and 80 th percentiles.Incident CVD was followed up until December 31,2016.The associations of baseline heart rate and heart rate change with incident CVD were assessed with multivariable Cox proportional hazards models.Results: Compared with moderate baseline heart rate,low baseline heart rate was associated with 19% higher risk of incident CVD(hazard ratio [HR]=1.19,95% CI 1.07~1.32).Compared with stable heart rate in the moderate baseline heart rate group,an increase of heart rate in high baseline heart rate group(HR=1.67,95% CI 1.02~2.71)or a decrease of heart rate in low baseline heart rate group(HR=2.48,95% CI 1.27~4.82)was associated with higher risk of incident CVD.Conclusions: This study suggested that an increase of heart rate in high baseline heart rate group or a decrease of heart rate in low baseline heart rate group was associated with higher risk of incident CVD.The availability of easily monitoring and tracking resting heart rate and heart rate change would provide approaches and evidences to manage the risk of incident CVD.Part 3 Association of Resting Heart Rate with Incident Cardiovascular Events: Mendelian Randomization Study Objectives: Prospective cohort studies have shown that resting heart rate is significantly associated with incident CVD.Whether there is a causal relationship between resting heart rate and incident CVD is unclear.Mendelian randomization method can avoid confounding bias and reverse causality,thus allow us to determine causal relationships and provide us a new way to investigate the pathogenesis of CVD.To explore whether there is a causal relationship between resting heart rate and incident CVD,we conducted a Mendelian randomization study in the Dongfeng-Tongji cohort.Methods: We performed a genome-wide scanning of 7601 participants.A total of 6326 participants were included in the Mendelian randomization analyses,excluding participants with history of CVD.Until December 31,2016,2854 incident CVD were recuited as cases and 3472 without CVD were recuited as controls.The association of resting heart rate with incident CVD was assessed with Logistic regression model.We used methods of genetic risk score(GRS)and inverse-variance weighting(IVW)to explore whether there was a causal relationship between resting heart rate and incident CVD.Results: Logistic regression analyses showed that compared with moderate baseline heart rate,low resting heart rate was associated with 22% higher risk of incident CVD(odd ratio [OR]=1.22,95% CI 1.04~1.44,P=0.02).Per 10 bpm higher resting heart rate was not significantly associated with the risk of incident CVD(OR=0.94,95% CI 0.89~1.01,P=0.06).The methods of GRS and IVW showed that per 10 bpm higher resting heart rate was not significantly associated with the risk of incident CVD(GRS: OR=0.92,95% CI 0.69~1.24,P=0.60;IVW: OR=0.93,95% CI 0.69~1.24,P=0.60).Conclusions: This study suggested that resting heart rate was significantly associated with incident CVD.Low resting heart rate was associated with higher risk of incident CVD.We did not find a causal relationship between resting heart rate and incident CVD.Considering the low statistical power in this study,whether there is a causal relationship between resting heart rate and incident CVD needs to be validated in multiple-center,large-sample studies.