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Preplanned Studies: Effect of Heart Rate on Major Adverse Cardiovascular Events in Hypertensive Patients with Different Ages and Genders

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  • Summary

    What is already known on this topic?

    The increase of heart rate will increase blood pressure, and the cardiovascular risk will increase when heart rate >80 beats/min (bpm) in patients with hypertension.

    What is added by this report?

    Compared with patients who were female, <65 years old, and with hypertension, patients who were male, ≥65 years old, and with hypertension had the lowest risk of major adverse cardiovascular events (MACE) at baseline heart rate (HR) of 70–74 bpm.

    What are the implications for public health practice?

    Patients with hypertension should control their blood pressure well, and the HR of male and elderly patients should be managed well at the same time.

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  • 21 cities: Beijing, Hangzhou, Shanghai, Xuzhou, Nanjing, Guangzhou, Shenzhen, Changsha, Yinchuan, Jilin, Xi’an, Wuhan, Shenyang, Dalian, Tianjin, Zhengzhou, Chongqing, Chengdu, Jinan, Shijiazhuang, Handan.
  • [1] Zhao MX, Zhao QH, Zheng MY, Liu T, Li Y, Wang M, et al. Effect of resting heart rate on the risk of all-cause death in Chinese patients with hypertension: analysis of the Kailuan follow-up study. BMJ Open 2020;10(3):e032699. http://dx.doi.org/10.1136/bmjopen-2019-032699CrossRef
    [2] Zhang X, Zhang M, Li C, Wang LH, Wu J, Huang ZJ, et al. Associations between hypertension status and increased heart rate - China, 2015. China CDC Wkly 2020;2(40):771 − 5. http://dx.doi.org/10.46234/ccdcw2020.209CrossRef
    [3] Kang E, Lee S, Ha E, Oh HJ, Ryu DR. The effects of blood pressure components on cardiovascular events in a Korean hypertensive population according to age and sex: a nationwide population-based cohort study. Medicine (Baltimore) 2019;98(33):e16676. http://dx.doi.org/10.1097/MD.0000000000016676CrossRef
    [4] Sun NL, Huo Y, Huang J. The current status of heart rate in Chinese hypertensive patients. Chin J Hypertens 2015;23(10):934 − 9. http://dx.doi.org/10.16439/j.cnki.1673-7245.2015.10.013 (In Chinese). CrossRef
    [5] Palatini P, Thijs L, Staessen JA, Fagard RH, Bulpitt CJ, Clement DL, et al. Predictive value of clinic and ambulatory heart rate for mortality in elderly subjects with systolic hypertension. Arch Intern Med 2002;162(20):2313 − 21. http://dx.doi.org/10.1001/archinte.162.20.2313CrossRef
    [6] Santosa A, Zhang Y, Weinehall L, Zhao GM, Wang N, Zhao Q, et al. Gender differences and determinants of prevalence, awareness, treatment and control of hypertension among adults in China and Sweden. BMC Public Health 2020;20(1):1763. http://dx.doi.org/10.1186/s12889-020-09862-4CrossRef
    [7] Gillis EE, Sullivan JC. Sex differences in hypertension: recent advances. Hypertension 2016;68(6):1322 − 7. http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.06602CrossRef
    [8] Esler M, Lambert G, Esler D, Ika Sari C, Guo L, Jennings G. Evaluation of elevated heart rate as a sympathetic nervous system biomarker in essential hypertension. J Hypertens 2020;38(8):1488 − 95. http://dx.doi.org/10.1097/HJH.0000000000002407CrossRef
    [9] Di Giosia P, Giorgini P, Stamerra CA, Petrarca M, Ferri C, Sahebkar A. Gender differences in epidemiology, pathophysiology, and treatment of hypertension. Curr Atheroscler Rep 2018;20(3):13. http://dx.doi.org/10.1007/s11883-018-0716-zCrossRef
    [10] Kim H, Lee S, Ha E, Kwon SH, Jeon JS, Noh H, et al. Age and sex specific target of blood pressure for the prevention of cardiovascular event among the treatment naive hypertensive patients. Sci Rep 2020;10(1):21538. http://dx.doi.org/10.1038/s41598-020-78641-3CrossRef
  • TABLE 1.  Blood pressure and heart rate at baseline and 24 months follow-up in hypertensive patients with different ages and genders.

    ItemSystolic blood pressure
    (mmHg)
    Diastolic blood pressure
    (mmHg)
    Heart rate (bpm)
    Baseline24 months follow-upBaseline24 months follow-upBaseline24 months follow-up
    ≥65 years old (n=4,591)145.03±17.27130.97±7.2882.41±10.3177.00±6.1972.90±8.6771.52±5.81
    <65 years old (n=5,400)145.78±17.52*130.27±6.9987.21±10.5278.21±5.7574.08±7.9371.81±5.42
    Male (n=5,045)145.40±17.09130.67±7.0985.52±10.7477.86±6.0471.73±8.2871.72±5.57
    Female (n=4,946)145.47±17.73130.51±7.1884.27±10.57§77.45±5.94§73.33±8.32§71.63±8.32
    Abbreviation: bpm=beats/min.
    Note: Compared before and after 24 months treatment, except heart rate of male patients, P values were <0.001; compared with ≥65 years old, *P<0.05, P<0.01; compared with male patients, §P <0.01.
    Download: CSV

    TABLE 2.  Effects of different baseline heart rate levels on MACE in hypertensive patients with different ages and genders.

    ItemBaseline heart rate (bpm)Hazard ratio (95%CI)PHazard ratio (95%CI)*P
    Male
    <700.996 (0.685−1.447)0.9810.871 (0.593−1.279)0.480
    70−740.639 (0.436−0.935)0.0210.593 (0.401−0.876)0.009
    75−790.756 (0.506−1.130)0.1730.751 (0.500−1.127)0.167
    ≥80RefRef
    Female
    <701.063 (0.719−1.570)0.7601.007 (0.676−1.501)0.973
    70−740.860 (0.584−1.266)0.4450.891 (0.601−1.321)0.567
    75−790.713 (0.461−1.104)0.1300.791 (0.509−1.230)0.298
    ≥80RefRef
    <65 years old
    <701.094 (0.696−1.720)0.6971.028 (0.644−1.641)0.909§
    70−740.941 (0.611−1.450)0.7840.963 (0.620−1.496)0.866§
    75−790.741 (0.458−1.199)0.2220.769 (0.473−1.249)0.288§
    ≥80RefRef
    ≥65 years old
    <700.892 (0.637−1.248)0.5050.853 (0.604−1.205)0.369§
    70−740.612 (0.432−0.867)0.0060.603 (0.422−0.861)0.005§
    75−790.751 (0.516−1.092)0.1340.784 (0.537−1.146)0.209§
    ≥80RefRef
    Abbreviation: MACE=major adverse cardiovascular events.
    * Adjusted for age/gender, baseline blood pressure, smoking, drinking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease, taking beta blockers.
    Adjusted for age, baseline blood pressure, smoking, drinking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease, and taking beta blockers.
    § Adjusted for gender, baseline blood pressure, smoking, drinking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease, and taking beta blockers.
    Download: CSV

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Effect of Heart Rate on Major Adverse Cardiovascular Events in Hypertensive Patients with Different Ages and Genders

View author affiliation

Summary

What is already known on this topic?

The increase of heart rate will increase blood pressure, and the cardiovascular risk will increase when heart rate >80 beats/min (bpm) in patients with hypertension.

What is added by this report?

Compared with patients who were female, <65 years old, and with hypertension, patients who were male, ≥65 years old, and with hypertension had the lowest risk of major adverse cardiovascular events (MACE) at baseline heart rate (HR) of 70–74 bpm.

What are the implications for public health practice?

Patients with hypertension should control their blood pressure well, and the HR of male and elderly patients should be managed well at the same time.

  • 1. Department of hypertension, Heart Center, Peking University People’s Hospital, Beijing, China
  • Corresponding author:

    Ningling Sun, sunnl@263.net

    Online Date: April 09 2021
    doi: 10.46234/ccdcw2021.084
  • The previous follow-up study of the Kailuan cohort in Tangshan City, Hebei Province found that resting heart rate (HR) was associated with all-cause death; the risk of all-cause death was the lowest when heart rate was 68–72 beats/min (bpm) and was the highest when heart rate exceeded 82 bpm (1). Compared with the normal population, the related risk was higher in hypertensive population when heart rate was > 80 bpm (2). The gender and age of patients with hypertension affected the prognosis of cardiovascular events (3), but whether it was related to heart rate was not clear. This study conducted cohort follow-up of patients with hypertension and analyzed the impact of baseline heart rate level on major adverse cardiovascular events (MACE) in patients with different ages and genders.

    The HR, blood pressure (BP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the patients were measured by Omron medical automatic electronic sphygmomanometers (model: hem-8102a). According to the baseline HR, patients were divided into 4 groups: <70 bpm, 70–74 bpm, 75–79 bpm, and ≥80 bpm. All patients with hypertension were treated with calcium antagonist (amlodipine). If the target BP was not met, other antihypertensive drugs would be added until the target BP was <140/90 mmHg. After 24 months of follow-up, the effects of baseline HR on MACE were analyzed in hypertensive patients of different ages (<65 years old/≥65 years old) and genders (male/female). The definition of MACE includes death, non-fatal stroke, non-fatal myocardial infarction, unstable angina pectoris, coronary intervention, coronary artery bypass grafting, newly onset atrial fibrillation, heart failure, and aortic dissection aneurysm, one of which criteria is enough for patient to be defined as MACE. All statistical analysis was performed by SAS (version 9.4, SAS Institute Inc., Cary, USA).

    A total of 9,991 patients with hypertension from 110 hospitals in 21 cities were enrolled in this study, including 5,045 males, 4,946 females, 5,400 patients aged <65 years, and 4,591 patients aged ≥65 years. The mean age was 64.46±10.65 years. The results showed that faster HR, younger age, and higher baseline SBP and DBP were all significant (all P<0.001) (Supplementary Table S1). After 24 months of antihypertensive drug treatment, SBP, DBP of hypertensive patients with different ages and genders were significantly lower than those at baseline (P<0.001). HR of female patients after treatment was significantly lower than that of baseline (P<0.001), but there was no significant difference in HR of male patients before and aftertreatment (Table 1).

    ItemSystolic blood pressure
    (mmHg)
    Diastolic blood pressure
    (mmHg)
    Heart rate (bpm)
    Baseline24 months follow-upBaseline24 months follow-upBaseline24 months follow-up
    ≥65 years old (n=4,591)145.03±17.27130.97±7.2882.41±10.3177.00±6.1972.90±8.6771.52±5.81
    <65 years old (n=5,400)145.78±17.52*130.27±6.9987.21±10.5278.21±5.7574.08±7.9371.81±5.42
    Male (n=5,045)145.40±17.09130.67±7.0985.52±10.7477.86±6.0471.73±8.2871.72±5.57
    Female (n=4,946)145.47±17.73130.51±7.1884.27±10.57§77.45±5.94§73.33±8.32§71.63±8.32
    Abbreviation: bpm=beats/min.
    Note: Compared before and after 24 months treatment, except heart rate of male patients, P values were <0.001; compared with ≥65 years old, *P<0.05, P<0.01; compared with male patients, §P <0.01.

    Table 1.  Blood pressure and heart rate at baseline and 24 months follow-up in hypertensive patients with different ages and genders.

    The results showed that after adjusting for baseline BP, smoking, drinking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease, and taking beta blockers, the relative risk of MACE at baseline HR of 70–74 bpm in male and ≥65 years old patients decreased by 41% and 40% [HR=0.593 (95%CI: 0.401–0.876), P=0.009; HR=0.603 (95%CI: 0.422–0.861), P=0.005] (Table 2).

    ItemBaseline heart rate (bpm)Hazard ratio (95%CI)PHazard ratio (95%CI)*P
    Male
    <700.996 (0.685−1.447)0.9810.871 (0.593−1.279)0.480
    70−740.639 (0.436−0.935)0.0210.593 (0.401−0.876)0.009
    75−790.756 (0.506−1.130)0.1730.751 (0.500−1.127)0.167
    ≥80RefRef
    Female
    <701.063 (0.719−1.570)0.7601.007 (0.676−1.501)0.973
    70−740.860 (0.584−1.266)0.4450.891 (0.601−1.321)0.567
    75−790.713 (0.461−1.104)0.1300.791 (0.509−1.230)0.298
    ≥80RefRef
    <65 years old
    <701.094 (0.696−1.720)0.6971.028 (0.644−1.641)0.909§
    70−740.941 (0.611−1.450)0.7840.963 (0.620−1.496)0.866§
    75−790.741 (0.458−1.199)0.2220.769 (0.473−1.249)0.288§
    ≥80RefRef
    ≥65 years old
    <700.892 (0.637−1.248)0.5050.853 (0.604−1.205)0.369§
    70−740.612 (0.432−0.867)0.0060.603 (0.422−0.861)0.005§
    75−790.751 (0.516−1.092)0.1340.784 (0.537−1.146)0.209§
    ≥80RefRef
    Abbreviation: MACE=major adverse cardiovascular events.
    * Adjusted for age/gender, baseline blood pressure, smoking, drinking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease, taking beta blockers.
    Adjusted for age, baseline blood pressure, smoking, drinking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease, and taking beta blockers.
    § Adjusted for gender, baseline blood pressure, smoking, drinking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease, and taking beta blockers.

    Table 2.  Effects of different baseline heart rate levels on MACE in hypertensive patients with different ages and genders.

    • The increase of HR is a common clinical phenotype of hypertension. A cross-sectional survey of 115,229 patients with hypertension in 21 cities in China showed that 38.2% of the patients with hypertension had a HR of ≥80 bpm (4). In European systolic hypertension trial, compared with patients with baseline HR <80 bpm, patients with baseline HR ≥80 bpm had an 89% increase in all-cause mortality risk after an average follow-up of 24 months (5). The previous studies in Chinese and Swedish suggested that there were age and gender differences in the prevalence, awareness, treatment, and control of hypertension (6). However, there are few studies on the optimal HR range of hypertensive patients of different ages and genders (7).

      The study compared baseline HR of patients with hypertension before treatment. The results showed that patients with faster baseline HR had higher baseline blood pressure and lower age. Previous studies have shown that increased HR is a biomarker of increased sympathetic activity (8). This study further suggested that the sympathetic activity was higher in younger patients with hypertension.

      Previous studies have shown that estrogen affects the cardiovascular system, including inducing vasodilation, inhibiting vascular remodeling, regulating renin-angiotensin-aldosterone system, and sympathetic nervous system. However, these protective effects can be significantly reversed in postmenopausal women (9). The mean age of hypertensive patients in this study was 64.46±10.65 years old, and the female patients at this age were lacking estrogen. The disappearance of estrogen’s protective effect in postmenopausal elderly women, which is closely related to increases in blood pressure variability, nocturnal blood pressure load, and cardiovascular events, is likely not related to MACE decreases in hypertensive patients with HR of 70–74 bpm. In addition, previous studies have suggested that elderly age is closely related to the occurrence of MACE, especially in patients with stage 2 hypertension, and the increased risk of MACE was only observed in ≥70 years old patients (10). The study showed that the relative risk of MACE was lower when HR was 70–74 bpm in hypertensive patients ≥65 years. Strengthening the management of HR may reduce risk of MACE.

      Furthermore, enrolled patients had been treated with standard antihypertensive drugs, which probably was one of the reasons that there was not much difference in systolic blood pressure between men and women and between younger and older people at baseline.

      This study was subjected to some limitations. First, 24-hour Holter was not used to evaluate HR variability, which was the deficiency of heart rate analysis in this study. Second, this study was not a prospective study, further studies were needed to confirm the relationship between HR and MACE.

      In summary, major adverse cardiovascular events increased when HR was ≥80 bpm in patients with hypertension. To better control the cardiovascular risk of male and elderly hypertensive patients over 65 years old, the HR should be controlled in the range of 70–74 bpm while the blood pressure is properly managed.

  • 21 cities: Beijing, Hangzhou, Shanghai, Xuzhou, Nanjing, Guangzhou, Shenzhen, Changsha, Yinchuan, Jilin, Xi’an, Wuhan, Shenyang, Dalian, Tianjin, Zhengzhou, Chongqing, Chengdu, Jinan, Shijiazhuang, Handan.
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