The mean resting heart rate in our population was 74 bpm that is more in comparison with noted reports. In light of the evidence, previous studies report resting heart rate must be ranges 60 to 65 in a healthy population.[20, 21] This superiority leads to an increasing prevalence of the cardiovascular disease in our society.[22, 23] Also, this discrepancy may be due to some underlying diseases in the selected population.
A significant negative correlation of aging with heart rate have been described by Ogliari et al. in 2015.[24] In this context, several studies have suggested that age could be related to RHR.[9, 25, 26] We demonstrated that there is a strong negative association between aging and RHR which is independent of other cardiovascular risk factors in both sex. Of course, the difference between men and women in the number of resting heart rate and its high rate in women is something that has been mentioned in previous studies.[27, 28] However, this increased heart rate at rest in women does not mean a higher risk of heart disease because the results of previous studies show that the power of the relationship between resting heart rate and all-cause mortality in women is weaker than men.[29]
As previous studies had shown, both systolic and diastolic blood pressures were significantly related to resting heart rate in a positive way. There are some investigations that demonstrated that the relationship between RHR and SBP is stronger than DBP, such as some studies in Finland, Norway, Belgium, and the USA.[12, 30] We demonstrated that this relationship is stronger in men than women like the results of Green et al. and Cirillo et al.[31, 32] Based on our knowledge, the interaction between aging and RHR on blood pressure still remains unexplained. The present study strongly indicated that gender had a significant effect on the relationship between aging and increased RHR. Figure 2 shows a significant positive rate-response relationship among SBP and RHR and inverse rate-response relationship with DBP above 80th quantile both in men and women for the first time. To shed new light on the mechanism of this relationship, previous data suggested that an increase in catecholamine concentration and sympathetic nervous system over-activity could be major mechanisms of this correlation.[33, 34]
The Results of the present study confirm and extend the finding of the Korea National Health and Nutrition Examination Survey(KNHANES) and the Third National Health and Nutrition Survey (NHANES III).[16, 35] We observed a significant association between waist circumference and RHR. Previous 20 years of longitudinal studies and HARVEST study demonstrated that RHR is an important predictor of overweight and obesity, and each 10 bpm increase in RHR, increases the risk of obesity by 30%.[25, 36] Our findings confirmed that central obesity constantly linked with higher RHR, which may be due to autonomic imbalance and adrenergic hyperactivity.[33]
Also, the findings of this study, similar to Piwońska et al. and Cooney et al. studies, demonstrated that there is a positive association between BMI and RHR in the general population.[8] [30] Furthermore, numerous studies have reported BMI and its positive relationship with all causes of mortality and coronary artery disease, especially in patients with higher RHR.[37-39]
A study in Japan on 3872 individuals demonstrated that resting heart rate is a predictor of the metabolic syndrome in the middle aged Japanese population.[40] We have provided further evidence that this relation is in both sexes. The suggested mechanism explains the pathway that starts by alteration in fat accumulation neuronal signals from the liver and visceral fat to the brain, this leads to modulate autonomic tone.[41, 42] Based on our observations, we conclude that: The effect of resting heart rate as a potential predictor of metabolic syndrome is biologically plausible.
Previous findings seem to demonstrated that there is a significant relationship between HR and hsCRP as an indicator of inflammation.[43] One of the explanations is a genetic predisposition that leads to the sympathetic nervous system (SNS) dysfunction which damages the blood vessel wall. This pathway starts neurohormonal inflammatory cascade and releases some cytokines such as TNF-α and IL-6, predominantly.[44] This pathway induced a chronic systemic inflammatory and oxidative stress state which lead to arterial stiffness and generation of the atherosclerotic plaque. [45, 46]
Compared to women, men had a higher level of triglyceride but this superiority has no clinical importance. On the other hand, Cholesterol, HDL, and LDL are significantly higher in women. Findings reveal that there is a weak relationship between triglyceride and RHR in both sexes. Our findings are in agreement with the results of SUN Ji Chao in china.[47] Few studies also have reported that significantly higher cholesterol and LDL levels correlate with higher levels of RHR in both genders. In contrast to these studies, our results seem to show no significant relationship between cholesterol and RHR.[48] Suggested theories propose that a higher concentration of TG is due to catecholamine action and leads to lipid metabolism alteration. This pathway catalyzes HDL synthesis and decreases the concentration of the LDL by stimulation.[48]
To the best of our knowledge, no previous study reported the relationship between RHR and Hb. In particular, we found a positive weak association between Hb and RHR. This relation has no definite and certain reason or explanation. It is possible that people with lower Hb, have a higher heart rate due to inadequate oxygen supply respectively. Then, our findings seem to show anemia may be considered as a minor cardiometabolic risk factor.
Our findings showed that there is a clear relationship between higher RHR and more blood glucose levels. Our result is in agreement with previous data which have been showing that increased risk of type 2 diabetes associated with increased heart rate.[10, 11, 35, 37] Similarly, Andrew Grandinetti et al. demonstrated that in the general population, a significant increase in insulin resistance titers observed in men and women with higher HR. [39] The same results were driven from analysis of the Chicago Heart Association Detection Project in Industry Study and Atherosclerosis Risk in the Communities (ARIC).[1, 38, 49] Some other theories have been suggested about this matter, one is genetic factors that determine cardiovascular fitness and also energy expenditure.[50-52] Another theory explains that increased activity of sympathetic nervous system tone can lead to an increase in HR and alter the regulation of the parasympathetic on the heart. Also, SNS overactivity stimulates hyperinsulinemia in the accompaniment of insulin resistance.[53, 54] Moreover, data reveals that patients with diabetes have increased sympathetic and decreased parasympathetic activity respectively.[55] Several studies have shown that a decrease in HR, even to a small extent, can consequently have significant public health benefits.[56]
Strengths and limitations
One of the most important strengths of this study is the large multiple biological and chemical variables that have been evaluated concerning RHR, which able us to take into account the potential confounding effect of many variables. To the best of our knowledge, this is the first study that assesses the relationship between a large panel of cardiovascular risk factors and biochemical data, and RHR.
Other strengths of this study are its type and large sample size. This is a cohort study with about 10,000 participants that leads to more generalizability of the results. Also, the two-modeling analysis confirms the consistency and importance of findings.
Some limitations of the present study are 1. The cross-sectional nature of the study did not allow us to draw causal conclusions due to the lack of follow-up data. 2. We used the average of only two readings of resting heart rate, taken only a few minutes apart, to represent the resting heart rate for each participant. 3. the interfering effect of white coat syndrome and in-office stress that might influence on blood pressure and heart rate, 4. lack of measurement of heart rate variability to improve the consistency of the findings and 5. the past medical and medication history of the participants did not be considered into the analysis.