Association of heart rate variability and C-reactive protein in patients with depression

ABSTRACT

Background:

Depression has been shown to be correlated with cardiovascular (CV) morbidity and mortality. Inflammation and autonomic nervous system (ANS) dysfunction are possible causes. Numerous clinical studies have found an association between inflammatory pathways and the ANS. The aim of this study was to investigate the relationship between different heart rate variability (HRV) parameters and C-reactive protein (CRP) levels in depressed patients without concomitant diseases.

Materials and Methods:

Sixty-five depressed patients who were not taking medication participated in this cross-sectional study. The Tenth Revision of the International Classification of Diseases and Related Health Problems (ICD-10) categorization of mental and behavioral disorders served as the basis for the diagnosis of depression. HRV processing and analysis were performed using ADInstrument’s Pro LabChart (PowerLab 8Pro) data analysis software. HRV was recorded for 5 min in an upright sitting position using a lead II electrocardiogram (ECG) (short-term HRV). CRP levels were measured using an ELISA (enzyme-linked immunosorbent assay) test.

Results:

None of the measures of HRV showed a significant relationship with pulse rate, systolic blood pressure, diastolic blood pressure, or body mass index (BMI). Weight and BMI were strongly positively related (r = 0.420, P = 0.003) to pRR50 (percentage of successive RR intervals differing by more than 50 ms). Very low frequency (VLF), low frequency (LF), and the LF/HF (high frequency) ratio were all strongly positively correlated with CRP (r = 0.595, P = 0.001), whereas HF was also significantly negatively correlated (r = 0.383, P = 0.007). CRP had a significant negative correlation with the logarithm (ln) HF and a significant positive correlation with lnVLF, lnLF, and lnLF/HF.

Conclusion:

Measurement of resting HRV and CRP may be helpful in detecting CV disease in depressed patients. Low HRV and elevated serum CRP should prompt physicians to begin treatment for risk CV as soon as possible.

Introduction

Depression is a serious human disease. It is prevalent throughout the world and is associated with severe cardiovascular (CV) morbidity and mortality.[1] It significantly increases the number of years spent in a disabling condition and contributes substantially to the burden of disease.[2] According to WHO (World Health Organization), more than 264 million people worldwide suffer from depression,[3] and 5% of Indians suffer from depression.[4] Recent studies have shown that depression is a strong and independent risk factor for CV disease (CVD), even in physically healthy people.[5]

In healthy people, the sympathetic and parasympathetic nervous systems of the autonomic nervous system (ANS) interact dynamically. At rest, the parasympathetic nervous system takes control, whereas the sympathetic nervous system is primarily responsible for the fight-or-flight response.[6,7] Numerous studies have found an inverse relationship between inflammatory biomarker concentrations and heart rate variability (HRV) parameters that are primarily influenced by parasympathetic activity, such as high frequency (HF), standard deviation of all R–R intervals (SDRR), and root mean square of successive differences (RMSSD)[7]

Autonomic activity and depression may be related, according to a previous study.[8] Autonomic activity has often been studied using HRV, a simple noninvasive method.[9] HF, low frequency (LF), and very LF (VLF) bands can be extracted from HRV data.[10] The HF band shows vagal activity, whereas the LF/HF ratio indicates sympathetic activity. The VLF band, representing the balance between sympathetic and vagal activity, is associated with the renin–angiotensin system, chronic inflammation, and the renin–angiotensin system.[7,11]

Biomarkers have been extensively studied in the context of the ANS and its effects on emotion regulation and dysregulation, for example, in the neurovisceral integration model[12] and polyvagal theory.[13] One potential biomarker is low HRV, which is indicative of vagal dysfunction.[14] Vagal efferent activation associated with the parasympathetic component of the ANS significantly decreases levels of proinflammatory cytokines, thereby reducing systemic inflammation, consistent with a cholinergic anti-inflammatory pathway.[15]

C-reactive protein (CRP) has both pro- and anti-inflammatory properties. In studies, major depressive disorder has been associated with elevated levels of proinflammatory cytokines.[16] It is well known that high CRP levels are a predictor of CVD and that people with depression are more likely to develop it than those without depression. The association between depression and elevated CRP levels may also contribute to the association between depression and a higher risk of CVD and mortality. Unfavorable associations between HRV measures and inflammatory biomarkers were found in a recent meta-analysis.[3] However, one study found an association between HRV measures and biomarkers related to inflammation.[7] In addition, most of the research conducted to date on the association between HRV measures and inflammation has been conducted in clinical settings or in depressed patients with comorbidities.[4] Therefore, the aim of the present study was to investigate the association between different HRV parameters and CRP levels in depressed patients without concomitant diseases.

Material and Methods

Single-center cross-sectional study: after approval by the institutional ethics committee (Ref. Code – 97 ECM II B – Thesis/P16), a total of 65 drug-naïve patients with depression were enrolled in the OPD (outpatient department) of the psychiatric department of King George’s Medical University Hospital, Lucknow, UP, India. Each patient gave explicit written consent, which was recorded on a form provided by the research department. Patients aged 18–40 years who had been recently diagnosed with depression were included. Patients with epilepsy, brain injury, other psychiatric disorders (on the basis of history), alcoholism, CVD, metabolic syndrome, and smoking were excluded from the study.

The Tenth Revision of the International Classification of Diseases and Related Health Problems (ICD-10) categorization of mental and behavioral disorders served as the basis for the diagnosis of depression. A depressive episode is described by ICD-10 code F32. In addition, the severity of depression is classified as mild, moderate, and severe. The basis for distinguishing between mild, moderate, and severe depressive episodes is a difficult clinical assessment that considers the amount, type, and severity of symptoms present. The patient typically suffers from depressed mood, loss of interest and pleasure, and low energy, leading to increased fatigue and decreased activity. It is common to feel tired after even light physical activity. Other typical symptoms include (a) loss of concentration and attention, (b) loss of self-confidence and self-esteem, (c) feelings of guilt and unworthiness (even in mild episodes), (d) gloomy and pessimistic views of the future, (e) self-harm or suicidal thoughts or actions, (f) sleep disturbances, and (g) loss of appetite.[17] Atypical courses are particularly common in adolescence, and the clinical picture varies widely from person to person.

A thorough history was obtained, with particular attention to the patient’s medical and personal history and to signs of other psychiatric disorders. Information on smoking and drug dependence was also obtained. The entire process was explained to the patients and their caregivers in plain English/Hindi, and direct written consent was obtained from each patient during the psychiatric consultation.

During a brief general physical examination, the following values were measured: Blood pressure, pulse, height, and weight. To rule out systemic disorders, a brief systemic examination of the respiratory and CV systems was also performed.

HRV processing and analysis were performed using Pro LabChart (PowerLab 8Pro) data analysis software from AD Instrument. Short-term HRV was recorded for 5 min in the upright sitting position with one lead II electrocardiogram (ECG). Electrocardiographic waveforms were recorded with a nine-channel recorder. Two negative electrodes on the right arm (red, white), two positive electrodes on the left arm (brown), one ground electrode on the right leg (green), and five leads were used to record the ECG.

After the ECG recording, we selected the HRV module and set the entire channel to zero ectopic beats. The ECG signal was continuously digitized, amplified, and stored in the computer for offline processing. Only cycles with beats that had typical morphological characteristics were used for analysis. Intervals between ectopic beats, between normal and ectopic beats, and intervals that were measured incorrectly because of artifacts were not considered in the analysis. The R–R interval was calculated and entered into the program for analysis (time and frequency domain), which showed that there were no ectopic beats or murmurs on the computerized ECG recording.

A total of 2 ml of blood was drawn and placed in an undecorated vial in our department. The serum was separated by centrifugation and stored at − 24°C. A commercially available enzyme-linked immunosorbent assay (ELISA) kit from Bioassay Technology Laboratory was used to measure serum levels of CRP according to the manufacturer’s instructions.

Statistical analysis

The results were analyzed using descriptive statistics and making comparisons among the various groups. Discrete (categorical) data were summarized as in proportions and percentages (%).

Results

Mean age 34.46 ± 7.13 years. Of the study participants, most (70.8%) were over 30 years of age, and among all participants, men were in the majority (58.3%), whereas the remaining 41.7% were women. The age distribution of the subjects was divided into two groups: 30 years. About 70.8% of the cases were in the >30 years group. Most of the subjects had a sedentary lifestyle (48%), whereas among women, the majority were housewives (35.4%). Field workers accounted for 16.7% of all cases. The mean height of the study participants was 158.67 ± 8.62 cm (range 140–172 cm), mean weight 57.67 ± 8.01 kg (range 45–87 kg), and mean body mass index (BMI) 22.93 ± 2.30 kg/m² (range 19.32–30.52 kg/m²). The mean pulse rate was 81.21 ± 6.43 b/min with a range of (68–100) b/min. Mean systolic blood pressure (SBP) was 129.54 ± 9.47 mmHg with a range of (108–146) mmHg, whereas mean diastolic blood pressure (DBP) was 82.38 ± 7.20 mmHg with a range of (64–90) mmHg. The mean CRP value was 2.02 ± 2.14 (0.41–5.83) [Table 1].

Table 1.

Age and gender distribution of depression cases

Parameter	Distribution of patient according to baseline characteristics	n	%
Age group	≤30 Yr	14	29.2
	>30 Yr	34	70.8
	Mean±SD	34.46±7.13 yrs
Gender	Male	28	58.3
	Female	20	41.7
Occupation	Sitting including students	23	48
	Fieldwork	8	16.7
	Housewife	17	35.4
Height (cm)	Mean±SD	158.67	8.62
Weight (kg)	Mean±SD	57.67	8.01
BMI (kg/m2)	Mean±SD	22.93	2.30
Pulse	Mean±SD	81.21	6.43
SBP	Mean±SD	129.54	9.47
DBP	Mean±SD	82.38	7.20
CRP levels	Mean±SD	2.02	2.14

SBP=Systolic blood pressure, CRP=C-reactive protein, DBP=Diastolic blood pressure, BMI=Body mass index, SD=Standard deviation

The mean SDNN is 52.71 ± 22.24 and ranges from (16.58–110.50). The RMSSD and percentage of successive RR intervals differing by more than 50 milliseconds (pRR50) values were 35.33 ± 22.33 (8.14–108.10) and 7.71 ± 9.02 (0.00–39.33), respectively. The VLF, LF, HF, and LF/HF values were 992.09 ± 701.77 (177.50–2747.00), 1647.85 ± 1925.22 (171.20–8177.00), 488.20 ± 706.77 (23.92–3312.00), and 4.40 ± 2.10 (1.63–11.15), respectively [Table 2].

Table 2.

Variables of heart rate variability

Variable	Mean	SD	Min.	Max.
Time domain
SDNN	52.71	22.24	16.58	110.50
RMSSD	35.33	22.33	8.14	108.10
pRR50	7.71	9.02	0.00	39.33
Frequency domain
VLF	992.09	701.77	177.50	2747.00
LF	1647.85	1925.22	171.20	8177.00
HF	488.20	706.77	23.92	3312.00
LF/HF	4.40	2.10	1.63	11.15
log n values
lnVLF	6.65	0.74	5.18	7.92
lnLF	6.95	0.93	5.14	9.01
lnHF	5.58	1.07	3.17	8.11
lnAvgrate	4.51	0.15	4.25	4.83

SD=Standard deviation, RMSSD=Root mean square of successive differences, pRR50=Percentage of successive RR intervals differing by >50 milliseconds, VLF=Very low frequency, LF=Low frequency, HF=High frequency, lnHF=The logarithm of high frequency, lnLF=The logarithm of low frequency, lnVLF=The logarithm of very low frequency, lnAvgrate=The logarithm of an average rate, SDNN=Standard deviation of normal-to-normal intervals

Since a large variability was observed between the heart rate parameters, it was possible to take the natural logarithm to detect correlations that could be linear in cases where the heart rate parameters were non-linear, as indicated by their large variability [Table 2].

After forming the natural logarithm, the values for the logarithm of (ln) VLF, ln LF, ln HF, and ln Avg rate were 6.65 ± 0.74 (5.18–7.92), 6.95 ± 0.93 (5.14–9.01), 5.58 ± 1.07 (3.17–8.11) and 4.51 ± 0.15 (4.25–4.83), respectively [Table 2].

Table 3 shows the correlations of anthropometry, pulse rate, systolic blood pressure, and diastolic blood pressure with HRV parameters and CRP. Pulse rate, systolic blood pressure, diastolic blood pressure, and BMI showed no significant correlation with any of the HRV parameters. Weight and BMI showed a significant positive correlation with pRR50 (r = 0.420, P = 0.003).

Table 3.

Correlations of anthropometry, pulse, systolic blood pressure, and diastolic blood pressure with parameters of heart rate variability and CRP

	Pulse		SBP		DBP		Height		Weight		BMI
	r	P	r	P	r	P	r	P	r	P	r	P
SDRR	0.07	0.619	0.15	0.312	0.15	0.298	0.10	0.502	−0.06	0.710	−0.13	0.394
RMSSD	0.10	0.502	0.16	0.278	0.18	0.228	0.14	0.334	−0.01	0.930	−0.11	0.456
pRR50	0.28	0.058	0.21	0.146	0.12	0.406	0.10	0.492	0.42	0.003	0.42	0.003
CRP	−0.09	0.566	0.03	0.821	0.12	0.415	−0.04	0.798	−0.10	0.482	−0.09	0.562
lnVLF	−0.26	0.073	−0.12	0.409	−0.10	0.503	0.06	0.664	−0.16	0.270	−0.27	0.063
lnLF	−0.02	0.896	0.11	0.439	0.14	0.344	0.14	0.341	−0.05	0.717	−0.19	0.207
lnHF	−0.04	0.792	0.07	0.645	−0.07	0.619	−0.20	0.169	−0.01	0.932	0.18	0.222
lnLF/HF	0.01	0.933	0.02	0.908	0.11	0.460	0.18	0.216	−0.02	0.898	−0.19	0.194

SDRR=Standard deviation of all R–R intervals, RMSSD=Root mean square of successive differences, pRR50=Percentage of successive RR intervals differing by >50 milliseconds, lnHF=The logarithm of high frequency, lnLF=The logarithm of low frequency, lnVLF=The logarithm of very low frequency, lnLF/HF=The logarithm of low frequency and high frequency ratio, CRP=C-reactive protein

The summaries of the correlations of CRP with heart rate parameters are shown in Table 4. CRP was significantly positively correlated with VLF (r = 0.595, P < 0.001), LF (r = 0,464, P = 0.001), LF/HF (r = 0.383, P = 0.007), whereas there was also a significant negative correlation with HF (r = −0.325, P = 0.024).

Table 4.

Correlation of CRP with heart rate variability parameters

Correlations	CRP
	r	P
SDRR	0.199	0.175
RMSSD	0.255	0.080
pRR50	−0.29	0.052
VLF	0.595	<0.001
LF	0.464	0.001
HF	−0.325	0.024
LF/HF	0.383	0.007

RMSSD=Root mean square of successive differences, pRR50=Percentage of successive RR intervals differing by >50 milliseconds, VLF=Very low frequency, LF=Low frequency, HF=High frequency, SDRR=Standard deviation of all R–R intervals, CRP=C-reactive protein

CRP was significantly positively correlated with lnVLF (r = 0.561, P < 0.001), lnLF (r = 0.420, P = 0.003), and lnLF/HF (r = 0.489, P < 0.001), whereas it was significantly negatively associated with lnHF (r = −0,508, P < 0.001), as shown in Table 5.

Table 5.

Correlation of CRP with log of heart rate variability parameters

Correlations	CRP
	r	P
lnVLF	0.561	<0.001
lnLF	0.420	0.003
lnHF	−0.506	<0.001
lnLF/HF	0.489	<0.001

lnHF=The logarithm of high frequency, lnLF=The logarithm of low frequency, lnVLF=The logarithm of very low frequency, lnLF/HF=The logarithm of low frequency and high frequency ratio, CRP=C-reactive protein

Discussion

Both CV morbidity and mortality and the number of depressed people have increased rapidly over the past decade. Both represent a significant clinical and financial burden to society. Major depression increases the risk of CV morbidity and mortality, as previous studies have shown.[18] One explanation could be the unfavorable pathophysiological changes that occur in depressed individuals, such as autonomic, hypothalamic-pituitary-adrenal (HPA) axis, metabolic, and immune-inflammatory dysregulations.[19] In addition, these patients lead unhealthy lifestyles that include smoking, physical inactivity, and poor dietary habits.[18] If the depressive symptoms are not treated quickly, the patient may become suicidal and commit suicide. Numerous CV risks, such as hypertension, stroke, atherosclerosis, myocardial infarction, and heart failure, are increased by long-term depression.[19] Recent research has shown that measurements of HRV and CRP are useful indicators of CV risk in depressed individuals. Normal vagus function is affected by both general lifestyle changes and targeted therapies such as vagus nerve stimulation (VNS). Patients with depression exhibit suppressed vagal activity as determined by HRV, and this decrease in HRV is negatively related to depression severity.[20]

Most cases in our study were between 30 and 40 years old. The results are consistent with the prevalence rate of depression in India, which indicates that there are more people in the age group of 30–40 years than in the age group of 18–30 years.[21] Data from around the world on the prevalence of depression have yielded similar results.[22] Both the frequency and severity of cases increase with age. Age-related feelings of discomfort, tension, and despair are the most common triggers. Many older people become accustomed to these feelings over time and restore their emotional balance, but for some this is not the case, and depression may result.[23]

In the current study, men were found to be affected more often than women. This finding is not consistent with our previous data suggesting that women are more commonly affected by depression than men at any age.[21,23] The hormonal and neurological changes that differ by gender during the pubertal transition may be the cause of the gender differences in depression.[24] Women, in turn, carry a “double burden” due to their involvement in work and family life.[25]

In our analysis, the distribution of patients by occupation revealed that the majority of cases were sedentary. Data from previous studies did not indicate such an association. Work is an obvious source of stress for most people, which may contribute to the development of depressive symptoms.

The majority of cases in our study were within the range of healthy BMI (18.5–24.9 kg/m²). None of the cases were underweight, few were overweight [25–29.9 kg/m²], and one was obese [>30.0 kg/m²]. BMI was almost identical in both sexes. Elevated BMI levels and depression have been linked in several ways, according to previous research. This association may be influenced by inflammation. Obesity and depression have been found to be inversely correlated.[26] Neuroendocrine abnormalities that develop in depressed patients may be the cause of the increase in BMI.[27]

In the current study, a mean pulse rate of 81.21 ± 6.43 b/min was measured with a range of 68–100 b/min. This is within the range of the usual pulse rate of a healthy person. Therefore, we can conclude that depression does not significantly alter heart rate. These results are consistent with those of other studies.[28]

In this study, the mean SBP ranged from 108–140 mmHg, whereas the mean DBP ranged from 64–90 mmHg. The mean SBP was 129.54 ± 9.47 mmHg. According to previous studies, hypertension (BP) is a significant risk factor for the development of CVD.[28] According to the results of another study, demographic factors such as pulse rate, SBP, and DBP were not significantly different from those of the healthy control group.[29]

The mean SDNN value in our study was 52.71, suggesting that depressed patients had poor health status and a significant risk of developing CVD. Patients were classified as ill, health impaired, or healthy depending on their SDNN values: below 50 ms, between 50 and 100 ms, and above 100 ms.[30]

The mean RMSSD in this sample was 35.33 ± 22.33 ms (8.14–108.10). The usual value is 35.11 ms in 30- to 39-year-olds and 43 ± 19 ms in 20- to 29-year-olds.[31] HRV decreases with increasing RMSSD value. Low HRV is defined as a value of less than 15 ms.[32] According to data from other studies, lower RMSSD values are associated with lower parasympathetic discharge and an increased risk of CVD.[33]

In our study, the pRR50 value was 7.71 ± 9.02 ms (0.00–39.33). The normal value is 18 ± 13 ms in the 20- to 29-year-old age group and 13 ± 9 ms in the 30- to 39-year-old age group.[31,34] The lower the value of pRR50, the lower the HRV. A value of less than < 0.75% is considered low HRV.[32] When the variability between successive RR intervals is low, it indicates low HRV, which further increases the likelihood of increased cardiovascular mortality and morbidity. These findings are consistent with previous studies.[35,36]

The VLF value in the current study was 992.09 ± 701.77 (177.50–2747.00). The typical range for this parameter in healthy subjects is 627 ± 215.[37] Here, we see that the VLF value of our research group is far above the range considered normal. This could be due to an increase in sympathetic and a decrease in parasympathetic central nervous system (CNS) outflow. The above results are consistent with previous studies showing that the relative magnitude of VLF is directly proportional to the degree of depression, suggesting that VLF may be related to the pathophysiology of depression.[38,39]

The LF value in the current study was 1647.85 ± 1925.22 ms² (171.20–8177.00). The typical range for this parameter in healthy subjects is 1170 ± 416 ms².[37] Here, we can conclude that the value of LF in our study group is significantly above the range of normal values, which shows that the sympathetic nervous system predominates over the parasympathetic nervous system in depressed individuals. Similar findings from other studies indicate that the LF component is increased in depressed patients.[4,20,40] These studies show that depressed individuals have decreased HRV, which is directly associated with increased CVD risk. An overactive sympathetic nervous system increases the risk of CV morbidity and mortality in these individuals. A few studies found that the LF component was not significantly higher in depressed individuals compared with the control group.[36,41]

The mean value of HF in the present study was 488.20 ± 706.77 ms² (23.92–3312.00). The typical range of this parameter in healthy subjects is 975 ± 203 ms².[37] The HF band is smaller in depressed individuals, as we can see above. Thus, our results indicate an altered HF component and suggest that severely depressed individuals have poor cardiac vagal control. This is consistent with studies conducted in adults in the past.[20,40] HF Performance suffers from any type of stress, anxiety, panic, or worry. Changes in vagal tone are necessary to maintain dynamic autonomic regulation of the heart, and failure to do so can lead to poor CV health.[42] According to a meta-analysis,[43] there was no apparent association between depressive symptoms and HF-HRV. Depressed individuals with altered HRV levels exhibit autonomic dysregulation, which accelerates the development of CVD and places them in a procoagulant and proinflammatory state. As a result, the threshold for psychological stress is lowered, leading to ischemia and prolongation of the QT interval.

The LF/HF ratio in the current study was 4.40 ± 2.10 ms2 (1.63–11.15). The usual range for this parameter in healthy subjects is 1.5–2.0 ms².[37] As can be seen from the above graph, depressed individuals have a higher LF/HF ratio than the general population. Similarly, previous studies have shown that overactivity of the sympathetic nervous system during drug treatment of depression increases the LF/HF ratio.[36]

Mean blood CRP levels in the current study were 2.02 ± 2.14 mg/L (0.41–5.83). In healthy individuals, CRP levels should range from 1.24 ± 1.18 mg/L (20–30 years old) to 1.40 and 0.86 mg/L (30–40 years old).[44] According to the above comparison, blood CRP levels are higher in depressed individuals. Our results are consistent with previous studies that have demonstrated a clear association between elevated levels of inflammatory markers and depression. A few studies contradict our findings and come to the opposite conclusion that CRP levels are not elevated in depressed patients.[45,46]

Measures of HRV did not correlate significantly with other data, such as pulse rate, SBP, DBP, or BMI. The only indicator of a significant positive correlation with weight and BMI was pRR50 (r = 0.420, P = 0.003). Compared to healthy adults, no significant association was found between demographic factors, including BMI, SBP/DBP, and HRV measures in previous studies.[29,36] Depressed women had significantly higher BMI, which is not consistent with the results of the current study.[47] In depressed patients, CRP levels did not correlate significantly with BMI, diastolic blood pressure, or systolic blood pressure.[46,48] In one study, BMI was found to be the only factor significantly correlated with plasma CRP levels.[35] It can be concluded that a sustained increase in blood pressure may be associated with a higher risk of CV morbidity and mortality. This may be a significant confounding element. Therefore, we included patients with normal blood pressure in our study group. On the other hand, high BMI could affect the hypothalamic-pituitary-adrenal axis, which may disturb the hormonal balance and increase the risk of CVD.

The relationship between temporal domain indices and CRP was not significantly correlated. CRP significantly correlated with VLF (r = 0.595, P = 0.001), LF (r = 0.464, P = 0.001), LF/HF (r = 0.383, P = 0.007), and HF (r = −0.325, P = 0.024). CRP correlates significantly negatively with HF. The most significant negative correlation of CRP is with lnHF (r = −0.508, P = 0.001), and there are significant positive correlations with lnVLF (r = 0.561, P = 0.001), lnLF (r = 0.420, P = 0.003), and lnLF/HF (r = 0.489, P = 0.001).

This correlation shows that CRP levels increase as HRV (a frequency domain metric) increases. CRP levels increase when the value of HF decreases, which is the opposite of what is observed at HF. The metrics VLF, LF, and LF/HF ratio have increased values, whereas HF has decreased, indicating LOW variability in heart rate. A shift in the autonomic control of the heart, such as a decrease in parasympathetic tone or dominance of the sympathetic nervous system, is indicated by decreased HRV. As a result, the patient is more susceptible to developing CVD. Patients with depression who have elevated CRP levels have persistent, chronic inflammation in their bodies. As a result, the patient is in a procoagulant state and is at high risk of soon developing CVD.

I am not aware of any studies of this nature that have established a relationship between the HRV of depressed patients and CRP levels. The following pathologies could be the cause of this correlation: inflammatory cytokines are released when a person experiences some form of physical, mental, or emotional stress, such as a chronic illness or the unexpected death of a loved one. These travel throughout the body and eventually enter the brain through the blood-brain barrier. Once in the brain, these cytokines trigger an inflammatory response via the neuroglial cells. As a result, the CNS releases less serotonin and other neurotransmitters. This exacerbates symptoms by further decreasing activation of the hypothalamic-pituitary-adrenal axis. The hypothalamus is also directly affected by emotional stress.

One of the study’s drawbacks is its limited sample size and single-center design, which may have made it difficult to find a connection between HRV measurements and high-sensitivity (hs) CRP levels that was statistically significant, as suggested by other research.

Conclusion

We can be concluded that both stress and inflammation impair hypothalamic function and ultimately lead to ANS dysfunction. To detect CVD in depressed patients, measurements of HRV at rest and CRP levels may be helpful. Elevated serum CRP levels and low HRV should prompt clinicians to act as soon as possible to reduce CV risk. We can use these methods for both diagnostic and therapeutic outcome monitoring in depressed individuals. To obtain accurate and reliable results for early diagnosis of comorbidity and mortality in depression, a study with larger sample size and longer duration should be conducted.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.