|Year : 2017 | Volume
| Issue : 4 | Page : 182-189
Association of prehypertension status with cardiovascular risks in subclinical hypothyroidism
Gopalakrishna Jayakrishnan1, Gopal Krushna Pal1, Sadishkumar Kamalanathan2, Pravati Pal1, Allampalli Sirisha1, Nivedita Nanda3
1 Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2 Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
3 Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
|Date of Web Publication||29-Jan-2018|
Gopal Krushna Pal
Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Karaikal - 605 006, Puducherry
Source of Support: None, Conflict of Interest: None
Background and Aim: Although attenuated baroreflex sensitivity (BRS) is known to promote cardiovascular (CV) risk, its status in subclinical hypothyroidism (SCH) has not been reported. Furthermore, the link of sympathovagal imbalance (SVI) to CV risk in SCH has not been reported. This study aimed to assess the association of BRS to hypertension status and CV risk in SCH. Methods: SCH patients (n = 32) and controls (n = 32) were recruited for the study. Body mass index, basal heart rate (HR), systolic blood pressure (BP), diastolic BP, BRS, autonomic function tests, HR variability (HRV), high-sensitive C-reactive protein, lipid profile, and atherogenic index were measured. Prediction of prehypertension status by BRS was assessed. Results: There was significant decrease in BRS, increased sympathetic and decreased parasympathetic reactivity, decreased HRV and high-density lipoprotein, and significant increase in all other lipid parameters, in SCH compared to controls. A significant association was found between BRS and low-frequency to high-frequency ratio in SCH group. BRS had a significant prediction of prehypertension status. Conclusion: SVI and decreased BRS were observed in SCH group that was linked to SVI. Reduced BRS that contributes to prehypertension status predisposes to subclinical hypothyroids to CV risks.
Keywords: Autonomic functions, baroreflex sensitivity, cardiovascular risks, prehypertension status, subclinical hypothyroidism, sympathovagal imbalance
|How to cite this article:|
Jayakrishnan G, Pal GK, Kamalanathan S, Pal P, Sirisha A, Nanda N. Association of prehypertension status with cardiovascular risks in subclinical hypothyroidism. Int J Clin Exp Physiol 2017;4:182-9
|How to cite this URL:|
Jayakrishnan G, Pal GK, Kamalanathan S, Pal P, Sirisha A, Nanda N. Association of prehypertension status with cardiovascular risks in subclinical hypothyroidism. Int J Clin Exp Physiol [serial online] 2017 [cited 2018 Apr 25];4:182-9. Available from: http://www.ijcep.org/text.asp?2017/4/4/182/224155
| Introduction|| |
Among endocrine disorders, hypothyroidism is second to diabetes mellitus in prevalence. In India, prevalence of overt hypothyroidism (OH) is 10.95% while the prevalence of subclinical hypothyroidism (SCH), an unquantified cause of morbidity, is reported to be between 3% and 15%., The presentation of OH varies from vague symptoms such as tiredness and weight gain to pericardial effusion and cardiac dysfunction, indicating a wide spectrum in terms of presentation and severity. The cardiovascular (CV) dysfunction in OH is well documented and is explained on the basis of decreased action of thyroid hormones on the CV system. The impact of SCH as an entity on CV morbidity of a community is underestimated; hence, numerous studies have been done in this regard. It is documented that patients with SCH invariably progress to OH and are also at CV risk, supported by echocardiograph evidence. Autoimmune thyroiditis, which is a major cause of thyroid dysfunction, is associated with low-grade inflammation that predisposes to atherosclerosis. Profound hyperlipidemia is an established biochemical phenomenon in hypothyroidism. Dyslipidemia in OH causes oxidative stress, which directly contributes to CV morbidity.
Hypothyroidism is considered to be a hypometabolic state. A report indicated reduced sympathetic drive and an increase in vagal activity. However, studies from our laboratory have revealed increased sympathetic drive in both hypothyroidism and hyperthyroidism contradicting earlier findings, which contributes to sympathovagal imbalance (SVI), with an increased sympathetic activity coupled with reduced vagal activity., Further, contribution of SVI to CV risk in SCH has not yet been documented. Conventional autonomic function tests (CAFTs), heart rate variability (HRV), and blood pressure variability (BPV) analysis have been used as noninvasive tools objectively to detect CV risks and to diagnose autonomic dysfunction at an early stage., Therefore, this study was designed to assess the role of inflammation and dyslipidemia as causal factors for CV risks and correlate it with SVI in SCH and also to assess the association of prehypertension status with baroreflex sensitivity (BRS), the marker of CV risk, in SCH.
| Materials and Methods|| |
This was an analytical case–control study conducted in subclinical hypothyroid group, designed to assess the CV function and autonomic status in subclinical hypothyroid group in comparison to age- and gender-matched healthy individuals and to assess the magnitude of cardiac dysfunction in relation to their biochemical profile and CV autonomic status. The study was conducted in the Autonomic Function Testing Laboratory, Department of Physiology, JIPMER. The sample size was estimated at 5% level of significance and 80% power using OpenEpi software (Version 2.3.1), in which the sample size was calculated to be 32. The approval of the Institute Research Council and Institute Ethics Committee for Human Studies was obtained before the commencement of the study.
Recruitment and grouping of subjects
Study group (cases)
Thirty-two cases were included in the study.
The cases were recruited from the outpatient unit of the Endocrinology Department of JIPMER.
- Inclusion criteria
- Freshly diagnosed cases of hypothyroidism aged between 18 and 45 years before initiation of treatment were included
- Exclusion criteria
- Hypothyroid patients receiving thyroxin replacement therapy
- Known cases of diabetes mellitus, hypertension, heart disease, autonomic failure, and any other endocrine disorders or on any hormonal therapy or drugs affecting autonomic function.
Thirty-two individuals were recruited.
- Inclusion criteria: Healthy age- and gender-matched normal individuals
- Exclusion criteria: Individuals suffering from any illness such as diabetes mellitus, hypertension, heart disease, autonomic failure, and any other endocrine disorders or on any hormonal therapy or drugs affecting autonomic function.
Written informed consent was obtained from all the participants before the commencement of the study.
The individuals were asked to report to autonomic function testing laboratory after overnight fasting and were advised to wear loose-fitting clothes. They were instructed to avoid caffeine for 12 h before the test. The individuals were told to refrain from medications known to influence CV system, namely., anticholinergics, antihistamines, over-the-counter cough and cold medications, diuretics, and sympathomimetic and parasympathomimetic agents for 48 h before the study. Individuals were advised to discontinue short-acting α and β antagonists 24 h before and long-acting antagonists 48 h before the test. In case of any adversity in the health of the individuals resulting in poor overnight sleep quality, or any prodromal symptoms of fever and body pain, the test was postponed. The individuals were advised to come after evacuation of bowels and emptying of bladder. Height and weight were measured, and body mass index (BMI) was calculated for each subject.
Recording of short-term heart rate variability
The individuals were asked to lie comfortably on a couch and relax for 10 min. They were informed about the procedure to alleviate anxiety. Appropriate transducers were connected to monitor the electrocardiography (ECG) (lead II). The data acquisition was done at the rate of 500 samples per se cond for each channel using PowerLab 8/30 ML 870 Data Acquisition System with LabChart Pro software. Basal supine blood pressure (BP) and heart rate (HR) were recorded by oscillometric method using automated BP monitor Omron MX3. Following this, the lead II ECG was recorded for next 5 min in total resting condition for short-term HRV analysis, following the procedure as described earlier. Power spectral analysis was done by fast Fourier transform and the frequency domain indices computed were very low frequency (LF), LF, and high frequency (HF); both in absolute powers given as ms 2 and in normalized unit (nu). The ratio of LF/HF in ms 2 was given as LF-HF ratio. The time domain measures included the various statistical measures from R-R interval (ms), standard deviation of normal to normal intervals (SDNN), root mean of standard deviations (RMSSD), normal to normal intervals (NN50) and pNN50.
Cardiovascular autonomic function tests
Heart rate response to standing
After 10 min of supine rest (from the basal recording measurements), the second recording of lead II ECG was started and the individuals were asked to stand after 30 s with a due marking on the graph. The postural change was obtained within 3 s. HR were serially measured for next 5 min of the stand, i.e. immediate and 1st, 2nd, 3rd, 4th, and 5th min. Following this, the individuals were asked to sit down and allowed to rest for 3 min to achieve baseline HR values. RR tachogram from the ECG recording was retrieved and copied to a Microsoft Excel worksheet. A graphical representation (line diagram) of the RR tachogram was used to identify the minimum and maximum R-R interval after standing. The shortest R-R interval at or around the 15th beat and the longest R-R interval at or around the 30th beat were calculated and thereby 30:15 ratio was computed.
Heart rate response to deep breathing
Deep breathing was performed at the rate of 6 breaths per minute with inspiratory and expiratory cycles for 5 s each. During the 3 min of rest period after standing, deep breathing synchronized to a voice metronome and if necessary guided by hand movement was demonstrated to the individuals. The individuals performed deep breathing for the next 1 min with continuous lead II ECG recording. Individuals were encouraged to perform deep and maximal respiration. A period of 3 min rest was given after the maneuver for the HR and BP to return to basal state. RR tachogram from the corresponding ECG recording was retrieved and transformed graphically into a line diagram on a Microsoft Excel worksheet. The maximum and minimum R-R interval averaged over 6 cycles of expiration (E) and inspiration (I) was calculated and the ratio was computed as E: I ratio.
Blood pressure response to sustained isometric handgrip
Initially, the maximal voluntary contraction (MVC) during sustained isometric handgrip by the individuals was measured using handgrip dynamometer (Inco, Ambala). Then, the individuals were instructed regarding sustaining the handgrip at one-third of their MVC. The ECG recordings were started, and at the 15th s, individuals were instructed to perform one-third of their MVC for 3 min. The maximum diastolic BP (DBP) attained during the maneuver was noted. The difference between this highest DBP recorded during sustained handgrip and baseline supine DBP was noted as the pressor response to the test. After the procedure, BP and HR were measured after 2 min to confirm if they have returned to basal levels. The magnitude of DBP rise during the maneuver (ΔDBPisg) was calculated as the difference between the maximum DBP attained during the handgrip and the supine basal values.
Recording of blood pressure variability parameter
The CV parameters and BRS were measured by continuous BPV method using Finapres (Finometer version 1.22a, Finapres Medical Systems BV, Amsterdam, The Netherlands), a noninvasive continuous hemodynamic CV monitor based on the principle of measurement of finger arterial pressure with the volume clamp technique of Penaz and the Physiocal criteria of Wesseling and as described earlier. The reconstructed brachial pressure from finger pressure was acquired via a PC-based data acquisition system. Baroreflex sensitivity (BRS) was assessed along with other BPV parameters.
Estimation of biochemical parameters
Five milliliters of venous blood (after 12 h of overnight fasting) was collected from both cases and controls under aseptic precautions for biochemical analysis of following parameters.
Estimation thyroid and lipid profile and inflammatory marker
Free triiodothyronine (fT3), free thyroxin (fT4), thyroid-stimulating hormone (TSH), using standard chemiluminescence method with ADVIA Centaur (Siemens, Germany), were calculated. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), very LDL-C (VLDL-C), high sensitivity C-reactive protein (hs-CRP) were estimated. Lipid risk ratios such as TC/TG, TC/HDL-C, LDL/HDL-C, TG/HDL-C, and atherogenic index (AI) = log (TG/HDL − C) were calculated.
Statistical analysis of data
SPSS version 20 (20, Chicago, USA) was used for statistical analysis. The data were subjected to Kolmogorov–Smirnov normality test. All the data were expressed as mean ± SD. The intergroup differences in mean between the controls and cases were compared using Student's unpaired t-test for normally distributed data. Mann–Whitney test was used as the appropriate nonparametric test, for the parameters not following normal distribution. The association between LF-HF ratio with basal HR, BP, AFT parameters, and biochemical parameters was assessed by Pearson's correlation analysis and Spearman's correlation test as nonparametric test when appropriate. Multiple regression analysis was done to assess the independent contribution of BRS and TSH to LF-HF ratio and bivariate logistic regression analysis was done to demonstrate prediction of prehypertension status by BRS in SCH group. The difference was considered statistically significant if probability of chance was <0.05.
| Results|| |
As shown in [Table 1], there was no significant difference in age, body weight, and BMI between control and study groups. [Table 2] shows the comparison of frequency domain indices between cases and controls. On analysis of the frequency domain parameters of short-term HRV, total power (TP) was significantly reduced among the cases (P < 0.0001). When the absolute powers were expressed in nu, significantly elevated LFnu (P = 0.0267) and a depressed HFnu (P = 0.0193) were observed in cases in comparison to controls. The LF-HF ratio was significantly elevated in cases (P = 0.0003). Significant decrease was observed in NN50 (P = 0.0047), pNN50 (P < 0.0001), RMSSD (P < 0.0001), and SDNN (P = 0.0258) among cases. The pNN50 observed in cases was 62.22% lower than controls [Table 2].
|Table 1: Age and anthropometric parameters of control and subclinical hypothyroid groups|
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|Table 2: Frequency and time domain indices of heart rate variability of control and subclinical hypothyroid group|
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[Table 3] depicts the comparison of basal CV and continuous BPV parameters between the cases and controls. There was significant elevation of basal CV parameters i.e. systolic BP (SBP, P = 0.0007), DBP (P = 0.0011) and mean arterial pressure (MAP, P = 0.0004) among the cases in comparison to the controls. Difference in HR was not significant between the groups (P = 0.3085). Among continuous BPV parameters, there was significant elevation of total peripheral resistance (TPR) (P = 0.0238) and decrease in BRS (P < 0.0001) among the cases. Stroke volume (P = 0.842) and cardiac output (P = 0.7200) were not significantly altered among the cases. Reduced left ventricular ejection time was observed in cases.
|Table 3: Continuous blood pressure variability parameters of control and subclinical hypothyroid group|
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[Table 4] shows the comparison of AFT parameters between controls and subclinical hypothyroid groups. There was a significant reduction in E: I ratio (P = 0.0003) among the cases. 30:15 ratio (P = 0.0153) and Δ DBP during isometric handgrip (P = 0.0375) were significantly elevated among the cases compared to controls.
|Table 4: Classical autonomic function testing parameters between control and subclinical hypothyroid groups|
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[Table 5] shows the comparison between the thyroid profile between control and subclinical hypothyroid subjects. Significantly elevated TSH values (P = 0.0012) was observed in cases while there was no significant difference in fT3 and fT4 levels when compared to controls. [Table 6] depicts the comparison of lipid profile and lipid risk ratios between the cases and controls. TG, LDL-C, and VLDL-C were significantly higher among the cases (P = 0.0173, P = 0.0246, and P = 0.0366, respectively). Significant reduction in HDL-C (P < 0.0001) was observed in cases. TC did not show significant difference between the two groups but was higher in cases. The lipid risk ratios TC/HDL-C, TG/HDL-C, and LDL/HDL and AI were significantly higher among the cases (P < 0.0001). [Table 6] compares the inflammatory marker hs-CRP between the cases and controls. hs-CRP was found to be significantly increased in cases compared to the controls (P < 0.0001).
|Table 5: Thyroid profile between control and subclinical hypothyroid groups|
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|Table 6: Lipid profile, lipid risk factors, and high-sensitive C-reactive protein between controls and subclinical hypothyroid groups|
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[Table 7] shows the correlation of LF-HF with the CV and lipid risk factor parameters. In the present study, there is strong correlation of LF-HF ratio with BRS (r = 0.342, P = 0.015) and TSH (r = 0. 325, P = 0.027). There was also significant positive correlation of TC/HDL (r = 0.344, P = 0.014), TG/HDL (r = 0.286, P = 0.046) and AI (r = 0.303, P = 0.030); however, there was no significant correlation of hs-CRP levels and with LF-HF ratio. Multiple regression analysis demonstrated significant independent contribution of BRS (B = 0.328, P = 0.012) and TSH (B = 0.356, P = 0.009) to LF-HF ratio [Table 8]. Furthermore, the bivariate logistic regression analysis demonstrated significant prediction of BRS by LF-HF ratio in SCH group (odds ratio [OR] = 2.17, P = 0.015) but not in control group (OR = 0.56, P = 0.175) [Table 9].
|Table 7: Correlation of low-frequency to high-frequency with various parameters of control and subclinical hypothyroid subjects|
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|Table 8: Multiple regression analysis of low-frequency to high-frequency ratio (as dependent variable) with various other associated factors (as independent variables) in subclinical hypothyroid group|
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|Table 9: Bivariate logistic regression analysis of prehypertension status (as dependent variable) with baroreceptor reflex sensitivity (as independent variable) in subclinical hypothyroidism group after adjusting for age, gender, and body mass index|
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| Discussion|| |
The present study was designed to assess the CV functional status in the subclinical hypothyroid group and to correlate the nature and degree of alteration in autonomic status with the biochemical and metabolic derangements. The significant increase in LF-HF ratio in SCH group compared to the control group [Table 2] represents considerable SVI in subclinical hypothyroid patients as LH-HF ratio is a sensitive marker of sympathovagal balance., Increase in LF-HF ratio in resting state indicates increased sympathetic activity and decreased vagal activity., This was supported by significant increase in LFnu in SCH group compared to that of the control group [Table 2] as increased LFnu is an index of increased cardiac sympathetic drive., In SCH subjects, significant decrease in HFnu indicates decreased parasympathetic tone in these patients as HFnu is an index of cardiac vagal drive., This was supported by a significant reduction in TP of HRV in SCH group as TP in general indicates the magnitude of vagal modulation of cardiac function., In addition, time domain indices of HRV (RMSSD, SDNN, NN50, and pNN50) were significantly less in SCH subjects [Table 2] further confirming decreased vagal tone in these patients, as time-domain indices of HRV represent cardiac parasympathetic drive., Thus, it is evident from the present study that SVI in subclinical hypothyroid subjects is due to a concomitant increased sympathetic and decreased vagal activity.
In addition, there was altered autonomic reactivities in SCH subjects as evident from changes in 30:15 ratio, E: I ratio, and ΔDBPIHG [Table 4]. HR response to standing (30:15 ratio) and deep breathing (E: I ratio) are parasympathetic function tests and BP response to isometric handgrip (DDBPIHG) is sympathetic function test. Significantly increased 30:15 ratio and decreased E: I ratio in SCH subjects compared to that of controls [Table 4] reflects lower vagal reactivity in subclinical hypothyroids. A heightened diastolic pressure response to isometric handgrip (DDBPIHG) in SCH subjects reflects increased sympathetic reactivity. This is consistent with the significantly high DBP in subjects of SCH group [Table 3] as increase in diastolic pressure in handgrip test depends primarily on vascular resistance that reflects sympathetic reactivity. Thus, the findings of the present study substantiate that the SVI in SCH is due to both increased sympathetic activity and reactivity and decreased parasympathetic activity and reactivity.
Subclinical hypothyroid people have a myriad of factors which can affect the autonomic system and cause this alteration in the autonomic modulation in them. Hence, we have attempted to assess the contribution of inflammation and dyslipidemia in subclinical hypothyroid people to the autonomic dysfunction. Not only there were dyslipidemia (hypertriglyceridemia, high LDL-hypercholesterolemia, high VLDL-hypercholesterolemia and low HDL-cholesterolemia) and increased lipid risk factors [Table 6] in SCH group compared to that of control group, but also important lipid-related parameters were significantly correlated with LF-HF ratio [Table 7]. However, the degree of dyslipidemia in SCH group was mild as the levels of serum lipids were borderline high. Nevertheless, all the lipid risk factors except TC/TG were appreciably high in SCH group [Table 6]. Moreover, AI, the most important CV risk factor had significant correlation with LF-HF ratio [Table 7] though the direct contribution assessed by multiple regression analysis was not significant [Table 8]. From among the lipid risk factors assessed in the present study, we selected AI for the regression model as AI has recently been reported to be the better indicator CV risk. Other lipid parameters were excluded from the same regression model to avoid multi-collinearity. Dyslipidemia is common in SCH,,, and hyperlipidemia has been reported to be associated with increased sympathetic activity, especially in females. Thus, from findings of the present study, it appears that chronic hyperlipidemia could be a major contributor to the SVI in SCH and AI may indirectly contribute to CV risk in this disorder.
There is report of low-grade immunological inflammation in subclinical hypothyroid subjects. In the present study, marker of inflammation such as hs-CRP was significantly more in subjects of SCH group [Table 6]. However, hs-CRP was not significantly correlated with LF-HF ratio in SCH group [Table 7]. Thus, it appears that inflammation might not have a direct role to play in the genesis of SVI in SCH. Recently, it has been reported that CV disease risk in SCH is contributed by hs-CRP. Therefore, we postulate that hs-CRP could be among possible links between SVI and CV risk in SCH, which needs further documentation in larger sample size. LF-HF ratio was significantly correlated with TSH in SCH group [Table 7], and TSH had independent contribution to LH-HF ratio [Table 8], indicating that the alteration in sympathovagal balance could be directly linked to the magnitude of SCH. However, further studies warrant the assessment of degree of SVI at different serum levels of TSH in subclinical hypothyroid patients to elucidate the association between autonomic imbalance and severity of SCH.
In the present study, SVI in subclinical hypothyroid subjects was associated with dyslipidemia, increased lipid risk factors, and inflammation that are known CV risk factors., Moreover, the reduction in HRV per se has been reported to be an important CV risk., In the present study, magnitude of HRV (represented by TP of HRV) was grossly reduced in subclinical hypothyroid patients compared to that of age- and BMI-matched control subjects [Table 2]. MAP was not significantly correlated with LF-HF ratio (SVI) in subjects of SCH group [Table 7]. As the age, gender, and BMI are known to influence SVI, the OR in logistic regression [Table 9] was calculated after adjusting for age, gender, and BMI (adjusted OR). SBP and DBP were significantly high in SCH group [Table 3]. Moreover, recently, we have reported the close association of SVI with increased vascular tone and hypertension status that increases CV risks in prehypertensives. Therefore, SVI might contribute to rise in BP in SCH, which is linked to decreased BRS. The less sample size (n = 32) in SCH group might be the cause for lack of significant correlation of MAP with LF-HF ratio. A recent report has indicated that persistent hypertension in subclinical hypothyroid patients contributes to the cluster of CV disease risk factors. Hence, it appears that SVI contributes to the CV risks in SCH. However, a study in larger sample size is warranted for elucidation of the link of SVI with hypertension status in SCH.
As there are reports of increased CV risks due to hyperlipidemia ,,, and low-grade inflammation , in SCH patients, and in the present study, we found significant correlation between AI to SVI, we propose that a considerable decrease in HRV, intense SVI, persistent hyperlipidemia in SCH patients are interdependent phenomena. All these interlinked processes predispose these patients to increased risk of CV in terms of morbidity and mortality and SVI could be the physiological basis of CV risks in SCH.
Arterial baroreceptors play a central role in BP regulation in response to various stimuli through alteration in both sympathetic and vagal activities, and therefore, assessment of baroreceptor reflex sensitivity (BRS) provides the state of autonomic imbalance in various CV disease states. BRS has been documented as a measure of SVI and CV risk. In the present study, BRS of SCH group was significantly reduced [Table 3] indicating attenuation of CV health of SCH patients as decreased BRS has been reported to be associated with CV morbidity. Furthermore, it has been documented earlier that decrease in BRS predicts cardiac mortality in myocardial infarction patients. The decrease in BRS was significantly correlated with LF-HF ratio [Table 7] and had significant independent association with LF-HF ratio [Table 8]. In addition, prediction of prehypertension by BRS was significant in SCH group [Table 9], as demonstrated by bivariate logistic regression. Thus, decreased BRS in SCH patient as observed in the present study could increase their CV risks and predispose them to adverse CV events. The present study is the first of its kind assessing the status of BRS with prehypertension status in SCH.
TPR was high in SCH group compared to control group [Table 3] though it was not significantly correlated with LF-HF ratio [Table 7]. TPR, an indicator of sympathetic vasoconstrictor tone, has been suggested as a predictor of CV disease risk in individuals who had more body size at birth. In addition, TPR has been directly correlated with ventricular hypertrophy in hypertensives. Thus, increase in TPR could also contribute cardiac morbidities in these subjects. In the present study, systolic prehypertension (SBP 120–139 mmHg) was observed in about 50% of SCH subjects, and decreased BRS had significant prediction of prehypertension status. Thus, it indicates that decreased BRS, which is a known CV risk, is closely linked to the development of prehypertension in SCH.
| Conclusion|| |
SVI and decreased BRS were observed in SCH group that was linked to SVI. Thus, it indicates that decreased BRS, which is a known CV risk, is closely linked to the development of prehypertension in SCH. Reduced BRS that contributes to prehypertension status predisposes to subclinical hypothyroids to CV risks.
Limitations of the study
The major limitation of the study is the modest number of sample size. In addition, we have not assessed the biochemical markers of sympathetic activity for assessment of SVI, and we have not done echocardiography for the assessment of cardiac dysfunctions in SCH subjects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Unnikrishnan AG, Kalra S, Sahay RK, Bantwal G, John M, Tewari N, et al.
Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian J Endocrinol Metab 2013;17:647-52.
Deshmukh V, Behl A, Iyer V, Joshi H, Dholye JP, Varthakavi PK, et al.
Prevalence, clinical and biochemical profile of subclinical hypothyroidism in normal population in Mumbai. Indian J Endocrinol Metab 2013;17:454-9.
Biondi B, Fazio S, Palmieri EA, Carella C, Panza N, Cittadini A, et al.
Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 1999;84:2064-7.
Kvetny J, Heldgaard PE, Bladbjerg EM, Gram J. Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin Endocrinol (Oxf) 2004;61:232-8.
Nanda N, Bobby Z, Hamide A, Koner BC, Sridhar MG. Association between oxidative stress and coronary lipid risk factors in hypothyroid women is independent of body mass index. Metabolism 2007;56:1350-5.
Xing H, Shen Y, Chen H, Wang Y, Shen W. Heart rate variability and its response to thyroxine replacement therapy in patients with hypothyroidism. Chin Med J (Engl) 2001;114:906-8.
Karthik S, Pal GK, Nanda N, Hamide A, Bobby Z, Amudharaj D, et al.
Sympathovagal imbalance in thyroid dysfunctions in females: Correlation with thyroid profile, heart rate and blood pressure. Indian J Physiol Pharmacol 2009;53:243-52.
Syamsunder AN, Pal GK, Pal P, Kamalanathan CS, Parija SC, Nanda N, et al.
Association of sympathovagal imbalance with cardiovascular risks in overt hypothyroidism. N Am J Med Sci 2013;5:554-61.
Freeman R. Assessment of cardiovascular autonomic function. Clin Neurophysiol 2006;117:716-30.
Heart rate variability: Standards of measurement, physiological interpretation and clinical use. Task force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation 1996;93:1043-65.
Syamsunder AN, Pal P, Kamalanathan CS, Parija SC, Pal GK, Jayakrishnan G, et al
. Dyslipidemia and low-grade inflammation are associated with sympathovagal imbalance and cardiovascular risks in subclinical and overt hypothyroidism. Int J Clin Exp Physiol 2014;1:26-33. [Full text]
Noritake M, Takase B, Kudoh K, Kugai N, Kurita A, Nagata N, et al.
Diurnal change in heart rate variability in healthy and diabetic subjects. Intern Med 1992;31:453-6.
Pal GK, Pal P, Nanda N, Lalitha V, Syamsunder AN, Saranya K, et al
. Decreased baroreceptor reflex Sensitivity in first-degree relatives of type 2 diabetics is linked to sympathovagal imbalance and cardiovascular risks. J Clin Diagn Res 2014;5:43-9.
Malliani A. Heart rate variability: From bench to bedside. Eur J Intern Med 2005;16:12-20.
Pal GK, Pal P. Autonomic function tests. In: Textbook of Practical Physiology. 3rd
ed. Chennai: Universities Press; 2010. p. 282-90.
Galetta F, Franzoni F, Fallahi P, Rossi M, Carpi A, Rubello D, et al.
Heart rate variability and QT dispersion in patients with subclinical hypothyroidism. Biomed Pharmacother 2006;60:425-30.
Popa CD, Arts E, Fransen J, van Riel PL. Atherogenic index and high-density lipoprotein cholesterol as cardiovascular risk determinants in rheumatoid arthritis: The impact of therapy with biologicals. Mediators Inflamm 2012;2012:785946.
Turhan S, Sezer S, Erden G, Guctekin A, Ucar F, Ginis Z, et al.
Plasma homocysteine concentrations and serum lipid profile as atherosclerotic risk factors in subclinical hypothyroidism. Ann Saudi Med 2008;28:96-101.
] [Full text]
Hueston WJ, King DE, Geesey ME. Serum biomarkers for cardiovascular inflammation in subclinical hypothyroidism. Clin Endocrinol (Oxf) 2005;63:582-7.
Santi A, Duarte MM, de Menezes CC, Loro VL. Association of lipids with oxidative stress biomarkers in subclinical hypothyroidism. Int J Endocrinol 2012;2012:856359.
Lambert E, Straznicky N, Sari CI, Eikelis N, Hering D, Head G, et al.
Dyslipidemia is associated with sympathetic nervous activation and impaired endothelial function in young females. Am J Hypertens 2013;26:250-6.
Türemen EE, Çetinarslan B, Şahin T, Cantürk Z, Tarkun İ. Endothelial dysfunction and low grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis. Endocr J 2011;58:349-54.
Yu YT, Ho CT, Hsu HS, Li CI, Davidson LE, Liu CS, et al.
Subclinical hypothyroidism is associated with elevated high-sensitive C-reactive protein among adult Taiwanese. Endocrine 2013;44:716-22.
Vinik AI. The conductor of the autonomic orchestra. Front Endocrinol (Lausanne) 2012;3:71.
Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol 2010;141:122-31.
Pal GK, Pal P, Nanda N, Amudharaj D, Adithan C. Cardiovascular dysfunctions and sympathovagal imbalance in hypertension and prehypertension: Physiological perspectives. Future Cardiol 2013;9:53-69.
Pal GK, Pal P, Lalitha V, Amudharaj D, Nanda N, Dutta TK, et al.
Increased vascular tone due to sympathovagal imbalance in normotensive and prehypertensive offspring of hypertensive parents. Int Angiol 2012;31:340-7.
Ashizawa K, Imaizumi M, Usa T, Tominaga T, Sera N, Hida A, et al.
Metabolic cardiovascular disease risk factors and their clustering in subclinical hypothyroidism. Clin Endocrinol (Oxf) 2010;72:689-95.
Danese MD, Ladenson PW, Meinert CL, Powe NR. Clinical review 115: Effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: A quantitative review of the literature. J Clin Endocrinol Metab 2000;85:2993-3001.
Mansourian AR. A review on cardiovascular diseases originated from subclinical hypothyroidism. Pak J Biol Sci 2012;15:58-67.
Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU, et al.
The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: Randomized, crossover trial. J Clin Endocrinol Metab 2007;92:1715-23.
La Rovere MT, Pinna GD, Raczak G. Baroreflex sensitivity: Measurement and clinical implications. Ann Noninvasive Electrocardiol 2008;13:191-207.
Rovere MT, Maestri R, Pinna GD. Baroreflex sensitivity assessment latest advances and strategies. Ann Noninvasive Electrocardiol 2011;7:89-92.
La Rovere MT, Bigger JT Jr., Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes after Myocardial Infarction) investigators. Lancet 1998;351:478-84.
Feldt K, Räikkönen K, Pyhälä R, Jones A, Phillips DI, Eriksson JG, et al.
Body size at birth and cardiovascular response to and recovery from mental stress in children. J Hum Hypertens 2011;25:231-40.
Chen HI. Hemodynamic mechanism of ventricular hypertrophy in hypertension. Chin J Physiol 2012;55:369-79.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]