Pravati Pal

Cardiovascular dysfunctions and sympathovagal imbalance in hypertension and prehypertension: physiological perspectives

Hypertension (HTN) and prehypertension (pre-HTN) have been identified as independent risk factors for adverse cardiovascular events. Recently, increased psychosocial stress and work stress have contributed to the increased prevalence of HTN and pre-HTN, in addition to the contribution of obesity, diabetes, poor food habits and physical inactivity. Irrespective of the etiology, sympathetic overactivity has been recognized as the main pathophysiologic mechanism in the genesis of HTN and pre-HTN. Sympathovagal imbalance owing to sympathetic overactivity and vagal withdrawal is reported to be the basis of many clinical disorders. However, the role played by vagal withdrawal has been under-reported. In this review, we have analyzed the pathophysiologic involvement of sympathovagal imbalance in the development of HTN and pre-HTN, and the link of sympathovagal imbalance to cardiovascular dysfunctions. We have emphasized that adaptation to a healthier lifestyle will help improve sympathovagal homeostasis and prevent the occurrence of HTN and pre-HTN.

Assessment of sympathovagal imbalance by spectral analysis of heart rate variability in prehypertensive and hypertensive patients in Indian population.

Though the incidence of hypertension has increased considerably in recent years, the pathophysiologic mechanism that causes progression from stage of prehypertension to hypertension has not been fully elucidated. Therefore, the present study was conducted to assess the sympathovagal imbalance in prehypertensives and hypertensives by spectral analysis of heart rate variability (HRV) to understand the nature of change in autonomic balance in this common dysfunction of mankind. Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), and spectral indices of HRV such as total power (TP), normalized low frequency power (LFnu), normalized high frequency power (HFnu), ratio of low frequency power to high frequency power (LF-HF ratio), mean heart rate (mean RR), square root of the mean squared differences of successive normal to normal intervals (RMSSD), the number of interval differences of successive NN intervals greater than 50 ms (NN50), and the proportion derived by dividing NN50 by the total number of NN intervals (pNN50) were assessed in three groups of subjects: normotensives (n = 32), prehypertensives (n = 28), and hypertensives (n = 31). Sympathovagal balance was analyzed and correlated with BMI, BHR, and BP in all the groups. It was observed that autonomic imbalance in prehypertensives was due to proportionate increased sympathetic activity and vagal inhibition, whereas in hypertensives, vagal withdrawal was more prominent than sympathetic overactivity. The LF-HF ratio, the sensitive indicator of sympathovagal balance, was significantly correlated with BMI, BHR, and BP. It was concluded that vagal inhibition plays an important role in the critical alteration of sympathovagal balance in the development of clinical hypertension in prehypertensive subjects.

Sympathovagal imbalance contributes to prehypertension status and cardiovascular risks attributed by insulin resistance, inflammation, dyslipidemia and oxidative stress in first degree relatives of type 2 diabetics.

Background Though cardiovascular (CV) risks are reported in first-degree relatives (FDR) of type 2 diabetics, the pathophysiological mechanisms contributing to these risks are not known. We investigated the association of sympathovagal imbalance (SVI) with CV risks in these subjects. Subjects and Methods Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate-pressure product (RPP), spectral indices of heart rate variability (HRV), autonomic function tests, insulin resistance (HOMA-IR), lipid profile, inflammatory markers, oxidative stress (OS) marker, rennin, thyroid profile and serum electrolytes were measured and analyzed in subjects of study group (FDR of type 2 diabetics, n = 72) and control group (subjects with no family history of diabetes, n = 104). Results BMI, BP, BHR, HOMA-IR, lipid profile, inflammatory and OS markers, renin, LF-HF (ratio of low-frequency to high-frequency power of HRV, a sensitive marker of SVI) were significantly increased (p<0.0001) in study group compared to the control group. SVI in study group was due to concomitant sympathetic activation and vagal inhibition. There was significant correlation and independent contribution of markers of insulin resistance, dyslipidemia, inflammation and OS to LF-HF ratio. Multiple-regression analysis demonstrated an independent contribution of LF-HF ratio to prehypertension status (standardized beta 0.415, p<0.001) and bivariate logistic-regression showed significant prediction (OR 2.40, CI 1.128–5.326, p = 0.002) of LF-HF ratio of HRV to increased RPP, the marker of CV risk, in study group. Conclusion SVI in FDR of type 2 diabetics occurs due to sympathetic activation and vagal withdrawal. The SVI contributes to prehypertension status and CV risks caused by insulin resistance, dyslipidemia, inflammation and oxidative stress in FDR of type 2 diabetics.

Spectral analysis of heart rate variability (HRV) may predict the future development of essential hypertension

Presently, essential hypertension (EH) is among the most common morbid disorders of mankind. The fundamental pathophysiology of EH is sympathetic overactivity. It has been observed that the people having common risk factors for hypertension such as obesity, insulin resistance and stress generally have increased sympathetic activity. Therefore, it is presumed that patients suffering from EH develop some degree of increased sympathetic activity much before they clinically develop hypertension. Spectral analysis of heart rate variability (HRV) has been demonstrated to accurately assess change in sympathovagal balance (autonomic activity) even when the alteration is in its minimal form. Therefore, in the present paper we hypothesize that spectral analysis of HRV could be utilized for early prediction of EH. We also suggest that the predictive knowledge of sympathovagal imbalance in the development of EH should be employed in elucidating the mechanisms for prevention of this dysfunction.

Cardiovagal Modulation, Oxidative Stress, and Cardiovascular Risk Factors in Prehypertensive Subjects: Cross-Sectional Study

BACKGROUND Hypertension, one of the modifiable risk factors for cardiovascular disease (CVD), is known to be associated with increased oxidative stress and reduced cardiovagal modulation. Similar to hypertension, prehypertension is associated with increased risk of adverse cardiovascular (CV) events. We planned this study to find the association between prehypertension, cardiovagal modulation, oxidative stress, and associated CV risk factors. METHODS We recruited 178 subjects through hypertension screening camps conducted in Puducherry, India. Subjects were grouped into prehypertensive (n = 97) and normotensive (n = 81) groups. They were further subdivided, based on age, as young (20-39 years) and middle-aged (40-60 years) adults. We measured basal physiological parameters, heart rate variability, oxidative stress (thiobarbituric acid reactive substance and total antioxidant capacity (TAC)), and CV risk factors. RESULTS We found significant increase in oxidative stress in prehypertensive subjects of both age groups but the cardiovagal modulation decreased significantly in young prehypertensive subjects when compared with normotensive subjects. Correlation of TAC with root mean square of the sum of successive R wave to R wave (RR) interval differences (RMSSD), a cardiovagal modulation parameter (r = 0. 437; P < 0.001), and mean arterial pressure (MAP) (r = -0.318; P < 0.001) was significant even after adjusting for CV risk factors. The correlation between MAP and RMSSD (r = 0.199; P = 0.009) was reduced after adjusting for CV risk factors. CONCLUSIONS Prehypertension in young adults is associated with increased oxidative stress and altered cardiovagal modulation. The risk factors for CVDs in prehypertensive young adults were found to be equivalent to that of middle-aged adults who are in the twilight zone for developing CV dysfunctions.

Body mass index contributes to sympathovagal imbalance in prehypertensives.

BackgroundThe present study was conducted to assess the nature of sympathovagal imbalance (SVI) in prehypertensives by short-term analysis of heart rate variability (HRV) to understand the alteration in autonomic modulation and the contribution of BMI to SVI in the genesis of prehypertension.MethodsBody mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP) and HRV indices such as total power (TP), low-frequency power (LF), normalized LF (LFnu), high-frequency power (HF), normalized HF (HFnu), LF-HF ratio, mean heart rate (mean RR), square root of the mean squared differences of successive normal to normal intervals (RMSSD), standard deviation of normal to normal RR interval (SDNN), the number of interval differences of successive NN intervals greater than 50 ms (NN50) and the proportion derived by dividing NN50 by the total number of NN intervals (pNN50) were assessed in three groups of subjects: normotensives having normal BMI (Group 1), prehypertensives having normal BMI (Group 2) and prehypertensives having higher BMI (Group 3). SVI was assessed from LF-HF ratio and correlated with BMI, BHR, BP and RPP in all the groups by Pearson correlation. The contribution of BMI to SVI was assessed by multiple regression analysis.ResultsLF and LFnu were significantly increased and HF and HFnu were significantly decreased in prehypertensive subjects in comparison to normotensive subjects and the magnitude of these changes was more prominent in subjects with higher BMI compared to that of normal BMI. LF-HF ratio, the sensitive indicator of sympathovagal balance had significant correlation with BMI (P = 0.000) and diastolic blood pressure (DBP) (P = 0.002) in prehypertensives. BMI was found to be an independent contributing factor to SVI (P = 0.001) in prehypertensives.ConclusionsIt was concluded that autonomic imbalance in prehypertensives manifested in the form of increased sympathetic activity and vagal inhibition. In prehypertensives with higher BMI, vagal withdrawal was predominant than sympathetic overactivity. Magnitude of SVI (alteration in LF-HF ratio) was linked to changes in BMI and DBP. BMI had an independent influence on LF-HF ratio. It was advised that life-style modifications such as yoga and exercise would enable achieve the sympathovagal balance and blood pressure homeostasis in prehypertensives.

Spectral Analysis of Heart Rate Variability for Early Prediction of Pregnancy-Induced Hypertension

The early prediction of pregnancy-induced hypertension (PIH), a common morbid disorder of pregnancy is unsatisfactory. Therefore, in the present study we have investigated the role of spectral analysis of heart rate variability (HRV) in the early prediction of PIH. Spectral analysis of HRV was performed in three groups of subjects (Group I: normal pregnant women; Group II: pregnant women with risk factors, but did not develop PIH; Group III: pregnant women with risk factors and developed PIH). It was observed that the LF-HF ratio, the most sensitive indicator of sympathovagal balance, was significantly high (p < 0.01) since early pregnancy in group III compared to other groups, which was significantly correlated with heart rate and blood pressure. It was suggested that the predictive knowledge of sympathovagal imbalance should be utilized in designing the prevention and management of PIH.

Association between cardiac autonomic function, oxidative stress and inflammatory response in impaired fasting glucose subjects: cross-sectional study.

Background The worldwide burden of diabetes in 2030 is projected around 552 million. Diabetes leads to higher risk for cardiovascular diseases (CVD). Altered cardiac autonomic function (CAF) measured by heart rate variability (HRV) is observed in early stages of diabetes but the relationship between impaired fasting glucose (IFG) and HRV is still debatable. The aim of the study was to evaluate the association between CAF, oxidative stress, insulin resistance (IR), and inflammatory response in IFG subjects. Subjects and Methods Cross-sectional blinded study. Volunteers recruited from health awareness camps underwent CAF and biochemical tests. Based on fasting plasma glucose (FPG) participants (n = 123) were divided into two groups, normal fasting glucose (n = 76) and IFG (n = 47). The comparison of parameters between the groups was carried out using student t test and Mann-Whitney U test for parametric and non-parametric data respectively. The correlation between the parameters was analyzed by Spearman’s rank correlation using SPSS 13.0. Results The resting cardiovagal modulation parameters, heart rate response to forced timed breathing, and orthostatic stress were reduced in IFG subjects. Fasting plasma lipid profile, coronary atherogenic lipid risk factors, IR, thiobarbituric acid reactive substance (TBARS), high sensitive C-reactive protein, and tumor necrosis factor alpha were increased and total antioxidant capacity (TAC) was decreased significantly in IFG group but no significant alteration was observed in high-density lipoprotein (HDL-c). Cardiovagal modulation parameters were negatively correlated with triglycerides, FPG, insulin, IR, TBARS, and inflammatory markers and positively with TAC. Conclusion There is a continuous interplay between the altered CAF, hyperinsulinemia, IR, oxidative stress parameters, inflammatory response, and IFG in which one factor perpetuates another leading to the progression of disease.

Association of sympathovagal imbalance with obesity indices, and abnormal metabolic biomarkers and cardiovascular parameters

PROBLEM Pathophysiological mechanisms contributing to abnormal cardiovascular (CV) parameters in obesity have not been fully elucidated. Role of sympathovagal imbalance (SVI) in the prediction of abnormalities in CV functions in obesity has not been studied. METHODS Anthropometric indices, CV parameters, autonomic function tests (AFTs) such as spectral heart rate variability (HRV) analysis, heart rate and blood pressure response to standing, deep breathing, and isometric-handgrip, and biochemical parameters like insulin resistance (HOMA-IR), lipid risk factors and inflammatory marker [high-sensitive C-reactive protein (hsCRP)] were assessed in control group (non-obese, n=43) and obese group (n=45). Association of anthropometric indices and abnormal CV parameters with low-frequency to high-frequency ratio (LF-HF) of HRV was performed by Pearsons correlation. Independent contribution of anthropometric indices and abnormal CV parameters to LF-HF was assessed by using a multiple regression analysis. LF-HF prediction of rate-pressure product (RPP), the indicator of CV dysfunction was assessed by logistic regression. RESULTS LF-HF, the marker of SVI was more in obese group compared to control group. AFTs of sympathetic activity were increased and of parasympathetic activity were reduced in obese group. Anthropometric indices, HOMA-IR, lipid risk factors and hsCRP were correlated with LF-HF. These metabolic biomarkers had independent contribution to SVI. Among, anthropometric indices, waist-to-height ratio (WHtR) had maximum association with LF-HF. LF-HF had significant prediction of RPP in obese group. CONCLUSION SVI in obesity is due to both increased sympathetic and decreased vagal activity. Abnormal CV parameters in obesity are linked to SVI, which is contributed by insulin resistance, dyslipidaemia and low-grade inflammation. LF-HF predicts abnormal CV parameters in obesity.

Sympathovagal Imbalance in Prehypertensive Offspring of Two Parents versus One Parent Hypertensive

Objective. Though prehypertension has strong familial predisposition, difference in pathophysiological mechanisms in its genesis in offspring of both parents and single parent hypertensive have not been elucidated. Methods. Body mass index (BMI), waist-hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), HR and BP response to standing, deep breathing difference, BP response to handgrip and spectral indices of heart rate variability (HRV) were analyzed in normotensive offspring of two parents hypertensive (Group I), normotensive offspring of one parent hypertensive (Group II), prehypertensive offspring of two parents hypertensive (Group III) and prehypertensive offspring of one parent hypertensive (Group IV). Results. Sympathovagal imbalance (SVI) in prehypertensive offspring was observed due to increased sympathetic and decreased vagal activity. In group III, SVI was more prominent with greater contribution by vagal withdrawal. LF-HF ratio, the marker of SVI was correlated more with diastolic pressure, 30 : 15 ratio and E : I ratio in prehypertensives and the degree of correlation was more in group III prehypertensives. Conclusion. Vagal withdrawal plays a critical role in development of SVI in prehypertensive offspring of hypertensive parents. The intensity of SVI was more in offspring of two parents hypertensive compared to single parent hypertensive.