Decreased baroreflex sensitivity is linked to the atherogenic index, retrograde inflammation, and oxidative stress in subclinical hypothyroidism.

Purpose/aim of the study: The present study investigated the link of hyperlipidemia, inflammation and oxidative stress (OS) to cardiovascular (CV) risks in subclinical hypothyroidism (SCH). MATERIALS AND METHODS: We enrolled 81 subclinical hypothyroid patients and 80 healthy subjects as control. Their CV and autonomic functions were assessed by spectral analysis of heart rate variability (HRV), continuous blood pressure variability (BPV) measurement and conventional autonomic function testing. Thyroid profile, lipid profile, immunological, inflammatory and OS markers were estimated and correlated with the baro-reflex sensitivity (BRS), the marker of sympathovagal imbalance (SVI) & CV risk. RESULTS: Mean arterial pressure (MAP, P<0.0001), total peripheral resistance (TPR, P<0.0001), ratio of low-frequency to high-frequency power of HRV (LF-HF ratio) (P<0.0001) were significantly higher and BRS (P<0.0001) was significantly lower in SCH group than the control group. BRS significantly correlated with heart rate, MAP, LF-HF ratio, lipid risk factors, anti-thyroperoxidase antibody, thyroid-stimulating hormone, high-sensitive C-reactive protein (hsCRP), malondialdehyde (MDA) and SCH. CONCLUSIONS: It was concluded that SVI is associated with SCH. Though dyslipidemia, inflammation and OS contributed to decreased BRS, SCH per se contributed maximally to it. Decreased BRS could be a physiological basis of increased CV risks in patients with SCH.

Endothelial nitric oxide synthase gene polymorphisms are associated with cardiovascular risks in prehypertensives.

Though endothelial nitric oxide synthase (eNOS) gene polymorphism is documented in the causation of hypertension, its role in prehypertension has not been investigated. The present study was conducted in 172 subjects divided into prehypertensives (n = 57) and normotensives (n = 115). Cardiovascular (CV) parameters including baroreflex sensitivity (BRS) by continuous BP variability assessment and sympathovagal imbalance (SVI) by heart rate variability analysis were recorded. Biochemical parameters for insulin resistance (homeostatic model for assessment of insulin resistance), oxidative stress, lipid risk factors, renin, and inflammatory parameters were measured. Genotyping for eNOS polymorphisms rs1799983 (298G>T) and rs2070744 (-786T>C) was performed by polymerase chain reaction-restriction fragment length polymorphism method. Multiple regression analysis was done to assess the association between SVI and metabolic markers, and multivariate logistic regression was done to determine the prediction of prehypertension status by genotype, BRS, and ratio of low-frequency to high-frequency in these subjects. The BP variability, heart rate variability, and biochemical parameters were significantly altered in prehypertensives. The eNOS polymorphisms were found to be associated with prehypertension. BRS, the marker of SVI, was significantly associated with BP, homeostatic model for assessment of insulin resistance, and tumor necrosis factor alpha in 298GG genotype of prehypertensive population. The eNOS gene polymorphisms appear to be associated with prehypertension. 298G>T and -786T>C contribute to SVI in young prehypertensives attributed by insulin resistance and inflammation. The CV risks were associated with prehypertension status in prehypertensives expressing both 298GG and -786TT genotypes. Association of CV risks with SVI appears to be stronger in prehypertensives expressing GG genotype.

Association of hypertension status and cardiovascular risks with sympathovagal imbalance in first degree relatives of type 2 diabetics.

AIMS/INTRODUCTION: As reports show cardiovascular (CV) risks in first-degree relatives (FDR) of type 2 diabetics, and autonomic imbalance predisposing to CV risks, in the present study we have assessed the contribution of sympathovagal imbalance (SVI) to CV risks in these subjects. MATERIALS AND METHODS: Body mass index (BMI), waist-to-hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP), and spectral indices of heart rate variability (HRV) were reordered and analyzed in FDR of type 2 diabetics (study group, n = 293) and in subjects with no family history of diabetes (control group, n = 405). RESULTS: The ratio of low-frequency (LF) to high-frequency (HF) power of HRV (LF-HF), a sensitive marker of SVI, was significantly increased (P < 0.001) in the study group compared with the control group. The SVI in the study group was due to concomitant sympathetic activation (increased LF) and vagal inhibition (decreased HF). In the study group, the LF-HF ratio was significantly correlated with BMI, WHR, BHR, BP and RPP. Multiple regression analysis showed an independent contribution of LF-HF to hypertension status (P = 0.000), and bivariate logistic regression showed significant prediction (odds ratio 2.16, confidence interval 1.130-5.115) of LF-HF to increased RPP, the marker of CV risk, in the study group. CONCLUSIONS: Sympathovagal imbalance in the form of increased sympathetic and decreased parasympathetic activity is present in FDR of type 2 diabetics. Increased resting heart rate, elevated hypertension status, decreased HRV and increased RPP in these subjects make them vulnerable to CV risks. SVI in these subjects contributes to CV risks independent of the degree of adiposity.

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.

Association of sympathovagal imbalance with cardiovascular risks in overt hypothyroidism.

BACKGROUND: Cardiovascular morbidities have been reported in hypothyroidism. AIMS: The objective of this study is to investigate the link of sympathovagal imbalance (SVI) to cardiovascular risks (CVRs) and the plausible mechanisms of CVR in hypothyroidism. MATERIALS AND METHODS: Age-matched 104 females (50 controls, 54 hypothyroids) were recruited and their body mass index (BMI), cardiovascular parameters, autonomic function tests by spectral analysis of heart rate variability (HRV), heart rate response to standing, deep breathing and blood pressure response to isometric handgrip were studied. Thyroid profile, lipid profile, immunological and inflammatory markers were estimated and their association with low-frequency to the high-frequency ratio (LF-HF) of HRV, the marker of SVI was assessed by multivariate regression. RESULTS: Increased diastolic pressure, decreased HRV, increased LF-HF, dyslipidemia and increased high-sensitive C-reactive protein (hsCRP) were observed in hypothyroid patients and all these parameters had significant correlation with LF-HF. BMI had no significant association with LF-HF. Atherogenic index (ß 1.144, P = 0.001) and hsCRP (b 0.578, P = 0.009) had independent contribution to LF-HF. LF-HF could significantly predict hypertension status (odds ratio 2.05, confidence interval 1.110-5.352, P = 0.008) in hypothyroid subjects. CONCLUSIONS: SVI due to sympathetic activation and vagal withdrawal occurs in hypothyroidism. Dyslipidemia and low-grade inflammation, but not obesity contribute to SVI and SVI contributes to cardiovascular risks.