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1.  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 
PLoS ONE  2013;8(11):e78072.
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.
doi:10.1371/journal.pone.0078072
PMCID: PMC3827034  PMID: 24265679
2.  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.
doi:10.4061/2011/263170
PMCID: PMC3202093  PMID: 22121472
3.  Association of hypertension status and cardiovascular risks with sympathovagal imbalance in first degree relatives of type 2 diabetics 
Abstract
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.
doi:10.1111/jdi.12166
PMCID: PMC4210069  PMID: 25411606
Autonomic imbalance; Cardiovascular risk; First‐degree relatives of type 2 diabetics
4.  Vagal Withdrawal and Sympathetic Overactivity Contribute to the Genesis of Early-Onset Pregnancy-Induced Hypertension 
Objective. In this study, we have assessed sympathovagal imbalance (SVI) by spectral analysis of heart rate variability (HRV) that contributes to the genesis of early-onset PIH. Methods. Body mass index (BMI), basal heart rate (BHR), blood pressure (BP) and HRV indices such as LFnu, HFnu, LF-HF ratio, mean RR, SDNN and RMSSD were assessed in normal pregnant women (Control group) and pregnant women having risk factors for PIH (Study group) at all the trimesters pregnancy. Retrospectively, those who did not develop PIH (Study group I) were separated from those who developed PIH (Study group II). Study group II was subdivided into early-onset and late-onset PIH. Sympathovagal balance (LF-HF ratio) was correlated with BMI, BHR and BP. Results. LF-HF ratio was significantly high in study group II compared to study group I and control group, and in early-onset PIH group compared to the late-onset category at all the trimesters of pregnancy, which was significantly correlated with BHR and BP. Alteration in HFnu in early-onset category was more prominent than the alteration in LFnu. Conclusion. Though the SVI in PIH is contributed by both sympathetic overactivity and vagal withdrawal, especially in early-onset type, SVI is mainly due to vagal inhibition.
doi:10.4061/2011/361417
PMCID: PMC3095942  PMID: 21629868
5.  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 (β 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.
doi:10.4103/1947-2714.118921
PMCID: PMC3818829  PMID: 24251274
Autonomic imbalance; Body mass index; Cardiovascular risks; Dyslipidemia; High-sensitive C-reactive protein; Hypothyroidism; Sympathovagal imbalance
6.  Impact of Prehypertension on Left Ventricular Structure, Function and Geometry 
Background: Awareness of prevalence, determinants, and prognosis of asymptomatic untreated prehypertension is still lacking especially in India and subcontinent. The present study was to assess the effects of prehypertension on structure, function and geometrical pattern of left ventricle on the basis of left ventricular mass (LVM), left ventricular mass indexed to height (LVMI/Ht), and relative wall thickness (RWT) recorded by echocardiography based on the American society of echocardiography (ASE) convention.
Methods: The study population included prehypertensives (n 61; 31 M, 30 F) and normotensives (n 38; 19 M, 19 F) between age 25 and 65 years, and were assessed by echocardiography.
Results: It was observed that the stroke volume (SV), cardiac output (CO), cardiac index (CI), body mass index (BMI), body surface area (BSA), were found to be little elevated but was not significant in hypertensive females compared to normotensives. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse pressure (PP), mean arterial pressure (MAP), end systolic stress (ESS), and end isovolumetric systolic stress (EISS) were significantly elevated (p<0.001) in female prehypertensives compared to normotensives. Left ventricular mass (LVM) was significantly (p< 0.05) elevated, indicating alterations in cardiac morphology and functions even during prehypertensive stage. However, in prehypertensive males, SBP, DBP, HR, PP, MAP, ESS, and EISS were significantly (<0.001) raised; ejection fraction (EF%) and fractional fibre shortening (FS%) were noted to be within normal range in both sexes. Prehypertensive males showed changes in left ventricular geometry in the form of concentric remodeling (CR-3.44%), eccentric hypertrophy (EH-3.44%) and concentric hypertrophy (CH-13.79%). Prehypertensive females showed (CR-6.45%), (EH-3.22%) and (CH-6.4%).
Conclusion: Such findings carry prognostic implication and require further population survey involving a larger group. Early diagnosis of prehypertension will help to take necessary preventive measures to reduce mainly the future cardiovascular complications. The care of prehypertensive subjects should include, to reduce the afterload in order to improve the left ventricular contractile state as early as possible. So it is advisable to do routine echocardiography after the age of 40 years.
doi:10.7860/JCDR/2014/8023.4277
PMCID: PMC4064896  PMID: 24959434
Prehypertension; Left ventricular mass; Relative wall thickness
7.  Linear and nonlinear analysis of heart rate variability in healthy subjects and after acute myocardial infarction in patients 
The objectives of this study were to evaluate and compare the use of linear and nonlinear methods for analysis of heart rate variability (HRV) in healthy subjects and in patients after acute myocardial infarction (AMI). Heart rate (HR) was recorded for 15 min in the supine position in 10 patients with AMI taking β-blockers (aged 57 ± 9 years) and in 11 healthy subjects (aged 53 ± 4 years). HRV was analyzed in the time domain (RMSSD and RMSM), the frequency domain using low- and high-frequency bands in normalized units (nu; LFnu and HFnu) and the LF/HF ratio and approximate entropy (ApEn) were determined. There was a correlation (P < 0.05) of RMSSD, RMSM, LFnu, HFnu, and the LF/HF ratio index with the ApEn of the AMI group on the 2nd (r = 0.87, 0.65, 0.72, 0.72, and 0.64) and 7th day (r = 0.88, 0.70, 0.69, 0.69, and 0.87) and of the healthy group (r = 0.63, 0.71, 0.63, 0.63, and 0.74), respectively. The median HRV indexes of the AMI group on the 2nd and 7th day differed from the healthy group (P < 0.05): RMSSD = 10.37, 19.95, 24.81; RMSM = 23.47, 31.96, 43.79; LFnu = 0.79, 0.79, 0.62; HFnu = 0.20, 0.20, 0.37; LF/HF ratio = 3.87, 3.94, 1.65; ApEn = 1.01, 1.24, 1.31, respectively. There was agreement between the methods, suggesting that these have the same power to evaluate autonomic modulation of HR in both AMI patients and healthy subjects. AMI contributed to a reduction in cardiac signal irregularity, higher sympathetic modulation and lower vagal modulation.
doi:10.1590/S0100-879X2012007500025
PMCID: PMC3854283  PMID: 22370707
Myocardial infarction; Heart rate variability; Autonomic nervous system; Spectral analysis; Nonlinear dynamics
8.  The effects of a glucose load and sympathetic challenge on autonomic function in obese women with and without type 2 diabetes 
This study examined the effect of glucose ingestion on cardiac autonomic function in non-obese women and obese women with and without type 2 diabetes. Heart rate variability (HRV) was measured via continuous ECG and beat-by-beat blood pressure was recorded with finger photoplethysmography (Portapress) in a fasted state and in response to a 75 g glucose load in 42 middle-aged women (40–60 yr). Upright tilt was also utilized as an orthostatic stress to provide a clinically relevant challenge to the cardiovascular system. Significant main effects for log transformed (Ln) total power (TP, msec2) were observed with upright tilt (P<0.01) and glucose challenge (P<0.05). LnTP decreased in all groups in both the fasted and fed state with upright tilt (P<0.01), but glucose ingestion resulted in higher LnTP in the supine position only (P=0.008). Tilt resulted in a significant main effect for low frequency (LFnu, normalized units) and high frequency (Hfnu) power (P<0.000), while the glucose challenge had no effect on LFnu or HFnu power. LFnu approached significance for group differences (P=0.07), such that the non-obese had lower LF power than either of the obese groups. Sympathovagal balance (LnLF/HF ratio) was affected by position (P<0.000) and group (P<0.05), with a lower LnLF/HF in the non-obese than in the obese women. Baroreceptor sensitivity decreased (P<0.01) during upright tilt but was not changed by the glucose challenge. In conclusion, basal sympathovagal balance is higher in obese individuals with and without type 2 diabetes. Women with type 2 diabetes showed no differences in autonomic function with an orthostatic challenge or glucose load than non-diabetic, obese women. The glucose load did alter total spectral power in all of these middle-aged women, but had no impact on baroreceptor sensitivity.
doi:10.1016/j.metabol.2007.02.001
PMCID: PMC1978097  PMID: 17512310
9.  Is Prehypertension a Risk Factor for the Development of Type 2 Diabetes? 
Diabetes Care  2009;32(10):1870-1872.
OBJECTIVE
Prehypertension is associated with cardiovascular disease and insulin resistance. However, whether subjects with prehypertension have more diabetes risk is not known. We examine whether prehypertension is a risk factor for developing type 2 diabetes.
RESEARCH DESIGN AND METHODS
Incident diabetes was examined in nondiabetic normotensive participants in the San Antonio Heart Study (n = 2,767; aged 25–65 years; median follow-up 7.8 years).
RESULTS
Incident diabetes was 12.4% in subjects with prehypertension and 5.6% in subjects with normal blood pressure. The odds of incident diabetes were 2.21 greater for individuals with prehypertension than for those with normal blood pressure (95% CI 1.63–2.98) after adjusting for age, sex, and ethnicity. Prehypertension was not associated with incident diabetes after additional adjustment for BMI, impaired glucose tolerance, insulin resistance and secretion, and family history of diabetes (odds ratio 1.42 [95% CI 0.99–2.02]).
CONCLUSIONS
Subjects with prehypertension are at increased risk of diabetes. Much of this risk is explained by disorders related to the insulin resistance syndrome.
doi:10.2337/dc09-0328
PMCID: PMC2752916  PMID: 19628813
10.  Blood Pressure and the Risk of Developing Diabetes in African Americans and Whites 
Diabetes Care  2011;34(4):873-879.
OBJECTIVE
We examined the association between high blood pressure and incident type 2 diabetes in African Americans and whites aged 35–54 years at baseline.
RESEARCH DESIGN AND METHODS
We combined data from the Atherosclerosis Risk in Communities (ARIC) study, the Coronary Artery Risk Development in Young Adults (CARDIA) study, and the Framingham Heart Study offspring cohort. Overall, 10,893 participants (57% women; 23% African American) were categorized by baseline blood pressure (normal, prehypertension, hypertension) and examined for incident diabetes (median follow-up 8.9 years).
RESULTS
Overall, 14.6% of African Americans and 7.9% of whites developed diabetes. Age-adjusted incidence was increasingly higher across increasing blood pressure groups (P values for trend: <0.05 for African American men; <0.001 for other race-sex groups). After adjustment for age, sex, BMI, fasting glucose, HDL cholesterol, and triglycerides, prehypertension or hypertension (compared with normal blood pressure) was associated with greater risks of diabetes in whites (hazard ratio [HR] for prehypertension: 1.32 [95% CI 1.09–1.61]; for hypertension: 1.25 [1.03–1.53]), but not African Americans (HR for prehypertension: 0.86 [0.63–1.17]; for hypertension: 0.92 [0.70–1.21]). HRs for developing diabetes among normotensive, prehypertensive, and hypertensive African Americans versus normotensive whites were: 2.75, 2.28, and 2.36, respectively (P values <0.001).
CONCLUSIONS
In African Americans, higher diabetes incidence among hypertensive individuals may be explained by BMI, fasting glucose, triglyceride, and HDL cholesterol. In whites, prehypertension and hypertension are associated with greater risk of diabetes, beyond that explained by other risk factors. African Americans, regardless of blood pressure, have greater risks of developing diabetes than whites.
doi:10.2337/dc10-1786
PMCID: PMC3064044  PMID: 21346180
11.  Early Inflammatory and Metabolic Changes in Association With AGTR1 Polymorphisms in Prehypertensive Subjects 
American journal of hypertension  2010;24(2):225-233.
BACKGROUND
The Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in 2003 created a prehypertension category for persons with blood pressures ranging from systolic blood pressure (SBP) of 120–139 mm Hg or diastolic blood pressure (DBP) from 80 to 89 mm Hg, due to increased risk of cardiovascular disease.
METHODS
Our study utilized the University of California-San Diego (UCSD) Twin Hypertension Cohort. We measured comprehensive plasma cholesterol levels and metabolic (glucose, insulin, leptin) and inflammatory markers (interleukin-6 (IL-6), C-reactive protein (CRP), free fatty acids) to determine the differences between normotensive and prehypertensive subjects. Additionally, we determined whether angiotensin II receptor type-1 (AGTR1) polymorphisms, previously associated with hypertension, could predict prehypertension.
RESULTS
A total of 455 white subjects were included in the study (mean age 37.1 years). Prehypertensive subjects were older with greater body mass index (BMI) than the normotensives, and after adjusting for sex and age, had greater plasma glucose, insulin, and IL-6. The common AGTR1 A1166C (rs5186) polymorphism in the 3′-UTR region, particularly the presence of the 1166C allele, which fails to downregulate gene expression, predicted greater likelihood of being in the prehypertension group and higher SBP. A lesser-studied polymorphism in intron-2 of AGTR1 (A/G; rs2276736) was associated with plasma high-density lipoprotein (HDL) and apolipoprotein A-1. In a subgroup analysis of nonobese subjects (N = 405), similar associations were noted.
CONCLUSION
Prehypertensive subjects already exhibit early pathophysiologic changes putting them at risk of future cardiovascular disease, and AGTR1 may also contribute to this increased risk. Further investigation is needed to confirm these findings and the precise molecular mechanisms of action.
doi:10.1038/ajh.2010.210
PMCID: PMC3101264  PMID: 20864943
AGTR1; angiotensin II receptor; blood pressure; hypertension; inflammation; prehypertension
12.  Prehypertension in young females, where do they stand? 
Indian Heart Journal  2012;64(3):280-283.
Background
To determine the prevalence of prehypertension in young females and its correlation to various parameters like body mass index (BMI), waist hip ratio (WHR), waist circumference (WC) and family history, and blood pressure (BP) response to exercise stress testing.
Methods
One hundred and fifty apparently healthy females of age group 18–25-years were randomly selected from the student population of Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, after satisfying all the inclusion criteria and written informed consent. Along with all the anthropometric parameters BMI, WHR, WC and family history of hypertension (HTN) and/or diabetes, resting BP, and BP response to exercise stress testing were measured in the study.
Results
Amongst 150 subjects, 63 (42%) subjects were normotensive and 87 (58%) were prehypertensive. Body mass index, WHR, WC and family history of HTN were significantly higher in prehypertensive group. Prehypertensive group also had an exaggerated BP response to exercise stress testing and higher BP during recovery.
Conclusion
Prevalence of prehypertension was found to be high in females, also there was a strong correlation between prehypertension and BMI, WHR and WC suggesting a positive correlation between obesity and prehypertension. Prehypertensive group also showed an exaggerated BP response to exercise stress testing.
doi:10.1016/S0019-4832(12)60087-X
PMCID: PMC3860851  PMID: 22664811
Exercise stress testing; Prehypertension; Young females
13.  Elevated serum neutrophil elastase is related to prehypertension and airflow limitation in obese women 
BMC Women's Health  2011;11:1.
Background
Neutrophil elastase level/activity is elevated in a variety of diseases such as atherosclerosis, systolic hypertension and obstructive pulmonary disease. It is unknown whether obese individuals with prehypertension also have elevated neutrophil elastase, and if so, whether it has a deleterious effect on pulmonary function. Objectives: To determine neutrophil elastase levels in obese prehypertensive women and investigate correlations with pulmonary function tests.
Methods
Thirty obese prehypertensive women were compared with 30 obese normotensive subjects and 30 healthy controls. The study groups were matched for age. Measurements: The following were determined: body mass index, waist circumference, blood pressure, lipid profile, high sensitivity C-reactive protein, serum neutrophil elastase, and pulmonary function tests including forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio.
Results
Serum neutrophil elastase concentration was significantly higher in both prehypertensive (405.8 ± 111.6 ng/ml) and normotensive (336.5 ± 81.5 ng/ml) obese women than in control non-obese women (243.9 ± 23.9 ng/ml); the level was significantly higher in the prehypertensive than the normotensive obese women. FEV1, FVC and FEV1/FVC ratio in both prehypertensive and normotensive obese women were significantly lower than in normal controls, but there was no statistically significant difference between the prehypertensive and normotensive obese women. In prehypertensive obese women, there were significant positive correlations between neutrophil elastase and body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low density lipoprotein cholesterol, high sensitivity C-reactive protein and negative correlations with high density lipoprotein cholesterol, FEV1, FVC and FEV1/FVC.
Conclusion
Neutrophil elastase concentration is elevated in obese prehypertensive women along with an increase in high sensitivity C-reactive protein which may account for dyslipidemia and airflow dysfunction in the present study population.
doi:10.1186/1472-6874-11-1
PMCID: PMC3031240  PMID: 21247478
14.  Cardio-metabolic risk factors and prehypertension in persons without diabetes, hypertension, and cardiovascular disease 
BMC Public Health  2013;13:730.
Background
Prehypertension has been shown to be an early risk factor of cardiovascular disease (CVD). We investigated the prevalence and pattern of cardiometabolic risk factors in prehypertension in three ethnic Asian populations in Singapore.
Methods
We examined data from Chinese (n = 1177), Malay (n = 774), and Indian (n = 985) adults aged 40–80 years who participated in three independent population based studies conducted from 2004–2011 in Singapore who were free of diabetes, hypertension and previous CVD. Prehypertension was defined as systolic blood pressure (BP) 120–139 mm Hg or diastolic BP 80–89 mm Hg. Random blood glucose, glycated haemoglobin (HbA1c), body mass index (BMI), triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were examined as indicators of adverse cardiometabolic profile. The association between metabolic variables and prehypertension was examined using logistic regression models adjusting for potential confounders.
Results
The prevalence of prehypertension was 59.8% (Chinese), 68.9% (Malays) and 57.7% Indians. Higher levels of blood glucose, HbA1c and BMI were significantly associated with prehypertension in all three ethnic groups, odds ratio (95% confidence interval) of prehypertension in Chinese, Malays and Indians were: 1.42 (1.10, 1.83), 1.53 (1.05, 2.24), 1.49 (1.13, 1.98) for high-glucose; 3.50 (1.01, 12.18), 3.72 (1.29, 10.75), 2.79 (1.31, 5.94) for high-HbA1c; 1.86 (1.34, 2.56), 2.96 (2.10, 4.18), 1.68 (1.28, 2.20) for high-BMI. In addition, higher levels of LDL cholesterol in Chinese and higher levels of triglycerides were significantly associated with prehypertension. These associations persisted when metabolic variables were analysed as continuous variables.
Conclusions
Higher levels of blood glucose, HbA1c and BMI were associated with prehypertension in all three ethnic groups in Singapore. Screening for prehypertension and lifestyle modifications could potentially reduce the burden of CVD in otherwise healthy Asian adults living in Singapore.
doi:10.1186/1471-2458-13-730
PMCID: PMC3751051  PMID: 23919264
Prehypertension; Metabolic syndrome; Indian; Cardiometabolic
15.  Prevalence of prehypertension and its relationship to risk factors for cardiovascular disease in Jamaica: Analysis from a cross-sectional survey 
Background
Recent studies have documented an increased risk of cardiovascular disease (CVD) in persons with systolic blood pressures of 120–139 mmHg and/or diastolic blood pressures of 80–89 mmHg, classified as prehypertension in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. In this paper we estimate the prevalence of prehypertension in Jamaica and evaluate the relationship between prehypertension and other risk factors for CVD.
Methods
The study used data from participants in the Jamaica Lifestyle Survey conducted from 2000–2001. A sample of 2012 persons, 15–74 years old, completed an interviewer administered questionnaire and had anthropometric and blood pressure measurements performed by trained observers using standardized procedures. Fasting glucose and total cholesterol were measured using a capillary blood sample. Analysis yielded crude, and sex-specific prevalence estimates for prehypertension and other CVD risk factors. Odds ratios for associations of prehypertension with CVD risk factors were obtained using logistic regression.
Results
The prevalence of prehypertension among Jamaicans was 30% (95% confidence interval [CI] 27%–33%). Prehypertension was more common in males, 35% (CI 31%–39%), than females, 25% (CI 22%–28%). Almost 46% of participants were overweight; 19.7% were obese; 14.6% had hypercholesterolemia; 7.2% had diabetes mellitus and 17.8% smoked cigarettes. With the exception of cigarette smoking and low physical activity, all the CVD risk factors had significantly higher prevalence in the prehypertensive and hypertensive groups (p for trend < 0.001) compared to the normotensive group. Odds of obesity, overweight, high cholesterol and increased waist circumference were significantly higher among younger prehypertensive participants (15–44 years-old) when compared to normotensive young participants, but not among those 45–74 years-old. Among men, being prehypertensive increased the odds of having >/=3 CVD risk factors versus no risk factors almost three-fold (odds ratio [OR] 2.8 [CI 1.1–7.2]) while among women the odds of >/=3 CVD risk factors was increased two-fold (OR 2.0 [CI 1.3–3.8])
Conclusion
Prehypertension occurs in 30% of Jamaicans and is associated with increased prevalence of other CVD risk factors. Health-care providers should recognize the increased CVD risk of prehypertension and should seek to identify and treat modifiable risk factors in these persons.
doi:10.1186/1471-2261-8-20
PMCID: PMC2551581  PMID: 18752689
16.  Autonomic and hemodynamic origins of prehypertension: Central role of heredity 
Objective
To better understand the origins and progression of prehypertension.
Background
Prehypertension is a risk factor for progression to hypertension, cardiovascular disease and increased mortality. We used a cross-sectional twin study design to probe the role of heredity in likely pathophysiological events (autonomic or hemodynamic) in prehypertension.
Methods
812 individuals (337 normotensive, 340 prehypertensive, 135 hypertensive) were evaluated in a sample of twin pairs, their siblings and other family members. They underwent non-invasive hemodynamic, autonomic and biochemical testing, as well as estimates of trait heritability (h2: % of trait variance accounted for by heredity) and pleiotropy (rG: genetic covariance or shared genetic determination of traits) by variance components.
Results
In the hemodynamic realm, an elevation of cardiac contractility (LV dP/dT max) prompted increased stroke volume, in turn increasing CO, which elevated blood pressure into the prehypertension range. Autonomic monitoring detected an elevation of norepinephrine secretion plus a decline in cardiac parasympathetic tone. Twin pair variance components documented substantial heritability as well as joint genetic determination for blood pressure and the contributory autonomic and hemodynamic traits. Genetic variation at a pathway locus also indicated pleiotropic effects on contractility and blood pressure.
Conclusions
Elevated blood pressure in prehypertension results from increased CO, driven by contractility as well as heart rate, which may reflect both diminished parasympathetic and increased sympathetic tone. In the face of increased CO, SVR fails to decline homeostatically. Such traits display substantial heritability and shared genetic determination, though by loci not yet elucidated. These findings clarify the role of heredity in the origin of prehypertension and its autonomic and hemodynamic pathogenesis. The results also establish pathways that suggest new therapeutic targets for prehypertension, or approaches to its prevention.
doi:10.1016/j.jacc.2012.02.040
PMCID: PMC3374873  PMID: 22676942
Hypertension; genetics; nervous system; autonomic
17.  Prevalence of prehypertension in young military adults & its association with overweight & dyslipidaemia 
Background & objectives:
Estimation of prevalence of prehypertension in a population and its association with risk factors of cardiovascular disease is important to design preventive programmes. This cross-sectional study was carried out in a healthy military population to assess the prevalence of prehypertension and its association with risk factors such as overweight, abdominal adiposity and dyslipidaemia.
Methods:
The study included 767 participants (130 officers and 637 from other ranks). The blood pressure, serum triglycerides and serum cholesterol (total, HDL and LDL) were assessed along with anthropometric measurements such as height, weight, waist-hip ratio in apparently healthy military personnel. Information on smoking, alcohol intake, dietary habits and physical activity was collected using pretested questionnaire. Prehypertension was defined as systolic blood pressure (SBP) 120-139 mm Hg and diastolic blood pressure (DBP) 80-89 mm Hg.
Results:
The overall prevalence of prehypertension was high (about 80%). The prevalence of other risk factors such as overweight (BMI>23 kg/m2), serum total cholesterol > 200 mg/dl, serum LDL cholesterol > 130 mg/dl, serum HDL cholesterol <40 mg/dl, serum triglyceride > 150 mg/dl in the total group was 30, 22, 22, 67, and 14 per cent, respectively. Most of the personnel undertook moderate or heavy exercise. A significantly higher proportion of individuals with prehypertension had clinical and behavioural risk factors such as overweight, dyslipidaemia and adverse dietary practices like saturated fat and added salt intake. On multivariate logistic regression analysis, prehypertension had significant positive association with BMI>23 kg/m2 (OR 1.75), age (OR 1.89), serum triglyceride >150 mg/dl (OR 2.25)and serum HDL cholesterol <40 mg/dl (OR 1.51).
Interpretation & conclusions:
The high prevalence of prehypertension and its association with overweight and dyslipidaemia in this young, physically active military population indicates an urgent need for targeted interventions to reduce the cardiovascular risk.
PMCID: PMC3181015  PMID: 21911967
Cardiovascular risk; dyslipidaemia; overweight; prehypertension
18.  Association between obesity and high blood pressure among Lithuanian adolescents: a cross-sectional study 
Background
Most epidemiological studies have shown that the prevalence of high blood pressure (BP) has significantly increased among children and adolescents in various countries of the world.
The aim of this study was to examine the associations between overweight, obesity, abdominal obesity and prehypertension and hypertension among Lithuanian adolescents aged 12–15 years.
Methods
The subjects with increased BP (≥90th percentile) were screened on two separate occasions. Data on the body mass index (BMI), waist circumference (WC), and BP were analysed in 7,457 adolescents aged 12–15 years. Adjusted odds ratios (aORs) with 95% confidence intervals (CI) for the associations were estimated using multivariate logistic regression models.
Results
After two screenings, the study participants were categorised as prehypertensive (12.8%), hypertensive (22.2%), and normotensive (65%). The overall prevalence of overweight, obesity, and abdominal obesity (if WC was in the ≥75th percentile) were 12.1%, 2.4%, and 9%, respectively. After adjusting for age and sex, significant associations were found between overweight and obesity and high BP, namely, prehypertension (overweight: aOR = 2.62; 95% CI 2.13–3.23; obesity: aOR = 4.81; 95% CI 3.08–7.52) and hypertension (overweight: aOR = 3.56; 95% CI 3.02–4.19; obesity: aOR = 6.64; 95% CI 4.65–9.49). Prehypertension was found to be significantly associated with WC in the 75th– < 90th percentiles (aOR = 3.16; 95% CI 2.43–4.10) and WC in the ≥90th percentile (aOR = 4.08; 95% CI 2.35–7.10). For hypertension, significant associations were detected with WC in the 75th– < 90th percentiles (aOR = 3.92; 95% CI 3.18–4.82) and WC in the ≥90th percentile (aOR = 7.41; 95% CI 4.97–11.05).
Conclusions
Overweight, obesity, and abdominal obesity were associated with prehypertension and hypertension.
doi:10.1186/s13052-014-0102-6
PMCID: PMC4265335  PMID: 25492217
Blood pressure; Prehypertension; Hypertension; Overweight; Obesity; Abdominal obesity; Adolescents
19.  Prehypertension-Associated Elevation in Circulating Lysophosphatidlycholines, Lp-PLA2 Activity, and Oxidative Stress 
PLoS ONE  2014;9(5):e96735.
Prehypertension is a risk factor for atherosclerosis. We investigated alterations in plasma metabolites that are associated with prehypertension. A group of 53 individuals was identified who remained within the range of prehypertension during repeated measurements in a 3-year period. This group was compared with the control group of 53 normotensive subjects who were matched for age and gender. Metabolomic profiles were analyzed with UPLC-LTQ-Orbitrap mass spectrometry. The prehypertensive group showed higher levels of lysophosphatidylcholines (lysoPCs) containing C14:0, C16:1, C16:0, C18:2, C18:1, C18:0, C20:5, C20:4, C20:3, and C22:6, higher circulating Lp-PLA2 activity, oxidized LDL (ox-LDL), interleukin 6 (IL-6), urinary 8-epi-PGF2α, and higher brachial-ankle pulse wave velocity (ba-PWV), before and after adjusting for BMI, WHR, smoking, alcohol consumption, serum lipid profiles, glucose, and insulin. LysoPC (16:0) was the most important plasma metabolite for evaluating the difference between control and prehypertensive groups, with a variable important in the projection (VIP) value of 17.173, and it showed a positive and independent association with DBP and SBP. In the prehypertensive group, the levels of lysoPC (16:0) positively and significantly correlated with ox-LDL, Lp-PLA2 activity, 8-epi-PGF2α, ba-PWV, and IL-6 before and after adjusting for confounding variables. Prehypertension-associated elevations in lysoPCs, Lp-PLA2 activity, ox-LDL, urinary 8-epi-PGF2α, IL-6, and ba-PWV could indicate increased oxidative stress from Lp-PLA2-catalyzed PC hydrolysis during increased LDL oxidation, thereby enhancing proinflammation and arterial stiffness.
doi:10.1371/journal.pone.0096735
PMCID: PMC4011750  PMID: 24800806
20.  Hyperhomocysteinemia, Insulin Resistance and High HS- CRP Levels in Prehypertension 
Background: Pre-hypertension refers to blood pressure in the range of 120 to 139 mm of Hg / 80 to 89 mm of Hg and its prevalence is increasing in India. Previous studies have documented the increase in homocysteine, C-reactive protein and insulin resistance and their role in the development of hypertension. In recent years much attention has been focused on subjects with prehypertension, as the risk for development of cardiovascular disease is higher in these subjects compared to those with normal blood pressure.
Objectives: To evaluate the serum homocysteine, hs-CRP level and insulin resistance in subjects with prehypertension.
Materials and Methods: Sixty prehypertensives and 32 normotensives were recruited according to Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of blood pressure (JNC 7) guidelines. Serum homocysteine, vitamin B12, folate, insulin, hs-CRP and lipid profile were analysed. Independent t-test was carried out to compare two groups and pearson correlation analyses were carried out between various parameters with systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Results: Cardiovascular risk factors like serum homocysteine, insulin resistance and inflammatory marker hs-CRP were significantly increased in prehypertensives. Total cholesterol, TG, LDL-C and VLDL-C were significantly increased when compared to normotensives. Serum homocysteine correlated positively and vitamin B12 and folate negatively with Systolic Blood Pressure.
Conclusion: The present study concludes that the established cardiovascular risk factors, homocysteine, insulin resistance, and hs-CRP which have roles in the etiopathogenesis of hypertension, were elevated in subjects with prehypertension. Thus, early detection and life style modification may reduce the risk or delay the onset of hypertension and other cardiovascular complications.
doi:10.7860/JCDR/2014/8945.4669
PMCID: PMC4190710  PMID: 25302190
hs-CRP; Hyperhomocysteinemia; Insulin resistance; Prehypertension
21.  Auricular acupuncture for prehypertension and stage 1 hypertension: study protocol for a pilot multicentre randomised controlled trial 
Trials  2013;14:303.
Background
Hypertension, a worldwide public health problem, is a major risk factor for cardiovascular and kidney disease, and the medical and economic burden of hypertension is increasing. Auricular acupuncture has been used to treat various diseases, including hypertension. Several studies have shown that auricular acupuncture treatment decreases blood pressure in patients with hypertension; however, the scientific evidence is still insufficient. Therefore, we aimed to perform a randomised controlled clinical trial in patients with prehypertension and stage 1 hypertension to evaluate the effect and safety of auricular acupuncture.
Methods/designs
This on-going study is a two parallel arm, assessor-blinded, randomised controlled trial. Sixty participants with prehypertension and stage 1 hypertension will be recruited and randomly allocated into two groups in a 1:1 ratio. Participants in the auricular acupuncture group will receive auricular acupuncture treatment two times per week for 4 weeks. Participants in the usual care group will not receive any acupuncture treatment during the study period. All participants in both groups will be provided with verbal and written educational materials regarding the dietary and physical activity habits for controlling high blood pressure, and they will self-manage their lifestyle, including diet and exercise, during the study. The primary outcome is the 24-h average systolic and diastolic blood pressure, as measured with an ambulatory monitor. The secondary outcomes are the mean change in the average systolic and diastolic blood pressure during day- and night-time, the circadian rhythm of blood pressure, the mean arterial pressure, the change in blood pressure before and after auricular acupuncture treatment, the EuroQOL-5D (EQ-5D), heart rate variability (HRV), body mass index (BMI) and laboratory examination, including lipid profile and high sensitivity C-reactive protein (hs-CRP). Safety will be assessed at every visit.
Discussion
This pilot multicentre randomised controlled trial will explore the feasibility of further auricular acupuncture research and provide important clinical evidence for the effect and safety of auricular acupuncture on blood pressure in patients with prehypertension and stage 1 hypertension compared with usual care.
Trial registration
Clinical Research Information Service: KCT0000169
doi:10.1186/1745-6215-14-303
PMCID: PMC3848952  PMID: 24053577
Hypertension; Auricular acupuncture; Effect; Safety; Clinical research protocol
22.  Plasma lipid profile in Nigerians with high - normal blood pressure 
BMC Research Notes  2014;7(1):930.
Background
High blood pressure levels have been associated with elevated atherogenic blood lipid fraction, but epidemiological surveys often give inconsistent results across population sub-groups. To determine the extent to which there are differences in lipid profile based on blood pressure levels, we assessed lipid profile of subjects with high-normal blood pressure and compared with those of hypertensives and optimally normal blood pressure.
Methods
The study was a cross–sectional comparative study conducted at Aminu Kano Teaching Hospital, Kano, Nigeria. Fasting lipid levels were examined among randomly selected patients with optimally normal blood pressure (group 1), high – normal blood pressure (group 2) and those with hypertension (group 3). Optimal blood pressure was defined as systolic blood pressure (SBP) of < 120 mmHg/or diastolic blood pressure (DBP) of < 80 mmHg; and high- normal blood pressure as SBP of 130 – 139 mmHg and/or DBP of 85 – 89 mmHg.
Results
A total of 300 subjects were studied, 100 in each group. The mean age of subjects in group 1 was 27.32 ± 8.20 years and 60% were female, while that of group 2 was 34.04 ± 6.25 years, and 53% were female, and that for group 3 was 52.81 ± 13.3 years and 56% were female. The mean total cholesterol (TC) for subjects in group1 (3.96 ± 0.40 mmol/L) was significantly lower than levels in group2 (4.55 ± 1.01 mmol/L); P = <0.001. Subjects in group 3 (5.20 ± 1.88 mmol/L), however had statistically significant higher mean TC when compared with group 2; (P = 0.03). The difference between the groups for low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) followed the same pattern as that of TC, with statistically significant increasing trend across the blood pressure categories. Levels of high density lipoprotein cholesterol (HDL-C) were however similar across the three groups (group 2 versus group 1; P = 0.49, group 2 versus group 3; P = 0.9). Increased TC (>5.2 mmol/L) was absent in group1, but found among 11% of group2 subjects and 40% of those in group 3 (P-value for trend <0.001). Mean fasting plasma glucose (FPG) was 3.8 ± 0.4 mmol/L, 4.7 ± 1.1 mmol/L, 5.1 ± 1.9 mmol/L and for subjects in groups 1, 2 and 3 respectively (p > 0.05 for groups 2 Vs 1 and p <0.001 for groups 2 Vs 3). The differences in mean body mass index (BMI) between the groups followed a similar trend as that of FPG. Multivariate logistic regression analysis showed that FPG, TG and BMI were the strongest predictors of prehypertension [odds ratio (OR) 10.14, 95% CI (confidence interval) 3.63 – 28.33, P = 0.000; OR 5.75, 95% CI 2.20 – 15.05, P = 0.000; and OR 2.03, 95% CI 1.57 – 2.62, P = 0.000 respectively].
Conclusion
The study has shown a significant increase in plasma TC, LDL-C and TG values as blood pressure levels increased from optimally normal, across high-normal to hypertensive levels. There was a similar trend for FPG and BMI, demonstrating the central role that blood pressure plays in these metabolic disorders in Nigerians. These findings are relevant in terms of both prevention and treatment of cardiovascular morbidities and mortality.
doi:10.1186/1756-0500-7-930
PMCID: PMC4301796  PMID: 25522744
High-normal blood pressure; Plasma lipids; Nigerians
23.  Power spectral analysis of heart rate variability and autonomic nervous system activity measured directly in healthy dogs and dogs with tachycardia-induced heart failure 
BACKGROUND
Heart rate variability (HRV), calculated in the frequency or time domain, decreases in congestive heart failure (CHF). In HRV power spectral analysis, the low-frequency (LF) component diminishes in patients with CHF and the decrease is related to an increased risk of sudden death.
OBJECTIVE
Our aim was to clarify the nature of HRV power spectral analysis in normal and CHF dogs.
METHODS
Using an implanted radiotransmitter, we directly studied integrated left stellate ganglion nerve activity (iSGNA), integrated vagal nerve activity (iVNA), and electrocardiographic tracings before and after pacing-induced CHF in 6 ambulatory dogs. In a short-term power spectral analysis of HRV, we measured power spectral density during high, medium, and low sympathetic and vagal nerve activity. We analyzed 38 data segments characterized by the same autonomic nerve activity patterns at baseline and after pacing-induced CHF.
RESULTS
As compared with baseline, the spectral variables during CHF showed decreased total power (P = .002), LF power (P < .0001), and the LF/high frequency (HF) ratio (P = .005) and increased iVNA and iSGNA (P < .0001 for both). Only at baseline, iSGNA correlated positively with LF power (P < .05, r = 0.314). Under the same condition iVNA correlated positively with the HF component expressed as normalized units (P < .05, r = 0.394) and negatively with the LF component expressed both as absolute power (P < .05, r = −0.464) and normalized units (P < .05, r = −0.425).
CONCLUSION
The spectral variables (LF power and the LF/HF ratio) and direct variables measuring sympathetic nerve activity (iSGNA) correlate at baseline but not during CHF. At baseline, the vagal activity (iVNA) is associated with an increase in HFnu and a decrease in LFnu. These data indicate that the reduction in LF power and LF/HF ratio observed in heart failure dogs are likely to reflect a diminished sinus node responsiveness to autonomic modulation or an abnormal baroreflex function rather than an increased sympathetic activity.
doi:10.1016/j.hrthm.2009.01.006
PMCID: PMC2756782  PMID: 19324318
Autonomic nervous system; Power spectral analysis; Heart rate variability; Congestive heart failure; Vagal nerve activity; Sympathetic nerve activity; Sudden death
24.  Impact of prehypertension on left ventricular mass and QT dispersion in adult black Nigerians 
Summary
Background
Prehypertension has been associated with target-organ damage. This study sought to determine the impact of prehypertension (PHT) on QT dispersion and left ventricular hypertrophy (LVH) in adult black Nigerians.
Methods
One hundred and one subjects with office blood pressure (BP) < 140/90 mmHg were categorised according to their office BP into normotensive (BP < 120/80 mmHg, n = 57) and prehypertensive (BP 120–139/80–89 mmHg, n = 44) groups. Echocardiography and electrocardiography (ECG) were performed on the subjects.
Results
Thirty-four males aged 53.65 ± 16.33 years and 67 females aged 52.42 ± 12.00 years were studied. The mean QT interval dispersion (QTd) of the normotensive (38.96 ± 11.06 ms) and prehypertensive (38.41 ± 11.81 ms) groups were similar (p = 0.81). Prehypertensive subjects had higher left ventricular mass (LVM) (165.75 ± 33.21 vs 144.54 ± 35.55 g, p = 0.024), left ventricular mass index 1 (LVMI-1) (91.65 ± 16.84 vs 80.45 ± 18.65 g/m2, p = 0.021) and left ventricular mass index 2 (LVMI-2) (54.96 ± 10.84 vs 47.51 ± 12.00 g/m2.7, p = 0.017). QTd was independent of echocardiographic and electrocardiographic LVH (p > 0.05).
Conclusion
Compared with normotension, prehypertension is associated with higher LVM but similar QTd. This suggests that structural remodelling precedes electrical remodelling in prehypertension.
doi:10.5830/CVJA-2014-010
PMCID: PMC4026767  PMID: 24844553
prehypertension; left ventricular hypertrophy; left ventricular mass; QT dispersion; adult black Nigerian
25.  Body Mass Index Relates to Blood Pressure Among Adults 
Background:
The blood pressure and anthropometric measurements are important for evaluating the health of children, adolescents as well as adults.
Aim:
The aim is to study the blood pressure and body dimensions and to find out the prevalence of overweight/obesity and hypertension among adults.
Materials and Methods:
A cross-sectional study was conducted of all the people belonging to the Punjabi community, residing in Roshanara area and Jaina building in Delhi, for the past 20 years and aged 18-50 years. The men were engaged in transport business and women were mainly housewives.
Results:
Mean values of all the measurements, that is, height, weight, upper arm circumference, pulse rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were higher among males as compared with females, except skinfold thicknesses. Body mass index (BMI) and fat percentage was found to be higher among females as compared with males. There was a significant positive correlation between BMI, fat percentage, and blood pressure both SBP as well as DBP. Odds ratio showed that overweight/obese subjects were more likely to have hypertension than those with normal BMI.
Conclusion:
Prevalence of prehypertension among overweight/obese suggested an early clinical detection of prehypertension and intervention including life style modification, particularly weight management.
doi:10.4103/1947-2714.127751
PMCID: PMC3968571  PMID: 24696830
Body mass index; Blood pressure (SBP and DBP); India; Punjabi adults; Obesity; Prehypertension

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