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Objective: Lifestyle measures including dietary sodium restriction and increased potassium intake are recognized to lower blood pressure (BP). Potassium was found to be effective in reducing BP at higher levels of sodium intake, but to have little effect when sodium intake is restricted. The humoral mechanisms underlying these sodium intake dependent effects of potassium are unknown. We investigated the effects of potassium supplementation on top of a fully controlled sodium-restricted diet on markers of osmoregulation and volume regulation., Methods: In this post-hoc analysis, we included 35 (pre)hypertensive individuals participating in a randomized, double-blind, placebo-controlled crossover trial. Individuals received capsules containing sodium [3.0 g (130 mmol)/day], potassium [2.8 g (72  mmol)/day], or placebo for three four-week periods. Linear mixed-effect models were used to estimate the effects of potassium supplementation compared with placebo. Skewed data were ln-transformed before analysis., Results: Increased potassium intake was associated with a significant decrease in 24-h BP (-3.6/-1.6 mmHg). Furthermore, we found a significant decrease in ln MR-proANP [-0.08 (95% confidence interval -0.15, -0.01) pmol/l, P = 0.03] and significant increases in 24-h heart rate [2.5 (0.9, 4.0) bpm, P = 0.002], ln plasma copeptin [0.11 (0.01, 0.20) pmol/l, P = 0.02], ln renin [0.34 (0.08, 0.60) μIU/ml, P = 0.01], and ln aldosterone [0.14 (0.07, 0.22) nmol/l, P < 0.001] compared with placebo., Conclusions: We found that potassium has BP-lowering effects during sodium restriction. These BP-lowering effects, however, seem mitigated by several counter regulatory mechanisms (i.e. increased secretion of vasopressin, stimulation of RAAS, and increased heart rate) that were activated to maintain volume homeostasis and counterbalance the decrease in BP.

Background: The DASH (Dietary Approaches to Stop Hypertension) dietary pattern, which is high in fruit, vegetables, and low-fat dairy foods, significantly lowers blood pressure as well as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol., Objective: The study was designed to test the effects of substituting full-fat for low-fat dairy foods in the DASH diet, with a corresponding increase in fat and a reduction in sugar intake, on blood pressure and plasma lipids and lipoproteins., Design: This was a 3-period randomized crossover trial in free-living healthy individuals who consumed in random order a control diet, a standard DASH diet, and a higher-fat, lower-carbohydrate modification of the DASH diet (HF-DASH diet) for 3 wk each, separated by 2-wk washout periods. Laboratory measurements, which included lipoprotein particle concentrations determined by ion mobility, were made at the end of each experimental diet., Results: Thirty-six participants completed all 3 dietary periods. Blood pressure was reduced similarly with the DASH and HF-DASH diets compared with the control diet. The HF-DASH diet significantly reduced triglycerides and large and medium very-low-density lipoprotein (VLDL) particle concentrations and increased LDL peak particle diameter compared with the DASH diet. The DASH diet, but not the HF-DASH diet, significantly reduced LDL cholesterol, HDL cholesterol, apolipoprotein A-I, intermediate-density lipoprotein and large LDL particles, and LDL peak diameter compared with the control diet., Conclusions: The HF-DASH diet lowered blood pressure to the same extent as the DASH diet but also reduced plasma triglyceride and VLDL concentrations without significantly increasing LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01404897., (© 2016 American Society for Nutrition.)

Objective: Serum bilirubin level has shown to be inversely associated with coronary atherosclerosis, and may serve as a protective biomarker of coronary artery disease. Serum bilirubin has also been shown to be negatively associated with brachial-ankle pulse wave velocity (baPWV) in men without a history of hypertension, and in men with hypertension. It is unknown whether such associations can be observed in the pre-hypertensive or normotensive population. This study thus aimed to investigate the relationship between serum bilirubin level and increased arterial stiffness in subjects with pre-hypertension and normotension for both genders., Methods: A cross-sectional sample of 3,399 apparently healthy subjects undergoing a medical check-up at National Cheng Kung University Hospital was enrolled between October 2006 and August 2009, after excluding subjects with serum total bilirubin level greater than 20.52 μmol/L. Increased arterial stiffness was defined as baPWV of 1,400 cm/s or higher as the dichotomous variable and bilirubin as the continuous variable., Results: Based on multiple linear regression analysis, serum bilirubin level was inversely associated with baPWV in non-hypertensive men (β = -0.066, p < 0.001) but not in non-hypertensive women. In addition, the inverse relationship between bilirubin level and baPWV was found statistically significant only in pre-hypertensive men (β = -0.110, p < 0.001). Multiple logistic regression analysis showed that serum bilirubin was inversely associated with increased arterial stiffness in men with pre-hypertension (odds ratio = 0.955, 95% confidence interval = 0.916-0.996, p < 0.05) but not normotension after adjustment for other confounding factors. However, the relationship between total bilirubin level and increased arterial stiffness did not reach statistical significance for female subjects with pre-hypertension and normotension., Conclusion: Serum bilirubin is inversely associated with increased arterial stiffness in men with pre-hypertension but not normotension. The association between bilirubin level and arterial stiffness was not found significant in women.

Objective: To evaluate the association of hypomagnesemia with prehypertension (preHTN) and hypertension in children., Study Design: A total of 3954 apparently healthy Mexican children were enrolled in a cross-sectional study. Exclusion criteria were type 2 diabetes; hepatic, renal, or endocrine disease; impaired fasting glucose; chronic diarrhea; and intake of vitamins or magnesium supplements in the previous 6 months. preHTN was defined by systolic and/or diastolic blood pressure ≥90th to <95th percentile and hypertension by systolic and/or diastolic blood pressure ≥95th percentile, according to age, sex, and height percentile. Hypomagnesemia was defined by serum magnesium concentration <1.8 mg/dL (<0.74 mmol/L). To control for potential sources of bias related to age, participants were allocated into 2 groups, aged 6-10 years and 11-15 years., Results: The prevalence of preHTN and hypertension was 12.2% and 6.4%, respectively, in children aged 6-10 years and 13.9% and 10.6% in those aged 11-15 years. Hypomagnesemia was identified in 59 children with preHTN (27.3%) and 52 (45.6%) with hypertension in the 6-10 year age group, and in 115 children with preHTN (36.0%) and 109 (49.6%) with hypertension in the 11-15 year age group. Adjusted multiple logistic regression analysis showed that in children in both age groups, hypomagnesemia was associated with both preHTN (6-10 years: OR, 2.18, P < .0005; 11-15 years: OR, 1.38, P = .018) and hypertension (6-10 years: OR, 4.87, P < .0005; 11-15 years: OR, 1.83, P = .0002)., Conclusion: Our results indicate that serum magnesium level <1.8 mg/dL is significantly associated with preHTN and hypertension in apparently healthy children., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cytokines play an important role in the pathogenesis of hypertension. The authors hypothesized that interleukin 17 (IL-17) might contribute to the prehypertensive state. This study evaluated the relationship between serum levels of IL-17 and prehypertension. A total of 394 participants were enrolled, after excluding for hypertension or treated hypertension, and divided into two groups (optimal blood pressure [BP] and prehypertension) based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification of BP. Optimal BP was defined as systolic BP <120 mm Hg and diastolic BP <80 mm Hg. Prehypertension was defined as systolic BP of 120 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg. IL-17A levels were determined by enzyme-linked immunosorbent assay. The mean serum IL-17 concentration in the prehypertension group was significantly higher than in the optimal BP group. The cohort was divided into quartiles Q1 (≤3.5 ng/L), Q2 (3.60 to 6.10 ng/L), Q3 (6.20 to 10.00 ng/L), and Q4 (≥10.10 ng/L) based on IL-17 levels. The Q2 to Q4 groups had increasing odds ratios for having prehypertension compared with the Q1 group. Elevated serum IL-17 was accompanied by a rise in systolic BP. Thus, increased serum IL-17 levels are associated with prehypertension., (© 2015 Wiley Periodicals, Inc.)

The concept of enhancing structural integrity of mitochondria has emerged as a novel therapeutic option for cardiovascular disease. Flow-induced increase in laminar shear stress is a potent physiological stimulant associated with exercise, which exerts atheroprotective effects in the vasculature. However, the effect of laminar shear stress on mitochondrial remodeling within the vascular endothelium and its related functional consequences remain largely unknown. Using in vitro and in vivo complementary studies, here, we report that aerobic exercise alleviates the release of endothelial microparticles in prehypertensive individuals and that these salutary effects are, in part, mediated by shear stress-induced mitochondrial biogenesis. Circulating levels of total (CD31(+)/CD42a(-)) and activated (CD62E(+)) microparticles released by endothelial cells were significantly decreased (∼40% for both) after a 6-mo supervised aerobic exercise training program in individuals with prehypertension. In cultured human endothelial cells, laminar shear stress reduced the release of endothelial microparticles, which was accompanied by an increase in mitochondrial biogenesis through a sirtuin 1 (SIRT1)-dependent mechanism. Resveratrol, a SIRT1 activator, treatment showed similar effects. SIRT1 knockdown using small-interfering RNA completely abolished the protective effect of shear stress. Disruption of mitochondrial integrity by either antimycin A or peroxisome proliferator-activated receptor-γ coactivator-1α small-interfering RNA significantly increased the number of total, and activated, released endothelial microparticles, and shear stress restored these back to basal levels. Collectively, these data demonstrate a critical role of endothelial mitochondrial integrity in preserving endothelial homeostasis. Moreover, prolonged laminar shear stress, which is systemically elevated during aerobic exercise in the vessel wall, mitigates endothelial dysfunction by promoting mitochondrial biogenesis., (Copyright © 2015 the American Physiological Society.)

Background: Prehypertension (preHTN) increases the risk of developing hypertension. The objectives of this study were to estimate the prevalence of preHTN in the Mexican adult population and evaluate the association between hypomagnesemia and preHTN., Methods: This study was a 2-phase, population-based study. In the first phase, 4,272 Mexican adults (aged 20-65 years) were enrolled to determine the prevalence of preHTN. In the second phase, a cross-sectional analysis was performed to evaluate the association between hypomagnesemia and preHTN. The exclusion criteria were chronic diarrhea, malignancy, hepatic and renal diseases, chronic inflammatory disease, and the intake of magnesium supplements. PreHTN was defined as a systolic blood pressure (BP) of 120-139 mm Hg and/or diastolic BP of 80-89 mm Hg, and hypomagnesemia was defined as a serum magnesium concentration <1.8 mg/dl., Results: The prevalence of preHTN was 37.5% (95% confidence interval (CI): 36.0-39.0): 46.7% were men (95% CI: 44.1-49.4) and 33.2% (95% CI: 31.5-5.0) were women. The serum magnesium data were available for 921 participants. Hypomagnesemia was identified in 276 (30.0%; 95% CI: 27.1-33.0) subjects; of them, 176 (63.8%; 95% CI: 58.3-69.6) had preHTN. Individuals with preHTN exhibited lower magnesium levels than individuals without preHTN (1.78±0.36 vs. 1.95±0.37, P < 0.0005). A multiple logistic regression analysis (adjusted for age, sex, smoking, body mass index, waist circumference, fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and triglycerides levels) indicated a significant association between hypomagnesemia and preHTN (odds ratio = 1.78; 95% CI: 1.5-4.0, P < 0.0005)., Conclusions: The prevalence of preHTN in the Mexican population is 37.5%, and hypomagnesemia is strongly associated with preHTN., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: overweight and obesity in adolescents are major public health problems with particular interest, because of their potential association with risk factors for development of diseases. The study aimed to determine the prevalence of overweight and obesity in adolescents in southern Portugal and investigate the association with risk factors for development of cardiovascular, respiratory and musculoskeletal diseases., Methods: the sample consisted of 966 adolescents aged 10 to 16 years. The calculation of body mass index (BMI), evaluation of blood glucose, total cholesterol and triglycerides, blood pressure, spirometry and application of low back pain (LBP) questionnaire were performed., Results: 178 (18.4%) adolescents were overweight and 52 (5.4%) obese. None of the variables revealed a statistically significant association with overweight and obesity. The presence of high blood pressure was observed in 200 (20.7%) individuals and hypertension in 158 (16.4%) adolescents. Overweight and obese adolescents are 2.3 times more likely to develop signs of pre-hypertension and hypertension. 559 (57.9%) students had restrictive respiratory disorders and 23 (2.4%) had obstructive disorders. Those who were overweight and obese had 0.64 probability of having restrictive respiratory disorders., Conclusion: there was a high prevalence of overweight and obesity in Portuguese adolescents and these showed a statistically significant relationship with the development of pre-hypertension and hypertension, and restrictive respiratory disorders.

Background: Consumption of flavonoid-rich foods such as cocoa and tea may reduce cardiovascular disease risk. The flavonoids epicatechin (in cocoa and tea) and quercetin (in tea) probably play a role by reducing endothelial dysfunction and inflammation, 2 main determinants of atherosclerosis., Objective: We studied the effects of supplementation of pure epicatechin and quercetin on biomarkers of endothelial dysfunction and inflammation., Methods: Thirty-seven apparently healthy (pre)hypertensive men and women (40-80 y) participated in a randomized, double-blind, placebo-controlled crossover trial. Participants ingested (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for a period of 4 wk, in random order. Plasma biomarkers of endothelial dysfunction and inflammation were measured at the start and end of each 4-wk intervention period. The differences in changes over time between the intervention and placebo periods (Δintervention - Δplacebo) were calculated and tested with a linear mixed model for repeated measures., Results: Epicatechin changed Δepicatechin - Δplacebo for soluble endothelial selectin (sE-selectin) by -7.7 ng/mL (95% CI: -14.5, -0.83; P = 0.03) but did not significantly change this difference (-0.30; 95% CI: -0.61, 0.01; P = 0.06) for the z score for endothelial dysfunction. Quercetin changed Δquercetin - Δplacebo for sE-selectin by -7.4 ng/mL (95% CI: -14.3, -0.56; P = 0.03), that for IL-1β by -0.23 pg/mL (95% CI: -0.40, -0.06; P = 0.009), and that for the z score for inflammation by -0.33 (95% CI: -0.60, -0.05; P = 0.02)., Conclusions: In (pre)hypertensive men and women, epicatechin may contribute to the cardioprotective effects of cocoa and tea through improvements in endothelial function. Quercetin may contribute to the cardioprotective effects of tea possibly by improving endothelial function and reducing inflammation. This trial was registered at clinicaltrials.gov as NCT01691404., (© 2015 American Society for Nutrition.)

Background: There are few data available on the association between serum uric acid (UA) and prehypertension when hypertension prevention efforts may be applicable., Methods: We performed a cross-sectional study to evaluate risk of prehypertension and its association with serum UA and other confounding factors. Levels of serum UA, blood pressure, body mass index (BMI) and some related factors were detected., Results: Participants with prehypertension had higher levels of serum UA and BMI. Compared to those with normotension, the multivariate-adjusted odds ratios [ORs, 95% confidence interval (CI)] for men with prehypertension were 1.33 (95% CI, 1.08-3.91) of serum UA and 1.21 (95% CI, 1.17-1.29) of BMI. In women, the ORs were 1.96 (95% CI, 1.21-3.46) and 1.28 (95% CI, 1.14-2.46), respectively. Increasing serum UA and BMI were associated with increased risk of prehypertension. Compared with the lowest quartiles, the highest serum UA and BMI quartiles entailed >4.4 times greater risk of prehypertension. In sex-specific analysis, OR was 2.41 (95% CI, 1.55-3.75) for men and 7.37 (95% CI, 4.16-13.0) for women., Conclusions: Both high serum UA and high BMI are associated with risk of prehypertension. Individuals with higher serum UA and BMI simultaneously have a higher risk for prehypertension, especially for women., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We studied concentrations of angiotensin II, HLDF24 peptide, endothelin proteins, S100B, and autoantibodies to them and serum levels of blood natriuretic peptide in patients with different categories of "normal" arterial BP and hypertension. The relationship between blood levels of the above factors and normotony, pre-hypertension, and hypertension in the examined groups was analyzed. The results suggest that the studied molecular factors can serve as potential predictors of arterial hypertension and used for personalized hypertension risk assessment.

Elevated blood pressure is regarded as an independent risk factor for cardiovascular diseases and diabetes. We examined the relation between hematocrit and pre-hypertension as well as the effect of sex, obesity, fasting glucose, and lipids in Chinese adults. The study samples were from a community-based health examination survey in China and included a total of 2,3691 patients with blood pressure in normal range. The odds ratios [ORs, 95 % confidence interval (CI)] of pre-hypertension across increasing quartiles of hematocrit were 1.000, 1.176 (1.050-1.318), 1.213 (1.081-1.363), and 1.364 (1.209-1.540) (P for trend < 0.001), when adjusted for age, sex, body mass index, glutamic-pyruvic transaminase, glutamic-oxalocetie transaminase, serum uric acid, glucose, and lipids. Associations were significant in both men and women, but not in individuals older than 60 years. In addition, low-density lipoprotein cholesterol significantly interacted with hematocrit (P for interaction <0.024). The associations were more evident in patients with low (P < 0.001) and median LDL-C levels (P < 0.013) than those with high glucose levels. Hematocrit was associated with pre-hypertension, and was independent of metabolic risk factors. These associations were not significant in older individuals and low-density lipoprotein cholesterol may modify these associations.

Background: A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension. This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited., Methods and Results: A double-blind, randomized, controlled trial was conducted at 4 sites in the United States. We enrolled 534 individuals 18 to 50 years of age with low vitamin D status (25-hydroxyvitamin D levels ≤25 ng/mL) and systolic blood pressure of 120 to 159 mm Hg. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. The primary end point was change in mean 24-hour systolic blood pressure. Secondary end points included change in ambulatory diastolic blood pressure and clinic systolic and diastolic blood pressures. The median age was 38 years, and 62% of participants were men. Forty-six percent of participants were white, and 48% were black. The median 25-hydroxyvitamin D level at baseline was 15.3 ng/mL. Four-hundred fifty-five participants (85%) had at least 1 follow-up blood pressure measurement; 383 participants (72%) completed the full 6-month study. At the end of the study, there was no significant difference in the primary end point (change in mean 24-hour systolic blood pressure, -0.8 versus -1.6 mm Hg in the high-dose and low-dose arms; P=0.71) or in any of the secondary end points. Furthermore, there was no evidence of association between change in 25-hydroxyvitamin D and change in 24-hour systolic blood pressure at 6 months (Spearman correlation coefficient, -0.05, P=0.34). Results were consistent across prespecified subgroups., Conclusions: Vitamin D supplementation did not reduce blood pressure in individuals with prehypertension or stage I hypertension and vitamin D deficiency. Our findings suggest that the association between vitamin D status and elevated blood pressure noted in observational studies is not causal., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01240512., (© 2014 American Heart Association, Inc.)

Salt preference has been reported to cause sympathovagal imbalance (SVI) and prehypertension. We investigated the role of inflammation, insulin resistance (IR), hyperlipidemia, and oxidative stress (OS) in genesis of SVI and cardiovascular (CV) risks in salt-preferring prehypertensives. The subjects were divided into no-salt-preferring (NSP, n = 87) and salt-preferring (SP, n = 89) group based on their preference for salted food. Body mass index (BMI), blood pressure (BP) variability parameters including baroreflex sensitivity (BRS), heart rate variability (HRV) indices, autonomic function tests, IR, lipid risk factors, inflammatory and OS markers, and renin were measured in both the groups. Based on the contribution of various cardiometabolic risks to low-frequency-high-frequency (LF-HF) ratio of HRV, the marker of SVI was assessed by multiple-regression analysis. Prediction of prehypertension status by the LF-HF ratio was assessed by bivariate logistic regression. BMI, heart rate, BP parameters, cardiac output, total peripheral resistance, LF-HF ratio, IR, atherogenic index, inflammatory, and OS markers were significantly increased, and BRS was significantly decreased in the SP group compared with the NSP group. There was an independent association of IR, atherogenic index, markers of inflammation and OS, and BRS with the LF-HF ratio in SP subjects, and the LF-HF ratio had significant prediction of prehypertension status in these subjects. It was concluded that IR, low-grade inflammation, atherogenic lipid profile, and OS contribute to SVI in SP subjects. Decreased BRS (the marker of CV risk) is linked to SVI, and SVI predicts prehypertension status in SP subjects.

Obesity-related hypertension is associated with increased activity of the renin-angiotensin-aldosterone system (RAAS), increasing arterial stiffness. Aerobic exercise decreases pulse wave velocity (PWV), therefore a treatment option for hypertension and obesity. Assess RAAS activity and PWV before and after 4 weeks of aerobic training in unmedicated, pre-to-stage-1 hypertensives. Ten obese subjects (52±3.2 years, body mass index=33.5±1.4) performed 30 min of aerobic exercise on a treadmill 3 days per week at 65% of peak oxygen consumption (VO2peak). Descriptive characteristics, systolic and diastolic blood pressure (SBP and DBP), PWV, and a blood draw was performed at baseline, following the 4-week control and training interventions. No differences in descriptive characteristics during the control period were observed, however, a significant decrease in plasma aldosterone (ALDO) (255.4±75 to 215.8±66 pg ml(-1), P=0.001), SBP (140±12 to 136±10.4 mm Hg; P=0.02), DBP (89±4.2 to 85±6.3 mm Hg; P=0.03) and central PWV (11.2±0.6 to 9.8±0.8 m s(-1); P=0.04) was shown pre-to-post exercise training. Four weeks of moderate-intensity aerobic training in obese, hypertensives decreases plasma ALDO independently of body weight and is significantly correlated to decreases in PWV reductions.

Objectives: To explore the neutrophil-lymphocyte ratio (NLR) in patients with prehypertension (PHT)., Background: Inflammation plays an important role in the development of cardiovascular diseases. A pathophysiological link also exists between inflammation and PHT. NLR is a simple marker for the assessment of inflammatory status. There is a lack of data regarding the association between NLR and pre-hypertensive state., Methods: The present cross-sectional study included 33 newly diagnosed PHT patients and 35 normotensive control subjects. Prehypertension was defined as a systolic blood pressure (BP) of 120-139 mm Hg and/or a diastolic BP of 80-89 mm Hg., Results: Patients were divided into tertiles based on NLR values: 1.17 (0.9-1.42) in tertile 1; 1.57 (1.43-1.78) in tertile 2; and 2.40 (1.82-4.5) in tertile 3. The frequency of PHT was significantly higher for patients in the upper NLR tertile compared to the middle and lower NLR tertiles (21 (91.3%), 7 (30.4%), and 5 (22.7%), respectively; p<0.001). Systolic BP and diastolic BP were significantly higher among patients in the upper NLR tertile than among those in the other NLR tertiles., Conclusion: An association exists between PHT and NLR. NLR measurement, as well as monocyte count, may be used to indicate increased risk of prehypertension (Tab. 2, Ref. 48).

The authors aimed to investigate the relationship between serum gamma-glutamyltransferase (GGT) and prehypertension, as well as the modification of other metabolic risk factors in a large cohort of Chinese individuals. The data were collected via a community-based health examination survey in central China. Blood pressure, body mass index (BMI), and levels of GGT, fasting blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid indicators were measured. In total, data from 18,302 patients with available biomarkers were included in the present study. Elevated blood pressure was associated with increased GGT concentration (P<.001). After adjusting for age, sex, BMI, fasting blood glucose, lipid indicators, AST, and family history of hypertension, the association between GGT levels and prehypertension remained significant (P=.021). The adjusted odds ratios (95% confidence interval) for prehypertension across quintiles of GGT level were 1.00, 1.057 (1.012-1.334), 1.068 (0.916-1.254), 1.024 (0.851-1.368), and 1.272 (1.027-1.593), respectively. In stratified analyses, the association between GGT levels and prehypertension was significant in women but was not significant in men. Moreover, additive effect of BMI and age on the effect of GGT levels on prehypertension (both P for interaction <.001) was observed. In summary, GGT levels were positively associated with prehypertension in women, independent of other metabolic factors. Furthermore, BMI and age may amplify the effects of GGT levels on prehypertension. These findings suggest that monitoring the levels of GGT could help in the diagnosis and monitoring of prehypertension., (©2014 Wiley Periodicals, Inc.)

We evaluated the association between serum uric acid (SUA) levels and prehypertension in a Chinese population. A cross-sectional study was performed during 2008 to 2010, and a total of 11199 participants without hypertension or other cardiovascular diseases (CADs), aged ≥35 years, were available for analysis. After adjusting for age, alcohol consumption, smoking status, body mass index, diabetes, total cholesterol, triglycerides, serum creatinine, the odds ratios (ORs) and 95% confidence intervals (CIs) of the prehypertension from the lowest (referent) to the highest levels of SUA were 1.00 (95% CI, 0.91-1.10), 1.12 (95% CI, 1.03-1.21), 1.17 (95% CI, 1.09-1.27), and 1.25 (95% CI, 1.13-1.39; linear trend P = .002). This association persisted in subgroup analysis by gender and was also consistent with separate analysis by classification of age, smoking status, alcohol usage, overweight, and diabetes mellitus. Independent of other cardiovascular risk factors, higher SUA levels are positively associated with prehypertension in a Chinese population without hypertension and CADs. Prospective trials should evaluate interventions that lower the SUA levels., (© The Author(s) 2013.)

Aims: To investigate the prevalence and risk factors of diabetes and impaired fasting glucose among urban university applicants in Eastern China., Method: The study uses data from the annual health examination among all students finishing high school who applied for university entrance in Changzhou City in 2012. In total, 6716 students aged 17-19 years had fasting blood glucose, alanine transaminase, height, weight and blood pressure measured. Impaired fasting glucose and diabetes were defined as fasting blood glucose ≥ 5.6 mmol/l (but < 7 mmol/l) and ≥ 7 mmol/l, respectively., Results: The overall prevalence of impaired fasting glucose and diabetes was 2.40% and 0.13%, respectively (3.67% and 0.09% in boys; 1.09% and 0.18% in girls). In total, 20.9% of boys and 10.6% of girls were overweight/obese. High socio-economic status was associated with an increased risk of diabetes/impaired fasting glucose, but the association was significant only among boys (adjusted odds ratio 1.94, 95% CI 1.26-2.98). Alanine transaminase levels were significantly and positively related to diabetes/impaired fasting glucose risk. Overweight/obesity was significantly associated with increased risk of impaired fasting glucose/diabetes in girls, but not in boys. Moreover, the number of the above-mentioned risk factors (i.e. overweight/obesity, elevated alanine transaminase, pre-hypertension) was significantly and positively related to diabetes/impaired fasting glucose among both boys and girls., Conclusions: Impaired fasting glucose was prevalent among urban university applicants, in particular boys and those of high socio-economic status in eastern China. Elevated levels of liver function enzyme appear to be the strongest risk factor for diabetes/impaired fasting glucose., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Blood pressure levels were evaluated among prehypertension patients with associated cardiovascular risk factors to determine the effect of different interventions with respect to new endpoint events. A total of 1112 patients were equally and randomly divided into control, lifestyle, drug, and lifestyle + drug groups, and were followed-up for 12 months. We collected the age, height, weight, blood pressure, heart rate, blood lipid levels, blood glucose levels, and other clinical data from all subjects at the baseline and at the end of the follow-up period. The average systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the intervention groups were significantly reduced after the intervention (lifestyle + drug > drug > lifestyle). SBP and DBP were higher in the control group than before intervention (P < 0.05). Age, gender, heart rate, triglyceride (TG) levels, body mass index (BMI), alcohol consumption, and family history were the major factors affecting blood pressure. Increased BMI, TG, high-sensitivity C-reactive protein, alcohol consumption, family history, SBP, and DBP were major risk factors of hypertension. At the end of the follow-up period, there were 67 cases of hypertension, 32 cases of diabetes, and 12 cases of the endpoint events. Hypertension and diabetes events were reduced in the intervention groups relative to the control group (P < 0.05). The number of cases with incident cardiovascular endpoints did not differ among the three intervention groups (P > 0.05). Therefore, hypertension and related cardiovascular events can be controlled with different interventions.

Context: Hypertension treatments include sodium restriction, pharmacological management, and lifestyle modifications. Although many cases of hypertension can be controlled by medication, individuals may experience side effects or incur out-of-pocket expenses, and some may not comply with the treatment regimen. Although some previous studies have shown a favorable effect for qigong on hypertension, well-designed, rigorous trials evaluating the effect of qigong on hypertension are scarce., Objective: This study aimed to evaluate the effect of qigong on prehypertension and mild hypertension and to calculate a sample size for a subsequent randomized, clinical trial (RCT)., Design: Participants were randomized to a qigong group or an untreated control group., Setting: This study was conducted at the Oriental Medical Center of Dongeui University, in the Republic of Korea., Participants: Participants were individuals between the ages of 19 and 65 y with systolic blood pressure (SBP) between 120 and 159 mm Hg and/or diastolic blood pressure (DBP) between 80 and 99 mm Hg., Intervention: The qigong group attended qigong classes 3 ×/wk and performed qigong at home at least 2 ×/wk. Participants in the control group did not receive any intervention for hypertension., Outcome Measures: Outcome measures for this study were (1) changes in blood pressure (BP); (2) quality of life (QOL) using 2 surveys: the Medical Outcomes Study (MOS) 36-item short form (SF-36) (Korean version) and the Measure Yourself Medical Outcome Profile 2 (MYMOP2); and (3) hormone levels., Results: Of 40 participants, 19 were randomly assigned to the qigong group, and 21 were assigned to the control group. After 8 wk, significant differences were observed between the qigong and the control groups regarding changes in SBP (P = .0064) and DBP (P = .0003). Among the categories of the MYMOP2 questionnaire, only wellbeing was significantly different between the 2 groups (P = .0322). The qigong group showed a significantly greater improvement in the physical component score of the SF-36 compared with the control group (P = .0373). Regarding changes in hormone levels, there was no significant difference between the qigong and the control groups. This pilot study demonstrates that regarding sample size, a RCT evaluating the effect of qigong on hypertension should include 22 participants based on DBP and 285 participants based on SBP in each group, thus allowing for a loss to follow-up rate of 20%., Conclusion: The results indicate that qigong may be an effective intervention in reducing BP in prehypertension and mild hypertension. Further studies should include an appropriate sample size and methodology to determine the mechanism of qigong on BP.

Several epidemiological studies in adults have suggested a favourable effect of frequent eating on blood lipid profiles, but evidence in younger populations is lacking. In the present cross-sectional study, we examined the associations of eating frequency (EF) with metabolic risk factors in British children aged 4-10 years (n 818) and adolescents aged 11-18 years (n 818). Dietary intake was assessed using a 7 d weighed dietary record. EF was calculated based on all eating occasions, except for those providing < 210 kJ of energy. Metabolic risk factors examined were total, HDL-cholesterol and LDL-cholesterol concentrations, TAG concentration, BMI z-score, waist:height ratio (WHtR; only adolescents), and systolic and diastolic blood pressures. Adjustment was made for age, sex, social class, physical activity levels, intakes of protein, fat, total sugar and dietary fibre, ratio of reported energy intake to estimated energy requirement (EI:EER) and BMI z-score (except for BMI z-score and WHtR). In children, EF was inversely associated with total cholesterol and LDL-cholesterol concentrations (n 324, P= 0·01 and 0·04, respectively). Conversely, EF was positively associated with BMI z-score in adolescents (P= 0·004). There were no associations between EF and other metabolic risk factors. In analyses in which only plausible energy reporters (EI:EER: 0·72-1·28) were included, similar results were obtained, except for an inverse association between EF and diastolic blood pressure in children. In conclusion, a higher EF is associated with lower total cholesterol and LDL-cholesterol concentrations in children but with a higher BMI z-score in adolescents.

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.

Background: The aim of our study was to evaluate the serum concentration of sialic acid (SA) and high-sensitivity C-reactive protein (hs-CRP) in prehypertensive patients and the possible correlations between these 2 factors with blood pressure in such patients., Material and Methods: We studied 61 prehypertensive patients, 70 hypertensive patients, and 50 controls with normal blood pressure. Lipid profile, hs-CRP, SA, and body mass index (BMI) were estimated in all groups. Associations between SA and hs-CRP and blood pressure were analyzed using multiple linear regressions., Results: SA and hs-CRP levels were higher in the prehypertension group than that in the control group and were lower than that in the hypertension group. Multiple linear regression demonstrated that fasting glucose, BMI, SA, and hs-CRP correlated with systolic blood pressure and that low-density lipoprotein, BMI, SA, and hs-CRP correlated independently with diastolic pressure (P<0.05)., Conclusions: Our findings suggest that in prehypertension, there is an association between serum SA and hs-CRP levels and blood pressure.

Objective: Evidence is accumulating, predominantly among clinical trials in adults, that yoga improves blood pressure (BP) control, with downregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) projected as underlying mechanisms. This pilot study assessed whether Hatha yoga has the potential to reduce BP among youth and whether dampening of the SNS and/or HPA activity is a likely pathway of change., Design: Thirty-one seventh graders were randomly assigned to a Hatha yoga program (HYP) or attention control (AC) music or art class. Baseline and 3-month evaluations included resting BP; overnight urine samples; and saliva collected at bedtime, upon awakening, and at 30 and 60 minutes after awakening for α-amylase and cortisol assays., Results: Twenty-eight (14 in the HYP group and 14 in the AC group) students were assessed both before and after the intervention. BP changes from pre- to post-intervention were -3.0/-2.0 mmHg for the HYP group and -0.07/-0.79 mmHg for the AC group (p=0.30 and 0.57, respectively). Changes in systolic BP (SBP)/diastolic BP (DBP) for the prehypertensive (75th-94th percentiles for SBP) subgroup analyses were -10.75/-8.25 mmHg for the HYP group (n=4) versus 1.8/1.0 mmHg for the AC group (n=5) (p for SBP=0.02; p for DBP=0.09). Although no statistically significant group differences were observed with changes in SNS or HPA awakening curves (area under curve for α-amylase and cortisol, respectively), a small to moderate effect size was seen favoring a reduction of α-amylase activation for the HYP group (Cohen d=0.34; prehypertensive d=0.20)., Conclusions: A school-based Hatha yoga program demonstrated potential to decrease resting BP, particularly among prehypertensive youth. Reduced SNS drive may be an underlying neurohormonal pathway beneficially affected by the program. A large-scale efficacy/effectiveness randomized clinical trial is warranted.

Background: Although cardiovascular (CV) risks are reported in first-degree relatives (FDRs) of type 2 diabetics, effects of gender on sympathovagal imbalance (SVI) and CV risks in these subjects have not been investigated., Methods: Body mass index (BMI), blood pressure variability parameters including baroreflex sensitivity (BRS), spectral indices of heart rate variability, autonomic function tests, insulin resistance, lipid profile, inflammatory markers (interleukin 6, high-sensitivity C-reactive protein, tumor necrosis factor α) and oxidative stress (OS) marker were measured and analyzed in control group (without family history of diabetes; 65 women, 60 men) and study group (FDRs of type 2 diabetics; 52 women, 49 men) subjects., Results: BMI, heart rate, blood pressure, rate-pressure product, stroke volume, left-ventricular ejection time, cardiac output, total peripheral resistance, homeostatic model of insulin resistance, lipid profile, inflammatory and OS markers, and ratio of low-frequency to high-frequency power of heart rate variability (LF-HF ratio), a sensitive marker of SVI, were significantly increased, and BRS was significantly decreased in study group men compared with women. SVI was more intense in men and was due to concomitant sympathetic activation and vagal inhibition. There was no SVI in control subjects. Multiple regression analysis demonstrated independent contribution of BMI, homeostatic model of insulin resistance, atherogenic index, inflammatory and OS markers, and BRS to LF-HF ratio. Logistic regression analysis demonstrated significant prediction of prehypertension status and rate-pressure product (markers of CV risk) by LF-HF, which was more prominent in men., Conclusions: SVI is more intense in male FDRs of type 2 diabetics, and SVI is associated with increased CV risk due to insulin resistance, dyslipidemia, inflammation, and oxidative stress in these subjects.

Background: Given the potential implications in the policies focused on the prevention of hypertension, we evaluate the relationship between low serum magnesium levels and prehypertension in otherwise healthy subjects., Methods: A cross-sectional study that enrolled 175 healthy men and non-pregnant women, 20 to 65 years of age was carried out. Type 2 diabetes, impaired fasting glucose, hypertension, chronic diarrhea, cancer, impaired renal function, as well as the intake of magnesium supplements in the previous six months, were the exclusion criteria. Hypomagnesemia was defined by serum magnesium concentration of <0.7 mmol/L and prehypertension by Systolic (S) and Diastolic (D) blood pressure (BP) of 120 to 139 and 80 to 89 mmHg. A multivariate logistic conditional forward analysis, adjusted by sex, age, alcohol consumption waist circumference, body mass index, fasting glucose and triglyceride levels was conducted to evaluate the association between hypomagnesemia and prehypertension., Results: Prehypertension was identified in 68 (13.2%) subjects who were compared with 107 (20.8%) control individuals without prehypertension. Individuals with prehypertension showed lower magnesium (0.73±0.20 vs. 0.77±0.21, p<0.001) and higher triglyceride levels (2.8±3.5 vs. 1.8±1.2, p=0.04) as compared with non-prehypertensive individuals. There were no other significant differences between the groups. The adjusted multivariate logistic conditional forward analysis showed a significant association between hypomagnesemia and prehypertension (OR 1.98; 95% CI 1.11-4.20, p=0.04)., Conclusions: Our finding suggests that low serum magnesium levels could play an important role in the pathophysiology of prehypertension in otherwise healthy subjects., (© 2013.)

There are few data available on the association between serum uric acid (SUA) levels and blood pressure (BP) categories earlier in the disease continuum, when efforts for its prevention may be applicable. We performed a cross-sectional study to examine the association between SUA and prehypertension in a community-dwelling sample of Japanese adults. Study participants without hypertension aged 19 to 90 years [567 men aged 56 ± 15 (mean ± standard deviation) years and 808 women aged 58 ± 13 years] were recruited for a survey at the community based annual medical check-up. The main outcome was the presence of prehypertension [systolic BP (SBP) 120-139 mmHg and/or diastolic BP (DBP) 80-89 mmHg]. After adjustments by gender and age, both SBP (p<0.001) and DBP (p<0.001) increased significantly and progressively with increasing SUA and triglycerides (TG) as well as body mass index, LDL cholesterol, and fasting plasma glucose (FPG). Compared to those with normotension, the multivariate-adjusted odds ratio (95% confidence interval) for participants with prehypertension was 1.15 (1.05-1.26) for SUA and 3.19 (1.66-6.14) for TG. The interaction between increased SUA and TG was a significant and independent determinant for SBP (β=-2.474, p=0.008), but not for DBP (β=-0.608, p=0.349). Higher SUA levels are associated with prehypertension in participants without hypertriglyceridemia (<150 mg/dL), but not in participants with hypertriglyceridemia (≥ 150 mg/dL). TG levels may modify the association between SUA and prehypertension.

Aim: The aim of this study, the YOung TAiwanese Cohort (YOTA) Study, was to investigate the relationship between a childhood overweight/obese status and young adult preclinical atherosclerosis, including assessments of the carotid intima-media thickness (CIMT) and prehypertension or hypertension., Methods: From among children who participated in the 1992-2000 mass urine screening program in Taiwan, we recruited 303 subjects with an elevated blood pressure (EBP) and 486 subjects with a normal BP in childhood during the period of 2006-2008. These 789 young adults received health check-ups for cardiovascular health, including examinations of blood and urine parameters, anthropometrics, BP and the CIMT, a subclinical cardiovascular risk index. Data analyses were used to evaluate the associated risks in both childhood and young adulthood., Results: The school students with a childhood overweight/obese status had a higher risk of prehypertension or hypertension, with a relative risk of 3.20 (1.40-7.33) for being overweight and 6.51 (3.36-12.63) for being obese in young adulthood at an average age of 21. A childhood overweight/obese status also predicted a higher risk of having a thicker CIMT, with a relative risk of 2.82 (1.26-6.28) and 4.17 (2.21-7.85) for being overweight and obese in adulthood, respectively, after a mean follow-up of 8.5 years. The body mass index exhibited a consistent trend from childhood to adulthood, with an adjusted R square of 0.551. The participants who were not overweight/obese in childhood also demonstrated a higher risk of prehypertension or hypertension if they became overweight or obese in adulthood., Conclusions: This study highlights the importance of preventing and treating an overweight or obese status in childhood for the primary prevention of cardiovascular disease in adulthood.

Background: Knowledge of hemodynamic factors accounting for the development of hypertension should help to tailor therapeutic approaches and improve blood pressure control. Few data exist regarding sex differences of hemodynamic factors contributing to hypertension progression among patients with untreated nondiabetic stage I and II prehypertension (PreHyp) as defined by the Joint National Committee-7 guidelines (JNC-7)., Methods: We utilized noninvasive impedance cardiography, applanation tonometry and plasma measures of angiotensin II, angiotensin (1-7), serum aldosterone, high-sensitivity C-reactive protein (hs-CRP) and cytokine biomarkers of inflammation to characterize the hemodynamic and hormonal profile of 100 patients with untreated hypertension (39 women)., Results: Despite there being no differences between women and men in terms of office blood pressure, heart rate and body mass index, men demonstrated lower values of pulse pressure, systemic vascular resistance, brachial artery pulse wave velocity and augmentation index. In each of the three hypertension categories, the increased blood pressure in men was associated with significant augmentations in stroke volume and cardiac output compared with women. Sex-related hemodynamic differences were associated in women with higher plasma levels of leptin, hs-CRP, plasma angiotensin II and serum aldosterone, and no differences in the serum concentrations of cytokinins. In women but not men, hs-CRP correlated with plasma concentrations of transforming growth factor β1 (TGFβ1) and body weight; in addition, plasma TGFβ1 correlated with levels of serum vascular cell adhesion molecule 1., Conclusion: The impact of sex differences in the hemodynamic factors accounting for the elevation in arterial pressure in subjects with essential hypertension has been poorly characterized or this information is not available. We suggest that this gap in knowledge may adversely influence choices of drug treatment since our study shows for the first time significant differences in the hemodynamic and hormonal mechanisms accounting for the increased blood pressure in women compared to men.

Several lines of evidence indicate that prehypertension is more atherogenic than normal blood pressure. Serum γ-glutamyltransferase (GGT) is known to be positively associated with prehypertensive status and the progression of hypertension. However, there have been no prospective studies of serum GGT level as a predictor of prehypertension. Apparently 13,435 healthy men (mean age 42.0 ± 6.6 yr) with normal blood pressure were included in a prospective cohort study in 2005 and were followed up to 2010 with the endpoint being incident of prehypertension. During the follow up period (median 2.80 ± 1.44 yr; actual follow-up 37,679.1 person-year), prehypertension was developed in 7,867 (58.6%) participants. Risk estimations for incident prehypertension were analyzed based on quartiles of serum GGT levels using multivariate adjusted Cox proportional hazards model. In unadjusted model, the hazard ratio for incident prehypertension for the highest 3 quartiles of baseline serum GGT level was 1.21 (1.13-1.29), 1.29 (1.21-1.38), and 1.57 (1.47-1.67) compared the lowest quartile of serum GGT level, respectively (P for trend < 0.001). These associations still remained statistically significant, even after adjusting for multiple covariates. These findings indicate that increased serum GGT level is independently associated with incident prehypertension in Korean men.

Recent studies in prehypertensive spontaneously hypertensive rats (SHR) have shown larger calcium transients and reduced norepinephrine transporter (NET) activity in cultured stellate neurons compared with Wistar-Kyoto (WKY) controls, although the functional significance of these results is unknown. We hypothesized that peripheral sympathetic responsiveness in the SHR at 4 wk of age would be exaggerated compared with the WKY. In vivo arterial pressure (under 2% isoflurane) was similar in SHRs (88 ± 2/50 ± 3 mmHg, n = 18) compared with WKYs (88 ± 3/49 ± 4 mmHg, n = 20). However, a small but significant (P < 0.05) tachycardia was observed in the young SHR despite the heart rate response to vagus stimulation (3 and 5 Hz) in vivo being similar (SHR: n = 12, WKY: n = 10). In isolated atrial preparations there was a significantly greater tachycardia during right stellate stimulation (5 and 7 Hz) in SHRs (n = 19) compared with WKYs (n = 16) but not in response to exogenous NE (0.025-5 μM, SHR: n = 10, WKY: n = 10). There was also a significantly greater release of [(3)H]NE to field stimulation (5 Hz) of atria in the SHR (SHR: n = 17, WKY: n = 16). Additionally, plasma levels of neuropeptide Y sampled from the right atria in vivo were also higher in the SHR (ELISA, n = 12 for both groups). The difference in [(3)H]NE release between SHR and WKY could be normalized by the NET inhibitor desipramine (1 μM, SHR: n = 10, WKY: n = 8) but not the α2-receptor antagonist yohimbine (1 μM, SHR: n = 7, WKY: n = 8). Increased cardiac sympathetic neurotransmission driven by larger neuronal calcium transients and reduced NE reuptake translates into enhanced cardiac sympathetic responsiveness at the end organ in prehypertensive SHRs.

Objective: To examine associations of urinary phthalate levels with blood pressure (BP) and serum triglyceride and lipoprotein levels in children., Study Design: We performed a cross-sectional analysis of a subsample of US children aged 6-19 years who participated in the National Health and Nutrition Examination Survey between 2003 and 2008. We quantified exposure to 3 families of phthalates--low molecular weight, high molecular weight and di-2-ethylhexylphthalate (DEHP)--based on molar concentration of urinary metabolites. We assessed descriptive, bivariate, and multivariate associations with BP and lipid levels., Results: Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass index, levels of metabolites of DEHP, a phthalate commonly found in processed foods, were associated with higher age-, sex-, and height-standardized BP. For each log unit (roughly 3-fold) increase in DEHP metabolites, a 0.041 SD unit increase in systolic BP z-score was identified (P = .047). Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products were not associated with BP. Phthalate metabolites were not associated with triglyceride levels, high-density lipoprotein level, or prehypertension., Conclusions: Dietary phthalate exposure is associated with higher systolic BP in children and adolescents. Further work is needed to confirm these associations, as well as to evaluate opportunities for intervention., (Copyright © 2013 Mosby, Inc. All rights reserved.)

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.

Although simple renal cysts are thought to be related to hypertension, no reports have examined the relationship between simple renal cysts and prehypertension. Here, we evaluated the effects of simple renal cysts on prehypertension and hypertension and the role of serum renin levels in the cyst-related prehypertension/hypertension in adults. A total of 14,995 patients were enrolled and divided into normotension, prehypertension, and hypertension groups. Simple renal cysts were classified into different categories based on number (1 vs. ≥ 2 cm) and size (<2 vs. ≥ 2 cm). In multivariate analysis, simple renal cysts were independently related to prehypertension/hypertension. Two or more simple renal cysts or cyst of ≥ 2 cm were independently associated with prehypertension/hypertension. However, the association between cyst of ≥ 2 cm and prehypertension/hypertension disappeared after further adjusting for serum renin level in an exposure-matched subgroup analysis. Thus, the presence of two or more simple renal cysts and cyst of ≥ 2 cm were the important determinants of prehypertension and hypertension in adults. One possible mechanism of cyst-related prehypertension/hypertension may be related to an increased serum renin level. We recommend close monitoring of blood pressure routinely among patients with two or more simple renal cysts.

Few previous studies in Western populations have reported an association between C-reactive protein (CRP) and prehypertension. However, no previous study has examined this association in Asians. We examined individuals who were free of hypertension from two independent population-based studies in Singapore: the Singapore Prospective Study Programme (SP2, n=2843 Chinese, Malay and Indians aged 24 years) and the Singapore Malay Eye Study (SiMES, n=957 Malays, aged 40-80 years). Prehypertension was defined as systolic blood pressure (BP) 120-139 mm Hg or diastolic BP 80-89 mm Hg. CRP was analyzed as categories (<1, 1-3, >3 mg l(-1)). The prevalence of prehypertension increased with increasing categories of CRP in both cohorts (P for trend <0.05 in both cohorts). After adjusting for potential confounders including body mass index (BMI), smoking and diabetes, persons with higher levels of CRP were more likely to have prehypertension in both SP2 (compared with CRP <1 mg l(-1), odds ratio (OR) 1.23, 95% confidence interval (CI) 1.03-1.48 for CRP 1-3 and OR 1.67, 95% CI 1.32-2.10 for >3 mg l(-1)) and SiMES (OR 1.45, 95% CI 1.04-2.01 and OR 1.56, 95% CI 1.07-2.27) respectively. In conclusion, data from two population-based Asian cohorts suggest that elevated serum CRP levels are associated with prehypertension.

Background: Consumption of a diet high in protein can cause glomerular hyperfiltration, a potentially maladaptive response, which may accelerate the progression of kidney disease., Study Design: An ancillary study of the OmniHeart trial, a randomized 3-period crossover feeding trial testing the effects of partial replacement of carbohydrate with protein on kidney function., Setting & Participants: Healthy adults (N=164) with prehypertension or stage 1 hypertension at a community-based research clinic with a metabolic kitchen., Intervention: Participants were fed each of 3 diets for 6 weeks. Feeding periods were separated by a 2- to 4-week washout period. Weight was held constant on each diet. The 3 diets emphasized carbohydrate, protein, or unsaturated fat; dietary protein was either 15% (carbohydrate and unsaturated fat diets) or 25% (protein diet) of energy intake., Outcomes: Fasting serum creatinine, cystatin C, and β2-microglobulin levels, estimated glomerular filtration rate (eGFR)., Measurements: Serum creatinine, cystatin C, and β2-microglobulin collected at the end of each feeding period., Results: Baseline cystatin C-based eGFR was 92.0±16.3 (SD) mL/min/1.73 m(2). Compared with the carbohydrate and unsaturated fat diets, the protein diet increased cystatin C-based eGFR by ~4 mL/min/1.73 m(2) (P < 0.001). The effects of the protein diet on kidney function were independent of changes in blood pressure. There was no significant difference between the carbohydrate and unsaturated fat diets., Limitations: Participants did not have kidney disease at baseline., Conclusions: A healthy diet rich in protein increased eGFR. Whether long-term consumption of a high-protein diet leads to kidney disease is uncertain., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Like hypertension, prehypertension is associated with cardiovascular disease., Aims: The aim of this study was to evaluate: a) the prevalence of prehypertension/hypertension in individuals with various dyslipidemic phenotypes; b) the relation between blood pressure (BP) and other risk factors for atherosclerosis; c) atherogenic potential of prehypertension by the assessment of intima-media thickness of the arteria carotis communis (IMT)., Methods: 667 clinically asymptomatic subjects were divided into four dyslipidemic phenotypes (DLP) according to apolipoprotein B (apoB) and triglycerides (TG): DLP1 (n=198, normo-apoB/normo-TG), DLP2 (n=179, normo-apoB/hyper-TG), DLP3 (n=87, hyper-apoB/normo-TG), DLP4 (n=203, hyper-apoB/hyper-TG). DLP1 served as a control group., Results: There was significantly higher prevalence of prehypertension and hypertension in subjects with dyslipidemia (DLP2 43.0%, 41.3%; DLP3 42.5%, 29.9%; DLP4 42.4%, 47.8%) than in normolipidemic individuals (DLP1 32.8%, 20.2%). Systolic and diastolic blood pressure (SBP + DBP) correlated with age, total cholesterol, TG, non-HDL-cholesterol, body mass index and waist circumference; SBP additionally with C-peptide, fasting glycemia; DBP additionally with apoB, homeostasis model assessment (HOMA) and plasminogen activator inhibitor-1. The IMT of hypertensive and of prehypertensive subjects was higher than that of subjects with normal BP in all DLPs., Conclusions: The prevalence of prehypertension was higher in all dyslipidemic patients. The common prevalence of prehypertension/hypertension was highest in the hypertriglyceridemic subjects. Prehypertensive and hypertensive patients had higher IMT than normotensive individuals in all DLPs.

Inflammation is a pathogenic factor for target-organ damage (TOD) in hypertension. This study examined the relationship between inflammatory parameters and urinary albumin excretion (UAE) in prehypertension. A total of 65 prehypertensive subjects (blood pressure (BP) 120-139/80-89 mm Hg) and 26 healthy volunteers with BP <120/80 mm Hg were included. High-sensitivity C-reactive protein (hs-CRP), and serum and urinary tumor necrosis factor-α (TNF-α) were measured as inflammatory markers. Prehypertensive individuals had higher levels of inflammatory parameters and UAE than healthy subjects. Analyses carried out in prehypertensive participants showed that BP was similar between individuals with normoalbuminuria or microalbuminuria (MAB) (UAE between 30 and 299 mg per day). However, serum hs-CRP and urinary TNF-α excretion were higher in prehypertensives with MAB. Multiple regression analysis showed that systolic blood pressure (r=0.29, P<0.01), hs-CRP (r=0.20, P<0.001), and urinary TNF-α (r=0.69, P<0.001) were independently correlated with UAE (adjusted R(2)=0.73, P<0.001). Finally, logistic regression analysis performed in the prehypertensive group with the absence or presence of MAB as the dependent variable demonstrated that hs-CRP (3.92 (1.45-10.58), P=0.007) and urinary TNF-α (1.69 (1.20-2.37), P=0.002) were independent risk factors for the presence of MAB. Inflammatory parameters are significantly and independently associated with UAE in prehypertensive subjects, suggesting that inflammation may be a pathogenic factor for the early vascular or TOD in these individuals.

Increased levels of circulating soluble type of E-selectin (sE-selectin), neutrophil counts and blood pressure are associated with the development of cardiovascular diseases (CVD). In this study, we conducted a cross-sectional study of men who participated in health check-ups, and selected those who were not diagnosed with or being treated for metabolic diseases such as diabetes, hypertension and lipid abnormality according to the health check-ups. We measured their basic clinical parameters including blood pressure and neutrophil count, plasma sE-selectin concentration and lifestyle factors, and assessed their interrelations by multivariate linear regression (MLR) analysis. A total of 351 subjects aged 47.5±8.41 (range, 30-64) y were recruited. Significantly correlated with sE-selectin concentration were neutrophil count, diastolic blood pressure (DBP), and systolic blood pressure (SBP) (Pearson's correlation coefficient, 0.194, 0.220 and 0.175, respectively). MLR analysis showed that sE-selectin concentration was independently positively related with DBP and neutrophil count, whereas neutrophil count was positively associated with sE-selectin concentration but not DBP. DBP, but not SBP, was independently positively correlated with sE-selectin concentration but not neutrophil count. These results indicate that circulating sE-selectin concentration may be a biomarker for indicating subsequent development of metabolic diseases, in particular CVD, from a healthy state.

We evaluate the relationship between different lipoproteins and atherogenic indices with pre-hypertension in 297 obese and 942 non-obese children with Tanner stage 1 enrolled in a multicentre, community-based cross-sectional study. Height, weight, fasting glucose and insulin levels, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), non-HDL-c, LDL/HDL-c, triglycerides/cholesterol and total cholesterol/HDL-c ratios were measured. Mean age was 8.4 ± 1.2 years; pre-hypertension was identified in 104 (8.4%) participants, 46 (15.5%) obese and 58 (6.1%) non-obese children. The pre-hypertensive non-obese children show a high proportion of family history of hypertension (41.6 and 24.7%, p = 0.002) and elevation of insulin at a relatively low body mass index. The triglycerides:HDL-c ratio, but not other lipoproteins or atherogenic indices, was associated with pre-hypertension in obese (1.15, 95% confidence intervals 1.06-1.26) and non-obese children (1.38 95% confidence intervals 1.22-1.57). The triglycerides:HDL-c ratio is related to pre-hypertension in children; the family history of hypertension seems to be a risk factor in developing pre-hypertension.

Objective: This randomized crossover trial assessed the effects of 5 weeks of consuming low-fat dairy (one serving/day each of 1% fluid milk, low-fat cheese, and low-fat yogurt) versus nondairy products (one serving/day each of apple juice, pretzels, and cereal bar) on systolic and diastolic blood pressures (SBP and DBP), vascular function (reactive hyperemia index [RHI] and augmentation index), and plasma lipids., Methods: Patients were 62 men and women (mean age 54.5 years, body mass index 29.2 kg/m(2)) with prehypertension or stage 1 hypertension (mean resting SBP/DBP 129.8 mmHg/80.8 mmHg) while not receiving antihypertensive medications. A standard breakfast meal challenge including two servings of study products was administered at the end of each treatment period., Results: Dairy and nondairy treatments did not produce significantly different mean SBP or DBP in the resting postprandial state or from premeal to 3.5 hours postmeal (SBP, 126.3 mmHg versus 124.9 mmHg; DBP, 76.5 mmHg versus 75.7 mmHg), premeal (2.35 versus 2.20) or 2 hours postmeal (2.33 versus 2.30) RHI, and premeal (22.5 versus 23.8) or 2 hours postmeal (12.4 versus 13.2) augmentation index. Among subjects with endothelial dysfunction (RHI ≤ 1.67; n = 14) during the control treatment, premeal RHI was significantly higher in the dairy versus nondairy condition (2.32 versus 1.50, P = 0.002). Fasting lipoprotein lipid values were not significantly different between treatments overall, or in subgroup analyses., Conclusion: No significant effects of consuming low-fat dairy products, compared with low-fat nondairy products, were observed for blood pressures, measures of vascular function, or lipid variables in the overall sample, but results from subgroup analyses were consistent with the hypothesis that dairy foods might improve RHI in those with endothelial dysfunction.

We investigated captopril effects, an ACE inhibitor, on hypertension development, on Ang II and Ang-(1-7) plasma concentrations, on Ang II-induced contraction in isolated kidneys, and on kidney AT1R from spontaneously hypertensive (SHR) rats. Five weeks-old SHR and Wistar Kyoto (WKY) rats were treated with captopril at 30 mg/kg/day, in drinking water for 2 or 14 weeks. Systolic blood pressure (SBP) was measured, and isolated kidneys were tested for perfusion pressure and AT1R expression; while Ang II and Ang-(1-7) concentrations were determined in plasma. Captopril did not modify SBP in WKY rats and avoided its increase as SHR aged. Plasma Ang-II concentration was ∼4-5 folds higher in SHR rats, and captopril reduced it (P<0.05); while captopril increased Ang-(1-7) by ∼2 fold in all rat groups. Captopril increased Ang II-induced pressor response in kidneys of WKY and SHR rats, phenomenon not observed in kidneys stimulated with phenylephrine, a α₁-adrenoceptor agonist. Captopril did not modify AT1R in kidney cortex and medulla among rat strains and ages. Data indicate that captopril increased Ang II-induced kidney perfusion pressure but not AT₁R density in kidney of WKY and SHR rats, due to blockade of angiotensin II synthesis; however, ACE inhibitors may have other actions like activating signaling processes that could contribute to their diverse effects., (© 2012 Blackwell Publishing Ltd.)

Aims: To determine if customary lower serum vitamin D concentrations in healthy African American (AA) adults are associated with modest elevations in fasting plasma glucose (FPG) and/or resting blood pressure (BP). Numerous health disparities between African American (AA) and Caucasian American (CA) adults, especially those which increase cardiovascular morbidity and mortality, have been attributed to lower serum vitamin D concentrations in the AA. Prediabetes (PreDM) and prehypertension (PreHTN) are significantly more prevalent in healthy disease free CA adults with serum vitamin D concentrations below the 75th percentile for the Caucasian cohort. We hypothesized that despite overall lower serum vitamin D concentrations in AA, an increase in the prevalence for PreDM and PreHTN would be seen in those with low vitamin D levels., Methods and Results: Disease free AA adults in the National Health and Nutrition Examination Survey 2001-2006 were assessed. PreDM and PreHTN were diagnosed using the ADA and JNC 7 criteria: (FPG) 100-125 mg/dL and resting systolic (SBP) 120-139 and/or diastolic (DBP) 80-89 mm Hg, respectively. Logistic regression was employed to assess effects of low vitamin D concentrations on the odds for PreDM and PreHTN (n = 621). Age, gender and BMI adjusted odds ratio for co-morbid PreDM and PreHTN in AA men (n = 343) and women (n = 278) with vitamin D levels ≤45.4 versus >45.4 nmol/L was 2.02 (1.11, 3.68), (p < 0.021)., Conclusions: Evaluating serum vitamin D levels, with consideration for supplementation in seemingly healthy AA adults with prediabetes, prehypertension, or co-existing prediabetes and prehypertension, has merit., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Mean platelet volume (MPV), an indicator of platelet activation, has been shown to be elevated in patients with hypertension. However, data available on the association between MPV level and prehypertension are limited. Prehypertension is also associated with an increase in cardiovascular morbidity and mortality. A cross-sectional study was performed among 80 545 standardized medical checkup participants <18 years in age without hypertension or diabetes in China between April 2009 and May 2010. Blood pressure was categorized as prehypertensive (systolic blood pressure, 120-140 mm Hg and/or diastolic blood pressure, 80 to 90 mm Hg, n= 36 586) and normotensive (systolic blood pressure, < 120 mm Hg and diastolic blood pressure, <80 mm Hg, n=43 959). Mean systolic blood pressure and the prevalence of prehypertension increased significantly with increasing MPV. After adjusting for demographics, body mass index, smoking and serum cholesterol, the odds ratio for prehypertension, when comparing the highest category of MPV (>12.0 fl) with the lowest category (<10.1 fl), was 1.08 (95% confidence interval, 1.02-1.13; P for trend=0.014). This association persisted in separate analysis among men but not among women. In nonparametric models, the positive association between MPV and prehypertension appeared to be present across the full range of MPV, without any threshold effect. Increased MPV is associated with prehypertension in a large sample of Chinese adults that are free of cardiovascular disease and hypertension.

Objective: The aim of this study was to establish the prevalence of cardiovascular disease (CVD) risk factors amongst South African colliery executives presenting normal blood pressure (normotensive), pre-hypertension and hypertension., Materials and Methods: Selected CVD risk factors of a non-randomized, available population of 143 Caucasian male executives from five South African collieries situated in Mpumalanga and Gauteng Provinces were recorded., Results: Executives with pre-hypertension and hypertension exhibited a higher prevalence of CVD risk factors, compared to the persons with normal blood pressure levels. The percentage of executives with CVD risk factors, with the exception of BMI, was greater amongst those with pre-hypertension than those with hypertension., Conclusion: The current study showed that a workplace CVD risk screening process was effective in identifying the relatively high prevalence of CVD risk factors amongst SA colliery executives. In addition, out of all the studied risk factors, undesirable body composition (BMI, WHR and fat %) exhibited the highest prevalence amongst pre-hypertensive and hypertensive SA colliery executives.

Aims: To elucidate the relationship between low circulating serum vitamin D levels and predisease conditions (ie, prediabetes and prehypertension) in healthy Mexican American adults., Methods: Analyses were conducted using data from the United States National Health and Nutrition Examination Survey (NHANES) from 2001 through 2006. Free-living (ie, community-dwelling, nonimprisoned) adult Mexican American subjects (N = 788; men, n = 443; women, n = 345) who had provided written informed consent and had no history of diabetes, hypertension, dyslipidemia, metabolic syndrome, and/or cardiovascular disease were included in this report. Participants were not ingesting any prescription medications, nor did they exhibit any evidence of malabsorption. Participants were determined to be disease free., Results: The mean serum vitamin D level for Mexican American adults (N = 788) of 50.5 nmol/L was significantly higher (P < 0.0001) than the mean of 35.9 nmol/L for non-Hispanic black adults (n = 621), and significantly lower (P < 0.0001) than the mean of 65.0 nmol/L for non-Hispanic white adults (n = 1711). Although age, sex, and body mass index were all significantly associated with prehypertension and prediabetes, no such association was found for serum vitamin D levels., Conclusion: A successive, incremental shift of approximately 15 nmol/L in vitamin D distribution was seen in the transition from the dark-skinned non-Hispanic black population to the brown-skinned Mexican American population, and from the brown-skinned Mexican American population to the non-Hispanic white population. In contrast to the non-Hispanic black and non-Hispanic white populations, wherein previous studies found that serum vitamin D levels below the 75th percentile were associated with prediabetes and prehypertension, no such association was detected among the Mexican American population. The reason for this lack of association among the Mexican American population is unclear.

Dyslipidemia has been reported as a risk factor for incident hypertension in a few prospective studies, however, no study has specifically assessed different lipid measures including the lipid ratios, that is, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs)/HDL-C as predictors of hypertension among Middle Eastern women with high prevalences of dyslipidemia and hypertension. The study population consisted of 2831 non-hypertensive women, aged ≥ 20 years. We measured lipoproteins, and calculated non-HDL-C and the lipid ratios. The risk-factor-adjusted odds ratios for incident hypertension were calculated for every 1 standard deviation (s.d.) change in TC, log-transformed TG, HDL-C, non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using multivariate logistic regression analysis. Over a mean follow-up of 6.4 years, 397 women developed hypertension. An increase of 1 s.d. in TG, TC/HDL-C and TG/HDL-C increased the risk of incident hypertension by 16, 19 and 18%, respectively, and 1 s.d. increase in HDL-C decreased the risk of hypertension by 14% in the multivariable model (all P ≤ 0.05). In models excluding women with diabetes and central or general obesity, TG, TG/HDL-C and TC/HDL-C remained as independent predictors of incident hypertension. In conclusion, dyslipidemia, using serum TG and TG/HDL-C, in particular, may be useful in identification of women at risk of hypertension, even in those without diabetes and central or general obesity.

Objective: The purpose of this study was to examine prepregnancy cardiometabolic and inflammatory markers and the subsequent risk of hypertensive disorders of pregnancy., Study Design: This was a retrospective cohort study of 3380 women who took part in a comprehensive multiphasic health checkup (MHC) examination between 1984 and 1996 and who subsequently delivered at Kaiser Permanente Northern California., Results: Two hundred five women were diagnosed with a hypertensive disorder of pregnancy. Prepregnancy measurements of overweight/obesity (body mass index, ≥25.0 kg/m(2)), prehypertension, and inflammation (leukocytes, ≥7.2 10(3)/μL) were associated independently with hypertensive disorder of pregnancy risk (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.3; OR, 2.1; 95% CI, 1.5-2.8; and OR, 1.6; 95% CI, 1.1-2.3, respectively). Being overweight/obese and having prehypertension before pregnancy was associated with a 3.5-fold increased risk of hypertensive disorder of pregnancy compared with women with normal levels of both risk factors., Conclusion: A prepregnancy cardiometabolic and inflammation risk profile may help clinicians identify high-risk women to target for early intervention or management of hypertensive disorder of pregnancy., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: Red cell distribution width (RDW) which is reported as part of complete blood count in routine clinical practice, is a measure of variability in size of the erythrocytes in the circulation. It is a novel predictor of mortality both in unselected populations and in some selected group of patients. We aimed to search whether RDW values differ between the healthy population and the patients with pre-hypertension and hypertension who are otherwise healthy, considering the widely accepted role of RDW as a prognostic marker especially for mortality., Patients and Methods: Patients who were diagnosed with prehypertension or hypertension for the first time according to the Joint National Committee (JNC) 7 criteria and otherwise healthy were enrolled to the study. One-hundred and twenty-eight patients with hypertension, 74 patients with prehypertension and 36 healthy controls participated in the study. Complete blood count, biochemistry and erythrocyte sedimentation rates were measured by standard methods. Hemoglobin, white blood cell count, mean corpuscular volume, platelet count and RDW were recorded., Results: After adjustment for age, hemoglobin level, presence of anemia, serum uric acid level, erythrocyte sedimentation rate and mean corpuscular volume, mean RDW values were 15.26 ± 0.82, 16.54 ± 0.91 and 13.87 ± 0.94 in prehypertensive, hypertensive and control groups, respectively (p < 0.05). Systolic and diastolic blood pressures were strongly correlated with RDW (r = 0.848 and r = 0.748, respectively; p < 0.01)., Conclusion: RDW is higher in prehypertensive and hypertensive patients compared with healthy controls independently of age, inflammatory status and anemia. Higher RDW values are strongly correlated with higher systolic and diastolic blood pressures.