Biomarkers of nondipper hypertension in prehypertensive and hypertensive patients.

Aim: The aim of this study was to evaluate the relation of gamma glutamyl transferase (GGT), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with nondipper hypertension. Methods: This study included a total of 409 patients. Patients were grouped into hypertension, prehypertension and normotensive groups, according to their clinical blood pressure. All patients were also followed by ambulatory blood pressure. Results: Mean PLR and NLR were higher in the nondippers compared with dippers among both prehypertensive and hypertensive patients. In addition, PLR (OR: 1.011; 95% CI: 1004-1017; p = 0.001), NLR (OR: 2.296, 95% CI: 1634-3225; p < 0.001), and GGT (OR: 1.067; 95% CI: 1042-1092; p < 0.001) were found to be associated with nondipper pattern among whole study population. Conclusion: The PLR, NLR and GGT values are easily accessible and fairly useful, independently associated with nondipper hypertension for both hypertensive and prehypertensive patients.

Effects of controlled physical activity on immune cell phenotype in peripheral blood in prehypertension - studies in preclinical model and randomised crossover study.

Hypertension (HT) is a global public health issue. There are many behavioural risk factors including unhealthy diet, tobacco use and alcohol consumption as well physical inactivity that contribute to the development of high blood pressure (BP) and its complications. Favourable effect of regular physical activity on treatment or prevention of hypertension by improvement of endothelial function is widely accepted however little is known about its relationship with immune system. Thus, the aim of this study was to assess the role of moderate regular physical activity on immune cell phenotype. T cell and monocyte subsets were characterised in 31 subjects with prehypertension (130 - 139 mmHg systolic and 85 - 89 mmHg diastolic blood pressure) who participated in moderate training (3 times/week) on cyclometers for 3 months in crossover study design. Complementary study was performed in murine model of Ang II-induced hypertension and ten-week-old animals were trained on a treadmill (5 times/week, 1 hour) for 2 weeks before and 1.5 weeks after minipumps implantation. In the context of elevated blood pressure regular physical activity had modest influence on immune cell phenotype. Both in human study and murine model we did not observe effects of applied exercise that can explain the mechanism of BP reduction after short-term regular training. Twelve-weeks regular training did not affect the activation status of T lymphocytes measured as expression of CD69, CD25 and CCR5 in human study. Physical activity resulted in higher expression of adhesion molecule CD11c on CD16+ monocytes (especially CD14 high) without any changes in leukocytes subpopulation counts. Similar results were observed in murine model of hypertension after the training. However the training caused significant decrease of CCR5 and CD25 expressions (measured as a mean fluorescence intensity) on CD8+ T cells infiltrating perivascular adipose tissue. Our studies show modest regulatory influence of moderate training on inflammatory markers in prehypertensive subjects and murine model of Ang II induced hypertension.

The Association Between Glycosylation of Immunoglobulin G and Hypertension: A Multiple Ethnic Cross-Sectional Study.

More than half of all known proteins, and almost all membrane and extra-cellular proteins have oligosaccharide structures or glycans attached to them. Defects in glycosylation pathways are directly involved in at least 30 severe human diseases.A multiple center cross-sectional study (China, Croatia, and Scotland) was carried out to investigate the possible association between hypertension and IgG glycosylation. A hydrophilic interaction chromatography of fluorescently labeled glycans was used to analyze N-glycans attached to IgG in plasma samples from a total of 4757 individuals of Chinese Han, Croatian, and Scottish ethnicity.Five glycans (IgG with digalactosylated glycans) significantly differed in participants with prehypertension or hypertension compared to those with normal blood pressure, while additional 17 glycan traits were only significantly differed in participants with hypertension compared to those of normal blood pressure. These glycans were also significant correlated with systolic blood pressure (SBP) or diastolic blood pressure (DBP).The present study demonstrated for the 1st time an association between hypertension and IgG glycome composition. These findings suggest that the individual variation in N-glycosylation of IgG contributes to pathogenesis of hypertension, presumably via its effect on pro- and/or anti-inflammatory pathways.

Association between the neutrophil to lymphocyte ratio and prehypertension.

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).

Serum C-reactive protein level and prehypertension in two Asian populations.

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.

Differential TNF production by monocyte subsets under physical stress: blunted mobilization of proinflammatory monocytes in prehypertensive individuals.

Elevated blood pressure (BP) and infiltration of the vasculature by monocytes contribute to vascular pathology; but, monocyte migratory characteristics based on differing inflammatory potential under adrenergic activation remains unclear. We compared nonclassical (CD14(+)CD16(++); HLA-DR(+)), intermediate (CD14(++)CD16(+); HLA-DR(++)), and classical (CD14(++)CD16(-); HLA-DR(+/-)) monocyte trafficking and their LPS-stimulated TNF production in response to a physical stressor (20-min treadmill exercise at 65-70% VO(2peak)) in participants with high prehypertension (PHT), mild PHT or normal BP (NBP). To determine adrenergic receptor (AR) sensitivity, pre-exercise cells were also treated with isoproterenol (Iso). When cells were stimulated with LPS, the CD16 molecules were downregulated, and monocyte subsets were differentiated based on HLA-DR expression. Monocyte subpopulations (as % of total monocytes) and intracellular TNF production were evaluated by flow cytometry. TNF production in all subsets decreased post-exercise and with ex-vivo incubation with Iso, irrespective of BP (p<0.001), with nonclassical and intermediate monocytes being a major source of TNF production. Overall, % nonclassical monocytes increased, % intermediate did not change, whereas % classical decreased post-exercise (p<0.001). However, % increase in nonclassical monocytes under exercise-induced adrenergic activation was blunted in high PHT individuals (p<0.05), but not in individuals with mild PHT and NBP. These findings extend our previous reports by showing that the mobilization of proinflammatory monocytes under physical stress is attenuated with even mild BP elevation. This may be indicative of monocytic AR desensitization and/or greater adhesion of "proinflammatory" monocytes to the vascular endothelium in hypertension with potential clinical implications of vascular pathology.

Plasma sE-selectin level is positively correlated with neutrophil count and diastolic blood pressure in Japanese men.

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.

Relationship between increased systemic inflammation and impaired aortic elasticity in young patients with prehypertension.

AIM: This study was designed to evaluate the possible relationship between vascular inflammatory status [namely, high-sensitivity C-reactive protein (hs-CRP) and white blood cell (WBC)] and aortic elasticity parameters in patients with prehypertension. MATERIALS AND METHODS: The study population consisted of 25 newly diagnosed prehypertensive individuals (18 men, mean age=34±6 years) and 25 healthy controls (16 men, mean age=33±6 years) eligible for this study. Aortic elasticity parameters were calculated from aortic diameters measured by echocardiography and blood pressures, simultaneously measured by sphygmomanometry. hs-CRP measurements were taken with latex-enhanced reagent using a Behring BN ProSpec analyzer. RESULTS: Baseline characteristics of patients with prehypertension and controls were homogeneous. Inflammatory markers were significantly higher in patients with prehypertension compared with those of controls [for WBC (×10(9)/l): 11.46±0.77 (11.50) vs. 8.94±0.91 (9.20), P<0.001; for hs-CRP (µg/dl): 137.84±50.71 (130.00) vs. 78.30±35.20 (65.27), P<0.001]. There was a strong positive correlation between the mean aortic stiffness index and markers of inflammation (for WBC, r=0.857, P<0.001; for hs-CRP, r=0.858, P<0.001), whereas strong negative correlations were observed between aortic elasticity parameters and markers of inflammation (for aortic distensibility of WBC and hs-CRP, r=-0.862, P<0.001; r=-0.869, P<0.001, respectively, and for aortic strain of WBC and hs-CRP, r=-0.890, P<0.001; r=-0.906, P<0.001, respectively). CONCLUSION: Young prehypertensives have increased markers of inflammation, namely, hs-CRP and WBC, compared with controls. More importantly, impaired arterial stiffness is significantly associated with the markers of inflammation in patients with prehypertension.

Early inflammatory and metabolic changes in association with AGTR1 polymorphisms in prehypertensive subjects.

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.

Oxidized low-density lipoprotein, angiotensin II and increased waist cirumference are associated with valve inflammation in prehypertensive patients with aortic stenosis.

INTRODUCTION: The progression of aortic stenosis (AS) has been shown to be faster in patients with the metabolic syndrome. We sought to determine the relationships between blood pressure, inflammation, oxidative stress and valvular inflammation in a population of normotensive and prehypertensive patients with AS. METHODS: In this study, 36 male patients (age: 61.5±2 years) with AS undergoing an aortic valve replacement were investigated. Plasma levels of adiponectin, oxidized-LDL (ox-LDL), angiotensinogen (AGN) and angiotensin I-II (Ang I-II) were measured. On explanted aortic valves, immunohistochemistry studies and quantitative PCR (q-PCR) analyses were performed to document the expression of inflammatory cytokines. RESULTS: Systolic blood pressure (SBP) was positively correlated with plasma level of ox-LDL (r=0.4; p=0.02), AGN (r=0.41; p=0.01), and white blood cells count (r=0.33; p=0.04), whereas it was inversely related to plasma level of adiponectin (r=-.35; p=0.04). After adjustment for covariates, plasma level of ox-LDL (p=0.01) remained significantly associated with SBP (p=0.01). Within the aortic valve, expression of TNF-α was significantly associated with plasma levels of ox-LDL (r=0.58; p=0.03), Ang II (r=0.69; p=0.013), and waist circumference (r=0.60; p=0.02), whereas valvular expression of IL-6 was associated with plasma level of Ang II (r=0.51; p=0.03). In explanted AS valves, ox-LDL was documented near calcified areas and colocalized with Ang II, IL-6, and TNF-α. CONCLUSION: Conditions associated with a higher oxidative stress and activation of the renin angiotensin system, such as encountered in viscerally obese and prehypertensive patients, contribute to higher valvular inflammation in AS.