Can we use copeptin as a biomarker for masked hypertension or metabolic syndrome in obese children and adolescents?

OBJECTIVES: Copeptin, the C-terminal part of arginine-vasopressin, is increased in hypertensive adolescents and closely associated with metabolic syndrome (MS). We aimed to investigate whether serum copeptin can be used to differentiate masked hypertension (MHT) and MS, and the role of sodium intake, natriuretic peptide response and renin-angiotensin-aldosterone system in MHT and MS in obese youth. METHODS: Obese children aged 10-18 years with normal office blood pressure measurements were included. Patients with MHT and normotension and those with MS and non-MS were evaluated separately. Biochemical parameters, copeptin, brain natriuretic peptide (BNP), aldosterone, renin, urine sodium, and protein were evaluated. Echocardiography, fundoscopic examination, and ambulatory blood pressure monitoring were performed. RESULTS: There were 80 (M/F=39/41) obese patients with a mean age of 13.78 ± 1.93 years. The cases with MHT, MS, and concomitant MHT and MS were 53,24, and 13%, respectively. Copeptin levels were similar among patients with and without MHT or MS (p>0.05). However, multivariate analysis revealed that copeptin significantly increased the probability of MHT (OR 1.01, 95% CI=1.001-1.018, p=0.033). Copeptin was positively correlated with daytime systolic and diastolic load, aldosterone, BNP, and urine microalbumin/creatinine levels (p<0.05). Linear regression analyses revealed that copeptin was significantly correlated with BNP regardless of having MHT or MS in obese youth. In the MHT group, 24-h sodium excretion was not significantly correlated with BNP. CONCLUSION: Copeptin may be a beneficial biomarker to discriminate MHT, but not MS in obese children and adolescents. An insufficient BNP response to sodium intake might be one of the underlying causes of MHT in obese cases.

Association of thyroid function with white coat hypertension and sustained hypertension.

This study aimed to explore the relationship of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels with hypertension subtypes. 1056 euthyroid adults were included as research samples. They underwent measurement of clinic blood pressure and 24-hours ambulatory blood pressure monitoring. Then, they were divided into normotension (NT), white coat hypertension (WCH), masked hypertension (MHT), and sustained hypertension (SHT) groups. The 24-hours dynamic electrocardiogram was performed to analyze the heart rate variability (HRV), so as to reflect the cardiac autonomic function. The relationship between hypertension subtypes, thyroid function, and HRV was analyzed. The TSH concentration was significantly higher in the SHT group than in the NT group (P = 0.001). The FT3 concentration was higher in the SHT group than in the NT and MHT groups (P = 0.013, P = 0.008), while the FT4 concentration was significantly higher in the WCH group than in the NT group (P = 0.002). The changes in HRV were observed between the SHT, WCH, and MHT groups and the NT groups, as well as between the SHT and the MHT groups. The multiple linear regression analysis also showed that FT3, HRV (RMSSD and PNN50), and blood pressure levels linearly correlated with one another (P < 0.05). Meanwhile, the linear regression analysis showed a linear negative correlation between FT4 and HRV (SDANN) in the WCH + NT group (P = 0.001). Thyroid function was closely related to hypertension subtypes such as WCH probably due to the changes in the cardiac autonomic function.

Early blood pressure alterations are associated with pro-inflammatory markers in type 1 diabetes mellitus.

The aim of this study was to evaluate the relationship between early blood pressure (BP) changes (detected using ambulatory BP monitoring; ABPM) with different markers of inflammation and endothelial dysfunction in patients with type 1 diabetes mellitus (T1DM). The study design was observational cross-sectional in 85 T1DM patients, clinically normotensive and with normo-albuminuria. We analyzed the relationships between ABPM-measured BP alterations over 24 h with the inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor-α and vascular endothelial growth factor (VEGF)) and the markers of endothelial damage (vascular adhesion molecule, intercellular adhesion molecule and plasminogen activator inhibitor-1 (PAI)). Despite being recorded as normotensive, 27 (31.8%) subjects presented with an average of pathological BP. VEGF levels were significantly elevated in the patients with an altered mean diurnal values compared with normotensives (112.33 (72.87-213.53) pg ml-1 vs 71.03 (37.71-107.92) pg ml-1; P=0.007). Further, VEGF levels correlated significantly with the parameters of diurnal BP and of 24 h values. IL-6 concentration was a risk factor in the patients with hypertension (OR=1.406; P=0.027). There were no modifications in the levels of markers of endothelial damage. Summarizing, there is an increase in pro-inflammatory cytokines, but not the endothelial adhesion molecules, in early stages of arterial hypertension in patients with T1DM.

Masked hypertension and its associated cardiovascular risk in young individuals: the African-PREDICT study.

Hypertension prevalence is increasing globally, yet little is known about the occurrence of masked hypertension (MHT) in young, sub-Saharan African adults, and how it relates to elevated cardiovascular risk. The African-PREDICT study (recruitment based on normotensive clinic blood pressure (BP)) determined the frequency of MHT and its relationship with arterial stiffness and biochemical markers of inflammation and endothelial activation. We included men and women (n=352), 20-30 years, screened for normotensive clinic BP (54% white, 40% men). Clinic BP, ambulatory blood pressure monitoring (ABPM), central systolic pressure, aortic pulse wave velocity (aPWV), augmentation index, anthropometry, physical activity and biochemical markers of cardiovascular risk were assessed (lipids, glucose, insulin, markers of endothelial activation and inflammation). Eighteen percent of the study population had MHT (60% white, 68% men). Those with MHT had increased adiposity, clinic-, ABPM- (24-h, day and night) and central-BP (within normal ranges), heart rate, aPWV and biochemical markers of cardiovascular risk, compared with normotensives (all P<0.05). Using multivariable adjusted odds ratios, we found that MHT was associated with increased likelihood for higher aPWV (odds ratio (OR)=1.567, P=0.010), insulin (OR=1.499, P=0.049), monocyte chemoattractant protein-1 (OR=1.499, P=0.026), vascular cellular adhesion molecule (OR=1.409, P=0.042) and C-reactive protein (OR=1.440, P=0.044). In a young adult (supposedly healthy) cohort, the occurrence of MHT is alarming, especially since MHT further demonstrated elevated cardiovascular risk via increased adiposity, arterial stiffness, endothelial activation and inflammation. Detection of MHT is crucial to increase awareness of elevated cardiovascular risk, and to ensure the required lifestyle and/or pharmaceutical interventions.

Is disulphide/thiol ratio related to blood pressure in masked hypertension?

Dynamic thiol/disulphide homeostasis plays a critical role in numerous intracellular enzymatic pathways including antioxidant defence and detoxification. In this study, we sought to investigate dynamic thiol/disulphide homeostasis in patients with masked hypertension (MHT) and its relationship with blood pressure. Forty patients (23 men, 17 women) with newly diagnosed MHT and not yet on medical therapy, and 40 healthy volunteers (21 men, 19 women) were enrolled. Blood thiol/disulphide homeostasis was measured in both groups. Serum native and total thiol levels were measured using the novel, fully automated colorimetric method developed by Erel et al. Serum disulphide level was calculated as (serum total thiol - serum native thiol)/2. Native and total thiol levels (p = 0.001) and native thiol/total thiol ratio (p = 0.023) were found to be lower in patients with MHT when compared to those of the control group. Disulphide level and ratios of disulphide/native thiol and disulphide/total thiol were higher in patients with MHT than in the control group (p = 0.001). A positive correlation of systolic blood pressure (SBP) and diastolic blood pressure (DBP) was observed with disulphide/native thiol ratio (p < 0.001). Stepwise multivariable regression analysis showed disulphide/native thiol ratio to be an independent risk factor of SBP and DBP, and SBP to be an independent risk factor of disulphide/thiol ratio (p = 0.001). In this study, we found that dynamic thiol/disulphide homeostasis shifted towards disulphide formation due to thiol oxidation in patients with MHT. Prospective randomised controlled studies are required to elucidate whether abnormal thiol/disulphide status lies in the pathogenesis of MHT or is a consequence of MHT.

Serum uric acid and carotid artery intima media thickness in patients with masked hypertension.

BACKGROUND: Serum uric acid is related to hypertension and cardiovascular diseases. Masked hypertension is associated with an increase in cardiovascular risk. The aim of our study was to evaluate the serum uric acid level and its relationship with carotid intima-media thickness (IMT) in patients with masked hypertension. SUBJECTS AND METHODS: A total of 114 untreated masked hypertension patients (62 men, 52 women; mean age 44.6 +/- 7.9 years) and 38 controls (20 men, 18 women; mean age 44.8 +/- 7 years) were included in the study. All patients underwent 24-hour ambulatory blood pressure. Serum uric acid and carotid IMT were measured. RESULTS: Serum uric acid was significantly higher in masked hypertension patients when compared to the control group (5.14 +/- 1.42 mg/dl, 4.84 +/- 1.45 mg/ dl, P = 0.01). Masked hypertension patients had significantly higher carotid IMT than control subjects (0.58 +/- 0.09, 0.52 +/- 0.09, P < 0.001). The masked hypertension group was also divided into two groups according to the median value of the serum uric acid levels (median value: 5 mg/dl). Carotid IMT was significantly higher in patients with a higher uric acid when compared to those with a lower uric acid (P < 0.001). We also found that the serum uric acid level was a good predictor of increased carotid IMT at the receiver-operating characteristic curve.The area under the curve was 66% (95% confidence interval, 0.56-0.77), and the serum uric acid level was significantly predictive of a high carotid IMT (P = 0.001). CONCLUSIONS: Our data suggest that the uric acid levels were significantly higher in the masked hypertension group and elevated uric acid levels were associated with increased carotid IMT, indicating that elevated serum uric acid levels might contribute to the increase in cardiovascular risk in masked hypertension.

Homocysteine levels in patients with masked hypertension.

OBJECTIVE: Masked hypertension is a clinical condition, the importance of which is agreed in recent years and which is characterized by increased cardiovascular mortality and morbidity and is thought to be important endothelial dysfunction in the pathophysiology. Plasma total homocysteine levels are accepted as a major independent biomarker for endothelial dysfunction and/or a contributor to hypertension and coronary artery disease. In this study, we aimed to measure the level of serum homocysteine and to evaluate the relationship between the parameters of ambulatory blood pressure monitoring in patients with masked hypertension. METHODS: This cross-sectional observational study included 37 subjects with normal blood pressure, 30 with masked-hypertension and 27 patients with obvious hypertension. Masked hypertension (MHT) was defined as office blood pressure <140/90 mm Hg and mean daytime ambulatory systolic blood pressure in 24 hours monitoring ≥135/85 mm Hg. Homocysteine levels of the subjects were measured by using HPLC system with fluorescent detector. Lipid parameters were measured by routine methods. Mann-Whitney U test was used for statistical analysis. RESULTS: In the analysis of homocysteine, it was observed that there was no difference between the control group and patients with MHT. Patients with high blood pressure showed higher homocysteine levels when compared to MHT (p=0.02). Homocysteine levels showed a weak positive correlation with average systolic blood pressure (r=0.335, p=0.043). Homocysteine levels were higher in smokers than non-smokers. compared with non-smokers group in all participants (p=0.036). CONCLUSION: We have reached the opinion that in the individuals with no obvious health problems but with MHT, homocysteine levels may not have any significant effect upon high blood pressure levels.

Significant correlation between uric acid levels and flow-mediated dilatation in patients with masked hypertension.

BACKGROUND: Serum uric acid (UA) level is associated with prognosis in cardiovascular disorders such as sustained hypertension, diabetes mellitus and chronic kidney diseases. Increased UA levels in sustained hypertension may reflect early renal vascular alterations. However, it remains unclear if serum UA is associated with endothelial dysfunction in masked hypertensive patients. METHODS: A total of 100 individuals (57% men and 43% women; mean 45 ± 8 years) with masked hypertension were included in the present study. The clinical and laboratory data were collected. Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. RESULTS: Univariate regression analysis showed that the FMD was significantly negative correlated with uric acid (r = -0.300, p = 0.002), ambulatory 24-h systolic blood pressure (SBP) (r = -0.275, p = 0.008), hs-CRP (r = -0.222, p = 0.033) and diastolic aortic diameter (r = -0.243, p = 0.019). In multivariate linear regression analysis, only uric acid levels and ambulatory 24-h SBP were significantly associated with FMD. CONCLUSION: There was an independent correlation between UA and FMD, and a higher UA level was related to worse endothelial function which may contribute to hypertension and cardiovascular morbidity.

The relationship between exercise capacity and masked hypertension in sedentary patients with diabetes mellitus.

AIM: Although exaggerated blood pressure responses (EBPR) to exercise have been related to future hypertension and masked hypertension (MHT), the relationship between exercise capacity and MHT remains unclear. A sedentary life style has been related to increased cardiovascular mortality, diabetes mellitus (DM), and hypertension. In this study, we aimed to examine the relationship between exercise capacity and MHT in sedentary patients with DM. METHODS: This study included 85 sedentary and normotensive patients with DM. Each patient's daily physical activity level was assessed according to the INTERHEART study. All patients underwent an exercise treadmill test, and exercise duration and capacity were recorded. Blood pressure (BP) was recorded during all exercise stages and BP values ≥ 200/110 mmHg were accepted as EBPR. MHT was diagnosed in patients having an office BP <140/90 mmHg and a daytime ambulatory BP >135/85 mmHg. Patients were divided into two groups according to their ambulatory BP monitoring (MHT and normotensive group). RESULTS: The prevalence of MHT was 28.2%. Exercise duration and capacity were lower in the MHT group than in the normotensive group (p<0.05) and were negatively correlated with age, HbA1c, mean daytime BP, and mean 24 hour BP. Peak exercise systolic BP and the frequency of EBPR were both increased in the MHT group (25.0% and 8.1%, respectively, p=0.03). According to a multivariate regression, exercise capacity (OR: 0.61, CI95%: 0.39-0.95, p=0.03), EBPR (OR: 9.45, CI95%: 1.72-16.90, p=0.01), and the duration of DM (OR: 0.84, CI95%: 0.71-0.96, p=0.03) were predictors of MHT. CONCLUSION: Exercise capacity, EBPR, and the duration of DM were predictors of MHT in sedentary subjects with DM.

Masked hypertension and atherogenesis: the impact of apelin and relaxin plasma levels.

Recent evidence demonstrates that masked hypertension (MH) is a significant predictor of cardiovascular disease, while apelin and relaxin are two novel factors with a significant role in vascular regulation. Apelin is an adipokine that elicits endothelium-dependent vasorelaxation and reduces arterial blood pressure, while relaxin is a protein hormone that induces the production of nitric oxide and vascular endothelial growth factor and inhibits endothelin and angiotensin II. This study aimed to investigate whether apelin and relaxin plasma levels are affected in patients with MH and compare the findings with those of healthy normotensives. One hundred-thirty (60 men, 70 women) healthy patients with a mean age of 45±12 years who had clinic blood pressure <140/90 mmHg were studied. The whole study population underwent 24-hour ambulatory blood pressure monitoring (ABPM). According to the ABPM recordings, 24 individuals (8 men, 16 women) had MH and the remaining 106 patients (52 men, 54 women) had normal ABPM recordings. Apelin and relaxin plasma levels were determined in both groups (enzyme-linked immunosorbent assay method). The apelin (220±121 vs 315±147 pg/mL, P=.001) and relaxin (35.2±6.7 vs 56.8±13.6 pg/mL, P<.001) plasma levels were significantly lower in the masked hypertensive group compared with normotensive controls. Our findings suggest that patients with masked hypertension have significantly lower apelin and relaxin levels. This observation may have prognostic significance for future cardiovascular events in patients with MH and needs further investigation.

Comparison of demographic, clinical, and laboratory parameters between patients with sustained normotension, white coat hypertension, masked hypertension, and sustained hypertension.

BACKGROUND: After measurement of office blood pressure (BP) and ambulatory BP monitoring (ABPM), 4 groups of patients were identified namely: (i) sustained normotensive patients (BPs are normal both clinically and by ABPM); (ii) white coat hypertensive patients (clinical BP were above limits, but ABPM were normal); (iii) masked hypertensive patients (clinical BP were normal, but ABPM were high); (iv) sustained hypertensive patients (both office and ABPM were high). The exact pathophysiologic mechanisms of these conditions are not exactly known. Besides in the literature there are only few studies that compare the 4 groups of patients together. Thus the study was carried out to compare patients with sustained normotension (SNT), white coat hypertension (WCHT), masked hypertension (MHT), and sustained hypertension (SHT). METHODS: All patients underwent history taking, physical examination, laboratory analysis, and ABPM. They were referred to the cardiology department for echocardiographic evaluation. RESULTS: In total 85 patients with SNT, 112 patients with WCHT, 31 patients with MHT, and 81 patients with SHT were included. Going from SNT to SHT, body mass index (p<0.0001), waist circumference (p<0.0001), fasting blood glucose (p=0.002), and uric acid (p=0.029) rose progressively. Presence of metabolic syndrome was also highest in SHT and lowest in SNT (p<0.0001). CONCLUSION: Most of the metabolic risk factors were higher in patients with MHT and SHT when compared to SNT and WCHT. Studies are needed to determine whether metabolic risk factors play a causative role for the development of MHT and SHT.

Increased platelet activation and inflammatory response in patients with masked hypertension.

Masked hypertension is associated with an increase in cardiovascular risk. Mean platelet volume (MPV), a determinant of platelet function, is a new risk factor for atherothrombosis. High-sensitive C-reactive protein (CRP) is an exquisitely sensitive systemic marker of inflammatory response. We designed this study to evaluate MPV and CRP in masked hypertensive patients and to compare those with essential hypertensive and healthy normotensive individuals. Forty-two untreated masked hypertensive patients, 53 untreated essential hypertensive patients and age-sex matched 37 normotensive healthy individuals were included in the study. Blood samples were collected and haematological parameters were measured. Plasma CRP level was measured by immunonephelometery method. The MPV was significantly higher in masked hypertensive (8.8 ±â€Š1.6 fl) and essential hypertensive patients (9.1 ±â€Š1.7 fl) than those of normotensive control individuals (7.8 ±â€Š0.8 fl) (P = 0.01 and P = 0.003, respectively), whereas there was no significant difference between the masked hypertensive and essential hypertensive individuals (P > 0.05). CRP levels were also significantly higher in masked hypertensive patients than in normotensives individuals (3.31 ±â€Š1.70, 1.98 ±â€Š1.56 mg/l, P < 0.001, respectively). There was a significant positive correlation between MPV and CRP levels (P < 0.001, r = 0.850) in masked hypertensive patients. Patients with masked hypertension have higher MPV and CRP values than controls. Increased MPV and CRP levels may be the possible mechanisms behind the increased cardiovascular risk in masked hypertensive patients.