Aldosterone Levels, Aortic Stiffness, and Wave Reflection in Essential Hypertensive Patients.

BACKGROUND: The aim of the present study was to evaluate the grade of arterial stiffening, in relation to aldosterone (ALDO) and plasma renin activity (PRA) levels, in essential never-treated hypertensive patients. MATERIALS AND METHODS: We studied 1,330 consecutive patients without clinical and/or laboratory findings of primary or secondary aldosteronism. Arterial stiffness indices Aix75 and carotid-femoral pulse wave velocity (PWVc-f) were measured and a 24-hour urine collection for ALDO was carried out to classify patients with low ALDO <12 mcg/24 hours and high ALDO >12 but <24 mcg/24 hours. Patients were divided according to PRA (high PRA > 1ng/ml/hour, low PRA < 1ng/ml/hour) and ALDO levels (high ALDO > 12 but <24 mcg/24 hours, low ALDO < 12 mcg/24 hours) in four groups. Also patients were grouped according to serum ALDO quartiles, 24-hour urine ALDO quartiles, PRA quartiles, and serum ALDO/PRA quartiles. RESULTS: Patients were classified in 4 groups: group I (high ALDO and low PRA), group II (high ALDO and high PRA), group III (low ALDO and low PRA), and finally group IV (low ALDO and high PRA). PWVc-f and AoAIx75 were significantly higher in group I followed by group II, III, and IV (P < 0.001). Comparison of arterial stiffness indices according to PRA quartiles and PWVc-f and AoAIx75 showed significantly higher in the 1st quartile compared to 2nd, 3rd, and 4th, respectively (P < 0.001). PWVc-f and AoAIx75 were also compared among the four quartiles of aldosterone-renin ratio and they were significantly higher (P < 0.001) in the 4th quartile followed by the 3rd, 2nd, and 1st, respectively. CONCLUSIONS: Arterial stiffness indices are higher among essential hypertensive patients with high normal serum and urine ALDO levels, pointing to a causal relationship between renin-angiotensin-aldosterone system activation and large artery properties.

Impaired glucose homeostasis in non-diabetic Greek hypertensives with diabetes family history. Effect of the obesity status.

Arterial hypertension (AH) and diabetes mellitus (DM) are established cardiovascular risk factors. Impaired glucose homeostasis (IGH; impaired fasting glucose or/and impaired glucose tolerance) or pre-diabetes, obesity, and DM family history identify individuals at risk for type 2 DM in whom preventive interventions are necessary. The aim of this study was to determine the glycemic profile in non-diabetic Greek adult hypertensive men and women according to DM family history and the obesity status. Diabetes family history, obesity markers (waist-to-hip ratio, WHR; body mass index, BMI), glycemic parameters (fasting and 2-hour post-load plasma glucose, if necessary; glycated hemoglobin, HbA1c; fasting insulin), insulin resistance indices (homeostasis model assessment, HOMA; quantitative insulin sensitivity check index, QUICKI; Bennett; McAuley), and IGH prevalence were determined in a large cohort of 11,540 Greek hypertensives referred to our institutions. Positive DM family history was associated with elevated fasting glucose (98.6 ± 13.1 vs 96.5 ± 12.3 mg/dL), HbA1c (5.58% ± 0.49% vs 5.50% ± 0.46%), fasting insulin (9.74 ± 4.20 vs 9.21 ± 3.63 µU/mL) and HOMA (2.43 ± 1.19 vs 2.24 ± 1.01) values, lower QUICKI (0.342 ± 0.025 vs 0.345 ± 0.023), Bennett (0.285 ± 0.081 vs 0.292 ± 0.078) and McAuley (6.73 ± 3.43 vs 6.95 ± 3.44) values, and higher IGH prevalence (45.3% vs 38.7%); P < .01 for all comparisons. The difference in the prevalence of IGH according to DM family history was significant (P < .01) in both genders and every WHR and BMI subgroup (except for women with BMI <20 kg/m(2)). Non-diabetic hypertensives with positive DM family history present with higher IGH prevalence and worse glycemic indices levels compared with those with negative family history, especially in the higher WHR/BMI subgroups.

The interplay of exercise heart rate and blood pressure as a predictor of coronary artery disease and arterial hypertension.

Delayed blood pressure (BP) and heart rate (HR) decline at recovery post-exercise are independent predictors of incident coronary artery disease (CAD). Delayed BP recovery and exaggerated BP response to exercise are independent predictors of future arterial hypertension (AH). This study sought to examine whether the combination of two exercise parameters provides additional prognostic value than each variable alone. A total of 830 non-CAD patients (374 normotensive) were followed for new-onset CAD and/or AH for 5 years after diagnostic exercise testing (ET). At the end of follow-up, patients without overt CAD underwent a second ET. Stress imaging modalities and coronary angiography, where appropriate, ruled out CAD. New-onset CAD was detected in 110 participants (13.3%) whereas AH was detected in 41 former normotensives (11.0%). The adjusted (for confounders) relative risk (RR) of CAD in abnormal BP and HR recovery patients was 1.95 (95% confidence interval [CI], 1.28-2.98; P=.011) compared with delayed BP and normal HR recovery patients and 1.71 (95% CI, 1.08-2.75; P=.014) compared with normal BP and delayed HR recovery patients. The adjusted RR of AH in normotensives with abnormal BP recovery and response was 2.18 (95% CI, 1.03-4.72; P=.047) compared with delayed BP recovery and normal BP response patients and 2.48 (95% CI, 1.14-4.97; P=.038) compared with normal BP recovery and exaggerated BP response individuals. In conclusion, the combination of two independent exercise predictors is an even stronger CAD/AH predictor than its components.

Prostate-specific antigen levels are associated with arterial stiffness in essential hypertensive patients.

INTRODUCTION: Prostate-specific antigen (PSA) has been recently related to cardiovascular system in a multifactorial way. Arterial stiffness is a independent predictor of cardiovascular events and is involved in the pathogenesis of hypertension. The aim of the present study was to investigate whether PSA values, are associated with arterial stiffness indices in patients with essential arterial hypertension. METHODS: The study comprised 150 consecutive male patients (mean age 60 years) with uncomplicated never-treated essential hypertension. All patients underwent a complete clinical and laboratory evaluation, including measurement of PSA levels. Aortic stiffness and arterial wave reflection assessment was made by using carotid-femoral (PWVc-f) pulse wave velocity and aortic augmentation index corrected for heart rate (AIx75). Patients with prostate cancer or benign prostate hyperplasia (PSA > 4 ng/mL) were excluded from the study. RESULTS: PSA was positively associated with waist-to-hip ratio (r = 0.235, P = 0.04), PWVc-f (r = 0.426, P < 0.001), AIx75 (r = 0.264, P = 0.001), and high sensitivity C-reactive protein (hsCRP; r = 0.376, P < 0.001). In categorization to PSA quartiles, patients in the higher quartile presented with higher waist-to hip ratio (P = 0.009), PWVc-f (P < 0.00001), AIx75 (P < 0.001) and hsCRP (P < 0.001) values. In multivariate analysis after adjustment for various confounders PSA remained a significant determinant of PWVc-f values (beta [SE] = 0.477 [0.13], R(2) = 0.405, P < 0.001). CONCLUSION: The present study points towards an association between PSA levels and aortic stiffness in untreated essential hypertensive males. Potential causal relationships between PSA and arterial stiffness remain to be further explored.

Relationships of osteoprotegerin with albuminuria and asymmetric dimethylarginine in essential hypertension: integrating vascular dysfunction.

OBJECTIVES: To investigate the inter-relationships of osteoprotegerin (OPG) with albumin to creatinine ratio (ACR) and asymmetric dimethylargine (ADMA) in hypertensive patients. METHODS: In 198 untreated non-diabetic hypertensive patients [130 males, mean age=51.5 years, office blood pressure (BP)=152/98 mmHg] ACR values and OPG and ADMA levels were determined. RESULTS: Based on the median value of OPG distribution (5.03 pmol/l) patients with high (n=101) compared with those with low OPG values (n=97) had greater 24-h systolic BP (152±5 versus 137±7 mmHg, p<0.0001), ACR [25.3 (5-190) versus 17.3 (5-92) mg/g, p=0.003) and ADMA [0.62 (0.58-0.68) versus 0.57 (0.48-0.62) µmol/l, p=0.001), independently of confounding factors. Multiple regression analyses revealed that ADMA (b=0.388, p<0.0001), 24-h systolic BP (b=0.228, p=0.01) and ACR (b=0.470, p<0.0001) were independent predictors of OPG (R2=0.398, p<0.0001). CONCLUSIONS: In hypertensive patients, high OPG levels are accompanied by pronounced albuminuria and endothelial dysfunction, as reflected by raised ADMA levels. Furthermore, the independent associations of OPG with ACR and ADMA, suggests a link between OPG and the progression of diffuse hypertensive vascular damage.

Association of serum uric acid level with aortic stiffness and arterial wave reflections in newly diagnosed, never-treated hypertension.

BACKGROUND: Serum uric acid (UA) plays a key role in the development and progression of hypertension. We investigated the association of UA levels and indices of arterial function in a cohort of newly diagnosed, never-treated hypertensive subjects. METHODS: One thousand two hundred and twenty-five patients with a new diagnosis of mild to moderate arterial hypertension for which they had never received treatment were enrolled in the study (mean age 52.9 years, 728 men). Serum UA, carotid-femoral pulse-wave velocity (cfPWV), an index of aortic stiffness and augmentation index (AIx), a composite marker of wave reflections and arterial stiffness were measured. RESULTS: In univariable analysis, UA levels correlated with cfPWV (r = 0.23, P < 0.001) and AIx (r = -0.24, P < 0.001). In multiple linear regression analysis, an independent positive association of cfPWV with UA levels was observed after adjusting for confounders (standardized regression coefficient ß = 0.169, P < 0.001, adjusted R² = 0.402), indicating an increase in aortic stiffness with higher values of UA. In contrast, an independent negative association of AIx with UA levels was observed after adjusting for confounders (standardized regression coefficient ß = -0.064, P = 0.011, adjusted R² = 0.557), indicating a decrease in wave reflections with higher values of UA. In gender-specific analyses, UA positively correlated with cfPWV in both genders, whereas a negative correlation with AIx existed only in females. CONCLUSIONS: Serum UA levels are independently associated with aortic stiffening and wave reflections in never-treated hypertensives. Future studies are warranted in order to explore its exact role on arterial function in the hypertensive setting.

Ambulatory blood pressure profile in hypertensive patients with ß-thalassemia minor.

ß-thalassemia trait (ß-TT) is a common genetic disorder in Mediterranean countries, including Greece. Previous studies have shown the protective effect of ß-TT against myocardial infarction. However, the ambulatory blood pressure (BP) profile of such patients has not yet been investigated. Thus, the purpose of the present study was to investigate the ambulatory BP monitoring (ABPM) profile of hypertensives with ß-TT, in comparison with all-cause anemic and non-anemic essential hypertensive patients. The study ultimately comprised of 8861 essential hypertensive, nondiabetic patients who were divided into three groups: group I (n=191, with ß-TT), group II (n=655, anemic) and group III (n=8015, nonanemic). All patients underwent full clinical, laboratory and echocardiographic evaluations, whereas all were subjected to ABPM. Anemia was defined as Hb <12 g per 100 ml for women and <13 g per 100 ml for men, whereas patients with ß-TT were self-referred. The distribution of dipping patterns among the three groups was 61.3 vs. 41.2 vs. 45.8% (P<0.001), whereas for nondippers it was 20.4 vs. 31.5 vs. 27.7% (P<0.001), for extreme-dippers it was 15.7 vs. 15.0 vs. 17.5% (P<0.001) and for reverse dippers it was 2.6 vs. 12.4 vs. 9.0% (P<0.001). Furthermore, mean daytime systolic BP (SBP) among the three groups was 140.13 ± 7.79 vs. 142.02 ± 11.61 vs. 141.99 ± 9.87 mm Hg (P=0.03), and mean nighttime SBP was 125.87 ± 10.4 vs. 131.13 ± 15.7 vs. 129.62 ± 13.31 mm Hg (P<0.001). In the multiple regression analysis, after adjustments for age, body mass index and lipid levels, the differences among daytime and nighttime SBP remained significant at 140.18 ± 9.84 vs. 142.02 ± 9.85 vs. 141.99 ± 9.85 mm Hg (P=0.04) and 125.99 ± 13.07 vs. 131.19 ± 13.08 vs. 129.61 ± 13.07 mm Hg (P<0.001), respectively. Hypertensive patients with ß-TT present with a better 24-h BP profile in comparison with anemic and nonanemic hypertensives. Thus, ß-TT may function protectively in their total cardiovascular risk profile.

Serum phosphate in white-coat hypertensive patients: focus on dipping status and metabolic syndrome.

Recent studies indicate an association between serum phosphate levels and blood pressure in hypertensive patients. A growing body of evidence suggests that white-coat hypertension (WCH) is associated with target organ damage. Furthermore, metabolic syndrome (MS) and a non-dipping pattern are associated with increased cardiovascular risk. The purpose of this study was to explore the nocturnal blood pressure fall in patients with WCH according to their serum phosphate levels and number of MS components fulfilled. The study included 2600 patients with WCH who attended our outpatient clinics. All patients underwent repeated office blood pressure measurements, 24-h ambulatory blood pressure monitoring and full clinical and laboratory evaluation. The diagnosis of MS was made according to the Adult Treatment Panel III criteria. Dipping pattern was defined as follows: 'dippers' had a nocturnal systolic blood pressure (NSBP) fall > or =10% but <20%; 'non-dippers' had an NSBP fall <10%; 'extreme dippers' had an NSBP fall > or =20% and 'reverse dippers' had an NSBP increase. There were 314 extreme dippers, 1337 dippers, 734 non-dippers and 116 reverse dippers. Reverse dippers presented with significantly lower levels of serum phosphate, whereas extreme dippers had significantly higher levels (3.39+/-3.29 vs. 3.58+/-3.52 mg per 100 ml, P<0.0001). The patients were classified according to the number of MS components and the main observation was the inverse relationship of serum phosphate with MS components (3.53+/-0.36, 3.50+/-0.38, 3.49+/-0.38, 3.44+/-0.36 and 3.35+/-0.31 mg per 100 ml, respectively, P=0.003). Patients with WCH and low serum phosphate levels appear to have a higher incidence of a non-dipping NSBP profile and an impaired metabolic profile. This observation may be important for the stratification of the cardiovascular risk in WCH patients.

Relationships of CRP and P wave dispersion with atrial fibrillation in hypertensive subjects.

BACKGROUND: Although inflammation has been shown to be implicated in the pathophysiology of atrial fibrillation (AF), little is known about its involvement in the accompanying atrial electrical remodeling expressed by P wave dispersion (P(disp)). METHODS: Fifty hypertensive subjects with documented paroxysmal AF (AF group) and 50 matched for body mass index, sex and office systolic blood pressure (BP) subjects with no history of AF (SR group) were subjected to electrocardiogram (ECG) and P(disp) assessment, hs-CRP determination, a complete echocardiographic study and 24-h ambulatory BP monitoring. RESULTS: The AF as compared to the SR subjects were older by 14 years (P < 0.0001) and they exhibited lower office and 24-h diastolic BP (7 mm Hg, P < 0.0001 and by 8 mm Hg, P < 0.0001, respectively) and higher office and 24-h pulse pressure (by 4 mm Hg, P = 0.03 and 6 mm Hg, P = 0.001, respectively) mean values. A higher mean of left atrial (LA) diameter index (by 1.9 mm/m(2), P < 0.0001) and left ventricular mass index (by 16 g/m(2), P < 0.0001) were observed in the AF vs. SR group. P(disp) mean and hs-CRP median values were higher in the AF group (by 22 ms, P < 0.0005 and by 4.63 mg/l, P < 0.0005, respectively). Standard multiple and multiple logistic regression analysis identified log(10)(hs-CRP) as independent determinant of P(disp) and log(10)(CRP) and P(disp) as independent determinants of AF. CONCLUSIONS: In hypertensive subjects hs-CRP and P(disp) are interrelated and associated with AF, suggesting an active implication of inflammation in the atrial electrophysiological remodeling predisposing to AF.

Leontio Lyceum ALbuminuria (3L Study) epidemiological study: aims, design and preliminary findings.

INTRODUCTION: The significance of microalbuminuria (MA) in paediatric essential hypertension has yet to be established. The Leontio Lyceum ALbuminuria Study (3L Study) was designed to determine the prevalence of MA among Greek schoolchildren and to evaluate these rates in relation to the children's anthropometric and lifestyle characteristics, and dietary habits. METHODS: During April 2009, 498 students from the Leontio Lyceum, aged 12-17 years (7th-12th grade), were asked to participate in the 3L Study. For each child a questionnaire was completed that was developed for the purposes of the study to retrieve information on socio-demographic and lifestyle characteristics, as well as dietary habits (through a semi-quantitative Food Frequency Questionnaire), and physical activity status. Overweight and obesity were defined using the international body mass index cut-off points established for children and young people. Office blood pressure (BP) was measured on two different occasions and those students who had BP >95th percentile for gender, age and height on both occasions were considered as hypertensives. Microalbuminuria was determined as albumin to creatinine ratio >or=22 mg/g in boys and >or=31 mg/g in girls in a morning spot urine sample using a quantitative assay (DCA 2000). RESULTS: The prevalence of MA was found to be 12.9% and that of childhood hypertension 5.2%. The prevalence of overweight status was 25.8% and 5.8% of the students were classified as obese. Low physical activity was reported by 7% of boys and girls, while 46.5% of the students reported participation in vigorous physical activities during a normal week. Based on the KIDMED score of each student, only 6% of them were classified as high adherers to a Mediterranean diet and 41.9% were classified as having very low diet quality. CONCLUSIONS: In this paper we present the aims, design and preliminary results of an epidemiological study on MA, hypertension, increased body size and lifestyle characteristics among Greek schoolchildren.