Never-treated Hypertensive Subjects Research Articles

Urine sodium excretion is related to extracellular water volume but not to blood pressure in 510 normotensive and never-treated hypertensive subjects

Purpose High sodium intake is an accepted risk factor for hypertension, while low Na+ intake has also been associated with increased risk of cardiovascular events. In this cross-sectional study, we examined the association of 24-h urinary Na+ excretion with haemodynamics and volume status. Materials and methods Haemodynamics were recorded in 510 normotensive and never-treated hypertensive subjects using whole-body impedance cardiography and tonometric radial artery pulse wave analysis. The results were examined in sex-specific tertiles of 24-h Na+ excretion, and comparisons between normotensive and hypertensive participants were also performed. Regression analysis was used to investigate factors associated with volume status. The findings were additionally compared to 28 patients with primary aldosteronism. Results The mean values of 24-h urinary Na+ excretion in tertiles of the 510 participants were 94, 148 and 218 mmol, respectively. Average tertile age (43.4–44.7 years), office blood pressure and pulse wave velocity were corresponding in the tertiles. Plasma electrolytes, lipids, vitamin D metabolites, parathyroid hormone, renin activity, aldosterone, creatinine and insulin sensitivity did not differ in the tertiles. In supine laboratory recordings, there were no differences in aortic systolic and diastolic blood pressure, heart rate, cardiac output and systemic vascular resistance. Extracellular water volume was higher in the highest versus lowest tertile of Na+ excretion. In regression analysis, body surface area and 24-h Na+ excretion were independent explanatory variables for extracellular water volume. No differences in urine Na+ excretion and extracellular water volume were found between normotensive and hypertensive participants. When compared with the 510 participants, patients with primary aldosteronism had 6.0% excess in extracellular water (p = .003), and 24-h Na+ excretion was not related with extracellular water volume. Conclusion In the absence of mineralocorticoid excess, Na+ intake, as evaluated from 24-h Na+ excretion, predominantly influences extracellular water volume without a clear effect on blood pressure.

Parathyroid hormone may play a role in the pathophysiology of primary hypertension.

Parathyroid hormone has been related with the risk of hypertension, but the matter remains controversial. We examined the association of parathyroid hormone with central blood pressure and its determinants in 622 normotensive or never-treated hypertensive subjects aged 19–72 years without diabetes, cardiovascular or renal disease, or cardiovascular medications. The methods were whole-body impedance cardiography and analyses of pulse wave and heart rate variability. Cardiovascular function was examined in sex-specific tertiles of plasma parathyroid hormone (mean concentrations 3.0, 4.3 and 6.5 pmol/L, respectively) during head-up tilt. Explanatory factors for haemodynamics were further investigated using linear regression analyses. Mean age was 45.0 (s.d. 11.7) years, BMI 26.8 (4.4) kg/m2, seated office blood pressure 141/90 (21/12) mmHg, and 309 subjects (49.7%) were male. Only five participants had elevated plasma parathyroid hormone and calcium concentrations. Highest tertile of parathyroid hormone presented with higher supine and upright aortic diastolic blood pressure (P < 0.01) and augmentation index (P < 0.01), and higher upright systemic vascular resistance (P < 0.05) than the lowest tertile. The tertiles did not present with differences in pulse wave velocity, cardiac output, or measures of heart rate variability. In linear regression analyses, parathyroid hormone was an independent explanatory factor for aortic systolic (P = 0.005) and diastolic (P = 0.002) blood pressure, augmentation index (P = 0.002), and systemic vascular resistance (P = 0.031). To conclude, parathyroid hormone was directly related to central blood pressure, wave reflection, and systemic vascular resistance in subjects without cardiovascular comorbidities and medications. Thus, parathyroid hormone may play a role in the pathophysiology of primary hypertension.

Leukocyte telomere length is inversely associated with arterial wave reflection in 566 normotensive and never-treated hypertensive subjects.

Telomeres are short segments in chromosome ends, the length of which is reduced during cell lifecycles. We examined the association of mean leukocyte telomere length (LTL) and short telomere proportion (STP) with hemodynamic variables in normotensive and never-treated hypertensive volunteers (n=566, 19-72 years). STP and mean LTL were determined using Southern blotting, and supine hemodynamics recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. The analyses were adjusted for age, body mass index (BMI), alcohol use, smoking, plasma chemistry, and estimated glomerular filtration rate (eGFR). In univariate analyses, mean LTL and STP both correlated with age, BMI, eGFR, aortic blood pressure, augmentation index, and pulse wave velocity (p<0.05 for all). Mean LTL also correlated with systemic vascular resistance (p<0.05). In linear regression analyses of all hemodynamic variables, mean LTL was only an independent explanatory factor for augmentation index (Beta -0.006, p=0.032), while STP was not an explanatory factor for any of the hemodynamic variables, in contrast to age, BMI and several cardiovascular risk factors. To conclude, augmentation index was predominantly related with chronological aging, but also with mean LTL, suggesting that this variable of central wave reflection is a modest marker of vascular biological aging.

Plasma total calcium concentration is associated with blood pressure and systemic vascular resistance in normotensive and never-treated hypertensive subjects

Purpose: The underlying causes of primary hypertension are not fully understood. Evidence on the relation of plasma calcium concentration with blood pressure (BP) is inconsistent and relies largely on studies utilizing office BP measurements in populations using cardiovascular drugs. In many studies adjustment for confounders was not optimal. In this cross-sectional study we examined the association of plasma total calcium concentration with the haemodynamic determinants of blood pressure.Subjects and methods: Supine haemodynamics were recorded using pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis in 618 normotensive or never-treated hypertensive subjects (aged 19–72 years) without diabetes, cardiovascular or renal disease, or cardiovascular medications. Linear regression analysis was used to investigate factors associated with haemodynamic variables.Results: Mean age was 45.0 years, body mass index 26.8 kg/m2, seated office BP 141/89 mmHg, and 307 subjects (49.7%) were male. Mean values of routine blood and plasma chemistry analyses were within the reference limits of the tests except for low-density lipoprotein cholesterol (3.05 mmol/l). In the laboratory, mean supine radial BP was 131/75 mmHg, and both systolic and diastolic BP correlated directly with plasma total calcium concentration (r = 0.25 and r = 0.22, respectively, p < 0.001 for both). In regression analysis plasma total calcium concentration was an independent explanatory variable for radial and aortic systolic and diastolic BP, and systemic vascular resistance, but not for cardiac output, pulse wave velocity, or any of the heart rate variability parameters.Conclusion: Plasma total calcium concentration was directly associated with systolic and diastolic BP and systemic vascular resistance in normotensive or never-treated hypertensive subjects without comorbidities and cardiovascular medications. Higher plasma calcium concentration potentially plays a role in primary hypertension via an effect on vascular resistance.

P36 Leukocyte Telomere Length is Inversely Associated with Wave Reflection in 566 Normotensive and Never-treated Hypertensive Subjects

BackgroundTelomeres are short segments in chromosome ends, the length of which is reduced during cell life-cycles. We examined the association of leukocyte telomere length and short telomere proportion with hemodynamic variables.MethodsAltogether 566 subjects (279 women and 287 men) without cardiovascular disease and medications with direct cardiovascular influences were subjected supine recordings for 5 minutes. Haemodynamics were captured using continuous tonometric pulse wave analysis and whole-body impedance cardiography. The analyses were adjusted for age, body mass index (BMI), alcohol use, smoking, plasma chemistry, and estimated glomerular filtration rate (eGFR).ResultsIn univariate analyses, leukocyte telomere length correlated with age, BMI, eGFR, aortic blood pressure, augmentation index, pulse wave velocity, and systemic vascular resistance (p < 0.05 for all). Short telomere proportion correlated with age, BMI, eGFR, aortic systolic blood pressure, augmentation index, and pulse wave velocity (p < 0.05 for all). In linear regression analyses of all hemodynamic variables, leukocyte telomere length was only an independent explanatory factor for augmentation index (Beta −0.006, p = 0.032), while short telomere proportion was not an explanatory factor for any of the hemodynamic variables, in contrast to age, BMI and several cardiovascular risk factors.ConclusionAugmentation index was predominantly related with chronological aging, but also with leukocyte telomere length, suggesting that this variable of central wave reflection is a moderate marker of vascular biological aging.

Atherogenic index of plasma is related to arterial stiffness but not to blood pressure in normotensive and never-treated hypertensive subjects

Background and aims: Atherogenic index of plasma (AIP), defined as the logarithm of triglycerides to high-density lipoprotein cholesterol (HDL-C) ratio, is a strong predictor of future cardiovascular disease. Our aim was to examine the association of AIP with haemodynamic variables in normotensive and never-treated hypertensive subjects in a cross-sectional study.Methods: Supine haemodynamics in 615 subjects without antihypertensive and lipid-lowering medications were examined using whole-body impedance cardiography and radial pulse wave analysis. Linear regression analysis was applied to investigate the association of AIP with haemodynamic variables and age, sex, body mass index (BMI), smoking status, alcohol consumption, plasma C-reactive protein, electrolytes, uric acid, low density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate, and quantitative insulin sensitivity check index.Results: The demographics and laboratory values of the study population were (mean ± 95% confidence interval): age 44.9 ± 1.0 years, BMI 26.8 ± 0.4 kg/m2, office blood pressure 140.6 ± 1.6/89.4 ± 1.0 mmHg, total cholesterol 5.2 ± 0.08, LDL-C 3.1 ± 0.08, triglycerides 1.2 ± 0.08, HDL-C 1.6 ± 0.04 mmol/l, and AIP −0.15 ± 0.02. Age (standardized coefficient Beta 0.508, p < .001) and aortic systolic blood pressure (Beta 0.239, p < .001) presented with the strongest associations with pulse wave velocity. However, AIP was also associated with pulse wave velocity (Beta 0.145, p < .001). AIP was not related with aortic or radial blood pressure, cardiac output, systemic vascular resistance, or augmentation index.Conclusions: AIP is directly and independently associated with arterial stiffness, a variable strongly related to cardiovascular risk. This supports more widespread use of AIP in standard clinical cardiovascular disease risk evaluation.

Sympathovagal balance and 1-h postload plasma glucose in normoglucose tolerant hypertensive patients.

Normoglucose tolerant (NGT) subjects with a 1-h postload plasma glucose (PLPG) value ≥155mg/dL have an increased risk of type-2 diabetes and subclinical organ damage. Heart rate variability (HRV) reflects cardiac autonomic balance, frequently impaired in course of diabetes. At this time, no data support the association between 1-h PLPG and HRV; thus, we investigated the possible association between 1-h PLPG and HRV. We enrolled 92 never-treated hypertensive subjects (56 women, 36 men), aged 55±9.8years. During OGTT, the patients underwent electrocardiographic recordings to evaluate HRV in the time domain (SDNN). Insulin sensitivity was assessed by Matsuda index. Among participants, 56 were NGT, 20 had impaired glucose tolerance (IGT), and 16 had type-2 diabetes. According to the 1-h PLPG cutoff point of 155mg/dL, we divided NGT subjects into: NGT<155 (n=38) and NGT≥155 (n=18). Glucose tolerance status was associated with a significant (P<0.0001) increase in PLPG and insulin and the reduction in Matsuda index. In all groups, the SDNN values significantly (P<0.0001) decreased during the first hour of OGTT. A complete recovery in NGT groups was observed at the end of the second hour; in IGT and type-2 diabetes, SDNN remained significantly lower with respect to baseline values. At multiple regression analysis, Matsuda index resulted in the only determinant of SDNN modification, explaining the 12.3% of its variability. Our data demonstrate that during OGTT, sympathovagal balance is acutely affected by both glucose and insulin modifications. Particularly, NGT≥155 subjects behave in the same way of IGT and type-2 diabetes patients.

A Randomized Controlled Study on the Effects of Bisoprolol and Atenolol on Sympathetic Nervous Activity and Central Aortic Pressure in Patients with Essential Hypertension

Objectiveβ-blockers (BBs) with different pharmacological properties may have heterogeneous effects on sympathetic nervous activity (SNA) and central aortic pressure (CAP), which are independent cardiovascular factors for hypertension. Hence, we analyzed the effects of bisoprolol and atenolol on SNA and CAP in hypertensive patients.MethodsThis was a prospective, randomized, controlled study in 109 never-treated hypertensive subjects randomized to bisoprolol (5 mg) or atenolol (50 mg) for 4–8 weeks. SNA, baroreflex sensitivity (BRS) and heart rate (HR) variability (HRV) were measured using power spectral analysis using a Finometer. CAP and related parameters were determined using the SphygmoCor device (pulse wave analysis).ResultsBoth drugs were similarly effective in reducing brachial BP. However, central systolic BP (−14±10 mm Hg vs −6±9 mm Hg; P<0.001) and aortic pulse pressure (−3±10 mm Hg vs +3±8 mm Hg; P<0.001) decreased more significantly with bisoprolol than with atenolol. The augmentation index at a HR of 75 bpm (AIxatHR75) was significantly decreased (29%±11% to 25%±12%; P = 0.026) in the bisoprolol group only. Furthermore, the change in BRS in the bisoprolol group (3.99±4.19 ms/mmHg) was higher than in the atenolol group (2.66±3.78 ms/mmHg), although not statistically significant (P>0.05). BRS was stable when RHR was controlled (RHR≤65 bpm), and the two treatments had similar effects on the low frequency/high frequency (HF) ratio and on HF.ConclusionBBs seem to have different effects on arterial distensibility and compliance in hypertensive subjects. Compared with atenolol, bisoprolol may have a better effect on CAP.Trial RegistrationClinicalTrials.gov NCT01762436

One‐hour post‐load plasma glucose and IGF‐1 in hypertensive patients

In normoglucose-tolerant subjects (NGT), 1-h post-load plasma glucose value ≥155 mg/dL, during an oral glucose tolerance test (OGTT), is associated with an increased risk of type-2 diabetes (T2D) and subclinical organ damage. Insulin-like growth factor-1 (IGF-1) is involved in the pathogenesis of insulin resistance (IR) and T2D. Moreover, hypertensives have different degrees of IR and different levels of IGF-1. Actually, there are no data supporting the association between post-load glucose and IGF-1; thus, the aim of the study was to investigate this relationship. We enrolled 1126 never-treated hypertensive subjects who underwent an OGTT and clinical characterization. Insulin sensitivity was assessed by the Matsuda index. IGF-1 was measured by a sensitive immunoradiometric assay. Among participants, 764 had NGT, 263 had impaired glucose tolerance (IGT) and 99 had T2D. According to the 1-h post-load plasma glucose cut-off point of 155 mg/dL, we divided NGT subjects into NGT < 155 mg/dL and NGT ≥ 155 mg/dL. NGT ≥ 155 in comparison with NGT < 155 had significantly reduced insulin sensitivity and IGF-1 levels. At multiple regression analysis, IGF-1 was the major determinant of 1-h post-load glucose in NGT ≥ 155 subjects, IGT and diabetics, accounting for 20·9%, 17·7% and 15·5% of its variation in the respective models. In hypertensive NGT ≥ 155 subjects, IGF-1 results strongly associated with 1-h post-load glucose, similarly to that observed in IGT and diabetics. This finding has clinical relevance because both low IGF-1 levels and 1-h post-load glucose in NGT subjects are associated with subclinical organ damage, an independent predictor of cardiovascular events.

Echocardiographic Abnormalities in the Assessment of Cardiac Organ Damage in Never-Treated Hypertensive Patients

Hypertension-related cardiac organ damage, other than left ventricular (LV) hypertrophy (LVH), has been described: in particular, concentric remodeling, LV diastolic dysfunction (DD), and left atrial (LA) enlargement are significantly associated with cardiovascular morbility and mortality in different populations. This study evaluated the prevalence of these latter morphofunctional abnormalities, in never-treated essential hypertensive patients and the role of such a serial assessment of hypertensive cardiac damage in improving cardiovascular risk stratification in these patients. A total of 100 never-treated essential hypertensive subjects underwent a complete clinical and echocardiographic evaluation. Left ventricular morphology, systolic and diastolic function, and LA dimension (linear and volume) were evaluated by echocardiography. Left ventricular hypertrophy was present in 14% of the patients, whereas concentric remodeling was present in 25% of the subjects. Among patients free from LV morphology abnormalities, the most frequent abnormality was LA enlargement (global prevalence 57%); the percentage of patients with at least one parameter consistent with DD was 22% in the entire population, but DD was present as the only cardiac abnormality in 1% of our patient. Left atrial volume indexed for body surface area was the most sensitive parameter in identifying hypertension-related cardiac modification. The global prevalence of cardiac alteration reached 73% in never-treated hypertensive patients. Left ventricular remodeling and LA enlargement evaluation may grant a better assessment of cardiac organ damage and cardiovascular risk stratification of hypertensive patients without evidence of LVH after routine examination.

Early adverse effect of abnormal glucose metabolism on arterial stiffness in drug naïve hypertensive patients

Arterial stiffness is independently related to increased cardiovascular risk in the hypertensive population. The aim of the present study was to investigate whether various stages of abnormal glucose metabolism may differently affect arterial stiffness in hypertensive patients and whether there is any difference in arterial stiffness among patients with normal glucose regulation. We studied 1375 never-treated hypertensive subjects. Participants were divided into four metabolic groups: normal glucose regulation (NG), impaired fasting glucose, impaired glucose tolerance and type-2 diabetes mellitus (DM 2). Hypertensive subjects with NG were subdivided into three groups according to glucose levels. Arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV). PWV showed a significant increase from patients with NG to DM 2 (from 7.74 ± 1.38 to 8.40 ± 1.30 to 8.86 ± 1.30 to 10.09 ± 2.07 m/s respectively, p<0.001). Among hypertensive subjects with NG there was an increase in PWV from low normal to high normal values of glucose (p<0.01). PWV was independently related to all glucose metabolic parameters (p<0.001 for all). In the present study, we demonstrated an association between arterial stiffness and glucose tolerance in hypertensive subjects. Given the prognostic significance of arterial stiffness, aims should be towards closer monitoring and intensive care of hypertensive patients with abnormal glucose metabolism.

Association between home arterial stiffness index and target organ damage in hypertension: Comparison with pulse wave velocity and augmentation index

ObjectivesTo clarify the implications of the home arterial stiffness index (HASI), we compared HASI with other arterial stiffness measures and investigated the association between HASI and hypertensive target organ damage (TOD). MethodsWe assessed brachial–ankle pulse wave velocity (baPWV) and the carotid augmentation index (cAIx) as measures of arterial stiffness and wave reflection, and the left ventricular mass index (LVMI), carotid intima-media thickness (IMT) using ultrasonography, and the urinary albumin/creatinine ratio (UACR) as measures of TOD in 356 never-treated hypertensive subjects. Home blood pressure (BP) was taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. HASI was defined as 1 minus the respective regression slope of diastolic on systolic BP. ResultsHASI was significantly correlated with age (r=0.32, P<0.001), home pulse pressure (r=0.36, P<0.001), morning–evening difference in home systolic BP (r=−0.29, P<0.001), baPWV (r=0.18, P<0.001), cAIx (r=0.16, P=0.002), carotid IMT (r=0.26, P<0.001), and UACR (r=0.24, P<0.001), but not with LVMI (r=0.05, P=0.38). After adjustment for age and sex, the significant correlation between HASI and baPWV/cAIx was lost. In multivariate regression analyses, HASI and baPWV were significantly associated with carotid IMT (standardized β=0.21, P<0.001; β=0.14, P=0.014) and UACR (β=0.13, P=0.018; β=0.21, P<0.001), independently of age, sex, and home mean arterial pressure. On the other hand, cAIx was independently associated only with LVMI (β=0.24, P<0.001). ConclusionThese findings indicate that HASI adds nothing to the existing measures of arterial stiffness, but might be a BP component that can aid in the detection of carotid atherosclerosis and renal damage, similar to PWV.

One-Hour Postload Plasma Glucose Levels and Diastolic Function in Hypertensive Patients

OBJECTIVETo address whether glucose tolerance status, and in particular 1-h postload plasma glucose levels, may affect diastolic function in 161 never-treated hypertensive white subjects. Impaired left ventricular relaxation, an early sign of diastolic dysfunction, represents the first manifestation of myocardial involvement in diabetic cardiomyopathy. A plasma glucose value ≥155 mg/dL for the 1-h postload plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high risk for type 2 diabetes and with subclinical organ damage.RESEARCH DESIGN AND METHODSSubjects underwent OGTT and standard echocardiography. Diastolic function was assessed by pulsed Doppler transmitral flow velocity and tissue Doppler imaging. Insulin sensitivity was assessed by Matsuda index.RESULTSAmong the participants, 120 had NGT, 26 had impaired glucose tolerance (IGT), and 15 had type 2 diabetes. According to the 1-h postload plasma glucose cutoff point of 155 mg/dL, we divided NGT subjects as follows: NGT <155 mg/dL (n = 90) and NGT ≥155 mg/dL (n = 30). Those with NGT ≥155 mg/dL had higher left atrium dimensions (P < 0.0001) and isovolumetric relaxation time (IVRT) (P = 0.037) than those with NGT <155 mg/dL. By contrast, early/late transmitral flow velocity and all tissue Doppler parameters were significantly lower in those with NGT ≥155 mg/dL than in those with NGT<155 mg/dL. At multiple regression analysis, 1-h glucose was the major determinant of left atrium area, IVRT, septal e′, septal e′-to-a′ ratio, lateral e′, and lateral e′-to-a′ ratio.CONCLUSIONSThe main finding of this study is that 1-h postload plasma glucose is associated with left ventricular diastolic dysfunction. Subjects with NGT ≥155 mg/dL had significantly worse diastolic function than those with NGT<155 mg/dL.

One-Hour Postload Plasma Glucose Levels and Left Ventricular Mass in Hypertensive Patients

OBJECTIVELeft ventricular hypertrophy (LVH), an independent risk factor for cardiovascular (CV) morbidity and mortality, recognizes a multifactorial pathogenesis. A plasma glucose value ≥155 mg/dL for the 1-h postload plasma glucose during an oral glucose tolerance test (OGTT) identifies subjects with normal glucose tolerance (NGT) at high risk for type 2 diabetes. We addressed the question if glucose tolerance status, particularly 1-h postload plasma glucose levels, affects left ventricular mass (LVM) and cardiac geometry in essential hypertension.RESEARCH DESIGN AND METHODSWe enrolled 767 never-treated hypertensive subjects, 393 women and 374 men (mean age 49.6 ± 8.5 years). All patients underwent an OGTT for the evaluation of glucose tolerance and standard echocardiography. LVM was calculated using the Devereux formula and normalized by body surface area (LVM index [LVMI]). Insulin sensitivity was assessed by the Matsuda index. Among all participants, 514 had NGT, 168 had impaired glucose tolerance (IGT), and 85 had type 2 diabetes. According to the 1-h postload plasma glucose cutoff point of 155 mg/dL, we divided normotolerant subjects into two groups: NGT <155 mg/dL (n = 356) and NGT ≥155 mg/dL (n = 158).RESULTSSubjects in the NGT ≥155 mg/dL group had worse insulin sensitivity than subjects in the NGT <155 mg/dL group (Matsuda index 63.9 vs. 88.8; P < 0.0001). Men with NGT ≥155 mg/dL had a higher LVMI than men with NGT <155 mg/dL (126.6 vs. 114.3 g/m2; P = 0.002) and a different LVH prevalence (41.1 vs. 25.8%; P < 0.0001). At multiple regression analysis, 1-h glucose resulted in the major determinant of LVMI in normotolerant, IGT, and diabetic groups.CONCLUSIONSThese data show that NGT ≥155 mg/dL subjects, compared with NGT <155 mg/dL subjects, have a higher LVMI and a greater prevalence of LVH similar to that of IGT and diabetic patients.

Maximum Value of Home Blood Pressure

The maximum office systolic blood pressure (SBP) has been shown to be a strong predictor of cardiovascular events, independently of the mean SBP level. However, the clinical implications of maximum home SBP have never been reported. We investigated the association between the maximum home SBP and target organ damage (TOD). We assessed the left ventricular mass index (LVMI) and carotid intima-media thickness (IMT) using ultrasonography and the urinary albumin/creatinine ratio (UACR) as measures of TOD in 356 never-treated hypertensive subjects. Home BP was taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. The maximum home SBP was defined as the maximum mean triplicate BP reading in the 14-day period for each individual and was significantly correlated with LVMI (r=0.51, P<0.001), carotid IMT (r=0.40, P<0.001), and UACR (r=0.29, P<0.001). The correlation coefficients with LVMI and carotid IMT were significantly larger for the maximum home SBP than the mean home SBP. In multivariate regression analyses, the maximum home SBP was independently associated with LVMI and carotid IMT, regardless of the mean home BP level. In the prediction of left ventricular hypertrophy and carotid atherosclerosis, the goodness-of-fit of the model was significantly improved when the maximum home SBP was added to the sum of the mean office and home BPs (P=0.002 and P<0.001, respectively). These findings indicate that assessment of the maximum home SBP, in addition to the mean home SBP, might increase the predictive value of hypertensive TOD in the heart and artery.

Exercise in hypertension: do skeletal muscle reflexes make this a dangerous proposition?

the benefits of exercise and exercise training are numerous, varying from increasing skeletal muscle strength to enhancing cardiovascular and respiratory fitness. These attributes of exercise are key elements to the maintenance of good health and the improvement of athletic performance. But are

PULSE WAVE VELOCITY AND AUGMENTATION INDEX ARE ASSOCIATED WITH 10-YEAR GENERAL CARDIOVASCULAR RISK AND HEART/VASCULAR AGE IN NEWLY DIAGNOSED, NEVER-TREATED HYPERTENSION: 6D.05

Background: The Framingham Heart Study group has proposed an algorithm for calculating the 10-year risk of developing cardiovascular disease (CVD) and heart/vascular age. The predictors used are age, diabetes, smoking, systolic blood pressure, total and high density cholesterol. We investigated the association of 10-year CVD risk, heart/vascular age with indices of arterial function, which are not currently included as predictors in the algorithm, in a cohort of newly diagnosed, never-treated hypertensive subjects. Methods: 1145 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 54 years, 670 men). Carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx) were measured. The general cardiovascular risk profile algorithm proposed by the Framingham Heart Study group was used in order to calculate the 10-year risk of developing CVD. Heart/vascular age was similarly calculated. Results: cfPWV positively correlated with 10-year general CVD risk (r = 0.451, P < 0.001) and heart/vascular age (r = 0.401, P < 0.001). This was also the case for AIx, as it correlated with 10- year general CVD risk (r = 0.173, P < 0.001) and heart/vascular age (r = 0.414, P < 0.001). Conclusion: Aortic stiffness and wave reflections are associated with 10-year general CVD risk and heart/vascular age in never treated hypertensives. This finding underscores the importance of cfPWV and AIx assessment in the setting of newly diagnosed, never treated hypertension, as predictors of future CVD events.

Low-Plasma Insulin-Like Growth Factor-I Levels Are Associated with Impaired Endothelium-Dependent Vasodilatation in a Cohort of Untreated, Hypertensive Caucasian Subjects

Accumulating evidence suggests that IGF-I has protective vascular effects, supporting the possibility that IGF-I deficiency may contribute to atherosclerosis. However, the relationship between plasma IGF-I levels and endothelium-dependent vasodilatation is still unsettled. We designed this present study to test the hypothesis that low-plasma IGF-I levels are associated with reduced endothelial function independently classical cardiovascular risk factors. Outpatients were included in the study. A total of 100 never-treated hypertensive Caucasian subjects participating in the CAtanzaro MEtabolic RIsk factors Study was recruited. Subjects underwent forearm blood flow (FBF) evaluation by strain-gauge plethysmography in response to increasing doses of acetylcholine (ACh) (Sigma, Milan, Italy) and sodium nitroprusside (Malesci, Florence, Italy). Insulin sensitivity was estimated by the homeostasis model assessment index. Plasma IGF-I levels were significantly correlated with age (r = -0.300; P = 0.001), high-density lipoprotein serum cholesterol (r = 0.211; P = 0.017), homeostasis model assessment index (r = -0.355; P <0.0001), systolic blood pressure (r = -0.174; P = 0.042), glomerular filtration rate (r = 0.228; P = 0.011), and ACh-stimulated FBF (r = 0.565; P <0.0001). In a stepwise forward multivariate regression analysis, the strongest predictors of ACh-stimulated FBF response were plasma IGF-I levels, accounting for 31.9% of its variation. These results demonstrate, for the first time, that low-plasma IGF-I levels are highly associated with reduced endothelial function, an early step in atherogenesis process.

A comparison of atenolol and nebivolol in isolated systolic hypertension

Some beta-blockers are less effective in reducing central blood pressure than other antihypertensive drugs, which may explain the higher rate of events in subjects randomized to atenolol in recent trials. We hypothesized that nebivolol, a mixed beta-blocker/nitro-vasodilator, would be more effective than atenolol in reducing central blood pressure and augmentation index (AIx). The aim of the present study was to test this in a double-blind, randomized, cross-over study, in a cohort of subjects with isolated systolic hypertension. Following a 2-week placebo run-in, 16 never-treated hypertensive subjects received atenolol (50 mg), nebivolol (5 mg) and placebo, each for 5 weeks, in a random order. Seated brachial blood pressure and heart rate were measured. Aortic blood pressure, AIx and pulse wave velocity (PWV) were assessed non-invasively. The placebo-corrected fall in brachial pressure was similar between nebivolol and atenolol, as was the reduction in PWV (mean change +/- SEM: -1.0 +/- 0.3 and -1.2 +/- 0.2 m/s; P = 0.2). However, there was less reduction in heart rate (-19 +/- 2 versus -23 +/- 2 beats/min; P < 0.01) and increase in AIx (+6 +/- 1 versus +10 +/- 1%; P = 0.04), following nebivolol. Aortic pulse pressure was significantly lower (50 +/- 2 versus 54 +/- 2 mmHg; P = 0.02) after nebivolol. N-terminal pro-B-type natriuretic peptide (proBNP) rose on both drugs (100 +/- 33 versus 75 +/- 80 pg/ml; P < 0.01 for both, NS for comparison). Nebivolol and atenolol have similar effects on brachial blood pressure and aortic stiffness. However, nebivolol reduces aortic pulse pressure more than atenolol, which may be related to a less pronounced rise in AIx and bradycardia. Whether this will translate into differences in clinical outcome requires further investigation.

Increased mechanoreceptor/metaboreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure

The following letters are in response to the Point:Counterpoint series “Increased mechanoreceptor/metaboreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure” that appears in this issue. To the Editor: The Point:Counterpoint concerning the issue of