Risk for cardiac involvement in essential hypertension

The evidence is inescapable that even mild essential hypertension is associated with left ventricular hypertrophy, regardless of the age of the patient. Increased left ventricular afterload must play a major role in the pathogenesis of the hypertrophy; however, further proof of this awaits our improved understanding of the quantitation of afterload in the clinical setting. Other factors, including the adrenergic nervous system and blood viscosity, may play an additional role, possibly mediated through alterations in afterload or by direct myocardial action. Left ventricular hypertrophy exerts a positive benefit by normalizing wall stress in patients with hypertension. Especially in patients without coexistent coronary abnormalities, systolic function is normal and abnormalities of diastolic function are of uncertain clinical importance. Because echocardiography now provides a convenient and sensitive noninvasive means of following patients with left ventricular hypertrophy, long-term studies are now needed to document the incremental risk (or benefit) of left ventricular hypertrophy over blood pressure itself in the eventual morbidity of essential hypertension. The recognition of left ventricular hypertrophy in a patient with borderline elevation of blood pressure poses a new clinical dilemma. Should treatment be instituted based on this additional finding? In view of the data correlating stress, exercise, and mean daily blood pressure with left ventricular hypertrophy and the reduction of left ventricular mass following lowering of blood pressure, it has been our practice to treat patients with left ventricular hypertrophy more readily than those without left ventricular hypertrophy. The rationale in this approach is not that left ventricular hypertrophy per se is harmful, but rather that it indicates a greater degree of afterload than may be evident from office blood pressure measurements.     

Non-invasive signs of cardiac involvement in essential hypertension

The relationship between various non-invasive signs of hypertensivecardiac involvement and blood pressure (BP) was studied in 120middle-aged men recruited from a BP-screening of a random populationsample. The men, representing a wide range of BP, were dividedinto four BP groups (normotensive, and borderline, mild andmoderate-severe hypertension), and were investigated by conventionalelectrocardiography (ECG), chest X-ray, echocardiography, apexcardiography/phonocardiographyand corrected orthogonal ECG. In the hypertensive groups a lower proportion of subjects withsigns of cardiac involvement were identified by conventionalECG and chest X-ray than by the other methods. A significantassociation between the prevalence of pathological findingsand level of blood pressure (P < 0.05–0.01) was foundfor conventional and corrected orthogonal ECG and apexcardiography/phonocardiography.With echocardiography, concomitant increased thickness (>12 mm) of both the interventricular septum and left ventricularposterior wall, but not of one structure alone, was significantlyassociated with BP (P < 0.05). In borderline subjects, pathological findings were surprisinglycommon. However, many of these subjects had single abnormalities,whereas those with higher BP had an increasing degree of multiplepathological findings. We conclude that in many hypertensives there are signs of cardiacinvolvement that can be revealed by means of sensitive non-invasivemethods. Single signs can be revealed in mild hypertension butthe number and severity of the different abnormalities increases(dramatically) with increasing BP. It is probable that thesevarious types of cardiac involvement carry prognostic informationthat could help in treatment decisions.     

Renal involvement follows cardiac enlargement in essential hypertension

To assess the relationship between early clinically detectable involvement of hypertensive vascular disease in heart and kidneys, we obtained systemic and renal hemodynamic and M-mode echocardiographic measurements in 65 patients with essential hypertension. The results indicate that patients with and without left ventricular hypertrophy had similar renal hemodynamic findings. In contrast, patients with altered renal hemodynamic measurements (ie, reduced renal distribution of cardiac output and, therefore, absolute renal blood flow with increased renal vascular resistance) and increased serum uric acid levels also had increased left ventricular posterior and septal wall thicknesses and mass index. Moreover, these data also demonstrated that in patients with altered renal hemodynamics, the lower the renal distribution of cardiac output and the higher the serum uric acid levels, the greater were the indexes of cardiac enlargement. These results demonstrated that the pathophysiological and hemodynamic effects of essential hypertension in the heart precede those in the kidneys.     

Determinants of inappropriate circadian blood pressure variability in children with essential hypertension

BACKGROUND:

Inappropriate daily profile of blood pressure deteriorates the clinical outcome of hypertension and increases distant cardiovascular risk. The problem is important, especially in children and adolescents in whom early intervention helps to prevent complications of hypertension such as left ventricular hypertrophy and hypertensive retinopathy.

OBJECTIVES:

To assess circadian blood pressure profile and basic determinants of inappropriate daily blood pressure variability in hypertensive children.

METHODS:

The project was conducted retrospectively in 106 children six to 18 years of age (mean [± SD] 14.9±2.5 years) with essential hypertension and no use of antihypertensive drugs. The study group included 43 children with inappropriate daily blood pressure variability (‘nondippers’) and 63 controls with appropriate daily blood pressure variability (‘dippers’).

RESULTS:

Nondippers, compared with dippers, had higher systolic and diastolic blood pressure at night (systolic, 123.9±10.3 mmHg versus 113.9±8.2 mmHg; diastolic, 65.1±7.6 mmHg versus 59.5±6.5 mmHg; P<0.0001), and higher blood pressure load at night (systolic, 61.9% versus 27.6%; diastolic, 20.0% versus 9.6%; P<0.0001). Male sex increased the risk for nondipping by 2.5 times (logistic OR=2.45; 95% CI 0.87 to 6.87). However, the increase was statistically nonsignificant (P=0.08). No differences were observed between dippers and nondippers in terms of anthropometric profile, family history of hypertension, morphological and biochemical blood parameters, and birth weight.

CONCLUSIONS:

Among hypertensive children, nondippers have a more severe degree of hypertension. Male sex increases the risk of nondipping. To assess determinants of nondipping more precisely, further clinical investigations are needed.     

Dietary salt intake. A determinant of cardiac involvement in essential hypertension

Because a given increase in afterload does not consistently produce the same degree of left ventricular hypertrophy, we evaluated several clinical, hemodynamic, and endocrine factors that are prone to modify the adaptation of left ventricular structure in patients with mild essential hypertension (World Health Organization stages I or II). Dietary salt intake assessed by sodium excretion over 24 hours was a powerful determinant of posterior wall thickness (r = 0.64, p less than 0.001), relative wall thickness (r = 0.67, p less than 0.001), and left ventricular mass (r = 0.37, p less than 0.05). In contrast, diastolic pressure, body mass index, hematocrit, and epinephrine were found to be weaker determinants of left ventricular structure (r = 0.31-0.40, p less than 0.05). A stepwise multiple regression analysis revealed that sodium excretion was the strongest predictor for posterior wall thickness (p less than 0.02) and relative wall thickness (p less than 0.05) independent of the other examined variables. These results identify dietary salt intake as a strong determinant of cardiac structural adaptation to a persistent increase in arterial pressure. Consequently, a high salt intake might aggravate and, conversely, dietary salt restriction might prevent (or at least mitigate) the development of left ventricular hypertrophy in patients with essential hypertension.     

Determinants of platelet activation in human essential hypertension

Experimental data suggest that oxidative stress might be enhanced in hypertension and contribute to platelet activation. We hypothesized that both oxidative stress and platelet activation could be related to the clinical characteristics of hypertensive patients. The urinary excretion of 11-dehydrothromboxane (TX) B2, reflecting in vivo platelet activation, was measured in 75 patients with mild to severe essential hypertension and 75 pair-matched, healthy controls. The urinary excretion of 8-iso-prostaglandin (PG) F2alpha was determined as an index of in vivo lipid peroxidation. Urinary 11-dehydro-TXB2 was significantly higher in essential hypertensives compared with controls. Although no statistically significant difference in urinary 8-iso-PGF2alpha was observed between patients and controls, plasma vitamin C was lower and plasma homocysteine higher in hypertensive patients than in controls. Both urinary 11-dehydro-TXB2 and 8-iso-PGF2alpha were higher in patients with advanced hypertensive retinopathy compared with patients without retinopathy. Multivariate linear regression analysis identified urinary 8-iso-PGF2alpha, plasma fibrinogen, homocysteine, and vitamin E as the only variables independently correlated with urinary 11-dehydro-TXB2. Logistic regression analysis showed that high urinary 8-iso-PGF2alpha, plasma fibrinogen, and homocysteine, as well as low plasma vitamin E, advanced retinopathy, elevated diastolic blood pressure, and the absence of antihypertensive treatment, were predictors of high urinary 11-dehydro-TXB2. We demonstrated increased oxidative stress and persistent platelet activation in essential hypertensives with advanced vascular lesions. These findings might help identify hypertensive patients who are at increased risk of cardiovascular events and who might benefit from long-term antiplatelet therapy.     

Determinants of arterial stiffness in offspring of families with essential hypertension

BACKGROUND: Arterial stiffness may be an early marker for vascular changes associated with hypertension in young adults. We investigated whether arterial stiffness measured as augmentation index and pulse wave velocity is increased in offspring of families with essential hypertension, and whether stiffness is related to various biochemical markers. METHODS: Two groups of subjects were investigated: offspring of families with essential hypertension (mean age 39 years), and normotensive control subjects (mean age 43 years). Pulse wave analysis was used to estimate augmentation index (AIx, %). Brachial pulse wave velocity (PWV, m/sec), blood pressure, homocysteine, and creatinine were determined by standard methods. RESULTS: The offspring had significantly higher systolic, diastolic, mean arterial pressures, as well as higher homocysteine, creatinine, and glucose levels compared with normotensive control subjects. Augmentation index, but not brachial pulse wave velocity, was significantly higher in offspring (P = .010) compared with control subjects. This group difference in AIx was evident in a regression model that corrected for the known cardiovascular risk factors (P = .027). In all subjects, homocysteine associated positively with brachial PWV (r = 0.15, P < .01) and negatively with AIx (r = -0.12, P < .05). AIx also associated inversely with creatinine in the whole group (r = -0.34; P < .001) and in offspring (r = -0.38; P < .001) only. A significant positive correlation was also observed between homocysteine and creatinine in all subjects (r = 0.30; P < .001), in men (r = 0.23; P < .05) and women (r = 0.26; P < .005), respectively. CONCLUSION: These data suggests that large artery abnormalities may be present early in subjects likely to develop hypertension.     

Determinants of circadian blood pressure rhythm in essential hypertension

It has been postulated that the lack of nocturnal blood pressure fall in patients called nondippers is associated with more serious end organ damages by hypertension than in dippers whose blood pressure falls during the night. Recently, we found that sodium restriction shifted circadian rhythm of blood pressure from that of a nondipper to a dipper in patients with essential hypertension. In the present study, we aimed to clarify these important findings from the different approaches, and examined which factors affected the diurnal rhythm of blood pressure. A total of 70 patients with essential hypertension were maintained on high and low sodium diets for 1 week each. Nocturnal fall in mean arterial pressure was calculated in each patient, and, based on multiple regression analysis, independent factors affecting this nocturnal fall were examined. Thirty-eight patients were classified as non–sodium-sensitive, whereas 32 were considered sodium sensitive, based on a >10% change in 24-h mean arterial pressure by sodium restriction. In all 70 patients, sodium sensitivity of blood pressure, as well as an interaction between sodium sensitivity and sodium restriction, were identified as independent factors affecting the nocturnal fall. In sodium-sensitive types, in addition to sodium restriction, glomerular filtration rate was identified, whereas, in non–sodium sensitive types, there was no significant factor.Based on multiple regression analysis, the present study reached the same important conclusion as our previous findings: namely, that the enhanced sodium sensitivity was an independent determinant for the diminished nocturnal fall in essential hypertension and that sodium restriction could restore the nocturnal decline, especially in patients with enhanced sodium sensitivity whose nocturnal decline was diminished. Reduced renal sodium excretory capability may be one of the mechanisms involved in nondipping.     

Blood pressure variability in children with essential hypertension

The aim of this study was to assess blood pressure variability (BPV) and its determinants in untreated hypertensive children. The study group consisted of 124 children, 91 boys and 33 girls, aged 14.9+/-2.5 with essential hypertension and no use of antihypertensive drugs. The subjects underwent routine examination, blood tests and ambulatory blood pressure (BP) monitoring. BPV was defined as the value of the standard deviation of BP for day- and night time periods. Daytime BPV was higher than night time BPV, and systolic BPV was higher than diastolic BPV. Significant positive correlations between 24-h, day- and night time systolic blood pressure (SBP), but not for diastolic blood pressure (DBP), and BPV were observed. In univariate analysis, day- and night time systolic BPVs were correlated with fasting glucose (r=0.609, P=0.02 and r=0.439, P=0.04); daytime systolic BPV, daytime diastolic BPV and night time systolic BPV were correlated with birth length (r=0.428, P=0.04; r=0.426, P=0.04 and r=0.439, P=0.04, respectively), and night time systolic BPV and night time diastolic BPV were correlated with age (r=0.604, P=0.02 and r=0.833, P=0.0001). However, in multiple linear regression analysis, daytime diastolic BPV was determined only by gender and systolic 24-h BP; night time systolic BPV depended on age, daytime SBP and DBP values, and daytime SBP and DBPs were determinants of night time diastolic BPV. The results highlighted the complex nature of BPV, with favourable role of host factors in its aetiology. The determinants of BPV in children are consistent with those in adults. Relationships between BPV and its determinants in untreated hypertensive subjects ought to be investigated in further researches.     

Determinants of early atherosclerosis in obese children and adolescents

CONTEXT: Obesity in childhood is associated with an increased mortality due to cardiovascular (CV) diseases in adulthood, independent of adult weight. Recent studies in children indicate that the atherosclerosis process starts at an early age and is linked to obesity. OBJECTIVE: The aim of the study was to investigate determinants of increased carotid intima-media thickness (IMT), an early marker of atherosclerosis, in obese children. DESIGN: A total of 104 obese children [age, 12.7 +/- 0.2 yr; body mass index (BMI)-z-score, 2.8 +/- 0.7] underwent an oral glucose tolerance test. Fasting levels of glucose, insulin, C-reactive protein and adhesion molecules (sICAM, sVCAM, sE-selectin), lipid profile, adiponectin, and resistin were determined. IMT was measured by ultrasound. Insulin resistance was estimated by the homeostatic model assessment index. Baseline measurements of blood parameters were obtained from 93 nonobese children (age, 13.0 +/- 0.2 yr; BMI-z-score, -0.2 +/- 0.9), and IMT was measured in 23 other control children with similar characteristics. RESULTS: Univariate analysis showed a significant positive correlation between IMT and relative BMI, the degree of systolic hypertension, fasting insulin levels, homeostatic model assessment-R index, and resistin concentrations, whereas an inverse correlation with adiponectin levels was found. No correlation was obtained between IMT and classical CV risk factors such as positive familial history of type 2 diabetes or precocious CV disease, visceral obesity, or the lipid profile. C-reactive protein and adhesion molecule levels were not associated with IMT in our obese population. When controlled for sex, Tanner stage, and relative BMI, only adiponectin levels remained an independent determinant of IMT. CONCLUSION: Adiponectin more than conventional CV risk factors and inflammation status may be related to early atherosclerosis in obese children.     

Control of cardiac output in essential hypertension

Cardiac and renal hemodynamics and cardiopulmonary and total blood volume were determined in 202 men, 101 with normotension and 101 of the same age with chronic essential hypertension, normal renal function and balanced sodium intake and urinary output. Cardiac output was identical in the two groups, whereas blood pressure and total peripheral resistance were significantly different. The two groups exhibited strong differences in the correlation study: (1) Correlations of blood pressure with, respectively, heart rate, cardiopulmonary blood volume and total blood volume were significant in the normotensive group but not in the hypertensive group. (2) Correlations of cardiac output with, respectively, heart rate, cardiopulmonary blood volume and total blood volume were significant in both groups. (3) Correlations of renal blood flow with, respectively, cardiac output, blood pressure and total blood volume were significant in the hypertensive group but not in the normotensive group.This study provides evidence that: (1) the volume and neural control of blood pressure are disrupted in hypertension whereas control of cardiac output is maintained; and (2) adaptive mechanisms involving renal function are necessary to the maintenance of normal cardiac output in patients with essential hypertension.     

Vasorenal hypertension in children and adolescents]

From among child-patients examined by the authors 41 were found to suffer from hypertension of vaso-renal genesis (58.5%). Major diagnostic tests were: functional intravenous urography, radioisotope renography, scintigraphy, angiography of the kidneys and also determination of the renin activity in the venous renal blood. The sole effective method of treating patients with vaso-renal hypertension is surgery.     

肥胖与原发性高血压患者心肌肥厚的相关性分析

目的　探讨肥胖对原发性高血压患者心肌肥厚的影响。方法　回顾性分析2012年1月至2015年12月于我院就诊的280例原发性高血压患者,按照国际糖尿病联盟设定的亚洲人肥胖的诊断标准,其中肥胖组130例,对照组150例。通过二维引导的M模式进行测量记录左心室结构,计算左心室质量指数及左室肥厚在两组患者中的发生率,应用多元线性逐步回归分析患者的年龄、性别、收缩压、舒张压、平均血压、脉压差,体质指数、血糖、糖化血红蛋白、TC、TG、LDL-C、HDL-C、肌酐、尿酸与心肌肥厚的相关性。结果　肥胖组患者的左心室质量指数显著高于对照组,且左室肥厚的发生率明显高于对照组,差异具有统计学意义(Ｐ<0.05)。患者的体重指数、血压、血糖、糖化血红蛋白、TC、TG、LDL-C及HDL-C与心肌肥厚相关。结论 除血压因素外,肥胖与高血压患者的左室肥厚发生密切相关,差异具有统计学意义(Ｐ<0.05)。     

High-sensitivity cardiac troponin T in essential hypertension

Background

Myocyte injury might be involved in the progression of essential hypertension (EHT) toward heart failure (HF). However, in the absence of high-sensitivity (hs) assay, cardiac troponin T (TnT) in EHT has not been measurable.

Methods and results

We studied 236 consecutive ambulatory patients (mean age = 65.5 years; 110 men) with treated EHT (mean systolic blood pressure = 134.3 mmHg, mean serum N-terminal pro-B-type natriuretic peptide = 86.6 pg/ml) for mean 65.6 months. Patients with a history of HF were excluded. Single and multiple variable analyses were performed in search of clinical correlates of elevated hs-TnT (≥0.003 ng/ml).Serum concentration of hs-TnT was ≥0.003 ng/ml (mean = 0.008 ng/ml) in 184 patients. By single variable analysis, age, uric acid, log-transformed N-terminal pro-B-type natriuretic peptide, brachial-ankle pulse wave velocity, Cornell electrocardiographic (ECG) voltage, and number of antihypertensive medications were associated with log-transformed hs-TnT, while hemoglobin and estimated glomerular filtration rate (eGFR) were inversely correlated with log-transformed hs-TnT. By multivariate analysis, age, eGFR and Cornell voltage were independent correlates of log-transformed hs-TnT, even after adjustment for clinical backgrounds including known prognostic biomarkers of EHT.

Conclusions

hs-TnT was ≥0.003 ng/ml in 78% of patients presenting with treated EHT and independently correlated with age, renal function, and ECG voltage of hypertrophy.     

The renin-angiotensin-aldosterone system in children and adolescents with nephrogenic hypertension

Renin-angiotensin-aldosterone (RAA) function was studied in children with secondary hypertension of 2 varieties: vasorenal hypertension (VRH) and arterial hypertension (AH) associated with chronic pyelonephritis. Children with VRH showed RAA activation that depended on the duration of the disease for its markedness. A direct correlation found between ABP, on the one hand, and plasma renin activity and blood aldosterone level, on the other, is evidence of the latter's involvement in VRH pathogenesis. In AH that is due to chronic pyelonephritis, RAA activation was also demonstrated, however, its pathogenetic involvement was only documented in children with urinary passage disorders (vesico-renal reflux), whereas in the rest RAA activation was not a primary cause of BP elevation.     

Severe cardiac involvement in children with systemic sclerosis and myositis

OBJECTIVE: To assess the outcome of children with systemic sclerosis (SSc) and features of polymyositis. METHODS: The charts of 4 children who met the American College of Rheumatology criteria for SSc and had features of polymyositis, as defined by the presence of proximal muscle weakness and elevated serum creatine phosphokinase or aldolase level, were retrospectively reviewed. RESULTS: All children had multivisceral involvement including (1) myocardial perfusion defects in all cases, with mild to severe dilated cardiomyopathy in 3; (2) lung restrictive syndrome in 3; (3) mild to severe esophageal involvement in all cases; and (4) severe intestinal dysfunction in one child. Combination therapy of corticosteroids, methotrexate (MTX), and cyclosporine resulted in improved skin thickness and muscle strength scores in all cases, as well as in lung restrictive syndrome in 2, but was not effective regarding the progression of intestinal malabsorption in one patient, esophageal dysmotility in 3 patients, and dilated cardiomyopathy in 3. Endstage cardiac failure caused 2 deaths. In one child, heart transplantation was performed for the first time in this indication. CONCLUSION: Children with diffuse cutaneous SSc and features of polymyositis are prone to develop severe cardiomyopathy. Combination therapy of corticosteroids, MTX, and cyclosporine seems to be active on muscle, skin, and lung involvement but does not impair progression of esophageal or myocardial dysfunction. Heart transplantation might be considered, as an experimental treatment, in young patients with severe cardiomyopathy and no other irreversible organ damage.     

Prevalence of hypertension in children and adolescents.

The children in the population of the district of Prague 4 were screened for the prevalence of hypertension. From the age group 6--11 years (1st--5th forms), a representative sample was selected, comprising 2 152 children; of the age group 12--19 years (6th--9th forms and adolescents), 90% of the population (11 323 individuals) were examined. The arbitrarily set criteria of hypertension 130/80 mmHg in the children aged 6--11 years and 135/80 mmHg in those aged 12--19 years, were found acceptable for identification of potential hypertonics. In the population examined, such or higher pressures were found in 0.5--3.4% of the subjects examined. By thorough clinical and laboratory examinations of children aged 11--15 years with elevated blood pressures the participation of secondary hypertension was determined. In comparison with a control group, these children exhibited statistically significantly more frequent diseases, obesity, and faulty regimen of living, as well as hypertension in their parents.     

Management of hypertension in children and adolescents with the metabolic syndrome

Because elevated blood pressure is one of the defining criteria of the metabolic syndrome, treatment of hypertension will be required in many, if not most, children and adolescents diagnosed with the metabolic syndrome. This review highlights several aspects of the approach to treatment of hypertension in young patients with the metabolic syndrome, including the definition of hypertension, use of nonpharmacologic measures, indications for instituting antihypertensive medications, and the potential adjunctive role that insulin-sensitizing agents may play in blood pressure reduction. The choice of antihypertensive agent is also discussed, along with consideration of the diabetogenic effects of various classes of antihypertensive agents. Consideration of all of these issues is important in achieving blood pressure control in children and adolescents with the metabolic syndrome, as appropriate treatment may help to forestall the development not only of type 2 diabetes but also of the cardiovascular disease that is frequently already present at the time of diagnosis of type 2 diabetes in adults.     

原发性高血压患者心脏电学改变研究进展

原发性高血压(essential hypertension,EH)可引起靶器官损害,早期可致心脏电学改变.这些改变主要包括心房除极的P波改变、心室除极的QRS波改变、心室除极和复极总时间的改变、ST-T改变和心律失常等.通过心电图检查可直接了解和观察心脏的电学变化.本文对近20多年来国内外关于EH患者心脏电学改变的研究...