Current Hypertension Reviews (v.8, #2)

Clinical Assessment of Central Blood Pressure by Hiroshi Miyashita (80-90).
Central aortic blood pressure (CBP) is increasingly considered a better cardiovascular prognostic marker than conventional cuff brachial blood pressure. Because CBP cannot be directly measured noninvasively, it has to be estimated from peripheral pressure pulses. To assess estimated CBP appropriately, the accuracy and features of the estimation method should be considered. The aim of this review is to provide basic knowledge and information useful for interpreting and assessing estimated CBP from a methodological point of view. Precise peripheral pressure pulse recording has been enabled by the introduction of arterial applanation tonometry, for which the radial artery may be the optimal site. An automated tonometry device utilizing a sensor array is preferable in terms of reproducibility and objectivity. Calibration of a peripheral pressure waveform has unresolved problems for any estimation method, due to imperfect brachial sphygmomanometry. However, if central and peripheral pressure calibrations are equivalent, two major methods to estimate CBP—those based on generalized pressure transfer function or radial late systolic pressure—may be comparable in their accuracy of CBP parameter estimation.

As central (aortic) blood pressures and augmentation indices predict cardiovascular outcomes beyond brachial blood pressures, there is growing clinical interest in the measurement of central haemodynamics. However, before these measurements can be implemented in clinical practice, determination of normal reference values is mandatory. A rigorous step-wise process is required to define accurate thresholds, so that misdiagnosis, inappropriate initiation of pharmacological therapy and unnecessary additional costs can be prevented. To-date there are limited data: age-specific thresholds have been defined using 95% prediction bands (4 studies); mean plus 2 standard deviation (2 studies) and 95th percentile (1 study) threshold values have been provided; and normative reference equations have been generated (3 studies), with only one study proving a means to estimate values above the normative population mean. There is lack of consistency in the thresholds defined in these studies, which indicates that we are far from achieving consensus even on the first step of the process. It is possible that different thresholds for central blood pressures may be required for measurement devices that differ in their technology and techniques. We recommend that experts in the field convene a consensus working group to resolve the controversies and plan a way forward. Importantly, thresholds would need to be confirmed in population studies; their utility in predicting cardiovascular risk and target organ changes tested and validated in prospective outcome-based studies; and their efficacy in diagnosis and treatment assessed in intervention studies.

Central Blood Pressure and End-organ Damage by Katsuhiko Kohara (100-107).
While the majority of cross-sectional publications report that central blood pressure (BP) is more closely associated with end organ damage, which includes left ventricular hypertrophy, carotid atherosclerosis, and brain and renal damage, than is peripheral BP, the superiority of central BP over peripheral BP has not been consistently observed in recent studies. This discrepancy may be due to a recent finding demonstrating the negative impact of obesity and obesityrelated disorders on central BP. Longitudinal studies are therefore necessary to demonstrate the clinical usefulness of central over peripheral BP in assessing the progression of end-organ damage.

Cardiovascular disease is the leading cause of death worldwide. Hypertension is a major contributor to cardiovascular risk, and the blood pressure serves as an important biomarker of the diagnosis, prognosis and treatment. Compared with the blood pressure conventionally measured in the brachial artery, the blood pressure in the central aorta is more strongly influenced by aortic stiffness and peripheral wave reflection, both of which relate to cardiovascular risk independently of the brachial blood pressure. The central blood pressure corresponds to the pressure exerted at the level of the heart, brain and kidney, and its elevation inevitably causes the simultaneous progression of vascular damage in these target organs, eventually leading to adverse outcomes due to cardiovascular, cerebrovascular and renal diseases. This review will focus on the current evidence as to the predictive value of central blood pressure measures in relation to cardiovascular events and also on the possible pathophysiological mechanisms connecting central hemodynamics and cardiovascular disease.

Recent evidence suggests that central blood pressure (BP) is a more important determinant of cardiovascular risk than is brachial BP. Antihypertensive drugs with vasodilating properties have a more beneficial effect on central systolic BP and pulse pressure by decreasing arterial stiffness and/or the magnitude of wave reflections than thiazide diuretics and β-blockers. These differential effects of antihypertensive drugs on central BP have been shown to account for the differential effects on cardiovascular prognosis. Furthermore, it has been reported that vasodilating drugs, such as angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, could contribute to both the reduction of central systolic BP and the regression of left ventricular hypertrophy, mainly through a reduction of the magnitude of wave reflections. Further studies are needed to demonstrate whether a therapeutic strategy aiming at normalizing central systolic BP will be more effective than a strategy targeting brachial systolic BP in preventing cardiovascular events.

Almost 10% of pregnancies are complicated with hypertension. Chronic hypertension, gestational hypertension, preeclampsia and preeclampsia superimposed on chronic hypertension is the most reliable classification in obstetrical practice. Blood pressure higher than 140/90 mmHg before 20 weeks of gestation is defined as chronic hypertension. Almost 25% of women with chronic hypertension will develop preeclampsia during pregnancy. Pharmaceutical approach is unnecessary for mild hypertension, while α-methyldopa, labetalol and nifedipine are the most common agents used for blood pressure more than 150/110mmHg. However, the above mentioned treatment does not improve perinatal outcomes neither preclude progress of the disease in preeclampsia. Gestational hypertension (elevated blood pressure after 20 weeks of gestation, without proteinuria) can be treated in the same manner. The former therapies contribute significantly to prevention of maternal end-organs damage. Preeclampsia is characterized by the development of hypertension and proteinuria after 20 weeks of gestation. It is a multiorgan disease in which the target organ is the endothelium, the brain (eclampsia), the liver, the coagulation system (HELLP syndrome), or the kidney (glomerular endotheliosis). Delivery still remains the only treatment in cases of severe preeclampsia and HELLP syndrome. Intravenous use of hydralazine, labetalol or nifedipine is the treatment of choice for the control of blood pressure in severe preeclampsia, while special care must be given to the use of anticonvulsive therapy for the prevention of seizures and to the administration of corticosteroids for fetal lung maturity acceleration. The management of hypertension in pregnancy must be individualized, while thorough counseling must be given to the parents concerning maternal health and fetal safety.

Diabetes and Gestational Hypertension by Anargyros Kourtis (127-129).
Gestational hypertension, preeclampsia, and diabetes are all associated with increased risks of poor maternal and perinatal outcome. In preeclampsia, exaggerated responses of insulin resistance, altered immune responses and inflammatory pathway activation are reminiscent of metabolic syndrome, and also are evident in gestational diabetes mellitus. Poor glycaemic control, preexisting hypertension and diabetic renal disease increase a diabetic woman’s risk for preeclampsia and associated maternal and fetal complications. In this short review, the possible link between diabetes and gestational hypertension is discussed.

Hypertensive disorders in pregnancy, such as preeclampsia/eclampsia, gestational hypertension and chronic hypertension, account for serious adverse outcome for mother and fetus. Oxidative stress, defined as the imbalance between oxidative and antioxidant mechanisms, is present in multiple disorders, as well as in pregnancy. It is characterized by increased free radical generation, affecting all macromolecules. Pathophysiology of pregnancies complicated with hypertension is characterized by more severe oxidative stress and by endothelial dysfunction. Preeclampsia and cardiovascular diseases seem to share common pathophysiology, such as dyslipidemia, oxidative stress, insulin resistance and endothelial dysfunction.

Manual blood pressure (BP) measurement performed according to established guidelines has been the standard method for assessing an individual’s BP status. However, manual BP readings in routine clinical practice rarely adhere to these guidelines with the result that routine office BP is relatively less accurate and about 10/5 mmHg higher than readings taken in the same patient as part of a research study. Automated office BP (AOBP) virtually eliminates officeinduced hypertension (white coat effect) with readings being similar to the awake ambulatory BP and home BP. AOBP also correlates significantly better with the awake ambulatory BP than does manual BP obtained in routine clinical practice. Several devices are now available to health professionals for recording AOBP in clinical practice. AOBP readings are consistent from visit to visit and when taken in different settings. Readings can be obtained during a 4 – 5 minute period with only a one minute interval between readings. AOBP is also not subject to digit preference (rounding off readings to zero values) which is common with routine manual BP. The three principles of AOBP include multiple readings taken with a fully automated sphygmomanometer with the patient being alone. The cut-point for a normal AOBP versus hypertension (135/85 mmHg) is the same as for both the awake ambulatory BP and home BP.

By the analysis of previous studies, functional and biochemical markers related to environmental tobacco smoke (ETS) exposure are discussed. 18 healthy never smokers, 12 men (67%) and 6 women (33%) aged from 21 to 55 years (mean: 34+/-9 ys.) underwent experimental procedures twice. in a smoking free environment and in the same environment polluted by 35 ppm carbon monoxide derived from smoked cigarettes. Brachial artery ultrasonography, exercise stress testing, heart rate (HR) and blood pressure (BP) monitoring, and carboxyhaemoglobin (COHb) concentrations were examined. Five markers related to ETS exposure of healthy individuals could be demonstrated: l. Impaired FMD as an effect of endothelial dysfunction, 2. Transient increase in systolic BP; 3. HR increase; 4. Diminished tolerance to exercise; 5. Increased COHb blood concentrations. Some of these feel the effects of sympathetic stimulation induced by both nicotine and carbon monoxide. Since both active and passive smoking are believed to be a chemical toxicosis, avoiding ETS exposure of healthy nonsmokers must be a categorical imperative.

Hypertension is one of the major risk factors for cardiovascular disease and fatal or non-fatal cardiac and cerebrovascular complications. Kidney and retina are also target organs of blood pressure rise. Progressive changes in the definition of hypertension have occurred in the years and blood pressure 130/85 mm Hg is considered as normal. Ischaemic heart disease, particularly myocardial infarction, often unrecognized, as well as stroke and transient ischaemic attack may be observed more frequently than other disorders in hypertensive patients. Conducted large-scale trials do not support the hypothesis that effective benefits are reached by current nonpharmacological or pharmacological prevention although some different opinions exist. Lowering blood pressure is, however, the main target to reach for reducing cardiovascular complications in hypertensive patients, in anyway that can be obtained. So doing, the ratio cost-benefit could be improved with a reduction of the costs supported by public health for hypertensive individuals.