Hypertensive End-organ Damage Research Articles

Blood pressure variability, cardiovascular risk and antihypertensive treatment.

TWENTY-FOUR HOUR BLOOD PRESSURE PARAMETERS: The use of ambulatory blood pressure monitoring techniques has shown clearly that 24-h average blood pressure is more closely related to the end-organ damage of hypertension than isolated office blood pressure readings. It has also provided evidence that the degree of blood pressure variability over a 24-h period may be independently related to the cardiovascular complications of hypertension. However, all the available data on this issue come from cross-sectional studies, and prospective evidence on the actual prognostic value of 24-h blood pressure parameters has only recently been provided for daytime blood pressure variability. There is still no prospective evidence concerning overall 24-h blood pressure variability. ANTIHYPERTENSIVE AGENTS AND BLOOD PRESSURE VARIABILITY: Available antihypertensive agents are unable to effectively buffer blood pressure variability. However, drugs with a long-lasting antihypertensive effect and an optimal trough: peak ratio may at least prevent further iatrogenic increases in the amplitude of blood pressure fluctuations. BEAT-TO-BEAT BLOOD PRESSURE MONITORING: The ability of antihypertensive agents to actually reduce 24-h blood pressure variability needs to be demonstrated in future studies, using beat-to-beat blood pressure monitoring which is now possible by means of non-invasive techniques.

The effect of sleep intervals on analysis of 24-h ambulatory blood pressure data

Twenty-four hour blood pressure exposure and circadian blood pressure variability may be important predictors of hypertensive end-organ damage. Since sleep is a major determinant of circadian blood pressure decline, day/night blood pressure changes may be affected by sleep intervals. The current study compares 24-h blood pressure results with and without adjustment for patient-specific sleep intervals. Forty male hypertensive patients (22 with renal insufficiency and 18 with normal renal function) underwent 24-h blood pressure study with SpaceLabs 90207 monitors. They also filled out sleep questionnaires to evaluate time awake and asleep during the day and night intervals. Data was analyzed with and without adjustment for daytime asleep and nighttime awake intervals. The percent change in systolic, diastolic, and mean arterial pressure as well as heart rate was not different statistically or clinically with or without adjustment for sleep intervals. Nevertheless, there was a progressive increase in the day versus night percent change in these hemodynamic parameters with adjustment for sleep intervals. When we used arbitrary cut-offs to define "non-dipper", ie, less than 10% drop in a given hemodynamic parameter, and used patient-specific sleep intervals, clinically and statistically different numbers of "non-dippers" were seen versus sleep unadjusted data (19 v 12, using diastolic BP, P < .01). In conclusion, it may not be necessary to adjust for sleep intervals when relating 24-h blood pressure and day/night blood pressure variability to hypertensive end-organ damage. However, arbitrary cut-offs to define "non-dippers" may be greatly and capriciously affected by sleep/awake intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of diabetes mellitus and hypertriglyceridaemia as coronary risk factors in treated hypertension: 15 years of follow-up of antihypertensive treatment in middle-aged men in the Primary Prevention Trial in Göteborg, Sweden.

To analyse the importance of diabetes mellitus and hypertriglyceridaemia as potential risk factors for coronary heart disease (CHD) in middle-aged, treated hypertensive men. A prospective, long-term observational study. Derived from a random population sample--686 hypertensive men aged 47-54 years at entry--followed for 15 years at a special out-patient hypertension clinic. The patients were mainly treated with beta-adrenoceptor blockers and/or thiazide diuretics. Cardiovascular morbidity was closely monitored during follow-up. In all, 133 subjects suffered a CHD event during follow-up. The presence of diabetes mellitus at entry more than doubled the CHD risk and a 1 mmol l-1 increment of the serum triglyceride level at entry increased the CHD risk by 21%. In multivariate analyses, smoking, the presence of diabetes mellitus at entry, serum cholesterol and signs or symptoms of hypertensive end organ damage were found to be independent risk factors for CHD. In absolute terms the existence of cardiovascular damage was of much greater prognostic importance than were the presence of various metabolic abnormalities. Of the mean in-study variables, both the average serum cholesterol level and the achieved diastolic blood pressure were significantly associated with CHD. However, new diabetes mellitus which developed during follow-up as well as mean serum triglyceride levels were not associated with CHD. Diabetes mellitus and hypertriglyceridaemia present at the start of treatment have a prognostic impact in treated hypertensive men, whereas when such metabolic disorders develop during drug treatment they seem to be of much less importance. Smoking and already existing evidence of hypertensive end organ damage are of utmost importance for the prognosis in this type of patient.

Blood pressure reduction and end-organ damage in hypertension.

VALUE OF AMBULATORY BLOOD PRESSURE MONITORING: Studies that have used ambulatory blood pressure monitoring techniques have shown that the average 24-h or daytime blood pressure values are more closely related to the end-organ damage associated with hypertension than are isolated office readings. IMPORTANCE OF BLOOD PRESSURE VARIABILITY IN PROGNOSIS: More recently, blood pressure variability, measured as the overall 24-h blood pressure standard deviation, has been shown to have a significant relationship to end-organ damage in hypertensive patients. The potential clinical relevance of blood pressure variability has been strengthened in a recent prospective study. The possible prognostic value of blood pressure variability has practical implications for antihypertensive treatment; it may mean, for example, that the optimal antihypertensive drug should reduce not only the mean 24-h values but also the degree of fluctuation in blood pressure. This is more likely to occur with long-acting drugs, which induce a more balanced reduction in blood pressure throughout the 24 h. USE OF THE TROUGH:PEAK RATIO: A proposed measure of a balanced 24-h blood pressure effect is the trough:peak ratio of the blood pressure fall. This ratio can be obtained by clinic blood pressure measurements but ambulatory blood pressure monitoring offers some distinct advantages. One of these advantages is that by revealing the possibility of an excessive fall in blood pressure at the time of the peak effect or an uncontrolled rise at the trough, ambulatory monitoring can also reveal the possible impact of pharmacological treatment on 24-h blood pressure variability.

Ambulatory blood pressure monitoring in hypertension.

Ambulatory blood pressure monitoring generates a greater interest among investigators and clinicians because of its potential to 1) study the mechanisms involved in cardiovascular control in daily life (particularly if monitoring is performed on a beat-to-beat basis) and 2) improve the diagnosis of hypertension, the estimate of the patient's risk and the assessment of the efficacy of antihypertensive treatment. This paper will discuss the evidence pros and cons the latter indications of this approach. It will be shown that 24 hour blood pressure values correlate more closely than clinic blood pressure with various measures of the end organ damage of hypertension, suggesting that it may reflect better than traditional blood pressure measurements the cardiovascular consequences of this condition. Wider use of ambulatory blood pressure monitoring in the medical practice, however, must await a more clear demonstration of its prognostic importance, by longitudinal studies based on cardiovascular morbidity and mortality or on surrogate end points with undisputable clinical significance (e.g. left ventricular hypertrophy). It must also await clear definition of ambulatory blood pressure normality based on population studies. Until then ambulatory blood pressure monitoring should be employed to resolve special problems, e.g. identification of white coat hypertension and false non response to treatment.

Determining Hypertensive End-Organ Damage in Trials

The determination of hypertensive end-organ damage is the most crucial aspect of any long-term hypertension trial. Definition of inclusion criteria and withdrawal rules, and the evaluation of the treatment regimen in light of the cardiovascular prognosis, are all largely dependent on the trialists' abilities to identify vascular lesions and/or functional deteriorations of the major target organs. Although the vascular complications of hypertension tend to be diffuse, some organs and tissues are particularly sensitive: brain, eye fundus, heart, conduit arteries, and kidneys. To achieve a modicum of diagnostic accuracy, trial investigators will have to combine clinical acumen with a selection of ancillary techniques. This article reviews the compromises resulting from weighing the available technological potential against such conflicting factors as convenience and compliance of trial subjects, and expenditure.

Relationship of stress testing blood pressure with electrocardiographic and fundoscopy indices of hypertensive end-organ damage.

In our study we tested firstly, whether BP changes induced by laboratory stress testing could be better related than resting blood pressure (BP) to hypertensive target-organ damage (TOD) and secondly, whether an exaggerated reactivity to stress testing might be associated with an increased prevalence of TOD. In 49 untreated essential hypertensives, BP measured at sitting rest and during a variety of stressful situations was related to the presence of TOD, assessed by electrocardiography (ECG) and fundoscopy examination. The degree of TOD was significantly correlated to resting SBP; neither SBP at peak of isometric or dynamic exercise, nor SBP during mental test showed a greater correlation with TOD than resting SBP (NS). A large variability of individual's level of BP reactivity across the different laboratory tests was observed. Patients were arbitrarily dichotomised into groups according to a hyperreactive or normoreactive response to each stress testing; patients classified as hyperreactive (SBP increase greater than upper 95% confidence limit) did not disclose a greater rate of cardiac and ocular damage than normoreactors (NS). In conclusion, stress BP does not increase the strength of relationship with TOD compared to resting BP. Cardiovascular reactivity differs according to the laboratory stimulus employed and an exaggerated BP rise during stress testing is not associated with an increased rate of TOD.

US 4,943,391 Stabilizers BASF

The renin-angiotensin system (RAS) is a widely studied hormonal system that comprises substrate-enzyme interactions, the end result of which is production of the active peptide angiotensin II (Ang II). Because Ang II affects blood pressure control, sodium and water homeostasis, and cardiovascular function and structure, a great deal of research effort has been directed toward blocking the RAS. Angiotensin II may also be involved in end-organ damage in hypertension, heart failure, and vascular disease. At least two subtypes of angiotensin II receptors have been identified: AT1 and AT2. The AT1 mediates all of the known actions of Ang II on blood pressure control. Additionally, research has indicated that the AT1 receptor modulates cardiac contractility and glomerular filtration, and increases renal tubular sodium reabsorption, and cardiac and vascular hypertrophy. Less is known regarding the function of the AT2 receptor. Evidence suggests that the AT2 receptor inhibits cell proliferation and reverses AT1-induced hypertrophy. Indeed, these receptors are thought to exert opposing effects.Angiotensin II AT1 receptor antagonists (AT1RA) inhibit the RAS at the receptor level by specifically blocking the AT1 receptor subtype. These drugs induce a dose-dependent blockade of Ang II effects, resulting in reduced blood pressure, urinary protein, and glomerular sclerosis. It is postulated that AT1RA may provide end-organ protection by blocking Ang II effects via the AT1 receptor, yet leaving the AT2 receptor unopposed. Consequently, these agents may reduce the morbidity and mortality that result from myocardial infarction (MI) and other conditions resulting from structural alterations in the heart, kidney, and vasculature.

Introduction to focused issue

Since their introduction in 1977 [1], the angiotensin converting enzyme (ACE) inhibitors have rapidly gained acceptance as suitable initial drug therapy for the treatment of high blood pressure [2]. Furthermore, they are becoming important members of a therapeutic armamentarium designed not only to lower blood pressure, but also to prevent and/or attenuate the development of hypertension end-organ damage. It is this latter theme that provided the rationale for the inception, birth, and growth of this particular focused issue on ACE inhibitors. To set the stage, this focused issue begins with a scholarly review by Dr. Gurdarshan Thind on the comparative structure, pharmacokinetics, and pharmacodynamics of three commercially available but chemically different ACE inhibitors. The focused issue then follows with three in-depth reviews on the renal effects of ACE inhibitors in a) essential hypertension (Drs. Garry Reams and John Bauer), b) nondiabetic chronic renal disease (Drs. John Opshal, Paul Abraham, and William Keane) and c) renovascular hypertension (Dr. Stephen Textor). Each of these investigators provide a review and assessment of the literature in their respective areas of research. The focused issue then proceeds with an informative and provocative review of the effects of ACE inhibitors on vascular smooth muscle structure in hypertension (Drs. Garry Gibbons and Victor Dzau). Finally, this issue concludes with a personal but balanced assessment on the cardiac effects of ACE inhibitors (Dr. Norman Sharpe). Each of these authors brings to the reader not only the fruits of his scholarly research, but also his clinical interpretation of the data. To each of them, I express my appreciation for allowing me to combine their individual expertise into one publication assessing the effects of ACE inhibitors on hypertensive endorgan structure and function.

Renal protective effect of long term antihypertensive therapy with enalapril.

This review focuses on recent human studies with the angiotensin-converting enzyme (ACE) inhibitor enalapril, prescribed either alone or in combination with a diuretic, to patients with essential hypertension and to patients with hypertension associated with moderate to severe renal parenchymal disease. Data suggest that enalapril therapy may provide a renal protective effect. In addition to lowering and controlling systemic arterial blood pressure, enalapril therapy is associated with stabilisation of, and/or improvement in effective renal plasma flow, glomerular filtration rate (GFR) and urinary protein excretion. Such renal protective effects are probably mediated by normalisation of both the systemic arterial blood pressure and intraglomerular capillary hydraulic pressure, and by an increase in the glomerular ultrafiltration coefficient. Drug therapy enabling control of both systemic and glomerular hypertension may prevent hypertensive renal end-organ damage and attenuate the natural progression of renal parenchymal disease.

Long-Term Treatment of Refractory Hypertensive Patients With Minoxidil

Twenty-nine hypertensive patients refractory to conventional medications were treated continuously with minoxidil, sympathetic suppressants, and diuretics for six months to five years (mean, 30 months). All had evidence of hypertensive end-organ damage before minoxidil therapy. Good blood pressure control was obtained in 21 (72%) of 29 patients when minoxidil was given in dosages up to 40 mg/day. No tolerance was found. In the remaining eight, good control was obtained in three when phenoxybenzamine therapy was added, and in one when clonidine therapy was added. Renal failure requiring hemodialysis developed in five of 29, one had temporary hemiparesis, and one had fatal cerebral hemorrhage. In the remainder, myocardial infarctions and strokes were effectively prevented. Patients receiving minoxidil and propranolol hydrochloride had elevated plasma norepinephrine levels while those receiving clonidine had normal plasma norepinephrine levels.