Cause Of Elevated Blood Pressure Research Articles

Renovascular Hypertension: An Update

Renovascular hypertension, the most common remediable cause of elevated blood pressure, is a controversial topic, but most authorities agree on several principles. The absolute risk of renovascular hypertension for a specific patient can be estimated using only clinical information, thereby sparing many patients further expensive and potentially dangerous evaluations. Patients with a high absolute risk of renovascular hypertension should have angiography only if they are willing to undergo revascularization if warranted. A screening test (captopril renography, Doppler ultrasonography, magnetic resonance angiography, or computed tomography) is recommended for those with an intermediate absolute risk. Angioplasty should be offered to patients with fibromuscular dysplasia. Whether intensive medical therapy (including an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker) for atherosclerotic renovascular hypertension is improved by angioplasty plus stent placement may be answered by ongoing studies, the largest of which may be the National Institutes of Health-funded Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial.

An Emergency Department Approach to Drug Treatment of Hypertensive Urgency and Emergency

Patients who present with hypertensive urgency or emergency require immediate attention to assess the severity of illness. Guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure are available but do little to address the management of acute elevations in blood pressure. Various treatment options, both old and new, exist to manage these patients in the emergency department. Decisions on therapy are patient specific and depend on the underlying cause of elevated blood pressure. This article sets out to describe specific patient presentations and reviews current available options in the management of hypertensive urgencies and emergencies.

Salivary Cortisol, a Biological Marker of Stress, Is Positively Associated with 24-Hour Systolic Blood Pressure in Patients with Acute Ischaemic Stroke

Background/Aim: The cause of elevated blood pressure (BP) in acute stroke is unknown. Stress is often suggested as a main contributing factor. We aimed to investigate the relationship between BP and stress in patients with acute stroke. Methods: 58 patients with clinical symptoms of stroke were recruited prospectively after exclusion of haemorrhage by CT scan within 14 h and 15 min (mean) after symptom onset (range 2 h and 45 min–23 h and 40 min). The mean age of the patients was 66 years (range 39–86 years), and the mean National Institute of Health Stroke Scale score was 7 (range 1–26). BP and pulse rate were recorded by non-invasive automatic monitoring hourly for 24 h. Stress was evaluated by testing the level of salivary cortisol. Four samples of saliva were obtained at inclusion, on the evening of the inclusion day (20.00–22.00 h), on the morning of the next day (7.00–9.00 h) and on the afternoon of the inclusion day/next day (15.00–17.00 h) within 24 h after inclusion in the study. Logarithmic transformation was done for cortisol levels. Results: The 24-hour mean cortisol level (geometric mean 13.6 nmol/l) was related to 24-hour mean systolic BP [SBP; r = 0.36, p = 0.01, multivariate p = 0.02], mean night-time (22.00–6.00 h) SBP (r = 0.43, p = 0.001, multivariate p < 0.005) and mean night-time diastolic BP (r = 0.31, p = 0.02, multivariate p = 0.02). Cortisol levels at inclusion (r = 0.31, p = 0.02, multivariate p = 0.05 for 24-hour SBP) and in the evening were also statistically significantly related to the above BP variables. The morning cortisol (r = 0.28, p = 0.04, multivariate p = 0.04) was related to night-time SBP. Conclusions: Salivary cortisol was positively correlated with 24-hour SBP and night-time BP, suggesting that stress is a contributing factor for high BP in acute stroke.

Hypertension as a Candidate for Disease Management Initiatives

Hypertension, i.e. high systemic arterial pressure, is quantitatively related to future cardiovascular and renal insufficiency. Furthermore, treatment of hypertension is beneficial. Hypertension is therefore, one of the most important cardiovascular risk factors accounting for preventable disease. For individual patients, initial diagnostic strategies for hypertension should consider: (i) the need to determine average or usual levels of systolic and diastolic pressure, sometimes by employing the supplemental methods of ambulatory blood pressure monitoring or home blood pressures; (ii) the presence or absence of non-hypertensive reversible cardiovascular risk factors, particularly smoking, elevated serum lipid levels or diabetes mellitus; (iii) the presence or absence of pathological states related to hypertension and the other risk factors affecting the heart, arteries and kidneys; and (iv) the possibility of reversible causes of elevated blood pressure (secondary hypertension).

Diabetic nephropathy. Its relationship to hypertension and means of pharmacological intervention.

Hypertension and diabetes mellitus are common chronic conditions which frequently coexist. Diabetic nephropathy is a major cause of elevated blood pressure in patients with insulin-dependent diabetes mellitus (IDDM). Diabetic nephropathy, arterial sclerosis, obesity and association of essential hypertension can be the causes of hypertension in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ambulatory blood pressure monitoring has revealed that the nocturnal fall of blood pressure is blunted in patients with diabetic nephropathy. A blunted diurnal blood pressure variation is seen in microalbuminuric diabetic patients and even in some normoalbuminuric patients. Accumulating data suggest that normalisation of blood pressure in hypertensive IDDM patients is most important to minimise the loss of kidney function. Angiotensin converting enzyme (ACE) inhibitors have been reported to be effective in postponing the development of nephropathy and in slowing its progression. Whether only ACE inhibitors have such beneficial renal effects on diabetic nephropathy is under discussion. While many studies have suggested that insulin resistance and hyperinsulinaemia are related to an elevated blood pressure in hypertensive patients, there does not seem to be enough evidence to prove that insulin per se can raise blood pressure in humans. Neither an insulin infusion within a physiological range nor sustained hyperinsulinaemia and insulin resistance (e.g. patients with insulinoma, cystic ovary syndrome) have been associated with an elevated blood pressure. Insulin resistance in some hypertensive patients may be a consequence of a decreased blood flow due to an increased peripheral resistance. Preliminary evidence suggests that low birth weight or impaired fetal growth is related to hypertension and NIDDM. Familial clustering of diabetic nephropathy suggests the contribution of genetic susceptibility and/or environmental inheritance. The frequent association of nephropathy with hypertension has led to research on the genes related to hypertension (ACE, angiotensinogen). Nevertheless, to date no reliable and clinically useful genetic marker has been found. Attempts to correct the metabolic abnormalities derived from diabetes are a new topic in the treatment of diabetic nephropathy. The effects of HMG CoA reductase inhibitors (antihypercholesterolaemic drugs), aldose reductase inhibitors (inhibitors of the polyol pathway) and glycation inhibitors (inhibitors of formation of advanced glycosylation end-products) on diabetic nephropathy have been evaluated in animal studies and in some clinical trials. Thus far, results with HMG CoA reductase and aldose reductase inhibitors have been somewhat conflicting. The potential therapeutic role of glycation inhibition in the treatment of diabetes deserves further study.

Production of ouabain-like factors of hypothalamo-pituitary origin, determined by a sensitive ELISA for ouabain, is increased in DOCA-salt hypertensive rats

Endogenous digitalis-like factors (EDLFs) are thought to be an important modulator for the sodium and water metabolism, and vascular tone. Consequently, it may be a cause of elevated blood pressure not only in hypertensive animal models but also in patients with essential hypertension. The most probable candidate for EDLF is now ouabain or its isomer, ouabain-like factor (OLF). In this report, we described the sensitive enzyme-linked immunosorbent assay (ELISA) for OLF with the amplification by catalyzed reporter deposition. The sensitivity was pg/ml order and applicable to the biological fluid extracts by a Sep-Pak C 18 column. The urinary level in DOCA-salt hypertensive rats was significantly higher than that in the sham rats, which positively correlated with systolic blood pressure. The pituitary, hypothalamic and adrenal OLF content was considerably higher than the plasma level of OLF in normotensive rats. These findings indicate that plasma levels of OLF are closely related to hypertension associated with overloading of sodium, and that the origin is of hypothalamo-pituitary axis.

New aspects of insulin resistance in hypertension.

Primary hypertension is a frequent polygenic disease with strong genetic and environmental components. During the last decade, evidence has been increasing that insulin resistance as a marker of increased risk for Type 2 diabetes and cardiovascular atherosclerotic disease is present not only in individuals with obesity, Type 2 diabetes and impaired glucose tolerance, but also in the majority of the hypertensive population. Insulin resistance describes a tissue- and pathway-specific defect of glucose metabolism present in the so called 'metabolic syndrome'. Hyperinsulinaemia compensates for insulin resistance, leading to a cluster of undesirable processes predisposing to diabetes, atheroma and, directly or indirectly, hypertension. Candidate mechanisms whereby this metabolic syndrome might lead to hypertension include renal sodium retention, vascular hyperresponsiveness, arteriolar smooth muscle cell proliferation, altered cellular electrolyte transport and composition, stimulation of sympatho-adrenergic activity and growth promoting effects. Insulin per se does not appear to be the cause of elevated blood pressure as frequently seen in insulin-resistant states, but it may act with other factors to promote hypertension and atherosclerotic cardiovascular disease.

Growth areas in hypertension.

Essential hypertension is an arbitrarily defined disorder to which both environmental and genetic factors contribute. Identifying these factors is a difficult task because individually their contribution is relatively small and apparent causality may be the result of secondary changes or genetic drift. Associations between elevated blood pressure and genetic or phenotypic characteristics are insufficient therefore to demonstrate a cause and effect relationship. This conclusion requires that stringent criteria are met including the presence of the abnormality at or before the first manifestation of hypertension, co-segregation of the relevant gene, reversibility of hypertension when the abnormality is removed (at least during the early phases of hypertension) and failure of the abnormality to resolve with the correction of hypertension. It is proposed that these conditions constitute 'Koch's postulates' for defining the causes of elevated blood pressure.

Blood pressure during sustained inhibitory breathing in the natural environment.

Previous studies reported that breathing frequency of laboratory dogs decreased preceding the onset of an avoidance task and that this decrease was accompanied by increases in blood pressure and decreases in heart rate. Low frequency/normal tidal volume breathing has also been observed in ambulatory humans, but the cardiovascular concomitants of this inhibitory breathing pattern remain to be determined. The present study recorded blood pressure and heart rate in humans during periods of inhibitory breathing in the natural environment. Systolic and mean pressure were higher during inhibitory breathing than at other times, but no differences in diastolic pressure or heart rate were observed. Inhibitory breathing was differentially associated with the workplace and with social situations. Thus, major components of a physiological pattern that predisposes laboratory animals to sodium-sensitive experimental hypertension have now been observed to covary in ambulatory humans. Whether inhibitory breathing in the natural environment is a correlate or a cause of elevated blood pressure remains to be determined.

The Transition from Experimental to Clinical Pharmacology

Modern molecular medicine is increasingly bridging the gap between basic research and experimental pharmacology and clinical therapeutics and practical medicine. The challenge in hypertension research is to elucidate the primary, genetic causes of elevated blood pressure. The problems with understanding primary (genetic) hypertension in humans are that (a) several genes are involved in the cardiovascular control mechanisms, (b) the genetics are complex, and (c) environmental factors that act over long spans of time confound the genotype/phenotype relationship individually, within a family, and regionally. Polygenetic diseases such as primary hypertension remain puzzles, which necessitates well-defined experimental models and new strategies in the genetics of human primary hypertension. This article will focus on the advances in molecular genetics of hypertension. Using gene technology it is possible to introduce new, additional genes in normotensive and hypertensive animals. In the mouse, it is possible to delete or mutate specific genes; similar technology is being developed for use in the rat.

Methodology of sodium sensitivity assessment. The example of age and sex.

This article addresses the methodology of sodium sensitivity assessment. There have been reports to suggest that a high sodium intake is a cause of elevated blood pressure and trials to indicate that a reduction in sodium intake may reduce blood pressure that is already high; the implications of these findings are discussed. Many studies on sodium sensitivity suffer from what could be called the "normal probability fallacy"; without appropriate control conditions, an intervention such as sodium restriction may incorrectly be assigned to a more pronounced response in a subgroup of the study population. As an example, findings are reviewed of age and sex as determinants of a response of blood pressure to variations in sodium intake. The limited data available suggest that subjects that are older and have higher blood pressure levels seem to benefit more from a reduction in sodium intake. In addition, elderly subjects at a high dietary sodium intake may have a higher risk of developing hypertension. Findings in both nonexperimental and experimental studies tend to support this view. Findings on sex differences are less consistent. A systematic approach to the assessment of factors and mechanisms responsible for sodium sensitivity in some subjects is needed to determine who might benefit most. Until more data are available, there is little basis to discriminate sodium-sensitive from sodium-resistant hypertensive subjects.

Post-transplant hypertension in the rat: Effects of captopril and native nephrectomy

In patients with well-functioning renal allografts, the presence of diseased native kidneys appears to be a common cause of elevated blood pressure. We evaluated the role of native kidneys in post-transplant hypertension using a rat model in which the confounding variables of rejection and immunosuppression could be eliminated. To produce disease in native kidneys. PVG rats were subjected to 5/6 nephrectomy. Four weeks following renal ablation, these hypertensive animals were transplanted with kidneys from syngeneic PVG donors. Four weeks later, the effects of captopril and native nephrectomy on blood pressure and renal hemodynamics were examined. Animals with remnant native kidneys which received non-rejecting renal isografts had sustained hypertension, elevated plasma renin levels and reduced transplant function. In these animals, administration of captopril reduced systemic blood pressure. Despite the reduction in blood pressure, PAH clearance by the transplanted kidney increased markedly while GFR rose modestly. Removal of the remnant native kidney also acutely lowered blood pressure. However, compared to captopril, native nephrectomy produced a more marked increase in GFR without significantly affecting renal blood flow. In this model of post-transplant hypertension in the rat, elevated blood pressure and reduced isograft function are mediated by the diseased native kidney, in part through the effects of angiotensin II. These data suggest that ACE inhibitors and native nephrectomy may have beneficial hemodynamic effects in patients with post-transplant hypertension caused by native kidneys.

Carbohydrates and blood pressure.

High blood pressure is recognized as a major risk factor for both coronary heart disease and stroke. The role of diet in the genesis of hypertension has been hotly disputed. Recently, sucrose was reported to augment the hypertensive effects of salt in experimental animals. A review of many reports suggests that not only carbohydrates but also proteins and fats can alter blood pressure. Whether salt retention is a cause of elevated blood pressure remains to be ascertained. We have shown recently that sucrose and glucose elevate blood pressure transiently, and sucrose and fructose cause different degrees of salt retention in humans who have been fasting.

Rationale for combined alpha-beta-adrenoceptor blockade: haemodynamic considerations.

Increased peripheral vascular resistance is the cause of elevated blood pressure in most forms of systemic hypertension. Both structural changes in response to increased wall stress and functional alterations in vascular smooth muscle itself appear to contribute to the elevated resistance. As mediators of the vasoconstrictor responses, alpha-adrenoceptors apparently play an important if not predominant role in the initiation and/or maintenance of high resistance and pressure. In contrast to beta-receptor blockade alone, combined alpha-beta-receptor blockade lowers blood pressure predominantly by alpha-receptor-mediated reduction of the systemic vascular resistance, both when induced acutely and, in particular, during long-term administration. Cardiac output is maintained at pretreatment level, as is left ventricular filling pressure. Since a well-balanced blockade of both alpha- and beta-receptors counteracts the pathophysiological changes causing and/or maintaining hypertension and tends to restore cardiovascular dynamics towards normal, combined alpha-beta-receptor blockade appears at present to be one of the most logical and rational therapeutic approaches to hypertension.

Essential hypertension: relationship between renin and blood pressure.

Supine (basal) plasma renin activity (PRA) and mean arterial pressure (MAP) were determined in 564 essential hypertensives grouped by age and sex. Mean supine PRA showed an age-dependent significant decrease (p < 0.001), whereas an increase in MAP was observed with age (p < 0.001). There were no sex-related differences both in PRA and MAP. In younger hypertensives (15-34 years) of both sexes an inverse correlation was obtained between PRA and MAP, whereas middle-aged men (35-50 years) and male and female hypertensives of older age (> 51 years) showed a positive relationship between these two parameters. No significant correlation was seen between PRA and MAP in middle aged women (35-50 years). The observed findings suggest a negative feed-back mechanism between blood pressure and renin release in younger hypertensives. In older patients this mechanism is disturbed probably through hypertension induced changes in the renovascular system resulting in an inappropriate large release of renin for a given level of blood pressure. This conversion from an inverse to a positive relationship between PRA and MAP occurred earlier in male than in female patients. Finally, our results support the assumption that in essential hypertension changes in renin secretion are rather the sequel than the cause of elevated blood pressure.

The Management of Hypertension

This report on the management of hypertension is presented as a part of the Drug Spotlight Program. We will attempt to answer two questions: "Who should be treated for elevated blood pressure?" and "How should hypertension be treated?" The diagnosis of specific causes of elevated blood pressure and the detailed pharmacology of antihypertensive drugs will not be considered. Life insurance data and epidemiologic studies show that increases of either systolic or diastolic blood pressure are associated with increased morbidity and mortality from cardiovascular, cerebrovascular, and renal disease. The Veterans Administration Cooperative Study^1-3showed that drug therapy will drastically reduce complications and deaths. Unfortunately, most of the persons with hypertension in the United States are unaware of their hypertension, or are untreated. A recent study⁴showed that 58.9% of hypertensives found in a survey were previously undetected. As many as 16.4% of hypertensives had had diagnoses on earlier examinations,

MEDICAL NEWS

<h3>The Early Diagnosis Of Aldosteronism</h3> Sufficient clinical experience has been accumulated to confirm that primary aldosteronism is the cause of elevated blood pressure in a significant number of patients previously regarded as essential hypertensives. In the two years since Jerome W. Conn, MD, and his co-workers at the University of Michigan School of Medicine first reported a case of<i>normokalemic</i>primary aldosteronism (<i>JAMA</i><b>193</b>:200-206 [July 19] 1965) the Michigan group has screened 184 patients with essential hypertension and found aldosteroneproducing tumors in 14 (7.6%). <h3>Significant Number</h3> "No one anywhere in the world has done enough work yet to know precisely how many people thought to have essential hypertension actually have primary aldosteronism, but it will be a significant number," Dr. Conn told the annual meeting of the Canadian Medical Association. Since hypertension in most patients with primary aldosteronism is cured or substantially alleviated by surgical removal of the

Renovascular Hypertension With a Congenital Solitary Kidney

WHEREAS HEREAS the modern medical management of hypertension offers a much brighter outlook than it formerly did for many patients, surgical intervention is indicated for those who have unilateral parenchymal or vascular renal disease. The development of this type of surgical aid has stemmed from the intensive investigation that has clarified some aspects of the pathogenesis of hypertension, even though its etiology is still unknown. Of prime importance were the experiment of Goldblatt and his colleagues, 1 who confirmed the theories of Fahr 2 that renal ischemia is one cause of elevated blood pressure, and the demonstration of the angiotensin mechanism. 3,4 Thus, surgical correction of renal ischemia by means of bypass repair of a narrowed renal artery results in decrease in systemic arterial blood pressure, although the persistence of such a fall is variable. All reports of renovascular corrective surgery have been in patients who have both kidneys; the

Evaluation of the Tyramine Test In Hypertensive Patients and Controls

Tyramine hydrochloride has been proposed for use as a provocative test for pheochromocytoma. It has been evaluated in 46 hypertensive patients and 58 normotensive controls by members of the US Public Health Service Cooperative Study. Positive tests were obtained preoperatively in two patients with elevated catecholamine and vanilmandelic acid (VMA) levels with proved pheochromocytomas. Seven patients with labile blood pressure responses also had a positive tyramine test. In the latter group, results of catecholamine and VMA determinations were all normal. The tyramine test is a useful and safe addition to the screening procedures in the evaluation of hypertensive patients for remediable causes of elevated blood pressure. Twenty-four-hour urine collections for catecholamine or VMA determinations still are required to confirm the diagnosis of pheochromocytoma.